The following cases and commentary, which address infectious diseases, are excerpted from ACP's Medical Knowledge Self-Assessment Program (MKSAP14).
Case 1: Sudden drop in blood pressure, onset of fever
A 60-year-old man is evaluated in the intensive care unit 30 minutes after a sudden drop in his blood pressure and onset of fever. He was admitted to the intensive care unit 14 days ago with necrotizing pancreatitis, and he underwent placement of a Foley catheter to monitor urine output. Twelve days ago, a left subclavian triple-lumen catheter was inserted for infusion of antibiotics and hyperalimentation. Eight days ago, a symptomatic Candida urinary tract infection developed for which he received a 7-day course of fluconazole.
Current medications are meropenem and morphine.
On physical examination, the patient has a left subclavian triple-lumen catheter. Temperature is 39°C (102.2°F), pulse rate is 120 beats/min, respiration rate is 24 breaths/min, and blood pressure is 90/60 mm Hg. The remainder of the physical examination is normal.
Laboratory values are as follows: leukocyte count, 13,500 cells/µL (13.5 × 109 cells/L) with 20% band forms; amylase level, 250 U/L; creatinine concentration, 2.3 mg/dL (203.3 µmol/L); and lipase level, 400 U/L. Blood cultures are positive for yeast.
In addition to removal of the central venous catheter, which of the following is the most appropriate next step in treatment?
A. Amphotericin B
E. No further antifungal therapy
Case 2: Odynophagia in AIDS
A 40-year-old man with recently diagnosed AIDS has a one-week history of odynophagia. He is able to ingest both solids and liquids but is uncomfortable when swallowing. The current CD4 cell count is 90 cells/µL (0.09 × 109 cells/L). Highly active antiretroviral therapy has not been started because he is awaiting results from his baseline viral genotype resistance studies, and his only medication is trimethoprim-sulfamethoxazole for Pneumocystis jiroveci pneumonia prophylaxis.
On physical examination, the patient appears chronically ill with obvious wasting. Temperature is 37.2°C (98.9°F), blood pressure is 112/68 mm Hg, pulse rate is 86 beats/min, and respiration rate is 12 breaths/min. White plaques are adhering to the hard palate. There are no oropharyngeal ulcers or rash. Cardiopulmonary examination is normal.
Which of the following is the most appropriate treatment at this time?
A. Amphotericin B
Case 3: Persistent sore on the forearm
A 30-year-old woman is evaluated in the emergency department for a sore she has had on the back of her right forearm for five days. Over the past two days, the lesion has evolved into a small pustule that is red, sore, and swollen. She has a remote history of injection drug use but has not used drugs for the past six months. Two weeks ago, she completed serving a three-month sentence in county jail. While in jail, she underwent HIV testing, results of which were negative. The remainder of the medical history is noncontributory, and she has no known drug allergies.
On physical examination, temperature is 37.2°C (99.0°F), pulse rate is 72 beats/min, respiration rate is 12 breaths/min, and blood pressure is 108/64 mm Hg. Cardiopulmonary examination is normal. Examination of the right forearm shows a draining pustule of about 0.5 cm in diameter surrounded by an area of erythema, tenderness, and warmth of about 6 cm in diameter.
Gram stain of fluid from the lesion discloses numerous polymorphonuclear leukocytes and gram-positive cocci in chains and clusters.
Which of the following is the most appropriate treatment at this time?
D. Trimethoprim-sulfamethoxazole plus amoxicillin
Answers and commentary
Correct answer: B. Anidulafungin.
Bloodstream infections with Candida species are often associated with sepsis syndrome and a high mortality rate. In patients with candidemia, nonpharmacologic management should include removal of all existing central venous catheters. These patients should also receive appropriate antifungal therapy, with the choice of agent based on the patient's clinical status, the probable infecting fungal species and its likely antifungal susceptibility, the relative drug toxicity, and the presence of organ dysfunction affecting drug clearance.
Anidulafungin is an echinocandin antifungal agent, and this class of agents has excellent broad-spectrum activity against Candida species and a low rate of treatment-related adverse effects; echinocandin antifungal agents should be considered first-line therapy in critically ill patients who are hemodynamically unstable with candidemia, especially when the infection is associated with previous or concurrent exposure to azole antifungal agents. Amphotericin B is effective against Candida species, but strains of C. lusitaniae may be resistant to this agent, and many C. glabrata and C. krusei organisms have reduced susceptibility to amphotericin B; furthermore, amphotericin B is associated with significant adverse effects.
Fluconazole generally has good activity against Candida species although strains of C. glabrata may be resistant such that fluconazole should not be used as empiric therapy in an unstable patient with candidemia. In addition, this patient received a course of fluconazole for candiduria and would more likely have a bloodstream isolate that is now resistant rather than susceptible. Patients with postcatheterization candiduria usually do not require specific antifungal therapy, but candiduria should be treated in patients who are symptomatic, are renal transplant recipients, are neutropenic, and have undergone urinary tract instrumentation. Flucytosine should never be used as a single agent to treat fungal infections because resistance develops in patients who receive monotherapy, and primary drug resistance is common in patients with Candida species.
- Echinocandin antifungal agents have broad-spectrum activity against Candida species, are well tolerated, and are efficacious in treating Candida bloodstream infections.
Correct answer: C. Fluconazole.
This patient has evidence of oropharyngeal candidiasis, which is the most common opportunistic infection in patients with AIDS. He also has symptoms consistent with esophageal candidiasis. Most fungal esophagitis is caused by Candida albicans, and the risk increases as the CD4 count decreases in patients with AIDS. An empiric course of antifungal therapy is recommended for at-risk patients with symptoms of odynophagia and/or dysphagia, particularly when they have plaques consistent with thrush. Approximately two-thirds of patients with Candida esophagitis have concomitant thrush. Because of the strong association between oral and esophageal candidiasis, patients with symptomatic thrush should receive a course of systemic antifungal therapy. Fluconazole is the preferred initial treatment because of its ease of use and high efficacy rates. Echinocandins (caspofungin, micafungin and anidulafungin) are equally effective and safe but need to be given parenterally. Patients should be closely observed for resolution of symptoms. If symptoms persist, upper endoscopy and biopsy are indicated, as the symptoms may be due to infection with resistant Candida species or some other cause.
Amphotericin B is an effective agent for fungal esophagitis. However, its intravenous administration, toxic side effects, and high cost restrict its use as empiric therapy.
Viral causes of esophagitis in patients with HIV include cytomegalovirus and herpes simplex virus. These viruses are a less frequent cause of esophagitis than Candida species, particularly in a patient with oropharyngeal candidiasis, and acyclovir is therefore not appropriate as initial therapy for this patient. However, viral causes may need to be considered in a patient with symptoms of odynophagia and dysphagia who is not responding to empiric therapy with fluconazole.
Fungal esophagitis requires systemic therapy and should not be managed with local agents, such as nystatin. Local therapy can be used when patients have mild oropharyngeal candidiasis without signs of deeper infection.
- Because of the strong association between oral and esophageal candidiasis, patients with symptomatic thrush should receive a course of systemic antifungal therapy.
- Fluconazole is the initial treatment for patients with HIV or AIDS who develop fungal esophagitis.
Correct answer: D. Trimethoprim-sulfamethoxazole plus amoxicillin.
The patient has a local abscess and surrounding cellulitis manifested by erythema, tenderness to touch, and warmth without significant fever. Her history of injection drug use and recent incarceration confers an increased risk for infection with Staphylococcus aureus, especially with community-associated strains of S. aureus that are methicillin-resistant (MRSA). She also has some risk of infection with streptococci (especially Streptococcus pyogenes) that are common etiologic agents of skin and soft-tissue infections. This patient is not ill enough to require hospitalization and can therefore be treated with oral antimicrobial therapy following abscess drainage. While she awaits results of wound culture to identify the responsible microorganism in addition to results of susceptibility testing, she should receive empiric antimicrobial therapy with adequate coverage against streptococci and community-associated MRSA. For patients without allergies to the agents involved, the combination of amoxicillin plus trimethoprim-sulfamethoxazole is the most appropriate therapeutic option for soft-tissue infection of unknown etiology. Trimethoprim-sulfamethoxazole alone would be adequate for most S. aureus infections, but it has weak activity against streptococci.
Cephalexin and other β-lactam antibiotics, such as amoxicillin or amoxicillin/clavulanate, are no longer considered reliable empiric treatment for community-acquired soft-tissue infections because of the proliferation of MRSA. The emergence of resistance to the fluoroquinolones, especially ciprofloxacin, limits their usefulness in treating community-associated MRSA. The newer fluoroquinolones, such as levofloxacin, have enhanced antistaphylococcal activity against ciprofloxacin-resistant strains, but their usefulness is limited by the emergence of resistance during therapy. Doxycycline and trimethoprim-sulfamethoxazole might be reasonable choices when community-associated MRSA soft-tissue infection is confirmed or strongly suspected based on the presence of purulent material and a positive Gram stain showing only gram-positive cocci in clusters and not a mix of chains and clusters.
While it is possible to identify certain groups of people who are at increased risk for MRSA (for example, those with a history of injection drug use; prison inmates; athletes; military recruits; Pacific Islanders; Alaskan Natives; Native Americans; and men who have sex with men), these risk factors for community-associated MRSA have poor specificity, sensitivity, and positive predictive value for differentiating between MRSA and methicillin-susceptible S. aureus. Therefore, the absence of these factors should not be the basis for withholding empiric coverage of MRSA. Routes of transmission of MRSA include close skin-to-skin contact, cuts or abrasions, contaminated items and surfaces, crowded living conditions, and poor hygiene. Some patients with community-associated MRSA may develop more serious illnesses, such as pneumonia, necrotizing fasciitis, or pyomyositis. Less commonly, they can develop osteomyelitis or systemic dissemination (for example, infective endocarditis).
- In patients with skin and soft-tissue infections of uncertain cause, empirical antimicrobial therapy should include treatment with agents that have activity against streptococci and community-associated MRSA.
- A lack of certain risk factors and presenting symptoms should not preclude empirical administration of appropriate antibiotics in patients in the community with skin and soft-tissue infection of uncertain cause.