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Adverse Reactions to Antibiotics in the Critical Care Unit
Published in Cheston B. Cunha, Burke A. Cunha, Infectious Diseases and Antimicrobial Stewardship in Critical Care Medicine, 2020
Diane M. Parente, Cheston B. Cunha, Michael Lorenzo
Amphotericin B can cause a renal tubular acidosis (distal or proximal), resulting in increased serum creatinine, along with wasting of potassium and magnesium. This risk is higher with conventional formulations, amphotericin B deoxycholate, and can be mitigated to some degree with the appropriate use of fluid administration and electrolyte replacement [93].
Infants: Yeasts are beasts in early life
Published in Mahmoud A. Ghannoum, John R. Perfect, Antifungal Therapy, 2019
Rachel G. Greenberg, Daniel K. Benjamin
Amphotericin B deoxycholate is the most often used agent for invasive candidiasis in infants [76]. However, there are limited pharmacokinetic data in infants. Two studies involving a total of 17 infants demonstrated a longer half-life of the drug in infants compared with adults [77,78]. Test doses are not recommended as the drug is much better tolerated in infants than in adults [77,79]. CSF penetration is poor in adult patients but was found to reach 40%–90% of serum levels in preterm infants [77]. Side effects observed in infants include electrolyte abnormalities and nephrotoxicity [80,81]. Amphotericin B deoxycholate is effective against most Candida species causing disease in infants except for C. lusitaniae [82]. A prospective observational study of 59 infants with invasive candidiasis found that all isolates were sensitive to amphotericin B deoxycholate [16].
Fungal Infections
Published in John C Watkinson, Raymond W Clarke, Louise Jayne Clark, Adam J Donne, R James A England, Hisham M Mehanna, Gerald William McGarry, Sean Carrie, Basic Sciences Endocrine Surgery Rhinology, 2018
Emily Young, Yujay Ramakrishnan, Laura Jackson, Shahzada K. Ahmed
Broad-spectrum antifungal therapy should be started as soon as a diagnosis of AIFR is suspected. Fungal cultures are essential in determining sensitivity to anti-fungal agents. Amphotericin B is a polyene antifungal with activity against both Mucorales and Aspergillus. Amphotericin B deoxycholate is used as the mainstay of treatment prior to identification of the causal fungus, usually at doses of 1–1.5 mg/kg per day. However, the toxicity of amphotericin B has led to the development of safer lipid-formulations of the drugs such as amphotericin B lipid complex and liposomal amphotericin B. These formulations are less nephrotoxic and can be used at higher concentrations for longer. Liposomal amphotericin B is used at doses of 5–10 mg/kg per day, and although expensive is safer and may be more effective than amphotericin B deoxycholate, particularly in cancer patients with mucormycosis.26
Evolution of antifungals for invasive mold infections in immunocompromised hosts, then and now
Published in Expert Review of Anti-infective Therapy, 2023
Zoe Freeman Weiss, Jessica Little, Sarah Hammond
Amphotericin B (AmB), one of the first effective systemic antifungals, was introduced in 1959 [3]. AmB is a polyene antifungal that binds ergosterol, an essential component of the fungal cell membrane, resulting in pore formation and efflux of monovalent ions, leading to fungal cell death. AmB has significant activity against yeasts, dimorphic fungi, and a wide range of filamentous molds (eg. Aspergillus, Mucor/Rhizomucor/Rhizopus, and dematiaceous fungi). Though primarily administered via intravenous route, intraperitoneal, intravitreal, intrathecal, intravesicular, and aerosolized forms are available. The original formulation, amphotericin B deoxycholate (AmB-d), is associated with difficult side effects including nephrotoxicity, phlebitis, electrolyte derangements, and profound infusion reactions [4]. To reduce severe toxicities and improve tolerability, lipid formulations (eg. liposomal amphotericin B (L-AmB), amphotericin B lipid complex (ABLC), and amphotericin B colloid dispersion (ABCD)) were subsequently developed and have largely replaced the original formulation in developed nations (see Figure 1) [5]. Access to newer formulations remains a significant problem worldwide [6]. Despite major concerns with drug tolerability, AmB and its lipid formulations remain primary agents for IMI due to the broad spectrum of activity and low risk of developing resistance.
Transcutaneous retrobulbar injection of amphotericin B in rhino-orbital-cerebral mucormycosis: a review
Published in Orbit, 2022
Akshay Gopinathan Nair, Tarjani Vivek Dave
AMB has long been regarded as the ‘gold standard’ among antifungal drugs as it has the broadest antifungal spectrum. The clinical application of amphotericin B requires monitoring of multiple parameters, primarily due to a high incidence of infusion-related adverse events and an incidence of renal toxicity. These adverse events are mostly associated with the traditional formulation – amphotericin B deoxycholate.45 Three lipid-associated formulations were developed – amphotericin B lipid complex, liposomal amphotericin B (L-AMB), and amphotericin B colloidal dispersion to reduce the toxicity and increase efficacy as compared to conventional AMB deoxycholate.46 Hirabayashi et al. and Safi et al. used AMB deoxycholate for the TRAMB in their reported cases.38,39 Mekonnen et al. injected L-AMB into their patient's.8 The series reported by Bayram et al. included eleven cases of ROCM – all of whom received L-AMB.24 Ashraf et al. in their retrospective series, which included 26 cases of ROCM, administered the liposomal formulation to most patients.44
Antifungal agents and the kidney: pharmacokinetics, clinical nephrotoxicity, and interactions
Published in Expert Opinion on Drug Safety, 2021
Athanasios Tragiannidis, Anastasia Gkampeta, Maria Vousvouki, Eleni Vasileiou, Andreas H. Groll
IFDs continue to be important threats to severely immunocompromised patients and those admitted to intensive care units. The tolerability of antifungal agents has been a major issue during their use over the past 60 years. Fungi are eukaryotes and so targets can be shared with mammalian cells, making the development of new drugs with distinct targets difficult. The historical gold-standard for the management of IFDs, amphotericin B deoxycholate, has a narrow therapeutic ratio and a high potential for adverse events of glomerular and tubular nephrotoxicity, which are highly relevant and problematic in fragile patients suffering from life-threatening medical conditions [20,21]. The triazoles constitute a heterogeneous class of antifungal agents, whose newer molecules have an extended spectrum of activity and no intrinsic nephrotoxicity. However, apart from the potentially toxic accumulation of the intravenous cyclodextrin carriers, clinicians should be aware of drug to drug interactions that may lead to the accumulation of concomitantly administered drugs with exposure-dependent nephrotoxicity [10]. A newer class of antifungal echinocandins is currently recommended as first-line therapy for the treatment of candidemia and other forms of invasive candidiasis, as they are exceptionally well tolerated and have a broad spectrum of invitro activity against all clinically relevant Candida spp. Echinocandins are better tolerated but possess a narrower antifungal spectrum and thus far lack an oral route of administration [10].