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Molecular epidemiology and antimicrobial resistance of vaginal Candida glabrata isolates in Namibia.Medical Mycology Jan 2024Candida glabrata is the most common non-albicans Candida species that causes vulvovaginal candidiasis (VVC). Given the intrinsically low susceptibility of C. glabrata to...
Candida glabrata is the most common non-albicans Candida species that causes vulvovaginal candidiasis (VVC). Given the intrinsically low susceptibility of C. glabrata to azole drugs, investigations into C. glabrata prevalence, fungal susceptibility profile, and molecular epidemiology are necessary to optimise the treatment of VVC. This molecular epidemiological study was conducted to determine antifungal drug profile, single nucleotide polymorphisms (SNPs) associated with phenotypic antifungal resistance and epidemic diversity of C. glabrata isolates from women with VVC in Namibia. Candida glabrata isolates were identified using phenotypic and molecular methods. Antifungal susceptibility of strains was determined for fluconazole, itraconazole, amphotericin B, and anidulafungin. Whole genome sequencing was used to determine SNPs in antifungal resistance genes and sequence type (ST) allocation. Among C. glabrata isolates, all (20/20; 100%) exhibited phenotypic resistance to the azole class antifungal drug, (fluconazole), and phenotypic susceptibility to the polyene class (amphotericin B), and the echinocandins (anidulafungin). Non-synonymous SNPs were identified in antifungal resistance genes of all fluconazole-resistant C. glabrata isolates including ERG6 (15%), ERG7 (15%), CgCDR1 (25%), CgPDR1 (60%), SNQ2 (10%), FKS1 (5.0%), FKS2 (5.0%), CgFPS1 (5.0%), and MSH2 (15%). ST15 (n = 8/20, 40%) was predominant. This study provides important insight into phenotypic and genotypic antifungal resistance across C. glabrata isolates from women with VVC in Namibia. In this study, azole resistance is determined by an extensive range of SNPs, while the observed polyene and echinocandin resistance-associated SNPs despite phenotypic susceptibility require further investigation.
Topics: Female; Humans; Antifungal Agents; Candida glabrata; Candidiasis, Vulvovaginal; Fluconazole; Amphotericin B; Anti-Bacterial Agents; Anidulafungin; Molecular Epidemiology; Namibia; Microbial Sensitivity Tests; Drug Resistance, Bacterial; Echinocandins; Azoles; Polyenes; Drug Resistance, Fungal
PubMed: 38308518
DOI: 10.1093/mmy/myae009 -
The International Journal of Artificial... Mar 2024With rates of ECMO utilization on the rise, prevention of nosocomial infections is of paramount importance. , an emerging highly pathogenic multidrug resistant fungus,...
With rates of ECMO utilization on the rise, prevention of nosocomial infections is of paramount importance. , an emerging highly pathogenic multidrug resistant fungus, is of particular concern as it is associated with persistent colonization of environmental surfaces, inability to be recognized by many diagnostic platforms, inconsistent laboratory susceptibility results, and high mortality rates. We describe a case of in a VV-ECMO patient successfully managed with a combination of anidulafungin, amphotericin B, and flucytosine.
Topics: Humans; Amphotericin B; Antifungal Agents; Candida; Candida auris; Microbial Sensitivity Tests
PubMed: 38281934
DOI: 10.1177/03913988231226357 -
Journal of Fungi (Basel, Switzerland) Jan 2024is a recently emerged human fungal pathogen that has posed a significant threat to public health. Since its first identification in 2009, this fungus has caused...
is a recently emerged human fungal pathogen that has posed a significant threat to public health. Since its first identification in 2009, this fungus has caused nosocomial infections in over 47 countries across all inhabited continents. As of May 2023, the whole-genome sequences of over 4000 strains have been reported and a diversity of mutations, including in genes known to be associated with drug resistance in other human fungal pathogens, have been described. Among them, 387 strains contained antifungal-susceptibility information for which different methods might be used depending on the drugs and/or investigators. In most reports on so far, the number of strains analyzed was very small, from one to a few dozen, and the statistical significance of the relationships between these genetic variants and their antifungal susceptibilities could not be assessed. In this study, we conducted genome-wide association studies on individual clades based on previously published isolates to investigate the statistical association between genomic variants and susceptibility differences to nine antifungal drugs belonging to four major drug categories: 5-fluorocytosine, amphotericin B, fluconazole, voriconazole, itraconazole, posaconazole, anidulafungin, caspofungin, and micafungin. Due to the small sample sizes for Clades II, V, and VI, this study only assessed Clades I, III, and IV. Our analyses revealed 15 single nucleotide polymorphisms (SNPs) in Clade I (10 in coding and 5 in noncoding regions), 24 SNPs in Clade III (11 in coding and 13 in noncoding regions), and 13 SNPs in clade IV (10 in coding and 3 in noncoding regions) as statistically significantly associated with susceptibility differences to one or more of the nine antifungal drugs. While four SNPs in genes encoding lanosterol 14-α-demethylase ) and the catalytic subunit of 1,3-beta-D-glucan synthase () were shared between clades, including the experimentally confirmed Ser639Phe/Pro missense substitutions in for echinocandin resistance, most of the identified SNPs were clade specific, consistent with their recent independent origins. Interestingly, the majority of the antifungal resistance-associated SNPs were novel, and in genes and intergenic regions that have never been reported before as associated with antifungal resistance. While targeted study is needed to confirm the role of each novel SNP, the diverse mechanisms of drug resistance in revealed here indicate both challenges for infection control and opportunities for the development of novel antifungal drugs against this and other human fungal pathogens.
PubMed: 38276031
DOI: 10.3390/jof10010086 -
Medicina 2024Acute cholangitis is a bile duct infection associated with bile duct obstruction. Bile culture is positive in most cases, and the most frequent etiological agent is...
Acute cholangitis is a bile duct infection associated with bile duct obstruction. Bile culture is positive in most cases, and the most frequent etiological agent is Escherichia coli. Candida sp acute cholangitis is a rare finding, which is more common in patients with immunosuppression, use of corticosteroids, prolonged antibiotic treatment or surgical procedures of the bile duct. We present the case of a 67-year-old woman with none of the above-mentioned history who consulted for fever, abdominal pain and jaundice. MRI of the abdomen revealed a lithiasic image in the common bile duct with dilation. It required endoscopic drainage of the biliary tract. Direct microscopic examination of the bile fluid revealed gram-negative bacilli and yeast, and in the culture of bile fluid Klebsiella pneumoniae producing extended spectrum beta-lactamase (ESBL) and Candida glabrata were isolated. The patient completed the antibiotic treatment with piperacillin tazobactam and anidulafungin with good evolution. Bile duct infection by association of Gram-negative bacilli and Candida sp is a rare entity, more in patients without underlying diseases.
Topics: Female; Humans; Aged; Klebsiella pneumoniae; Candida glabrata; Cholangitis; Anti-Bacterial Agents; Bile; Gram-Negative Bacteria; Escherichia coli
PubMed: 38271946
DOI: No ID Found -
Mycologia 2024spp. has emerged as an opportunistic etiological agent with clinical manifestations varying from localized infections to deep-seated systemic disease. It is also a...
spp. has emerged as an opportunistic etiological agent with clinical manifestations varying from localized infections to deep-seated systemic disease. It is also a phytopathogen of economic impact. There are few reports on the species diversity of this genus, and no comprehensive studies on the epidemiology nor the antifungal susceptibility of in Mexico. The present multicentric study aims to shed light on the species distribution and antifungal susceptibility patterns of 116 strains of isolated from clinical and environmental samples. Isolates were identified by standard phenotypic characteristics and by sequencing of the ITS (internal transcribed spacer), (translation elongation factor 1-α), (RNA polymerase II core subunit), and/or (calmodulin) regions. Susceptibility tests were carried out against 15 antifungals of clinical and agricultural use. Regarding distribution, we identified 27 species belonging to eight different species complexes. The most frequently isolated species for both clinical and environmental samples were (34%), sensu stricto (12%), (8%), and sensu stricto (8%). All isolates showed minimum inhibitory concentrations (MICs) equal to or above the maximum concentration evaluated for fluconazole, 5-fluocytosine, caspofungin, micafungin, and anidulafungin. All isolates had a MIC of ≤16 µg/mL for voriconazole, with a mode of 4 µg/mL. appeared to be the most susceptible to all antifungals tested.
Topics: Antifungal Agents; Fusarium; Mexico; Microbial Sensitivity Tests
PubMed: 38232343
DOI: 10.1080/00275514.2023.2293296 -
Antimicrobial Agents and Chemotherapy Feb 2024Invasive candidiasis is a major hospital-acquired infection. Usually, echinocandins are considered first-line treatment. However, resistant phenotypes have emerged....
Invasive candidiasis is a major hospital-acquired infection. Usually, echinocandins are considered first-line treatment. However, resistant phenotypes have emerged. Ibrexafungerp (IBX) is a new antifungal substance with potent anti- activity. We challenged IBX with a library of 192 pheno-/genotypically echinocandin-resistant isolates, focusing on the substance susceptibility, its activity on certain hotspot (HS) mutated strains, and applying WTULs (wild-type upper limits). Therefore, a 9-year-old strain and patient data collection provided by the German National Reference Center for Invasive Fungal Infections were analyzed. Species identification was confirmed through ITS-sequencing. Molecular susceptibility testing was performed by sequencing HS of the gene. Anidulafungin (AND) and IBX EUCAST-broth-microdilution was conducted. The four most common echinocandin-resistance mediating mutations were found in [112/192 isolates; F659-(43×) and S663-(48×)] and [63/192 isolates; F641-(15×) and S645-(39×)]. Mutations at the HS-start sequence were associated with higher IBX MIC-values (F659 and F641 (MIC 50/90 mg/L: >4/>4 and 2/4 mg/L) in comparison to AND (F659 and F641 (MIC 50/90: 1/4 and 0.25/1 mg/L). MIC-values in HS-center mutations were almost equal [MIC50/90 in S663: 2/4 (AND and IBX); in S645: 0.5/1 (AND) and 0.25/1 (IBX) mg/L]. In total, 61 vs 78 of 192 echinocandin-resistant isolates may be classified as IBX wild type by applying WTULs, whereas the most prominent effect was seen in [48% (30/63) vs 70% (44/63)]. IBX shows activity against echinocandin-resistant and thus is an addition to the antifungal armory. However, our data suggest that this effect is more pronounced in and strains harboring mutations, affecting the HS-center.
Topics: Humans; Child; Echinocandins; Antifungal Agents; Candida; Glycosides; Candida albicans; Candida glabrata; Microbial Sensitivity Tests; Drug Resistance, Fungal; Triterpenes
PubMed: 38206004
DOI: 10.1128/aac.01324-23 -
Transplantation Jun 2024Ex situ normothermic liver perfusion (NMP) in a blood-based perfusate is associated with a risk of microbe growth, resulting in life-threatening posttransplant sepsis....
BACKGROUND
Ex situ normothermic liver perfusion (NMP) in a blood-based perfusate is associated with a risk of microbe growth, resulting in life-threatening posttransplant sepsis. Antibiotics are widely used, but the pharmacokinetics of these agents are unknown as is their efficacy. We wished to assess the perfusate concentrations of the meropenem and fluconazole that we use and to audit the incidence of infection with this antimicrobial therapy.
METHODS
Fluconazole and meropenem (100 mg each) were added to the perfusate before NMP began, and serial samples were taken and assayed for drug concentrations. Perfusate cultures were available from 210 of the 242 perfusions performed between February 1, 2018, and April 6, 2023; these were reviewed.
RESULTS
Following administration of 100 mg fluconazole, levels fell slightly from a median of 24.9 mg/L at 1 h to 22.6 mg/L at 10 h. In contrast, meropenem concentrations fell over time, from a median of 21.8 mg/L at 1 h to 9.4 mg/L at 10 h. There were 4 significant microorganisms grown in the perfusions, including 3 Candida species and an Enterococcus faecium . All the Candida -infected livers were transplanted with no adverse consequences, the recipients being treated with anidulafungin upon identification of the infecting organism; the Enterococcus -infected liver was not transplanted.
CONCLUSIONS
Serious infection is a risk with NMP but appears to be mitigated with a protocol combining fluconazole and meropenem. This combination may not be appropriate in areas where resistance is prevalent. Routine culture of NMP perfusate is essential to identify breakthrough organisms early and enable recipient treatment.
Topics: Humans; Perfusion; Meropenem; Liver Transplantation; Fluconazole; Incidence; Male; Female; Middle Aged; Anti-Bacterial Agents; Antifungal Agents; Organ Preservation; Antibiotic Prophylaxis; Retrospective Studies; Liver; Candidiasis
PubMed: 38196099
DOI: 10.1097/TP.0000000000004897 -
Biomaterials Science Feb 2024Fungal infections contribute substantially to human morbidity and mortality. A particular concern is the high rate of mortality associated with invasive fungal...
Fungal infections contribute substantially to human morbidity and mortality. A particular concern is the high rate of mortality associated with invasive fungal infections, which often exceeds 50.0% despite the availability of several antifungal drugs. Herein, we show a self-assembling antifungal peptide (AFP), which is able to bind to chitin on the fungal cell wall and form AFP nanofibers, wrapping fungi. As a result, AFP limits the proliferation of fungi, slows down the morphological transformation of biphasic fungi, and inhibits the adhesion of fungi to host cells and the formation of biofilms. Compared to the broad-spectrum antifungal fluconazole, AFP achieved a comparable inhibitory effect (MIC = 3.5 μM) on fungal proliferation. In addition, AFP significantly inhibited the formation of fungal biofilms with the inhibition rate of 69.6% at 1 μM, better than fluconazole (17.2% at 1 μM). In a skin infection model of mice, it was demonstrated that AFP showed significantly superior efficacy to fluconazole. In the systemic candidiasis mouse model, AFP showed similar efficacy to first-line antifungal amphotericin B (AmpB) and anidulafungin (AFG). This study provides a promising wrapping strategy for anti-fungal infection.
Topics: Humans; Animals; Mice; Antifungal Agents; Fluconazole; alpha-Fetoproteins; Peptides; Fungi
PubMed: 38193333
DOI: 10.1039/d3bm01845h -
Breastfeeding Medicine : the Official... Feb 2024Anidulafungin has poor oral bioavailability, with hardly any available information on how it affects breast milk, oral absorption, or gastrointestinal side effects in...
Anidulafungin has poor oral bioavailability, with hardly any available information on how it affects breast milk, oral absorption, or gastrointestinal side effects in the infant. A 40-year-old woman who recently gave birth to a healthy infant was treated for a period of 14 days for a C with 100 mg anidulafungin once a day. The department of clinical pharmacy was consulted to provide advice on how long the patient had to wait after ceasing anidulafungin before it was safe to start breastfeeding, with regard to preventing possible side effects of the drug to the infant, such as diarrhea or cholestasis and increase in liver enzyme values. The advice of the hospital pharmacist was pragmatic: to start breastfeeding within 2 days after the medication was discontinued based on half-time. Owing to this lack of information, we measured anidulafungin concentrations in breast milk and found low levels. We concluded that anidulafungin is detectable in breast milk until 32 hours after anidulafungin treatment was stopped, and that no side effects were observed by the infant.
Topics: Adult; Female; Humans; Anidulafungin; Antifungal Agents; Breast Feeding; Diarrhea; Milk, Human; Infant, Newborn
PubMed: 38174985
DOI: 10.1089/bfm.2023.0246 -
International Journal of Antimicrobial... Feb 2024The use of extracorporeal membrane oxygenation (ECMO) as a cardiocirculatory or respiratory support has tremendously increased in critically ill patients. In the setting...
BACKGROUND AND OBJECTIVE
The use of extracorporeal membrane oxygenation (ECMO) as a cardiocirculatory or respiratory support has tremendously increased in critically ill patients. In the setting of ECMO support, invasive fungal infections are a severe cause of morbidity and mortality. This vulnerable population is at risk of suboptimal antifungal exposure due to an increased volume of distribution (Vd), drug sequestration and decreased clearance. Here, we aimed to summarize ex-vivo and clinical studies on the potential impact of ECMO on the pharmacokinetics (PK) of antifungal agents and dosing requirements.
METHODS
A systematic search of the literature within electronic databases PubMed and EMBASE was conducted from database inception to 30 April 2023. Inclusion criteria were as follows: critically ill patients receiving ECMO regardless of age and reporting at least one PK parameter.
RESULTS
Thirty-six studies met inclusion criteria, including seven ex-vivo experiments and 29 clinical studies evaluating three classes of antifungals: polyenes, triazoles and echinocandins. Based on the available ex-vivo PK data, we found a significant sequestration of highly lipophilic and protein-bound antifungals within the ECMO circuit such as voriconazole, posaconazole and micafungin but the PK of several antifungals remains to be addressed such as amphotericin B, isavuconazole and anidulafungin. Most clinical studies have shown increased Vd of some antifungals like fluconazole and micafungin, particularly in the pediatric population. Conflicting data exist about caspofungin exposure.
CONCLUSIONS
The available literature on the antifungal PK changes in ECMO setting is scarce. Whenever possible, therapeutic drug monitoring is highly advised to personalize antifungal therapy.
Topics: Humans; Antifungal Agents; Caspofungin; Critical Illness; Extracorporeal Membrane Oxygenation; Micafungin
PubMed: 38161046
DOI: 10.1016/j.ijantimicag.2023.107078