-
Journal of Fungi (Basel, Switzerland) Mar 2021In December 2020, emerged in Brazil in the city of Salvador. The first two colonized patients were in the same COVID-19 intensive care unit. Antifungal susceptibility...
In December 2020, emerged in Brazil in the city of Salvador. The first two colonized patients were in the same COVID-19 intensive care unit. Antifungal susceptibility testing showed low minimal inhibitory concentrations of 1 µg/mL, 2 µg/mL, 0.03 µg/L, and 0.06 µg/mL for amphotericin B, fluconazole, voriconazole, and anidulafungin, respectively. Microsatellite typing revealed that the strains are clonal and belong to the South Asian clade . The travel restrictions during the COVID-19 pandemic and the absence of travel history among the colonized patients lead to the hypothesis that this species was introduced several months before the recognition of the first case and/or emerged locally in the coastline Salvador area.
PubMed: 33803060
DOI: 10.3390/jof7030220 -
International Microbiology : the... Jan 2021In spite of evidence that domestic and wild birds may act as carriers of human pathogenic fungi, data on the role of laying hens as reservoirs of drug resistant and...
In spite of evidence that domestic and wild birds may act as carriers of human pathogenic fungi, data on the role of laying hens as reservoirs of drug resistant and virulent yeasts is lacking. Here, we assess several virulence factors (phospholipase and haemolysin activity) and the antifungal susceptibility profiles of 84 Candida albicans and 17 Candida catenulata strains isolated from cloacae (group A), faeces (group B) and eggs (group C) of laying hens. Of these strains, 95% C. albicans and 23% C. catenulata strains displayed phospholipase and haemolytic activities. For C. albicans, the highest values of phospholipase (Pz = 0.62) and haemolytic activities (Hz = 0.49) were recorded among the strains from group C whilst for C. catenulata (Pz = 0.54; Hz = 0.49) among those from group A. High minimum inhibitory concentration (MIC) values for azoles and amphotericin B (AmB) were recorded irrespective of their sources in all C. albicans strains. A total of 22 C. albicans strains were multidrug resistant, displaying resistance to fluconazole, itraconazole (ITZ), voriconazole (VOR) and posaconazole (POS). All C. catenulata strains from group C were resistant to ITZ, POS, micafungin and anidulafungin and susceptible to AmB. In this study, C. albicans and C. catenulata isolated from the cloacae, faeces and eggs of laying hens produced phospholipase and haemolysin and might be multidrug resistant. In the environment (faeces) or in eggs, C. albicans and C. catenulata strains might acquire pathogenic virulence traits and/or show multidrug resistance profiles. Based on these results, breeding and handling of laying hens and/or eggs may have implications for human and animal health.
Topics: Animals; Antifungal Agents; Candida; Candida albicans; Chickens; Drug Resistance, Fungal; Eggs; Feces; Female; Microbial Sensitivity Tests; Virulence
PubMed: 32772220
DOI: 10.1007/s10123-020-00141-1 -
European Journal of Clinical... Apr 2015Echinocandins and triazoles were proven to be effective antifungal drugs against invasive fungal infections (IFI), which may cause significant morbidity and mortality in... (Comparative Study)
Comparative Study Meta-Analysis Review
Echinocandins and triazoles were proven to be effective antifungal drugs against invasive fungal infections (IFI), which may cause significant morbidity and mortality in immunocompromised patients. The aim of this study was to compare the efficacy and safety between echinocandins and triazoles for the prophylaxis and treatment of fungal infections. PubMed, Embase, and the Cochrane Library were searched to identify relevant randomized controlled trials (RCTs) up to July 2014. The quality of trials was assessed with the Jadad scoring system. The primary outcomes of interest were treatment success, microbiological success, breakthrough infection, drug-related adverse events (AEs), withdrawals due to AEs, and all-cause mortality. Ten RCTs, involving 2,837 patients, were included, as follows: caspofungin versus fluconazole (n = 1), caspofungin versus itraconazole (n = 1), anidulafungin versus fluconazole (n = 1), micafungin versus fluconazole (n = 4), micafungin versus voriconazole (n = 2), and micafungin versus itraconazole (n = 1). Echinocandins and triazoles showed similar effects in terms of favorable treatment success rate [relative risk (RR) = 1.02, 95% confidence interval (CI), 0.97-1.08], microbiological success rate (RR = 0.98, 95% CI, 0.90-1.15), breakthrough infection (RR = 1.09; 95% CI, 0.59-2.01), drug-related AEs (RR = 0.94; 95% CI, 0.71-1.15), and all-cause mortality (RR = 0.85; 95% CI, 0.66-1.10) in the prophylaxis and treatment of fungal infections. Additionally, echinocandins were more effective than triazoles for prophylaxis in patients undergoing hematologic malignancies or those who received hematopoietic stem cell transplantation (HSCT; RR = 1.08; 95% CI, 1.02-1.15). Echinocandins significantly decreased the AE-related withdrawals rate compared with triazoles (RR = 0.47; 95% CI, 0.33-0.67). This meta-analysis revealed that echinocandins are as effective and safe as triazoles for the prophylaxis and treatment of patients with fungal infections.
Topics: Antifungal Agents; Chemoprevention; Drug Therapy; Drug-Related Side Effects and Adverse Reactions; Echinocandins; Humans; Mycoses; Randomized Controlled Trials as Topic; Survival Analysis; Treatment Outcome; Triazoles
PubMed: 25502737
DOI: 10.1007/s10096-014-2287-4 -
Antimicrobial Agents and Chemotherapy Feb 2018There is currently a small number of classes of antifungal drugs, and these drugs are known to target a very limited set of cellular functions. We derived a set of...
There is currently a small number of classes of antifungal drugs, and these drugs are known to target a very limited set of cellular functions. We derived a set of approximately 900 nonessential, transactivator-defective disruption strains from the tetracycline-regulated GRACE collection of strains of the fungal pathogen This strain set was screened against classic antifungal drugs to identify gene inactivations that conferred either enhanced sensitivity or increased resistance to the compounds. We examined two azoles, fluconazole and posaconazole; two echinocandins, caspofungin and anidulafungin; and a polyene, amphotericin B. Overall, the chemogenomic profiles within drug classes were highly similar, but there was little overlap between classes, suggesting that the different drug classes interacted with discrete networks of genes in We also tested two pyridine amides, designated GPI-LY7 and GPI-C107; these drugs gave very similar profiles that were distinct from those of the echinocandins, azoles, or polyenes, supporting the idea that they target a distinct cellular function. Intriguingly, in cases where these gene sets can be compared to genetic disruptions conferring drug sensitivity in other fungi, we find very little correspondence in genes. Thus, even though the drug targets are the same in the different species, the specific genetic profiles that can lead to drug sensitivity are distinct. This implies that chemogenomic screens of one organism may be poorly predictive of the profiles found in other organisms and that drug sensitivity and resistance profiles can differ significantly among organisms even when the apparent target of the drug is the same.
PubMed: 29203491
DOI: 10.1128/AAC.02365-17 -
Antimicrobial Agents and Chemotherapy Dec 2022Candida albicans is an opportunistic human fungal pathogen that causes invasive infections in immunocompromised individuals. Despite the high anticandidal activity among...
Candida albicans is an opportunistic human fungal pathogen that causes invasive infections in immunocompromised individuals. Despite the high anticandidal activity among the echinocandins (ECNs), a first-line therapy, resistance remains an issue. Furthermore, many clinical isolates display decreased ECN susceptibility, a physiological state which is thought to lead to resistance. Determining the factors that can decrease susceptibility is of high importance. We searched for such factors genome-wide by comparing the transcriptional profiles of five mutants that acquired decreased caspofungin susceptibility in the absence of canonical resistance mutations. The mutants were derived from two genetic backgrounds and arose due to independent mutational events, some with monosomic chromosome 5 (Ch5). We found that the mutants exhibit common transcriptional changes. In particular, all mutants upregulate five genes from Ch2 in concert. Knockout experiments show that all five genes positively influence caspofungin and anidulafungin susceptibility and play a role in regulating the cell wall mannan and glucan contents. The functions of three of these genes, orf19.1766, orf19.6867, and orf19.5833, were previously unknown, and our work expands the known functions of and . Importantly, orf19.1766 and have no human orthologues. Our results provide important clues as to basic mechanisms of survival in the presence of ECNs while identifying new genes controlling ECN susceptibility and revealing new targets for the development of novel antifungal drugs.
Topics: Antifungal Agents; Candida albicans; Caspofungin; Drug Resistance, Fungal; Echinocandins; Fungal Proteins; Lipopeptides; Microbial Sensitivity Tests
PubMed: 36354349
DOI: 10.1128/aac.00977-22 -
Open Forum Infectious Diseases 2017The objective of this study was to review our clinical experience on the safety and efficacy of anidulafungin, an echinocandin antifungal, in the treatment of invasive...
BACKGROUND
The objective of this study was to review our clinical experience on the safety and efficacy of anidulafungin, an echinocandin antifungal, in the treatment of invasive fungal infections (IFIs) in patients with moderate to severe abnormal liver function tests or multiorgan failure and IFI, in a large United Kingdom Liver Centre.
METHODS
The clinical records of the first 50 consecutive patients treated for IFI with anidulafungin between January 7, 2009 and March 2, 2011 were analyzed. Data were collected on demographics, underlying disease, disease characteristics, hematological and biochemical parameters, IFI, concomitant bacterial and viral infections, response to anidulafungin, and anidulafungin-related adverse events.
RESULTS
The patients' median age was 54.3 years (range, 19.6-75.9); 60% were male. Twenty-two (44%) patients were liver transplant recipients. Others had hepatopancreaticobiliary disease (n = 15, 30%) or chronic liver disease (n = 11, 22%). Invasive fungal infection (predominantly spp) was proven in 36 (72%) patients, probable in 14 (28%). Of 46 evaluable patients, 35 (76%) had a favorable anidulafungin treatment outcome. Forty-nine (98%) had abnormal liver function tests (LFTs) pretreatment; 31 (62%) had ≥1 LFT raised to ≥2× baseline during anidulafungin treatment.
CONCLUSIONS
In this highly specialized group of patients, anidulafungin treatment was efficacious and well tolerated by those with decompensated liver disease, multiorgan failure, and high-risk liver transplant with proven or probable IFI.
PubMed: 28480239
DOI: 10.1093/ofid/ofw241 -
Journal of Fungi (Basel, Switzerland) Sep 2020Rezafungin is a novel echinocandin drug being developed as a first-line option for treatment and prevention of invasive fungal infections. As a result of a structural... (Review)
Review
Rezafungin is a novel echinocandin drug being developed as a first-line option for treatment and prevention of invasive fungal infections. As a result of a structural modification in its parent molecule anidulafungin, rezafungin has acquired unique chemical stability conferring prolonged pharmacokinetics, as well as an administration advantage in the clinical setting compared to other drugs in the same class. Rezafungin displays potent in vitro activity against a wide spectrum of fungal pathogens, which is reflected in robust in vivo efficacy and/or pharmacodynamic studies using various animal models as well as in promising clinical trials data. This review describes in vivo characterization of rezafungin using animal models, current status of clinical development and key findings from these studies.
PubMed: 32998224
DOI: 10.3390/jof6040192 -
Antibiotics (Basel, Switzerland) Mar 2022fracture-related infection (FRI) is a rare, but severe complication in trauma surgery. The optimal antifungal treatment for osteomyelitis, including FRI, has not been... (Review)
Review
fracture-related infection (FRI) is a rare, but severe complication in trauma surgery. The optimal antifungal treatment for osteomyelitis, including FRI, has not been established yet, as only cases have been documented and data on bone penetration of antifungal drugs are scarce. We describe a patient with FRI of the tibia who was treated with isavuconazole after developing liver function disturbances during voriconazole therapy. Isavuconazole, the active moiety formed after hydrolysis of the prodrug isavuconazonium sulfate by plasma esterases, was administered in a maintenance dose of 200 mg q24 h, followed by 150 mg q24 h. The patient completed a six-month antifungal treatment course. Although fracture union was not achieved during six months of follow-up after therapy cessation, no confirmatory signs of FRI were observed. Additionally, two literature searches were conducted to review available data on antifungal treatment of osteomyelitis and bone penetration of antifungals. One hundred and eight cases of osteomyelitis, including six (5.6%) FRI cases, were identified. Voriconazole and (lipid formulations of) amphotericin B were the most commonly used antifungals. In three (2.8%) cases isavuconazole was prescribed as salvage therapy. Data on antifungal bone penetration were reported for itraconazole, voriconazole, amphotericin B, anidulafungin and 5-fluorocytosin. Isavuconazole might be a promising alternative for the treatment of osteomyelitis. However, standardized case documentation is needed to evaluate the efficacy of isavuconazole and other antifungals in the treatment of osteomyelitis, including FRI.
PubMed: 35326807
DOI: 10.3390/antibiotics11030344 -
Mycopathologia Apr 2023Until recently, little was known about the susceptibility pattern of Cyberlindnera fabianii (Cy. fabianii) planktonic cells and biofilms regarding the most frequently...
Until recently, little was known about the susceptibility pattern of Cyberlindnera fabianii (Cy. fabianii) planktonic cells and biofilms regarding the most frequently administered systemic antifungals, despite the high mortality rate and its potential role in catheter-related infections. In the current study, the activity of fluconazole, amphotericin B and echinocandins (anidulafungin, caspofungin and micafungin) was determined against planktonic and sessile cells of Cy. fabianii clinical isolates (n = 8). Planktonic minimum inhibitory concentrations (MICs) ranged from 1 to 2, from 0.25 to 1, from 0.015 to 0.06, from 0.03 to 0.12 and from 0.25 to 0.5 mg/l for fluconazole, amphotericin B, anidulafungin, caspofungin and micafungin, respectively. One-day-old biofilms were highly resistant to fluconazole (MIC ranged from 512 to > 512) compared to planktonic counterparts, but not to amphotericin B (MIC ranged from 0.25 to 2 mg/l) and echinocandins (MIC ranged from 0.06 to 2 mg/l). Based on the calculated planktonic killing rates, the highest activity was observed in the case of anidulafungin (k values ranged from 0.37 to 2.09), while micafungin, caspofungin, amphotericin B and fluconazole exerted 0.46-1.47, 0.14-0.86, -0.03 to 2.08 and -0.15 to 0.09 killing rate value ranges, respectively. The obtained in vitro planktonic and sessile susceptibility patterns suggest that echinocandins and amphotericin B may be the most reliable treatment option for the treatment of Cy. fabianii infections.
Topics: Echinocandins; Amphotericin B; Fluconazole; Anidulafungin; Caspofungin; Micafungin; Biofilms
PubMed: 36399230
DOI: 10.1007/s11046-022-00688-9 -
Antimicrobial Agents and Chemotherapy Jun 2018We examined the rapid evaluation of susceptibility to echinocandins in spp. using the Etest performed directly on positive blood cultures and anidulafungin-containing...
We examined the rapid evaluation of susceptibility to echinocandins in spp. using the Etest performed directly on positive blood cultures and anidulafungin-containing agar plates. We prospectively collected 80 positive blood cultures (Bactec-FX system, Becton-Dickinson, Cockeysville, MD, USA) with echinocandin-susceptible spp. ( = 60) and echinocandin-intermediate ( = 20) from patients with candidemia. Additionally, blood culture bottles of nonfungemic/bacteremic patients were spiked with 35 echinocandin-resistant species isolates. A total of 2 to 4 drops of medium from each bottle were stroked directly onto both RPMI 1640 agar plates with micafungin and anidulafungin Etest strips (ET) and Sabouraud agar plates containing 2 mg/liter of anidulafungin. The isolates were tested according to the EUCAST method and Etest standard (ET). Essential and categorical agreement between the methods was calculated. The essential agreement and categorical agreement between the EUCAST method and ET and ET were both >97.4%. The essential agreement between ET and the EUCAST method for both echinocandins was >97%. The categorical agreement between the sequence and ET was 97.4%. The ET MICs of anidulafungin and micafungin (≥0.19 mg/liter and ≥0.064 mg/liter, respectively) effectively separated all susceptible wild-type isolates from the resistant mutant isolates. The categorical agreement (62.6%) between the EUCAST method and growth on anidulafungin-containing plates was poor, with the best agreement observed for (94.2%). When performed directly on positive blood cultures from patients with candidemia, the Etest with micafungin and anidulafungin is a reliable procedure for the rapid testing of susceptibility to echinocandins in species isolates.
Topics: Anidulafungin; Antifungal Agents; Candida parapsilosis; Candidemia; Disk Diffusion Antimicrobial Tests; Echinocandins; Humans; Micafungin; Prospective Studies
PubMed: 29712651
DOI: 10.1128/AAC.00162-18