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Amphotericin B Deoxycholate
Published in M. Lindsay Grayson, Sara E. Cosgrove, Suzanne M. Crowe, M. Lindsay Grayson, William Hope, James S. McCarthy, John Mills, Johan W. Mouton, David L. Paterson, Kucers’ The Use of Antibiotics, 2017
Neil R. H. Stone, Tihana Bicanic
AMB-based therapies remain the cornerstone of antifungal therapy of mucormycosis, although liposomal formulations are increasingly favored over AMB deoxycholate in international guidelines due to their toxicity profiles (Skiada et al., 2013), and most new studies use liposomal AMB. Liposomal AMB has been associated with better outcomes than those treated with AMB deoxycholate (Pagano et al., 2004). Liposomal AMB is discussed in Chapter 143, Amphotericin B lipid complex. Posaconazole is an option as a step-down therapy following AMB-based therapy (Tacke et al., 2014). Although the most effective therapy, experience with AMB has been relatively poor, with large reviews reporting a mortality of over 60% (Roden et al., 2005). The highest tolerated dose should be used, as a cumulative dose of over 2 g AMB was associated with a better outcome (Kontoyiannis et al., 2000). The duration of treatment required is not known and should be individualized to the patient’s clinical response, and is usually continued until resolution of symptoms and reversal of immunosuppression (Kontoyiannis and Lewis, 2011). Early initiation has been found to be important in optimizing treatment outcomes (Chamilos et al., 2008). Infection with Cunninghamella spp. appears to be a risk factor for worse outcome (Cohen-Abbo et al., 1993). There are reports of mucormycosis with AMB-resistant organisms such as Apophysomyces elegans, which was found to have a minimum inhibitory concentration (MIC) for AMB of 16 μg/ml (Biswas et al., 2015).
Epidemiology of fungal infections: What, where, and when
Published in Mahmoud A. Ghannoum, John R. Perfect, Antifungal Therapy, 2019
Frederic Lamoth, Sylvia F. Costa, Barbara D. Alexander
Data from the Transplant-Associated Infection Surveillance Network show a 12-month cumulative incidence of 0.29% in BMT recipients and 0.07% in SOT [120]. In SOT recipients, mucormycosis is associated with corticosteroid treatment, with 78.9% of infected patients having received a cumulative dose of ≥600 mg of prednisone [283]. Clinical presentations were as mentioned above and were similar among the various organ transplant groups. Interestingly, all kidney transplant recipients had infection of the allograft in one series [283]. The genus most frequently isolated was Rhizopus (73%) followed by Mucor (13%). In a series of 263 consecutive BMT patients, 1.9% developed invasive zygomycosis over 10 years, 80% thereof >100 days after transplant [286]. Interestingly, no cases of disseminated infection occurred. Iron overload, neutropenia, and GvHD were reported as risk factors for death in BMT recipients. Breakthrough mucormycosis after voriconazole administration (as prophylaxis, empirical, preemptive, and targeted therapy for IA), in patients following allogeneic BMT, and following intensive chemotherapy in patients with hematologic malignancies, has been increasingly reported [47,280,282,284,285,291]. Most of these infections occurred late in the posttransplant/chemotherapy period, and lungs and sinuses were the most frequently affected sites. Rhizopus was again the most common genus isolated in culture [47,282]. Overall mortality for mucormycosis breaking through voriconazole therapy was very high, with a 69%–73% attributable mortality reported [282,284]. Infections with Cunninghamella bertholletiae, though rare, have been reported in patients following both BMT and SOT [275,276,292–298].
The antifungal pipeline for invasive fungal diseases: what does the future hold?
Published in Expert Review of Anti-infective Therapy, 2023
Chin Fen Neoh, Wirawan Jeong, David CM Kong, Monica A Slavin
Ibrexafungerp also displayed enhanced in vitro activity against the majority of Aspergillus spp. studied [49] (Figure 1). It has potent in vitro activity against both azole susceptible and azole resistant A. fumigatus sensu stricto strains [50]. Likewise, ibrexafungerp is active against most of the cryptic Aspergillus species tested, except for A. ustus complex species (i.e. A. insuetus and A. keveii - marginal activity) and A. alliaceus (least activity) [50]. In combination with amphotericin B, isavuconazole or voriconazole, ibrexafungerp was reported to have synergistic activity against most azole-susceptible Aspergillus strains (i.e. A. fumigatus, A. flavus, A. terreus), Cunninghamella bertholettiae, Fusarium spp. (i.e. F. oxysporum, F. solani species complexes), and Scedosporium apiospermum [51]; this synergistic activity is also demonstrated in the neutropenic rabbit model of invasive pulmonary aspergillosis [52]. Similar synergistic effect against resistant cyp51A mutants was noted in the combined therapy of ibrexafungerp and amphotericin B as well [53], indicating that ibrexafungerp could potentially be used in combination therapy for invasive aspergillosis that is difficult to treat. For non-Aspergillus molds, ibrexafungerp has potent activity against Alternaria spp., Cladosporium spp., Paecilomyces variotii and Penicillium citrinum with marginal activity against L. prolificans, Scedosporium spp. and Scopulariopsis spp., but it is inactive against Purpureocillium lilacinum, Fusarium spp. and Mucorales [54,55] (Figure 2).
Recent advances in the molecular diagnosis of mucormycosis
Published in Expert Review of Molecular Diagnostics, 2018
Sanjeet S. Dadwal, Dimitrios P. Kontoyiannis
Mucormycosis is an infection caused by fungi from the Mucorales order [1], with Rhizopus spp., (Rhizopus oryzae and Rhizopus arrhizus are used equivalently in medical literature although the taxonomists favor the term R. arrhizus) the most common cause, followed by Mucor spp., Lichtheimia corymbifera [2], and less commonly by Cunninghamella spp., Rhizomucor spp., and Apophysomyces spp. The spectrum of disease caused by Mucormycetes is broad and includes rhinosinusitis, pneumonia, gastrointestinal tract involvement, dissemination to internal organs, and skin/soft tissue infection [3].
Part 1: Mucormycosis: prevalence, risk factors, clinical features, and diagnosis
Published in Expert Review of Anti-infective Therapy, 2023
Joseph P. Lynch, Michael C. Fishbein, Fereidoun Abtin, George G. Zhanel
Significant differences in genera and species exist among different geographic regions [15]. Rhizopus spp. are common in virtually all geographic regions [15–17]. Lichtheimia are common in Europe, whereas Apophysomyces variabilis thrive in tropical and subtropical climates (particularly in Asia) [11,16–21]. Cunninghamella bertholletiae is the most virulent Mucorales species in humans and is associated with the highest mortality rates [15,17,22–25]. MCR exhibits a marked propensity to invade blood vessels, leading to thrombosis, necrosis and infarction of tissue, and high mortality [10,22].