Chapter 8: Infectious Diseases

Flu season is right around the corner and you are preparing your clinic for the onslaught. First things first … you need to know how much vaccine to order and who will be receiving it. The Centers for Disease Control and Prevention (CDC) annually publishes recommendations for administering influenza vaccine to the American public.

Question 8.1.1 The CDC recommends vaccination for all of the following groups, EXCEPT:

A) Healthcare workers

B) Nursing home residents

C) Egg-allergic, febrile neonates

D) Diabetics

E) The elderly

Answer 8.1.1 The correct answer is "C." We start this chapter with an easy one. Patients 6 months of age or younger should not be vaccinated nor should children who are febrile. The only other absolute contraindication to influenza vaccination is a known hypersensitivity to eggs or to other components of the influenza vaccine. Patients with an egg allergy can get the recombinant flu vaccine. The egg based vaccine can still be used in those who's only reaction to eggs is hives if they are observed for thirty minutes after the injection (CDC 2016).

Oh, no! The virus has struck. Like a zombie apocalypse, it started with just a few cases, but now it's out of control. Every other patient who calls complains of influenza-like illness.

Question 8.1.2 During this outbreak, what intervention(s) is/are most appropriate for all your unvaccinated, frail nursing home patients who have no symptoms of febrile respiratory illness?

A) Antiviral prophylaxis with oseltamivir

B) Antiviral prophylaxis with amantadine

C) Influenza immunization

D) A and C given together

E) B and C given together

Answer 8.1.2 The correct answer is "D." Persons at high risk for complications of influenza can still be vaccinated after an outbreak of influenza has begun in the community, but development of antibodies in adults can take up to 2 weeks. Thus, chemoprophylaxis should be considered for persons at high risk during the time from vaccination until immunity has developed. "A" alone might be appropriate for individuals who have a contraindication to vaccination and wish to protect themselves from influenza. "B" is not correct because influenza A is increasingly resistant to M2 drugs (e.g., amantadine, rimantadine), and influenza B has never been sensitive them. Vaccination alone ("C") can be used in individuals without known high-risk conditions (chronic disorders including asthma, diabetes, renal dysfunction, immunodeficiency or cardiovascular disease). But, as noted above, vaccine alone is inadequate for those who are institutionalized or have significant comorbidities. These higher risk patients also need to be covered by oseltamivir until immunity has developed (2 weeks).

Question 8.1.3 Which of these patients would qualify for antiviral therapy during an influenza outbreak?

A) A healthy 29-year-old male who presents 72 hours after onset of symptom onset and has a positive rapid test for influenza

B) A 70-year-old patient hospitalized with influenza who presents 72 hours after onset of symptoms

C) A pregnant women who presents within 48 hours of symptom onset and has a positive rapid test for influenza

D) B and C

E) All of the above

Answer 8.1.3 The correct answer is "D." In outpatients, antiviral drugs are reserved for high-risk groups including pregnancy, age >65 years, significant underlying medical illness (DM, immunosuppression, morbid obesity, asthma, etc.), nursing home residents and children age <2 years. Normal risk outpatients should be prioritized lower on the treatment ladder. However, the CDC does recommend that antiviral drugs be considered for otherwise healthy outpatients with confirmed influenza who can start medication within 48 hours of symptom onset. All hospitalized patients should be treated even if it is >48 hours after onset of symptoms.

The director of nursing at your community nursing home calls about an outbreak of febrile respiratory infections. In the last 24 hours, three patients have become ill on the dementia care unit. All residents of the home were vaccinated with the current year's influenza vaccine in November. Several of the aides have not been vaccinated and two recently left work after complaining of feeling tired, feverish, and achy.

Question 8.1.4 You suspect an influenza outbreak and take the following actions EXCEPT:

A) Quarantine the nursing home and restrict access for visitors, new admissions, and ill staff

B) Hospitalize all patients suspected of having influenza

C) Limit the interaction of ill residents with non-ill residents

D) Administer antiviral prophylaxis to all well residents

E) Provide influenza vaccine to any unvaccinated residents and staff

Answer 8.1.4 The correct answer is "B." Moving sick patients only risks spreading the infection to the hospital. In addition to measures above, employees should be assigned to one work area only to prevent spread via the staff. Activities, visits, and gatherings in central common areas should be curtailed during the outbreak.

Question 8.1.5 Time to update the pneumococcal vaccine protocol at your nursing home! In accordance with 2015 CDC recommendations for older adults, you institute the following schedule for all patients at age 65 who have not yet received a pneumococcal vaccination:

A) 23-valent pneumococcal polysaccharide vaccine (PPSV23) once only

B) 13-valent pneumococcal conjugate vaccine (PCV13) once only

C) PPSV23 followed by PCV13 one year later

D) PCV13 followed by PPSV23 one year later

E) Cowpox … lots and lots of cowpox

Answer 8.1.5 The correct answer is "D." Indications for pneumococcal vaccination include patients with chronic illness at high risk for invasive pneumococcal disease (e.g., diabetes, chronic pulmonary disease, and cardiovascular disease), institutionalization, age 65 or older, immunocompromised state, and tobacco use. Note that the tobacco use indication is relatively recent and applies to all patients age 19 to 64 years old. There are two pneumococcal vaccinations, (Pneumovax) and 13-valent pneumococcal polysaccharide conjugate vaccine (PCV13 or Prevnar-13). All adults aged 65 or older should receive both vaccines. PCV13 should be administered before PPSV23 when practicable. PCV13 is also recommended for patients with end-stage renal disease, asplenia, HIV, and many other conditions. PVC13 vaccine is not indicated for those < age 65 only on the basis of smoking or the presence of lung disease (as of 2015). However PPSV23 is indicated for both smokers and those with COPD who are <65 years of age.

Objectives: Did you learn to…

• Describe who should receive influenza and pneumococcal vaccines?

• Identify appropriate interventions to halt the transmission of influenza in community and care facility outbreaks?

• Lead a successful influenza prevention program in a healthcare setting?

• Prescribe influenza antivirals appropriately?

The clinic triage nurse comes to you with a concern about a patient who has just walked into clinic and is at the front desk. She is a 28-year-old Peace Corps worker who returned 10 days ago from a western African country in the midst of an Ebola epidemic. She is otherwise healthy but started having a fever suddenly last night. She describes fatigue, night sweats, myalgia, and temperature of 38.5°C. This morning she notes vomiting and diarrhea with blood in the stool. The patient thinks that she has a benign viral illness ("everyone was coughing on the plane") and does not recall any contacts with persons with Ebola.

You tell the nurse:

A) "We will work her in. Just have her hang out in the waiting room."

B) "Give her any mask you can find and send her to the ER. Pronto."

C) "Isolate the patient immediately in an examination room (preferably negative laminar flow if available) and call the health department."

D) "Shut down the whole clinic! We're on lockdown!"

The correct answer is "C." This patient has been in an area of Ebola epidemic, has the classic symptoms of Ebola (fever, diarrhea, vomiting, bleeding [in this case in her stools]). Other symptoms include meningoencephalitis, diffuse rash, a relative bradycardia for the degree of fever (similar to that seen with typhoid). Treat her as though she has Ebola until proven otherwise. Ebola is highly contagious and is spread by contaminated body fluids, including aerosolized droplets. You should endeavor to limit exposure of others to the ill patient, so "A" and "B" are incorrect, as both options expose more persons. The health department in your area should be involved immediately, and they would be in contact with the CDC. The CDC recommends symptomatic patients at risk for Ebola exposure be isolated (a private examination room with doors closed is likely sufficient) and treated at the direction of public health authorities. "D" is incorrect. Despite its contagious nature, causal exposure to a patient with Ebola (e.g., sitting 10 ft away in the reception area as she walks by) is unlikely to result in transmission. Remember that the persons at highest risk during the 2014 to 2015 Ebola outbreak in West Africa were healthcare workers and caregivers of the Ebola patients. The incubation period of Ebola is 2 to 21 days. The virus can persist in the sperm, eye, breast milk and CNS for months after symptoms have resolved.

An 80-year-old female fell, broke her hip, and underwent intraoperative repair with pinning of the fracture. She developed a local infection at the site of the repair and was treated with a 10-day course of oral clindamycin. She was transferred to the nursing home for rehabilitation and has developed loose, watery stools. Today when you visit her, she reports feeling diffuse abdominal discomfort and has had 10 bowel movements. She is very concerned because she cannot work with the therapist and risks losing her Medicare benefit for skilled nursing.

Question 8.2.1 You plan to do the following:

A) Begin loperamide (Imodium) as needed to prevent diarrhea during the therapy sessions.

B) Obtain stool specimens for Clostridium difficile toxin.

C) Obtain an abdominal CT scan looking for evidence of obstruction.

D) Ask your favorite gastrointestinal (GI) doctor to perform emergency endoscopy for evaluation of lower GI bleed.

E) Obtain stool specimens for ova and parasites.

Answer 8.2.1 The correct answer is "B." C. difficile is the most common bacterial cause of infectious diarrhea in hospitalized patients in the United States (Campylobacter jejuni is the most common bacterial cause overall). Multistep diagnostic algorithms using polymerase chain reaction (PCR) for the toxin gene(s) have the best test performance characteristics (sensitivity 68–100% and specificity 92–100%). Testing should be performed on only symptomatic patients. There is no benefit from testing more than one stool specimen. Although symptomatic therapy is important, "A" is incorrect because antiperistaltic agents should be avoided in patients with C. difficile. Although other causes of diarrhea are possible, the most cost-effective approach in this patient would be laboratory testing for C. difficile according to local laboratory protocol prior to any other more invasive procedure.

A stool specimen reveals the presence of C. difficile toxin A gene. The patient is nontoxic with a normal complete blood count (CBC) and creatinine.

Question 8.2.2 The preferred, first line, treatment of this patient should include:

A) Dificid (fidaxomicin)

B) Lactose restriction and acidophilus milk products

C) Metronidazole 500 mg PO TID for 10 days

D) Vancomycin 250 mg PO QID for 10 days

E) B and C

Answer 8.2.2 The correct answer is "C." Treatment of C. difficile infection (CDI) includes supportive care, discontinuation of the offending antimicrobial agent, and initiation of oral metronidazole 250 mg four times daily or 500 mg three times for 10 days. Metronidazole has been preferred over vancomycin ("D") for the treatment of mild CDI because of lower cost and lower theoretical risk of promotion of vancomycin resistant Enterococcus faecalis (VRE). Based on a recent study that showed lower clinical success rate for metronidazole versus vancomycin, it may be reasonable consider vancomycin first line for mild to moderate CDI and always if the patient has severe CDI (white blood cell [WBC] >15000, creatinine >1.5× baseline). Dificid (fidaxomicin) was approved for treating CDI in 2011. Randomized studies demonstrate similar cure rates between fidaxomicin and oral vancomycin, with fewer recurrences with fidaxomicin. Fidaxomicin—at a much higher cost—may be used for recurrent CDI or when there is a high risk of recurrence. Fecal microbiota transplantation is associated with resolution of recurrent CDI but its role in primary and severe CDI has not been established. There is limited evidence that use of probiotics is effective in the treatment of C. difficile infection and prevention of recurrence. Please see helpful tip below.

Question 8.2.3 Risk factors for C. difficile infection in nursing home patients include:

A) Advanced age

B) Recent acute hospitalization

C) Proton pump inhibitor (PPI) use

D) Long-term residence in a chronic care facility

E) All of the above

Answer 8.2.3 The correct answer is "E." Risk factors for acquisition of CDI in nursing home patients are similar to that of hospitalized patients and include hospitalization, advanced age, GI surgery/procedures, antibiotic exposure, and importantly PPI use.

Failure to resolve C. difficile-associated diarrhea after a 10-day course antibiotic therapy is common. Guess what? Your patient's diarrhea has persisted.

Question 8.2.4 The most reasonable treatment approach is to:

A) Repeat a course of oral metronidazole

B) Treat with a course of oral vancomycin

C) Treat with a course of intravenous (IV) vancomycin

D) A or B

E) B or C

Answer 8.2.4 The correct answer is "D." Relapse and/or recurrence is very common. Typically about 20% of patients have a recurrence of symptoms within about 1 week of completing therapy. These patients usually respond to re-treatment with either metronidazole or oral vancomycin. IV vancomycin is ineffective treatment of C. difficile since vancomycin does not enter into the GI tract from the vascular space.

Objectives: Did you learn to…

• Recognize the presentation of C. difficile infection?

• Identify risk factors for the development of C. difficile diarrhea and colitis?

• Treat patients with initial and recurrent C. difficile infections?

You are called to the emergency department (ED) to examine a 40-year-old man with fever (temperature of 39°C) and headache. His past history is remarkable only for a splenectomy secondary to trauma at age 10. He is not allergic to any antibiotics. Upon examination you note that he has meningeal signs. Nondilated fundal examination shows sharp disc margins, and he is neurologically intact with a nonfocal examination.

Question 8.3.1 The most appropriate action is:

A) Obtain a head CT so that you can safely proceed with lumbar puncture (LP).

B) Order IV penicillin as you prepare to perform LP.

C) Perform a LP immediately and begin antibiotic therapy empirically.

D) Order IV erythromycin as you prepare to perform LP.

E) Order IV vancomycin and IV ceftriaxone as you wait for the CBC. If the CBC is abnormal, you will do the LP.

Answer 8.3.1 The correct answer is "C." Once you suspect bacterial meningitis, rapid diagnostic evaluation and emergent treatment are imperative, including LP and blood cultures. If LP is going to be delayed, then appropriate empiric antimicrobial and adjunctive therapy should be given without delay. Head CT is necessary only in those who are immunocompromised (HIV/AIDS, those receiving immunosuppressive drugs, transplant recipients), have a history of CNS disease (brain tumor and stroke), develop new onset seizures, display papilledema on examination, or who have an abnormal/focal neurologic deficit or abnormal level of consciousness. Antibiotics for a 40-year-old male should cover Neisseria meningitidis and S. pneumoniae, and would include vancomycin and ceftriaxone ("E"). However, "E" is not the best choice. Never wait for a CBC to determine if an adult needs an LP. The decision to do an LP is a clinical one.

Results of the cerebrospinal fluid (CSF) obtained after LP are as follows: cloudy, WBC count 5,000 cells/mm³, 95% neutrophils, glucose 20 mg/dL, and Gram-positive cocci in pairs.

Question 8.3.2 The most likely pathogen is:

A) S. pneumoniae

B) Listeria monocytogenes

C) S. aureus

D) N. meningitidis

E) Pseudomonas species

Answer 8.3.2 The correct answer is "A." Gram stain examination of CSF may permit rapid identification of the causative organism in bacterial meningitis with a sensitivity of 60% to 90%. Prior antibiotic therapy (e.g., a partially treated meningitis … not a single dose of antibiotics in the ED) may reduce the sensitivity by 20%. The likelihood of a positive Gram stain is highest in cases of S. pneumoniae (a Gram-positive diplococcus). Only about one-third of L. monocytogenes meningitis cases demonstrate a positive Gram stain. "D" requires special mention. N. meningitidis is a diplococcus but is Gram negative.

Question 8.3.3 An adjunctive therapy that has been shown to improve neurologic outcomes in pneumococcal meningitis is:

A) Dexamethasone

B) Activated protein C

C) Vasopressors

D) CSF shunt implantation

E) Monoclonal antibody directed against the capsule antigen of the bacterium.

Answer 8.3.3 The correct answer is "A." The Infectious Disease Society of America (IDSA) guideline recommends adjunctive dexamethasone to be administered to all adult patients with pneumococcal meningitis. No other adjunctive therapy has proven benefit. Since the organism is not usually known at the time of initiation of therapy, dexamethasone should be given empirically until the causative organism is identified. If the meningitis is not due to S. pneumoniae, dexamethasone should be discontinued.

Patients should receive standard supportive therapies in an intensive care setting. Complications, when they occur, usually develop within the first 2 to 3 days of therapy. Complications include sepsis, mental status changes, and electrolyte abnormalities.

Question 8.3.4 Highly resistant S. pneumoniae infections of the CNS should be treated with:

A) Third-generation cephalosporin

B) Vancomycin and a third-generation cephalosporin

C) High-dose penicillin G

D) Ampicillin

E) Vancomycin, gentamycin, and rifampin

Answer 8.3.4 The correct answer is "B." Vancomycin should be combined with a third-generation cephalosporin (e.g., ceftriaxone and cefotaxime) for highly resistant pneumococcus. Do not use vancomycin alone; it does not cover Gram-negative organisms. The newer generation fluoroquinolones have enhanced in vitro activity against S. pneumoniae and may be used as alternative agents. However, fluoroquinolones are not recommended unless the patient cannot tolerate or is allergic to standard drugs.

Objectives: Did you learn to…

• Diagnose meningitis?

• Identify the most likely causative organism based on epidemiology and patient characteristics?

• Describe proper use of empiric antibiotics and steroid therapy for bacterial meningitis?

What is the most common bacterial cause of meningitis in college-aged patients who live in dormitories?

A) N. meningitidis

B) S. pneumococcus

C) L. monocytogenes

D) Haemophilus influenzae

E) Escherichia coli

The correct answer is "A." Although S. pneumococcus is the most common cause of bacterial meningitis in the adult population in the United States, N. meningitidis remains the leading cause in adolescents despite vaccination and is particularly prevalent in the setting of dormitory living (e.g., college or military). In addition, the presence of petechial (or purpuric) rash in the lower extremities and pressure points is typical of N. meningitidis. The advent of vaccination has made H. influenzae a less common cause. L. monocytogenes is more prevalent in those over age 50, infants, and the immunocompromised. E. coli is a common cause for meningitis in neonates and infants but is very uncommon in adolescents and adults.

Patients undergoing elective splenectomy should receive all of the following EXCEPT:

A) PCV13 followed by PPSV23 at least 8 weeks later

B) H. influenzae type B conjugate vaccine

C) Influenza vaccine

D) Meningococcal vaccine

E) Oral polio vaccine

The correct answer is "E." Oral polio vaccine is no longer recommended in the United States for anyone. The risk of developing polio from the live vaccine outweighs the benefit of oral administration. All patients undergoing elective splenectomy should receive preoperative vaccination against encapsulated organisms at least 14 days prior to splenectomy; this includes vaccines against S. pneumoniae, meningococcus, and H. influenzae type B (all encapsulated bacteria). New recommendations for all pneumococcal vaccine-naive immunosuppressed adults, including those with asplenia, advise vaccination with a dose of PCV13 first, followed by a dose of PPSV23 at least 8 weeks later. Splenectomized individuals should be re-immunized against pneumococcus in 5 years with a second PPSV23. Patients who have undergone splenectomy need to be educated about seeking prompt medical attention for fever.

A 74-year-old woman is in your office for a complete physical. As part of her routine labs, you obtain a urinalysis (although why is beyond us … there is no recommendation for a screening urinalysis for any nonpregnant patients). On further questioning, she has actually had stress urinary incontinence for a number of years, which is unchanged. She reports no fevers, hematuria, dysuria, flank pain, or other symptoms. The urinalysis shows 10 to 20 WBC/hpf and is nitrite positive on dipstick. A culture of the urine shows 100,000 cfu/mL of E. coli.

Question 8.4.1 How should you treat this patient?

A) Trimethoprim-sulfamethoxazole DS 1 tab PO BID for 10 days

B) Erythromycin 500 mg PO q 6 hours for 14 days

C) Ampicillin 250 mg PO q 6 hours for 10 days

D) Ceftriaxone 1 g IM every day for 3 days

E) With courtesy and respect, but not with antibiotics

Answer 8.4.1 The correct answer is "E." A positive urine culture in an asymptomatic patient (i.e., asymptomatic bacteriuria) should not be treated with antibiotics except during pregnancy. Asymptomatic bacteriuria is a very common finding, especially in elderly females, persons with indwelling catheters, and institutionalized persons. Treatment does not reduce the incidence of symptomatic infection. Treatment also does not reduce mortality in frail elderly patients, and does not improve chronic urinary incontinence symptoms. Persistent asymptomatic bacteriuria does not result in renal insufficiency or the development of hypertension.

Question 8.4.2 Which statement is true of asymptomatic bacteriuria?

A) The finding of pyuria in a urinalysis distinguishes urinary tract infection (UTI) from asymptomatic bacteriuria and guides treatment decisions.

B) The prevalence of asymptomatic bacteriuria in women is unrelated to age, function, or hormonal status.

C) Asymptomatic bacteriuria need not be treated in the pregnant patient.

D) None of the above.

Answer 8.4.2 The correct answer is "D." None of the statements are true. "A" is incorrect because the finding of pyuria with low numbers of WBCs in a urinalysis specimen is nonspecific, common, and frequently unrelated to infection. "B" is incorrect. The prevalence of asymptomatic bacteriuria in women increases with age, declining functional capabilities, and institutionalization. More than 10% of community-dwelling women over the age of 65 and up to 50% of elderly women in nursing homes will have asymptomatic bacteriuria. "C" is incorrect. Pregnancy is one state in which treating asymptomatic pyuria/bacteriuria is indicated. The risk of infection from asymptomatic bacteriuria is high in pregnant patients.

A few years later, the same patient is now 80 years old (you're still paying off your med school loans and will probably work until you're 80), and she is admitted to a nursing home. Her initial tuberculin skin test (TST) with 5-tuberculin unit injection of purified protein derivative was interpreted as 0 mm diameter of induration after 48 hours.

Question 8.4.3 What is your next step?

A) Repeat a TST now

B) Repeat a TST in 2 weeks

C) Repeat a TST in 1 year

D) Declare the patient free of TB

E) Obtain a chest x-ray

Answer 8.4.3 The correct answer is "B." Because the prevalence of a positive TST (Mantoux test) doubles between the first and second tests in initial nonresponders, the U.S. Public Health Task Force recommends a two-step TST by the Mantoux method for screening high-risk populations (e.g., persons living in nursing homes). If the first TST is negative, a second test should be performed approximately 2 weeks later in order to detect the "booster phenomenon." Individuals admitted to a nursing home with a positive TST and no symptoms of active TB may be presumed to have a distant history of infection.

The TST is repeated 2 weeks later and is interpreted again as 0 mm diameter of induration after 48 hours. You reassure the patient that her tuberculin test is negative.

Question 8.4.4 What would most accurately represent a positive TST in THIS patient?

A) Erythema 5 mm in diameter

B) Induration 5 to 10 mm in diameter

C) Erythema of 10 mm in diameter

D) Induration 10 mm in diameter

E) Erythematous induration of any size

Answer 8.4.4 The correct answer is "D." Here is the bottom line. Routine screening is not recommended for low-risk patients (e.g., community dwelling individuals from a low-risk country). Screen only the following: contacts of those with TB, HIV infected patients, IV drug users, those with predisposing factors to TB infection (diabetes, immunosuppressive drugs, lung cancer, etc.), foreign-born individuals arriving in the United States within the last 5 years, healthcare workers, nursing home and other institutionalized individuals and the homeless. Measure the induration and not the erythema. The definition of a positive TST changes with the population tested. See Table 8-1.

A year later, the nursing home calls about her annual TST. You examine the patient and find the diameter of induration is 12 mm. The patient denies cough, weight loss, fever, or chills.

Question 8.4.5 The most appropriate next step in this case is to:

A) Obtain a chest radiograph and, if normal, initiate isoniazid 300 mg and pyridoxine for 9 months.

B) Obtain a chest radiograph and, if normal, observe the patient annually for signs of active TB (weight loss, cough, fever, etc.).

C) Obtain a chest radiograph and, if abnormal, initiate isoniazid 300 mg once daily and pyridoxine for 9 months.

D) Obtain sputum specimens for acid-fast bacilli (AFB) stains and mycobacterial culture and sensitivity testing; and initiate therapy with isoniazid, pyridoxine, pyrazinamide, and rifampin for 6 months.

E) Obtain an interferon-gamma release assay, and if negative, observe the patient annually for signs of active TB (weight loss, cough, fever, etc.).

Answer 8.4.5 The correct answer is "A." The patient lives in a high-risk setting (nursing home). The results of her TST 1 year ago suggest that she was not infected with Mycobacterium tuberculosis at that time. She has newly converted—probably due to exposure to an active case of TB in the facility. The risk of developing active disease following TB infection is greatest in the first 2 years following infection. The risk/benefit ratio favors prophylactic therapy with isoniazid (INH) for the patient who has converted within the last 2 years, as long as there is no sign of active disease and the chest x-ray is negative. Pyridoxine should also be given to prevent peripheral neuropathy. A negative chest x-ray does not mean that you can forego prophylactic therapy, and thus "B" is incorrect. "C" is incorrect because an abnormal chest radiograph must be followed with collection of sputum specimens for AFB staining and culture. "D" is incorrect because a chest radiograph is necessary to evaluate all patients with a positive Mantoux skin test. Sputum specimens should be collected and multiple drug regimens initiated only in patients with signs and symptoms of active disease based on clinical history, examination, and radiographic findings. "E" is incorrect. Since this patient has converted from 0 to 12 mm induration in 1 year, her pretest probability is high enough that performing an IGRA adds nothing.

The patient's son is somewhat distraught that his mother has TB. He asks if she should have received a vaccine before coming into the nursing home.

Question 8.4.6 Regarding the BCG vaccine, which of the following statements is true?

A) Foreign-born persons who received the BCG vaccine should never have a TST administered.

B) The BCG vaccine is most efficacious for older adults, and children benefit much less from the vaccine.

C) A TST in an individual with a remote history of BCG vaccine should be interpreted as if the BCG had not been given.

D) The BCG vaccine is made from killed M. tuberculosis.

Answer 8.4.6 The correct answer is "C." The TST should be interpreted exactly the same way whether or not the patient has received the BCG. "B" is incorrect. BCG is most efficacious in children but protection from the vaccine wanes over a few years. Even in children, it is a poor vaccine, protecting children from TB only about 50% of the time. Persons vaccinated with BCG should still be evaluated by TST when appropriate and an induration of >10 mm (age <35 years) or >15 mm (age ≥35 years) is considered positive. "D" is incorrect. The BCG vaccine is made from attenuated Mycobacterium bovis.

Prior to starting INH, you measured the patient's aminotransferase levels, which were normal. Now, 3 months into treatment, her alanine aminotransferase (ALT) is 42 IU/L (about twice the upper limit of normal).

Question 8.4.7 Your next step is to:

A) Stop her INH since she has had a few months of treatment.

B) Continue the INH as scheduled and follow up with clinical and laboratory monitoring.

C) Switch to rifampin and pyrazinamide.

D) Refer her to a hepatologist for liver biopsy.

E) Start her on milk thistle.

Answer 8.4.7 The correct answer is "B." While liver injury is a significant problem with isoniazid, the drug need not be stopped unless the liver enzymes rise to more than three times the upper limit of normal. Others would suggest that even then the drug can be continued and that only signs and symptoms of hepatitis (fatigue, anorexia, nausea, and vomiting) along with further liver enzyme elevations should prompt discontinuation of the drug. "A" is incorrect because she should have 9 months of prophylactic therapy. "C" is incorrect because rifampin and pyrazinamide have potentially more hepatotoxicity than INH. Finally, "D" and "E" are incorrect. Neither liver biopsy nor milk thistle (touted for its benefit in liver disease) is likely to be useful.

Objectives: Did you learn to…

• Determine who needs to be treated for asymptomatic bacteriuria?

• Interpret TST results?

• Describe the BCG vaccine and how patients who receive it should be approached?

• Recommend appropriate treatment of a positive TST?

• Recognize complications of isoniazid therapy?

• Define and recognize the importance of drug-resistant TB?

A 37-year-old woman with a history of mitral valve prolapse and mitral regurgitation presents for evaluation. She reports no symptoms of shortness of breath or exercise intolerance. She plans to undergo health-screening procedures, including dental exams for routine cleaning and filling of several caries, pelvic examination with removal of an intrauterine device (IUD), and colonoscopy in the next year.

Question 8.5.1 According to the American Heart Association (AHA) 2007 guidelines on prevention of infective endocarditis, what should she receive prior to these procedures?

A) Amoxicillin 2 g orally

B) Azithromycin 500 mg orally

C) Clindamycin 600 mg orally

D) Nothing

Answer 8.5.1 The correct answer is "D." Even now it seems the news has not made it to every corner of the world. But in 2007 there were major changes to the AHA guidelines on infective endocarditis prevention. The one change that would seem to affect the greatest number of patients in primary care practices is the "downgrading" of mitral valve prolapse with regurgitation, which is no longer considered a high-risk condition. If the patient had a condition for which prophylaxis was warranted, all of the other regimens ("A," "B," "C") are options depending on the patient's allergies and other medications, conditions, etc.

Question 8.5.2 According to the AHA 2007 guidelines on the prevention of infective endocarditis, which of the following conditions is NOT a high-risk condition for the adverse outcome of infective endocarditis?

A) Bioprosthetic aortic valve

B) Mechanical aortic valve

C) Congenital heart disease completely repaired with prosthetic material

D) Bicuspid aortic valve

E) Previous history of infective endocarditis

Answer 8.5.2 The correct answer is "D." The guidelines recommend antibiotic prophylaxis for conditions considered to be high risk for adverse outcomes of infective endocarditis. High-risk conditions include prosthetic valves (bioprosthetic homograft and allograft valves and mechanical valves), previous infective endocarditis, and complex cyanotic congenital heart disease.

Question 8.5.3 If your patient had a mechanical aortic valve, appropriate endocarditis prophylaxis might include:

A) Ampicillin IV 2 hours prior to colonoscopy if biopsy of lesions is anticipated

B) Ampicillin IV 2 hours prior to pelvic examination and IUD removal

C) Amoxicillin PO 2 hours prior to routine dental cleaning

D) Amoxicillin PO 2 hours prior to any injection of local anesthesia and filling of caries

E) All of the above

Answer 8.5.3 The correct answer is "C." For high-risk conditions (e.g., mechanical aortic valve), antibiotic prophylaxis is recommended by the AHA prior to cleaning of teeth and removal of plaque. The risk of endocarditis is highest for dental procedures that might traumatize the oral mucosa, such as tooth extractions, periodontal procedures, and cleaning of teeth with removal of adherent plaque. "A," "B," and "D" are incorrect. Prophylaxis is not recommended prior to these procedures. The risk of endocarditis is low for procedures such as lower GI endoscopy and pelvic examination with IUD removal, because the microorganisms likely to cause transient bacteremia following these interventions are not capable of adhering to cardiac valve tissues. Antibiotic prophylaxis is not recommended for restorative dental procedures (e.g., fillings).

All of the evaluations, including the dental examination, seem to go well. However, 1 month later, she returns to see you for gradually (perhaps even subacutely?) worsening fever, malaise, and night sweats. You are concerned that she may have developed infective endocarditis.

Question 8.5.4 The evaluation of a patient suspected of having subacute bacterial endocarditis (SBE) should include all of the following EXCEPT:

A) Three sets of blood cultures obtained at 1-hour intervals within the first 24 hours of assessment

B) Auscultation of chest for evidence of new or changing murmur

C) Transthoracic or transesophageal echocardiogram

D) Spiral chest CT

E) Electrocardiogram

Answer 8.5.4 The correct answer is "D." Spiral chest CT is not indicated in the diagnosis of SBE. History is important: onset of infection can sometimes be related to a recent dental extraction, IV drug abuse, or invasive medical procedure. Symptoms generally begin insidiously and may include weakness, fatigue, fever, night sweats, arthralgias/myalgias, and hematuria. "C," echocardiography, is indicated. The yield for visualization of vegetations for transthoracic echocardiography is 60% to 77% and increases to 96% with transesophageal echocardiography. A prolongation of the PR interval on an electrocardiogram may suggest involvement of the cardiac conduction system.

You carefully examine the patient and find that she is febrile and slightly tachycardic.

Question 8.5.5 You look for signs of infective endocarditis, paying particular attention to all of the following EXCEPT:

A) Osler nodes

B) Painless erythematous macules on the palms and soles

C) Splinter hemorrhages

D) Painless nodules over bony prominences

E) Roth spots

Answer 8.5.5 The correct answer is "D." Classical physical examination findings of SBE include intermittent fever; petechiae; conjunctival hemorrhage; splinter hemorrhages under the nails; erythematous painful nodules on the fingers, palms, and soles (Osler nodes); fundic hemorrhages (Roth spots); painless erythematous macules on the palms and soles (Janeway lesions); and a new diastolic murmur. "D" is not a physical examination finding in SBE. Painless nodules over bony prominences are observed in rheumatic fever and are one of the Jones criteria. Remember that in a modern medical practice, most patients with SBE will not present with these findings, and you must maintain a high degree of suspicion for SBE in the appropriate clinical scenario.

Question 8.5.6 Which of the following is/are included in the major criteria of the modified Duke criteria for endocarditis?

A) Positive blood cultures

B) Janeway lesions (painless macules on palms and soles)

C) Echocardiographic evidence of valvular vegetation

D) A and B

E) A and C

Answer 8.5.6 The correct answer is "E." The modified Duke criteria were developed to provide clinicians with standardized criteria for the diagnosis of endocarditis. They have been validated by pathologic examination and are more sensitive than other endocarditis criteria systems. See Table 8-2.

You draw a CBC, which shows leukocytosis with a "left shift" (e.g., a high percentage of bands and other immature neutrophils). Chest x-ray and urinalysis are unrevealing. You draw blood cultures and admit her to the hospital and start antibiotics. The next morning two blood cultures are reported to grow Gram-positive cocci in clusters. You start IV vancomycin and order a transesophageal echocardiogram. Indeed, the echocardiogram shows a small vegetation on her mitral valve. Blood cultures return showing methicillin-sensitive S. aureus.

Question 8.5.7 What is the most appropriate treatment of this patient now?

A) Nafcillin 2 g IV q 4 hours for 4 to 6 weeks

B) Penicillin G 2 million units IV q 2 hours for 4 to 6 weeks

C) Vancomycin 1 g IV q 12 hours for 4 to 6 weeks

D) Ceftriaxone 1 g IV q 24 hours for 2 weeks

E) Levofloxacin 500 mg IV q 24 hours for 4 to 6 weeks

Answer 8.5.7 The correct answer is "A." Nafcillin is the drug of choice for the treatment of methicillin-sensitive S. aureus endocarditis. Vancomycin should be reserved for patients with penicillin allergy or patients with methicillin-resistant S. aureus (MRSA). Neither ceftriaxone nor levofloxacin would be considered appropriate therapy for staphylococcal endocarditis.

While hospitalized, the patient develops symptoms of heart failure and worsening mitral regurgitation by echocardiogram. The heart failure is managed medically, but the regurgitation is now categorized as "severe." She has had 3 days of antibiotics and is currently hemodynamically stable.

Question 8.5.8 Which of the following is the most appropriate course of action?

A) Complete 6 weeks of antibiotics and manage her heart failure medically for the foreseeable future.

B) Complete 6 weeks of antibiotics and manage her heart failure medically, if possible; plan for valve replacement after 6 weeks of antibiotics.

C) Refer her for emergent valve replacement surgery, then complete the course of antibiotics.

D) Refer her for immediate coronary catheterization, and continue antibiotics.

E) Refer her for heart transplant.

Answer 8.5.8 The correct answer is "C." Progressive heart failure due to moderate-to-severe valvular dysfunction is an indication for surgery. There is evidence that early surgery reduces mortality and embolic complications especially in patients who have left-sided endocarditis associated with large vegetations and severe valvular dysfunction. This is true even in the absence of congestive heart failure and in the presence of less virulent pathogens. Thus, "B" is incorrect. Also, "A" is incorrect, as the patient should have surgery. "D" and "E" are incorrect, as there is no indication for coronary catheterization or heart transplant.

Question 8.5.9 Which of the following organisms is most often responsible for causing infective endocarditis?

A) E. coli

B) Streptococcus viridans

C) Proteus mirabilis

D) None of the above

Answer 8.5.9 The correct answer is "B." S. viridans is the most likely organism to cause endocarditis. Gram-negative organisms, such as E. coli and P. mirabilis, are infrequent causes of infective endocarditis. Other organisms that cause endocarditis include the HACEK organisms (Haemophilus species, Actinobacillus actinomyces comitantes, Cardiobacterium hominis, Eikenella species, and Kingella kingae). In summary, organisms typically found causing endocarditis are S. aureus, S. viridans, enterococci (aerobic, Gram-positive organisms in chains that are GI or vaginal flora), Streptococcus bovis, and HACEK organisms.

Objectives: Did you learn to…

• Determine who is an appropriate candidate for infective endocarditis prophylaxis?

• Recognize signs and symptoms of infective endocarditis?

• Diagnose infective endocarditis?

• Prescribe appropriate treatment for infective endocarditis?

Which of the following medications is/are contraindicated in patients taking linezolid?

A) MAOIs

B) SSRIs

C) Gentamicin

D) Vancomycin

E) A and B

The correct answer is "E." Linezolid can cause serotonin syndrome when combined with SSRIs, lithium, MAOIs, and other serotonergic drugs.

A 10-year-old boy presents with his mother, complaining of intense itching, worse at night, since the first week of school. He has numerous excoriations in the interdigital web spaces, wrists, and anterior axillary folds. His infant sister (10 kg) has recently developed intensely pruritic linear lesions on her palms, soles, face and scalp. Their mother works in a nursing home and has developed pruritus and reddish-brown nodular lesions in her axillae and perineum that have persisted several months after she treated herself with a lotion that was provided at her place of work. As you examination the patient, your skin begins to itch—you need to solve this puzzle quickly.

Question 8.6.1 The most likely ectoparasite affecting this family is:

A) Head lice (pediculosis)

B) Chiggers (mites)

C) Ticks

D) Fleas

E) Scabies

Answer 8.6.1 The correct answer is "E." Scabies' mites (Sarcoptes scabiei) burrow into the epidermis, lay eggs, and hatch larvae in cycles of 3 to 4 days. The most notable clinical symptom is intense pruritus that is worse at night. The typical lesion is small, erythematous, and papular and may resemble eczema in quality and distribution. About 7% of individuals develop a nodular variant (like the mother in this case). Transmission is typically by direct contact and infestations may appear as epidemics in institutions like nursing homes. The organism may be spread by fomites as well, although to a lesser extent. Young children and infants often have involvement of palms, soles, face, and scalp. A clinical diagnosis may be made in the setting of pruritic rash, typical distribution and multiple family members affected.

Question 8.6.2 What is the next best step in this case (remember that one child weighs 10 kg)?

A) Removal of the individual organisms.

B) Tetracycline 10 mg/kg divided TID for all affected family members.

C) Single-dose oral ivermectin 200 μg/kg, repeated in 2 weeks for all affected family members.

D) Symptomatic treatment with topical steroids and oral antihistamines.

E) Single-dose oral ivermectin 200 μg/kg repeated in 2 weeks for the mother; one application of 5% permethrin cream for all other family members for 8 to 14 hours, followed by bathing.

Answer 8.6.2 The correct answer is "E." Permethrin cream is the topical medication of choice. Ivermectin, an antihelmintic medication, is indicated for adults with nodular disease (like the mother in this case), in epidemic settings and for treatment of scabies crustosa. "B" is incorrect because tetracycline is not helpful in this situation and should be avoided in children. "C" is incorrect because oral ivermectin should be avoided in infants weighing <15 kg due to concerns about increased penetration of the blood–brain barrier. Finally, "D" is incorrect because scabies should be treated with specific therapy rather than simply symptomatic therapy. Oh, and "A" is just insane—how could you do that? Is there even a CPT code for that?

You successfully treated the whole family. They are now comfortable, happy, and totally confident in your abilities. The mother returns with her girl, who is now 3 years old, with a new complaint. Apparently, the girl's "bottom" is hurting, a symptom that her mother has interpreted to mean her perineal pain. The pain is worse at night, even waking her at night with vaginal pain. The mother thinks that she may have a bladder infection, but there are no urinary symptoms. In the office, the patient complains only of "itchy butt" and her examination is normal.

Question 8.6.3 What is the next best step in diagnosis of this problem?

A) Reassurance that this is "just a stage"

B) Vaginal speculum examination with cultures

C) "Scotch tape" test

D) Stool collection for ova and parasites

E) Psychiatry consultation for the mother who obviously has Munchausen by proxy syndrome

Answer 8.6.3 The correct answer is "C." The presentation is consistent with pinworm (Enterobius vermicularis) infection. Clinical manifestations of pinworm infection are related to the life cycle of the parasite, in which the adult worm resides in the colon, exits the anus at night, lays eggs in the perianal skin, and may also infest the female GU tract. Typical symptoms include pruritus ani, vulvitis, vaginal pain, poor sleep, and—rarely—abdominal pain (pinworms can migrate and cause appendicitis, and other intra-abdominal illness). The diagnostic test of choice is the "Scotch tape" test. Clear cellophane tape is wrapped around a tongue depressor, sticky side up, and used to sample the perianal area first thing in the morning before bathing. Multiple specimens should be obtained and stored in a refrigerator (it's a good thing OSHA has no jurisdiction in the home). The tape is then examined microscopically for the characteristic ova.

Your "Scotch tape" test is a success, proving your clinical suspicions.

Question 8.6.4 The best intervention is to:

A) Treat the patient with mebendazole 100 mg orally once, repeat in 2 weeks, and encourage good hand washing for the whole family

B) Treat the patient and the entire family with mebendazole 100 mg orally daily for 14 days

C) Treat the patient and the entire family with mebendazole 100 mg orally once, and repeat in 2 weeks

D) Treat the patient with metronidazole 500 mg orally once, and repeat in 2 weeks

Answer 8.6.4 The correct answer is "C." As with scabies, the entire family should be treated. Mebendazole is the agent of choice, although other antiparasitic agents (e.g., albendazole, pyrantel pamoate) may also be used. Pyrantel pamoate is second-line and only has a 90% response rate. "D," metronidazole, is not used for helminthic infections but is effective against protozoal infections, including amebiasis and trichomoniasis. Make sure to wash all of the bed linens and clothing: eggs can stay viable for 20 days (although 3 days is more typical).

Objectives: Did you learn to…

• Diagnose and treat scabies infestations?

• Diagnose and treat pinworm infections?

A 54-year-old construction worker with no significant travel history presents with a fever. He developed the fever 4 weeks ago and has been febrile daily since. He saw another doctor recently. He was evaluated but received no antibiotics or other treatment. His evaluation, including history, physical examination, CBC with differential, urinalysis, serum chemistries, and chest x-ray, has been unrevealing. Today his temperature is 38.5°C.

Which of the following is the most appropriate next step in the evaluation and management of this patient?

A) ESR and/or CRP

B) Chest CT scan

C) Bone scan

D) PSA

E) Vancomycin 1 g IV daily and ceftriaxone 1 g IV daily for 2 weeks

The correct answer is "A." This patient has a fever of unknown origin (FUO). FUO in adults is defined as fever greater than 38.3°C of at least 3 weeks duration with no obvious cause despite extensive evaluation. Infections are the most common source of FUO in children and young adults. The most common infections include tuberculosis and abscesses. In older adults (sorry to say that this patient's age of 54 counts!), collagen-vascular diseases, such as giant cell arteritis and rheumatoid arthritis, are more likely sources of FUO. Therefore, tests for inflammatory markers, like ESR and CRP, are indicated. Other tests to consider at this point include ANA, rheumatoid factor, creatine kinase (CK), and blood and urine cultures. Although malignancy is a consideration, chest CT ("B") and PSA ("D") should not be ordered without other symptoms associated with underlying lung and prostate disease, respectively. A bone scan ("C") would be indicated to look for osteomyelitis, which is an unlikely occult source of fever in this patient with no other reason to believe he has a bone infection. There is no indication for antibiotics ("E") at this point—wait until you have something to treat.

A 45-year-old physician who has recently returned from an early summer fishing vacation (in reality he mostly studied for his upcoming board examination) in rural North Carolina presents for a febrile illness. He reports a 5-day history of fever, malaise, headache, and vomiting. Today, he has developed a nonpruritic rash that began on his extremities and has spread to his body. On examination he has a fever of 38.3°C with a pulse of 120 bpm and otherwise normal vitals. The rash is maculopapular and generalized, involving his palms and soles. Oral mucosa is dry but intact, and the examination is otherwise nonspecific.

Question 8.7.1 What is the most appropriate next step?

A) Reassurance and symptomatic treatment

B) CBC, electrolytes, BUN, creatinine

C) Dermatology referral

D) Punch biopsy of leading edge of rash

E) Admission to the ICU

Answer 8.7.1 The correct answer is "B." This gentleman is sick (pulse of 120 bpm, dry oral mucosa, headache, vomiting). We would be amiss to simply reassure or refer this patient. A CBC and electrolytes may give us an indication of the degree of dehydration and help us narrow the differential (bacterial, viral, etc.). Blood cultures would also be indicated at this time.

The test results return quickly. CBC shows mild thrombocytopenia but is otherwise normal. BUN and creatinine are at the upper limits of normal, and the electrolytes are normal.

Question 8.7.2 The most likely diagnosis is:

A) Chicken pox

B) Syphilis

C) Parvovirus B19

D) Rocky Mountain spotted fever (RMSF)

E) Human monocytic ehrlichiosis

Answer 8.7.2 The correct answer is "D." RMSF is a tick-borne (dog or wood tick) disease caused by Rickettsia rickettsii. It presents with a prodrome of fever and headache several days before the onset of the characteristic rash—a maculopapular eruption that begins at the wrists and ankles and spreads centrally. Eventually, the rash becomes petechial. Despite its name, RMSF is endemic in the southeastern United States, the Atlantic states, and the northern Rocky Mountains. Laboratory manifestations of RMSF are generally nonspecific: mild thrombocytopenia (rarely becoming severe), hyponatremia, azotemia, elevated transaminases, and prolonged PTT and PT.

"B" is incorrect because the secondary stage of syphilis is characterized by a generalized maculopapular rash (including the palms and soles) and is not associated with systemic symptoms.

"E" is also incorrect. Human monocytic ehrlichiosis is caused by Ehrlichia chaffeensis and other related bacteria and presents with a fever and non-specific "flu like" symptoms (headache, fever, myalgias, chills, cough). Rarely a rash, maculopapular or petechial, is seen. Thus, it may be easily confused with RMSF (and in fact some physicians refer to ehrlichiosis as "Rocky Mountain Spotless Fever"). Patients are often leukopenic and thrombocytopenic. The disease is tick-borne and endemic to midwestern, south central, and southeastern states. So, if you think you have a case of RMSF but there is no rash, consider human monocytic ehrlichiosis. See Table 8-4 for more details on tick-borne illnesses. Yeah … we know … everything presents with fever, headache and myalgias. They all sound the same to us too …

Question 8.7.3 What is the appropriate next step for this patient?

A) Obtain serologic studies and await results while treating symptomatically.

B) Obtain skin biopsy and await results while treating symptomatically.

C) Obtain serologic studies and start doxycycline 100 mg orally BID.

D) Obtain skin biopsy and start levofloxacin 500 mg orally daily.

E) Hospitalize and start ceftriaxone 1 g IV daily until fever has resolved.

Answer 8.7.3 The answer is "C." Early treatment for RMSF is essential. Individuals treated after 5 days of symptoms have worse outcomes than those treated earlier. Awaiting serologic studies is inappropriate and treatment should not be delayed. The drug of choice in the treatment of RMSF is doxycycline 100 mg PO BID for 14 days. This is true for children as well! Pregnant women should be treated with chloramphenicol. Agents such as penicillin, fluoroquinolones and cephalosporins are inappropriate in this situation.

Objectives: Did you learn to…

• Identify and diagnose RMSF?

• Initiate treatment of RMSF?

• Recognize other tick-borne illnesses?

A 27-year-old male carpenter presents with pain, redness, and swelling of the distal aspect of the right index finger. He reports getting a splinter in the site 2 days ago while working. The pain is now so severe that he cannot work. On examination, the patient is afebrile, the right index fingertip is extremely tender, and there is an area of fluctuance at the palmar aspect of the finger. All of the redness and warmth are distal to the proximal interphalangeal joint.

What is the most appropriate diagnosis?

A) Paronychia

B) Felon

C) Whitlow lesion

D) Tenosynovitis

E) Achy-breaky-finger

The correct answer is "B." A felon is an abscess of the distal fingertip, most commonly occurring in the index finger and thumb. It can be distinguished from paronychia ("A") because a felon is located in the fat pad of the finger and not the tissue around the nail. Often, an area of fluctuance is palpable. A felon can spread quickly and can involve the periosteum and bone. Appropriate management includes x-ray of the finger (to rule out osteomyelitis), antibiotics, and incision and drainage. "C" is incorrect because a whitlow lesion results from inoculation of broken skin of the hand with type 1 or 2 herpes simplex virus. The whitlow lesion is often typical of herpes (vesicles on erythematous papules) but can also be confused with paronychia or felon if at the distal finger. "D" is incorrect as well. Tenosynovitis should not involve the distal aspect of the digit without affecting the rest of the tendon sheath. "E" is just silly but could be another big country hit!

The Smith family presents to your office in December seeking travel vaccines for a trip to Nigeria. John (34) and Jane (35) Smith have two children, Jack (7) and Jill (5). They will be in Nigeria for a month and will be living in a suburb of Lagos, Nigeria's largest city (Boko Haram not withstanding). They expect to take sightseeing trips into less developed areas. John has no previous medical problems. Jane is currently taking venlafaxine (Effexor) for depression and is known to have a sulfa allergy. Jack has had occasional bouts of reactive airway disease and also has a sulfa allergy. Jill is healthy. Everyone in the family is up-to-date on all routine North American vaccines.

Question 8.8.1 Regarding pathogens they might encounter in Africa, which of the following is caused by a virus?

A) Plasmodium ovale

B) Plasmodium falciparum

C) Dengue fever

D) Entamoeba histolytica

E) All of the above

Answer 8.8.1 The correct answer is "C." Dengue fever (aka "break bone" fever) is a viral infection caused by Flavivirus (more below). "A" and "B," P. falciparum and P. ovale, are two species of malaria parasites. P. falciparum tends to produce more severe infections that can be rapidly fatal in malaria naive patients. "D," E. histolytica, is the intestinal protozoan parasite responsible for amebiasis.

Question 8.8.2 Mr. Smith asks for advice on the use of insect repellent. What do you recommend?

A) Any repellent will do, they're all the same. Just use the cheapest

B) Pleasant-smelling repellents, such as Avon SkinSo-Soft^TM, are just as effective as any DEET-containing formulation

C) Use repellent with DEET concentrations of at least 50% for the children, since their protection is so vital

D) Apply permethrin insecticide to the skin to enhance any other repellent's efficacy

E) Use DEET or picaridin-containing repellents, as they are the most efficacious insect repellents available, but avoid DEET concentrations greater than 30% in children

Answer 8.8.2 The correct answer is "E." Repeated experiments clearly show DEET- and picaridin-containing repellents to be the most effective for deterring bites and these are the two recommended by the CDC. Picaridin-containing insect repellents do not cause neurotoxicity. The American Academy of Pediatrics recommends not exceeding 30% DEET concentration in repellants for children, due to a slight risk of toxicity seen in frequent applications over a long period of time. Applying DEET to clothing rather than skin reduces the risk of toxicity. Adults can theoretically use any concentration, but 30% is usually sufficient for most situations. Often, more cosmetically pleasing products, such as Avon brand SkinSo-Soft, are less effective and last a mere fraction of the duration of DEET compounds. Permethrin insecticide, when applied to clothes, tents, and bed nets, is synergistic with insect repellent, but permethrin itself is not formulated for use as an insect repellent on skin. Of note, many countries have a combination DEET-Permethrin product available for use on cloths.

Mrs. Smith reports that her friends get sick with diarrhea every time they travel abroad. She would like to avoid this.

Question 8.8.3 Which of the following is (are) true about traveler's diarrhea?

A) Enterotoxigenic E. coli (ETEC) is the most common cause of this condition

B) Even carefully avoiding the consumption of tap water or unwashed vegetables may not be sufficient to prevent the disease

C) Fluoroquinolones can help to rapidly cure this condition but are contraindicated in pregnancy and young children

D) The use of loperamide is effective in reducing the duration of symptoms but is contraindicated in children <2 years of age

E) All of the above are true

Answer 8.8.3 The correct answer is "E." In most parts of the world, including Africa, ETEC is the most common cause of travelers' diarrhea. Although it is advisable to avoid tap water, unwashed foods, and raw foods, these measures are usually insufficient to completely eliminate the risk of contracting the disease. A traveler may drink only bottled liquids, but might forget that the ice in the glass is made from tap water. Although the disease is self-limited, a single dose of ciprofloxacin 750 mg (see note below) may shorten the course of symptoms significantly. The dose for moderate or severe disease is ciprofloxacin 500 mg BID. A patient's symptoms can be further shortened by adding loperamide, which is safe in the absence of bloody stools. Loperamide is potentially toxic to infants and toddlers.

Finally, you discuss the medication options for malaria prophylaxis.

Question 8.8.4 Which of the following is TRUE?

A) Mefloquine (Lariam) is relatively contraindicated for Jane due to her history of psychiatric illness

B) Doxycycline would be a safe and effective option for the whole family

C) Although malaria is resistant to chloroquine in many parts of the world, it can still be used for prophylaxis in West Africa

D) Atovaquone/proguanil (Malarone) is contraindicated for Jane and Jack due to their sulfa allergy

E) A month is too long a time to use malaria prophylaxis safely; recommend against it

Answer 8.8.4 The correct answer is "A." Mefloquine is an effective, once-a-week prophylaxis for malaria. However, it carries a significant risk of CNS side effects including vivid or disturbing dreams. There have been case reports of the medication inducing psychosis, so the drug is relatively contraindicated for patients with a history of psychiatric illness (such as Jane Smith). "B," doxycycline, may be a good option for the parents, but is contraindicated in children because of their age and risk of tooth discoloration. "C" is incorrect. Malaria throughout Africa, India, Southeast Asia, and South America is now assumed to be resistant to chloroquine. Finally, "D" atovaquone/proguanil is relatively contraindicated in patients with G6PD deficiency due to a risk of hemolysis, but it does not contain sulfa. Of particular note is answer "E." Medications used to provide malarial chemoprophylaxis have been shown to be well-tolerated for at least a year or more (http://www.cdc.gov/malaria/about/faqs.html). Therefore, one month is not too long to use malaria prophylaxis safely and it should be recommended to the family for their travel.

Weeks pass, and you hear nothing more until you are called to the acute care clinic, where Jack Smith has been brought in by his parents for fever and lethargy. Jack had been treated in Lagos, Nigeria, for malaria with an unknown medication, and he subsequently recovered. Jack was apparently well until 10 days after returning home, when he developed rapid onset of a fever and shaking chills. He also complained to his parents of generalized abdominal pain and watery, non-bloody diarrhea. The parents treated him at home for a day with ibuprofen and acetaminophen, but he seemed to worsen. He became lethargic, stopped drinking and eating, and the fever continued.

Jack appears drowsy and listless but is arousable. He does not respond to questions about current symptoms, but cooperates with an examination. Findings are temperature 39.1°C, pulse 136 bpm, blood pressure 100/50 mm Hg, and respiratory rate 24. His neck is supple with mild lymphadenopathy. He is tachycardic with a mild flow murmur. His abdomen is nontender with a palpable spleen. No rash or petechiae are noted. The rest of the examination is unremarkable. A recurrence of malaria is suspected.

Question 8.8.5 What is the best method for confirming this diagnosis?

A) Blood culture

B) Malaria serology

C) Malaria antigen test

D) Thin and thick blood smears

E) Stool ova and parasite

Answer 8.8.5 The correct answer is "D." Malaria is usually diagnosed by blood smear. The thick blood smear is the more sensitive screening test, and the thin blood smear is used to identify the species of parasite. There are rapid antigen tests available they have higher false positives and false negatives than a smear. In addition, they do not allow identification of the species. Thus, if one suspects malaria and the rapid test is negative, thick and thin smears are still indicated. The blood smear remains the gold standard. Malaria serology and cultures are used only in experiments and are not helpful for diagnosis of an individual patient. Of note, PCR-based testing has excellent sensitivity and specificity but is expensive and not widely available. The malaria parasite cannot be identified in stool.

You begin IV fluids and arrange hospital admission. The relevant laboratory tests are drawn and sent, including CBC, blood cultures, tests for malaria, chemistry profile, blood type and screen, and urinalysis. LP is performed and the CSF is normal. In the meantime, the laboratory calls with the report that P. falciparum has been identified.

Question 8.8.6 What antimicrobial should be chosen as initial therapy?

A) Oral hydroxychloroquine (Plaquenil), since many hospitals do not stock chloroquine

B) Oral mefloquine (Lariam)

C) Oral quinine

D) IV quinidine, since IV quinine is not generally available in the United States

E) IV atovaquone/proguanil (Malarone)

Answer 8.8.6 The correct answer is "D." Clearly, since this patient is ill and not tolerating oral intake, an IV route for malaria treatment is indicated. IV atovaquone/proguanil does not exist, so the only available option is quinine. But IV quinine is not available in the United States, so its isomer, quinidine (the antiarrhythmic) is used instead. In patients from chloroquine-sensitive zones (currently Central America and the Middle East), treatment with chloroquine is acceptable. Hydroxychloroquine is an option if chloroquine is not available.

Despite a frightening hospital course that included generalized seizures, hypoglycemia, hematuria, renal insufficiency, and an exchange transfusion, Jack eventually recovers completely. The Smith family thanks you for your help and hopes you'll accompany them on their next trip to Africa.

Objectives: Did you learn to…

• Identify important elements of a patient's travel plans and unique risks when providing counseling for overseas travel?

• Identify preventative measures for malaria, including chemoprophylaxis and insect bite avoidance?

• Diagnose travelers' diarrhea and describe its prevention and treatment?

• Recognize the signs and symptoms of malaria, describe methods of diagnosis, and initiate therapy?

A family comes to see you because the two children, ages 7 and 4, have developed itchy scalps. The parents seem unaffected. So far, they have not tried any treatments. On examination of both children, you find erythematous papules on the occiput and small white eggs firmly attached to the hair shaft about 1 cm from the scalp. Upon leaving the room, you head straight for the shower and scrub your scalp for 5 minutes.

The most appropriate treatment for the suspected diagnosis is:

A) Application of 1% permethrin cream to all family members for 10 minutes followed by rinsing, combing out all nits with a special louse comb, and decontaminating affected garments and bed linens. Repeat in 7 days

B) Elimination of animal or fomite sources of infestation and use of insect repellents

C) Removal of any adherent organisms and oral doxycycline for 14 days

D) Application of 5% permethrin cream to all family members for 8 to 14 hours, followed by showering

E) Shave everyone's head

The correct answer is "A." These are head lice. Pediculosis infestations of the hair and scalp are usually asymptomatic but can present with itching. The diagnosis is made by demonstration of the louse or nits, which fluoresce a pale blue under a Wood's light. Treatment with topical agents such as permethrin cream for two applications and wet combing to remove nits is recommended by the CDC. Ivermectin may be effective in cases of resistant organisms. It is reasonable to recommend washing clothing and bedclothes of an infested person, but head lice do not survive off the scalp longer than 48 hours. "B" is appropriate for chiggers (mites) or fleas. "C" is appropriate for ticks (if also at risk for a tick-borne illness). "D" is a treatment of scabies (note the difference in strength of permethrin). Of note, there is no benefit to keeping children with head lice out of school. Avoid sharing hats, etc. Just try to get this one past the school nurse.

A 19-year-old female college student presents to student health services with "the flu." She has noted a fever of 38.9°C and myalgias. She is treated with symptomatic care and discharged back to her dormitory. Three hours later her roommate finds her lethargic and difficult to arouse, so she calls 911. On examination, her blood pressure is 70/30 mmHg with a pulse of 145 bpm. Her neck is supple, but she is lethargic and complaining of severe muscle aches. She denies headache. There is a fine macular rash over her abdomen.

Question 8.9.1 You need to obtain a little more history. The most important historical factor in this case is:

A) History of splenectomy

B) History of acetaminophen overdose

C) History of tobacco use

D) Sexual history

Answer 8.9.1 The correct answer is "A." "A" is important since patients with a splenectomy can get sick rather rapidly from pneumococci and other encapsulated bacteria. The rest are much less important. Shock is not a prominent feature of acetaminophen overdose ("B")—if it occurs at all. In addition, acetaminophen overdose is not associated with a rash. "C" and "D" are incorrect. These elements of social history, while important to her overall care, will not aid you in the diagnosis and immediate management. Another very pertinent historical feature would be tampon use, which is important because this patient may have toxic shock syndrome.

The patient is able to give you the additional history that she does not use tampons and has not taken any medication except for occasional acetaminophen and ibuprofen in recommended doses. She has her spleen … in a jar in her dorm room—no, wait, we mean in her left upper quadrant. It's her ex-boyfriend's spleen in the jar.

Question 8.9.2 On the basis of this information you decide that:

A) It is unlikely that this is toxic shock syndrome given that she does not use tampons.

B) The combination of acetaminophen and ibuprofen in this patient with the flu has led to hypotension.

C) Given that she is immunocompetent and has her spleen intact, this cannot be sepsis since it started so quickly.

D) Toxic shock, which was a big problem in the 1980 s and early 1990 s, no longer occurs since the advent of less absorbent tampons.

E) None of the above.

Answer 8.9.2 The correct answer is "E." "A" is incorrect because up to 50% of cases of toxic shock occur as the result of staphylococcal infections unrelated to tampons. These may be ingrown toenails, infected abrasions, etc. "B" is incorrect. Acetaminophen and ibuprofen are frequently combined without difficulty. "C" is also incorrect. Splenectomized patients are more prone to sepsis from encapsulated organisms, but the fact that the patient has a spleen does not grant invincibility. Sepsis obviously occurs in the normal host as well. Finally, "D" is incorrect. While absorbent tampons are a major culprit in toxic shock syndrome, as noted above, there are other causes. Thus, toxic shock syndrome is not going away anytime soon.

Question 8.9.3 The organism(s) responsible for toxic shock syndrome is (are):

A) Staphylococcus

B) H. influenzae

C) Streptococcus

D) A and B

E) A and C

Answer 8.9.3 The correct answer is "E." There are two types of toxic shock syndrome, one caused by Staphylococcus and the other by Streptococcus. There are certain subtypes of these bacteria that make the toxin responsible for toxic shock syndrome and only certain hosts are thought to be susceptible. Of note, most patients with streptococcal toxic shock are bacteremic, whereas those with staphylococcal toxic shock are not.

Question 8.9.4 Which of the following would you NOT expect to find on laboratory testing of this patient with suspected toxic shock syndrome?

A) Creatinine of 2.0 mg/dL (normal 1 mg/dL)

B) Elevated ALT/AST

C) Platelets of 450,000/mm³

D) Elevated CPK

Answer 8.9.4 The correct answer is "C." By the definition of toxic shock syndrome, the platelet count should be <100,00 mm³ in Staphylococcal-related toxic shock. All of the other findings are representative of the multisystem dysfunction that categorizes toxic shock syndrome.

Your patient is a little more alert, most likely due to your charming wit. A second set of vitals shows: blood pressure 72/44 mm Hg, pulse 140 bpm, respirations 24, temperature 39°C. Labs are pending.

Question 8.9.5 What is the single best next step in the care of this patient?

A) Start IV nafcillin

B) Place two large-bore IV lines and start aggressive fluid replacement

C) Start IV norepinephrine

D) Give a single dose of IV dexamethasone

E) Transfuse two units of packed red cells

Answer 8.9.5 The correct answer is "B." Treatment is mainly supportive. She's in shock. Two large-bore IV lines should be placed with fluids running wide open, and norepinephrine (or other pressor) should be available if her pressure does not improve rapidly. "A" is of special note. Patients with classic toxic shock syndrome (staphylococcal) are not bacteremic. They are suffering from the effects of a localized infection that has produced a toxin that is the causative agent in their illness. Therefore, while an anti-staphylococcal drug is important (as is locally treating the site of infection with incision and drainage, toenail removal, etc.), the anti-staphylococcal drug is not to treat bacteremia. However, the patient should receive empiric antibiotics (IV clindamycin and vancomycin) to treat a suspected localized infection, with narrowing of the spectrum when more data (e.g., cultures and susceptibilities) become available. "D" and "E" are incorrect since neither steroids nor blood products are currently indicated.

Objectives: Did you learn to…

• Identify signs and symptoms of toxic shock syndrome?

• Describe the pathophysiology of toxic shock syndrome?

• Initiate management for a patient with sepsis and toxic shock syndrome?

A 15-year-old male presents with his mother who had to drag him in to your clinic. He won't look up from his iPhone as his mother gives an exasperated history. He's had "boils" several times on his buttocks and legs that he prefers to "pop" rather than to have treated by a medical professional. Today he has a large red lump on his anterior left thigh. On examination, you find a healthy-looking male with normal vital signs and a 3 cm area of erythema with central pustule and fluctuance. You incise the lesion, obtain a sample for culture and drain it completely (just in time for lunch).

If the culture returns with MRSA as you suspect it will, you must treat with:

A) Good local wound care

B) Packing the wound daily

C) Chlorhexidine baths and mupirocin to nares daily

D) Doxycycline orally for 2 weeks

E) Oritavancin (trade name Orbactiv) 1,200 mg IV, single dose

The correct answer, and the only thing you must do for this patient, is "A." You have already treated the local infection, the abscess on his skin, with incision and drainage. Unless his has an extending cellulitis or is systemically ill (e.g., febrile), he does not require systemic antibiotics, so "D" and "E" are incorrect. Packing a small abscess after incision and drainage ("B") is a time-honored method of inflicting mild torture on patients. This practice is grounded in tradition and perceived benefits of packing large, deep soft tissue wounds. However, wound packing has not been shown to benefit small skin abscesses (e.g., less than 5 cm), but it has been shown to increase pain, prolong healing and result in greater healthcare utilization. "C" sounds good for a patient who has a history of skin abscesses and is probably worth a try in patients with recurrent MRSA skin infections; but the benefits are minimal at best. Even after clearing MRSA, the little bugger has a tendency to recur; re-colonization rates are as high as 75% several months after decolonization. Finally, decolonization with "bleach bathes" has also been tried, and these seem to be marginally effective if they are effective at all (Clin Infect Dis. 2014;58:679).

If treating a MRSA cellulitis, many options are available, including "D" and "E." Antibiotic therapy should be dictated by culture and susceptibility when available. Empiric oral antimicrobials that are generally regarded as effective against MRSA include trimethoprim-sulfamethoxazole, tetracyclines (e.g. doxycycline), and linezolid. For more serious MRSA infections and those failing to respond to empiric oral antibioitics, vancomycin (30 mg/kg per 24 hours) is still first-line IV therapy. Other options include daptomycin, ceftaroline, lipoglycopeptides, and tigarcycline (3rd or 4th line due to increased mortality risk). The newer lipoglycopeptides (e.g., oritavancin, dalbavancin) are long-acting antimicrobials that have the advantage of infrequent administration—in fact, oritavancin is given as a single dose. The lipoglycopeptides are expensive and have no medical advantage over less expensive options. In addition, they are for skin infections only and not systemic infections. There is too much resistance to clindamycin to recommend it when treating MRSA.

One of your patients has recently been in Indonesia for a prolonged period of time. Upon return to the United States, he develops a febrile illness 5 days after landing in Iowa (yes, we have airports). When he presents to the ED, he recalls being bitten by a particularly large and persistent mosquito just before boarding the airplane. On arrival to the ED, he complains of severe, diffuse body pain, headache, and eye pain and eye redness. Vitals show a temperature of 38.5°C, pulse 145 bpm. Labs show a low white count and thrombocytopenia. He does NOT note cyclic fevers. His eosinophil count is normal. A Giemsa stain of the blood shows no organisms.

Question 8.10.1 The most likely cause of this illness is:

A) Pneumococcal sepsis

B) Dengue fever

C) Malaria

D) Filariasis

E) Kuru

Answer 8.10.1 The correct answer is "B." This patient has Dengue fever. Dengue fever is most common in Asia but also occurs in Africa, South and Central America, and the Caribbean (and may eventually occur in the southern United States if global temperatures continue to rise). Patients typically present with fever, conjunctivitis, headache, retro-orbital pain, leukopenia, and thrombocytopenia. The sine-qua-non of Dengue fever is severe myalgias and arthralgias, hence the moniker "break bone fever." More mild forms do occur, however. "A" is incorrect since patients with pneumococcal sepsis will generally not have thrombocytopenia and a low WBC count (yes, we know there are exceptions). "C" is incorrect because the patient does not have cyclic fevers and a blood smear is negative (plus, we've already had our malaria case. Why would we repeat it?). Filariasis, "D," presents with eosinophilia and microfilaria in the bloodstream. Again, this should be evident on the blood smear. "E," kuru, is a prion-driven degenerative neurological disease found in Papua, New Guinea. This patient does not have any evidence of neurological disease, aside from a headache, which also makes this option less likely.

With supportive care, the patient recovers. However, not having learned his lesson he returns to Indonesia. When he comes home to Iowa again, he presents again to the ED, suspecting that he has Dengue fever.

Question 8.10.2 Signs and symptoms of a second occurrence of Dengue fever include all of the following EXCEPT:

A) Capillary leak with hypovolemia and hemoconcentration

B) Hemorrhagic complications including capillary fragility

C) Onset >14 days after exposure

D) Severe thrombocytopenia

Answer 8.10.2 The correct answer is "C." If a returning traveler presents more than 14 days after returning home, Dengue fever can be effectively ruled out. In this case, think of other infectious diseases including malaria. The incubation period of Dengue fever is 3 to 7 days. The rest are correct. Patients with their second or subsequent episode of Dengue fever can present with capillary leak syndrome, marked thrombocytopenia, and severe hemorrhage. It is usually the second or subsequent infection that leads to mortality.

Objectives: Did you learn to…

• Describe the presentation of Dengue fever?

• Distinguish the difference between the first and subsequent episodes of Dengue fever?