The following cases and commentary, which involve judicious use of antibiotics, are excerpted from ACP's Medical Knowledge Self-Assessment Program (MKSAP 15).
Case 1: De-escalation of therapy
A 61-year-old homeless man is hospitalized after being “found unconscious” in an alley on a cold morning in March. On physical examination, the patient is barely arousable. Temperature is 33.0°C (91.5°F), blood pressure is 90/50 mm Hg, pulse rate is 50/min, and respiration rate is 10/min. Numerous draining skin lesions are noted.
Active internal rewarming is undertaken, and intravenous fluid resuscitation is initiated. The chest radiograph is normal. Urine and blood culture specimens are obtained, and cefepime and vancomycin are begun. Blood cultures and aspirates of deep soft tissue lesions grow methicillin-susceptible Staphylococcus aureus. All other culture results are negative.
His clinical course improves by hospital day 3, and the antibiotic stewardship team recommends changing cefepime and vancomycin to nafcillin alone.
Which of the following is the most important reason for making this recommendation?
B. Need for fewer daily infusions
C. Reduced risk of nephrotoxicity
D. Reduction of selection for resistant colonizing organisms
Case 2: Vancomycin dosing
A 48-year-old woman with breast cancer is hospitalized with fever and chills. She previously had breast-conserving surgery and was receiving adjuvant chemotherapy. Peripheral blood cultures and cultures from the chemotherapy port are obtained. All specimens are positive for coagulase-negative staphylococci. The patient is reluctant to have the port removed because of the convenience it affords her.
Vancomycin, twice daily, is begun and quickly controls the fever and chills. All blood culture specimens drawn after starting antibiotic therapy are negative, and drug levels are at target values.
After 5 days of in-hospital vancomycin, the patient is ready for discharge and will complete the 14-day antibiotic course at home. She weighs 58 kg (128 lb). Her serum creatinine level is 1.0 mg/dL (88.4 µmol/L).
After the patient has been home for 5 days (day 10 of the 14-day regimen), the home infusion aide reports a serum creatinine level of 0.9 mg/dL (79.6 µmol/L).
Which of the following is the most appropriate management of the antibiotic therapy?
A. Adjust the vancomycin dose to a peak level of greater than 40 µg/mL
B. Adjust the vancomycin dose to a trough level of greater than 20 µg/mL
C. Complete vancomycin therapy without drug-level monitoring
D. Reduce the vancomycin dose by 50%
Case 3: Soft tissue infection
A 48-year-old man undergoes emergency department evaluation for a painful, swollen right thigh following a recent fall at home. The patient has multiple sclerosis and is taking a tapering course of corticosteroids. He also has long-standing type 2 diabetes mellitus complicated by peripheral sensory neuropathy and recurrent gastroparesis. Current medications are prednisone and insulin glargine and insulin lispro.
On physical examination, temperature is 38.4°C (101.2°F). BMI is 17.5. The right thigh has a fluctuant, erythematous, tender mass surrounded by an area of skin thickening and erythema extending 7 cm beyond the bulging area. Neurologic examination findings are consistent with multiple sclerosis as well as areflexia and lack of sensation and proprioception in the feet.
While in the emergency department, the patient vomits twice and is given intravenous fluids. In the operating room, the surgeons incise and drain the thigh lesion, and cultures are obtained. Imipenem, vancomycin, and intravenous fluids are begun, and the patient is hospitalized.
Laboratory studies immediately following surgery find a leukocyte count of 24,000/µL (24 × 109/L) with a left shift and creatinine of 0.4 mg/dL (35.4 µmol/L). Gram stain of surgical drainage fluid shows many leukocytes and occasional gram-negative rods.
On hospital day 2, his condition has stabilized and he is no longer vomiting. The culture of the drained fluid shows Klebsiella oxytoca that is resistant to ampicillin and cefazolin but susceptible to all carbapenems, trimethoprim-sulfamethoxazole, and colistin. The patient asks to be discharged for home care by his wife.
Which of the following is the most appropriate therapy?
C. Imipenem and vancomycin
Case 4: MRSA pneumonia
A 64-year-old woman who resides in a nursing home and has a history of end-stage kidney disease for which she receives hemodialysis presents with fever, copious sputum production, and hypoxemia. Chest radiograph shows a right-sided infiltrate. She is intubated and started on vancomycin, levofloxacin, and piperacillin-tazobactam for treatment of diffuse right-sided pneumonia.
On day 3 in the hospital, she has been afebrile for 48 hours, and her secretions are scant and white. On physical examination, the temperature is 36.9°C (98.5°F), pulse rate is 88/min, respiration rate is 14/min, and blood pressure is 140/86 mm Hg; oxygen saturation is 96% on FiO2 0.4. There are diffuse right-sided inspiratory crackles. Leukocyte count is 9600/µL (9.6 × 109/L) (20,400/µL [20.4 × 109/L] on admission). Admission sputum culture is now growing methicillin-resistant Staphylococcus aureus; blood cultures are negative. Chest radiograph shows slight improvement in the right-sided infiltrate compared with admission.
Which of the following is the most appropriate antibiotic therapy at this time?
A. Complete an 8-day course of all three antibiotics
B. Complete an 8-day course of vancomycin and discontinue the other antibiotics
C. Complete a 14-day course of all three antibiotics
D. Complete a 14-day course of vancomycin and discontinue the other antibiotics
E. Discontinue all antibiotics
Case 5: Acutely ill with gram-positive bacilli
A 35-year-old male customs inspector is brought to the emergency department because of a 2-day history of fever, shortness of breath, and chest pain. He has had no recent known contact with ill persons.
On physical examination, the patient is diaphoretic and appears acutely ill. He is oriented only to person. Temperature is 38.0°C (100.4°F), blood pressure is 88/60 mm Hg, pulse rate is 110/min, and respiration rate is 28/min. Coarse bronchial breath sounds are heard.
The leukocyte count is 15,000/µL (15 × 109/L). A chest radiograph shows a widened mediastinum and bilateral pleural effusions.
A buffy coat Gram stain of a peripheral blood smear shows box car-shaped gram-positive bacilli.
Which of the following is the most appropriate treatment?
A. Ciprofloxacin, rifampin, and vancomycin
B. Erythromycin, clindamycin, and rifampin
C. Erythromycin, vancomycin, and rifampin
D. Penicillin, rifampin, and vancomycin
Case 6: Recurrent pneumonia hospitalizations
A 54-year-old woman is hospitalized for recurrent pneumonia, the present episode of which began 3 days ago. She has been hospitalized twice over the past 2 months for pneumonia that was treated with 2-week regimens of amoxicillin plus clavulanic acid and clarithromycin plus ceftriaxone, respectively, with improvement within 1 to 3 days of therapy. Each episode was characterized by the sudden onset of fever, chest tightness, dyspnea, nonproductive cough, and diffuse interstitial pulmonary infiltrates on chest radiograph.
Medical history is otherwise unremarkable. For the past 2 months, she has been house-sitting for a friend who has a hot tub that she uses occasionally.
On physical examination, she is mildly dyspneic. Temperature is 37.7°C (99.9°F), blood pressure is 135/80 mm Hg, pulse rate is 90/min, and respiration rate is 22/min. Arterial oxygen saturation is 90% on ambient air. Diffuse fine crackles are heard throughout both lung fields. The leukocyte count is 7600/µL (7.6 × 109/L), and the serum lactate dehydrogenase level is 450 U/L.
A chest radiograph shows an interstitial micronodular pattern most prominent in the lower and mid-lung zones. HIV serology and bronchoscopic lavage results of routine cultures and rapid testing for influenza; parainfluenza 1, 2, and 3; adenovirus; respiratory syncytial virus; Chlamydophila pneumoniae; and Mycoplasma pneumoniae are negative. The results of a mycobacterial smear are negative, and cultures are pending.
Which of the following is the most appropriate treatment?
A. Ceftriaxone and azithromycin
D. Ethambutol and clarithromycin
Answers and commentary
Correct answer: D. Reduction of selection for resistant colonizing organisms.
Antibiotic stewardship is the process of adapting antibiotic usage to newly acquired diagnostic information in an effort to reduce overall drug toxicity to the patient and minimize adverse effects to the patient and the hospital flora. The early use of aggressive antibiotic treatment is widely accepted for critically ill patients before confirmation of a specific diagnosis. In this patient, the infection source was difficult to determine, and use of broad-spectrum antibiotics (including those for Pseudomonas coverage) was prudent. However, once the diagnosis is known, excessively broad coverage is no longer beneficial because the risk of selecting for resistant colonizing organisms is increased. Willingness to de-escalate therapy can be challenging in a patient who has responded well to broad-spectrum antibiotic coverage. However, failure to curtail excess antibiotic use is an ecologic hazard for that patient and for the medical unit as a whole. Although de-escalation has been tested most often in patients with nosocomial pneumonia (for which an ultimate microbial diagnosis can almost always be established), this principle is now being applied more broadly.
The cost difference between the two regimens is minimal because generic versions of all three drugs are available. Changing to nafcillin will reduce Pseudomonas coverage rather than increase coverage for this pathogen. However, this is an acceptable risk because Pseudomonas is easy to cultivate in the laboratory and, even when present, may represent colonization in a critically ill hospitalized patient.
The number of daily infusions of the two regimens is comparable (nafcillin every 4 to 6 hours and cefepime and vancomycin every 12 hours). This may be affected by variations in renal function, which will tend to reduce the number of infusions of cefepime and vancomycin but will have no impact on nafcillin.
Changing to nafcillin alone will not reduce the risk of drug toxicity, which is increased only when greatly excessive vancomycin doses are administered.
- Antibiotic stewardship is the process of adapting antibiotic usage to newly acquired diagnostic information in an effort to reduce overall drug toxicity to the patient and minimize adverse effects to the patient and the hospital flora.
Correct answer: C. Complete vancomycin therapy without drug-level monitoring.
The rapid and accurate measurement of vancomycin serum levels is now widely available, but the rationale for monitoring can still be confusing. This patient requires only four more doses of vancomycin. Her outcome has been satisfactory, kidney function is unaltered, and the infection is not considered severe. Therefore, additional monitoring is not needed. Dosing based on algorithms (including the patient's weight, age, and kidney function) is usually associated with predictably good drug levels. Patients who have already achieved target drug levels do not require additional measurements.
Controversy continues about when to measure vancomycin serum levels for patients with serious Staphylococcus aureus infections or with infection caused by any organism that has a relatively high vancomycin minimal inhibitory concentration (MIC). Measurements are indicated for patients with fluctuating renal function. When monitoring is needed, peak levels are rarely obtained because they correlate poorly with predicting outcome or determining toxicity. Since vancomycin is considered a time-dependent antibiotic, maintaining trough levels above the MIC, with a target level of 10 µg/mL to 20 µg/mL, is more relevant than achieving high peak levels. Similarly, reducing the dose to avoid toxicity is unlikely to be helpful and may result in therapeutic failure.
- Patients taking vancomycin do not need constant monitoring of drug levels if renal function is stable and initial levels were satisfactory.
Correct answer: B. Ertapenem.
This patient's health is significantly impaired by malnutrition, use of corticosteroids, and advanced diabetes mellitus. Therefore, in addition to draining the thigh abscess, administering antibiotics was appropriate. This patient's early aggressive antibiotic treatment was meant to address the results of the Gram stain of the surgical drainage fluid and the uncertainty regarding the infecting microbe. Although imipenem and vancomycin are appropriate empiric antibiotics in the hospital, ertapenem is a more efficient and convenient drug for home care. In addition to having a good spectrum of activity for Klebsiella, ertapenem can be given once daily at home, which is much easier than the six daily infusions required for imipenem and vancomycin administration.
Colistin has the necessary spectrum of activity for Klebsiella but is potentially too nephrotoxic and neurotoxic for use when other agents are available.
Linezolid is approved by the U.S. Food and Drug Administration for treatment of vancomycin-resistant Enterococcus faecium infections (including bacteremia), community-acquired and nosocomial pneumonia, and skin and skin structure infections. Oxazolidinones are active against most gram-positive organisms such as streptococci, enterococci, and staphylococci, including strains resistant to other classes of antibiotics. Linezolid also has in vitro activity against some anaerobes, such as Fusobacterium, Prevotella, Porphyromonas, Bacteroides, and Peptostreptococcus species. However, linezolid does not have a spectrum of activity that covers Klebsiella and is therefore inappropriate.
- Parenteral ertapenem is an effective and convenient drug for home care in a patient with a soft tissue infection.
Correct answer: B. Complete an 8-day course of vancomycin and discontinue the other antibiotics.
The patient has had a good clinical response to treatment for methicillin-resistant Staphylococcus aureus (MRSA) pneumonia and, therefore, does not need antibiotic therapy beyond 7 to 9 days. The patient's residence in a nursing home and chronic hemodialysis place her at risk for infection with resistant organisms, including MRSA and Pseudomonas aeruginosa, and she received appropriate empiric coverage for health care-associated pneumonia. Now that MRSA has been isolated from her sputum, empiric coverage for other organisms should be discontinued. In the absence of bacteremia, it appears treatment for MRSA pneumonia can be safely limited to approximately 8 days. Patients with P. aeruginosa pneumonia appear to have a greater risk of recurrent infection when antibiotic therapy is limited to 8 rather than 15 days.
- Most causes of health care-associated pneumonia, including ventilator-associated pneumonia, require only approximately 8-day antibiotic courses.
Correct answer: A. Ciprofloxacin, rifampin, and vancomycin.
This patient's clinical presentation is compatible with inhalational anthrax. The Centers for Disease Control and Prevention's recommended treatment includes a fluoroquinolone or doxycycline plus one or two additional agents (for example, penicillin, erythromycin, vancomycin, rifampin, or clindamycin) pending results of antimicrobial susceptibility testing.
The inhalational form of anthrax is most likely to be associated with bioterrorism. Inhaled spores migrate to mediastinal lymph nodes, where they germinate, disseminate, and produce toxins that cause edema and cell death with hemorrhage. The prodrome is described as flu-like with malaise, fever, headache, a nonproductive cough, substernal chest pain, myalgia, nausea, and abdominal pain. The second phase develops over the next 24 to 36 hours and is fulminant. Severe dyspnea, respiratory distress, and shock occur, and about 50% of patients with advanced disease have meningitis. Enlarged hilar and mediastinal lymph nodes are highly characteristic of inhalational anthrax and result in a widened mediastinum. Pleural effusions are also prominent. Bacillus anthracis is also suggested by the initial report of the buffy coat Gram stain.
The other antibiotics or antibiotic combinations are not recommended for the treatment of inhalational anthrax because they do not contain either a fluoroquinolone or doxycycline.
- The initial therapy for inhalational anthrax should include a fluoroquinolone or doxycycline plus one or two additional agents (for example, penicillin, erythromycin, vancomycin, rifampin, or clindamycin).
Correct answer: B. Corticosteroids.
This patient most likely has hypersensitivity pneumonitis (extrinsic allergic alveolitis) caused by exposure to Mycobacterium avium complex (MAC) from the hot tub, also known as “hot tub lung.” There are many causes of hypersensitivity pneumonitis, and the offending agent is generally suggested by the exposure obtained in the history. Hot tub lung presents as an interstitial pneumonia in immunocompetent individuals and can be easily misdiagnosed as an infection with an atypical agent such as Mycoplasma pneumoniae or Chlamydophila pneumoniae. However, infectious pneumonias very rarely recur after response to treatment, and three episodes of pneumonia over the course of 2 months is unlikely in a healthy person. The chest radiograph in hypersensitivity pneumonitis typically shows a micronodular interstitial pattern in the lower and mid-lung zones, and the serum lactate dehydrogenase level is often elevated during the acute phase of the illness and normalizes with improvement. Most patients with hot tub lung will grow MAC on respiratory specimens; the hot tub water can also be cultured to confirm the diagnosis. Treatment includes prevention of re-exposure to MAC by ensuring adequate chlorination of hot tubs to prevent bacterial growth and corticosteroids in patients whose condition is severe or not rapidly improving.
This patient's clinical scenario does not represent a true infection with MAC and should not be treated with ethambutol and clarithromycin. Most patients improve without treatment, and antibiotics are of no benefit.
- Treatment of “hot tub lung” includes prevention of re-exposure and systemic corticosteroids in severe cases.