You are taking care of a patient with renal failure secondary to anti-fungal therapy. The patient is a 66-year-old male being treated for cryptococcal meningitis. This drug has a variety of known side effects including acute febrile reactions to infusions, anemia, hypokalemia and hypomagnesemia. What is the mechanism of action of this drug?

Pore formation secondary to ergosterol binding

Inhibition of squalene epoxidase

Disruption of microtubule formation

Inhibition of 1,3-beta-glucan synthase

A 69-year-old man with metastatic colon cancer is brought to the emergency department because of shortness of breath, fever, chills, and a productive cough with streaks of blood for the past 5 days. He has a history of emphysema. The patient does not have abdominal pain or headache. He receives chemotherapy with 5-fluorouracil, leucovorin, and oxaliplatin every 6 weeks; his last cycle was 3 weeks ago. His temperature is 38.3°C (101°F), pulse is 112/min, and blood pressure is 100/70 mm Hg. Pulse oximetry on room air shows an oxygen saturation of 83%. A few scattered inspiratory crackles are heard over the right lung. His mucous membranes are dry. Cardiac examination is normal. Laboratory studies show: Hemoglobin 9.3 mg/dL Leukocyte count 700/mm3 Segmented neutrophils 68% Lymphocytes 25% Eosinophils 4% Monocytes 3% Platelet count 104,000/mm3 Serum Glucose 75 mg/dL Urea nitrogen 41 mg/dL Creatinine 2.1 mg/dL Galactomannan antigen Positive Which of the following is the most appropriate initial pharmacotherapy?

Rifampin, isoniazid, pyrazinamide, and ethambutol

A 29-year-old woman, gravida 2, para 1, at 10 weeks' gestation comes to the physician for a prenatal visit. Over the past two weeks, she has felt nauseous in the morning and has had vulvar pruritus and dysuria that started 5 days ago. Her first child was delivered by lower segment transverse cesarean section because of macrosomia from gestational diabetes. Her gestational diabetes resolved after the child was born. She appears well. Ultrasound confirms fetal heart tones and an intrauterine pregnancy. Speculum exam shows a whitish chunky discharge. Her vaginal pH is 4.2. A wet mount is performed and microscopic examination is shown. Which of the following is the most appropriate treatment?

Intravaginal treatment with lactobacillus

A 62-year-old man is brought to the emergency department from a senior-care facility after he was found with a decreased level of consciousness and fever. His personal history is relevant for colorectal cancer that was managed with surgical excision of the tumor. Upon admission, he is found to have a blood pressure of 130/80 mm Hg, a pulse of 102/min, a respiratory rate of 20/min, and a body temperature 38.8°C (101.8°F). There is no rash on physical examination; he is found to have neck rigidity, confusion, and photophobia. There are no focal neurological deficits. A head CT is normal without mass or hydrocephalus. A lumbar puncture was performed and cerebrospinal fluid (CSF) is sent to analysis while ceftriaxone and vancomycin are started. Which of the following additional antimicrobials should be added in the management of this patient?

Trimethoprim-sulfamethoxazole (TMP-SMX)

A 45-year-old man presents to the emergency department with difficulties swallowing food. He states that he experiences pain when he attempts to swallow his medications or when he drinks water. He reveals that he was diagnosed with HIV infection five years ago. He asserts that he has been taking his antiretroviral regimen, including emtricitabine, rilpivirine, and tenofovir. His temperature is 98°F (37°C), blood pressure is 100/60 mmHg, pulse is 90/min, respirations are 22/min, and oxygen saturation is 99% on room air. His physical exam is notable for a clear oropharynx, no lymphadenopathy, and a normal cardiac and pulmonary exam. No rashes are noted throughout his body. His laboratory results are displayed below: Hemoglobin: 12 g/dL Hematocrit: 37 % Leukocyte count: 8,000/mm^3 with normal differential Platelet count: 160,000/mm^3 Serum: Na+: 138 mEq/L Cl-: 108 mEq/L K+: 3.5 mEq/L HCO3-: 26 mEq/L BUN: 35 mg/dL Glucose: 108 mg/dL Creatinine: 1.1 mg/dL CD4+ count: 90/mm^3 HIV viral load: 59,000 copies/mL What is the best next step in management?

Esophageal endoscopy and biopsy

A 57-year-old woman with non-small cell lung cancer comes to the physician 4 weeks after her tumor was resected. She takes no medications. The physician starts her on a treatment regimen that includes vinblastine. This treatment puts the patient at highest risk for which of the following?

Progressive multifocal leukoencephalopathy

Treatment guidelines for invasive fungal infections — USMLE Lesson

Empiric Therapy - First Strike Fungi

Indicated for high-risk, febrile neutropenic patients with persistent or recurrent fever after 4-7 days of broad-spectrum antibiotics, with no other identified cause.
Goal: Preemptively cover the most probable fungal pathogens, primarily Candida species and Aspergillus.
De-escalate to targeted therapy once a pathogen is identified and susceptibilities are determined.

⭐ Echinocandins are favored as initial therapy for most patients with suspected invasive candidiasis, particularly those who are hemodynamically unstable or had recent azole exposure.

Invasive Candidiasis - Crushing Candida

Empiric First-Line: Echinocandins (e.g., caspofungin, micafungin) for most patients, especially if moderately to severely ill or recent azole exposure.
Step-Down Therapy: Transition to Fluconazole within 5-7 days if patient is stable, isolates are susceptible, and blood cultures are negative.
Specific Species:
- C. krusei: Intrinsically resistant to fluconazole; use echinocandins.
- C. glabrata: May have dose-dependent susceptibility to fluconazole; echinocandins are safer.
Duration: Treat for 14 days after the first negative blood culture and clinical resolution.

⭐ Source control is paramount. If a central line is the suspected source, it must be removed as soon as possible.

Invasive Aspergillosis - Voriconazole's Victory

Primary Therapy: Voriconazole is the drug of choice, demonstrating superior efficacy over Amphotericin B.
- Requires therapeutic drug monitoring (TDM) due to variable metabolism.
- Key ADRs: Visual disturbances (flashing lights), photosensitivity, ↑LFTs.
Alternative Agents:
- Liposomal Amphotericin B (L-AMB).
- Isavuconazole (less hepatotoxicity and no photosensitivity).

⭐ Exam Favorite: Voriconazole is active against Candida (including krusei) and Aspergillus, but critically lacks coverage for Zygomycetes (Mucor, Rhizopus).

Other Key Pathogens - Crypto & Mucor Mayhem

Cryptococcus neoformans (Meningitis)
- 📌 Amp-ho-Flu → Flu: Amphotericin B + Flucytosine, then Fluconazole.
- Induction: Liposomal Amphotericin B + Flucytosine (≥2 weeks).
- Consolidation & Maintenance: Fluconazole (high-dose for 8 weeks, then low-dose ≥1 year).
Mucormycosis (e.g., Rhizopus, Mucor)
- Cornerstone: Aggressive surgical debridement.
- Medical: High-dose Liposomal Amphotericin B.
- Alternatives: Posaconazole, Isavuconazole.

Mucormycosis: Broad non-septate hyphae at 90-degree angles

⭐ Voriconazole is ineffective against Mucorales. Prior voriconazole prophylaxis is a risk factor for breakthrough mucormycosis.

Invasive Aspergillosis: Voriconazole is the drug of choice; alternatives include isavuconazole or liposomal amphotericin B.

Invasive Candidiasis: First-line therapy is an echinocandin (e.g., caspofungin, micafungin); fluconazole for step-down.

Cryptococcal Meningitis: Induction with amphotericin B + flucytosine, followed by fluconazole for consolidation and maintenance.

Mucormycosis: Requires aggressive surgical debridement plus liposomal amphotericin B.

Febrile Neutropenia: Add empiric antifungals if fever persists on broad-spectrum antibiotics.

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