Chapter 42. Infectious Disease Emergencies

Septic Shock

Essentials of Diagnosis

• Hyperthermia or hypothermia
• Tachycardia
• Tachypnea
• Leukocytosis or leukopenia
• Clinical evidence of infection

Sepsis is a state of systemic inflammation triggered by infection, affecting virtually every organ system. Although the mortality rate from sepsis has been falling, its incidence is increasing and septic shock now accounts for 10% of admissions to ICUs. Septic shock peaks in the sixth decade of life, and factors that can predispose to it include immunodeficiency, cancer, malnutrition, and genetics. Early recognition of sepsis is essential to providing effective care.

The systemic inflammatory response syndrome (SIRS) is characterized by a complicated interplay of multiple inflammatory mediators and may result from trauma, infection, burns, or diseases such as pancreatitis. It is defined as two or more alterations in the following physiologic parameters:

• Body temperature >38°C or <36°C
• Heart rate >90 beats per minute
• Respiratory rate >20, Paco2 <32 mm Hg, or need for mechanical ventilation
• White blood count (WBC) >12,000/mm3 or <4000/mm3, or >10% bands

Sepsis is defined as SIRS with a documented infection, with the identification of microorganisms from a normally sterile fluid or visual inspection of a focus of infection. Severe sepsis consists of sepsis with evidence of end-organ hypoperfusion or dysfunction (eg, prolonged capillary refill, ARDS, mental status changes, or elevated lactate). Septic shock is severe sepsis with persistent hypotension despite adequate fluid resuscitation, with refractory septic shock defined as septic shock requiring high doses of vasopressors.

Immediate Measures

Maintain Airway and Ventilation

Provide supplemental oxygen in order to maintain pulse oximetry >92%. Patients with profound mental status changes or hypoxia unresponsive to noninvasive ventilation may require intubation. Early on, arterial blood gas samples may show a respiratory alkalosis, with a metabolic acidosis becoming more prominent as the disease state progresses.

Establish Adequacy of Circulation

Adequate intravenous access should be obtained early on; consideration should be given to placing a central venous line that will allow monitoring of central venous pressure (CVP) as well as central venous oxygen saturation and allow the rapid infusion of crystalloid. Central venous lines also allow for the prolonged infusion of vasopressors if necessary; norepinephrine and dopamine are first-line agents. Routine use of low-dose (“renal protective”) dopamine is not recommended. An arterial line should be considered for all patients receiving vasopressors.

Traditional clinical measures of perfusion (urine output, capillary refill, tachycardia) may miss hypoperfusion in a significant number of patients. In patients with an elevated lactate >4 or systolic pressure <90, early goal-directed therapy (EGDT) should be considered and aggressive resuscitation with crystalloid should be initiated until a CVP of 8–12 is reached.

Early Goal-Directed Therapy (EGDT)

EGDT reduces mortality in patients with sepsis. Although not completely clear, treatment should be initiated aggressively in a 6-hour window for optimal results. Patients who meet the SIRS criteria mentioned above and have a suspected infectious etiology along with either a SBP <90 or a lactate >4 mmol/L are candidates for EGDT. Patients should initially be given crystalloid infusion until a CVP of 8–12 is reached. Vasoactive agents are then added to maintain a mean arterial pressure (MAP) greater than 65 mm Hg using either norepinephrine or dopamine. There may be some benefit from addition of low-dose vasopressin in refactory shock. Once the desired MAP is reached, check a mixed venous or central venous oxygen saturation. Those with <70% saturation should be transfused with PRBCs to maintain a hematocrit of at least 30%. Patients with a mixed venous O2 saturation <70% despite an adequate hematocrit should be given inotropic support with dobutamine starting at 2.5 μg/kg/min and titrating to a maximum dose up to 20 μg/kg to improve cardiac output.

Antibiotic Therapy

In accordance with current guidelines, appropriate antibiotics should be given within the first hour after sepsis is recognized. Remember to obtain needed cultures such as blood, urine, and fluid cultures prior to initiation of therapy, but do not delay treatment for such purposes. Recent literature has suggested that β-lactam monotherapy or later generation cephalosporins such as cefepime are effective and demonstrate equal efficacy compared to β-lactam and aminoglycoside dual therapy without the added nephrotoxicity. Local resistance patterns in the hospital and community as well as the patient's particular risk for resistant organisms should be considered in antibiotic selection. Gram-positive organisms are now more common as a source for sepsis than gram-negative organisms. Sepsis due to fungal organisms, although carrying a high mortality rate, is rare; routine antifungal coverage is not recommended unless the clinical picture dictates.

Source Control

When possible, the infectious etiology should be identified and removed surgically. A thorough examination for the source of infection is warranted, particularly in debilitated patients in whom complaints that would prompt evaluation of perineal infection or perirectal abscesses may be absent.

Adjunctive Therapies

Glycemic control is still encouraged with most sources recommending “moderate” control keeping glucose levels below 150 mg/dL but not in the normal range Corticosteroid therapy has been well researched with most recommendations indicating a “low-dose” steroid approach with no more than 200–300 mg of hydrocortisone per day. This has a higher grade of evidence in patients who fail to respond to a cosyntropin test or have fluid and vasopressor refractory hypotension. Continuation of this low dose and gradual tapering is encouraged. Efficacy regarding recombinant human activated protein C (RhAPC) is still debated but current guidelines continue to recommend RhAPC for patients with an APACHE II score >25 who are at high risk for mortality. Contraindications continue to include recent surgery or other risks for increased bleeding. The presence of disseminated intravascular coagulation (DIC) should not influence the decision to give RhAPC.

Laboratory Findings

Cultures

Obtain cultures of blood, urine, and sputum if indicated on all patients with severe sepsis. Other sources such as wound, CSF, peritoneal fluid, intravenous catheter sites, and joint fluid may be sent for Gram stain and culture if clinically indicated.

Other Laboratory Studies

A CBC may show an increased or, more ominously, decreased WBC with evidence of left shift. Thrombocytopenia should prompt evaluation for DIC, with evaluation of fibrinogen and fibrin split products as well as partial thromboplastin (PT) and partial thromboplastin time (PTT). Elevated blood urea nitrogen (BUN) and creatinine may result from renal hypoperfusion, and elevated liver function tests (LFTs) may result from hepatic hypoperfusion. Blood glucose may be increased or decreased, and electrolyte abnormalities are common.

Radiologic Studies

Chest X-ray as well as focused imaging of other potential sources of infection should be pursued as needed.

Pediatric Considerations

Vasopressors should only be initiated after adequate fluid resuscitation. Bolus of 20 mL/kg crystalloid should be given initially, with most patients responding after 40–60 mL/kg although larger amounts may be required. Dopamine is the first choice of support for pediatric patients with refractory hypotension despite fluid resuscitation. Patients with low cardiac output and high peripheral resistance may benefit from short-acting vasodilators such as nitroprusside. Infants are at higher risk for hypoglycemia and warrant more frequent monitoring. Blood pressure is not a reliable end point of resuscitation in children as they are able to maintain pressure by peripheral vasoconstriction and increased heart rate to a much greater degree than adults. Hypotension often heralds cardiovascular collapse.

Disposition

All patients with severe sepsis or septic shock require hospitalization in an ICU.

Identification and Evaluation of the Immunocompromised Patient with Suspected Infection

Classification of Immune Dysfunction

Those who have acquired their immunodeficiencies at birth or later in life through disease or medical treatment provide the emergency physician with a challenge to both recognize the specific problem and treat it appropriately. Excluding a defect in the skin, our primary host defense, we encounter problems associated with diseases of cell mediated and humoral immunity. In addition, there are infections associated with granulocytes in both function and quantity.

Neutropenia

Neutrophils ordinarily make up the majority of circulating WBCs. An absolute neutrophil count below 1000 is clinically significant. Most of these patients have undergone chemotherapy or irradiation. However, acquired neutropenia can come from an untoward response to a drug. The presence of fever >38.5°C, with neutropenia, suggests a related infection. For the evaluation of the source of infection, empiric therapy with admission to the hospital is indicated. Infections with pyogenic organisms such a Staphylococcus aureus and Pseudomonas aeruginosa are common. People with short-term neutropenia have a better prognosis than those chronically affected.

Cellular immune dysfunction

Problems with cell-mediated immunity involve the relationships between tissue macrophages, effector T cells, and cytotoxic T cells. Persons with AIDS, immunosuppression with antirejection drugs or antineoplastic drugs, as well as those with congenital T cell problems suffer from this. What is unique is that they are plagued by infections that are caused by intracellular pathogens. Mycobacteria, cytomegalovirus (CMV), and herpes simplex are a few examples.

Humoral immune dysfunction

It refers to decrease in antibody production or function as well as cytokine production, including pathogen and toxin neutralization, complement activation, and opsonin promotion of phagocytosis. From skin infection and vaginitis to frank sepsis, defects in humoral immunity result in a variety of conditions.

Clinical Findings

Symptoms and Signs

Fever is the most reliable sign of infection in immunocompromised patients and must never be ascribed to an underlying disease until infection has been excluded. In patients with neutropenia with skin and soft tissue infections, there may be lack of abscess formation with persistent redness and pain being the only symptom. A careful evaluation of the lungs, mucous membranes, and the skin may give clues. Because of the relatively low pathogenicity of some of the offending organisms, even infections of the meninges may be subtle.

Laboratory and X-Ray Findings

The CBC is useful in evaluating the immunocompromised patient. With it, the absolute neutrophil count may be estimated by multiplying the percent of observed neutrophils by the total. The usual evaluations of the chest and urine as well as cultures of blood and other fluids will be helpful. Evaluation of the spinal fluid may involve testing for Cryptococcus or CMV, and also staining for AFB.

Treatment

Antibiotics

In febrile patients with granulocyte counts under 1000, antibiotic therapy should be started immediately after material for routine culture has been obtained. Frequently, when the low count has been suspected, the neutropenic patient will have been started on antibiotics by their physician. Antibiotic adsorbing cultures should be used in this case. Circumstances that strengthen the directive for urgent empiric therapy include (1) a rapidly falling granulocyte count, (2) a very low granulocyte count (<500 further increases the risk of infection; <100 is frequently associated with fulminant infection), and (3) other clinical findings suggesting infection.

Current therapy for neutropenic fever varies depending on the illness severity and the “risk classification” of the patient based on disease process and overall health. Current literature identifies successful oral therapy for low risk, otherwise nonseptic, neutropenic patients. Combinations of fluoroquinolones and extended spectrum penicillins have been supported such as ciprofloxacin and amoxicillin/clavulanate.

For high risk or apparently toxic patients, hospital admission and monotherapy are often appropriate. Numerous recent articles support monotherapy, especially with late generation cephalosporins such as ceftazidime and cefepime. Other plausible monotherapy agents include ciprofloxacin and piperacillin–tazobactam. Classical dual therapy combines one of the above with an aminoglycoside such as gentamycin. Patients with risk factors for methicillin-resistant Staph. aureus (MRSA) colonization such as indwelling catheters, skin structure infections, or unknown origin sepsis may have vancomycin added to the regimen until cultures identify an organism.

Isolation

Neutropenic patients should be hospitalized in private rooms, and strict hand-washing precautions observed. Protective isolation as usually practiced (ie, masks and gowns) does not appear to be effective. Most infections neutropenic patients are derived from their own flora as opposed to infections from other persons and health care providers. This may explain why standard contact isolation procedures are usually minimally effective in preventing infections. Patients should be prescribed a diet free of fresh fruits and vegetables, which are often heavily contaminated with gram-negative bacilli.

Disposition

All immunocompromised patients with new findings of fever or other signs of infection should be hospitalized.

Meningitis and Meningoencephalitis

Essentials of Diagnosis

• Fever
• Nuchal rigidity
• Mental status change
• Photophobia
• Headache
• CSF findings

General Considerations

Meningitis is defined as inflammation of the meninges; it is the major infectious syndrome affecting the CNS. When meningitis is accompanied by parenchymal involvement, it is referred to as meningoencephalitis. The epidemiology of meningitis has changed drastically since Haemophilus influenzae immunizations became available. The incidence of meningitis caused by this agent has decreased by 94%. The average age of meningitis cases peaks in a bimodal fashion. Infants and young adults around the age of 18 are at highest risk in terms of incidence and disease burden. The current mortality according to the Centers for Disease Control (CDC) is 10–14% but with 11–19% of survivors have some permanent neurologic sequelae. Survival depends on prompt recognition and early treatment.

Clinical Findings

Symptoms and Signs

Patients with meningitis present with fever, headache, nuchal rigidity, and mental dysfunction. Seizures and cranial nerve deficits are also common. Infants with meningitis may present with only vomiting, lethargy, irritability, and poor feeding. Elderly patients may present with only low-grade fever and delirium. The headache associated with meningitis is continuous and throbbing and, although generalized, is usually most prominent over the occiput. The pain is increased by jugular vein compression or any other maneuver that increases intracranial pressure (eg, coughing, sneezing, and straining at stool). Neck stiffness and other signs of meningeal irritation must be sought with care because they may not be obvious early and may disappear during coma. Patients with meningitis may be divided into two groups on the basis of the presentation of the disorder.

Acute presentation (septic meningitis)

Symptoms and signs have been present for less than 24 hours and are rapidly progressive. The causative organisms are usually pyogenic bacteria, and the mortality rate is approximately 50%.

Subacute presentation

Symptoms and signs have been present for 1–7 days. Meningitis is due to bacteria, viruses, or fungi, and the death rate due to bacterial infection is much lower than in patients with acute presentation of disease. Aseptic meningitis is typically caused by viruses (enteroviruses, herpes simplex virus [HSV], or Epstein–Barr virus). Suggestive features such as respiratory tract syndrome and hand–foot–mouth syndrome strengthen the diagnosis. Chronic meningitis is defined as meningitis present for more than 4 weeks; the major infectious causes are tuberculous meningitis and cryptococci.

Laboratory Findings

Perform lumbar puncture immediately in the absence of papilledema and focal neurologic findings. For contraindications to lumbar puncture, see Table 42–1. Interpretation of CSF findings is shown in Table 42–2. Draw blood for serum glucose measurement and for culture. Gram staining of CSF will allow presumptive identification of the causative agent. Even if no organisms are seen on Gram-stained smears of CSF, bacterial meningitis is a likely diagnosis and warrants empiric antimicrobial therapy if total CSF leukocytes number more than 1000, if polymorphonuclears (PMNs) make up at least 85% of the white cells in CSF, or if the CSF glucose is less than 50% of the serum glucose level in a simultaneously drawn blood sample. The differential diagnosis in patients in whom PMNs are less than 85% of the CSF white count must include several possible causes of acute lymphocytic meningitis (Table 42–3). Prior treatment with antibiotics could result in sterile cultures of CSF.

Treatment

Antimicrobial Therapy

Acute presentation

When bacterial meningitis is suspected, begin administration of appropriate empiric antibiotics immediately (Table 42–4). Give the first dose as soon as samples of CSF and blood have been collected for tests; the goal is to begin intravenous administration of antimicrobials within 30 minutes after a patient with acute presentation of meningitis has sought treatment. If lumbar puncture must be delayed for computed tomography (CT) scan, obtain two blood samples for culture and begin appropriate antimicrobials. Perform lumbar puncture after mass lesion has been excluded and obtain CSF for microscopic examination as soon as possible. For pathogen-specific antibiotic therapy for bacterial meningitis, see Table 42–5.

Subacute presentation

Treatment is based on results of Gram staining of CSF and other tests. If meningitis is likely but Gram staining is negative, begin empiric treatment based on the patient's clinical characteristics pending the results of CSF studies.

Suspected brain abscess

In patients thought to have a brain abscess, begin intravenous therapy with a combination of penicillin and metronidazole or a third-generation cephalosporin. Obtain an emergency CT scan.

Corticosteroids

Studies have failed to clearly define the utility of corticosteroids in the patient with bacterial meningitis. However, evidence does suggest a potential benefit and no prominent negative effects. Therefore, use is recommended, especially with S. pneumoniae meningitis in adults and in children older than 2 months. Dexamethasone 10 mg should be administered to adults preferably prior to, or along with antibiotics. Utilization after antibiotic administration has been found not to be helpful.

Supportive Care

General supportive care measures should be started in the emergency department. Protect the patient's airway, and provide padded rails or restraints for agitated or delirious patients. If seizures occur, begin anticonvulsant therapy. Avoid overhydration, which may worsen cerebral edema.

Disposition

Immediate hospitalization is warranted for all patients, except those with aseptic (viral) meningitis who appear well and can be observed at home.

Pneumonia

Pneumonia in Neonates (Aged <2 Weeks)

Essentials of Diagnosis

• Grunting, tachypnea
• Focal lung exam
• Radiographic findings

Clinical Findings

Symptoms and Signs

The early neonatal period, birth to 2 weeks, is dominated by group B Streptococcus, Listeria, and gram-negative Escherichia coli and Klebsiella pneumoniae. These are acquired at birth. These infants will have poor feeding, paradoxical irritability, grunting, and tachypnea. Cough may only be an infrequent feature. Sepsis or meningitis may accompany the pneumonia.

Laboratory and X-Ray Findings

A total sepsis workup is clearly indicated for these infants. Laboratory findings will vary, but the diagnosis will be confirmed with the chest X-ray.

Treatment and Disposition

Appropriate antibiotic therapy is outlined in Table 42–6. All neonates should be hospitalized.

Pneumonia in Infants and Children (Aged 2 Months to 5 Years)

Clinical Findings

Symptom and Signs

In infants over 2 months of age, more classic signs and symptoms of pneumonia are present but tachypnea predominates. Cough, grunting, rales, and wheezing may be seen and fever is variable.

Laboratory and X-Ray Findings

As viruses predominate this age group, an elevation of the WBC above 15,000/mm3 is suggestive but not diagnostic for bacterial infection. Arterial blood gas analysis may be obtained to assess the adequacy of ventilation. Electrolyte levels and BUN are useful in assessing the degree of dehydration, the most frequent complication seen in this age group. Obtaining sputum is difficult without direct tracheal aspiration, or pneumocentesis. Blood cultures though frequently obtained are rarely positive as H. influenzae and S. pneumoniae have become rarer. Indirect identification of respiratory syncytial virus (RSV) and influenza have been very helpful in confirming the etiology of the pneumonia.

Treatment and Disposition

Appropriate antibiotic therapy should be guided by age and is outlined in Table 42–6. Severely ill infants (ie, with respiratory distress, hyperthermia, or Po2 <70) should be hospitalized.

Pneumonia in Older Children (Aged 5–18 Years)

Clinical Findings

Symptoms and Signs

Infection with Mycoplasma pneumoniae begins to predominate. Cough rales and wheezing may be seen. Bullous myringitis helps confirm the etiology and thus tailor appropriate treatment. Fever is very common with pneumonia in this age group, while cough may be present, abdominal pain may be the child's chief complaint.

Laboratory and X-Ray Findings

In pneumonia due to M. pneumoniae, the white cell count is usually normal or slightly elevated, and chest X-ray reveals scattered segmental infiltrates, atelectasis, interstitial disease, or, less frequently, lobar consolidation.

In pneumonia due to bacteria other than M. pneumoniae, the white cell count usually exceeds 15,000. Chest X-ray abnormalities include patchy infiltrates, increased bronchovascular markings, lobar consolidation, cavitary infiltrates, and pleural effusions or empyema. Gram-stained smears of sputum may allow for a presumptive diagnosis if numerous PMNs, few epithelial cells, and a predominant microorganism are found. Pleural fluid should be examined if present.

Treatment and Disposition

Appropriate antibiotic therapy is outlined in Table 42–6. Hospitalization is indicated for patients with pneumonia who require oxygen or have intractable vomiting. In addition, patients with preexisting pulmonary disease and all patients with bilateral bacterial pneumonia should be hospitalized.

Pneumonia in Adults

General Considerations

Complete CDC data from 2006 indicates pneumonia and respiratory infection to be the 8th leading cause of death in the United States. Over 1.2 million patients were admitted with pneumonia with an average of 5.1 days hospital stay. This contributes to a multibillion dollar cost related to pneumonia care. S. pneumoniae remains the most common cause of community-acquired pneumonia (CAP) in the adult population, with atypical organisms such as M. pneumoniae and Chlamydiapneumoniae common in young adults. Patients with structural lung disease, the elderly, nursing home residents, alcoholics, those with recent antibiotic exposure, and those who are immunosuppressed (>10 mg/d of prednisone) or have recently been hospitalized are more likely to be infected with resistant S. pneumoniae or gram-negative organisms. Influenza, varicella, and RSV (particularly in nursing home residents) are common viral causes of CAP.

Clinical Findings

Symptoms and Signs

Atypical or viral pneumonias may develop insidiously with focal respiratory complaints preceded by a 3- to 5-day history of malaise, fever, myalgias, and sore throat. Auscultation of the lungs typically reveals diffuse findings such as wheezing or fine rales, which may be slightly more prominent in the lung bases. Bacterial pneumonias are characterized by an abrupt onset of fever, chills, cough often productive of purulent or blood-tinged sputum, and pleuritic chest pain. Physical examination reveals a focal area of rales and possible consolidation. Legionella pneumonia presents as a severe form of lobar pneumonia and is classically associated with diarrhea. The diagnosis of pneumonia in nursing-home residents requires a high index of suspicion as they often have nonspecific presentations, often in the absence of cough, fever, and dyspnea. Aspiration pneumonia is more common in the elderly, those with poor dentition, and alcoholics, and is characterized by very foul-smelling sputum.

Laboratory and X-Ray Findings

A chest X-ray should be obtained to confirm the diagnosis of pneumonia, help guide initial treatment, and exclude other etiologies. Chest X-ray findings with the associated organisms are outlined in Table 42–7. A right lower lobe or right upper lobe infiltrate in the setting of aspiration may represent aspiration pneumonitis rather than pneumonia if other clinical indicators of infection are absent. CT may be helpful in differentiating between lung abscess and empyema when the chest X-ray is equivocal. An oxygen saturation should be obtained on all patients with an arterial blood gas reserved for severely ill patients. Gram staining and culture of the sputum is the most valuable study for patients in whom it is important to determine an etiology (critically ill, those at risk for resistant organisms). Urinary antigen testing for Legionella pneumophila and S. pneumoniae is more sensitive at detecting infection with these organisms than are blood cultures but provides no data on antibiotic sensitivity. In patients younger than 50 years with no significant comorbidities, who are not hypoxic, and who do not have any of the abnormal physical examination findings, no further laboratory testing may be needed. Leukocytosis is a common but nonspecific finding, while leukopenia in the setting of clinical infection is often ominous. Elderly patients commonly show prerenal azotemia, and hyponatremia with elevated LFTs are associated with Legionella pneumonia.

Treatment

Initial treatment is empiric and based on the presumed causative organism for the patient's clinical presentation. Hospitalized patients should be divided into one of three categories: CAP, health care associated pneumonia (HCAP) early or with no risk factors for multidrug resistant pathogens (MDR), and HCAP late or with risk factors for MDR (Table 42–8).

Recommended empiric antibiotic regimens for both CAP and HCAP are listed in Table 42–9. Current literature reviews have failed to demonstrate any statistically significant research demonstrating higher therapeutic success with any one outpatient regimen for CAP. Prompt recognition and treatment with a variety of agents as initial therapy seem appropriate. Although coinfection with atypical organisms is common, it is not clear whether adding atypical coverage is beneficial in younger patients. Initial enteral treatment recommendations include macrolides as a common first-line choice with amoxicillin/clavulanate and doxycycline cited as appropriate other choices. Respiratory fluoroquinolones are commonly second-line therapy for failed treatment or high-risk patients and should probably be reserved for this use.

Hospitalized patients should be treated with a β-lactam agent and macrolide or a fluoroquinolone as monotherapy, with consideration given to resistant organisms and appropriate gram-negative coverage, particularly for ICU patients. Administration of antibiotics rapidly following presentation and diagnosis is critical. Although classically the standard goal for administration of parenteral antibiotics has been 4 hours, data has shown that time periods up to 6 hours may still be acceptable. Clearly earlier administration is preferable and decreases mortality, even if the diagnosis remains unclear and the initial antibiotic regimen may not be optimal.

Disposition

The use of validated scoring systems such as the Pneumonia PORT Severity Index has been demonstrated to determine effectively that patients may be safely treated on an outpatient basis (see Table 42–10). Classes I, II, and III (≤ 90 points) patients are at sufficiently low risk for death that they can be considered for outpatient treatment or an abbreviated course of inpatient care. Class IV and V patients should be hospitalized.

Bronchiolitis

Essentials of Diagnosis

• Wheezing
• Cough
• Low-grade fever
• Tachypnea

General Considerations

Bronchiolitis is an acute inflammation of the bronchioles, most commonly resulting from a viral infection. It typically affects children from birth to age 2 years and occurs mostly during the winter months (November to March). RSV is the cause in 60–90% of cases; the remaining cases are caused by parainfluenza, adenovirus, rhinovirus, and influenza and human Bocavirus.

Clinical Findings

Symptoms and Signs

The child with bronchiolitis typically has a 4-day history of clear profuse rhinorrhea and congestion, usually accompanied by low-grade fever followed by the development of a cough, tachypnea, and wheezing. Signs of respiratory distress including cyanosis and accessory muscle use may be evident, and inspiratory wheezing and crackles are typically heard on auscultation of the patient's lungs. Apnea can occur, and approximately 2–7% of children ill enough to require hospitalization develop respiratory failure, and require intubation.

Laboratory and X-Ray Findings

A nasopharyngeal aspirate can be sent for rapid identification of RSV and influenza and have become the standard for diagnosis. A positive test does not preclude the diagnosis of asthma that is also an inflammatory process. A chest X-ray is recommended for all patients who do not already have chronic respiratory problems and may show findings characteristic of bronchiolitis: hyperinflation, atelectasis, peribronchial thickening, and diffuse interstitial infiltrates.

Treatment

Oxygen rapidly relieves hypoxemia and is the most important therapeutic agent for bronchiolitis. A trial of bronchodilators is indicated. Studies evaluating the use of glucocorticoids show no improvement in outcome, provided that asthma can be excluded. Ribavirin is a synthetic nucleoside analogue that has virostatic activity against RSV and is recommended for use in patients with a history of congenital heart disease or chronic lung disease, preterm infants, infants younger than 6 weeks, and infants ventilated for RSV infection.

Disposition

Criteria suggestive of severe disease include the following: ill or toxic appearing, oxygen saturation less than 95%, gestational age less than 34 weeks, respiratory rate greater than 70 breaths/min, atelectasis on X-ray, and age less than 3 months. The infant's oxygen saturation while feeding is the single best objective measure of severe disease.

Septic Arthritis

Essentials of Diagnosis

• Fever
• Painful joint
• Joint effusions
• Arthrocentesis findings

General Considerations

Left untreated, septic arthritis rapidly destroys articular cartilage, causing permanent joint damage. Delay between the onset of symptoms and treatment is the major determining factor for prognosis. Joint infection may occur by hematogenous route, direct inoculation, or spread of contiguous infections. Hematogenous infection in children was the most common route, but HIB immunization has decreased this significantly. The peak incidence occurs in children under age 3 years, and boys are affected twice as often as girls. However, with the increasing frequency of prosthetic joints, a new group has emerged that may be the most problematic.

Septic arthritis typically affects only one or a few asymmetrically distributed joints. Because joint infection superimposed on rheumatoid arthritis sometimes occurs, any joint that develops inflammation out of proportion to that in other affected joints should be aspirated to rule out the possibility of infection in patients with rheumatoid arthritis. There are about 20,000 cases of septic arthritis in the United States annually with gonococcus being the leading cause and Staph. aureus in second place. People with existing joint damage from rheumatoid arthritis and surgery are at risk. Other groups at high risk include intravenous drug abusers and patients on hemodialysis. Aspiration of the affected joint in the emergency department is often necessary to differentiate septic arthritis from other causes of synovitis, such as gout or pseudogout.

Clinical Findings

Symptoms and Signs

Patients with septic arthritis usually have acute or subacute onset of pain, erythema, swelling, and limitation of motion in the affected joints. The patients most likely will show signs of systemic infection with fever chills and an ill appearance. The arthritis more commonly affects the large joints, especially the knee. In infants or neonates, failure to feed or pseudoparalysis of the extremity may be present.

Laboratory Findings

Definitive diagnosis is established by demonstration of the infecting organism in synovial tissue or joint fluid. Blood cultures may be positive even though cultures of joint fluid are negative and should be obtained for all patients thought to have septic arthritis.

Joint fluid analysis

Joint fluid typically shows high leukocyte counts, usually over 50,000, although the count may not be strikingly elevated in early disease. Synovial fluid should be considered inflammatory and possibly infectious if the count is above 7500. The higher the white cell count in joint fluid, the greater the likelihood of bacterial or fungal arthritis. The glucose content of synovial fluid is usually lower than normal but occasionally may be normal. If no antimicrobial therapy has been given, smears and cultures often reveal the causative organism. A synovial fluid lactic acid test may be useful in excluding septic arthritis; the test has a negative predictive value of 97%. Results of other laboratory tests are variable, and plain X-rays of affected joints are usually negative early in the disease.

Gonococcal arthritis

In gonococcal arthritis, Gram-stained smears and cultures of joint fluid are negative in 50–75% of cases, although in 86% of patients, cultures of exudates from the cervix, urethra, pharynx, or rectum demonstrate gonococci. Because the gonococcus is a fastidious organism, demonstration of its growth in cultures depends on prompt processing of specimens by the laboratory. Because special handling is also required, all specimens submitted should bear the instruction “Rule out gonorrhea.” Prompt response to antimicrobial therapy helps confirm the diagnosis of gonococcal arthritis.

Treatment

Aspiration

Aspirate affected joints. Aspiration is necessary except for infections in inaccessible joints. Open drainage is almost never required in gonococcal arthritis.

Antibiotics

High doses of intravenous antibiotics should be given (Table 42–11). Intra-articular instillation of antibiotics is unnecessary because high antibiotic levels are attained in synovial fluid when drugs are given intravenously. If no organisms are seen on Gram-stained smears of synovial fluid, but other findings suggest septic arthritis, empiric antibiotic therapy based on the type of patient and clinical findings should be started depending on the results of culture and sensitivity.

Disposition

Hospitalize all patients with suspected or documented septic arthritis.

Osteomyelitis

Essentials of Diagnosis

• Pain, fever
• Increased erythrocyte sedimentation rate
• Biopsy findings

General Considerations

Osteomyelitis is an infection of bone that affects all age groups. The infecting organisms are bacteria, mycobacteria, or fungi. For purposes of discussion, osteomyelitis can be classified according to the pathogenic mechanism: (1) hematogenous osteomyelitis and (2) osteomyelitis secondary to contiguous focus of infection. Hematogenous osteomyelitis is common in children, although its incidence is increasing in older age groups. Hematogenous osteomyelitis in adults usually involves the vertebral bodies. Spread of disease from a contiguous focus of infection is the most common pathogenic mechanism in adults. In both children and adults, the most commonly involved bones are the long bones, especially those of the lower extremities; this is particularly true in children. Orthopedic procedures or traumatic wounds predispose to osteomyelitis of the extremities. Sometimes a third classification of osteomyelitis from peripheral vascular disease is included, but this is likely a predisposing condition to contiguous spread.

Clinical Findings

Symptoms and Signs

Hematogenous osteomyelitis

The abrupt onset of high fever, systemic toxicity, and physical findings of local suppuration surrounding the involved bone (local pain, swelling, and tenderness) are typical. The disease may be more indolent, particularly in patients with vertebral osteomyelitis. Patients with vertebral osteomyelitis may have low-grade or intermittent fever or back pain that may be either severe or only nagging and may not cause extreme discomfort or immobility until late in the disease. Focal tenderness over the dorsal spines of the involved vertebral bodies may be the only physical finding.

Osteomyelitis secondary to contiguous infection

The most common predisposing factor is postoperative infection, such as that following open reduction in fractures. Extension of soft tissue infections to bone from infected fingers and toes, infected teeth, or infected sinuses also occurs. Most patients are over age 50 years and may present with fever, swelling, and erythema in the initial episode. During recurrences, sinus formation and drainage are the major presenting signs.

Osteomyelitis associated with vascular insufficiency

Patients with osteomyelitis associated with vascular insufficiency invariably have diabetes mellitus or severe peripheral vascular disease. The toes and small bones of the feet are usually affected. Local signs and symptoms such as pain, swelling, redness, or frank cellulitis with deep ulcers in the soft tissue are prominent. Pain is often absent because of diabetic neuropathy.

Laboratory Findings

Routine laboratory tests are of limited value in the diagnosis of osteomyelitis. The leukocyte count is often elevated in acute disease but may be normal in more chronic infection. The erythrocyte sedimentation rate and C-reactive protein are elevated in most patients. Radiographic procedures are the primary diagnostic tool, although plain X-rays may not show signs of disease until 10–14 days after symptom onset. The earliest visible X-ray changes are adjacent soft tissue swelling and periosteal reaction. Lytic lesions and areas of sclerosis may then develop. If osteomyelitis is suspected and plain X-rays fail to reveal signs of disease, MRI or bone scan should be performed. The diagnosis is confirmed by culture and histologic examination of bone. Bacteriologic findings vary, and cultures should be obtained from bone (via needle aspiration or surgical biopsy) or blood (results are positive in 50% of cases in patients with acute hematogenous osteomyelitis).

Treatment

The most important therapeutic measures are systemic antibiotics and surgery to drain abscesses or for debridement of necrotic tissue. The selection of an antibiotic depends on identification of the causative organism. If the disease is uncomplicated (ie, involves a long bone in a patient without underlying medical problems), if the patient is a child, or if the patient is critically ill, then antistaphylococcal therapy should be initiated because Staph. aureus is the most common infective organism.

Surgery in acute osteomyelitis should be limited to biopsy for diagnosis, drainage of suppurative areas, and debridement of necrotic bone. Surgical drainage is also indicated if neurologic abnormalities are present or develop in patients with vertebral or cranial osteomyelitis or if infection spreads to the hip joint in a child.

Disposition

Patients with acute osteomyelitis should be hospitalized for intravenous antimicrobial therapy.

Pharyngitis

Essentials of Diagnosis

• Sore throat
• Fever
• Erythematous pharynx
• Odynophagia

General Considerations

Acute pharyngitis is a common presenting complaint, particularly in the winter months, and is caused by a multitude of organisms (see Table 42–12). The vast majority of cases are caused by viruses, although 15–30% of children and 5–10% of adults will have pharyngitis caused by group A β-hemolytic streptococci (GABHS), the single most common etiology. Judicious antibiotic use is warranted to prevent over treatment; over 70% of adults receive antibiotic treatment despite the low prevalence of GABHS in this age group.

Clinical Findings

Symptoms and Signs

Group A streptococcal infection

GABHS most commonly occurs between the ages of 5 and 15 years and is prevalent in late winter and early spring. Onset is typically sudden and may include fever, sore throat, anterior cervical lymphadenopathy, a “beefy red” uvula and pharynx, and tonsillar exudates. Children more commonly present with headache, vomiting, and abdominal pain with a nontender abdomen. A scarlatiniform rash and palatal petechiae may also be present. The absence of cough, coryza, and diarrhea support the diagnosis of GABHS. Several organizations have published guidelines regarding the use of rapid-antigen testing, but questions remain over whether these guidelines are sufficiently specific.

Infectious mononucleosis

Clinical findings in infectious mononucleosis may be identical to those in GABHS, although the onset and course are usually more indolent. Generalized lymphadenopathy, particularly posterior cervical, and hepatosplenomegaly are common and resolve over 3–6 weeks. Laboratory testing for specific antibodies to Epstein–Barr virus, heterophile antibody, and a CBC to document atypical lymphocytosis support the diagnosis.

Diphtheria

Diphtheria is rare but should be considered in patient for whom immunization status is uncertain in the face of a membranous or exudative pharyngitis. A “bull neck” appearance due to prominent anterior and posterior cervical lymphadenopathy, tachycardia out of proportion to fever, and a grayish-brown pseudomembrane that may extend down the pharynx to include the tracheobronchial tree are classic findings.

Vincent angina

Vincent angina is a polymicrobial infection, typically limited to the gingiva, and characterized by foul breath, cervical lymphadenopathy, and fever. In immunocompromised individuals, it may extend to include a necrotic gray pseudomembrane on the pharynx.

Lemierre's Syndrome

Lemierre's Syndrome is a rare complication of the anaerobic bacteria Fusobacterium necrophorum. Its hallmark is a thrombosis of the ipsilateral jugular vein and is associated with dissemination of abcesses in the throat, chest and mediastinum.

Laboratory Findings

Definitive diagnosis of group A streptococcal pharyngitis can be made by results on culture of exudates from the throat. Rapid streptococcal antigen tests are highly specific but not as sensitive as culture. The American Heart Association has revised its recommendation for throat cultures before antibiotic therapy. Throat cultures are considered “valuable” for children and adolescents and “not as essential” for adults. They are indicated primarily to avoid the unnecessary use of antibiotics for the 70–80% of adult patients with pharyngitis due to virus.

An elevated white cell count (>12,000) suggests bacterial pharyngitis. Obtain a heterophil agglutination test or mononucleosis spot test for patients thought to have infectious mononucleosis. A CBC with differential may also reveal a lymphocytosis with atypical lymphocytes.

Treatment

Treatment of GABHS appears to reduce the duration of symptoms by approximately 1 day when begun in the middle of the illness as is common. Suppurative complications are reduced by antibiotic treatment as in acute rheumatic fever, and there is a trend toward reduction in post-streptococcal glomerulonephritis. Patients with symptoms suggestive of GABHS pharyngitis who have close contact with a documented infection (eg, parents of school-age children) or in high-prevalence areas should be treated without laboratory confirmation, but rapid antigen testing with or without confirmatory culture is warranted in most others.

Cephalosporins are twice as likely to result in clinical and bacteriological cure as oral penicillin. Many antibiotic regimens have been shown to be effective, including oral or intramuscularly penicillin, amoxicillin, cephalosporins, and macrolides. Dexamethasone is beneficial in acute pharyngitis but multiple doses may be required in infectious mononucleosis.

Disposition

Patients with uncomplicated pharyngitis may be discharged home with appropriate supportive therapy and antibiotics, if indicated. Hospitalization with appropriate consultation is indicated for diphtheria, Vincent angina, Lemierre's Syndrome, and epiglottis. Patients with infectious mononucleosis should follow up with their primary-care physician before returning to sports because of the risk of splenic rupture.

Urinary Tract Infections

Acute Lower Urinary Tract Infection (Uncomplicated Cystitis)

Essentials of Diagnosis

• Dysuria
• Frequency and urgency
• Suprapubic pain
• Hematuria
• Pyuria

General Considerations

Uncomplicated bacterial cystitis is defined as a urinary tract infection confined to the bladder. It affects women more commonly than men and tends to recur even in the absence of anatomic abnormalities. Many patients with apparent lower urinary tract infection also have asymptomatic involvement of the upper urinary tract (absence of fever, chills, or flank pain). Children present with cystitis without the complaint of dysuria much more commonly than do adults. Conditions such as vesicoureteral reflux may predispose children to infections, and an aggressive workup to evaluate for these possibilities is required. Prior to age 1 year, the incidence is nearly equal in males and females, but after age 1 year, females are 30 times more likely to develop a urinary tract infection until age 50 years, when men begin developing an increased incidence of these infections.

Most cystitis is caused by bacterial infection, usually E. coli (80%) and other enteric gram-negative bacilli such as Proteus mirabilis, K. pneumoniae, and P. aeruginosa. Gram-positive bacteria such as Streptococcus faecalis, Streptococcus epidermis, and Streptococcus viridans are less common causes. Adenovirus is a common cause of hemorrhagic cystitis in children (typically males) and occasionally young adults.

Clinical Findings

Symptoms and Signs

A history of urinary tract infections is frequently elicited. Dysuria and urinary frequency and urgency are the most common symptoms in adults, although they may be absent in children. Patients may report that their urine is cloudy, smelly, or dark.

Suprapubic discomfort and tenderness are common. Patients are usually afebrile or have a low-grade fever. The presence of high fever (>38.3°C [101°F]) or rigors is inconsistent with a diagnosis of uncomplicated cystitis and suggests pyelonephritis. Nausea and vomiting, though uncommon in adults, are not unusual in children with uncomplicated cystitis.

Neonates may present with poor feeding, vomiting, jaundice, or irritability and may not always have fever. Young children may present with new bed-wetting or loss of bladder training.

Laboratory Findings

Urinalysis

Accurate diagnosis of urinary tract infection depends on obtaining a urine specimen uncontaminated by perineal secretions. The presence of squamous epithelial cells or of mixed flora on Gram-stained smears suggests contamination, and the specimen should be discarded and a better one obtained. Urine should be examined while it is fresh (within 1 hour) or should be refrigerated if delay is expected. Urine should be obtained by catheter or clean-catch specimens only because bagged specimens are usually contaminated.

Chemistry

Mild degrees of proteinuria and hematuria are common on dipstick tests of urine. If the infection is caused by a urea-splitting bacterium (eg, P. mirabilis), urinary pH may be abnormally high (eg, 6–8). The leukocyte esterase and nitrite dipstick tests are a reliable indicators of infection, made even more likely with the positive presence of both. Chemical tests for the presence of bacteria in urine (eg, nitrate reduction) are not sensitive and specific enough to be generally recommended.

Sediment

Many leukocytes and often some erythrocytes are present. Clumps of leukocytes must be differentiated from WBC casts, which signify upper urinary tract involvement. In most cases, numerous bacteria are visible.

Gram-stained smears

Microscopic examination of Gram-stained specimens of urinary sediment from centrifuged urine usually shows bacteria of a single morphologic type. If uncentrifuged urine is examined, and an average of one bacterium is found per oil-immersion field, there is about an 80% probability that there are 105 organisms per milliliter of urine (strongly indicative of infection).

Urine culture

In women of child-bearing age with a history of recurrent cystitis (two to three times per year) who are otherwise healthy, treatment may be started on the basis of urinalysis results alone, and urine culture may be postponed until 1 week after treatment (test-of-cure culture) or may be omitted in patients who respond well to treatment. In all other patients, quantitative urine cultures should be obtained. Growth of at least 105 organisms of a single species per milliliter of urine indicates a high probability of active urinary tract infection.

A urine culture should be ordered for all febrile infants under age 2 years, for children with a history of urinary tract infection, for children who are taking suppressive antibiotic therapy, and for children in whom antibiotic therapy is started regardless of urinalysis results. Smaller numbers (102–104/mL) of bacteria (especially of a single species) are significant and indicate the need for therapy (see the Dysuria–Frequency Syndrome section below).

Treatment

Antimicrobials

Nonpregnant women of child-bearing age who have a history of and findings compatible with uncomplicated cystitis may be given a short course (3 days) of therapy. Single-dose therapy has fallen into disfavor because of the frequency of relapse and because it requires that the patient be seen 2–4 days later for a test-of-cure urine culture. All other patients should receive multidose therapy for at least 7–10 days. Because men often harbor occult infection in the prostate or kidney, some authorities recommend that treatment be extended for at least 3 weeks in an effort to prevent relapse of infection.

Current AAP guidelines recommend treatment for children for 7–14 days with coverage by antibiotics until radiologic studies are completed and urologic referral conducted.

For uncomplicated cystitis, no clear consensus exists on a leading antimicrobial agent for treatment (Table 42–13) Expert data suggests that treatment with trimethoprim/sulfamethoxazole (TMP-SMZ), a fluoroquinolone, nitrofurantoin, or amoxicillin/clavulanate are all effective choices and acceptable treatment. Some authorities suggest that early generation cephalosporins and simple penicillins are less effective than the above. However, as resistance patterns change and specifically E. coli becomes more resistant to fluoroquinolones, one should periodically become familiar with resistance rates in your area to guide TMP-SMZ and ciprofloxacin, because of their good penetration into the prostate and high level of activity against uropathogens, are recommended for men with urinary tract infection who have normal serum creatinine levels.

Adjunctive Measures

Phenazopyridine (Pyridium, many others), 200 mg orally three times a day, may help relieve severe dysuria. The drug should be taken for only 2–3 days. Warn patients that their urine will turn orange.

Follow-Up

In uncomplicated cystitis, follow-up urine cultures are optional in patients who respond to therapy. Patients given single-dose or 3-day therapy and whose symptoms recur should have urine culture and be given a 10-day course of therapy.

Disposition

Infants, children, and men with diagnosed urinary tract infection should receive treatment and be referred to a urologist. Hospitalization is indicated for children younger than age 3 months and for children with dehydration, toxicity, vomiting, or failure of outpatient regimen. Urologic referral is also recommended for women with frequent recurrences of cystitis (monthly) and probably also for those who have had three or more infections in 1 year, although the latter recommendation is controversial. Hospitalization is not indicated for patients with uncomplicated cystitis.

Upper Urinary Tract Infection (Pyelonephritis)

General Considerations

Acute pyelonephritis is a bacterial infection of the kidney. It is invariably an ascending infection from the bladder. It is usually caused by the same organisms that cause cystitis (ie, E. coli, P. mirabilis). In elderly men, pyelonephritis may be caused by Strep. faecalis. In patients who have received prior antimicrobial therapy (eg, during recent hospitalization, because of chronic indwelling Foley catheter) and in nursing home patients, the infecting organisms may be resistant to commonly used antimicrobials. Because of the changes in anatomy, pregnant women are prone to pyelonephritis. Moreover, pyelonephritis in pregnancy is associated with an increased risk of premature delivery. Thus, pregnant patients with urinary tract infection should always receive multidose antimicrobial therapy.

Chronic pyelonephritis is more indolent. About 20% of people with end-stage renal disease have chronic pyelonephritis causing scaring and decreased function. Patients with multiple urinary tract infections need to be followed up closely to prevent this. Emphysematous pyelonephritis is acute pyelonephritis associated with gas in the collecting system; it typically occurs in patients with diabetes. This disease has a 75% mortality rate and is treated with emergency nephrectomy if required.

Clinical Findings

Symptoms and Signs

Pyelonephritis is characterized by symptoms of cystitis (dysuria, urgency, and frequency) accompanied by flank pain and tenderness. Fever, rigors, and, in patients with complicating bacteremia or endotoxemia, systemic signs of sepsis (eg, hypotension, delirium) may be present. In young children, fever is the predominant symptom; only 32% of boys and 40% of girls display dysuria as a symptom, and flank pain is an even less common symptom. In pyelonephritis occurring as a complication of nephrolithiasis, severe flank pain radiating to the groin may be the most prominent symptom.

In patients with sickle cell disease, diabetes, or nephropathy caused by analgesic abuse, necrosis of the renal papillae with sloughing into the ureters occurs as a complication of renal infection, and the patient may present with symptoms of ureteral obstruction that mimic nephrolithiasis.

Laboratory Findings

Urine

The findings on urinalysis, microscopic examination, and culture are the same as in cystitis (see above), except that leukocyte casts (granular casts) occur only with pyelonephritis. Gross hematuria and pain suggest pyelonephritis-complicating urolithiasis. For all patients with suspected pyelonephritis, send urine for culture and susceptibility testing.

Other laboratory studies

Serum electrolyte, BUN, and creatinine measurements should be obtained because azotemia may be present. The white cell count is usually elevated. A normal or low white cell count with a shift to the left in a patient with suspected pyelonephritis is often a sign of sepsis, indicating the need for hospitalization.

X-Ray and Other Findings

Some authorities suggest that excretory urography be performed in all nonpregnant women with pyelonephritis after the infection has cleared. In patients with pyelonephritis in whom urinary obstruction is suspected, radiologic and other examinations should be performed as soon as possible. Ultrasonography is a safe and sensitive means of assessing hydronephrosis and may reveal intrarenal and perinephric abscesses. Remember that in pregnancy, some degree of ureteral dilatation (usually greater in the right ureter than the left) is normal.

Treatment

Antimicrobials

See Table 42–13.

Patients with anatomic abnormalities of the urinary tract or concomitant prostatitis may require up to 6 weeks of therapy. In patients with suspected bacteremia or suspected infection due to antibiotic-resistant organisms, an aminoglycoside should be added.

General Measures

If vomiting or dehydration is present, begin intravenous fluid replacement with crystalloid solutions. Provide analgesia for flank pain if needed. Give antipyretics for high fever regularly (rather than as needed) until the patient is afebrile.

Disposition

Patients who meet the criteria listed below or who have any of the following conditions should be hospitalized:

• Inability to maintain oral hydration or take medications
• Concern about compliance or follow-up
• Diagnostic uncertainty
• Severe illness with high fevers, severe pain, and marked debility
• Comorbid illness (eg, diabetes, renal failure, immunosuppression)
• Failure of outpatient therapy

Patients who are not hospitalized should have a follow-up appointment within 1–2 days to assess their response to therapy.

Some patients with pyelonephritis, especially young women, may not be sick enough for hospitalization but do not appear well enough to go home. For these patients, a 12–24-hour period of intravenous antimicrobial therapy, intravenous hydration, and observation in the emergency department may be indicated. If rapid resolution of signs and symptoms occurs, the patient may be discharged with a prescription for oral antimicrobials and a follow-up appointment in 1–2 days.

Dysuria–Frequency Syndrome

General Considerations

The dysuria–frequency syndrome (urethral syndrome) occurs by definition only in women, usually young women. These patients have symptoms of lower urinary tract infection but have urine cultures that are sterile or contain fewer than 105 organisms per milliliter of urine. Patients with dysuria–frequency syndrome may be divided into two groups: those with accompanying pyuria (> 10 leukocytes per high power field) and those without. In women with pyuria, symptoms are usually due either to a low-grade bacterial cystitis (bacteriuria with <100,000 organisms per milliliter of urine) or to chlamydial urethritis with or without accompanying chlamydial cervicitis. Neisseria gonorrhoeae also causes urethritis. HSV causes urethritis during primary infection and, on occasion, during recurrent infection. In some patients with pyuria and in most patients who lack pyuria, no causative agent can be identified.

Clinical Findings

Symptoms and Signs

The principal symptoms are those of cystitis: dysuria, urgency, and frequency. The dysuria is “internal” dysuria as opposed to the “external” dysuria occurring in vaginitis or genital HSV infection and results from urine coming into contact with denuded skin. Findings on physical examination are normal except that there may be urethral inflammation or mucopurulent cervical discharge and cervical edema in patients whose symptoms are due to gonococcal or chlamydial infection. Pelvic examination is important to diagnose vaginitis, which may also cause dysuria.

Laboratory Findings

The urine may be normal or may contain PMNs with few or no bacteria. Swabs of urethral discharge should be obtained for smear and culture for N. gonorrhoeae in patients with a history of gonorrhea, in those with multiple sexual partners, and in those whose recent sexual partner has had urethritis. Urine culture shows scant growth or no growth of organisms. A cervical swab for Chlamydia antigen (fluorescent or ELISA slide test) is indicated in sexually active women with cervicitis accompanying this syndrome because this organism causes concurrent cervicitis and urethritis.

Treatment

Antimicrobial therapy is usually reserved for patients with pyuria. Tetracyclines and erythromycin are the most effective drugs for suspected chlamydial infection; other bacterial pathogens may be resistant to these drugs. Optimal treatment of chlamydial infection requires 7 days of therapy. Short-course, for example, 3-day therapy, may be tried initially in patients with low-grade bacteriuria. None of the single-dose regimens provides reliable empiric therapy for both chlamydial and bacterial infection.

Disposition

Because of the difficulties of empiric therapy in the urethral syndrome, a follow-up visit to a primary-care physician should be arranged. If ordinary bacterial cultures of urine are sterile in patients with pyuria, the patient's sexual partners should be screened for urethritis and Chlamydia infection.

Diseases of the Female Genitourinary Tract

See also the Sexually Transmitted Diseases section later in this chapter.

Pelvic Inflammatory Disease

Essentials of Diagnosis

• Lower abdominal pain
• Vaginal discharge
• Fever
• Cervical motion tenderness
• Bilateral lower adnexal tenderness

General Considerations

Infection of the uterine tubes may be acute or chronic and unilateral or bilateral. It may lead to pyosalpinx or tubo-ovarian abscess. Pelvic peritonitis is frequently present. Causative agents include Chlamydia trachomatis, N. gonorrhoeae, anaerobic bacteria (which include Bacteroides and gram-positive cocci), facultative gram-negative bacilli (such as E.coli), Mycoplasma hominis, and rarely Actinomyces israelii. Because it is often impossible to differentiate among these agents in individual patients, treatment regimens that are active against the broadest possible range of these pathogens should be used. Risk factors for pelvic inflammatory disease (PID) include young age, multiple sexual partners, intrauterine device insertion, vaginal douching, tobacco smoking, chlamydial or gonococcal infection, and bacterial vaginosis.

Clinical Findings

Symptoms and Signs

Patients are usually young (< age 30 years) and sexually active. Symptoms include fever (sometimes with rigors), severe pelvic pain that may be either continuous or crampy (pelvic pain is usually bilateral and is the most common presenting symptom), dyspareunia, menstrual disturbances, vaginal discharge, and gastrointestinal disturbances (anorexia, nausea and vomiting, constipation). Patients usually are menstruating or just finished their periods (risk of ascending infection is increased secondary to the loss of the cervical mucus plug during menses).

Physical examination in acute cases discloses marked tenderness on manipulation of the cervix and palpation of the adnexa. There is a unilateral tender adnexal mass if tubo-ovarian abscess or pyosalpinx is present. The clinical spectrum in PID includes a gradual progression from subclinical endometritis to salpingitis to pyosalpinx to tubo-ovarian abscess to pelvic peritonitis to perihepatitis. A ruptured tubo-ovarian abscess carries with it a mortality rate of 7% and may require emergency surgery. Table 42–14 presents the physical examination criteria.

Laboratory Tests and Special Examinations

There is usually leukocytosis or an elevated erythrocyte sedimentation rate or C-reactive protein. Obtain a serum pregnancy test. Purulent fluid should be cultured for aerobic and anaerobic pathogens, specifically for N. gonorrhoeae and Chlamydia. Ultrasonography may be helpful in detecting or assessing the size of tubo-ovarian abscess.

Treatment

Antibiotic Therapy

Table 42–15 presents treatment options. No single agent is active against the entire spectrum of pathogens. Several antibiotic combinations provide a broad spectrum of activity against the major pathogens, but none have been adequately evaluated. Treatment with penicillin, ampicillin, amoxicillin, or a cephalosporin alone is not recommended.

Reevaluation

Patients who are not hospitalized should be reevaluated in 2–4 days and hospitalized if their condition has not improved markedly.

Adjunctive Measures

Relieve pain. Narcotics are frequently required. If present, an intrauterine device should be removed as soon as adequate antibiotic levels are achieved in the blood. Surgery should be delayed at least 2–3 days, until the effect of antibiotic therapy can be assessed, even if pyosalpinx or tubo-ovarian abscess is present. Pelvic abscesses often regress with antibiotic therapy alone or may drain externally via the vagina or rectum. Repeated ultrasound examinations help to determine the patient's progress.

Disposition

There is an increasing trend toward the outpatient management of PID. Indications for admission include uncertain diagnosis, pelvic abscess, pregnancy, adolescence, severe illness, failure of outpatient management, inability to arrange follow-up, and HIV-positive status.

Vaginitis

Essentials of Diagnosis

• Abnormal vaginal discharge
• Pruritus, irritation, odor
• Inflamed cervix

General Considerations

Vaginitis is a common and annoying disorder that in the absence of other symptoms or signs rarely indicates serious disease. Common pathogens include Candida albicans, Trichomonas vaginalis, Gardnerella vaginalis with anaerobic bacteria (bacterial vaginosis), and gonococci (in prepubertal girls). Other common causes are estrogen deficiency (atrophic vaginitis) and vaginal foreign body. Systemic antibiotics (especially tetracyclines), oral contraceptives, diabetes mellitus, primary genital HSV infection, and pregnancy predispose to the development of candidiasis. Less common causes include allergy, cervicitis, polyps, tumors, vaginal ulcer, shigellosis, irradiation for cancer, and certain bubble bath preparations.

Clinical Findings

Symptoms and Signs

Vaginal discharge and pruritus are the chief symptoms. Vaginal discharge with varying degrees of inflammation of the vaginal wall (minimal in atrophic vaginitis) is usually found. Search for foreign bodies in the vagina, particularly in young girls, and examine for associated disorders (eg, salpingitis).

Laboratory Findings

Examination of smears

Gram stain

Look for Candida and Gardnerellavaginitis (small gram-negative rods usually adherent to epithelial cells; “clue cells”). Methylene blue stain also demonstrates clue cells. Vaginitis due to Candida or Trichomonas is usually associated with a PMN exudate, whereas inflammatory cells are absent in bacterial vaginosis caused by G. vaginalis. In prepubertal girls with gonococcal vulvovaginitis, Gram stain of smears usually shows typical gram-negative intracellular diplococci, but cultures should be performed to confirm the diagnosis.

Saline wet mount

Look for motile trichomonads. Candida and clue cells of G. vaginalis may also be seen.

Potassium hydroxide wet mount

Addition of a few drops of potassium hydroxide to a sample of vaginal secretions releases a typical amine odor (fishy) in cases of bacterial vaginosis due to G. vaginalis. Microscopic examination reveals Candida in cases of Candida vaginitis, but Gram staining is more sensitive and specific.

Urinalysis

Obtain a clean-catch urine specimen for analysis and culture if dysuria is present.

Other tests

Obtain fasting blood glucose measurement in cases of recurrent candidiasis, to rule out diabetes mellitus.

Treatment

General Measures

Advise patients to avoid intercourse for a few days after treatment. Partners also should receive treatment, as described below.

Specific Measures

C. albicans vaginitis

Imidazole regimens

Virtually all azole intravaginal regimens are effective for candidal vaginitis. (1) Miconazole nitrate (vaginal suppositories, 200 mg) or clotrimazole (vaginal suppositories, 200 mg), intravaginally at bedtime for 3 days, or (2) butoconazole (2% cream, 5 g), intravaginally at bedtime for 3 days, or (3) terconazole, 80 mg suppository or 0.4% cream, intravaginally at bedtime for 3 days. (2) Fluconazole 150mg PO single dose.

Reinfection

The male partner should wear a condom, or both partners should abstain from intercourse for 2–3 days. Balanitis due to Candida occurs almost exclusively in uncircumcised men. Occasionally the patient's gastrointestinal tract is a reservoir for Candida, in which case oral nonabsorbable antifungal preparations (eg, nystatin) are necessary.

T. vaginalis vaginitis

Give the patient and her sexual partner metronidazole, 2 g orally in a single dose (eight 250-mg tablets). This regimen is curative in about 95% of cases. An alternative regimen involves metronidazole, 500 mg orally three times daily for 7 days. Resistance of T. vaginalis to metronidazole has been observed but is rare. Timidazole 2 g and azithromycin 1 g orally can also be used. If treatment fails, the patient should receive the same treatment regimen again.

Bacterial vaginosis

Several species of vaginal bacteria (including G. vaginalis) interact to produce this syndrome. Some evidence supports the efficacy of intravaginal lactobacillus treatment in low-risk patients. Metronidazole, 500 mg orally two times daily for 7 days, is an effective treatment. Warn the patient about side effects. Clindamycin, 300 mg orally twice daily for 7 days, may be used in pregnant patients. Treatment of pregnant women with BV continues to be debated but current ACOG guidelines do not support routine treatment of normal, low-risk pregnancies. In pregnancy, treatment should be confined to oral therapy only. Treatment of male sexual partners does not reduce the risk of recurrence of bacterial vaginosis in the index case.

Atrophic vaginitis

Prescribe estrogen suppositories or creams. Diethylstilbestrol, one 0.5-mg vaginal suppository every 3 days for 3 weeks, followed by 1 week without treatment, may be tried.

Gonococcal vaginitis

See the Gonorrhea section below.

Disposition

Patients should have a follow-up appointment with a gynecologist or primary-care physician in 7–10 days so that the results of treatment can be assessed and follow-up cultures obtained.

Genital Abscesses

Essentials of Diagnosis

• Labial pain, swelling
• Fluctuant lesion

General Considerations

Vulvar abscesses may rise in a sebaceous gland or Bartholin gland (Bartholin cyst). Skene glands, adjacent to the urethra, may also be the site of abscess formation. N. gonorrhoeae is responsible for some vulvar abscesses; the remainder are caused by a variety of bacteria, often in mixed culture.

Clinical Findings

The patient complains of tender swelling of the labia majora that is confirmed by examination. Gram stain and culture of pus from the abscess help to identify the causative organism. Endocervical culture for N. gonorrhoeae should be performed, if possible.

Treatment

Nonfluctuant Lesions

If lesions are not fluctuant, incision and drainage are not indicated. If gonorrhea is suspected, give ceftriaxone, 250 mg intramuscularly. In addition, give a broad-spectrum antibiotic such as amoxicillin–clavulanate, 500 mg three times daily. Prescribe sitz baths and application of warm compresses. Ask the patient to return in 1–2 days for reevaluation of the need for incision and drainage.

Fluctuant Lesions

When drainage is performed, pack the abscess or place a Word catheter. Administer antimicrobials as described above. Have the patient return in 2–3 days.

Disposition

Gynecologic follow-up is mandatory because surgery may be necessary. Occasionally marsupialization may be performed at the time of diagnosis of acute bartholinitis.

Mucopurulent Cervicitis

Essentials of Diagnosis

• Vaginal discharge
• Pruritus
• Cervical exudate

General Considerations

The presence of mucopurulent endocervical exudates strongly suggests cervicitis due to chlamydial or gonococcal infection.

Clinical Findings

Symptoms and Signs

Vaginal discharge and pruritus may be present. Mucopurulent endocervical exudate may be observed.

Laboratory Findings

PCR test

The current gold standard and mainstay of both chlamydial and gonococcal diagnosis is PCR obtained from endocervical and vaginal swabs. This test is both highly sensitive and specific when appropriate samples are obtained. In most cases results will require 48 hours to obtain, and thus empiric treatment usually takes place if clinically indicated.

Swab test

Mucopurulent secretion from the endocervix may appear yellow or green when viewed on a white cotton-tipped swab. Cervicitis is present if bleeding occurs when the first swab culture for gonococci is taken or if erythema or edema is present within a zone of cervical ectopy.

Slide test

Fluorescent antibody or ELISA slide test should be used to diagnose Chlamydia.

Gram stain

Gram-stained smears of endocervical secretions show greater than 10 PMNs per microscopic oil-immersion field. The presence of gram-negative, diplococci suggests infection with N. gonorrhoeae, but this is not diagnostic. Culture is necessary to confirm infection with N. gonorrhoeae.

Treatment

Empiric treatment with ceftriaxone 250 mg intramuscularly or cefixime 400 mg PO or plus azithromycin 1 g PO or doxycycline 100 mg PO b.i.d. for 7 days.

Diseases of the Male Genitourinary Tract

Acute Bacterial Prostatitis

Essentials of Diagnosis

• Fever
• Low back pain
• Dysuria
• Urgency
• Prostatic tenderness

Clinical Findings

Symptoms and Signs

Patients with acute bacterial prostatitis often have chills, fever, low back and perineal pain or pressure, malaise, dysuria, urgency, and difficulty voiding or decreased urinary stream. Recurring attacks of acute prostatitis are common. Urethral discharge may be present if prostatitis is secondary to urethritis (uncommon). The prostate is tender and enlarged. Prostatic abscess should be suspected when localized prostatic tenderness, swelling, or fluctuance is present. Prostatic massage is contraindicated in severe, acute prostatitis because it may induce bacteremia. A simple rectal examination may be performed, however. Prostatitis is the most common urologic diagnosis in men over age 50 years; as many as 50% of men are affected in their lifetime. Consider N. gonorrhea and C. trachomatis in males younger than 35 years with prostatitis.

Laboratory Findings

When acute bacterial prostatitis is suspected based on the patient's symptoms and physical examination, presumptive diagnosis may be made based on the results of urinalysis and urine Gram stain and culture. The bacterial pathogen found in the urine will usually be the same as that infecting the prostate. The presence of bacteria should be confirmed by culture and susceptibility testing. Leukocytosis is common. Azotemia suggests obstructive uropathy. Obtain blood cultures for all patients who have high fever or rigors.

Treatment

Antimicrobials

Fluoroquinolones are the first-line agents of choice for outpatient therapy. For patients under age 35 years, give ofloxacin 400 mg PO X1 then 300 mg PO b.i.d. for a 28-day course. An alternative regimen is ceftriaxone 250 mg intramuscularly followed by doxycycline 100 mg PO b.i.d. for 10–14 days. For those over age 35, give ciprofloxacin 500 mg PO b.i.d. for 28 days. An alternative is TMP-SMZ one double strength tablet b.i.d. for 28 days.

Enterococcal prostatitis may require inpatient treatment with intravenous ampicillin and gentamicin. Other inpatient regimens include TMP-SMZ intravenously in two divided doses or an aminoglycoside. Although there is no US consensus on treatment, European consensus statements advocate late generation cephalosporins plus gentamycin for inpatient parenteral treatment. Other regimens include stand-alone aminoglycoside and TMP-SMZ regimens. The addition of ampicillin may be warranted if enterococcal species are suspected.

Adjunctive Measures

Analgesics (often including a narcotic) should be provided. Hot sitz baths may provide relief. Bed rest is usually helpful. α-1-Blockers may be useful to decrease pain and recurrence rates.

Disposition

Patients with acute bacterial prostatitis causing systemic symptoms (high fever, rigors) or with suspected prostatic abscess should be hospitalized for treatment with parenteral antibiotics and consultation with a urologist.

Patients who are not hospitalized should return for follow-up in 3–4 days to ensure that recovery is progressing and again 7–10 days after stopping antimicrobial therapy for a test-of-cure culture of expressed prostatic secretions or of urine. Refer the patient to a urologist or to a source of regular medical care.

Acute Epididymitis

Essentials of Diagnosis

• Testicular pain
• Epididymal tenderness

General Conditions

Epididymitis usually results from retrograde spread of urethral or urinary tract infection into the epididymis. Epididymitis is therefore usually caused by the same pathogens causing urethritis (eg, gonococci, Chlamydia) or urinary tract infection (eg, E. coli). The former pathogens are found more commonly in men younger than 35 years, and E. coli is seen more often in men over age 35 years.

Clinical Findings

Symptoms and Signs

Pain and tenderness of the epididymis is present on one or both sides. Epididymitis must be differentiated from testicular torsion and from torsion of the testicular appendage. Ultrasound with Doppler flow will demonstrate an increased flow in epididymitis and a decreased or absence of flow in testicular torsion. In orchitis the testicle is diffusely and tensely swollen, warm, firm, and tender.

Urethritis or urinary tract infection usually coexists with epididymitis, and evidence of these conditions must be sought with appropriate laboratory tests. At a minimum, Gram or methylene blue stain of urethral exudates (or swab of material in the anterior urethra if no exudates can be obtained) and a clean-voided midstream urine specimen should be obtained for analysis.

Treatment

Antimicrobials

Epididymitis with urinary tract infection

Give TMP-SMZ for 10 days. This regimen may be added onto that below if clinical concern exists for sexually transmitted infection (STI).

Epididymitis in sexually active heterosexual men younger than age 35 years

Regardless of whether N. gonorrhoeae is demonstrated, the (CDC) recommends treatment for gonorrhea and Chlamydia. Administer ceftriaxone 250 mg intramuscularly followed by doxycycline 100mg or tetracycline for 10 days. Levofloxacin 500mg daily for 10 days is an alternative.

Epididymitis in sexually active heterosexual men older than age 35 years

Empiric therapy with ciprofloxacin 500 mg PO b.i.d. 10 days or levofloxacin 500 mg daily for 10 days is recommended. TMP-SMZ double strength for 14 days is an alternative. Again, if any concern for STI exists, treat concurrently with ceftriaxone and doxycycline.

Adjunctive Measures

Prescribe analgesics as needed. Hot sitz baths may be helpful. Bed rest and scrotal elevation for 1–2 days will provide symptomatic relief. If the patient must be ambulatory, an athletic supporter may be helpful.

Disposition

Refer the patient to a urologist or primary-care physician within a few days. Hospitalization is indicated for orchitis that does not respond within 48 hours to oral therapy and adjunctive measures.

Sexually Transmitted Diseases

The management of all sexually transmitted diseases should include counseling regarding safe sex practices and the performance of HIV antibody test in consenting patients.

Gonorrhea

N. gonorrhoeae causes primary genitourinary tract infections, localized infections, and the disseminated arthritis–dermatitis syndrome. Approximately 600,000 new cases are diagnosed each year.

Clinical Findings

Symptoms and Signs

In men, gonococcal urethritis is characterized by acute onset of dysuria, sometimes with hematuria, and a copious creamy urethral discharge. Less profuse urethral discharge requiring milking of the penile urethra may also occur. Local extension of infection may produce inflammation of preputial glands, epididymitis, seminal vasculitis, and prostatitis.

In women, gonococcal cervicitis may be asymptomatic or patients may present with vaginal discharge or symptoms of accompanying urethritis (eg, dysuria, frequency). Occasionally a Bartholin gland abscess is the initial complaint. Patients with gonococcal salpingitis complain of lower abdominal pain (unilateral or bilateral), vaginal discharge, and metromenorrhagia. Pain on cervical motion and adnexal tenderness are usual; nausea and vomiting and marked abdominal tenderness or rebound suggest pelvic peritonitis.

Rectal infection with N. gonorrhoeae is usually asymptomatic, although patients occasionally present with proctitis (rectal pain, discharge, tenesmus, and constipation). Pharyngeal infection is almost always asymptomatic.

Patients with gonococcal conjunctivitis present with marked conjunctival erythema and purulent discharge, often unilateral. In adults, it usually follows contact between contaminated fingers and the eye.

Laboratory Findings

In men, obtain a Gram-stained smear of urethral discharge, examine it microscopically, and obtain culture and antimicrobial susceptibility testing. The presence of leukocytes (usually PMNs) and intracellular gram-negative diplococci on the smear is more than 99% specific for gonorrhea. A smear showing only PMNs with no gram-negative diplococci is a predictor of a negative gonococcal culture in over 90% of patients, although culture for gonorrhea is generally recommended. These patients should receive treatment for nongonococcal urethritis. Culture of the pharynx and rectum is necessary if there is a history of oral or receptive rectal intercourse because negative results on Gram-stained smears from these areas do not rule out gonorrhea.

In women, findings on Gram-stained smears of cervical secretions may suggest gonorrhea (PMNs with intracellular gram-negative diplococci), but culture should be performed to confirm the diagnosis. Culture of rectal secretions is recommended in all women because sometimes it is the only site yielding positive cultures.

Culture of pharyngeal secretions is necessary in patients with a history of oral sexual intercourse. Express the exudates in purulent conjunctivitis, and examine a Gram-stained smear. Gram-negative diplococci confirm a diagnosis of gonococcal conjunctivitis. Send a sample of the exudates for culture.

Culture on Thayer–Martin media remains the gold standard for diagnosis. The Gonorrhea PCR test is 97–99% sensitive, with specificity of 99%. A serologic test for syphilis (eg, VDRL) should be ordered for all patients.

Treatment

Because there has been worldwide spread of strains of N. gonorrhoeae that are resistant to penicillin, amoxicillin, tetracycline, and fluoroquinolones, these agents are no longer recommended for empiric treatment of gonococcal infections. Use ceftriaxone, 125 mg intramuscularly. Alternative treatment includes cefotaxime 500 mg intramuscularly. In the β-lactam allergic patient, fluoroquinolone therapy can be used but sensitivity of the patient's strain to quinolones must be evaluated and test of cure obtained, or azithromycin 2 g single dose can be considered. Because of the high frequency of coexisting chlamydial infection (up to 45%), a tetracycline, doxycycline, or azithromycin regimen should follow the treatment of gonococcal infections.

Patients with gonococcal conjunctivitis may be hospitalized and should receive ophthalmologic consultation. Therapy consists of ceftriaxone, 1 g intramuscularly or intravenously once daily for at least 5 days, combined with immediate and at least hourly irrigation of the eye with saline or buffered ophthalmic solutions. Simultaneous ophthalmic infection with C. trachomatis can also occur. Careful ophthalmic follow-up is necessary to prevent ocular complications.

Disposition

Hospitalization is not required for patients with localized gonococcal infection, except for gonococcal conjunctivitis. Sexual partners with gonorrhea must be notified and receive treatment. Cases of gonorrhea must be reported to the local public health department.

Nongonococcal Urethritis (Nonspecific Urethritis)

Nongonococcal urethritis, or nonspecific urethritis, is due to infection with C. trachomatis in over half the cases. Genital Mycoplasmas (Ureaplasma), HSV, and Trichomonas are occasional causes.

Clinical Findings

Symptoms and Signs

Most male patients have urethral discharge and dysuria. Symptoms are often insidious in onset, with urethral discharge that is scanty, mucoid, watery, and most prominent in the morning. Women may be asymptomatic or may complain of dysuria or frequency. Infection may involve the cervix as well and extend to the oviducts, producing low-grade fever.

Laboratory Findings

Urethral discharge should be stained with Gram stain and examined microscopically. The presence of more than four leukocytes per high-power field confirms the diagnosis of urethritis. If no organisms morphologically consistent with gonococci are found, then presumptive diagnosis of nongonococcal urethritis can be made. A Gram-stained smear with findings diagnostic of gonorrhea does not exclude nongonococcal urethritis because dual infection with Chlamydia and the gonococcus is common, particularly in a heterosexual population. The specimen should be sent for culture but because of difficulties in culturing this organism, culture is 80% sensitive. PCR testing is the most sensitive (93–99%), with specificity of 99–100%. A serologic test for syphilis should also be considered.

Treatment

First-line agents recommended by the CDC include single-dose azithromycin or a 7-day course of doxycycline or levofloxacin 500 mg PO for 7 days. If nongonococcal urethritis is suspected (negative or equivocal findings on Gram-stained smear with culture results pending) or documented (culture negative for nongonococcal urethritis), sexual partners should also receive treatment.

Disposition

Patients with nongonococcal urethritis can receive treatment on an outpatient basis.

Genital Herpes Simplex Virus Infection

Essentials of Diagnosis

• Fever, adenopathy
• Vesicles on an erythematous base
• Pain

General Considerations

HSV is a major cause of recurrent genital lesions. The initial (primary) infection is the most severe, although it is sometimes asymptomatic. After the primary lesion has healed, the virus remains latent in the paraspinous ganglia, where it periodically causes reactivation of infection. Genital infection is usually caused by HSV type 2, and about 99% of patients with recurrent disease will be infected by type 2 virus. Spread of infection is almost exclusively by sexual intercourse.

Clinical Findings

Symptoms and Signs

First clinical episode of genital HSV

The first clinical attack of HSV is usually the most severe. Patients may present with fever, malaise, myalgias, and arthralgias. Aseptic meningitis occurs in 10–20% of cases, particularly in women. Associated symptoms may include dysuria, dyspareunia, and urinary retention. Successive crops of grouped vesicles on an erythematous base denude, form ulcers, and heal by secondary intention, usually in 2–3 weeks but sometimes not until after 6 weeks. Genital edema is common. Local pain and regional adenopathy are usually marked. In men, the glans and penile shaft are involved. In women, the vulva, vagina, and cervix are the usual sites of involvement. Male or female patients with herpetic proctitis present with fever, tenesmus, constipation, and rectal pain.

Recurrent HSV episodes

Recurrent infection is common and may be triggered by a variety of stimuli (eg, friction, menstruation, sexual intercourse, pregnancy, or stress). Recurrent attacks are frequently heralded by a prodrome consisting of local itching, pain, or aching in the buttocks or leg. Initially, a papule develops that rapidly vesiculates, breaks down into an ulcer, and then heals, usually within 7–10 days. The virus may be recovered as long as lesions are moist. Patients should avoid direct skin-to-skin contact until the area is completely dried and healed.

The presence of HSV may be confirmed by the Tzanck test (about 60% sensitivity and 80% specificity) or virus culture. Virus culture is recommended in most cases.

Treatment

Antipyretics and analgesics may help to relieve systemic symptoms. Antiviral regimens (Table 42–16) accelerate resolution of the signs and symptoms of herpetic eruptions but do not affect the subsequent risk, frequency, or severity of recurrences after the drug is discontinued. Immunocompromised patients (especially AIDS patients) with extensive, ulcerative, or progressive mucocutaneous herpes should receive oral therapy. Continuous therapy is necessary in some patients.

Hospitalization for intravenous therapy may be warranted if the patient is unable to take medications orally or if the lesions are extensive. Antibiotics are not necessary unless Gram-stained smears suggest bacterial superinfection. Women with primary genital herpes frequently have associated Candida vaginitis, which should be treated as described above. The patient should bathe the exposed affected areas with warm tap water, or apply warm compresses every 4 hours. Because lesions shed infectious virus, patients should avoid manipulating lesions with their bare hands and should wash their hands after exposure (autoinoculation of the eye or other sites may occur). Any other contact with the lesions (eg, sexual) should be avoided until they have healed.

Disposition

Hospitalization is occasionally indicated for patients with primary HSV infection because of severe pain, systemic symptoms, and other complications (urinary retention, obstipation, aseptic meningitis, dehydration). Hospitalization is also required for patients with extensive, large, or rapidly progressive lesions.

Patients with genital HSV infection are often frightened and confused about the nature and transmission of the disease and may suffer both physically and psychologically. Counseling should be initiated and provided in the emergency department, if possible, and patients should be referred to a gynecologist or primary-care provider who is experienced in treating HSV infection and can explain the disease, answer any questions, and provide information on various methods of treatment so that the patient can make an informed evaluation of the associated efficacy, risks, and side effects. Obtain obstetric consultation for pregnant patients with HSV infection.

Syphilis

Essentials of Diagnosis

• Chancre (painless)
• Rash
• Positive VDRL, RPR, FTA-ABS

General Considerations

Disease following infection due to Treponema pallidum may be divided into primary, secondary, latent, and tertiary stages. Infection with T. pallidum has been identified as an important risk factor for HIV infection. An HIV antibody test should be obtained for all consenting patients with syphilis.

Clinical Findings

Symptoms and Signs

Primary stage

A chancre develops at the site of entry of the spirochete between 10 days and 6 weeks after exposure. The ulcer, located on the genitals or occasionally on extragenital sites (finger, mouth), is nontender and has a depressed center and rolled, pearly edges. Associated inguinal adenopathy, if present, is usually firm, hard, and nontender.

Secondary stage

Secondary disease develops about 4 weeks after the appearance of the chancre. Clinical manifestations reflect the presence of spirochetes in the bloodstream. Most common is a rash that ranges from macular to maculopapular to plaques (condyloma lata). The rash is generally distributed over the thorax, abdomen, and extremities; it may involve the palms and soles; and it is nonpruritic. Associated findings may include low-grade fever, generalized lymphadenopathy, hepatitis, meningitis, alopecia, and weight loss.

Latent stage

A positive serologic test is the only sign, and this stage may last from 1 to 2 months up to more than 20 years.

Tertiary stage

This stage is characterized by destructive lesions of the aorta, CNS, skeletal structures, and skin.

Laboratory Findings

The diagnosis of infectious syphilis is confirmed by serologic testing or by positive results on microscopic darkfield examination of scrapings from the chancre or lesions of secondary disease. Obtain blood for serologic testing (eg, VDRL or RPR); if results are positive, perform a treponemal antibody test (eg, FTA-ABS or MHA-TP).

Treatment

Infectious Syphilis

Benzathine penicillin G

The treatment of choice is benzathine penicillin G (2.4 million units intramuscularly). Patients who claim to be allergic to penicillin should be tested (ie, skin testing) and desensitized, if necessary.

Doxycycline

An alternative regimen for penicillin-allergic patients is doxycycline, 100 mg orally twice daily, or tetracycline, 500 mg four times daily for 14 days.

Erythromycin

Patients who cannot take penicillin, doxycycline, or tetracycline and who are reliable and can be followed closely can take erythromycin, 500 mg orally four times daily for 14 days.

Jarisch–Herxheimer Reaction

Aspirin or acetaminophen may be prescribed for the Jarisch–Herxheimer reaction that commonly occurs within a few hours after treatment of secondary syphilis has been started. The reaction is characterized by malaise, fever, faintness, and intensification of the rash. Patients with secondary syphilis who are released from the emergency department following penicillin therapy should be warned about the symptoms of the reaction and should be told that it is not due to penicillin allergy.

Syphilis in HIV-Infected Patients

A lumbar puncture should be performed in HIV-infected patients with early syphilis because of increased risk of treatment failure and CNS relapse. If the CSF cell count is normal and the VDRL test nonreactive, give one to three doses of benzathine penicillin G therapy. Serum VDRL testing must be repeated at monthly intervals for at least 3 months. Tetracyclines are probably inadequate therapy for HIV-infected patients with syphilis. Ceftriaxone, 250 mg intramuscularly once daily for 10 days, can be tried.

Disposition

Patients may receive treatment on an outpatient basis. Cases of syphilis must be reported to the local public health department. Sexual partners of patients should be notified and receive treatment. Arrangements must be made for follow-up serologic testing.

Chancroid

Essentials of Diagnosis

• Erythematous pustule
• Adenopathy
• Pain
• Gram stain or culture

General Considerations

Chancroid is an ulcerating genital infection caused by Haemophilus ducreyi. It is common in tropical and subtropical regions and is believed to be underdiagnosed in the United States.

Clinical Findings

Chancroid is manifested by the appearance of a small pustule that rapidly ulcerates with an irregular and purulent exudative base that is painful. It is associated with tender inguinal lymphadenopathy in 50% of cases.

Definitive diagnosis requires growth on culture media, and the diagnosis should be considered for any patient who has painful genital ulceration and for whom darkfield fluoroscopy and HSV testing are negative.

Treatment

Recommended treatments include azithromycin orally or ceftriaxone intramuscularly; ciprofloxacin and erythromycin are alternatives.

Trichomoniasis

Clinical Findings

Symptoms and Signs

Most men with T. vaginalis infections develop nongonococcal urethritis, but women typically develop malodorous yellow–green frothy discharge, dysuria, dyspareunia, vulvar irritation, and pruritus.

Laboratory Findings

Motile parasites are seen on a wet-mount smear.

Treatment

Single-dose metronidazole or metronidazole therapy for 7 days is the only treatment option. No effective alternatives are available. While some intravaginal dosing regimens have been identified, therapy in pregnant women should be confined to the PO route.

Skin and Soft Tissue Infections

Superficial Soft Tissue Infections

General Considerations

Initial evaluation of soft tissue infections should focus on three factors: (1) what is the probable organism; (2) what is the depth of infection; and (3) is the infection life- or limb-threatening? Most infections are caused by gram-positive organisms, particularly Staphylococcus pyogenes and Staph. aureus. Although most infections are benign, complicating factors such as comorbid conditions (diabetes, HIV), high-risk areas (face, hands, perineum), or signs of deep-tissue involvement should prompt more aggressive interventions, including possible surgical consultation in the case of deep-tissue involvement.

Clinical Findings

Symptoms and Signs

Impetigo

Impetigo is a superficial infection most commonly seen in children and may manifest in bullous and nonbullous forms. Nonbullous impetigo begins as vesicles that rupture and form a golden-yellow, “honey-crusted” purulent discharge. Bullous impetigo results from toxin formation and begins as a small vesicle that rapidly enlarges to a bulla. Lesions are painless and systemic symptoms are rare.

Ecthyma

Ecthyma is a slightly deeper form of impetigo with resultant scarring and ulceration.

Staphylococcal scalded skin syndrome (SSSS)

SSSS is a toxin-mediated disease resulting in widespread bulla formation and exfoliation, often in the extremities. Children are affected more commonly than adults.

Erysipelas

Erysipelas is an acute inflammation of the superficial layers of skin particularly involving cutaneous lymphatics. It most often occurs on the face and results in fiery red, edematous lesion that is raised and clearly demarcated from the surrounding tissue. Lymphangitis and lymphadenopathy are common, as are systemic symptoms such as fever and chills. Approximately 10% of cases will progress to involve deeper soft tissue layers.

Cellulitis

Cellulitis is an infection of the lower dermis and subcutaneous tissue that is characterized by an ill-defined erythema, swelling, warmth, and pain. Systemic symptoms are common in more severe cases. Diabetes and peripheral vascular disease places the patient at higher risk for infection with gram-negative organisms and anaerobes.

Laboratory Findings

Laboratory studies are of little utility in uncomplicated cases. Blood cultures are rarely positive but should be obtained in rapidly progressive or otherwise severe infection. Gram stain and culture of material from the leading edge of the lesion or vesicles may be helpful in rare cases.

Treatment

Impetigo and Ecthyma

Topical treatment with warm soaks to remove crusting and mupirocin is effective for most cases. Oral anti-staphylococcal agents should be considered in bullous impetigo.

Staphylococcal Scalded Skin Syndrome

Oral antistaphylococcal agents and a meticulous search for the initiating infection with appropriate treatment are necessary. Cool saline compresses and local wound care as needed should be applied to desquamated areas. Corticosteroids are not beneficial.

Erysipelas

Penicillin remains the first-line treatment of uncomplicated erysipelas. In the presence of lymphedema or chronic venous insufficiency, a first-generation cephalosporin, clindamycin, or macrolide may be used.

Cellulitis

Mild cases may be treated with oral agents such as a first-generation cephalosporin, dicloxacillin or clindamycin. More severe infection thought to be due to streptococci or staphylococci in patients who are not critically ill may be treated with intravenous first-generation cephalosporin, nafcillin. Addition of an aminoglycoside should be considered when gram-negative bacteria are suspected. Immobilization and elevation of the affected extremity are helpful.

Disposition

Patients with early, mild disease may be discharged home on oral antibiotics. Nontoxic patients with cellulitis that has progressed over 12–24 hours may be given parental therapy and discharged with follow-up within 24 hours. Failure to respond to outpatient therapy, cellulitis of the face or hand, and complicating factors such as diabetes, venous/lymphatic insufficiency, or systemic toxicity may require inpatient treatment.

Community-Acquired MRSA

General Considerations

A growing number of skin and soft tissue infections are caused by a strain of MRSA that appears to be clinically and epidemiologically distinct from that traditionally associated with nosocomial infection. Unlike health care associated MRSA, CAMRSA is commonly resistant only to β-lactams. CAMRSA isolates often produce a Panton-Valentine leukocidin toxin, which is associated with soft tissue infections and a severe necrotizing pneumonia. Populations at higher risk for CA-MRSA infection include children (particularly in day-care centers), soldiers, prisoners, intravenous drug users, homeless persons, and men who have sex with men. The apparent common demographic feature seems to center around increased population density.

Clinical Findings

Recurrent furunculosis and cutaneous abscesses are the most common presentation of CA-MRSA infection, with dermonecrotic lesions occasionally present. Recurrent furunculosis and transmission to close contacts such as family members or sports teammates are also suggestive of CAMRSA. CA-MRSA pneumonia, although rare, may occur following influenza.

Treatment

Surgical drainage of any abscesses should be performed. For those in whom outpatient treatment is appropriate, TMP-SMZ, doxycycline, minocycline, and clindamycin are all appropriate agents. However, treatment failure may result from inducible clindamycin resistance. If infection with β-hemolytic streptococci is considered likely, cephalexin may be added. Hospitalized patients may be treated with vancomycin or linezolid.

Deep Soft Tissue Infections

Deep soft tissue infections, characterized by involvement of subcutaneous tissues with possible extension to the muscles and fascial planes, are uncommon and often difficult to diagnose. Various classification systems have been used to help delineate various microbiologic or anatomic features of the infection; however, the utility of these systems in the emergency department is limited. Instead, a uniform approach to all patients with necrotizing soft tissue infections (NSTIs) may help minimize misdiagnosis and ensure timely treatment.

General Considerations

NSTIs are usually associated with introduction of pathogenic organisms through minor trauma, insect bites, or surgical incision. “Skin popping” by intravenous drug users is a significant risk factor. Spontaneous infections are most likely to occur in the perineum (Fournier gangrene). Most infections are polymicrobial and GABHS are frequently present, rarely as the only organism isolated. Rapidly progressive surgical infections in the first 24 hours postoperatively frequently harbor Clostridium species as well. Chronic illnesses such as diabetes, renal insufficiency, and alcoholism are commonly present, although up to 30% of cases occur in otherwise healthy individuals.

Clinical Findings

Symptoms and Signs

NSTIs may occur anywhere on the body, with the perineum and extremities most frequently involved. Early physical findings may be minimal and include cellulitis or a small ulcer with erythema, warmth, and edema in overlying skin, skin anesthesia, and pain out of proportion to examination findings. Later findings include tense edema with bronze discoloration of the skin progressing to hemorrhagic bullae and a seropurulent (“dishwater pus”), foul-smelling exudate. Crepitus is common with clostridial infections but may be absent in GABHS infections. As the disease progresses, patients may become septic with tachycardia, hyperthermia, and hypotension, with 10% of patients with massive GABHS meeting the criteria for streptococcal toxic shock syndrome (STSS). Key early findings include tachycardia and fever out of proportion to the apparent extent of the skin lesion and tenderness that extends well beyond the lesion.

Laboratory Findings

Common laboratory abnormalities include leukocytosis, hyponatremia, azotemia, and hypocalcemia. Radiographic imaging may confirm the presence of subcutaneous emphysema on plain films, but this finding is absent 50% of the time and a negative result does not rule out the diagnosis. CT scanning may show asymmetric thickening or stranding of fascial planes and is more useful for suspected perineal NSTIs. Needle aspiration with gram staining may also be useful in equivocal cases.

Treatment

Aggressive resuscitation with fluids and broad-spectrum antibiotic coverage should be initiated early when a NSTI is suspected. Triple coverage with a penicillin, clindamycin or metronidazole, and an aminoglycoside is appropriate pending the results of cultures. Prompt surgical debridement is imperative and appropriate surgical consultation should be obtained as soon as possible.

Disposition

All patients with NSTIs should be admitted for surgical exploration and debridement, followed by hospitalization in an intensive care setting.

Acute Meningococcemia

Essentials of Diagnosis

• Fever
• Petechial rash
• Hypotension
• Shock

Clinical Findings

Symptoms and Signs

Invasive meningococcal disease is often associated with a recent or current upper respiratory infection and is most common in infants, with a second peak around 18 years of age. Meningococcemia may present as meningitis, sepsis, pneumonia, epiglottitis, conjunctivitis, pericarditis, or arthritis, although meningitis and sepsis are the most common and rapid progression is typical. Overcrowding, smoking, and complement deficiencies are risk factors for invasive disease. Mucosal petechiae may appear first, followed by skin petechiae that may become confluent as microvascular thrombosis progresses. However, petechiae may be absent in up to 20% of children with meningococcemia. Peripheral circulatory failure is common in meningococcal sepsis, and ventricular dysfunction with elevated CVP is also seen in severe disease. Waterhouse-Friderichsen syndrome results from adrenal hemorrhage with resultant corticosteroid deficiency and causes circulatory collapse.

Laboratory Findings

Routine laboratory studies should be obtained, including blood cultures and CSF studies, if septic shock or coagulopathy does not preclude lumbar puncture. Evaluation for DIC (PT, INR, PTT, fibrinogen, and fibrin degradation products) should also be performed. CSF antigen detection is no more sensitive than microscopy and culture. PCR is the gold standard of diagnosis and does not require that the meningococci be alive at the time material is collected. Although it is preferable to obtain material for culture prior to the administration of antibiotics, antibiotics should not be unduly delayed.

Treatment

Empiric treatment with ceftriaxone or cefotaxime should be instituted as soon as possible when the diagnosis is seriously entertained, along with EGDT for severe sepsis or septic shock as indicated. Steroids are indicated for the treatment of adrenal insufficiency, and dexamethasone should be given in meningococcal meningitis. Chemoprophylaxis of close contacts of those with invasive disease (including health-care workers directly involved in their care) may be accomplished with rifampin, ciprofloxacin, or ceftriaxone.

Disposition

All patients with invasive meningococcal disease should be hospitalized, preferably in an intensive care setting.

Rocky Mountain Spotted Fever

Essentials of Diagnosis

• Fever
• Headache
• Petechial rash (palms or soles)

General Considerations

Rocky mountain spotted fever (RMSF) is an acute febrile tick-borne illness caused by Rickettsia rickettsii. Although it has been reported in most states in the United States, it is most common in the southern Atlantic and south central states and in Oklahoma. Most cases occur in warm months, when ticks are most active. Eighty percent of patients have a history of tick bite.

Clinical Findings

Symptoms and Signs

The classic triad of fever, headache, and rash associated with a recent tick bite is absent in most patients who develop RMSF, and 30–40% will have no history of tick bite. Virtually all adults and older children will have a headache initially, accompanied by myalgias and malaise. Children will often have gastrointestinal complaints, including nausea, vomiting, and abdominal pain. The rash of RMSF typically begins as a maculopapular exanthem on the ankles or wrists and progressing toward the body that then evolves into a petechial rash. Neuropsychiatric symptoms indicate a more severe course and worse prognosis.

Laboratory Findings

Thrombocytopenia is typical, and hyponatremia with elevated transaminases may also be seen. Elevated serum creatinine is associated with increased mortality. IFA testing for IgG and IgM can confirm the diagnosis but is not readily available, and early treatment may result in negative testing.

Treatment

Treatment must begin on clinical grounds and is most effective when begun in the first 3–5 days of illness. Doxycycline is the treatment of choice for both adults and children. In the past, chloramphenicol was recommended for younger children, although studies have demonstrated that brief courses of tetracyclines do not result in perceptible staining of teeth in younger children and both the AAP and CDC recommend doxycycline for children younger than age 9.

Disposition

Patients with neurologic symptoms, vomiting, elevated creatinine, or unstable vital signs should be admitted.

Infective Endocarditis

Essentials of Diagnosis

• Fever, chills
• New or changing murmur
• Cutaneous lesions

General Consideration

Infective endocarditis denotes infection of the endothelial surface of the heart, most often the cardiac valves. The disease may either be acute or subacute and may affect normal valves, previously damaged cardiac valves, or prosthetic valves. It is usually caused by bacteria, but fungi are also common pathogens in intravenous drug abusers with acute endocarditis. Seeding of bacterial emboli or deposition of immune complexes in the skin may cause characteristic skin lesions that can alert the physician to the correct diagnosis before progressive damage to the heart leads to circulatory collapse. Common pathogenic organisms include Strep. viridans, Streptococcus bovis, and the HACEK group of gram-negative organisms (Haemophilus, Actinobacillus, Cardiobacterium, Eikenella, and Kingella). Staph. aureus is particularly virulent, and infection is associated with a high mortality rate. S. epidermis and coagulase-negative staphylococci are the leading causes of infective endocarditis in patients with prosthetic valves.

Clinical Findings

Symptoms and Signs

Patients usually present with fever and malaise. In subacute endocarditis, there may be a history of anorexia, night sweats, and weight loss. Patients may also present in cardiac failure, with a stroke due to cerebral embolism, or with a cold extremity due to arterial emboli. Patients with infective endocarditis of the tricuspid valve (usually seen in intravenous drug abusers) commonly present with acute, often bilateral, embolic pneumonia. Examination of the heart often reveals a murmur, although heart murmurs are commonly absent in right-sided endocarditis.

Characteristic (but not specific) cutaneous and mucosal lesions in bacterial endocarditis include conjunctival and palatal petechiae, subungual (splinter) hemorrhages, Osler nodes, and Janeway lesions. Osler nodes are tender erythematous nodules with opaque centers that appear on the pulp of the fingertips and toes. Janeway lesions are nontender, red or maroon macules or nodules that develop on the palms and soles. Careful ophthalmologic examination may also reveal Roth spots (pale oval areas surrounded by hemorrhage) near the optic disk.

The Duke criteria were developed to aid in the diagnosis of endocarditis. The diagnosis requires two major criteria, or one major and three minor criteria, or five minor criteria (Table 42–17).

Laboratory Findings

Laboratory findings are variable and nonspecific for infective endocarditis. A normochromic normocytic anemia may be present, especially for patients with subacute disease. The white cell count may be elevated, especially in acute disease. The erythrocyte sedimentation rate is usually elevated. Microscopic hematuria is present in 30–50% of patients. Immune complex glomerulonephritis with renal failure may occur. Transthoracic echocardiography is 98% specific for endocarditis, but sensitivity may be less than 60%. Transesophageal echocardiography is close to 100% sensitive for examination of native valves and 84–94% sensitive for prosthetic valves.

Definitive diagnosis depends on isolating the causative organisms in blood cultures; however, 5–20% of patients with clinical endocarditis have persistently negative blood cultures (termed culture-negative endocarditis). Gram-stained smears of aspirates from skin lesions (usually Janeway lesions) occasionally permit rapid diagnosis. In patients with embolic pneumonia, Gram-stained smears of sputum may demonstrate the causative agent (usually Staph. aureus); however, in intravenous drug abusers, possible concurrent infection with other organisms (streptococci, gram-negative bacilli) must be treated pending blood culture results.

Treatment

In patients who are not acutely ill and in whom symptoms and signs of cardiac failure or major emboli are absent, antibiotic therapy may be withheld pending blood culture results. In all other patients, empiric antibiotic therapy should be initiated after samples of blood, urine, and (when present) sputum and aspirates from skin lesions have been obtained for culture.

Abnormal Cardiac Valve or Congenital Heart Disease

Usual pathogens in patients with abnormal cardiac valves or congenital heart disease are Strep. viridans and group D streptococci. Aqueous penicillin G intravenously is an acceptable empiric regimen. Vancomycin intravenously may be substituted for penicillin.

Prosthetic Cardiac Valves

Many pathogens cause prosthetic cardiac valve endocarditis. Infection occurring less than 6 months postoperatively may be caused by Staph. aureus, S. epidermidis, gram-negative aerobic bacilli, diphtheroids, or fungi. Infection occurring more than 6 months after prosthetic valve insertion is usually caused by Strep. viridans, aerobic gram-negative bacilli, enterococci, or staphylococci. Because growth of some of these organisms requires multiple blood cultures using special techniques, it is best to avoid early empiric therapy whenever possible. In a patient who requires immediate surgery because of hemodynamic decompensation, empiric therapy may be started with vancomycin and gentamycin.

Parenteral Drug Abuse

The usual pathogens in intravenous drug abusers are Staph. aureus, Pseudomonas sp., and streptococci, including group D streptococci. Empiric treatment should include vancomycin and gentamicin with substitution for vancomycin with penicillin and nafcillin, oxacillin, or methicillin in patients with compromised renal function.

Disposition

Patients with suspected bacterial endocarditis should be hospitalized. Obtain cardiothoracic surgical consultation for patients with infected prosthetic heart valves, new onset of cardiac failure, or emboli in major vessels because emergency valve replacement is often necessary.

Disseminated Gonococcemia

Essentials of Diagnosis

• Fever
• Skin lesions
• Septic arthritis
• Positive culture results

General Considerations

As bacteremia occurs in 3% of patients, it is not surprising that it is the leading cause of septic arthritis in adults. It should be recognized easily in the adolescent with arthritis or dermatitis.

Clinical Findings

Symptoms and Signs

Frequently, there is two distinct phases with disseminated gonorrhea. Initially there is bacteremia associated with fever arthralgias and dermatitis. This is followed by a frank septic arthritis. The skin lesions usually develop on the extremities. Lesions vary and range from petechiae and erythematous, palpable purpura to vesiculopustules with an erythematous halo, and they often have necrotic centers. About one-fourth of patients have tenosynovitis, usually affecting the wrist or ankle. Acute septic arthritis, affecting one or more large joints, may follow disseminated gonococcemia or may occur in its absence.

Laboratory Findings

The white cell count may be elevated. Blood cultures are often positive in disseminated gonococcemia. Although Gram stains and culture of skin lesions are generally negative, cultures of all sites are negative in as many as 50% of patients, and a presumptive diagnosis is based instead on the prompt response to ceftriaxone therapy.

Treatment

Antimicrobial Therapy

Give ceftriaxone (1 g intravenously or intramuscularly every 24 hours).

Disposition

Most patients with septic arthritis should be hospitalized, but outpatient treatment with daily visits for joint aspiration is an acceptable alternative for reliable patients. Many patients with only dermatitis or tenosynovitis may receive outpatient treatment with close follow-up.

Toxic Shock Syndrome

Essentials of Diagnosis

• Erythroderma
• Hypotension
• Multisystem organ dysfunction

General Considerations

Toxic shock syndrome results from absorption of toxin from localized Staph. aureus colonization or infection. In the past, most cases occurred in young women who had vaginal colonization with Staph. aureus that produce toxic shock syndrome toxin-1 (TSST-1); however, nonmenstrual-related cases currently outnumber menstrual-related cases. Most of the nonmenstrual cases occur in the postoperative setting. The toxin functions as a superantigen that allows the antigen to bind directly to the MHC-II (major histocompatibility complex) receptor in a nonspecific fashion. This may result in activation of 5–30% of the total T-cell population, leading to massive cytokine production. The mortality rate in STSS is five times higher than in toxic shock syndrome.

Clinical Findings

Menstrual-related toxic shock syndrome usually starts abruptly during menses. It occurs most commonly in women using tampons or contraceptive sponges. In nonmenstrual cases associated with postoperative infection, signs of localized infection in the wound may be absent.

Symptoms and Signs

There is a short prodrome consisting of various combinations of the following symptoms and signs: fever, myalgias, vomiting, diarrhea, and pharyngitis. Patients then develop shock (SBP <80 mm Hg) with fever (>39°C) and signs of multiple organ dysfunction. At the time of presentation to the emergency department or within 24 hours of admission to the hospital, a diffuse, blanching, macular erythema appears, accompanied by signs of mucous membrane inflammation (pharyngitis, conjunctivitis, vaginitis, and strawberry tongue). The rash fades in about 3 days, but desquamation of the hands and feet occurs in all patients 5–12 days after the rash disappears. Patients typically prefer to remain motionless in bed because of intense myalgias. Confusion and agitation occur in about half of patients. Pedal edema is common.

Laboratory Findings

Laboratory findings reflect dysfunction of several organ systems. There may be leukocytosis and thrombocytopenia, elevated BUN and creatinine levels, hyperbilirubinemia, elevated hepatic enzymes, or sterile pyuria. The prothrombin, INR, and PTTs may be elevated, with or without thrombocytopenia. Other laboratory abnormalities include acidosis, elevated creatine kinase levels (indicating rhabdomyolysis), hypocalcemia, decreased serum albumin and total protein due to capillary leakage, and elevated liver enzyme levels. Cultures of material from the vagina or cervix are usually positive for Staph. aureus. Blood cultures are negative in 85% of patients with toxic shock syndrome and in 50% of patients with STSS.

Treatment and Disposition

Remove the vaginal tampon or nasal or wound packing if present. Begin volume replacement with saline or colloid solutions and with vasopressors, if necessary. Admit the patient to an ICU, and monitor hemodynamic status. Start treatment with a first-generation cephalosporin, penicillinase-resistant synthetic penicillin, or vancomycin intravenously.

Group a Streptococcal Infections Associated with a Toxic Shock–Like Syndrome

An infection with group A streptococci that is remarkable for severity of local tissue destruction, life-threatening systemic toxicity, and toxic-shock-like syndrome has been described in adults. Clinical isolates frequently produce pyrogenic exotoxin A. The portal of entry may be the skin or the mucous membranes, or infection may occur subsequent to a surgical procedure, but many patients do not have obvious evidence of a portal of entry.

Clinical Findings

Symptoms and Signs

Pain is the most common initial symptom and is frequently severe and abrupt in onset. The pain usually involves the extremity but may be intra-abdominal. Before symptom onset, some patients complain of an influenza-like syndrome characterized by fever, chills, myalgia, vomiting, and diarrhea. Patients often have oral temperatures above 37°C, may have confusion that rapidly deteriorates into coma, or may be combative. Shock is apparent at the time of presentation or within hours with evidence of hypotension, renal dysfunction, and respiratory failure. Most patients present with soft tissue infection, such as cellulitis or necrotizing fasciitis. Deeper infections may be present, including osteomyelitis, myometritis, peritonitis, suppurative phlebitis, or endophthalmitis. The mortality rate is approximately 30%.

Laboratory Findings

Laboratory findings reflect dysfunction of several organ systems. There may be leukocytosis and thrombocytopenia. The hematocrit is initially normal but may drop within 48–72 hours. Serum creatinine and creatine kinase levels are elevated, but calcium and albumin levels are low. Microscopic hematuria is often present and correlates with the presence of renal impairment. Group A streptococci are cultured from the blood, body fluid, or tissues of all patients who have not received antibiotic therapy.

Treatment and Disposition

Intensive fluid replacement, central venous or pulmonary capillary wedge pressure monitoring, and timely surgical debridement are essential. Start antibiotic therapy with intravenous penicillin or a cephalosporin. Admit patients to the ICU.

Lyme Borreliosis

Lyme borreliosis (Lyme disease, Lyme arthritis) is a chronic disease caused by the spirochete Borrelia burgdorferi. Transmission is by several tick vectors (Ixodes, Amblyomma, Rhipicephalus) and occurs throughout the United States. The highest prevalence is found in the Northeast and Midwest. In stage 1, a rash is present, sometimes accompanied by fever. Timely treatment at this stage may prevent disease progression.

Clinical Findings

Symptoms and Signs

Between 3 and 32 days following the tick bite, which the patient may not notice, a gradually expanding area of redness with clearing (erythema migrans) occurs at the bite site. The involved skin is warm but not particularly tender to touch. About half of affected patients will develop smaller lesions of similar morphology at areas remote from the bite site over ensuing days to weeks.

In stage-1 disease (erythema migrans), often there are fever, chills, malaise, and regional lymphadenopathy. In stage 2 (days to weeks after infection), symptoms related to the multisystemic nature of Lyme borreliosis often appear, such as meningitis, hepatitis, sore throat, dry cough, heart block and other cardiac abnormalities, musculoskeletal pain, and neuropathy. Fatigue and lethargy are prominent and may persist for months after the skin lesions have disappeared.

A persistent illness (stage 3) may linger for months to years and usually involves the musculoskeletal system (chronic arthritis), neurologic system (both central and peripheral), and skin (acrodermatitis chronica atrophicans). Stage-3 illness responds more slowly to treatment, and treatment at this stage has higher failure rates compared to stages 1 and 2.

Laboratory Findings

Laboratory testing is currently not reliable or standardized. Diagnosis depends on recognition of the pathognomonic rash. Serodiagnosis by either indirect immunofluorescence or ELISA may be negative in early infection. Nonspecific laboratory abnormalities include an elevated erythrocyte sedimentation rate, mild anemia, and transient elevations in SGOT (AST), SGPT (ALT), and lactate dehydrogenase enzyme levels.

Treatment and Disposition

The treatment of choice for early Lyme borreliosis is tetracycline for at least 10 days, or for 20 or 30 days if symptoms persist or recur. For children under age 12 years, give amoxicillin or penicillin V. In pediatric patients with penicillin allergy, give erythromycin for 15–30 days. For more serious disease (eg, Lyme carditis or meningitis), use intravenous therapy with ceftriaxone or penicillin G for 14–21 days.

See Table 42–18.

General Considerations

AIDS is the end stage of chronic infection by HIV, a lymphotrophic retrovirus. Transmission occurs by sexual contact, perinatally, and by contact with infected blood. The virus causes slow destruction of the helper T-cell subset and in most affected individuals leads to fatal immunosuppression.

AIDS patients can present in extremis, with shock, ARDS, or multiple organ failure secondary to overwhelming infection. Acute adrenal failure can occur secondary to CMV and tuberculosis affecting the adrenals. AIDS and HIV can complicate virtually any organ system, and a detailed history and physical examination are necessary.

Clinical Findings

Assess mental status carefully because mental status changes may be early signs of CNS infection or neuropsychiatric problems such as HIV dementia. Examine the eyes carefully for retinal lesions such as yellowish exudates and large hemorrhages seen in CMV or toxoplasma retinitis. The presence of nuchal rigidity may not be a presenting symptom of meningitis in an HIV-positive patient but should be assessed. Examine the mouth for evidence of oral candida (thrush) or leukoplakia, herpes, and Kaposi sarcoma. Pulmonary examination could reveal tachypnea or unequal breath sounds. A cardiac examination is essential in evaluating for murmurs that could be secondary to an infectious endocarditis (especially in intravenous drug abusers). Examine genitalia for lesions such as the chancre of syphilis. An anorectal examination can reveal fissures or fistulas, perianal abscesses, or prostatitis. A careful neurologic examination can disclose a CNS lesion that could be either infectious or neoplastic in origin.

Organ-System-Specific Presentations

Pulmonary

The most common presenting complaint for an HIV-positive patient is pulmonary in origin. Pneumocystis carinii pneumonia (PCP) is the most common identifiable cause of death in AIDS patients and remains common (70% of HIV-positive patients will get it, and 70% of those will get reinfected). PCP is typically associated with fever and nonproductive cough, in contrast to bacterial pneumonia, in which the cough tends to be productive. Other causes of pulmonary pathology include tuberculosis, CMV, Cryptococcus, Histoplasma, and neoplasms (Kaposi sarcoma, lymphoma).

Neurologic

Ninety percent of patients with AIDS and 10–20% of HIV-positive patients will present with neurologic symptoms at some point (eg, seizure, mental status change, and headache). It is crucial not only to rule out infectious causes (Cryptococcus, bacterial meningitis, Histoplasma, CMV, progressive multifocal leukoencephalopathy, HSV, neurosyphillis, tuberculosis) but also to consider HIV encephalopathy (also known as AIDS dementia or subacute encephalitis; occurring in up to 15% of AIDS patients), lymphoma, cerebrovascular accident, and metabolic encephalopathy.

Gastrointestinal

Fifty percent of HIV-positive patients will have a gastrointestinal complication, presenting with complaints such as odynophagia, abdominal pain, bleeding, or diarrhea. Common infections include Shigella, Salmonella, E. coli, Campylobacter, Cryptosporidium, Isospora, CMV, or Mycobacterium avium complex (MAV). Bacterial infection is typically fulminant. If bacterial infection is suspected, give a fluoroquinolone empirically. Hepatitis is commonly seen secondary to high rates of coinfection with hepatitis B and C but can also be due to CMV, Cryptosporidium, or MAV. Proctocolitis is common in HIV-positive patients, and unless a careful examination is carried out, this diagnosis is easily overlooked (common causative organisms include Campylobacter, Shigella, Salmonella, gonococcus, and Chlamydia).

Systemic

Acute HIV infection causes an acute flulike illness in 50–90% of patients. Patients may present with fever, weight loss, adenopathy, or fatigue. MAV causes disseminated disease in up to 50% of AIDS patients (with fever, weight loss, and diarrhea). Fever is a common symptom and, in the absence of organ-specific clues, needs to be evaluated carefully. It may be due to HIV infection itself or another infectious cause. Patients with PCP may present with fever in the absence of respiratory symptoms. Cryptococcal meningitis can begin as fever without headache. Also consider Mycobacterium tuberculosis, MAV, endocarditis (especially if the patient is an intravenous drug abuser), and fever associated with neoplasm (lymphoma).

Ophthalmologic

The most common ocular finding is retinal microvasculopathy (“cotton wool spots”). CMV retinitis is common, and patients with this disorder present with visual loss, blindness, photophobia, scotomata, and floaters. On examination, CMV retinitis appears as fluffy white perivascular lesions with hemorrhage. HSV ophthalmicus is a worrisome complication; patients present with conjunctivitis, episcleritis, iritis, and keratitis.

Renal

HIV-positive patients not only commonly display prerenal azotemia secondary to volume depletion but also must deal with the consequences of drug nephrotoxicity, HIV nephropathy (focal segmental glomerulosclerosis), and renal tubular acidosis (hyperchloremic metabolic acidosis nonanion-gap acidosis), which are common in HIV infection and AIDS.

Skin

Patients can display a multitude of symptomology related to the skin. Infections are common (eg, Staphylococcus, Pseudomonas, HSV, herpes zoster, syphilis, intertriginous Candida), as are xerosis or pruritus associated with HIV infection.

Drug Reactions

Complications of the antiviral medications are common and are summarized in Table 42–19.

Laboratory Data

Obtain an arterial blood gas measurement to aid in investigating pulmonary complaints (Pao2 <60 or oxygen saturation <90 is suggestive of pneumonitis). A fall in oxygen saturation of greater than 3% with activity is 80% sensitive for PCP. A chest X-ray can be useful in narrowing the differential diagnosis of pulmonary complaints based on appearance, but these findings are often nonspecific. Chest X-rays are read as negative in 15–20% of patients with documented PCP. Obtain blood and urine cultures (remember fungal and mycobacterial studies) as needed to evaluate systemic complaints or for focal complaints related to possible infection. Sputum culture and Gram stain are particularly useful for pulmonary complaints.

A CBC is helpful as a general index to evaluate for infection and forhematologic complications of HIV infection. In the absence of a CD4 count, an absolute lymphocyte count can be helpful. If the total lymphocyte count is less than 1000, then the CD4 is likely less than 200. CMV or MAV usually do not occur unless CD4 is less than 50. CSF should be sent for typical studies such as opening–closing pressures, cell count, glucose, protein, Gram stain, and culture, as well as other studies in selected cases: India ink, viral culture, fungal culture, Toxoplasma and cryptococci antigens, and coccidioidomycosis titer.

Evaluation of gastrointestinal complaints should proceed by sending stool for Wright stain, ova and parasite testing, acid-fast stain, and culture. Send standard stool cultures, Thayer–Martin culture, Chlamydia culture or immunoassay, and viral culture for HSV if proctocolitis is suspected on clinical examination.

HIV-positive patients should receive a head CT scan prior to lumbar puncture if mental status changes are present. MRI scans are superior to CT scan for detection of cerebral toxoplasmosis and other lesions.

Treatment

Manifestations of HIV infection can range from asymptomatic to life threatening and can affect any organ system. Because of the complexity of opportunistic infections and malignancies occurring in HIV-positive patients, the diagnosis often cannot be made in the emergency department.

Disposition

Disposition depends on the organ system in question. Ensure that the patient is adequately resuscitated. Final diagnoses may require biopsy or complicated studies to obtain a final diagnosis. In general, admit patients if a fever of unknown source or CNS findings are present or in the event of seizure, suspected PCP, hypoxia worse than baseline, intractable diarrhea, disseminated Herpes zoster, marrow suppression, extreme weakness, or inability to care for self or obtain follow-up.

Influenza and Pandemic Flu

Essentials of Diagnosis

• Fever
• Cough
• Sore throat
• Influenza known to be in community

General Considerations

Influenza, a staple of emergency medicine practice, took a new twist in April 2009 with the emergence of a new strain of Influenza A H1N1. So genetically different from previous strains that many predicted a pandemic, an epidemic of huge geographical proportions. The virus, which originated in Mexico, spread to the United States and nearly 80 other countries worldwide. An outbreak is when there are more cases of an infection than expected in a community or region. An epidemic occurs when a disease spreads rapidly to many people. A pandemic occurs when there is a global disease outbreak. Responding to a pandemic situation is key at both a departmental and community level.

Between 5% and 20% of the population is infected with influenza yearly and over 200,000 hospitalizations are related to influenza. Influenza viruses that infect humans occur in 3 major types: A, B, and C. Of these, types A and B cause the majority of human illness. While both are associated with seasonal epidemics, only influenza A has been responsible for pandemics; namely, the Spanish Flu of 1918, the Asian Flu of 1957, and the Hong Kong Flu of 1968. About 36,000 deaths/y are caused by influenza. Influenza A viruses have surface proteins, hemagglutinin (H), and neuraminidase (N) that classify them. Subtle changes that occur continuously called antigenic drift do not affect disease or transmission. Major changes in the surface proteins in both human and animal viruses are called antigenic shift. When a shift occurs and there is transmission to a human population that lacks immunity, a pandemic may result. While most transmission of the virus is most commonly from respiratory droplets, both inanimate objects, and other bodily fluids can spread disease. The very young, the elderly, pregnant, and the physically and immune impaired are at greatest risk from pandemic influenza.

Clinical Findings

The incubation period is between 1 and 7 days, and individuals with influenza are contagious 1 day before symptoms emerge. The symptoms of fever, cough, sore throat, rhinorrhea, myalgias, and headache are common to influenza. Up to 15% of patients may be afebrile. The CDC defines a person with an influenza-like illness (ILI), to have only the following symptoms: Fever ≥100° F plus cough and/or sore throat. Lower respiratory symptoms may be present also, and importantly pregnant women present more often with shortness of breath then nonpregnant ones. These symptoms coupled with testing or merely an epidemiological link would define a case of influenza. Testing may be done with one of numerous ways and may be strain specific or just identify Influenza A to be accurate.

Laboratory Data

The CDC recommends that most patients with an illness consistent with influenza who reside in an area where influenza viruses are circulating do not require diagnostic influenza testing. Patients who should be considered for influenza diagnostic testing include hospitalized patients with suspected influenza, patients for whom a diagnosis of influenza will help decisions regarding clinical care, infection control, or management of close contacts, and patients who died of an acute illness in which influenza was suspected.

Treatment and Disposition

The decision to treat influenza (see Table 42–20) should be based on the time of presentation but more importantly on risk factors for severe disease. Because of the variable incubation period, the broad scope of influenza-like illnesses, and the safety of antiviral therapies, most should be considered for treatment, when influenza is in the community. It should be started as soon as possible regardless of testing. Those without risk factors for severe disease can be excluded from treatment if deemed to be recovering. The following risk factors put individuals at a greater threat for severe disease:

• Children less than 2 years old
• Adults over 65 years old
• Pregnant women up to 2 weeks postpartum regardless of how the pregnancy ended.
• Asthma
• Neurological and neurodevelopmental conditions
• Chronic lung disease
• Heart disease
• Blood disorders
• Endocrine disorders
• Kidney disorders
• Liver disorders
• Metabolic disorders
• Immune system disease or steroids
• People younger than 19 years of age who are receiving long-term aspirin therapy

Postexposure antiviral prophylaxis is indicated for patients at high risk of complications from influenza (eg, pregnancy) and should be considered for health care workers who were not using appropriate personal protective equipment during close contacts with a confirmed, probable, or suspected case. This chemoprophylaxis is for 10 days.

Admission should be considered if there are resources for those with risk factors, though many may be discharged with careful planning and follow-up.

Departmental and Community Preparedness and Response

The presence of a pandemic, or epidemic presents additional challenges to the emergency physician beyond the individual patient. The department, the prehospital system, and the community all must be managed to optimize emergency care. There are four tasks that need to be considered in both planning for a pandemic and while in the midst. They include increasing bed availability, developing strategies to deal with the potential staffing shortages, developing strategies for dealing with potential critical equipment and pharmaceutical shortages, and, lastly, the implementation of education, training, and communication strategies for their health care workers and the public they serve.