amphotericin B
Sources réglementaires consultées
Indications approuvées
- Infections fongiques systémiques graves, traitement empirique de la neutropénie fébrile et méningite cryptococcique associée au VIH selon les schémas liposomaux.
Contre-indications
Absolues
- Hypersensibilité à l’amphotéricine B ou aux composants, sauf si l’infection engage le pronostic vital et qu’il n’existe pas d’alternative.
Mises en garde cliniques
- Elle peut provoquer une anaphylaxie et des réactions sévères à la perfusion ; surveiller pendant l’administration et ralentir ou arrêter en cas de réaction. — DailyMed, set_id 02aadef1-390b-4270-b56d-33452eb89dde
- Il peut provoquer une néphrotoxicité, une hypokaliémie, une hypomagnésémie, des cytopénies et une dysfonction hépatique ; surveiller la fonction rénale, les électrolytes, la numération et la fonction hépatique. — DailyMed, set_id 02aadef1-390b-4270-b56d-33452eb89dde
Interactions médicamenteuses
- SévèreAutres médicaments néphrotoxiques
Mécanisme: La néphrotoxicité peut être additive.
Recommandation: Éviter ou intensifier la surveillance rénale et électrolytique.
DailyMed, set_id 02aadef1-390b-4270-b56d-33452eb89dde
- SévèreCorticostéroïdes, ACTH ou digitaliques
Mécanisme: L’hypokaliémie peut s’aggraver et augmenter la toxicité digitalique.
Recommandation: Surveiller le potassium, le magnésium, l’ECG et la toxicité digitalique.
DailyMed, set_id 02aadef1-390b-4270-b56d-33452eb89dde
- SévèreFlucytosine
Mécanisme: Il peut augmenter la captation et la toxicité de la flucytosine.
Recommandation: Surveiller les concentrations et la numération.
DailyMed, set_id 02aadef1-390b-4270-b56d-33452eb89dde
- SévèreTransfusions leucocytaires
Mécanisme: L’administration concomitante a été associée à une toxicité pulmonaire aiguë.
Recommandation: Éviter l’administration concomitante ; si les deux sont nécessaires, les espacer autant que possible et surveiller la fonction pulmonaire.
DailyMed, set_id 02aadef1-390b-4270-b56d-33452eb89dde
- SévèreAgents antinéoplasiques
Mécanisme: Ils peuvent augmenter la néphrotoxicité, le bronchospasme et l’hypotension.
Recommandation: N’utiliser simultanément que sous surveillance étroite des fonctions rénale, respiratoire et hémodynamique.
DailyMed, set_id 02aadef1-390b-4270-b56d-33452eb89dde
- SévèreMyorelaxants
Mécanisme: L’hypokaliémie induite par l’amphotéricine B peut potentialiser le bloc neuromusculaire.
Recommandation: Surveiller le potassium et la fonction neuromusculaire et adapter le myorelaxant.
DailyMed, set_id 02aadef1-390b-4270-b56d-33452eb89dde
- ModéréeAntifongiques azolés
Mécanisme: Un antagonisme pharmacodynamique possible a été observé dans des études précliniques.
Recommandation: Ne pas présumer d’un bénéfice de l’association ; individualiser avec un avis spécialisé.
DailyMed, set_id 02aadef1-390b-4270-b56d-33452eb89dde
Effets indésirables
Communs (≥1%)
Fièvre, frissons, nausées, vomissements, hypokaliémie et élévation de la créatinine
Rares mais graves
Anaphylaxie, insuffisance rénale, arythmie liée aux électrolytes et cytopénies sévères
Grossesse et allaitement
Utiliser pendant la grossesse uniquement si le bénéfice l’emporte sur le risque. Décider d’arrêter soit l’allaitement, soit le traitement.
Bibliographie récente (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.