Multicenter Evaluation of MIC Distributions for Epidemiologic Cutoff Value Definition To Detect Amphotericin B, Posaconazole, and Itraconazole Resistance among the Most Clinically Relevant Species of Mucorales

Espinel-Ingroff, Ana; Chakrabarti, Arunaloke; Chowdhary, Anuradha; Córdoba, Susana; Dannaoui, Éric; Dufresne, Philippe J.; Fothergill, Annette W.; Ghannoum, Mahmoud A.; González, Gloria M.; Guarro, Josep; Kidd, Sarah; Lass‐Flörl, Cornelia; Meis, Jacques F.; Peláez, Teresa; Tortorano, Anna Maria; Turnidge, John

doi:10.1128/aac.04435-14

Cited by 111 publications

(97 citation statements)

References 33 publications

(48 reference statements)

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“…Similar dose‐response relationships were seen for Mucor species and R oryzae. Compared to A fumigatus isolates, the MICs of Mucorales are often higher with a geometric mean CLSI MIC of 0.39 mg/L and an epidemiological cut‐off value of 1 mg/L for L corymbifera , R oryzae and R microspores and 4 mg/L for M circinelloides (Figure ) . Furthermore, the EUCAST MICs for Mucorales are higher than CLSI MICs for most species .…”

Section: Discussionmentioning

confidence: 97%

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High‐dose posaconazole for azole‐resistant aspergillosis and other difficult‐to‐treat mould infections

Schauwvlieghe

Buil

Verweij

et al. 2019

Mycoses

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Summary Background Oral follow‐up therapy is problematic in moulds with reduced azole‐susceptibility, such as azole‐resistant Aspergillus fumigatus infection. Currently, only intravenous liposomal amphotericin B (L‐AmB) is advocated by guidelines for the treatment of azole‐resistant aspergillosis infections. Preclinical research indicates that high‐dose posaconazole (HD‐POS) might be a feasible option provided that high drug exposure (ie POS serum through levels >3 mg/L) can be achieved and is safe. Objectives To describe our experience with the use of oral HD‐POS as treatment strategies for patients infected with pathogens with a POS MIC close to the clinical breakpoint. Patients/Methods We review evidence supporting the use of HD‐POS and describe our experience on safety and efficacy in 16 patients. In addition, we describe the adverse events (AE) observed in 25 patients with POS concentrations at the higher end of the population distribution during treatment with the licensed dose. Results Sixteen patients were treated intentionally with HD‐POS for voriconazole‐resistant invasive aspergillosis (7/16), mucormycosis (4/16), salvage therapy for IA (4/16) and IA at a sanctuary site (spondylodiscitis) in 1. Grade 3‐4 AEs were observed in 6, and all of them were considered at least possibly related. Grade 3‐4 AEs were observed in 5 of the 25 patients with spontaneous high POS serum through levels considered at least possibly related using Naranjo scale. Conclusions High‐dose posaconazole is a treatment option if strict monitoring for both exposure and for AE is possible.

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Section: Discussionmentioning

confidence: 97%

“…Posaconazole minimal inhibitory concentrations (MICs) distributions of most common Mucorales species: Rhizopus oryzae, Mucor circinelloides, Rhizopus microspores and Lichtheimia corymbifera . MICs were extracted from Espinel‐Ingroff et al MICs were determined according to the CLSI method for susceptibility testing of moulds (M38‐A2)…”

Section: Discussionmentioning

confidence: 99%

High‐dose posaconazole for azole‐resistant aspergillosis and other difficult‐to‐treat mould infections

Schauwvlieghe

Buil

Verweij

et al. 2019

Mycoses

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“…Apophysomyces spp. also retains susceptibility to itraconazole unlike other agents of mucormycosis, while the clinical relevance of above is yet to be determined …”

Section: Discussionmentioning

confidence: 99%

Mucormycosis—A clinicoepidemiological review of cases over 10 years

Manesh

Rupali

Sullivan

et al. 2019

Mycoses

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Summary Background Limited data exist for epidemiology and outcomes of various agents causing mucormycosis in various clinical settings from developing countries like India. Objectives To study the epidemiology and outcomes of various agents causing mucormycosis in different clinical settings in a tertiary care hospital from South India. Patients and methods We reviewed details of 184 consecutive patients with culture‐proven mucormycosis with consistent clinical syndrome and supporting features from September 2005 to September 2015. Results The mean age of patients was 50.42 years; 70.97% were male. Unlike developed countries, R microsporus (29/184; 15.7%) and Apophysomyces elegans (20/184; 10.8%) also evolved as important pathogens in addition to R arrhizus in our setting. Paranasal sinuses (136/184; 73.9%) followed by musculoskeletal system (28/184; 15.2%) were the common areas of involvement. Apophysomyces elegans typically produced skin and musculoskeletal disease in immune‐competent individuals with trauma (12/20; 60%) and caused significantly lower mortality (P = 0.03). R microsporus was more common in patients with haematological conditions (25% vs 15.7%) and was less frequently a cause for sinusitis than R arrhizus (27.58% vs 10.9%). The overall mortality was 30.97%. Combination therapy with surgery and antifungals offered the best chance for cure. Conclusions Agents causing mucormycosis may have unique clinical and epidemiological characteristics.

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“…For species/antifungals with no breakpoints, epidemiological cutoff values (ECVs) are being established, but data on ECVs for C. lusitaniae have not been well described (16–20). The ECV is the MIC value that defines the upper limit of the wild type population of MIC values and is meant to distinguish between a wild type isolate and a non-wild type isolate that may have acquired resistance or reduced susceptibility to the given antifungal agent.…”

mentioning

confidence: 99%

Candida lusitaniae MICs to the echinocandins are elevated but FKS -mediated resistance is rare

Lockhart

Pham

Kuykendall

et al. 2016

Diagnostic Microbiology and Infectious Disease

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MIC values were generated for caspofungin, micafungin and anidulafungin against 106 isolates of C. lusitaniae and these values were compared to established epidemiologic cutoff values. The majority of isolates were wild type both by MIC value as well as by FKS1 hotspot sequencing. Although C. lusitaniae isolates have MIC values to the echinocandins that are elevated compared to other common species, with regards to known mechanisms of resistance to the echinocandins, isolates with MIC values at or below the ECVs of 0.5 and 1 µg/mL for micafungin and anidulafungin, respectively, should be considered wild type.

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Multicenter Evaluation of MIC Distributions for Epidemiologic Cutoff Value Definition To Detect Amphotericin B, Posaconazole, and Itraconazole Resistance among the Most Clinically Relevant Species of Mucorales

Cited by 111 publications

References 33 publications

High‐dose posaconazole for azole‐resistant aspergillosis and other difficult‐to‐treat mould infections

High‐dose posaconazole for azole‐resistant aspergillosis and other difficult‐to‐treat mould infections

Mucormycosis—A clinicoepidemiological review of cases over 10 years

Candida lusitaniae MICs to the echinocandins are elevated but FKS -mediated resistance is rare

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