amphotericin B
Regulatory sources consulted
Approved indications
- Serious systemic fungal infections, empiric therapy in febrile neutropenia, and HIV-associated cryptococcal meningitis under liposomal regimens.
Contraindications
Absolute
- Hypersensitivity to amphotericin B or components, unless infection is life-threatening and no alternative exists.
Clinical warnings
- It may cause anaphylaxis and severe infusion reactions; monitor during administration and slow or stop if a reaction occurs. — DailyMed, set_id 02aadef1-390b-4270-b56d-33452eb89dde
- It may cause nephrotoxicity, hypokalemia, hypomagnesemia, cytopenias, and hepatic dysfunction; monitor renal function, electrolytes, blood counts, and liver function. — DailyMed, set_id 02aadef1-390b-4270-b56d-33452eb89dde
Drug interactions
- HighOther nephrotoxic drugs
Mechanism: Nephrotoxicity may be additive.
Recommendation: Avoid or intensify renal-function and electrolyte monitoring.
DailyMed, set_id 02aadef1-390b-4270-b56d-33452eb89dde
- HighCorticosteroids, ACTH, or digitalis
Mechanism: Hypokalemia may worsen and increase digitalis toxicity.
Recommendation: Monitor potassium, magnesium, ECG, and digitalis toxicity.
DailyMed, set_id 02aadef1-390b-4270-b56d-33452eb89dde
- HighFlucytosine
Mechanism: It may increase flucytosine uptake and toxicity.
Recommendation: Monitor concentrations and blood counts.
DailyMed, set_id 02aadef1-390b-4270-b56d-33452eb89dde
- HighLeukocyte transfusions
Mechanism: Concomitant administration has been associated with acute pulmonary toxicity.
Recommendation: Avoid concomitant use; if both are necessary, separate administrations as much as possible and monitor pulmonary function.
DailyMed, set_id 02aadef1-390b-4270-b56d-33452eb89dde
- HighAntineoplastic agents
Mechanism: They may increase nephrotoxicity, bronchospasm, and hypotension.
Recommendation: Use concomitantly only with close renal, respiratory, and hemodynamic monitoring.
DailyMed, set_id 02aadef1-390b-4270-b56d-33452eb89dde
- HighSkeletal muscle relaxants
Mechanism: Amphotericin B-induced hypokalemia may potentiate neuromuscular blockade.
Recommendation: Monitor potassium and neuromuscular function and adjust the relaxant.
DailyMed, set_id 02aadef1-390b-4270-b56d-33452eb89dde
- ModerateAzole antifungals
Mechanism: Possible pharmacodynamic antagonism has been observed in preclinical studies.
Recommendation: Do not assume combination benefit; individualize with specialist input.
DailyMed, set_id 02aadef1-390b-4270-b56d-33452eb89dde
Adverse events
Common (≥1%)
Fever, chills, nausea, vomiting, hypokalemia, and increased creatinine
Rare but serious
Anaphylaxis, renal failure, electrolyte-related arrhythmia, and severe cytopenias
Pregnancy and lactation
Use during pregnancy only if benefit outweighs risk. Decide whether to discontinue breastfeeding or treatment.
Recent literature (PubMed)
Candida auris is a multidrug-resistant fungal pathogen that presents a serious threat to global human health. Since the first reported case in 2009 in Japan, C. auris infections have been reported in more than 40 countries, with mortality rates between 30% and 60%. In addition, C. auris has the potential to cause outbreaks in health care settings, especially in nursing homes for elderly patients, owing to its efficient transmission via skin-to-skin contact. Most importantly, C. auris is the first fungal pathogen to show pronounced and sometimes untreatable clinical drug resistance to all known antifungal classes, including azoles, amphotericin B, and echinocandins. In this review, we explore the causes of the rapid spread of C. auris. We also highlight its genome organization and drug resistance mechanisms and propose future research directions that should be undertaken to curb the spread of this multidrug-resistant pathogen.
Influenza-associated pulmonary aspergillosis (IAPA) and COVID-19-associated pulmonary aspergillosis (CAPA) are increasingly recognised as important complications in patients requiring intensive care for severe viral pneumonia. The diagnosis can typically be made in 10-20% of patients with severe influenza or COVID-19, but only when appropriate diagnostic tools are used. Bronchoalveolar lavage sampling for culture, galactomannan testing, and PCR forms the cornerstone of diagnosis, whereas visual examination of the tracheobronchial tract during bronchoscopy is required to detect invasive Aspergillus tracheobronchitis. Azoles are the first-choice antifungal drugs, with liposomal amphotericin B as an alternative in settings where azole resistance is prevalent. Despite antifungal therapy, IAPA and CAPA are associated with poor outcomes, with fatality rates often exceeding 50%. In this Review, we discuss the mechanistic and clinical aspects of IAPA and CAPA. Moreover, we identify crucial knowledge gaps and formulate directions for future research.
Invasive aspergillosis (IA) is a severe fungal infection caused by Aspergillus species, particularly Aspergillus fumigatus, although new species, sometimes resistant to antifungals are becoming more common. IA predominantly affects immunocompromised patients, such as those with haematological malignancies, solid organ transplant recipients, and critically ill patients. However, new at-risk populations have emerged in recent years, such as IA associated with severe viral infections. Advanced diagnostic methods are crucial, especially considering the rising concern of antifungal resistance. Early detection is critical for successful treatment, typically involving antifungal medications like voriconazole or amphotericin B, but new antifungals are arriving to complete the therapeutic strategies. Despite advancements, mortality rates remain high, underscoring the importance of timely interventions and ongoing research. Healthcare providers should maintain a high index of suspicion, especially in immunocompromised patients and other new risk factors that are arising, to promptly diagnose and manage invasive aspergillosis.
Cryptococcal meningitis is a leading cause of human immunodeficiency virus (HIV)-related death in sub-Saharan Africa. Whether a treatment regimen that includes a single high dose of liposomal amphotericin B would be efficacious is not known. In this phase 3 randomized, controlled, noninferiority trial conducted in five African countries, we assigned HIV-positive adults with cryptococcal meningitis in a 1:1 ratio to receive either a single high dose of liposomal amphotericin B (10 mg per kilogram of body weight) on day 1 plus 14 days of flucytosine (100 mg per kilogram per day) and fluconazole (1200 mg per day) or the current World Health Organization-recommended treatment, which includes amphotericin B deoxycholate (1 mg per kilogram per day) plus flucytosine (100 mg per kilogram per day) for 7 days, followed by fluconazole (1200 mg per day) for 7 days (control). The primary end point was death from any cause at 10 weeks; the trial was powered to show noninferiority at a 10-percentage-point margin. A total of 844 participants underwent randomization; 814 were included in the intention-to-treat population. At 10 weeks, deaths were reported in 101 participants (24.8%; 95% confidence interval [CI], 20.7 to 29.3) in the liposomal amphotericin B group and 117 (28.7%; 95% CI, 24.4 to 33.4) in the control group (difference, -3.9 percentage points); the upper boundary of the one-sided 95% confidence interval was 1.2 percentage points (within the noninferiority margin; P<0.001 for noninferiority). Fungal clearance from cerebrospinal fluid was -0.40 log10 colony-forming units (CFU) per milliliter per day in the liposomal amphotericin B group and -0.42 log10 CFU per milliliter per day in the control group. Fewer participants had grade 3 or 4 adverse events in the liposomal amphotericin B group than in the control group (50.0% vs. 62.3%). Single-dose liposomal amphotericin B combined with flucytosine and fluconazole was noninferior to the WHO-recommended treatment for HIV-assoc
Candidiasis is a highly pervasive infection posing major health risks, especially for immunocompromised populations. Pathogenic Candida species have evolved intrinsic and acquired resistance to a variety of antifungal medications. The primary goal of this literature review is to summarize the molecular mechanisms associated with antifungal resistance in Candida species. Resistance can be conferred via gain-of-function mutations in target pathway genes or their transcriptional regulators. Therefore, an overview of the known gene mutations is presented for the following antifungals: azoles (fluconazole, voriconazole, posaconazole and itraconazole), echinocandins (caspofungin, anidulafungin and micafungin), polyenes (amphotericin B and nystatin) and 5-fluorocytosine (5-FC). The following mutation hot spots were identified: (1) ergosterol biosynthesis pathway mutations (ERG11 and UPC2), resulting in azole resistance; (2) overexpression of the efflux pumps, promoting azole resistance (transcription factor genes: tac1 and mrr1; transporter genes: CDR1, CDR2, MDR1, PDR16 and SNQ2); (3) cell wall biosynthesis mutations (FKS1, FKS2 and PDR1), conferring resistance to echinocandins; (4) mutations of nucleic acid synthesis/repair genes (FCY1, FCY2 and FUR1), resulting in 5-FC resistance; and (5) biofilm production, promoting general antifungal resistance. This review also provides a summary of standardized inhibitory breakpoints obtained from international guidelines for prominent Candida species. Notably, N. glabrata, P. kudriavzevii and C. auris demonstrate fluconazole resistance.