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Current Medical Mycology Sep 2022Candidemia is a major cause of morbidity and mortality among patients receiving immunosuppressive therapy and those hospitalized with serious underlying diseases. Here,...
BACKGROUND AND PURPOSE
Candidemia is a major cause of morbidity and mortality among patients receiving immunosuppressive therapy and those hospitalized with serious underlying diseases. Here, we investigated the epidemiological, clinical, and mycological features of candidemia in Tehran, Iran.
MATERIALS AND METHODS
A prospective observational study of all patients diagnosed with candidemia was performed at two referral teaching hospitals in Tehran, Iran, from February to December 2018. Demographic characteristics, underlying diseases, risk factors, clinical symptoms, and laboratory analyses of candidemic patients with positive culture were mined. isolates were molecularly identified by sequencing of the internal transcribed spacer region (ITS1-5.8S-ITS2). The antifungal susceptibility testing for fluconazole, itraconazole, voriconazole, posaconazole, amphotericin B, caspofungin, micafungin, and anidulafungin against the isolates was performed using CLSI broth microdilution reference method (M27-A3).
RESULTS
A total of 89 episodes were identified, with an incidence of 2.1 episodes/1000 admissions. The common underling disease were malignancy (46%), renal failure/dialysis (44%), and hypertension (40%). The overall crude mortality was 47%. (44%) was the most frequent causative agent, followed by (21%), complex (15%), (11%), and (3.5%). All the isolates were susceptible to amphotericin B. The activity of all four azoles was low against species, especially .
CONCLUSION
The increase in non- species with reduced susceptibility to antifungal drugs might be alarming in high-risk patients. Therefore, accurate knowledge of predisposing factors and epidemiological patterns in candidemia are effective steps for managing and decreasing the mortality rate in candidemia.
PubMed: 37051552
DOI: 10.18502/cmm.8.3.11207 -
Euro Surveillance : Bulletin Europeen... Apr 2023A difficult-to-control outbreak of is ongoing in a large tertiary care hospital in Liguria, Italy, where it first emerged in 2019. In a retrospective analysis, 503...
A difficult-to-control outbreak of is ongoing in a large tertiary care hospital in Liguria, Italy, where it first emerged in 2019. In a retrospective analysis, 503 cases of carriage or infection were observed between July 2019 and December 2022. Genomic surveillance identified putative cases that no longer occurred as part of one defined outbreak and the emergence of echinocandin (pandrug) resistance following independent selection of S639F and F635Y mutants upon prolonged exposure to caspofungin and/or anidulafungin.
Topics: Humans; Echinocandins; Antifungal Agents; Candida auris; Retrospective Studies; Candida; Disease Outbreaks; Microbial Sensitivity Tests; Drug Resistance, Fungal
PubMed: 37022211
DOI: 10.2807/1560-7917.ES.2023.28.14.2300161 -
Journal of Medical Microbiology Mar 2023The complex can be divided into , , and subtypes. It is uncommon for drug sensitivity tests to type them. In routine susceptibility reports, drug susceptibility of...
The complex can be divided into , , and subtypes. It is uncommon for drug sensitivity tests to type them. In routine susceptibility reports, drug susceptibility of complex subtypes is lacking. The aim of this study is to investigate the antifungal susceptibility and clinical distribution characteristics of the complex subtypes causing deep infection in patients. Non-repetitive strains of complex isolated from deep infection from 2017 to 2019 were collected. Species-level identification was performed using a matrix-assisted laser desorption/ionization time-of-flight mass spectrometer and confirmed using gene sequencing, when necessary. Antifungal susceptibility testing was performed using the Sensititre YeastOne system method. A total of 244 cases were included in the study, including 176 males (72.13 %, 60.69±13.43 years) and 68 females (27.87 %, 60.21±10.59 years). The primary diseases were cancer (43.44 %), cardiovascular disease (25.00 %), digestive system diseases, (18.44 %), infection (6.97 %), and nephropathy (6.15 %). Strains were isolated from the bloodstream (63.11 %), central venous catheters (15.16 %), pus (6.56 %), ascites (5.74 %), sterile body fluid (5.33 %), and bronchoalveolar lavage fluid (BALF, 4.09 %). Of the 244 complex strains, 179 (73.26 %) were identified as , 62 (25.41 %) were , and three (1.23 %) were . Only one strain was resistant to anidulafungin, micafungin, caspofungin, and voriconazole, and it was non-wild-type (NWT) to amphotericin B. Furthermore, six strains were resistant to fluconazole, and one was dose-dependent susceptible. Five strains were NWT to posaconazole. Only one strain was NWT for anidulafungin, micafungin, caspofungin, fluconazole, voriconazole, amphotericin B, and posaconazole, while the rest of the strains were wild-type. was the main clinical isolate from the complex in our hospital. Most strains were isolated from the bloodstream. The susceptibility rate to commonly used antifungal drugs was more than 96 %. Furthermore, most of the infected patients were elderly male cancer patients.
Topics: Female; Humans; Male; Aged; Antifungal Agents; Candida parapsilosis; Fluconazole; Candida; Amphotericin B; Voriconazole; Caspofungin; Micafungin; Anidulafungin; Microbial Sensitivity Tests; Drug Resistance, Fungal
PubMed: 36920840
DOI: 10.1099/jmm.0.001640 -
CPT: Pharmacometrics & Systems... Jun 2023In vitro combination of echinocandins and isavuconazole against the emerging species Candida auris is mainly synergistic. However, this combination has not been...
In vitro combination of echinocandins and isavuconazole against the emerging species Candida auris is mainly synergistic. However, this combination has not been evaluated in clinical settings. A pharmacokinetic/pharmacodynamic modeling and simulation approach based on in vitro data may be helpful to further study the therapeutic potential of these combinations. Therefore, the aims of this study were to characterize the time course of growth and killing of C. auris in response to the combination of the three approved echinocandins and isavuconazole using a semimechanistic model and to perform model-based simulations in order to predict the in vivo response to combination therapy. In vitro static time-kill curve data for isavuconazole and echinocandins combinations against six blood isolates of C. auris were best modeled considering the total killing of the fungal population as dependent on the additive effects of both drugs. Once assessed, the predictive performance of the model using simulations of different dosing and fungal susceptibility scenarios were conducted. Model-based simulations revealed that none of the combinations at standard or higher dosages would be effective against the studied isolates of C. auris and it was predicted that the combinations of isavuconazole with anidulafungin or caspofungin would be effective for minimum inhibitory concentrations up to 0.03 and 0.06 mg/L respectively, whereas the combination with micafungin would lead to treatment failure. The current approach highlights the importance of bridging the in vitro results to the clinic.
Topics: Humans; Echinocandins; Antifungal Agents; Candida auris; Candida; Microbial Sensitivity Tests
PubMed: 36915233
DOI: 10.1002/psp4.12949 -
Viruses Feb 2023Echinocandin antifungal drugs, including micafungin, anidulafungin, and caspofungin, have been recently reported to exhibit antiviral effects against various viruses...
Echinocandin antifungal drugs, including micafungin, anidulafungin, and caspofungin, have been recently reported to exhibit antiviral effects against various viruses such as flavivirus, alphavirus, and coronavirus. In this study, we focused on micafungin and its derivatives and analyzed their antiviral activities against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The micafungin derivatives Mi-2 and Mi-5 showed higher antiviral activity than micafungin, with 50% maximal inhibitory concentration (IC) of 5.25 and 6.51 µM, respectively (3.8 to 4.7-fold stronger than micafungin) and 50% cytotoxic concentration (CC) of >64 µM in VeroE6/TMPRSS2 cells. This high anti-SARS-CoV-2 activity was also conserved in human lung epithelial cell-derived Calu-3 cells. Micafungin, Mi-2, and Mi-5 were suggested to inhibit the intracellular virus replication process; additionally, these compounds were active against SARS-CoV-2 variants, including Delta (AY.122, hCoV-19/Japan/TY11-927/2021), Omicron (BA.1.18, hCoV-19/Japan/TY38-873/2021), a variant resistant to remdesivir (R10/E796G C799F), and a variant resistant to casirivimab/imdevimab antibody cocktail (E406W); thus, our results provide basic evidence for the potential use of micafungin derivatives for developing antiviral agents.
Topics: Humans; Antiviral Agents; COVID-19; Micafungin; RNA Replication; RNA, Viral; SARS-CoV-2
PubMed: 36851666
DOI: 10.3390/v15020452 -
Journal of Fungi (Basel, Switzerland) Feb 2023is emerging as one of the most common species causing opportunistic infections in Latin America. Outbreak events caused by were reported, and antifungal resistant...
is emerging as one of the most common species causing opportunistic infections in Latin America. Outbreak events caused by were reported, and antifungal resistant isolates are on the rise. In order to investigate population genomics and look into antifungal resistance, we applied a short tandem repeat (STR) genotyping scheme and antifungal susceptibility testing (AFST) to 230 clinical and environmental isolates from Latin American countries. STR genotyping identified 164 genotypes, including 11 clusters comprised of three to seven isolates, indicating outbreak events. AFST identified one isolate as anidulafungin-resistant and harboring a S659P substitution. Moreover, we identified 24 clinical and environmental isolates with intermediate susceptibility or resistance to one or more azoles. sequencing revealed each of these isolates harboring a Y132F and/or Y257H/N substitution. All of these isolates, except one, were clustered together in two groups of closely related STR genotypes, with each group harboring distinct substitutions. The ancestral strain of these isolates likely acquired the azole resistance-associated substitutions and subsequently spread across vast distances within Brazil. Altogether, this STR genotyping scheme for proved to be useful for identifying unrecognized outbreak events and better understanding population genomics, including the spread of antifungal-resistant isolates.
PubMed: 36836321
DOI: 10.3390/jof9020207 -
Revista Do Instituto de Medicina... 2023Rare emerging pathogens such as Saprochaete clavata are associated with invasive fungal diseases, high morbidity, mortality, rapidly fatal infections, and outbreaks....
Rare emerging pathogens such as Saprochaete clavata are associated with invasive fungal diseases, high morbidity, mortality, rapidly fatal infections, and outbreaks. However, little is known about S. clavata infections, epidemiology, risk factors, treatment, biofilms, and disease outcomes. The objective of this study was to describe a new case of severe S. clavata infection in a patient diagnosed at a referral children's hospital in Brazil, including antifungal minimal inhibitory concentration, S. clavata biofilm characterization, and molecular characterization. The S. clavata isolated from an immunocompromised 11-year-old male patient was characterized using MALDI-TOF, Gram staining, scanning electron microscopy (SEM), and next generation sequencing (NGS) of genomic DNA. Biofilm production was also evaluated in parallel with determining minimal inhibitory concentration (MIC) and biofilm sensitivity to antifungal treatment. We observed small to medium, whitish, farinose, dry, filamentous margin colonies, yeast-like cells with bacillary features, and biofilm formation. The MALDI-TOF system yielded a score of ≥ 2,000, while NGS confirmed S. clavata presence at the nucleotide level. The MIC values (in mg L-1) for tested drugs were as follows: fluconazole = 2, voriconazole ≤ 2, caspofungin ≥ 8, micafungin = 2, amphotericin B = 4, flucytosine ≤ 1, and anidulafungin = 1. Amphotericin B can be active against S. clavata biofilm and the fungus can be susceptible to new azoles. These findings were helpful for understanding the development of novel treatments for S. clavata-induced disease, including combined therapy for biofilm-associated infections.
Topics: Child; Male; Humans; Saccharomyces cerevisiae; Antifungal Agents; Amphotericin B; Brazil; Biofilms
PubMed: 36722674
DOI: 10.1590/S1678-9946202365012 -
Revista Do Instituto de Medicina... 2023Candidemia and other forms of invasive candidiasis (C/IC) are serious conditions, especially for immunosuppressed individuals with prolonged hospitalization in intensive...
Candidemia and other forms of invasive candidiasis (C/IC) are serious conditions, especially for immunosuppressed individuals with prolonged hospitalization in intensive care units (ICU). This study analyzed the incremental cost-effectiveness and budgetary impact (BI) of treatment for IC with anidulafungin compared to amphotericin B lipid complex (ABLC) and amphotericin B deoxycholate (ABD) or conventional amphotericin B (CAB), in the Brazilian Unified Health System (SUS). A decision model was conducted with a time horizon of two weeks from the perspective of SUS. The primary effectiveness endpoints were survival and treatment response rate. All patients were followed up until successful therapy or death. BI analysis was performed based on the measured demand method. A five-year time horizon was adopted based on the number of hospitalizations (per 1,000 hospitalizations). For effectiveness measured in the successful response rate (SRR), anidulafungin dominated the ABLC and ABD formulations. In the results of the analysis with the effectiveness measured according to survival, anidulafungin had a better cost-effectiveness ratio (R$988.26/survival) compared to ABD (R$16,359.50/survival). The BI estimate related to the incorporation of anidulafungin suggests savings of approximately 148 million reais in 5 years when comparing it to ABD. The economic evaluation of anidulafungin and its comparators found it to be cost-effective. The consensus of international scientific societies recommends it as a first-line drug for IC, and its incorporation by SUS would be important.
Topics: Humans; Candidemia; Anidulafungin; Brazil; Cost-Effectiveness Analysis; Candidiasis, Invasive
PubMed: 36722671
DOI: 10.1590/S1678-9946202365009 -
Enfermedades Infecciosas Y... Dec 2023Biofilm formation causes virulence and resistance in Candida albicans. However, little is known about breakthrough candidemia isolates. We evaluated the antifungal...
Comparison of amphotericin B lipid complex, deoxycholate amphotericin B, fluconazole, and anidulafungin activity against Candida albicans biofilm isolated from breakthrough candidemia.
INTRODUCTION
Biofilm formation causes virulence and resistance in Candida albicans. However, little is known about breakthrough candidemia isolates. We evaluated the antifungal activity of fluconazole, anidulafungin, deoxycholate amphotericin B (dAMB), and amphotericin B lipid complex (ABLC) against biofilms of C. albicans isolated from patients with breakthrough candidemia.
METHODS
The present study used strains of C. albicans isolated from breakthrough and non-breakthrough candidemia patients (control group). The susceptibility of planktonic cells to amphotericin B, anidulafungin, and fluconazole was determined by broth microdilution. Antifungal activity in sessile cells was evaluated using the minimum biofilm eradication concentration (MBEC), metabolic activity was estimated by reducing MTT, and biomass was estimated using crystal violet retention.
RESULTS
The planktonic strains were susceptible to amphotericin B, anidulafungin, and fluconazole, with minimum inhibitory concentrations of 1, ≤0.03, and 2mg/L, respectively. However, fluconazole and anidulafungin did not exert an antifungal effect on biofilms. Additionally, dAMB and ABCL reduced the metabolic activity and biomass. However, eradication was only achieved using 16mg/L dAMB. C. albicans isolates of breakthrough candidemia exhibited strong biofilm production, and the in vitro activity of available therapeutic options was poor.
CONCLUSION
In the present study, only dAMB and ABCL exhibited antibiofilm effects against sessile breakthrough candidemia isolates.
Topics: Humans; Amphotericin B; Antifungal Agents; Anidulafungin; Fluconazole; Candida albicans; Candidemia; Candida; Biofilms; Deoxycholic Acid
PubMed: 36707288
DOI: 10.1016/j.eimce.2022.07.009 -
BMC Infectious Diseases Jan 2023Nannizziopsis is a genus of fungi with several known cases in reptiles of pyogranulomatous infections at cutaneous and musculoskeletal level, of rapid and fatal...
BACKGROUND
Nannizziopsis is a genus of fungi with several known cases in reptiles of pyogranulomatous infections at cutaneous and musculoskeletal level, of rapid and fatal evolution. There are few cases of this genus described in humans, mainly skin affection but also with visceral abcesses, typically in immunosuppressed patients, with a recent visit to Africa.
CASE PRESENTATION
A 45-year-old woman immunosuppressed after renal transplantation and with a recent visit to Nigeria presented with a painless breast abcess, ulceration to the skin and bleeding, and non hematic telorrhea. The mammogram, also completed with an ultrasound scan, showed a polylobulated nodule, BI-RADS 4C. Due to the suspicion of breast cancer, a core needle biopsy was performed and the pathology study showed abundant presence of fungal spores and hyphae. It was identified by genomic amplification of the internal transcription spacer region-2 and a percentage of similarity with sequences of Nannizziopsis obscura from GenBank of 98% was obtained. An empiric treatment with anidulafungin was initiated, and after the surgical resection, it was replaced by isavuconazole, with a total time of treatment of one month.
CONCLUSIONS
This is the first case report of a successful treatment of Nannizziopsis obscura with isavuconazole, with the shortest time of treatment published for this fungi. We highlighted the importance of referring difficult to diagnose species to reference centers, as well as achieving the most complete resection in order to shorten the antibiotic therapy.
Topics: Female; Humans; Middle Aged; Kidney Transplantation; Nigeria; Abscess; Fungi; Immunocompromised Host
PubMed: 36694138
DOI: 10.1186/s12879-022-07958-3