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American Journal of Health-system... Apr 2023Echinocandins are favored drugs for the treatment of fungal infections. There is growing evidence that obese patients treated with echinocandins have lower exposures due... (Review)
Review
PURPOSE
Echinocandins are favored drugs for the treatment of fungal infections. There is growing evidence that obese patients treated with echinocandins have lower exposures due to pharmacokinetic (PK) alterations. We conducted a scoping review to characterize, evaluate, and summarize the available evidence on echinocandins exposures in obese patients.
SUMMARY
A comprehensive search of PubMed, Embase, and Cochrane Library for studies on echinocandins published from database inception to October 28, 2022, was conducted using PRISMA-ScR methodology. A total of 25 studies comprising more than 3,174 subjects (8 micafungin studies, 7 caspofungin studies, 9 anidulafungin studies, and 1 rezafungin study) were included in this review. Seventeen studies reported lower echinocandins exposures in overweight and obese individuals compared with normal-weight individuals; the authors of these studies recommended dose adjustments. Conversely, 8 studies did not find significant differences in echinocandin exposure among subjects in varying body weight categories. Clinicians may consider dose adjustments of echinocandins in obese patients; however, there is limited evidence on the ideal dose adjustment strategy to overcome the low echinocandins exposures in obese patients.
CONCLUSION
This scoping review shed light on a growing body of evidence indicating that obese patients have lower echinocandin exposures relative to targeted PK indices, which may lead to negative therapeutic implications. Currently, a lack of high-quality evidence impedes reaching consensus on recommendations for echinocandin dosing adjustment in obese patients. Future research evaluating the optimal echinocandin dosing strategy for obese patients is needed.
Topics: Humans; Antifungal Agents; Body Weight; Echinocandins; Lipopeptides; Microbial Sensitivity Tests; Obesity; Overweight
PubMed: 36680786
DOI: 10.1093/ajhp/zxad021 -
Microorganisms Dec 2022is a prevalent fungal pathogen of humans. Understanding the development of decreased susceptibility to ECN drugs of this microbe is of substantial interest, as it is...
is a prevalent fungal pathogen of humans. Understanding the development of decreased susceptibility to ECN drugs of this microbe is of substantial interest, as it is viewed as an intermediate step allowing the formation of resistance mutations. We used six previously characterized mutants that decreased caspofungin susceptibility either by acquiring aneuploidy of chromosome 5 (Ch5) or by aneuploidy-independent mechanisms. When we exposed these caspofungin-adapted mutants to caspofungin again, we obtained 60 evolved mutants with further decreases in caspofungin susceptibility, as determined with CLSI method. We show that the initial adaptation to caspofungin is coupled with the adaptation to other ECNs, such as micafungin and anidulafungin, in mutants with no ploidy change, but not in aneuploid mutants, which become more susceptible to micafungin and anidulafungin. Furthermore, we find that the initial mechanism of caspofungin adaptation determines the pattern of further adaptation as parentals with no ploidy change further adapt to all ECNs by relatively small decreases in susceptibility, whereas aneuploid parentals adapt to all ECNs, primarily by large decrease in susceptibilities. Our data suggest that either distinct or common mechanisms can govern adaptation to different ECNs.
PubMed: 36677315
DOI: 10.3390/microorganisms11010023 -
International Journal of Molecular... Jan 2023Yeast acquisition begins at birth; however, the contribution of the mother on yeast transmission to the offspring and associated resistance is yet to be clarified. The...
Yeast acquisition begins at birth; however, the contribution of the mother on yeast transmission to the offspring and associated resistance is yet to be clarified. The aim of this study was to explore the vertical transmission of yeasts and their antifungal susceptibility profile in early life. Oral, fecal, and breastmilk samples were collected from 73 mother-child pairs four to twelve weeks after delivery and cultured on Sabouraud dextrose agar with chloramphenicol. The isolates were identified by MALDI-TOF MS. The vertical transmission was studied by microsatellite genotyping. Antifungal susceptibility was determined for fluconazole, voriconazole, miconazole, anidulafungin, and nystatin by broth microdilution assay, following CLSI-M60 guidelines. A total of 129 isolates were identified from 53% mother-child pairs. We verified the vertical transmission of (n = three mother-child pairs) and (n = one mother-child pair) strains, including an antifungal resistant strain transmitted from breastmilk to the gut of a child. Most isolates were susceptible to the tested antifungals, with the exception of four isolates and one isolate. The vertical transmission of yeasts happens in early life. This is the first work that demonstrated the role of the mother as a source of transmission of antifungal-resistant yeasts to the child.
Topics: Infant, Newborn; Humans; Antifungal Agents; Milk, Human; Candida; Yeasts; Mouth; Mother-Child Relations; Microbial Sensitivity Tests; Drug Resistance, Fungal
PubMed: 36674962
DOI: 10.3390/ijms24021449 -
Current Medical Mycology Jun 2022This study aimed to evaluate the species distribution and susceptibility pattern of the strains isolated from Candida colonization in pediatric patients staying at...
BACKGROUND AND PURPOSE
This study aimed to evaluate the species distribution and susceptibility pattern of the strains isolated from Candida colonization in pediatric patients staying at pediatric intensive care unit (ICU) and infant ICU of Children's Medical Center in Tehran, Iran.
MATERIALS AND METHODS
This study was conducted in the Children's Medical Center in Tehran, Iran. In total, 440 samples from 56 patients with oral cavity, skin surrounded catheters, and ear, throat, nasal, and urine cultures were collected. All patients were evaluated in terms of colonization on the admission day as well as the days 7, 14, and 28 according to the previous studies. CHROMagar medium was applied for primary/multiple species identification and the isolates were identified by using polymerase chain reaction-based methods to the species-specific complex level. The antifungal susceptibility test was performed according to the Clinical and Laboratory Standards protocol published as M27-A3 and M60 documents.
RESULTS
In total, 136 yeast samples from 26 individuals (30.9%) out of 440 samples were considered colonization. The most prevalent species in IICU was (27%, n=20) followed by (24 %, n=18) and (16%, n=12). In PICU, the predominant species was (40%, n=24) followed by (18%, n=11) and (16%, n=10). Among the 40 tested isolates from both units, fluconazole-resistant isolates (n=11, 8.15%) were determined according to the new breakpoints. In the case of echinocandins, 2 isolates, including C. albicans (n=1) and C. krusei (n=1) were resistant against both caspofungin and anidulafungin (totally 1.48%).
CONCLUSION
In the present study, since is intrinsically-resistance against fluconazole, emphasizing the importance of species-level identification of isolates is outstanding. However, according to the antifungal susceptibility testing results, only 7.2% of the strains were resistant to fluconazole. It would be beneficial to monitor the ICU patients who are at high risk of invasive infection.
PubMed: 36654792
DOI: 10.18502/cmm.8.2.10329 -
Current Medical Mycology Jun 2022Invasive candidiasis is a life-threatening condition that kills a large number of immunocompromised patients each year worldwide. We used post-antifungal effect studies...
BACKGROUND AND PURPOSE
Invasive candidiasis is a life-threatening condition that kills a large number of immunocompromised patients each year worldwide. We used post-antifungal effect studies to analyze the activities of anidulafungin (AFG), as a clinically crucial antifungal drug, amphotericin B (AMB), and fluconazole (alone and in combinations) against FLC-susceptible and -resistant () isolates obtained from the cancer patients.
MATERIALS AND METHODS
We tested the phenomenon of post antifungal effects of FLC, AMB, AFG, and combinations of FLC+AFG, AFG+AMB, and FLC+AMB against 17 isolates obtained from the oral cavity of cancer patients. Isolates that had not been exposed to antifungals, served as a control group. Colony counts were performed at 0, 2, 4, 6, and 24 h after a brief (1 h) exposure to antifungal.
RESULTS
The FLC had no detectable post-antifungal effect independent of antifungal concentration and resembled drug-free FLC (control). Significant variations in the post-antifungal effect were observed when all AMB and AFG were compared to FLC. The combination of AFG and AMB with FLC resulted in effective activity compared to FLC alone. Combination regimens were rated as indifferent in general. Interestingly, low dosages of the AFG displayed increasing fungistatic action as it approached a fungistatic endpoint against isolates (n=17).
CONCLUSION
Our findings suggested that brief exposure to AFG, in combination with FLC and AMB, at low concentrations of the medicines utilized, could be effective in the evaluation and optimization of new dosage regimens to manage candidiasis. However, future studies will determine the clinical utility of our findings.
PubMed: 36654787
DOI: 10.18502/cmm.8.2.10327 -
Journal of Global Infectious Diseases 2022has turned up as a multidrug-resistant nosocomial agent with outbreaks reported worldwide. The present study was conducted to evaluate the antifungal drug...
INTRODUCTION
has turned up as a multidrug-resistant nosocomial agent with outbreaks reported worldwide. The present study was conducted to evaluate the antifungal drug susceptibility pattern of .
METHODS
Isolates of were obtained from clinically suspected cases of candidemia from January 2019 to June 2021. Identification was done with matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) and panfungal DNA polymerase chain reaction (PCR), followed by sequencing. Antifungal susceptibility testing was performed with broth microdilution method.
RESULTS
Out of 50 isolates , 49 were identified by MALDI-TOF and one isolate was identified with panfungal DNA PCR followed by sequencing. For fluconazole, 84% ( = 42) isolates were found to be resistant and 16% ( = 8) isolates were susceptible (minimum inhibitory concentrations [MICs] range 0.5-16). Posaconazole exhibited potent activity, followed by itraconazole. For amphotericin B, only 6% ( = 3) isolates were resistant with MICs ≥2 μg/mL. Only 4% ( = 2) isolates exhibited resistance to caspofungin. No resistance was noted for micafungin and anidulafungin. One (2%) isolate was found to be panazole resistant. One (2%) isolate was resistant to fluconazole, amphotericin B, and caspofungin.
CONCLUSION
Correct identification of can be obtained with the use of MALDI-TOF and sequencing methods. A small percentage of fluconazole-sensitive isolates are present. Although elevated MICs for amphotericin B and echinocandins are not generally observed, the possibility of resistance with the irrational use of these antifungal drugs cannot be denied. Pan azole-resistant and pan drug-resistant strains of are on rise.
PubMed: 36636301
DOI: 10.4103/jgid.jgid_44_22 -
Molecules (Basel, Switzerland) Jan 2023The use of essential oils is increasingly being investigated among new therapeutic approaches based on medicinal plants and their extracts. With the wide use of... (Review)
Review
The use of essential oils is increasingly being investigated among new therapeutic approaches based on medicinal plants and their extracts. With the wide use of synthetic and semi-synthetic antimicrobial drugs, the spread of drug-resistant clinical isolates has increased, and research is directed towards natural products, such as essential oils, as useful antimicrobial resources. In the context of a prospective infection, we compared the impact of essential oils and common antimicrobial agents on the microbicidal activity of human phagocytes. Here, we present the results of our decades-long investigation into the effectiveness of thyme red oil (26.52% thymol chemotype), tea tree oil (TTO), and Mentha of Pancalieri [( (Huds) var. (Sole), form (Camus) ()] essential oils on human polymorphonuclear leukocytes (PMNs) capacity to kill clinical strains of and when compared to three antifungal drugs used to treat candidiasis (fluconazole, anidulafungin, and caspofungin) These essential oils demonstrate antifungal drug-like and/or superior efficacy in enhancing intracellular killing by PMNs, even at subinhibitory concentrations. Our results are compared with data in the literature on essential oils and immune system interactions. This comparison would aid in identifying therapeutic solutions to the increasingly prevalent antibiotic resistance as well as filling in any remaining knowledge gaps on the bioactivity of essential oils.
Topics: Humans; Oils, Volatile; Antifungal Agents; Prospective Studies; Fluconazole; Plant Oils; Anti-Infective Agents; Microbial Sensitivity Tests
PubMed: 36615625
DOI: 10.3390/molecules28010435 -
Infection and Drug Resistance 2022spp. infection in immunocompromised patients results in increasing morbidity and mortality. This study investigated clinical and microbiological characteristics of...
BACKGROUND
spp. infection in immunocompromised patients results in increasing morbidity and mortality. This study investigated clinical and microbiological characteristics of aspergillosis in a Chinese tertiary teaching hospital.
METHODS
A total of 114 patients with aspergillosis were included over a 5-year period at Ruijin Hospital. In sum, 114 strains were isolated and identified at species level using matrix-assisted laser desorption ionization time-of-flight mass spectrometry, confirmed by ITS gene region and β-tubulin () gene sequencing. Sensititre YeastOne was used in vitro to test susceptibility to antifungal drugs: amphotericin B, itraconazole, voriconazole, posaconazole, isavuconazole, micafungin, anidulafungin, and caspofungin.
RESULTS
The median age of the patients was 61 (19) years, men accounted for 53.5% (n=61) of the sample, about 64% were immunocompromised, and 36% had underlying diseases. Pulmonary diseases accounted for 27.2%. isolates were mainly isolated from sputum (n=42, 36.8%). Antifungal therapy was administered to 106 (93.0%) patients and voriconazole (n=76, 66.7%) was the most frequently used as empirical therapy. (n=69, 60.5%) was the most common species. There was a 73.7% concordance between MALDI-TOF MS and molecular identification. All isolates showed good susceptibility to anidulafungin and caspofungin.
CONCLUSION
Immunocompromised patients are an at-risk population for aspergillosis, and voriconazole was used as empirical therapy in Ruijin Hospital, China. was the predominant species causing aspergillosis, and - as non species are increasing - the second-leading cause of aspergillosis. Anidulafungin and caspofungin were the most active in vitro against the isolates tested. The MALDI-TOF MS method showed good accuracy for identification of common spp. In vitro antifungal-susceptibility testing is crucially important for decisions on effective therapy with aspergillosis.
PubMed: 36533254
DOI: 10.2147/IDR.S391069 -
Clinical Microbiology and Infection :... May 2023To determine the epidemiological cut-off values (ECVs) of ten antifungal agents in a wide range of yeasts and Aspergillus spp. using gradient concentration strips.
OBJECTIVES
To determine the epidemiological cut-off values (ECVs) of ten antifungal agents in a wide range of yeasts and Aspergillus spp. using gradient concentration strips.
METHODS
The minimum inhibitory concentrations for amphotericin B, anidulafungin, caspofungin, micafungin, flucytosine, fluconazole, itraconazole, isavuconazole, posaconazole, and voriconazole, determined with gradient concentration strips at 35 French microbiology laboratories between 2002 and 2020, were retrospectively collected. Then, the ECVs were calculated using the iterative method and a cut-off value of 97.5%.
RESULTS
Minimum inhibitory concentrations were available for 17 653 clinical isolates. In total, 48 ECVs (including 32 new ECVs) were determined: 29 ECVs for frequent yeast species (e.g. Candida albicans and itraconazole/flucytosine, and Candida glabrata species complex [SC] and flucytosine) and rare yeast species (e.g. Candida dubliniensis, Candida inconspicua, Saccharomyces cerevisiae, and Cryptococcus neoformans) and 19 ECVs for Aspergillusflavus SC, Aspergillusfumigatus SC, Aspergillusnidulans SC, Aspergillusniger SC, and Aspergillusterreus SC.
CONCLUSIONS
These ECVs can be added to the already available gradient concentration strip-specific ECVs to facilitate minimum inhibitory concentration interpretation and streamline the identification of nonwild type isolates.
Topics: Humans; Antifungal Agents; Itraconazole; Flucytosine; Saccharomyces cerevisiae; Retrospective Studies; Phylogeny; Fluconazole; Aspergillus; Microbial Sensitivity Tests; Drug Resistance, Fungal
PubMed: 36509375
DOI: 10.1016/j.cmi.2022.11.030 -
Emerging Microbes & Infections Dec 2023is becoming a predominant non- cause of invasive candidiasis (IC). Echinocandins are the preferred choice for IC treatment and prophylaxis. Resistance to echinocandins...
is becoming a predominant non- cause of invasive candidiasis (IC). Echinocandins are the preferred choice for IC treatment and prophylaxis. Resistance to echinocandins in has emerged in several countries, but little is known about the susceptibility profile in China or about mechanisms of resistance. Here, we investigated the echinocandin susceptibilities of 2523 isolates collected from China and further explored the resistance mechanism among echinocandin-resistant isolates. Anidulafungin exhibited the highest MICs (MIC, 1 and 2 µg/mL; GM, 0.948 µg/mL), while caspofungin showed better activity (0.5 and 1 µg/mL; 0.498 µg/mL). Significantly higher echinocandin MICs were observed among blood-derived isolates compared to others, especially for caspofungin (GM, 1.348 µg/mL vs 0.478 µg/mL). Isolates from ICU and surgical wards also showed higher MICs. Twenty isolates showed intermediate phenotypes for at least one echinocandin. One was resistant to all three echinocandins, fluconazole and voriconazole, which caused breakthrough IC during long-term exposure to micafungin. WGS revealed this isolate carried a mutation S656P in hotspot1 region of Fks1. Bioinformatics analyses suggested that this mutation might lead to an altered protein conformation. CRISPR Cas9-mediated introduction of this mutation into a susceptible reference strain increased MICs of all echinocandins 64-fold, with similar results found in the subspecies, and . This is the first report of a multi-azole resistant and pan-echinocandin resistant isolate, and the identification of a conferring pan-echinocandin resistance. Our study underscores the necessity of rigorous management of antifungal use and of monitoring for antifungal susceptibility.
Topics: Antifungal Agents; Candida parapsilosis; Candidemia; Caspofungin; China; Echinocandins; Microbial Sensitivity Tests; Humans; Drug Resistance, Fungal
PubMed: 36440795
DOI: 10.1080/22221751.2022.2153086