In Vitro
 Susceptibilities of Worldwide Isolates of Intrapulmonary
 Aspergillus
 Species and Important
 Candida
 Species in Sterile Body Sites against Important Antifungals: Data from the Antimicrobial Testing Leadership and Surveillance Program, 2017–2020

Jean, Shio-Shin; Yang, Hung‐Jen; Hsieh, Po-Chuen; Huang, Yu-Tsung; Ko, Wen–Chien; Hsueh, Po-Ren

doi:10.1128/spectrum.02965-22

Cited by 3 publications

(6 citation statements)

References 46 publications

(61 reference statements)

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“…However, these MIC 90 are far above the maximum MIC values covered by concentrations in peritoneal fluid. This implies that the percentage of isolates from sterile sites covered by anidulafungin would be < 10% considering the MIC distribution in a recent worldwide surveillance study [ 41 ]. Suboptimal drug concentrations in peritoneal fluid represent a risk for emergence of antifungal resistance in intraabdominal Candida , making of intraabdominal microbiota a reservoir of non-susceptible isolates, as occurs with bacteria.…”

Section: Discussionmentioning

confidence: 99%

“…Three drug classes, azoles, echinocandins and polyenes, represent the main antifungal armamentarium against Candida infections. C. albicans continues to be the most frequent species isolated from IACs, but others, some less susceptible to antifungals, begin to gain weight [ 41 , 42 ]. In the SENTRY antifungal surveillance programme, the frequency of C. albicans decreased from 57.4% in 1997–2001 to 46.4% in 2015–2016 [ 42 ].…”

Section: Pk/pd Analysis Of Antifungal Options For the Treatment Of Iacmentioning

confidence: 99%

“…According to Table 3 , except for anidulafungin against C. albicans and C. glabrata , MIC 90 values do not exceed breakpoints values; however, they are far from the maximum MIC values covered by concentrations in peritoneal fluid (Table 4 ). If MIC values in Table 4 are considered, the percentage of isolates from sterile sites covered by anidulafungin would be 10.3% for C. albicans and < 1% for other Candida species according to the MIC distribution in a recent worldwide surveillance study [ 41 ]. Therefore, since drug concentrations are suboptimal in peritoneal fluid, there is a real chance of promoting emergence of antifungal resistance in intraabdominal Candida , making of intraabdominal microbiota a reservoir of non-susceptible isolates, as occurs with bacteria.…”

Section: Pk/pd Analysis Of Antifungal Options For the Treatment Of Iacmentioning

confidence: 99%

“…A published case series in paediatric patients concluded that peritoneal liposomal amphotericin B concentrations were significantly lower than in plasma, hampering to attain the Cmax/MIC target value [ 93 ]. Considering MIC 90 values for the different Candida species (MICs of 0.5–1 mg/L) [ 41 , 52 , 53 ], Cmax of liposomal amphotericin B in peritoneum should be at least 4.5 mg/L. To our knowledge, no more data on peritoneum concentrations are available, making difficult its PK/PD assessment for IAC.…”

Section: Analysis Of Potential Alternativesmentioning

confidence: 99%

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Critical appraisal beyond clinical guidelines for intraabdominal candidiasis

Maseda,

Martín-Loeches,

Zaragoza

et al. 2023

Crit Care

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Background Regardless of the available antifungals, intraabdominal candidiasis (IAC) mortality continues to be high and represents a challenge for clinicians. Main body This opinion paper discusses alternative antifungal options for treating IAC. This clinical entity should be addressed separately from candidemia due to the peculiarity of the required penetration of antifungals into the peritoneal cavity. Intraabdominal concentrations may be further restricted in critically ill patients where pathophysiological facts alter normal drug distribution. Echinocandins are recommended as first-line treatment in guidelines for invasive candidiasis. However, considering published data, our pharmacodynamic analysis suggests the required increase of doses, postulated by some authors, to attain adequate pharmacokinetic (PK) levels in peritoneal fluid. Given the limited evidence in the literature on PK/PD-based treatments of IAC, an algorithm is proposed to guide antifungal treatment. Liposomal amphotericin B is advocated as first-line therapy in patients with sepsis/septic shock presenting candidemia or endophthalmitis, or with prior exposure to echinocandins and/or fluconazole, or with infections by Candida glabrata. Other situations and alternatives, such as new compounds or combination therapy, are also analysed. Conclusion There is a critical need for more robust clinical trials, studies examining patient heterogeneity and surveillance of antifungal resistance to enhance patient care and optimise treatment outcomes. Such evidence will help refine the existing guidelines and contribute to a more personalised and effective approach to treating this serious medical condition. Meanwhile, it is suggested to broaden the consideration of other options, such as liposomal amphotericin B, as first-line treatment until the results of the fungogram are available and antifungal stewardship could be implemented to prevent the development of resistance.

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Section: Discussionmentioning

confidence: 99%

Section: Pk/pd Analysis Of Antifungal Options For the Treatment Of Iacmentioning

confidence: 99%

Section: Pk/pd Analysis Of Antifungal Options For the Treatment Of Iacmentioning

confidence: 99%

Section: Analysis Of Potential Alternativesmentioning

confidence: 99%

See 2 more Smart Citations

Critical appraisal beyond clinical guidelines for intraabdominal candidiasis

Maseda,

Martín-Loeches,

Zaragoza

et al. 2023

Crit Care

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“…However, triazole-resistant strains of A. fumigatus are increasing at a concerning rate ( 10 , 11 ), with 16.15% of A. fumigatus isolates showing resistance to at least one azole. This complicates treatment and increases fatality rates ( 12 , 13 ). Most published studies concur that the original mutations most likely occurred because of the usage of azole-based fungicides in agriculture, as hypothesized by Snelders et al.…”

Section: Introductionmentioning

confidence: 99%

Succinylation modification provides new insights for the treatment of immunocompromised individuals with drug-resistant Aspergillus fumigatus infection

Chen

Meng

et al. 2023

Front. Immunol.

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Invasive Aspergillus fumigatus infection poses a serious threat to global human health, especially to immunocompromised individuals. Currently, triazole drugs are the most commonly used antifungals for aspergillosis. However, owing to the emergence of drug-resistant strains, the effect of triazole drugs is greatly restricted, resulting in a mortality rate as high as 80%. Succinylation, a novel post-translational modification, is attracting increasing interest, although its biological function in triazole resistance remains unclear. In this study, we initiated the screening of lysine succinylation in A. fumigatus. We discovered that some of the succinylation sites differed significantly among strains with unequal itraconazole (ITR) resistance. Bioinformatics analysis showed that the succinylated proteins are involved in a broad range of cellular functions with diverse subcellular localizations, the most notable of which is cell metabolism. Further antifungal sensitivity tests confirmed the synergistic fungicidal effects of dessuccinylase inhibitor nicotinamide (NAM) on ITR-resistant A. fumigatus. In vivo experiments revealed that treatment with NAM alone or in combination with ITR significantly increased the survival of neutropenic mice infected with A. fumigatus. In vitro experiments showed that NAM enhanced the killing effect of THP-1 macrophages on A. fumigatus conidia. Our results suggest that lysine succinylation plays an indispensable role in ITR resistance of A. fumigatus. Dessuccinylase inhibitor NAM alone or in combination with ITR exerted good effects against A. fumigatus infection in terms of synergistic fungicidal effect and enhancing macrophage killing effect. These results provide mechanistic insights that will aid in the treatment of ITR-resistant fungal infections.

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Assessing Diagnosis of Candida Infections: A Study on Species Prevalence and Antifungal Resistance in Northern Morocco

Ahaik,

Nunez-Rodríguez,

Abrini

et al. 2024

JoF

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The incidence of Candida infections has increased in the last decade, posing a serious threat to public health. Appropriately facing this challenge requires precise epidemiological data on species and antimicrobial resistance incidence, but many countries lack appropriate surveillance programs. This study aims to bridge this gap for Morocco by identifying and phenotyping a year-long collection of clinical isolates (n = 93) from four clinics in Tetouan. We compared the current standard in species identification with molecular methods and assessed susceptibility to fluconazole and anidulafungin. Our results identified limitations in currently used diagnostics approaches, and revealed that C. albicans ranks as the most prevalent species with 60 strains (64.52%), followed by C. glabrata with 14 (15.05%), C. parapsilosis with 6 (6.45%), and C. tropicalis with 4 (4.30%). In addition, we report the first identification of C. metapsilosis in Morocco. Susceptibility results for fluconazole revealed that some isolates were approaching MICs resistance breakpoints in C. albicans (2), and C. glabrata (1). Our study also identified anidulafungin resistant strains in C. albicans (1), C. tropicalis (1), and C. krusei (2), rendering the two strains from the latter species multidrug-resistant due to their innate resistance to fluconazole. These results raise concerns about species identification and antifungal resistance in Morocco and highlight the urgent need for more accurate methods and preventive strategies to combat fungal infections in the country.

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In Vitro Susceptibilities of Worldwide Isolates of Intrapulmonary Aspergillus Species and Important Candida Species in Sterile Body Sites against Important Antifungals: Data from the Antimicrobial Testing Leadership and Surveillance Program, 2017–2020

Cited by 3 publications

References 46 publications

Critical appraisal beyond clinical guidelines for intraabdominal candidiasis

Critical appraisal beyond clinical guidelines for intraabdominal candidiasis

Succinylation modification provides new insights for the treatment of immunocompromised individuals with drug-resistant Aspergillus fumigatus infection

Assessing Diagnosis of Candida Infections: A Study on Species Prevalence and Antifungal Resistance in Northern Morocco

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