Meningitis and Meningoencephalitis
- Nuchal rigidity
- Mental status change
- CSF findings
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.
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%.
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.
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.
Table 42–1. Contraindications to Lumbar Puncture. ||Download (.pdf)
Table 42–1. Contraindications to Lumbar Puncture.
- Impending or established septic shock
- Glasgow Coma Scale score of less than 13 or deteriorating score
- Other signs of raised intracranial pressure (marked instability of blood pressure or heart rate)
- Focal neurologic signs
- Confident diagnosis of meningococcal infection
- Infection at the planned lumbar puncture site
- Bleeding disorder
- Immune compromised patient with known decrease in CD4 count w/o therapy
Table 42–2. Cerebrospinal Fluid Findings in Meningitis. ||Download (.pdf)
Table 42–2. Cerebrospinal Fluid Findings in Meningitis.
|Measure||Normal||Bacterial Meningitis||Viral Meningitis||Fungal Meningitis||Tuberculous Meningitis||Abscess|
|Lymphocytes (%)||>50||<50||>50||>80||Increased monocytes||Variable|
|CSF–blood glucose ratio||0.6||<0.4||0.6||<0.4||<0.4||0.6|
Table 42–3. Some Causes of Acute Lymphocytic Meningitis. ||Download (.pdf)
Table 42–3. Some Causes of Acute Lymphocytic Meningitis.
- Early or partially treated bacterial meningitis
- Viral meningitis and meningoencephalitis (including HIV)
- Tuberculous or fungal meningitis
- Parameningeal infection (e.g., brain abscess)
- CNS collagen vascular disease
- CNS tumor, leukemia, lymphoma, or carcinomatosis
- Intracranial injury (e.g., subdural hematoma)
- Subarachnoid hemorrhage
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.
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.
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.
Table 42–4. Recommended Empiric Antimicrobial Therapy for Bacterial Meningitis Based on Age. ||Download (.pdf)
Table 42–4. Recommended Empiric Antimicrobial Therapy for Bacterial Meningitis Based on Age.
|Age||Major Pathogens||Antibiotic Regimen||Alternative Regimens||Comment|
|Less than 3 months||Group B streptococci, Listeria monocytogenes, Escherichia coli, Strep. pneumoniae||Ampicillin plus ceftriaxone (or cefotaxime)||Chloramphenicol plus gentamicin||CSF levels are not reliable in low-birth-weight infants and should be monitored|
|3 months–18 years||Neisseria meningitidis, S. pneumoniae, Haemophilus influenzae||Ceftriaxone (or cefotaxime)||Meropenem or Chloramphenicol||Add vancomycin in areas with greater than 2% incidence of highly drug resistant S. pneumoniae|
|18–50 years||S. pneumoniae, N. meningitides, H. influenzae||Ceftriaxone (or cefotaxime)||Meropenem or chloramphenical||Add vancomycin in areas with greater than 2% incidence of highly drug resistant S. pneumoniae|
|50 years and older||S. pneumoniae, L. monocytogenes, gram-negative bacilli||Ampicillin plus ceftraxone (or cefotaxime)||Ampicillin plus fluoroquinolone (ciprofloxacin, levofloxacin)||Add vancomycin in areas with greater than 2% incidence of highly drug resistant S. pneumoniae; for patients who have major penicillin allergy, TMP-SMZ can substitute for ampicillin to treat L. monocytogenes infection|
Table 42–5. Pathogen-Specific Therapy for Patients WHO Have Bacterial Meningitis.
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.
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.
Immediate hospitalization is warranted for all patients, except those with aseptic (viral) meningitis who appear well and can be observed at home.
Assiri AM, Alasmari FA, Zimmerman VA
, Baddour LM, Erwin PJ, Tleyjeh IM: Corticosteroid administration and outcome of adolescents and adults with acute bacterial meningitis: A meta-analysis. Mayo Clin Proc. 2009;84:403–409.
Chaudhuri A, Martinez-Martin P, Kennedy PG, Andrew Seaton R, Portegies P, Bojar M, Steiner I; EFNS Task Force: EFNS guideline on the management of community-acquired bacterial meningitis: Report of an EFNS Task Force on acute bacterial meningitis in older children and adults. Eur J Neurol 2008;15:649–659
van de Beek, de Gans J, Tunkel AR, Wijdicks EF: Community-acquired bacterial meningitis in adults. N Engl J Med 2006 Jan;354:44–53
van de Beek D, de Gans J, McIntyre P, Prasad K: Corticosteroids for acute bacterial meningitis. Cochrane Database of Sys Rev 2007;CD004405
Tunkel AR, Hartman BJ, Kaplan SL, et al: Practice guidelines for the management of bacterial meningitis. Clin Infect Dis 2004;39:1267–1284
Pneumonia in Neonates (Aged <2 Weeks)
- Grunting, tachypnea
- Focal lung exam
- Radiographic findings
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.
Table 42–6. Empiric Antibiotic Treatment of Pneumonia in the Pediatric Population.
Pneumonia in Infants and Children (Aged 2 Months to 5 Years)
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)
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.
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.
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.
Table 42–7. Chest X-Ray Findings in Pneumonia. ||Download (.pdf)
Table 42–7. Chest X-Ray Findings in Pneumonia.
|Lobar consolidation||Nonsegmental, homogenous consolidation involving one lobe; may have air bronchograms|
- S. pneumoniae
- K. pneumoniae
- L. pneumophila
|Bronchopneumonia||Peribronchial thickening, poorly defined air space opacities (“patchy” consolidation)|
- S. aureus
- H. influenzae, most gram-negative rods, fungi
|Interstitial pneumonia||Edema and infiltrate in alveolar septa, surrounding small airway/vessels|
- M. pneumoniae
- P. carinii
|Abscess||Air–fluid level, often with adjacent parenchymal consolidation|
- S. aureus
- P. aeruginosa
|Effusion||Assumes shape of pleural space; if air–fluid level present, longer on lateral view||Any; more common in severe pneumonia ~10% S. pneumoniae; almost 50% of L. pneumophila and H. influenzae|
|Pneumatocele||Thin-walled, gas-filled spaces within parenchyma||Present in up to 50% S. aureus pneumonias in children|
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).
Table 42–8. Pneumonia Classification. ||Download (.pdf)
Table 42–8. Pneumonia Classification.
|Community-acquired pneumonia (CAP)—No recent contact with health care system or hospital admissions in past|
|Health care associated pneumonia, early/low-risk (HCAP)—Includes patients within 5 days of hospital admission to non-ICU setting, not intubated. Otherwise not meeting multi drug resistant (MDR) pathogen risk below.|
|Health care associated pneumonia, late/MDR risk (HCAP)—Includes patients with the following risk factors:
- Antimicrobial therapy in preceding 90 days
- Current hospitalization of 5 days or more
- High frequency of antibiotic resistance in the community or in the specific hospital unit
- Hospitalization for 2 days or more in the preceding 90 days
- Residence in a nursing home or extended care facility
- Home infusion therapy (including antibiotics) or home wound care
- Chronic dialysis within 30 days
- Family member with multidrug-resistant pathogen
- Immunosuppressive disease and/or therapy
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.
Table 42–9. Empiric Antibiotic Treatment of Pneumonia in Adults.
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.
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.
Table 42–10. Pneumonia Port Severity Index.a ||Download (.pdf)
Table 42–10. Pneumonia Port Severity Index.a
|Nursing Home Resident||+10|
|Physical Examination Findings|
|Altered mental status||+20|
|Respiratory rate ≥30/min||+20|
|SBP <90 mm Hg||+20|
|Temperature <35 or > 40||+15|
|Arterial pH <7.35||+30|
|BUN >30 mg/dL||+20|
|Sodium <130 mmol/L||+20|
|Glucose ≥250 mg/dL||+10|
|Pao2 <60 mm Hg||+10|
|Risk Group (# of points)||Mortality|
|I (pts not calculated)||0–0.4%|
American Thoracic Society; Infectious Diseases Society of America: Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia. Am J Respir Crit Care Med 2005;171:388–416
Bjerre LM, Verheij TJM, Kochen MM: Antibiotics for community acquired pneumonia in adult outpatients. Cochrane Database Sys Rev 2009;CD002109
Cincinnati Children's Hospital Medical Center. Evidence based care guideline for community acquired pneumonia in children 60 days through 17 years of age. Cincinnati, OH, 2006. www.guideline.gov/summary/summary.aspx?doc_id=9690
(last accessed August 17, 2010).
Lutfiyya MN, Henley E, Chang LF, Reyburn SW: Diagnosis and treatment of community-acquired pneumonia. Am Fam Physician 2006;73:442–450
Mandell LA, Wunderink RG, Anzueto A, et al: Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis 2007;44:S27–S72
Zhanel GG, DeCorby M, Laing N, et al: Antimicrobial-resistant pathogens in intensive care units in Canada: results of the Canadian National Intensive Care Unit (CAN-ICU) study, 2005-2006. Antimicrob Agents Chemother 2008;52:1430–1437
- Low-grade fever
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.
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.
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.
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.
Allander T, Jartti T, Gupta S, Niesters HG, Lehtinen P, Osterback R, Vuorinen T, Waris M, Bjerkner A, Tiveljung-Lindell A, van den Hoogen BG, Hyypiä T, Ruuskanen O: Bocavirus and acute wheezing in children. Clin Infect Dis 2007;44:904–910
Rafei K, Lichenstein R: Airway infectious disease emergencies. Pediatr Clin North Am 2006;53:215–242
- Painful joint
- Joint effusions
- Arthrocentesis findings
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.
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.
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 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.
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.
Aspirate affected joints. Aspiration is necessary except for infections in inaccessible joints. Open drainage is almost never required in gonococcal arthritis.
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.
Table 42–11. Treatment of Septic Arthritis. ||Download (.pdf)
Table 42–11. Treatment of Septic Arthritis.
|Age Group||Cause||Primary Treatment||Alternative Treatment|
|Infant (<3 months)|
- S. aureus
- Group B streptococci, N. gonorrhoeae
|Antistaphylococcal penicillin + third-generation cephalosporin||Antistaphylococcal penicillin + aminoglycoside|
|Children (3 months–14 years)|
- Staph. aureus
- Streptococcus pyogenes
- Strep. pneumoniae
- Haemophilus influenzae
|Antistaphylococcal penicillin + third-generation cephalosporin||Vancomycin + third-generation cephalosporin|
|Adults (acute monoarticular; sexually active)||N. gonorrhoeae||Ceftriaxone or cefotaxime or ceftizoxime||Nafcillin if gram-positive organisms are found|
|Adults (acute monoarticular; not sexually active)|
- Staph. aureus
- Streptococci gram-negative bacilli
|Antistaphylococcal penicillin + third-generation cephalosporin||Antistaphylococcal penicillin + ciprofloxacin|
|Adult (polyarticular)||N. gonorrhoeae||Ceftriaxone|
Hospitalize all patients with suspected or documented septic arthritis.
- Pain, fever
- Increased erythrocyte sedimentation rate
- Biopsy findings
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.
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.
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).
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.
Patients with acute osteomyelitis should be hospitalized for intravenous antimicrobial therapy.
Calhoun JH, Manring MM. Adult osteomyelitis. Infect Dis Clin North Am 2005;19:765–786
Gutierrez K: Bone and joint infections in children. Pediatr Clin North Am 2005;52:779–794
Smith JE, Chalupa P, Shabaz Hasan M: Infectious arthritis: Clinical features, laboratory findings and treatment. Clin Microbiol Infect 2006;12:309–314
- Sore throat
- Erythematous pharynx
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.
Table 42–12. Bacterial Etiologies of Acute Pharyngitis. ||Download (.pdf)
Table 42–12. Bacterial Etiologies of Acute Pharyngitis.
- Group A
- Group C and G
- Mixed anaerobes
- N. gonorrheae
- Corynebacterium diphtheriae
- Arcanobacterium haemolyticum
- Yersinia enterocolitica
- Yersinia pestis
- Francisella tularensis
- Mycoplasma pneumoniae
- Chlamydia psittaci
- Chlamydia pneumoniae
- Fusobacterium necrophorum
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.
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 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 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 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.
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 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.
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.
Casey JR, Pichichero ME: Meta-analysis of cephalosporins versus penicillin for treatment of group A streptococcal tonsillopharyngitis in adults. Clin Infect Dis 2004;38:1526–1534
Gerber MA: Diagnosis and treatment of pharyngitis in children. Pediatr Clin North Am 2005;52:729–747
Lai C, Vummidi DR: Lemierre's Syndrome. N Engl J Med 2004 Apr 15;350(16):e14
Smith A, Lamagni TL, Oliver I, Efstratiou A, George RC, Stuart JM: Invasive group A streptococcal disease: Should close contacts routinely receive antibiotic prophylaxis? Lancet Infect Dis 2005;5:494–500
Acute Lower Urinary Tract Infection (Uncomplicated Cystitis)
- Frequency and urgency
- Suprapubic pain
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.
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.
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.
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.
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.
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).
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).
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.
Table 42–13. Empiric Antibiotic Therapy for Urinary Tract Infection. ||Download (.pdf)
Table 42–13. Empiric Antibiotic Therapy for Urinary Tract Infection.
|Type of Infection||First-Line Therapy||Alternative Regimens||Comments|
|Uncomplicated cystitis (including mild pyelonephritis)||Fluoroquinolone, Bactrim DS, nitrofurantoin.||Amoxicillin–clavulanate, third-generation cephalosporin|
|Urinary tract infection with pyelonephritis (inpatient therapy)||Intravenous fluoroquinolone, ampicillin + gentamicin, third-generation cephalosporin, or antipseudomonal penicillin||Ticarcillin–clavulanate, ampicillin–sulbactam, or piperacillin–tazobactam|
|Complicated urinary tract infection (obstruction, reflux, indwelling catheter)||Ampicillin + gentamicin, piperacillintazobactam Ticarcillin–clavulanate, imipenem, or meropenem||Intravenous fluoroquinolone||Rule out obstruction|
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.
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.
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)
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
American College of Obstetricians and Gynecologists. ACOG Practice Bulletin No. 91: Treatment of urinary tract infections in nonpregnant women. Obstet Gynecol 2008;111:785–794
Grabe M, Bishop MC, Bjerklund-Johansen TE, et al: Guidelines on the management of urinary and male genital tract infections. European Association of Urology (EAU), 2008 Mar. pp. 1–116.
Hodson EM, Willis NS, Craig JC: Antibiotics for acute pyelonephritis in children. Cochrane Database of Sys Rev 2007;CD003772
Diseases of the Female Genitourinary Tract
See also the Sexually Transmitted Diseases section later in this chapter.
Pelvic Inflammatory Disease
- Lower abdominal pain
- Vaginal discharge
- Cervical motion tenderness
- Bilateral lower adnexal tenderness
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.
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.
Table 42–14. Criteria for Diagnosis of Pelvic Inflammatory Disease. ||Download (.pdf)
Table 42–14. Criteria for Diagnosis of Pelvic Inflammatory Disease.
- Minimum Criteria
- Lower abdominal tenderness
- Adnexal tenderness
- Cervical motion tenderness
- Additional Criteria
- Oral temperature > 101°F
- Abnormal cervical or vaginal discharge
- Elevated erythrocyte sedimentation rate
- Elevated C-reactive protein
- Laboratory documentation of cervical infection with N. gonorrhoeae or C. trachomatis
- Elaborate Criteria
- Histopathologic evidence of endometritis on endometrial biopsy
- Transvaginal sonography or other imaging techniques showing thickened, fluid-filled tubes with or without free pelvic fluid or tubo-ovarian complex
- Laparoscopic abnormalities consistent with pelvic inflammatory disease
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.
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.
Table 42–15. Antimicrobial Therapy for Pelvic Inflammatory Disease.
Patients who are not hospitalized should be reevaluated in 2–4 days and hospitalized if their condition has not improved markedly.
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.
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.
- Abnormal vaginal discharge
- Pruritus, irritation, odor
- Inflamed cervix
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.
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).
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.
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.
Obtain a clean-catch urine specimen for analysis and culture if dysuria is present.
Obtain fasting blood glucose measurement in cases of recurrent candidiasis, to rule out diabetes mellitus.
Advise patients to avoid intercourse for a few days after treatment. Partners also should receive treatment, as described below.
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.
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.
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.
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.
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.
See the Gonorrhea section below.
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.
- Labial pain, swelling
- Fluctuant lesion
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.
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.
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.
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.
Gynecologic follow-up is mandatory because surgery may be necessary. Occasionally marsupialization may be performed at the time of diagnosis of acute bartholinitis.
- Vaginal discharge
- Cervical exudate
The presence of mucopurulent endocervical exudates strongly suggests cervicitis due to chlamydial or gonococcal infection.
Vaginal discharge and pruritus may be present. Mucopurulent endocervical exudate may be observed.
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.
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.
Fluorescent antibody or ELISA slide test should be used to diagnose Chlamydia.
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.
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.
Acute Bacterial Prostatitis
- Low back pain
- Prostatic tenderness
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.
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.
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.
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.
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.
- Testicular pain
- Epididymal tenderness
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.
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.
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.
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.
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.
N. gonorrhoeae causes primary genitourinary tract infections, localized infections, and the disseminated arthritis–dermatitis syndrome. Approximately 600,000 new cases are diagnosed each year.
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.
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.
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.
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.
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.
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.
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.
Patients with nongonococcal urethritis can receive treatment on an outpatient basis.
Genital Herpes Simplex Virus Infection
- Fever, adenopathy
- Vesicles on an erythematous base
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.
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 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.
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.
Table 42–16. Outpatient Treatment of Genital Herpes Infections.
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.
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.
- Chancre (painless)
- Positive VDRL, RPR, FTA-ABS
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.
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 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.
A positive serologic test is the only sign, and this stage may last from 1 to 2 months up to more than 20 years.
This stage is characterized by destructive lesions of the aorta, CNS, skeletal structures, and skin.
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).
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.
An alternative regimen for penicillin-allergic patients is doxycycline, 100 mg orally twice daily, or tetracycline, 500 mg four times daily for 14 days.
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.
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.
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.
- Erythematous pustule
- Gram stain or culture
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.
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.
Recommended treatments include azithromycin orally or ceftriaxone intramuscularly; ciprofloxacin and erythromycin are alternatives.
Most men with T. vaginalis infections develop nongonococcal urethritis, but women typically develop malodorous yellow–green frothy discharge, dysuria, dyspareunia, vulvar irritation, and pruritus.
Motile parasites are seen on a wet-mount smear.
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.
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. London, United Kingdom, 2008 (last accessed August 17, 2010).
Superficial Soft Tissue Infections
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.
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 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 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 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 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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
All patients with NSTIs should be admitted for surgical exploration and debridement, followed by hospitalization in an intensive care setting.
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