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Frontiers in Cellular and Infection... 2023Opportunistic fungal infections by species arise among cancer patients due to the weakened immune system following extensive chemotherapy. Prophylaxis with antifungal...
OBJECTIVE
Opportunistic fungal infections by species arise among cancer patients due to the weakened immune system following extensive chemotherapy. Prophylaxis with antifungal agents have developed the resistance of spp. to antifungals. Accurate identification of yeasts and susceptibility patterns are main concerns that can directly effect on the treatment of patients.
METHODS
Over a period of three years, 325 cancer patients suspected to infections were included in the current investigation. The clinical isolates were molecularly identified by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). All strains, were examined for susceptibility to the amphotericin B, itraconazole, fluconazole, and anidulafungin according to the CLSI M27 document.
RESULTS
Seventy-four cancer patients had infections (22.7%). was the most common species (83.8%). Antifungal susceptibility results indicated that 100% of the isolates were sensitive to amphotericin B; however, 17.6%, 9.4%, and 5.4% of clinical isolates were resistant to anidulafungin, fluconazole, and itraconazole, respectively.
CONCLUSION
The findings of the present work shows a warning increase in resistance to echinocandins. Since all fluconazole resistance isolates were obtained from candidemia, we recommend amphotericin B as the first line therapy for this potentially fatal infection.
Topics: Humans; Antifungal Agents; Fluconazole; Amphotericin B; Itraconazole; Anidulafungin; Microbial Sensitivity Tests; Candidiasis; Candida; Candidemia; Neoplasms; Drug Resistance, Fungal
PubMed: 37249981
DOI: 10.3389/fcimb.2023.1152552 -
Pharmaceutics Apr 2023is a multidrug-resistant pathogen against which echinocandins are the drug of choice. However, information on how the chitin synthase inhibitor nikkomycin Z influences...
is a multidrug-resistant pathogen against which echinocandins are the drug of choice. However, information on how the chitin synthase inhibitor nikkomycin Z influences the killing activities of echinocandins against is currently lacking. We determined the killing activities of anidulafungin and micafungin (0.25, 1, 8, 16 and 32 mg/L each) with and without nikkomycin Z (8 mg/L) against 15 isolates representing four clades (South Asian n = 5; East Asian n = 3; South African n = 3; South American n = 4, two of which were of environmental origin). Two and one isolates from the South Asian clade harbored mutations in the hot-spot 1 (S639Y and S639P) and 2 (R1354H) regions of the gene, respectively. The anidulafungin, micafungin and nikkomycin Z MIC ranges were 0.015-4, 0.03-4 and 2->16 mg/L, respectively. Anidulafungin and micafungin alone exerted weak fungistatic activity against wild-type isolates and the isolate with a mutation in the hot-spot 2 region of but was ineffective against the isolates with a mutation in the hot-spot 1 region. The nikkomycin Z killing curves were always similar to their respective controls. Twenty-two of sixty (36.7%) anidulafungin plus nikkomycin Z and twenty-four of sixty (40%) micafungin plus nikkomycin Z combinations produced at least 100-fold decreases in the CFUs (synergy), with a 41.7% and 20% fungicidal effect, respectively, against wild-type isolates. Antagonism was never observed. Similar results were found with the isolate with a mutation in hot-spot 2 of , but the combinations were ineffective against the two isolates with prominent mutations in hot-spot 1 of . The simultaneous inhibition of β-1,3 glucan and chitin synthases in wild-type isolates produced significantly greater killing rates than either drug alone. Further studies are warranted to verify the clinical efficacy of echinocandin plus nikkomycin Z combinations against echinocandin susceptible isolates.
PubMed: 37242607
DOI: 10.3390/pharmaceutics15051365 -
Antimicrobial Agents and Chemotherapy Jun 2023We determined the echinocandin susceptibility and genotypes of 13 clinical isolates of Candida auris that were recovered from 4 patients at a tertiary care center in...
We determined the echinocandin susceptibility and genotypes of 13 clinical isolates of Candida auris that were recovered from 4 patients at a tertiary care center in Salvador, Brazil. Three isolates were categorized as echinocandin-resistant, and they harbored a novel mutation that led to an amino acid change W691L located downstream from hot spot 1. When introduced to echinocandin-susceptible C. auris strains by CRISPR/Cas9, Fks1 W691L induced elevated MIC values to all echinocandins (anidulafungin, 16 to 32×; caspofungin, >64×; micafungin, >64×).
Topics: Humans; Antifungal Agents; Candida auris; Fungal Proteins; Echinocandins; Caspofungin; Microbial Sensitivity Tests; Drug Resistance, Fungal
PubMed: 37222585
DOI: 10.1128/aac.00423-23 -
Rapid automated antifungal susceptibility testing system for yeasts based on growth characteristics.Frontiers in Cellular and Infection... 2023Fungal pathogens are a major threat to public health, as they are becoming increasingly common and resistant to treatment, with only four classes of antifungal medicines...
Fungal pathogens are a major threat to public health, as they are becoming increasingly common and resistant to treatment, with only four classes of antifungal medicines currently available and few candidates in the clinical development pipeline. Most fungal pathogens lack rapid and sensitive diagnostic techniques, and those that exist are not widely available or affordable. In this study, we introduce a novel automated antifungal susceptibility testing system, Droplet 48, which detects the fluorescence of microdilution wells in real time and fits growth characteristics using fluorescence intensity over time. We concluded that all reportable ranges of Droplet 48 were appropriate for clinical fungal isolates in China. Reproducibility within ±2 two-fold dilutions was 100%. Considering the Sensititre YeastOne Colorimetric Broth method as a comparator method, eight antifungal agents (fluconazole, itraconazole, voriconazole, caspofungin, micafungin, anidulafungin, amphotericin B, and 5-flucytosine) showed an essential agreement of >90%, except for posaconazole (86.62%). Category agreement of four antifungal agents (fluconazole, caspofungin, micafungin, and anidulafungin) was >90%, except for voriconazole (87.93% agreement). Two isolates and anidulafungin showed a major discrepancy (MD) (2.60%), and no other MD or very MD agents were found. Therefore, Droplet 48 can be considered as an optional method that is more automated and can obtain results and interpretations faster than previous methods. However, the optimization of the detection performance of posaconazole and voriconazole and promotion of Droplet 48 in clinical microbiology laboratories still require further research involving more clinical isolates in the future.
Topics: Antifungal Agents; Caspofungin; Micafungin; Anidulafungin; Voriconazole; Fluconazole; Reproducibility of Results; Candida; Microbial Sensitivity Tests; Yeasts
PubMed: 37201120
DOI: 10.3389/fcimb.2023.1153544 -
Mycoses Aug 2023Epidemiological knowledge is important to guide antifungal therapy.
BACKGROUND
Epidemiological knowledge is important to guide antifungal therapy.
OBJECTIVE
This multicentre study aimed to investigate the species distribution and antifungal susceptibility of Aspergillus isolates in Taiwan.
METHOD
Four hundred and ninety-two clinical Aspergillus isolates, collected during 2016-2020, were identified by calmodulin sequencing and tested for antifungal susceptibility using CLSI M38-A3. The Cyp51A sequences of azole-resistant Aspergillus fumigatus and Aspergillus flavus isolates were analysed.
RESULTS
This collection comprised 30 species from eight Aspergillus sections-Flavi (33.5%), Nigri (26.0%), Fumigati (24.2%), Terrei (10.0%), Nidulantes (5.1%), Circumdati (0.8%), Restricti (0.2%) and Aspergillus (0.2%). Sections Fumigati, Flavi and Terrei were primarily represented by A. fumigatus (99.2%), A. flavus (95.8%) and A. terreus (100%), respectively. Section Nigri comprised nine species, mostly A. welwitschiae (60.2%), A. niger (12.5%), A. brunneoviolaceus (10.9%) and A. tubingensis (10.2%). A. fumigatus (39.6%) and A. flavus (26.4%) predominated among 53 isolates from lower respiratory samples, whereas section Nigri species (46.2%) and A. terreus (29.2%) predominated among 65 isolates from ear samples. Reduced susceptibility to amphotericin B (minimal inhibitory concentration (MIC) > 1 μg/mL) was noted in A. flavus (7.0%), A. terreus (6.1%), A. nidulans and section Circumdati (A. flocculosus, A. subramanianii and A. westerdijkiae) isolates. Acquired azole resistance was observed in seven A. fumigatus (5.9%), all of which carried TR /L98H or TR /L98H/S297T/F495I mutation, and three A. flavus (1.9%), one of which carried G441S mutation. Reduced susceptibility to itraconazole (MIC >1 μg/mL) was noted in 55.5% of section Nigri isolates, mainly in A. welwitschiae, A. niger and A. tubingensis, whereas A. brunneoviolaceus, A. aculeatinus and A. japonicus were hypersusceptible to azoles. Anidulafungin was active against all isolates except for one isolate.
CONCLUSIONS
This study depicted the molecular epidemiology and species-specific characteristics of Aspergillus in Taiwan, which aids in appropriate antifungal therapy and underlines the need of speciation and susceptibility testing of disease-causing Aspergillus.
Topics: Humans; Antifungal Agents; Taiwan; Aspergillus; Itraconazole; Azoles; Aspergillus fumigatus; Microbial Sensitivity Tests; Drug Resistance, Fungal; Fungal Proteins
PubMed: 37186489
DOI: 10.1111/myc.13593 -
Antimicrobial Agents and Chemotherapy Jun 2023Candida auris is an emerging, multidrug-resistant fungal pathogen that causes refractory colonization and life-threatening, invasive nosocomial infections. The high...
Candida auris is an emerging, multidrug-resistant fungal pathogen that causes refractory colonization and life-threatening, invasive nosocomial infections. The high proportion of C. auris isolates that display antifungal resistance severely limits treatment options. Combination therapies provide a possible strategy by which to enhance antifungal efficacy and prevent the emergence of further resistance. Therefore, we examined drug combinations using antifungals that are already in clinical use or are undergoing clinical trials. Using checkerboard assays, we screened combinations of 5-flucytosine and manogepix (the active form of the novel antifungal drug fosmanogepix) with anidulafungin, amphotericin B, or voriconazole against drug resistant and susceptible C. auris isolates from clades I and III. Fractional inhibitory concentration indices (FICI values) of 0.28 to 0.75 and 0.36 to 1.02 were observed for combinations of anidulafungin with manogepix or 5-flucytosine, respectively, indicating synergistic activity. The high potency of these anidulafungin combinations was confirmed using live-cell microfluidics-assisted imaging of the fungal growth. In summary, combinations of anidulafungin with manogepix or 5-flucytosine show great potential against both resistant and susceptible C. auris isolates.
Topics: Antifungal Agents; Anidulafungin; Flucytosine; Candida auris; Candida; Microbial Sensitivity Tests
PubMed: 37162367
DOI: 10.1128/aac.01645-22 -
BMC Oral Health Apr 2023Patients with advanced cancer are prone to develop different opportunistic oral infection due to anti-cancer treatment or the malignancies themselves. Studies of oral... (Observational Study)
Observational Study
BACKGROUND
Patients with advanced cancer are prone to develop different opportunistic oral infection due to anti-cancer treatment or the malignancies themselves. Studies of oral fungal samples show an increased prevalence of non-Candida albicans species in mixed oral infections with Candida albicans. Non-C. albicans and C. albicans are associated with varying degrees of resistance to azoles, which may have implications for treatment. This study aimed to assess the diversity and antifungal susceptibility of Candida species detected in the oral cavity.
METHODS
An observational study with microbiological analysis was conducted. Clinical fungal isolates were collected from patients in a hospice unit in 2014-2016. Isolates were re-grown on chromID® Candida plates in 2020. Single colony of each species was re-cultivated and prepared for biochemical identification with a VITEK2® system and verified by gene sequencing. Etest was performed on RPMI agar, and the antifungals fluconazole, amphotericin B, anidulafungin and nystatin were applied.
RESULTS
Fifty-six isolates from 45 patients were identified. Seven different Candida species and one Saccharomyces species were detected. The results of biochemical identification were confirmed with sequencing analysis. Thirty-six patients had mono infection, and nine out of 45 patients had 2-3 different species detected. Of C. albicans strains, 39 out of 40 were susceptible to fluconazole. Two non-C. albicans species were resistant to fluconazole, one to amphotericin B and three to anidulafungin.
CONCLUSION
C. albicans was the predominant species, with a high susceptibility to antifungal agents. Different Candida species occur in both mono and mixed infections. Identification and susceptibility testing may therefore lead to more effective treatment and may prevent the development of resistance among patients with advanced cancer.
TRAIL REGISTRATION
The study Oral Health in Advanced Cancer was registered at ClinicalTrials.gov (#NCT02067572) in 20/02/2014.
Topics: Humans; Candidiasis, Oral; Fluconazole; Amphotericin B; Anidulafungin; Microbial Sensitivity Tests; Antifungal Agents; Candida; Candida albicans; Neoplasms; Drug Resistance, Fungal
PubMed: 37072843
DOI: 10.1186/s12903-023-02950-y -
Mycopathologia Jun 2023Aspergillus species are important causes of invasive fungal disease, particularly among those with an impaired immune system. Increasing reports have revealed a rising...
BACKGROUND
Aspergillus species are important causes of invasive fungal disease, particularly among those with an impaired immune system. Increasing reports have revealed a rising incidence of antifungal drug resistance among Aspergillus spp., particularly among cryptic species. Understanding local antifungal susceptibility patterns is paramount to delivering optimal clinical care.
METHODS
Aspergillus spp. recovered from clinical specimens between 2000 and 2021 from Pathology Queensland were collected. Aspergillus spp. were identified routinely morphologically, and where there was ambiguity or a lack of sporulation, by sequencing of the internal transcribed spacer (ITS) region. All Aspergillus spp. that underwent antifungal susceptibility testing according to the CLSI M38-A3 method and were recorded and included in the study. Amphotericin B, voriconazole, posaconazole, isavuconazole, micafungin, caspofungin, and anidulafungin were tested. Pathology Queensland services all public healthcare facilities in Queensland, Australia.
RESULTS
236 Aspergillus spp. were identified from clinical specimens during the study period. The most frequent species identified were Aspergillus section Fumigati (n = 119), Aspergillus section Flavi (n = 35), Aspergillus terreus (n = 32) and Aspergillus niger (n = 29). Overall, MIC values for voriconazole, posaconazole, itraconazole, and isavuconazole were 0.25/1, 0.25/0.5, 0.25/0.5, and 0.5/2 mg/L respectively. Echinocandins demonstrated low MIC values overall with micafungin and anidulafungin both having an MIC of 0.015/0.03 mg/L. A total of 15 cryptic species were identified; high triazole MIC values were observed with a voriconazole MIC of 2/8 mg/L. From 2017 to 2021 we observed an increase in incidence of isolates with high voriconazole MIC values. There was no difference in voriconazole MIC values between Aspergillus spp. acquired in North Queensland when compared to Southeast Queensland, Australia.
CONCLUSION
Increasing reports of antifungal resistance among Aspergillus spp. is concerning and warrants further investigation both locally and worldwide. Active surveillance of both the emergence of different Aspergillus spp. and changes in antifungal susceptibility patterns over time is crucial to informing clinicians and treatment guidelines.
Topics: Humans; Antifungal Agents; Voriconazole; Anidulafungin; Micafungin; Queensland; Aspergillus; Mycoses; Microbial Sensitivity Tests; Drug Resistance, Fungal
PubMed: 37067664
DOI: 10.1007/s11046-023-00713-5 -
Southern African Journal of Infectious... 2023Worldwide, the leading cause of invasive candidiasis and the fourth leading cause of hospital-acquired infections are the Candida species (spp.) group. One of the most...
BACKGROUND
Worldwide, the leading cause of invasive candidiasis and the fourth leading cause of hospital-acquired infections are the Candida species (spp.) group. One of the most important tools in fighting such drug-resistant fungi is the appropriate use of antifungal agents.
OBJECTIVES
The study aimed to determine echinocandins' general prescribing patterns and how they are associated with the treatment period.
METHOD
A quantitative, observational, and descriptive was used, and included patients receiving antifungal treatment in a private hospital in Gauteng, South Africa between 01 January 2015 to 31 December 2015.
RESULTS
Of the 146 patient files included, 102 patients (69.9%) received caspofungin and 44 patients (30.1%) were treated with anidulafungin. For the former, 99 (97.1%) patients received a loading dose (LD) of 70 mg, while 200 mg anidulafungin was only prescribed to 30 patients (68.2%). In line with maintenance dose guidelines, the majority (98.1%) of caspofungin-treated patients received 50 mg IV daily, whereas 4 (3.9%) patients were treated at higher doses (70 mg daily). Anidulafungin was administered at various maintenance doses, including 400 mg (2.3% of patients), 200 mg (52.3%), 100 mg (43.2%) and 50 mg (2.3%) IV daily.
CONCLUSION
Our results can be utilised to produce a hospital-specific algorithm in terms of Candida-infected patients.
CONTRIBUTION
These findings contribute to our understanding of prescribing patterns of antifungal agents and the impact thereof on treating spp. Infections.
PubMed: 37063450
DOI: 10.4102/sajid.v38i1.470 -
Brazilian Journal of Microbiology :... Jun 2023The study aimed to evaluate the clinical aspects, molecular identification, biofilm formation, and antifungal susceptibility profile of Candida species isolated from...
The study aimed to evaluate the clinical aspects, molecular identification, biofilm formation, and antifungal susceptibility profile of Candida species isolated from fungal keratitis. Thirteen Candida isolates from 13 patients diagnosed with Candida keratitis were retrieved and grown in pure culture. Species identification was performed by micromorphology analysis and ITS-rDNA sequencing. The broth microdilution method tested the minimum inhibitory concentration (MIC) of four antifungal drugs (fluconazole, amphotericin B, voriconazole, and anidulafungin). The biofilms were cultured and incubated with antifungal drugs for 24 h. The XTT reduction assay measured the biofilm activity. Biofilm MICs were calculated based on a 50% reduction in metabolic activity compared with the activity of the drug-free control. Among isolates, two were C. albicans, 10 were C. parapsilosis (sensu stricto), and one was C. orthopsilosis. All isolates were classified as susceptible or intermediate to all four antifungal drugs. Four isolates were very low biofilm producers (30%). Nine isolates were biofilm producers, and all biofilm samples were unsusceptible to all drugs tested. Previous ocular surgery was the most common underlying condition for fungal keratitis (84.6%), and C. parapsilosis was the most frequent Candida species (76.9%). Four patients (30.7%) needed keratoplasty, whereas two (15.3%) required evisceration. The biofilm formation ability of Candida isolates decreased antifungal susceptibility compared with planktonic cells. Despite in vitro antifungal susceptibility, almost half of the patients were unresponsive to clinical treatment and needed surgery.
Topics: Humans; Antifungal Agents; Candida; Amphotericin B; Candida parapsilosis; Keratitis; Candida albicans; Microbial Sensitivity Tests; Biofilms; Drug Resistance, Fungal
PubMed: 37055625
DOI: 10.1007/s42770-023-00964-w