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Mishra SK, Kuppusamy R, Nguyen C, Doeur J, Atwal H, Attard S, Sørensen K, Lin JS, Wong EHH, Hui A, Barron AE, Kumar N, Willcox M. Evaluation of the Synergistic Activity of Antimicrobial Peptidomimetics or Colistin Sulphate with Conventional Antifungals Against Yeasts of Medical Importance. J Fungi (Basel) 2025; 11:370. [PMID: 40422704 DOI: 10.3390/jof11050370] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2025] [Revised: 05/04/2025] [Accepted: 05/05/2025] [Indexed: 05/28/2025] Open
Abstract
With rising multidrug-resistant yeast pathogens, conventional antifungals are becoming less effective, urging the need for adjuvants that enhance their activity at lower doses. This study evaluated the synergistic activity of antimicrobial peptidomimetics (TM8 and RK758) or colistin sulphate in combination with conventional antifungals against Candida albicans, C. tropicalis, C. parapsilosis, Meyerozyma guilliermondii, Nakaseomyces glabratus, Pichia kudriavzevii and Kluyveromyces marxianus, and Candidozyma auris using the checkerboard microdilution test. RK758 was synergistic with fluconazole in 78% of isolates, with the remaining 22% of isolates still showing partial synergy; it showed synergy with amphotericin B in 56% of isolates, and with caspofungin, 78% of isolates exhibited either synergy or partial synergy. TM8 showed synergy with fluconazole in 44% (with partial synergy in another 44%) of isolates, with amphotericin B in 67% of isolates, and with caspofungin in 44% (with partial synergy in another 44%) of isolates. Colistin with fluconazole or caspofungin exhibited synergy or partial synergy in 56% of the isolates. No antagonism was observed in any of the combinations. Additionally, a time-kill assay further demonstrated synergistic activity between fluconazole and TM8 or RK758. The effects of these peptidomimetics on cell membrane integrity were demonstrated in an ergosterol binding assay, supported by SYTOX Green and cellular leakage assays, both indicating a lytic effect. These results suggest that peptidomimetics can synergise with conventional antifungals, offering a potential strategy for combination therapy against yeast infections. The membrane lytic activity of the peptidomimetics likely plays a role in their synergistic interaction with antifungals, thereby enhancing the antimicrobial activities of both compounds at sub-MIC levels.
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Affiliation(s)
- Shyam Kumar Mishra
- School of Optometry and Vision Science, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW 2052, Australia
- Department of Microbiology, Maharajgunj Medical Campus, Institute of Medicine, Tribhuvan University, Kathmandu 44600, Nepal
| | - Rajesh Kuppusamy
- School of Optometry and Vision Science, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW 2052, Australia
- School of Chemistry, Faculty of Science, University of New South Wales, Sydney, NSW 2052, Australia
| | - Christina Nguyen
- School of Optometry and Vision Science, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW 2052, Australia
| | - Jennifer Doeur
- School of Optometry and Vision Science, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW 2052, Australia
| | - Harleen Atwal
- School of Optometry and Vision Science, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW 2052, Australia
| | - Samuel Attard
- School of Chemistry, Faculty of Science, University of New South Wales, Sydney, NSW 2052, Australia
| | - Kristian Sørensen
- Department of Bioengineering, School of Medicine and School of Engineering, Stanford University, Stanford, CA 94305, USA
| | - Jennifer S Lin
- Department of Bioengineering, School of Medicine and School of Engineering, Stanford University, Stanford, CA 94305, USA
| | - Edgar H H Wong
- School of Chemical Engineering, Faculty of Engineering, University of New South Wales, Sydney, NSW 2052, Australia
| | - Alex Hui
- School of Optometry and Vision Science, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW 2052, Australia
- School of Optometry & Vision Science, University of Waterloo, Waterloo, ON N2L 3G1, Canada
| | - Annelise E Barron
- Department of Bioengineering, School of Medicine and School of Engineering, Stanford University, Stanford, CA 94305, USA
| | - Naresh Kumar
- School of Chemistry, Faculty of Science, University of New South Wales, Sydney, NSW 2052, Australia
| | - Mark Willcox
- School of Optometry and Vision Science, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW 2052, Australia
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Yao D, Chen J, Zhang G. Clinical Features, Outcomes, and Antifungal Susceptibility Profiles of Invasive Candida Infections in a Tertiary Care Hospital in China. Infect Drug Resist 2025; 18:2271-2282. [PMID: 40353202 PMCID: PMC12065533 DOI: 10.2147/idr.s510389] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2024] [Accepted: 04/18/2025] [Indexed: 05/14/2025] Open
Abstract
Purpose Given the increasing incidence of invasive Candida infection worldwide, particularly among immunocompromised and critically ill patients, we aimed to assess the distribution of Candida species as well as their clinical features and responses to common antifungal agents through a retrospective analysis of patient data in a Chinese traditional medicine hospital. Patients and Methods In this retrospective single-center study, we analyzed data from 301 patients with invasive Candida infection at our hospital between 2020 and 2022, We report the clinical characteristics, species distribution, and in-vitro susceptibility profiles of Candida isolates to eight antifungal agents. Logistic regression analysis was employed for multivariate assessments to analysis the correlation between clinical symptoms and prognosis. Kaplan-Meier survival analysis was used for survival analysis. Results Candida albicans was the most prevalent species (38.9%, 117/301), followed by C. tropicalis (28.2%, 85/301) and C. glabrata (22.9%, 69/301). Age, department of admission, underlying disease, and presence of risk factors differed significantly among patients with different Candida infections. Kaplan-Meier survival analysis showed that C. krusei infection was associated with a higher seven-day mortality than other Candida spp. infections. Multivariate logistic regression analyses showed that age, presence of sepsis, insertion of the central venous catheter, and administration of total parenteral nutrition were independent predictors of mortality. C. tropicalis was most resistant to azoles, with 36.26% of the strains being fluconazole-resistant, 35.16% being non-wild type to itraconazole, and 34.52% being non-wild type to voriconazole. Non-susceptibility to echinocandins was found in 11 C. glabrata strains (10.39%, 3.90%, and 1.30% of isolates for caspofungin, micafungin, and anidulafungin, respectively). Conclusion Our findings underscore the need for close monitoring of azole resistance in C. tropicalis and echinocandin resistance in C. glabrata, and highlight age, sepsis, CVC insertion, and parenteral nutrition as key predictors of mortality in invasive Candida infections.
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Affiliation(s)
- Dongting Yao
- Department of Laboratory Medicine, The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200030, People’s Republic of China
- Shanghai Key Laboratory of Embryo Original Diseases, Shanghai, 200030, People’s Republic of China
| | - Jia Chen
- Department of Laboratory Medicine, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200030, People’s Republic of China
| | - Guanyi Zhang
- Department of Laboratory Medicine, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200030, People’s Republic of China
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Dishan A, Ozkaya Y, Temizkan MC, Barel M, Gonulalan Z. Candida species covered from traditional cheeses: Characterization of C. albicans regarding virulence factors, biofilm formation, caseinase activity, antifungal resistance and phylogeny. Food Microbiol 2025; 127:104679. [PMID: 39667852 DOI: 10.1016/j.fm.2024.104679] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2024] [Revised: 10/31/2024] [Accepted: 11/04/2024] [Indexed: 12/14/2024]
Abstract
This study has provided characterization data (carriage of virulence, antifungal resistance, caseinase activity, biofilm-forming ability and genotyping) of Candida albicans isolates and the occurrence of Candida species in traditional cheeses collected from Kayseri, Türkiye. Phenotypic (E-test, Congo red agar and microtiter plate tests) and molecular tests (identification, virulence factors, biofilm-formation, antifungal susceptibility) were carried out. The phylogenetic relatedness of C. albicans isolates was obtained by constructing the PCA dendrogram from the mass spectra data. Of 102 samples, 13 (12.7%) were found to be contaminated with C. albicans, 15 (14.7%), 10 (9.8%) and five (4.9%) were found to be contaminated with C. krusei, C. lusitane and C. paraplosis, respectively. While seven (16.2%) of 43 Candida spp. isolates were obtained from cheese collected from villages, 36 (83.7%) belonged to cheeses collected from traditional retail stores. The carriage rate of C. albicans isolates belonging to virulence factors HSP90 and PLB1 genes was 30.7%. ALST1, ALST3, BCR, ECE, andHWP (virulence and biofilm-associated) genes were harbored by 30.7%, 23%, 38.4%, 53.8%, and 38.4% of the 13 isolates. According to the microplate test, eight (61.5%) of 13 isolates had strong biofilm production. ERG11 and FKS1 (antifungal resistance genes) were found in 46.1% and 23% of 13 isolates, respectively. Due to missense mutations, K128T, E266D and V488I amino acid changes were detected for some isolates regarding azole resistance. As a result of the E-test, of the 13 isolates, one (7.6%) was resistant to flucytosine, four (30.7%) were resistant to caspofungin, and nine (69.2%) were resistant to fluconazole. The PCA analysis clustered the studied isolates into two major clades. C. albicans isolates of traditional cheese collected from villages were grouped in the same cluster. Among the C. albicans isolates from village cheese, there were those obtained from the same dairy milk at different times. Samples from the same sales points produced at different dairy farms were also contaminated with C. albicans. Concerning food safety standards applied from farm to fork, in order to prevent these pathogenic agents from contaminating cheeses, attention to the hygiene conditions of the sale points, conscious personnel, prevention of cross contamination will greatly reduce public health threats in addition to the application of animal health control, milking hygiene, pasteurization parameters in traditional cheese production.
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Affiliation(s)
- Adalet Dishan
- Yozgat Bozok University, Faculty of Veterinary Medicine, Dept. of Food Hygiene and Technology, Yozgat, Turkiye.
| | - Yasin Ozkaya
- Erciyes University, Faculty of Veterinary Medicine, Dept. of Veterinary Public Health, Kayseri, Turkiye
| | - Mehmet Cevat Temizkan
- Yozgat Bozok University, Faculty of Veterinary Medicine, Dept. of Veterinary Genetics, Yozgat, Turkiye
| | - Mukaddes Barel
- Erciyes University, Faculty of Veterinary Medicine, Dept. of Veterinary Public Health, Kayseri, Turkiye
| | - Zafer Gonulalan
- Erciyes University, Faculty of Veterinary Medicine, Dept. of Veterinary Public Health, Kayseri, Turkiye
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Coutinho TDNP, Rodrigues FAM, de Assis DA, Rebouças LM, Ferreira TL, Cabral VPDF, Rodrigues DS, Sá LGDAV, Lopes FFDS, do Nascimento GA, Mattos ALA, Cavalcanti BC, Júnior HVN, da Silva CR, Ricardo NMPS. Microspheres based on galactomannan and Spondias purpurea L. extract to increase antifungal and antibiofilm efficacy against Candida spp. Int J Biol Macromol 2025; 297:139788. [PMID: 39805454 DOI: 10.1016/j.ijbiomac.2025.139788] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2024] [Revised: 12/29/2024] [Accepted: 01/10/2025] [Indexed: 01/16/2025]
Abstract
The ongoing problem of an increasing resistance of Candida spp. to available antifungals, has made it necessary the search for new therapeutic alternatives. The aim of this work was to develop a microsphere based on Caesalpinia ferrea galactomannan and Spondias purpurea L. stem bark extract using the spray drying technique and evaluate its antimicrobial effect on biofilm formation and planktonic cells of Candida spp. Differential scanning calorimetry (DSC), infrared analysis (IR) and scanning electron microscopy (SEM) were used to characterize the microsphere, in addition to the encapsulation efficiency by HPLC to quantify the extract in the microsphere. In microbiological analyses, broth microdilution and antibiofilm tests were carried out. The results of the minimum inhibitory concentration (MIC) for the stem bark extract (SBE) were within 0.5-2 μg mL-1 and the galactomannan microsphere (GMB) 1-8 μg mL-1. As for the biofilm, the microsphere compared to the extract showed a statistically significant improvement at 8xMIC for C. albicans 1, while for C. auris, it was at 4xMIC and 8xMIC. Furthermore, SBE and GMB did not present toxicity. The study revealed that the synthesized microspheres have the potential to be used as an antifungal agent.
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Affiliation(s)
- Tatiana do N P Coutinho
- Laboratory of Polymers and Materials Innovation, Department of Organic and Inorganic Chemistry, Sciences Center, Federal University of Ceará, Campus of Pici, Zip Code 60440-900 Fortaleza, CE, Brazil; Department of Clinical and Toxicological Analysis, Faculty of Pharmacy, Laboratory of Bioprospection in Antimicrobial Molecules (LABIMAN), Federal University of Ceará, Fortaleza, Ceará, Brazil; Center for Research and Development of Medicines, Federal University of Ceará, Fortaleza, Ceará, Brazil
| | - Francisco A M Rodrigues
- Laboratory of Polymers and Materials Innovation, Department of Organic and Inorganic Chemistry, Sciences Center, Federal University of Ceará, Campus of Pici, Zip Code 60440-900 Fortaleza, CE, Brazil
| | - David A de Assis
- Laboratory of Polymers and Materials Innovation, Department of Organic and Inorganic Chemistry, Sciences Center, Federal University of Ceará, Campus of Pici, Zip Code 60440-900 Fortaleza, CE, Brazil.
| | - Louhana M Rebouças
- Laboratory of Polymers and Materials Innovation, Department of Organic and Inorganic Chemistry, Sciences Center, Federal University of Ceará, Campus of Pici, Zip Code 60440-900 Fortaleza, CE, Brazil; Federal Institute of Education, Science and Technology of Ceará, Fortaleza, CE 60410-426, Brazil
| | - Thais L Ferreira
- Department of Clinical and Toxicological Analysis, Faculty of Pharmacy, Laboratory of Bioprospection in Antimicrobial Molecules (LABIMAN), Federal University of Ceará, Fortaleza, Ceará, Brazil; Center for Research and Development of Medicines, Federal University of Ceará, Fortaleza, Ceará, Brazil
| | - Vitória P de F Cabral
- Department of Clinical and Toxicological Analysis, Faculty of Pharmacy, Laboratory of Bioprospection in Antimicrobial Molecules (LABIMAN), Federal University of Ceará, Fortaleza, Ceará, Brazil; Center for Research and Development of Medicines, Federal University of Ceará, Fortaleza, Ceará, Brazil
| | - Daniel S Rodrigues
- Department of Clinical and Toxicological Analysis, Faculty of Pharmacy, Laboratory of Bioprospection in Antimicrobial Molecules (LABIMAN), Federal University of Ceará, Fortaleza, Ceará, Brazil; Center for Research and Development of Medicines, Federal University of Ceará, Fortaleza, Ceará, Brazil
| | - Lívia G do A V Sá
- Department of Clinical and Toxicological Analysis, Faculty of Pharmacy, Laboratory of Bioprospection in Antimicrobial Molecules (LABIMAN), Federal University of Ceará, Fortaleza, Ceará, Brazil; Center for Research and Development of Medicines, Federal University of Ceará, Fortaleza, Ceará, Brazil
| | - Francisco F da S Lopes
- Laboratory of Chemistry of Natural Products, Postgraduate Program in Biotechnology, Ceará State University, Itaperi Campus s/N° CEP, 60714/903 Fortaleza, Ceará, Brazil
| | - Gabriela A do Nascimento
- NutriFisher Study Group, Postgraduate Program in Nutrition and Health, State University of Ceará, Fortaleza 60714-903, CE, Brazil.
| | - Adriano L A Mattos
- Embrapa Tropical Agroindustry, Pici campus, Zip Code 60511-110 Fortaleza, CE, Brazil.
| | - Bruno C Cavalcanti
- Center for Research and Development of Medicines, Federal University of Ceará, Fortaleza, Ceará, Brazil
| | - Hélio V N Júnior
- Department of Clinical and Toxicological Analysis, Faculty of Pharmacy, Laboratory of Bioprospection in Antimicrobial Molecules (LABIMAN), Federal University of Ceará, Fortaleza, Ceará, Brazil; Center for Research and Development of Medicines, Federal University of Ceará, Fortaleza, Ceará, Brazil
| | - Cecília R da Silva
- Department of Clinical and Toxicological Analysis, Faculty of Pharmacy, Laboratory of Bioprospection in Antimicrobial Molecules (LABIMAN), Federal University of Ceará, Fortaleza, Ceará, Brazil; Center for Research and Development of Medicines, Federal University of Ceará, Fortaleza, Ceará, Brazil.
| | - Nágila M P S Ricardo
- Laboratory of Polymers and Materials Innovation, Department of Organic and Inorganic Chemistry, Sciences Center, Federal University of Ceará, Campus of Pici, Zip Code 60440-900 Fortaleza, CE, Brazil.
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Hizlisoy H, Dishan A, Bekdik IK, Barel M, Koskeroglu K, Ozkaya Y, Aslan O, Yilmaz OT. Candida albicans in the oral cavities of pets: biofilm formation, putative virulence, antifungal resistance profiles and classification of the isolates. Int Microbiol 2025; 28:423-435. [PMID: 38955904 DOI: 10.1007/s10123-024-00552-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2024] [Revised: 06/20/2024] [Accepted: 06/25/2024] [Indexed: 07/04/2024]
Abstract
The study aimed to investigate Candida albicans presence, antifungal resistance, biofilm formation, putative virulence genes, and molecular characterization in oral samples of dogs and cats. A total of 239 oral samples were collected from cats and dogs of various breeds and ages at Erciyes University, Faculty of Veterinary Medicine Clinics, between May 2017 and April 2018. Among 216 isolates obtained, 15 (6.95%) were identified as C. albicans, while 8 (3.7%) were non-albicans Candida species. Antifungal susceptibility testing revealed sensitivities to caspofungin, fluconazole, and flucytosine in varying proportions. Molecular analysis indicated the presence of fluconazole and caspofungin resistance genes in all C. albicans isolates. Additionally, virulence genes ALS1, HWP1, and HSP90 showed variable presence. Biofilm formation varied among isolates, with 46.7% strong, 33.3% moderate, and 20% weak producers. PCA analysis categorized isolates into two main clusters, with some dog isolates grouped separately. The findings underscore the significance of oral care and protective measures in pets due to C. albicans prevalence, biofilm formation, virulence factors, and antifungal resistance in their oral cavity, thereby aiding clinical diagnosis and treatment in veterinary medicine.
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Affiliation(s)
- Harun Hizlisoy
- Faculty of Veterinary Medicine, Department of Veterinary Public Health, Erciye University, Kayseri, Türkiye.
| | - Adalet Dishan
- Faculty of Veterinary Medicine, Department of Food Hygiene and Technology, Bozok University, Yozgat, Türkiye
| | - Ilknur Karaca Bekdik
- Faculty of Veterinary Medicine, Department of Internal Medicine, Erciyes University, Kayseri, Türkiye
| | - Mukaddes Barel
- Faculty of Veterinary Medicine, Department of Veterinary Public Health, Erciye University, Kayseri, Türkiye
| | | | - Yasin Ozkaya
- Health Sciences Institute, Erciyes University, Kayseri, Türkiye
| | - Oznur Aslan
- Faculty of Veterinary Medicine, Department of Internal Medicine, Erciyes University, Kayseri, Türkiye
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Huang X, Dong Q, Zhou Q, Fang S, Xu Y, Long H, Chen J, Li X, Qin H, Mu D, Cai X. Genomics insights of candidiasis: mechanisms of pathogenicity and drug resistance. Front Microbiol 2025; 16:1531543. [PMID: 40083780 PMCID: PMC11903725 DOI: 10.3389/fmicb.2025.1531543] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2024] [Accepted: 02/12/2025] [Indexed: 03/16/2025] Open
Abstract
Candidiasis, a prevalent class of human infections caused by fungi belonging to the Candida genus, is garnering increasing attention due to its pathogenicity and the emergence of drug resistance. The advancement of genomics technologies has offered powerful tools for investigating the pathogenic mechanisms and drug resistance characteristics of Candida. This comprehensive review provides an overview of the applications of genomics in candidiasis research, encompassing genome sequencing, comparative genomics, and functional genomics, along with the pathogenic features and core virulence factors of Candida. Moreover, this review highlights the role of genomic variations in the emergence of drug resistance, further elucidating the evolutionary and adaptive mechanisms of Candida. In conclusion, the review underscores the current state of research and prospective avenues for exploration of candidiasis, providing a theoretical basis for clinical treatments and public health strategies.
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Affiliation(s)
- Xin Huang
- Key Laboratory of Biodiversity Conservation and Characteristic Resource Utilization in Southwest Anhui, Anqing Forestry Technology Innovation Research Institute, School of Life Sciences, Anqing Normal University, Anqing, China
- State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, China
| | - Qin Dong
- Key Laboratory of Biodiversity Conservation and Characteristic Resource Utilization in Southwest Anhui, Anqing Forestry Technology Innovation Research Institute, School of Life Sciences, Anqing Normal University, Anqing, China
| | - Qi Zhou
- Key Laboratory of Biodiversity Conservation and Characteristic Resource Utilization in Southwest Anhui, Anqing Forestry Technology Innovation Research Institute, School of Life Sciences, Anqing Normal University, Anqing, China
| | - Shitao Fang
- Key Laboratory of Biodiversity Conservation and Characteristic Resource Utilization in Southwest Anhui, Anqing Forestry Technology Innovation Research Institute, School of Life Sciences, Anqing Normal University, Anqing, China
| | - Yiheng Xu
- Key Laboratory of Biodiversity Conservation and Characteristic Resource Utilization in Southwest Anhui, Anqing Forestry Technology Innovation Research Institute, School of Life Sciences, Anqing Normal University, Anqing, China
| | - Hongjie Long
- Key Laboratory of Biodiversity Conservation and Characteristic Resource Utilization in Southwest Anhui, Anqing Forestry Technology Innovation Research Institute, School of Life Sciences, Anqing Normal University, Anqing, China
| | - Jingyi Chen
- Key Laboratory of Biodiversity Conservation and Characteristic Resource Utilization in Southwest Anhui, Anqing Forestry Technology Innovation Research Institute, School of Life Sciences, Anqing Normal University, Anqing, China
| | - Xiao Li
- Key Laboratory of Biodiversity Conservation and Characteristic Resource Utilization in Southwest Anhui, Anqing Forestry Technology Innovation Research Institute, School of Life Sciences, Anqing Normal University, Anqing, China
| | - Huaguang Qin
- Key Laboratory of Biodiversity Conservation and Characteristic Resource Utilization in Southwest Anhui, Anqing Forestry Technology Innovation Research Institute, School of Life Sciences, Anqing Normal University, Anqing, China
| | - Dan Mu
- Key Laboratory of Biodiversity Conservation and Characteristic Resource Utilization in Southwest Anhui, Anqing Forestry Technology Innovation Research Institute, School of Life Sciences, Anqing Normal University, Anqing, China
| | - Xunchao Cai
- Department of Gastroenterology and Hepatology, Shenzhen University General Hospital, Shenzhen University, Shenzhen, China
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ElFeky DS, El-Wakil DM, Mwafy MM, Atia MMA, Gohar NM. Comparative evaluation of antifungal susceptibility testing methods of invasive Candida species and detection of FKS genes mutations in caspofungin intermediate and resistant isolates. BMC Infect Dis 2025; 25:114. [PMID: 39856577 PMCID: PMC11760087 DOI: 10.1186/s12879-024-10435-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2024] [Accepted: 12/31/2024] [Indexed: 01/27/2025] Open
Abstract
BACKGROUND Fungal invasive infections caused by Candida species pose a substantial public health risk with limited therapeutic options. Antifungal susceptibility testing (AFST) is necessary to optimize the therapy. The study aimed to compare different AFST methods of Candida spp. and detect FKS gene mutations among caspofungin-intermediate and resistant isolates. METHODS A total of 60 non-replicative invasive Candida isolates recovered from various clinical samples were included. In-vitro AFST was carried out using the ATB FUNGUS 3, Vitek-2 AST-YS08, and E-test. Hotspot (HS) regions of FKS genes were sequenced for caspofungin-intermediate and resistant isolates. RESULTS Candida albicans (58.3%) was the most predominant spp., followed by C. glabrata (28.3%). Based on the clinical breakpoints (CBPs), fluconazole resistance was found in C. albicans (45.7%), C. tropicalis (25%), and the C. parapsilosis isolate, while 35.3% of C. glabrata were susceptible dose-dependent (SDD). None of C. albicans, C. tropicalis, or C. parapsilosis isolates were resistant to voriconazole. Using the epidemiological cut-off values (ECVs) for amphotericin B, 6.7% of isolates were non-wild type (non-WT), including C. guilliermondii (50%), C. tropicalis (25%), and C. glabrata (11.8%), while all C. albicans, C. parapsilosis, and C. kefyr isolates were classified as wild-type (WT). ATB FUNGUS 3 and Vitek-2 had the highest categorical agreement (CA) (83.1%) for amphotericin B, while a lower concordance was detected with voriconazole (23.2%) and fluconazole (52.2%). For caspofungin, Vitek-2 and E-test had a CA of 89.8%. Eleven isolates (10 C. glabrata and one C. parapsilosis) exhibited resistance or intermediate susceptibility to caspofungin (MICs: 0.25‒>32 µg/ml). Molecular characterization of the FKS gene demonstrated that FKS1 mutations V47I, V52K, V56T, D57S, L62F, I71Y, I71Q in the HS1 region, and G7S, P11H mutations in the HS2 region were associated with increased caspofungin MIC values (16 µg/ml). Mutations at the HS1 of the FKS2 gene; K33V, W35K, and W35V; were associated with the highest caspofungin MICs of > 32 µg/ml. CONCLUSIONS ATB FUNGUS 3 demonstrated acceptable performance for AFST, however, azole activity against Candida spp. should be interpreted carefully. Novel mutations within HS regions of FKS genes elucidated different levels of caspofungin resistance in C. glabrata and C. parapsilosis isolates.
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Affiliation(s)
- Dalia Saad ElFeky
- Department of Medical Microbiology and Immunology, Faculty of Medicine, Cairo University, Al-Saray Street, Al-Manial, Cairo, 11562, Egypt
| | - Doaa Mahdy El-Wakil
- Department of Medical Microbiology and Immunology, Faculty of Medicine, Cairo University, Al-Saray Street, Al-Manial, Cairo, 11562, Egypt.
| | - Mai M Mwafy
- Department of Medical Microbiology and Immunology, Faculty of Medicine, Tanta University, Tanta, Egypt
| | - Mohamed M A Atia
- Genome Mapping Department, Agricultural Genetic Engineering Research Institute (AGERI), Agricultural Research Center (ARC), Giza, Egypt.
| | - Noha Mahmoud Gohar
- Department of Medical Microbiology and Immunology, Faculty of Medicine, Cairo University, Al-Saray Street, Al-Manial, Cairo, 11562, Egypt
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Gedefie A, Shimeles G, Motbainor H, Kassanew B, Genet C. Vaginal colonization and vertical transmission of Candida species: prevalence and associated factors among pregnant women and their neonates at public health facilities of Northeast Ethiopia. BMC Pregnancy Childbirth 2025; 25:22. [PMID: 39789438 PMCID: PMC11716415 DOI: 10.1186/s12884-024-07103-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2024] [Accepted: 12/23/2024] [Indexed: 01/12/2025] Open
Abstract
BACKGROUND Vaginal colonization by Candida can lead to vulvovaginal candidiasis, which is the second most prevalent vaginal condition globally. It is frequently associated with sepsis and adverse neonatal outcomes in pregnant women. This issue is worsening in Sub-Saharan Africa, including Ethiopia. However, evidence of the existing problem is very scarce yet crucial. Thus, this study aimed to determine the vaginal colonization and vertical transmission of Candida species and their associated factors among pregnant women and their neonates in public health facilities of northeast Ethiopia. METHODS A facility-based cross-sectional study was conducted at selected public health facilities in Dessie town from April 1 to June 30, 2023, among 348 pregnant women and their newborns, using convenience sampling techniques. Socio-demographic, and clinical-related data were collected using a pre-tested, semi-structured questionnaire. Vaginal swab samples from pregnant women and pooled swabs from the external ear, nasal area, and umbilical areas of the newborns were collected and transported using Amies transport media. The samples were inoculated into Sabouraud Dextrose Agar for isolation, followed by inoculation onto a standard CHROM agar Candida plate for species identification, and a germ-tube test confirmed pseudophyphae of C.albicans. Data was entered into Epi Data version 4.6.0 software and exported and analyzed by SPSS version 25.0. A stepwise logistic regression model was used to identify the associated factors. Variables with p < 0.05 and their 95% confidence interval were considered statistically significant. RESULT A total of 348 pregnant women attending vaginal delivery were included in the study. The maternal and neonatal colonization rates of Candida species were 14.1% (49/348) and 6.3% (22/348), respectively. The overall proportion of vertical transmission of Candida species was 44.9% (22/49, 95% CI: 41.2, 49.7). Among Candida isolates, 63.3% (31/49) were C. albicans and 36.7% (18/49) were C. krusei. Gestational diabetes mellitus (AOR: 4.2, 95% CI: 1.23-38.6, P = 0.047) and HIV (AOR: 1.58, 95% CI: 1.11-6.12, P = 0.049) were independently associated with maternal colonization of Candida species. Moreover, rural residence (AOR = 3.6, 95% CI: 1.37-9.5, P = 0.010) and maternal age above 28 years (AOR = 2.39, 95% CI: 1.97-5.89, P = 0.048) were independently associated with vertical transmission of Candida species. CONCLUSION The findings of this study highlight the need for effective screening and treatment of Candida colonization during antenatal care.
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Affiliation(s)
- Alemu Gedefie
- Department of Medical Laboratory Sciences, College of Medicine and Health Sciences, Wollo University, Dessie, Ethiopia.
| | - Getnet Shimeles
- Department of Medical Laboratory Sciences, College of Medicine and Health Sciences, Bahir Dar University, Bahir Dar, Ethiopia
- Gishe Rabel Health Center, Debre Birhan, Ethiopia
| | - Hilina Motbainor
- Department of Medical Laboratory Sciences, College of Medicine and Health Sciences, Bahir Dar University, Bahir Dar, Ethiopia
| | - Brhanu Kassanew
- Department of Medical Laboratory Sciences, College of Health Sciences, Woldia University, Woldia, Ethiopia
| | - Chalachew Genet
- Department of Medical Laboratory Sciences, College of Medicine and Health Sciences, Bahir Dar University, Bahir Dar, Ethiopia
- Institute of Biotechnology, Bahir Dar University, Bahir Dar, Ethiopia
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Sznajder W, Jankowska-Polańska B, Tański W. A Narrative Review of Fungal Periprosthetic Joint Infections of the Hip and Knee: Risk Factors, Microbiological Profiles, and Treatment Challenges. J Clin Med 2025; 14:206. [PMID: 39797289 PMCID: PMC11721793 DOI: 10.3390/jcm14010206] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2024] [Revised: 12/23/2024] [Accepted: 12/28/2024] [Indexed: 01/13/2025] Open
Abstract
Fungal periprosthetic joint infections (PJIs) are rare but increasingly recognized complications following total joint arthroplasty (TJA). While Candida albicans remains the most common pathogen, non-albicans Candida species and other fungi, such as Aspergillus, have gained prominence. These infections often present with subtle clinical features and affect patients with significant comorbidities or immunosuppression. Compared to bacterial PJIs, fungal infections pose unique diagnostic and therapeutic challenges, including biofilm formation, limited antifungal susceptibility, and protracted treatment courses. This narrative review synthesizes current evidence from research articles and review/metanalysis papers, focusing on fungal PJIs. The literature search encompassed publications from 2015 to 2024, identifying key insights on epidemiology, risk factors, microbiological profiles, diagnostic methods, therapeutic strategies, and outcomes. Both classical references and recent studies addressing emerging diagnostic biomarkers and biofilm-active therapies were included. It was shown that C. albicans remains the primary fungal pathogen in PJIs but non-albicans Candida species and other fungi are associated with more complex clinical scenarios, higher recurrence rates, and reduced infection-free survival. Patients commonly exhibit multiple comorbidities, compromised immune status, and previous prosthetic revisions. Diagnosis is complicated by slow-growing organisms and nonspecific inflammatory markers, prompting interest in novel diagnostics such as alpha-defensin, calprotectin, and next-generation sequencing. Two-stage revision arthroplasty, supplemented by prolonged targeted antifungal therapy, is considered the gold standard for chronic infections, although outcomes remain inferior to bacterial PJIs. Emerging strategies, including antifungal-impregnated beads and biofilm-disrupting agents, may improve local infection control. In conclusion, fungal PJIs constitute a challenging clinical entity demanding tailored diagnostic and therapeutic approaches. Further research into standardized diagnostic criteria, optimized antifungal regimens, biomarker validation, and refined surgical strategies is essential. Multidisciplinary collaboration, enhanced patient optimization, and innovative biofilm-directed therapies hold promise for improving outcomes and reducing the burden of fungal PJIs.
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Affiliation(s)
- Wojciech Sznajder
- Department of Orthopedics and Traumatology, 4th Military Clinical Hospital, 50-981 Wroclaw, Poland
| | | | - Wojciech Tański
- Department of Internal Medicine, 4th Military Clinical Hospital, 50-981 Wroclaw, Poland;
- Faculty of Medicine, Wrocław University of Science and Technology, 50-376 Wroclaw, Poland
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Rachel R, Anuradha M, Leela K. Evaluating the Antifungal Potential of Cinnamaldehyde: A Study of its Efficacy against Candida Species. JOURNAL OF PURE AND APPLIED MICROBIOLOGY 2024; 18:2438-2445. [DOI: 10.22207/jpam.18.4.16] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2025] Open
Abstract
Candida species exist as commensals in nature, colonizing the mucous membranes, gastrointestinal tract, vagina as well as the skin and usually cause infections in immunocompromised patients. C. albicans are known to be the most prevalent Candida species associated with infections, while there has been a significant surge in the incidence of Non-Candida albicans Candida species (NCAC) recently. The recent occurrences of the antifungal resistance in Candida, especially in NCAC species are quite alarming which raises the need for a safe and efficient alternative antimycotic drug. This study analyses the efficacy of cinnamaldehyde against Candida species, which is known to cause the majority of the fungal infections in humans. Cinnamaldehyde is a natural antimicrobial compound derived from cinnamon and has demonstrated significant antimycotic properties. Antifungal susceptibility profiles of cinnamaldehyde against Candida species were studied by disc diffusion as well as by broth microdilution assays. The mean diameter of the inhibition zone (IZ) formed by direct contact and disc volatilization assays were 61.26 mM and 65.20 mM, respectively. Both the minimum inhibitory concentration (MIC) and the minimum fungicidal concentration (MFC) of cinnamaldehyde ranged from 16-256 mg/L with mean MIC of 60.61 mg/L and a mean MFC of 81.94 mg/L. Co-incubation of Candida cells with cinnamaldehyde resulted in the loss of viable cells within 4 hours of incubation. Cinnamaldehyde was found to exhibit both fungistatic and fungicidal properties, making it a potent natural alternative for conventional antifungal agents.
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11
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Subedi A, Upreti MK, Rana JC, Sapkota RP, Thapa Shrestha U. Vulvovaginal candidiasis, an increasing burden to women in the tropical regions attending Bharatpur Hospital, Chitwan. J Mycol Med 2024; 34:101509. [PMID: 39276531 DOI: 10.1016/j.mycmed.2024.101509] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2024] [Revised: 07/26/2024] [Accepted: 09/02/2024] [Indexed: 09/17/2024]
Abstract
Vulvovaginal candidiasis is a yeast infection commonly caused by the overgrowth of Candida species in and around the vulva and vagina. Abnormal vaginal discharge, itching and irritation, swelling and redness of the vaginal area, pain during sexual intercourse, and dyspareunia are important clinical findings of the infection. Currently, the infection is one of the growing burdens to married women. Moreover, the infection with antifungal-resistant Candida species adds challenges to managing the disease. Hence, this study was conducted to identify the different Candida species causing vulvovaginal candidiasis and to determine its susceptibility pattern against different antifungal drugs. A hospital-based cross-sectional and quantitative study was conducted for the period of six months from September 2022 to March 2023 among symptomatic married women in the Gynecology and Obstetrics Department of Bharatpur Hospital, Chitwan. A total of 300 symptomatic cases were enrolled in the study. Candida species were isolated from vaginal swabs following standard microbiological procedures and antifungal susceptibility testing was performed with different antifungal agents. The total prevalence of vulvovaginal candidiasis was found to be 37.3 % (112/300). Among different isolates, Candida albicans was found to be the most predominant (52.6 %), followed by Candida glabrata (29.3 %) among non-albicans. Women from the age group 25-35 years were found to be more infected (47.3 %) and the relationship between contraceptive use and vulvovaginal candidiasis was found to be statistically significant (p < 0.05). Candida species showed higher susceptibility toward Amphotericin-B (68.1 %), followed by fluconazole (Diflucan), and Clotrimazole (50.9 %). Whereas the least susceptibility was observed to Voriconazole (27.6 %) and Itraconazole (35.30 %). Candida albicans was comparatively more susceptible to different antifungal drugs than non-albicans species. Candida parapsilosis was only susceptible to Amphotericin-B and the increasing incidence of vaginal candidiasis due to non-albicans Candida indicates the need for routine speciation of Candida.
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Affiliation(s)
- Anisha Subedi
- Department of Microbiology, Goldengate International College, Battisputali, Kathmandu
| | - Milan Kumar Upreti
- Department of Microbiology, Goldengate International College, Battisputali, Kathmandu
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12
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Makled AF, Ali SAM, Labeeb AZ, Salman SS, Shebl DZM, Hegazy SG, Sabal MS. Characterization of Candida species isolated from clinical specimens: insights into virulence traits, antifungal resistance and molecular profiles. BMC Microbiol 2024; 24:388. [PMID: 39367309 PMCID: PMC11453005 DOI: 10.1186/s12866-024-03515-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2024] [Accepted: 09/11/2024] [Indexed: 10/06/2024] Open
Abstract
BACKGROUND Candida species have emerged as a significant cause of opportunistic infections. Alongside the expression of various virulence factors, the rise of antifungal resistance among Candida species presents a considerable clinical challenge. AIM This study aimed to identify different Candida species isolated from clinical specimens, evaluate their antifungal sensitivity patterns, identify key genes regulating virulence mechanisms using multiplex PCR and to assess any correlation between their virulence profiles and antifungal resistance patterns. METHOD A total of 100 Candida spp. was isolated from 630 different clinical specimens and identified to the species level. Their antifungal susceptibility was phenotypically evaluated in accordance with CLSI guidelines using the Vitek-2 Compact System. Virulence markers, including biofilm formation capacity, protease production, melanin production, coagulase production and hemolysin production, were also phenotypically detected. The genetic determinants for biofilm formation and extracellular hydrolytic enzymes were assessed using a multiplex PCR assay. RESULTS The prevalence of Candida spp. was 15.9%, with C. albicans (48%) and C. glabrata (16%) being the most common. C. albicans showed the highest virulence, with strong biofilm formation, and high proteinase and melanin production. Multiplex PCR revealed Hlp in 22.0%, Hwp in 80.0%, Als in 56.0%, and Sap genes in 56.0% of isolates. Virulence genes were more common in C. albicans than in non-albicans Candida (NAC). Resistance patterns significantly correlated with virulence profiles, with notable associations between flucytosine resistance and the presence of Hlp and Hwp genes. CONCLUSION The significant correlation between virulent markers such as germination, coagulase, hemolysin production and resistance patterns among different Candida isolates is crucial for predicting the severity and outcomes of Candida infections. This understanding aids in guiding tailored treatment strategies.
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Affiliation(s)
- Amal F Makled
- Department of Medical Microbiology and Immunology, Faculty of Medicine, Menoufia University, Shebin al Kom, Egypt
| | - Sahar A M Ali
- Department of Medical Microbiology and Immunology, Faculty of Medicine, Menoufia University, Shebin al Kom, Egypt
| | - Azza Z Labeeb
- Department of Medical Microbiology and Immunology, Faculty of Medicine, Menoufia University, Shebin al Kom, Egypt
| | - Samar S Salman
- Department of Clinical Pathology, Faculty of Medicine, Menoufia University, Shebin al Kom, Egypt
| | - Doaa Z M Shebl
- Department of Clinical Pharmacology, Faculty of Medicine, Menoufia University, Shebin al Kom, Egypt
| | - Sarah G Hegazy
- Department of Medical Microbiology and Immunology, Faculty of Medicine, Menoufia University, Shebin al Kom, Egypt.
| | - Mona S Sabal
- Department of Medical Microbiology and Immunology, Faculty of Medicine, Menoufia University, Shebin al Kom, Egypt
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Nguyen TA, Kim HY, Stocker S, Kidd S, Alastruey-Izquierdo A, Dao A, Harrison T, Wahyuningsih R, Rickerts V, Perfect J, Denning DW, Nucci M, Cassini A, Beardsley J, Gigante V, Sati H, Morrissey CO, Alffenaar JW. Pichia kudriavzevii (Candida krusei): A systematic review to inform the World Health Organisation priority list of fungal pathogens. Med Mycol 2024; 62:myad132. [PMID: 38935911 PMCID: PMC11210618 DOI: 10.1093/mmy/myad132] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2023] [Revised: 11/26/2023] [Accepted: 12/11/2023] [Indexed: 06/29/2024] Open
Abstract
In response to the growing global threat of fungal infections, in 2020 the World Health Organisation (WHO) established an Expert Group to identify priority fungi and develop the first WHO fungal priority pathogen list (FPPL). The aim of this systematic review was to evaluate the features and global impact of invasive infections caused by Pichia kudriavzevii (formerly known as Candida krusei). PubMed and Web of Science were used to identify studies published between 1 January 2011 and 18 February 2021 reporting on the criteria of mortality, morbidity (defined as hospitalisation and length of stay), drug resistance, preventability, yearly incidence, and distribution/emergence. Overall, 33 studies were evaluated. Mortality rates of up to 67% in adults were reported. Despite the intrinsic resistance of P. kudriavzevii to fluconazole with decreased susceptibility to amphotericin B, resistance (or non-wild-type rate) to other azoles and echinocandins was low, ranging between 0 and 5%. Risk factors for developing P. kudriavzevii infections included low birth weight, prior use of antibiotics/antifungals, and an underlying diagnosis of gastrointestinal disease or cancer. The incidence of infections caused by P. kudriavzevii is generally low (∼5% of all Candida-like blood isolates) and stable over the 10-year timeframe, although additional surveillance data are needed. Strategies targeting the identified risk factors for developing P. kudriavzevii infections should be developed and tested for effectiveness and feasibility of implementation. Studies presenting data on epidemiology and susceptibility of P. kudriavzevii were scarce, especially in low- and middle-income countries (LMICs). Thus, global surveillance systems are required to monitor the incidence, susceptibility, and morbidity of P. kudriavzevii invasive infections to inform diagnosis and treatment. Timely species-level identification and susceptibility testing should be conducted to reduce the high mortality and limit the spread of P. kudriavzevii in healthcare facilities.
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Affiliation(s)
- Thi Anh Nguyen
- Faculty of Medicine and Health, School of Pharmacy, The University of Sydney, Sydney, NSW, Australia
- Sydney Infectious Diseases Institute, The University of Sydney, Sydney, NSW, Australia
| | - Hannah Yejin Kim
- Faculty of Medicine and Health, School of Pharmacy, The University of Sydney, Sydney, NSW, Australia
- Sydney Infectious Diseases Institute, The University of Sydney, Sydney, NSW, Australia
- Department of Pharmacy, Westmead Hospital, Sydney, NSW, Australia
| | - Sophie Stocker
- Faculty of Medicine and Health, School of Pharmacy, The University of Sydney, Sydney, NSW, Australia
- Sydney Infectious Diseases Institute, The University of Sydney, Sydney, NSW, Australia
- Department of Clinical Pharmacology and Toxicology, St Vincent's Hospital, Sydney, NSW, Australia
| | - Sarah Kidd
- National Mycology Reference Centre, Microbiology and Infectious Diseases, SA Pathology, Adelaide, SA, Australia
| | - Ana Alastruey-Izquierdo
- Mycology Reference Laboratory, National Centre for Microbiology, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain
| | - Aiken Dao
- Sydney Infectious Diseases Institute, The University of Sydney, Sydney, NSW, Australia
- Westmead Institute for Medical Research, Sydney, NSW, Australia
| | - Thomas Harrison
- Institute of Infection and Immunity, St George's University London, London, UK
- MRC Centre for Medical Mycology, University of Exeter, Exeter, UK
| | - Retno Wahyuningsih
- Department of Parasitology, Faculty of Medicine, Universitas Kristen Indonesia, Jakarta, Indonesia
| | | | - John Perfect
- Division of Infectious Diseases and International Health, Duke University School of Medicine, Durham, NC, USA
| | - David W Denning
- Manchester Fungal Infection Group (MFIG), Manchester Academic Health Science Centre, The University of Manchester, Manchester, UK
| | - Marcio Nucci
- Department of Internal Medicine, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Alessandro Cassini
- Cantonal Doctor Office, Public Health Department, Canton of Vaud, Lausanne, Switzerland
| | - Justin Beardsley
- Sydney Infectious Diseases Institute, The University of Sydney, Sydney, NSW, Australia
- Westmead Institute for Medical Research, Sydney, NSW, Australia
| | - Valeria Gigante
- AMR Division, World Health Organisation, Geneva, Switzerland
| | - Hatim Sati
- AMR Division, World Health Organisation, Geneva, Switzerland
| | - C Orla Morrissey
- Department of Infectious Diseases, Alfred Health, Melbourne, VIC, Australia
- Department of Infectious Diseases, Central Clinical School, Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, VIC, Australia
| | - Jan-Willem Alffenaar
- Faculty of Medicine and Health, School of Pharmacy, The University of Sydney, Sydney, NSW, Australia
- Sydney Infectious Diseases Institute, The University of Sydney, Sydney, NSW, Australia
- Department of Pharmacy, Westmead Hospital, Sydney, NSW, Australia
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14
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Parambath S, Dao A, Kim HY, Zawahir S, Alastruey Izquierdo A, Tacconelli E, Govender N, Oladele R, Colombo A, Sorrell T, Ramon-Pardo P, Fusire T, Gigante V, Sati H, Morrissey CO, Alffenaar JW, Beardsley J. Candida albicans-A systematic review to inform the World Health Organization Fungal Priority Pathogens List. Med Mycol 2024; 62:myae045. [PMID: 38935906 PMCID: PMC11210619 DOI: 10.1093/mmy/myae045] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2023] [Revised: 10/20/2023] [Accepted: 04/27/2024] [Indexed: 06/29/2024] Open
Abstract
Candida albicans is a common fungal pathogen and amongst the leading causes of invasive candidiasis globally. This systematic review examines the characteristics and global impact of invasive infections caused by C. albicans. We searched on PubMed and Web of Science for studies reporting on criteria such as mortality, morbidity, drug resistance, preventability, yearly incidence, and distribution/emergence during the period from 2016 to 2021. Our findings indicate that C. albicans is the most common Candida species causing invasive disease and that standard infection control measures are the primary means of prevention. However, we found high rates of mortality associated with infections caused by C. albicans. Furthermore, there is a lack of data on complications and sequelae. Resistance to commonly used antifungals remains rare. Although, whilst generally susceptible to azoles, we found some evidence of increasing resistance, particularly in middle-income settings-notably, data from low-income settings were limited. Candida albicans remains susceptible to echinocandins, amphotericin B, and flucytosine. We observed evidence of a decreasing proportion of infections caused by C. albicans relative to other Candida species, although detailed epidemiological studies are needed to confirm this trend. More robust data on attributable mortality, complications, and sequelae are needed to understand the full extent of the impact of invasive C. albicans infections.
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Affiliation(s)
- Sarika Parambath
- Sydney Infectious Diseases Institute, The University of Sydney, Sydney, NSW, Australia
| | - Aiken Dao
- Sydney Infectious Diseases Institute, The University of Sydney, Sydney, NSW, Australia
- Westmead Institute for Medical Research, Westmead, NSW, Australia
- Westmead Hospital, Westmead, NSW, Australia
| | - Hannah Yejin Kim
- Sydney Infectious Diseases Institute, The University of Sydney, Sydney, NSW, Australia
- Faculty of Medicine and Health, School of Pharmacy, The University of Sydney, Sydney, NSW, Australia
- Westmead Hospital, Department of Pharmacy, Westmead, NSW, Australia
| | - Shukry Zawahir
- Sydney Infectious Diseases Institute, The University of Sydney, Sydney, NSW, Australia
- Central Clinical School, The University of Sydney Faculty of Medicine and Health, Sydney NSW, Australia
| | - Ana Alastruey Izquierdo
- Mycology Reference Laboratory, National Centre for Microbiology, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain
| | - Evelina Tacconelli
- Department of Diagnostics and Public Health, Verona University, Verona, Italy
| | - Nelesh Govender
- National Institute for Communicable Diseases, Division of the National Health Laboratory Service, Johannesburg, South Africa
- Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
- Institute of Infection and Immunity, St George's University of London, London, UK
- MRC Centre for Medical Mycology, University of Exeter, Exeter, UK
| | - Rita Oladele
- Department of Medical Microbiology and Parasitology, College of Medicine, University of Lagos, Lagos, Nigeria
| | | | - Tania Sorrell
- Sydney Infectious Diseases Institute, The University of Sydney, Sydney, NSW, Australia
- Westmead Institute for Medical Research, Westmead, NSW, Australia
- Westmead Hospital, Westmead, NSW, Australia
| | - Pilar Ramon-Pardo
- Antimicrobial Research Division, World Health Organization, Geneva, Switzerland
| | - Terence Fusire
- Antimicrobial Research Division, World Health Organization, Geneva, Switzerland
| | - Valeria Gigante
- Antimicrobial Research Division, World Health Organization, Geneva, Switzerland
| | - Hatim Sati
- Antimicrobial Research Division, World Health Organization, Geneva, Switzerland
| | - C Orla Morrissey
- Department of Infectious Diseases, Alfred Health, VIC, Australia
- Monash University, Department of Infectious Diseases, Melbourne, VIC, Australia
| | - Jan-Willem Alffenaar
- Sydney Infectious Diseases Institute, The University of Sydney, Sydney, NSW, Australia
- Westmead Hospital, Westmead, NSW, Australia
- Faculty of Medicine and Health, School of Pharmacy, The University of Sydney, Sydney, NSW, Australia
| | - Justin Beardsley
- Sydney Infectious Diseases Institute, The University of Sydney, Sydney, NSW, Australia
- Westmead Institute for Medical Research, Westmead, NSW, Australia
- Westmead Hospital, Westmead, NSW, Australia
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15
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Shelke YP, Tidake AA, Ugemuge S, Nakate P, Patil S, Lambhore S, Bankar NJ, Bandre GR. Identification of Yeast and Yeast-Like Fungi at a Tertiary Care Center: A Retrospective Study. Cureus 2024; 16:e62680. [PMID: 39036264 PMCID: PMC11258929 DOI: 10.7759/cureus.62680] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2024] [Accepted: 06/19/2024] [Indexed: 07/23/2024] Open
Abstract
Background Fungal infections pose a significant global health challenge. Despite their substantial impact, these ubiquitous fungi can become pathogenic but have not received adequate attention in public health, leading to infections that are often underestimated by the general public and healthcare professionals. Candida species and Cryptococcus species play a key role in these infections, with emerging multidrug resistance in Candida species posing considerable challenges. This study aimed to understand the prevalence of yeast and yeast-like infections, particularly in the COVID-19 era, and to assess the antifungal susceptibility pattern. Methodology A retrospective observational study was conducted at a rural tertiary care medical college in Maharashtra, India. Retrospective records of samples processed for fungal culture were analyzed in the microbiology department. Yeast identification and antifungal susceptibility were performed using the VITEK-2 automated system. Results Among 95 fungal isolates, 86 (90.52%) were yeast isolates, primarily non-albicans Candida (NAC) species. Candida albicans accounted for 41 (47.67%) yeast isolates. In 14 isolates, NAC species were not identified by the VITEK-2 system up to the species level. Isolates from urine samples contributed the highest percentage of 61% (58) of yeast isolates. C. albicans showed high sensitivity to most antifungal agents. Other Candida species, such as Candida famata, Candida parapsilosis, and Candida guilliermondii, were sensitive to all antifungal agents. Candida auris showed complete resistance to amphotericin B and fluconazole but sensitivity to other agents. Mixed sensitivity patterns were observed in Candida ciferri and Candida lusitaniae, with some resistance to voriconazole, caspofungin, and micafungin. Conclusions This study shows the increasing prevalence of yeast and yeast-like infections, particularly NAC, during the COVID-19 era. Improved yeast identification and susceptibility testing are crucial for guiding the appropriate treatment and mitigating the impact of these infections, emphasizing the need for comprehensive future studies in this area.
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Affiliation(s)
- Yogendra P Shelke
- Microbiology, Bhaktshreshtha Kamalakarpant Laxmanrao Walawalkar Rural Medical College, Chiplun, IND
| | - Ashwini A Tidake
- Microbiology, Datta Meghe Medical College, Datta Meghe Institute of Higher Education and Research, Wardha, IND
| | - Sarita Ugemuge
- Microbiology, Datta Meghe Medical College, Datta Meghe Institute of Higher Education and Research, Wardha, IND
| | - Prasanna Nakate
- Microbiology, Bhaktshreshtha Kamalakarpant Laxmanrao Walawalkar Rural Medical College, Chiplun, IND
| | - Suvarna Patil
- Microbiology, Bhaktshreshtha Kamalakarpant Laxmanrao Walawalkar Rural Medical College, Chiplun, IND
| | - Shailesh Lambhore
- Microbiology, Shri Vithalrao Joshi Charities Trust's College of Advanced Studies, Chiplun, IND
| | - Nandkishor J Bankar
- Microbiology, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Wardha, IND
| | - Gulshan R Bandre
- Microbiology, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Wardha, IND
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Novais MHG, Farias NS, Dos Santos AG, Fonseca VJA, Ribeiro-Filho J, De Menezes IRA, Coutinho HDM, Morais-Braga MFB. Pharmacological potential of limonene against opportunistic fungi: Impact on Candida virulence. Acta Trop 2024; 253:107168. [PMID: 38432404 DOI: 10.1016/j.actatropica.2024.107168] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2024] [Revised: 02/26/2024] [Accepted: 02/29/2024] [Indexed: 03/05/2024]
Abstract
The present article aims to evaluate the antifungal and antivirulence effect of the phytoconstituent Limonene against Candida spp. Antifungal assays were performed, where the concentration capable of inhibiting 50 % of fungal growth, the growth inhibition curve, the minimum fungicidal concentration, the evaluation of the modifying effect with fluconazole, the inhibitory effect of the substances on the morphological transition of Candida spp. and the statistical analysis of the results were determined. With this study, it was seen that limonene demonstrated growth inhibition for the strains tested and when associated the natural compound with Fluconazole, there was potentiation of the effect of the drug, since the inhibition of growth by the combination occurred at lower concentrations against all strains tested, when compared to the drug alone, which inhibited growth at the highest concentration. In the test to determine the Minimum Fungicidal Concentration of the products tested alone and in combination, it was found that in the case of Candida strains, growth inhibition by limonene occurred at a concentration of 1024 μg/mL. For Fluconazole, growth impairment ranged from > 1024 μg/mL to 256 μg/mL for the strains. And when combined, limonene potentiated the action of FCZ, making fungal colonization unfeasible at concentrations below 1024 μg/mL. Regarding the morphological transition from yeast to hyphae, limonene was used at concentrations of 1024 μg/mL and 512 μg/mL, and it was found that, for CA and CK, the filaments were reduced in number and size at the highest concentration and against CT, the morphological transition from yeast to hyphae/pseudohyphae was totally inhibited, and if compared to the growth control, limonene was able to reduce fungal growth at concentrations greater than 512 μg/mL. This compound has antimicrobial activity described, due to its ability to interfere in the gene expression of the fungus, the limited therapeutic options and the recent emergence of multidrug-resistant Candida species represent a significant challenge for human medicine and highlight the need for new therapeutic approaches, and in this study a great potential of limonene was revealed in relation to the perspective of increasing the efficiency of commercial drug. This work can bring an important contribution to the scientific database, while emphasizing that in-depth studies and tests on the subject, in order to better investigate its effectiveness and mechanisms by which they exert their effects, are still necessary.
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Ahmady L, Gothwal M, Mukkoli MM, Bari VK. Antifungal drug resistance in Candida: a special emphasis on amphotericin B. APMIS 2024; 132:291-316. [PMID: 38465406 DOI: 10.1111/apm.13389] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2023] [Accepted: 02/12/2024] [Indexed: 03/12/2024]
Abstract
Invasive fungal infections in humans caused by several Candida species, increased considerably in immunocompromised or critically ill patients, resulting in substantial morbidity and mortality. Candida albicans is the most prevalent species, although the frequency of these organisms varies greatly according to geographic region. Infections with C. albicans and non-albicans Candida species have become more common, especially in the past 20 years, as a result of aging, immunosuppressive medication use, endocrine disorders, malnourishment, extended use of medical equipment, and an increase in immunogenic diseases. Despite C. albicans being the species most frequently associated with human infections, C. glabrata, C. parapsilosis, C. tropicalis, and C. krusei also have been identified. Several antifungal drugs with different modes of action are approved for use in clinical settings to treat fungal infections. However, due to the common eukaryotic structure of humans and fungi, only a limited number of antifungal drugs are available for therapeutic use. Furthermore, drug resistance in Candida species has emerged as a result of the growing use of currently available antifungal drugs against fungal infections. Amphotericin B (AmB), a polyene class of antifungal drugs, is mainly used for the treatment of serious systemic fungal infections. AmB interacts with fungal plasma membrane ergosterol, triggering cellular ion leakage via pore formation, or extracting the ergosterol from the plasma membrane inducing cellular death. AmB resistance is primarily caused by changes in the content or structure of ergosterol. This review summarizes the antifungal drug resistance exhibited by Candida species, with a special focus on AmB.
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Affiliation(s)
- Lailema Ahmady
- Department of Biochemistry, School of Basic Sciences, Central University of Punjab, Bathinda, India
| | - Manisha Gothwal
- Department of Biochemistry, School of Basic Sciences, Central University of Punjab, Bathinda, India
| | | | - Vinay Kumar Bari
- Department of Biochemistry, School of Basic Sciences, Central University of Punjab, Bathinda, India
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18
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Acosta-Mosquera Y, Tapia JC, Armas-González R, Cáceres-Valdiviezo MJ, Fernández-Cadena JC, Andrade-Molina D. Prevalence and Species Distribution of Candida Clinical Isolates in a Tertiary Care Hospital in Ecuador Tested from January 2019 to February 2020. J Fungi (Basel) 2024; 10:304. [PMID: 38786659 PMCID: PMC11122525 DOI: 10.3390/jof10050304] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2024] [Revised: 04/03/2024] [Accepted: 04/09/2024] [Indexed: 05/25/2024] Open
Abstract
The incidence of candidemia in healthcare centers is associated with high morbidity and mortality. Frequency varies significantly among regions, with some species being more prevalent than others in Latin America. In this study, 191 clinical Candida isolates were collected from a major hospital in Ecuador from January 2019 to February 2020 aiming to assess their prevalence and distribution. After data processing, 168 isolates characterized by the VITEK 2 system were subsequently identified by ITS sequencing. Results showed diverse Candida species distributions, with C. albicans and C. tropicalis being the most prevalent across different clinical sources. In hospitalized individuals, C. tropicalis (38%) and C. albicans (37%) were the most prevalent, followed by, C. parapsilosis (16%), C. glabrata (5%), and other non-Candida albicans (NCA) species (6%). Conversely, C. parapsilosis (48%), C. albicans (20%), and C. glabrata (14%), associated with candidemia, were the most common in blood and CSF. Additionally, uncommon NCA species such as C. haemulonii, C. kefyr, and C. pelliculosa were identified in Ecuador for the first time. Discrepancies in species identification were observed between the VITEK 2 system and ITS sequencing, coinciding at 85%. This highlights the need for ongoing surveillance and identification efforts in Ecuador's clinical and epidemiological settings.
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Affiliation(s)
| | - Juan Carlos Tapia
- Omics Science Laboratory, Faculty of Health Science, Universidad Espíritu Santo, Samborondon 092301, Ecuador; (J.C.T.); (M.J.C.-V.)
| | - Rubén Armas-González
- Instituto Interamericano de Cooperación para la Agricultura (IICA), Representación Ecuador-Proyecto-5CN-1RBT, Quito 170518, Ecuador;
- Faculty of Health Science, Universidad Espíritu Santo, Samborondon 092301, Ecuador
| | - María José Cáceres-Valdiviezo
- Omics Science Laboratory, Faculty of Health Science, Universidad Espíritu Santo, Samborondon 092301, Ecuador; (J.C.T.); (M.J.C.-V.)
| | - Juan Carlos Fernández-Cadena
- African Genome Center, University Mohammed VI Polytechnic (UM6P), Lot 660, Hay Moulay Rachid, Ben Guerir 43150, Morocco
| | - Derly Andrade-Molina
- Omics Science Laboratory, Faculty of Health Science, Universidad Espíritu Santo, Samborondon 092301, Ecuador; (J.C.T.); (M.J.C.-V.)
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Park J, Kim H, Kang DD, Park Y. Exploring the Therapeutic Potential of Scorpion-Derived Css54 Peptide Against Candida albicans. J Microbiol 2024; 62:101-112. [PMID: 38589765 PMCID: PMC11021323 DOI: 10.1007/s12275-024-00113-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2023] [Revised: 01/23/2024] [Accepted: 01/23/2024] [Indexed: 04/10/2024]
Abstract
Candida albicans (C. albicans) is one of the most common opportunistic fungi worldwide, which is associated with a high mortality rate. Despite treatment, C. albicans remains the leading cause of life-threatening invasive infections. Consequently, antimicrobial peptides (AMPs) are potential alternatives as antifungal agents with excellent antifungal activity. We previously reported that Css54, found in the venom of Centrurodies suffusus suffusus (C. s. suffusus) showed antibacterial activity against zoonotic bacteria. However, the antifungal activity of Css54 has not yet been elucidated. The objective of this study was to identify the antifungal activity of Css54 against C. albicans and analyze its mechanism. Css54 showed high antifungal activity against C. albicans. Css54 also inhibited biofilm formation in fluconazole-resistant fungi. The antifungal mechanism of action of Css54 was investigated using membrane-related assays, including the membrane depolarization assay and analysis of the membrane integrity of C. albicans after treatment with Css54. Css54 induced reactive oxygen species (ROS) production in C. albicans, which affected its antifungal activity. Our results indicate that Css54 causes membrane damage in C. albicans, highlighting its value as a potential therapeutic agent against C. albicans infection.
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Affiliation(s)
- Jonggwan Park
- Department of Bioinformatics, Kongju National University, Kongju, 32588, Republic of Korea
| | - Hyeongsun Kim
- Department of Biomedical Science, Chosun University, Gwangju, 61452, Republic of Korea
| | - Da Dam Kang
- Department of Biomedical Science, Chosun University, Gwangju, 61452, Republic of Korea
| | - Yoonkyung Park
- Department of Biomedical Science, Chosun University, Gwangju, 61452, Republic of Korea.
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20
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Benson M, Turyamuhika L, Mwesigwa A, Nalumaga PP, Kabajulizi I, Njovu IK, Mwebesa E, Luggya T, Ocheng F, Kateete DP, Itabangi H, Mboowa G, Sande OJ, Achan B. Distribution and antifungal susceptibility profile of oropharyngeal Candida species isolated from people living with HIV in the era of universal test and treat policy in Uganda. Ther Adv Infect Dis 2024; 11:20499361241255261. [PMID: 38812710 PMCID: PMC11135083 DOI: 10.1177/20499361241255261] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2023] [Accepted: 04/30/2024] [Indexed: 05/31/2024] Open
Abstract
Background Despite the increased frequency of oropharyngeal candidiasis among people living with human immunodeficiency virus (HIV), its management is no longer effective due to empirical treatment and emergence of antifungal resistance (AFR). This study sought to investigate the prevalence of oropharyngeal candidiasis and assess the antifungal susceptibility profile of oropharyngeal Candida species isolated from people living with human immunodeficiency virus. Additionally, we evaluated the correlation between oropharyngeal candidiasis and CD4 T cell as well as viral load counts. Methods A descriptive cross-sectional study was carried out from April to October 2023 in which 384 people living with HIV underwent clinical examination for oral lesions. Oropharyngeal swabs were collected and cultured on Sabouraud Dextrose agar to isolate Candida species which were identified using the matrix assisted laser desorption ionization time of flight mass spectrometry. Additionally, the antifungal susceptibility profile of Candida isolates to six antifungal drugs was determined using VITEK® (Marcy-l'Étoile, France) compact system. Data on viral load were retrieved from records, and CD4 T cell count test was performed using Becton Dickinson Biosciences fluorescent antibody cell sorter presto. Results The prevalence of oropharyngeal candidiasis was 7.6%. Oropharyngeal candidiasis was significantly associated with low CD4 T cell count and high viral load. A total of 35 isolates were obtained out of which Candida albicans comprised of 20 (57.1%) while C. tropicalis and C. glabrata comprised 4 (11.4%) each. C. parapsilosis, C. dubliniensis and C. krusei accounted for 2 (5.7%) each. Additionally, 7 (20%) isolates were resistant to fluconazole, 1 (2.9%) to flucytocine and 0.2 (5.7%) isolates were intermediate to caspofungin. However, specific specie isolates like C. albicans showed 20% (4/20), C. glabrata 50% (2/4) and C. krusei 50% (1/2) resistance to fluconazole. Additionally, C. krusei showed 50% resistance to flucytosine. Conclusion The prevalence of oropharyngeal candidiasis (OPC) among people living with HIV was low, and there was a significant association between OPC and CD4 T cell count as well as viral load. C. albicans was the most frequently isolated oropharyngeal Candida species. C. glabrata and C. krusei exhibited the highest AFR among the non-albicans Candida species. The highest resistance was demonstrated to fluconazole.
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Affiliation(s)
- Musinguzi Benson
- Department of Immunology and Molecular Biology, School of Biomedical Sciences, College of Health Sciences, Makerere University, Kampala, Uganda
- Department of Medical Laboratory Sciences, Faculty of Health Sciences, Muni University, Arua, Uganda
| | - Laban Turyamuhika
- Department of Immunology and Molecular Biology, School of Biomedical Sciences, College of Health Sciences, Makerere University, Kampala, Uganda
| | - Alex Mwesigwa
- Department of Microbiology and Immunology, School of Medicine, Kabale University Kabale, Uganda
| | - Pauline Petra Nalumaga
- Mycology Unit, Department of Microbiology, Faculty of Medicine, Mbarara University of Science and Technology, Mbarara, Uganda
| | - Immaculate Kabajulizi
- Mycology Unit, Department of Microbiology, Faculty of Medicine, Mbarara University of Science and Technology, Mbarara, Uganda
| | - Israel Kiiza Njovu
- Mycology Unit, Department of Microbiology, Faculty of Medicine, Mbarara University of Science and Technology, Mbarara, Uganda
| | - Edson Mwebesa
- Department of Mathematics, Faculty of Science, Muni University, Arua, Uganda
| | - Tonny Luggya
- Department of Immunology and Molecular Biology, School of Biomedical Sciences, College of Health Sciences, Makerere University, Kampala, Uganda
| | - Francis Ocheng
- Department of Dentistry, School of Health Sciences, College of Health Sciences, Makerere University, Kampala, Uganda
| | - David Patrick Kateete
- Department of Immunology and Molecular Biology, School of Biomedical Sciences, College of Health Sciences, Makerere University, Kampala, Uganda
| | - Herbert Itabangi
- Department of Microbiology and Immunology, Faculty of Health Sciences, Busitema University, Mbale, Uganda
| | - Gerald Mboowa
- Department of Immunology and Molecular Biology, School of Biomedical Sciences, College of Health Sciences, Makerere University, Kampala, Uganda
- African Centre of Excellence in Bioinformatics and Data Intensive Sciences, The Infectious Diseases Institute, College of Health Sciences, Makerere University, Kampala, Uganda
| | - Obondo James Sande
- Department of Immunology and Molecular Biology, School of Biomedical Sciences, College of Health Sciences, Makerere University, Kampala, Uganda
| | - Beatrice Achan
- Department of Medical Microbiology, School of Biomedical Sciences, College of Health Sciences, Makerere University, P.O. Box 7072, Kampala, Uganda
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21
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Ordaya EE, Clement J, Vergidis P. The Role of Novel Antifungals in the Management of Candidiasis: A Clinical Perspective. Mycopathologia 2023; 188:937-948. [PMID: 37470902 PMCID: PMC10687117 DOI: 10.1007/s11046-023-00759-5] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2023] [Accepted: 05/31/2023] [Indexed: 07/21/2023]
Abstract
Mucosal and invasive candidiasis can be challenging to treat in the setting of drug intolerance, antifungal resistance, drug-drug interactions, or host immune status. Antifungals with novel mechanisms of action and distinct pharmacokinetic/pharmacodynamic properties have been developed in recent years. Rezafungin is an echinocandin with high-tissue penetration and an extended half-life that allows for once-weekly administration, making it a convenient treatment option for invasive candidiasis while obviating the need for central catheter placement. Ibrexafungerp is an oral glucan synthase inhibitor that is active against most echinocandin-resistant Candida species. At present, it is approved for the treatment of acute vulvovaginal candidiasis and is under investigation as an oral step-down therapy following initial treatment with an echinocandin for cases of invasive candidiasis. Oteseconazole is a long-acting tetrazole that exhibits a higher affinity for the fungal enzyme CYP51, resulting in a potentially lower risk of drug-drug interactions and side effects compared to other azoles. It is currently approved for the treatment of recurrent vulvovaginal candidiasis. Fosmanogepix has a novel mechanism of action and potent activity against several Candida strains resistant to other antifungals. Due to its considerable bioavailability and tissue penetration, it holds promise as a potential treatment option in patients with invasive candidiasis, including those with chorioretinitis or meningitis. Results from clinical trials and observational studies will further delineate the role of these agents in the management of candidiasis. As the usage of these novel antifungals becomes widespread, we expect to acquire a greater understanding of their efficacy and potential benefits.
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Affiliation(s)
- Eloy E Ordaya
- Division of Public Health, Infectious Disease, and Occupational Medicine, Mayo Clinic, 200 First St SW, Rochester, MN, 55905, USA.
| | - Josh Clement
- Department of Pharmacy, Mayo Clinic, Rochester, MN, USA
| | - Paschalis Vergidis
- Division of Public Health, Infectious Disease, and Occupational Medicine, Mayo Clinic, 200 First St SW, Rochester, MN, 55905, USA
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22
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Fakhim H, Vaezi A, Morovati H, Bandegani A, Abbasi K, Emami S, Nasiry D, Hashemi SM, Ahangarkani F, Badali H. In-vivo efficiency of the novel azole compounds (ATTAF-1 and ATTAF-2) against systemic candidiasis in a murine model. J Mycol Med 2023; 33:101437. [PMID: 37804566 DOI: 10.1016/j.mycmed.2023.101437] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2023] [Revised: 09/25/2023] [Accepted: 09/28/2023] [Indexed: 10/09/2023]
Abstract
BACKGROUND Antifungal resistance is the main health concern in the control of invasive fungal infections. This research was designed to further assess the antifungal activity of aryl-1,2,4-triazole-3-ylthio analogs of fluconazole (ATTAFs) against Candida albicans systemic candidiasis in the murine model. MATERIALS & METHODS The murine model of systemic candidiasis was designed via the inoculation of 1 × 106 CFU of Candida albicans. The treatment dosages of 3.5 and 35 mg/kg per day were selected for ATTAFs and fluconazole, respectively. The median survival time (MST) was assayed for 30 days post-infection. The quantitative and qualitative (via histopathology staining) fungal burden was also assessed. Furthermore, immunohistochemistry and biochemistry assays were performed to monitor anti-inflammatory activity using the Cyclooxygenase-2 (Cox-2) marker and changes in serum protein levels. RESULTS ATTAFs considerably improved the survival of the murine model (P < 0.003). Compared with fluconazole, the antifungal activity of ATTAFs and their MST showed no difference (P > 0.05). However, these compounds decreased the fungal burden in the kidneys, spleen, and liver. CONCLUSION Our research indicates that ATTAF-1 and ATTAF-2 are effective therapeutic agents due to their fungal clearing and increasing the MST in the murine model of systemic candidiasis. Although we concluded that these components are novel and promising candidates for the management of invasive candidiasis, further studies are warranted to correlate these findings with clinical outcomes.
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Affiliation(s)
- Hamed Fakhim
- Infectious Diseases and Tropical Medicine Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Afsane Vaezi
- Department of Medical Laboratory Sciences, School of Allied Medical Sciences, Iran University of Medical Sciences, Tehran, Iran
| | - Hamid Morovati
- Department of Parasitology and Mycology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Azadeh Bandegani
- Department of Medical Mycology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
| | - Kiana Abbasi
- Department of Microbiology, Zanjan Branch, Islamic Azad University, Zanjan, Iran
| | - Saeed Emami
- Department of Medicinal Chemistry and Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran
| | - Davood Nasiry
- Amol Faculty of Paramedicine, Mazandaran University of Medical Sciences, Sari, Iran
| | - Seyedeh Mahdieh Hashemi
- Department of Medicinal Chemistry and Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran
| | - Fatemeh Ahangarkani
- Antimicrobial Resistance Research Center, Communicable Diseases Institute, Mazandaran University of Medical Sciences, Sari, Iran
| | - Hamid Badali
- Department of Molecular Microbiology & Immunology, South Texas Center for Emerging Infectious Diseases, The University of Texas at San Antonio, San Antonio, Texas, USA.
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23
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da Silva CR, Silveira MJCB, Soares GC, de Andrade CR, Cabral VPDF, Sá LGDAV, Rodrigues DS, Moreira LEA, Barbosa AD, da Silva LJ, da Silva AR, Gomes AOCV, Cavalcanti BC, de Moraes MO, Nobre Júnior HV, de Andrade Neto JB. Analysis of possible pathways on the mechanism of action of minocycline and doxycycline against strains of Candida spp. resistant to fluconazole. J Med Microbiol 2023; 72. [PMID: 37801011 DOI: 10.1099/jmm.0.001759] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/07/2023] Open
Abstract
Species of the genus Candida, characterized as commensals of the human microbiota, are opportunistic pathogens capable of generating various types of infections with high associated costs. Considering the limited pharmacological arsenal and the emergence of antifungal-resistant strains, the repositioning of drugs is a strategy used to search for new therapeutic alternatives, in which minocycline and doxycycline have been evaluated as potential candidates. Thus, the objective was to evaluate the in vitro antifungal activity of two tetracyclines, minocycline and doxycycline, and their possible mechanism of action against fluconazole-resistant strains of Candida spp. The sensitivity test for antimicrobials was performed using the broth microdilution technique, and the pharmacological interaction with fluconazole was also analysed using the checkerboard method. To analyse the possible mechanisms of action, flow cytometry assays were performed. The minimum inhibitory concentration obtained was 4-427 µg ml-1 for minocycline and 128-512 µg ml-1 for doxycycline, and mostly indifferent and additive interactions with fluconazole were observed. These tetracyclines were found to promote cellular alterations that generated death by apoptosis, with concentration-dependent reactive oxygen species production and reduced cell viability. Therefore, minocycline and doxycycline present themselves as promising study molecules against Candida spp.
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Affiliation(s)
- Cecília Rocha da Silva
- School of Pharmacy, Laboratory of Bioprospection of Antimicrobial Molecules (LABIMAN), Federal University of Ceará, Fortaleza, CE, Brazil
- Drug Research & Development Center, Federal University of Ceará, Fortaleza, CE, Brazil
| | - Maria Janielly Castelo Branco Silveira
- School of Pharmacy, Laboratory of Bioprospection of Antimicrobial Molecules (LABIMAN), Federal University of Ceará, Fortaleza, CE, Brazil
- Drug Research & Development Center, Federal University of Ceará, Fortaleza, CE, Brazil
- Christus University Center (UNICHRISTUS), Fortaleza, CE, Brazil
| | | | | | - Vitória Pessoa de Farias Cabral
- School of Pharmacy, Laboratory of Bioprospection of Antimicrobial Molecules (LABIMAN), Federal University of Ceará, Fortaleza, CE, Brazil
- Drug Research & Development Center, Federal University of Ceará, Fortaleza, CE, Brazil
| | - Lívia Gurgel do Amaral Valente Sá
- School of Pharmacy, Laboratory of Bioprospection of Antimicrobial Molecules (LABIMAN), Federal University of Ceará, Fortaleza, CE, Brazil
- Drug Research & Development Center, Federal University of Ceará, Fortaleza, CE, Brazil
- Christus University Center (UNICHRISTUS), Fortaleza, CE, Brazil
| | - Daniel Sampaio Rodrigues
- School of Pharmacy, Laboratory of Bioprospection of Antimicrobial Molecules (LABIMAN), Federal University of Ceará, Fortaleza, CE, Brazil
- Drug Research & Development Center, Federal University of Ceará, Fortaleza, CE, Brazil
| | - Lara Elloyse Almeida Moreira
- School of Pharmacy, Laboratory of Bioprospection of Antimicrobial Molecules (LABIMAN), Federal University of Ceará, Fortaleza, CE, Brazil
- Drug Research & Development Center, Federal University of Ceará, Fortaleza, CE, Brazil
| | - Amanda Dias Barbosa
- School of Pharmacy, Laboratory of Bioprospection of Antimicrobial Molecules (LABIMAN), Federal University of Ceará, Fortaleza, CE, Brazil
- Drug Research & Development Center, Federal University of Ceará, Fortaleza, CE, Brazil
| | - Lisandra Juvêncio da Silva
- School of Pharmacy, Laboratory of Bioprospection of Antimicrobial Molecules (LABIMAN), Federal University of Ceará, Fortaleza, CE, Brazil
- Drug Research & Development Center, Federal University of Ceará, Fortaleza, CE, Brazil
| | | | | | | | | | - Hélio Vitoriano Nobre Júnior
- School of Pharmacy, Laboratory of Bioprospection of Antimicrobial Molecules (LABIMAN), Federal University of Ceará, Fortaleza, CE, Brazil
- Drug Research & Development Center, Federal University of Ceará, Fortaleza, CE, Brazil
| | - João Batista de Andrade Neto
- School of Pharmacy, Laboratory of Bioprospection of Antimicrobial Molecules (LABIMAN), Federal University of Ceará, Fortaleza, CE, Brazil
- Drug Research & Development Center, Federal University of Ceará, Fortaleza, CE, Brazil
- Christus University Center (UNICHRISTUS), Fortaleza, CE, Brazil
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24
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Xiao G, Liu Y, Chen Y, He Z, Wen Y, Hu M. The Development and Validation of a Predictive Model for Voriconazole-Related Liver Injury in Hospitalized Patients in China. J Clin Med 2023; 12:4254. [PMID: 37445289 DOI: 10.3390/jcm12134254] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2023] [Revised: 06/13/2023] [Accepted: 06/20/2023] [Indexed: 07/15/2023] Open
Abstract
Voriconazole is widely used in the treatment and prevention of invasive fungal diseases. Common drug-induced liver injuries increase the economic burdens and the risks of premature drug withdrawal and disease recurrence. This study estimated the disposal cost of voriconazole-related liver injury, explored the risk factors of voriconazole-related liver injury in hospitalized patients, and established a predictive model of liver injury to assist clinicians and pharmacists in estimating the probability or risk of liver injury after voriconazole administration to allow for early identification and intervention in patients at high risk of liver injury. A retrospective study was conducted on the selected inpatients whose blood concentration of voriconazole was measured in the West China Hospital of Sichuan University from September 2016 to June 2020. The incidence and disposal cost of voriconazole-related liver injuries were calculated. The incidence of voriconazole-related liver injury was 15.82% (217/1372). The disposal cost has been converted to 2023 at a discount rate of 5%. The median (P25, P75) disposal cost of severe liver injury (n = 42), general liver injury (n = 175), and non-liver injury (n = 1155) was 993.59 (361.70, 1451.76) Chinese yuan, 0.00 (0.00, 410.48) yuan, and 0.00 (0.00, 0.00) yuan, respectively, with a statistically significant difference (p < 0.001). Single factor analysis and multiple factor logistic regression were used to analyze the risk factors of voriconazole-related liver injury. The voriconazole-related liver injury was related to the trough concentration (Cmin, OR 1.099, 95% CI 1.058-1.140), hypoproteinemia (OR 1.723, 95% CI 1.126-2.636), and transplantation status (OR 0.555, 95% CI 0.325-0.948). The prediction model of liver injury was Logit (P)= -2.219 + 0.094 × Cmin + 0.544 × Hydroproteinemia - 0.589 × Transplantation, and the prediction model nomogram was established. The model validation results showed that the C-index of the derivation set and validation set was 0.706 and 0.733, respectively. The area under the curve (AUC) of the receiver operating characteristic (ROC) curve was 0.705 and 0.733, respectively, indicating that the model had good prediction ability. The prediction model will be helpful to develop clinical individualized medication of voriconazole and to identify and intervene in the cases of patients at high risk of voriconazole-related liver injury early on, in order to reduce the incidence of voriconazole-related liver injuries and the cost of treatment.
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Affiliation(s)
- Guirong Xiao
- Department of Pharmacy, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Yiyao Liu
- West China School of Pharmacy, Sichuan University, Chengdu 610041, China
- West China Biomedical Big Data Center, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Yanhua Chen
- Department of Pharmacy, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, China
| | - Zhiyao He
- Department of Pharmacy, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Yan Wen
- Department of Pharmacy, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Ming Hu
- West China School of Pharmacy, Sichuan University, Chengdu 610041, China
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Husni R, Bou Zerdan M, Samaha N, Helou M, Mahfouz Y, Saniour R, Hourani S, Kolanjian H, Afif C, Azar E, El Jisr T, Mokhbat J, Abboud E, Feghali R, Abboud E, Matta H, Karayakouboglo G, Matar M, Moghnieh R, Daoud Z. Characterization and susceptibility of non-albicans Candida isolated from various clinical specimens in Lebanese hospitals. Front Public Health 2023; 11:1115055. [PMID: 36969669 PMCID: PMC10036786 DOI: 10.3389/fpubh.2023.1115055] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2022] [Accepted: 02/21/2023] [Indexed: 03/12/2023] Open
Abstract
BACKGROUND Invasive fungal infections have presented a challenge in treatment. In the past, it was known that the frontrunner in such infections is Candida albicans with little emphasis placed on non-albicans Candida species (NAC). Studies worldwide have shown a rise in fungal infections attributed to non-albicans Candida species. The aim of this study is to describe the epidemiology of NAC infections along with an overview of resistance in Lebanese hospitals. METHODS This is a two-year observational multi-central descriptive study. Between September 2016 and May of 2018, a total of 1000 isolates were collected from 10 different hospitals distributed all over the country. For the culture, Sabouraud Dextrose Agar was used. Antifungal Susceptibility was evaluated by determining the Minimum Inhibitory Concentration (MIC) in broth (microdilution) of the different antifungal treatments. RESULTS Out of the 1000 collected isolates, Candida glabrata, being the most isolated species (40.8%), followed by Candida tropicalis: 231(23.1%), Candida parapsilosis: 103(10.3%), and other NAC species at lower percentage. Most of these isolates (88.67%) were susceptible to posaconazole, 98.22% were susceptible to micafungin, and 10% were susceptible to caspofungin. CONCLUSION The change of etiology of fungal infections involving a significant increase in NAC cases is alarming due to the different antifungal susceptibility patterns and the lack of local guidelines to guide the treatment. In this context, proper identification of such organisms is of utmost importance. The data presented here can help in establishing guidelines for the treatment of candida infections to decrease morbidity and mortality. Future surveillance data are needed.
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Affiliation(s)
- Rola Husni
- Lebanese American University, School of Medicine, Beirut, Lebanon
- Department of Internal Medicine, Lebanese American University-Rizk Hospital, Beirut, Lebanon
| | - Maroun Bou Zerdan
- Department of Internal Medicine, SUNY Upstate Medical University Hospital, Syracuse, NY, United States
| | - Nadia Samaha
- Georgetown University School of Medicine, Washington, DC, United States
| | - Mariana Helou
- Lebanese American University, School of Medicine, Beirut, Lebanon
- Department of Internal Medicine, Lebanese American University-Rizk Hospital, Beirut, Lebanon
| | - Youssef Mahfouz
- Faculty of Medicine and Medical Sciences, University of Balamand, Tripoli, Lebanon
| | - Rim Saniour
- Faculty of Medicine and Medical Sciences, University of Balamand, Tripoli, Lebanon
| | - Sawsan Hourani
- Faculty of Medicine and Medical Sciences, University of Balamand, Tripoli, Lebanon
| | - Harout Kolanjian
- Lebanese American University, School of Medicine, Beirut, Lebanon
- Department of Internal Medicine, Lebanese American University-Rizk Hospital, Beirut, Lebanon
| | - Claude Afif
- Department of Internal Medicine, Saint George Hospital-University Medical Center, Beirut, Lebanon
| | - Eid Azar
- Department of Internal Medicine, Saint George Hospital-University Medical Center, Beirut, Lebanon
| | - Tamima El Jisr
- Department of Laboratory, Makased General Hospital, Beirut, Lebanon
| | - Jacques Mokhbat
- Lebanese American University, School of Medicine, Beirut, Lebanon
- Department of Internal Medicine, Lebanese American University-Rizk Hospital, Beirut, Lebanon
| | - Emma Abboud
- Department of Laboratory, Mount Liban Hospital, Hazmiyeh, Lebanon
| | - Rita Feghali
- Department of Laboratory, Rafic Hariri University Hospital, Beirut, Lebanon
| | - Edmond Abboud
- Department of Laboratory, The Middle East Institute of Health University Hospital, Mount Lebanon, Lebanon
| | - Hiam Matta
- Saint Georges Ajaltoun Hospital, Ajaltoun, Lebanon
| | | | - Madonna Matar
- Department of Internal Medicine, Notre Dame de Secours University Hospital, Byblos, Lebanon
| | - Rima Moghnieh
- Lebanese American University, School of Medicine, Beirut, Lebanon
- Department of Internal Medicine, Lebanese American University-Rizk Hospital, Beirut, Lebanon
| | - Ziad Daoud
- College of Medicine, Central Michigan University, Saginaw, MI, United States
- Department of Clinical Microbiology and Infection Prevention, Michigan Health Clinics, Saginaw, MI, United States
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Rhimi W, Chebil W, Ugochukwu ICI, Babba H, Otranto D, Cafarchia C. Comparison of virulence factors and susceptibility profiles of Malassezia furfur from pityriasis versicolor patients and bloodstream infections of preterm infants. Med Mycol 2022; 61:6982906. [PMID: 36626926 DOI: 10.1093/mmy/myad003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2022] [Revised: 01/04/2023] [Accepted: 01/09/2023] [Indexed: 01/12/2023] Open
Abstract
In spite of the increasing medical interest in Malassezia yeasts, the virulence factors of Malassezia furfur causing bloodstream infections (BSI) were never investigated. Therefore, phospholipase (Pz), lipase (Lz), hemolysin (Hz), biofilm production, and in vitro antifungal susceptibility profiles were evaluated in M. furfur strains, isolated from both pityriasis versicolor (PV) patients (n = 18; Group 1) or from preterm infants BSI (n = 21; Group 2). All the test stains exhibited Pz activity, whereas 92.3% and 97.4% of strains exhibited Lz and Hz activities, respectively. Pz, Lz, and Hz activities were higher (i.e., lower values) within Group 1 strains (i.e., 0.48, 0.40, and 0.77) than those within Group 2 (i.e., 0.54, 0.54, and 0.81). The biofilm production was higher within Malassezia isolates from Group 2 (0.95 ± 0.3) than from Group 1 (0.72 ± 0.4). Itraconazole and posaconazole were the most active drugs against M. furfur, followed by amphotericin B and fluconazole. The minimum inhibitory concentrations (MIC) values varied according to the origin of M. furfur strains being statistically lower in M. furfur from Group 1 than from Group 2. This study suggests that M. furfur strains produce hydrolytic enzymes and biofilm when causing PV and BSI. Data show that the phospholipase activity, biofilm production, and a reduced antifungal susceptibility profile might favor M. furfur BSI, whereas lipase and hemolytic activities might display a synergic role in skin infection.
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Affiliation(s)
- Wafa Rhimi
- Dipartimento di Medicina Veterinaria, Università degli Studi "Aldo Moro", Bari, Italy
| | - Wissal Chebil
- Laboratory of Medical and Molecular Parasitology-Mycology, Department of Clinical Biology, Faculty of Pharmacy, University of Monastir, Monastir 5000, Tunisia
| | - Iniobong Chukwuebuka Ikenna Ugochukwu
- Dipartimento di Medicina Veterinaria, Università degli Studi "Aldo Moro", Bari, Italy.,Department of Veterinary Pathology and Microbiology, University of Nigeria, Nsukka, Nigeria
| | - Hamouda Babba
- Laboratory of Medical and Molecular Parasitology-Mycology, Department of Clinical Biology, Faculty of Pharmacy, University of Monastir, Monastir 5000, Tunisia
| | - Domenico Otranto
- Dipartimento di Medicina Veterinaria, Università degli Studi "Aldo Moro", Bari, Italy.,Department of Pathobiology, Faculty of Veterinary Sciences, Bu-Ali Sina University, Hamedan, Iran
| | - Claudia Cafarchia
- Dipartimento di Medicina Veterinaria, Università degli Studi "Aldo Moro", Bari, Italy
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Gebretekle GB, Fentie AM, Gebremariam GT, Ali EE, Erku DA, Alemayehu T, Abebe W, Sander B. Cost-utility analysis of caspofungin and fluconazole for primary treatment of invasive candidiasis and candidemia in Ethiopia. BMC Health Serv Res 2022; 22:1302. [PMID: 36309674 PMCID: PMC9618213 DOI: 10.1186/s12913-022-08662-3] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2022] [Revised: 08/22/2022] [Accepted: 09/30/2022] [Indexed: 11/17/2022] Open
Abstract
Background Invasive candidiasis and/or candidemia (IC/C) is a common fungal infection leading to significant health and economic losses worldwide. Caspofungin was shown to be more effective than fluconazole in treating inpatients with IC/C. However, cost-effectiveness of caspofungin for treating IC/C in Ethiopia remains unknown. We aimed to assess the cost-utility of caspofungin compared to fluconazole-initiated therapies as primary treatment of IC/C in Ethiopia. Methods A Markov cohort model was developed to compare the cost-utility of caspofungin versus fluconazole antifungal agents as first-line treatment for adult inpatients with IC/C from the Ethiopian health system perspective. Treatment outcome was categorized as either a clinical success or failure, with clinical failure being switched to a different antifungal medication. Liposomal amphotericin B (L-AmB) was used as a rescue agent for patients who had failed caspofungin treatment, while caspofungin or L-AmB were used for patients who had failed fluconazole treatment. Primary outcomes were expected quality-adjusted life years (QALYs), costs (US$2021), and the incremental cost-utility ratio (ICUR). These QALYs and costs were discounted at 3% annually. Cost data was obtained from Addis Ababa hospitals while locally unavailable data were derived from the literature. Cost-effectiveness was assessed against the recommended threshold of 50% of Ethiopia’s gross domestic product/capita (i.e.,US$476). Deterministic and probabilistic sensitivity analyses were conducted to assess the robustness of the findings. Results In the base-case analysis, treatment of IC/C with caspofungin as first-line treatment resulted in better health outcomes (12.86 QALYs) but higher costs (US$7,714) compared to fluconazole-initiated treatment followed by caspofungin (12.30 QALYs; US$3,217) or L-AmB (10.92 QALYs; US$2,781) as second-line treatment. Caspofungin as primary treatment for IC/C was not cost-effective when compared to fluconazole-initiated therapies. Fluconazole-initiated treatment followed by caspofungin was cost-effective for the treatment of IC/C compared to fluconazole with L-AmB as second-line treatment, at US$316/QALY gained. Our findings were sensitive to medication costs, drug effectiveness, infection recurrence, and infection-related mortality rates. At a cost-effectiveness threshold of US$476/QALY, treating IC/C patient with fluconazole-initiated treatment followed by caspofungin was more likely to be cost-effective in 67.2% of simulations. Conclusion Our study showed that the use of caspofungin as primary treatment for IC/C in Ethiopia was not cost-effective when compared with fluconazole-initiated treatment alternatives. The findings supported the use of fluconazole-initiated therapy with caspofungin as a second-line treatment for patients with IC/C in Ethiopia.
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Talapko J, Meštrović T, Škrlec I. Growing importance of urogenital candidiasis in individuals with diabetes: A narrative review. World J Diabetes 2022; 13:809-821. [PMID: 36311997 PMCID: PMC9606786 DOI: 10.4239/wjd.v13.i10.809] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2022] [Revised: 08/06/2022] [Accepted: 09/07/2022] [Indexed: 02/05/2023] Open
Abstract
Both diabetes and fungal infections contribute significantly to the global disease burden, with increasing trends seen in most developed and developing countries during recent decades. This is reflected in urogenital infections caused by Candida species that are becoming ever more pervasive in diabetic patients, particularly those that present with unsatisfactory glycemic control. In addition, a relatively new group of anti-hyperglycemic drugs, known as sodium glucose cotransporter 2 inhibitors, has been linked with an increased risk for colonization of the urogenital region with Candida spp., which can subsequently lead to an infectious process. In this review paper, we have highlighted notable virulence factors of Candida species (with an emphasis on Candida albicans) and shown how the interplay of many pathophysiological factors can give rise to vulvovaginal candidiasis, potentially complicated with recurrences and dire pregnancy outcomes. We have also addressed an increased risk of candiduria and urinary tract infections caused by species of Candida in females and males with diabetes, further highlighting possible complications such as emphysematous cystitis as well as the risk for the development of balanitis and balanoposthitis in (primarily uncircumcised) males. With a steadily increasing global burden of diabetes, urogenital mycotic infections will undoubtedly become more prevalent in the future; hence, there is a need for an evidence-based approach from both clinical and public health perspectives.
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Affiliation(s)
- Jasminka Talapko
- Laboratory for Microbiology, Faculty of Dental Medicine and Health, Josip Juraj Strossmayer University of Osijek, Osijek 31000, Croatia
| | - Tomislav Meštrović
- University North, University Centre Varaždin, Varaždin 42000, Croatia
- Institute for Health Metrics and Evaluation, Department for Health Metrics Sciences, University of Washington School of Medicine, Seattle, Washington 98195, United States
| | - Ivana Škrlec
- Department of Biophysics, Biology, and Chemistry, Faculty of Dental Medicine and Health, J. J. Strossmayer University of Osijek, Osijek 31000, Croatia
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Maikan HK, Jabbar S, Al-Haishawi H. Isolation and Identification of Candida tropicalis as a Cause of Cutaneous Candidiasis in Kalar District, Iraq. ARCHIVES OF RAZI INSTITUTE 2022; 77:1377-1382. [PMID: 36883146 PMCID: PMC9985788 DOI: 10.22092/ari.2022.357613.2066] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Received: 01/19/2022] [Accepted: 02/06/2022] [Indexed: 03/09/2023]
Abstract
Fungal infections are currently causing health issues all over the world, among which are Candida species that cause cutaneous infection. Numerous dermatological studies concentrated on a single species. However, the virulence factors and the spread of specific candidiasis in specific areas have remained poorly understood. Therefore, the current study was designed to shed light on Candida tropicalis, which has been identified as the most prevalent yeast among Candida non-albicans species. Forty specimens were collected from patients with cutaneous fungal infection (25 females and 15 males) and underwent examination. According to conventional identification based on macroscopic and microscopic examinations, eight isolates were identified as C. tropicalis from Candida non-albicans. Molecular diagnosis for internal transcribed spacers (ITS1 and ITS4) using conventional polymerase chain reaction (PCR) yielded an amplicon of 520 bp for all isolates. Further investigation of PCR-restriction fragment length using Mitochondrial sorting protein; Msp1 enzyme revealed two bands of 340 and 180 bp. The ITS gene sequence in one isolated species was found to be 98% identical to C. tropicalis strain MYA-3404 chromosome R ATCC CP047875.1. Another isolate shared 98.02% identity with C. tropicalis strain MA6 18S ribosomal RNA gene DQ666188.1, indicating C. tropical species identity, implying that non-Candida species should be considered when diagnosing candidiasis. This study demonstrated the significance of Candida non-albicans, particularly C. tropicalis, in terms of pathogenic potential, the ability to cause potentially fatal systemic infections and candidiasis, and acquired flucozonal resistance with a high mortality rate.
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Affiliation(s)
- H K Maikan
- Department of Biology, College of Education, University of Garmian, Sulaymaniyah, Iraq
| | - S Jabbar
- Department of Biology, College of Science, University of Kirkuk, Kirkuk, Iraq
| | - H Al-Haishawi
- Department of Physiology, College of Medicine, University of Misan, Misan, Iraq
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ALÇİ G, KEÇELİ SA, SARITAŞ BM. Distribution of Candida Species Isolated from Different Clincal Specimens and Their Antifungal Susceptibility Profile: A 5 Year Retrospective Analysis. KOCAELI ÜNIVERSITESI SAĞLIK BILIMLERI DERGISI 2022. [DOI: 10.30934/kusbed.1037788] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
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Focused library of phenyl-fused macrocyclic amidinoureas as antifungal agents. Mol Divers 2022; 26:3399-3409. [PMID: 35143033 PMCID: PMC8830944 DOI: 10.1007/s11030-022-10388-7] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2021] [Accepted: 01/13/2022] [Indexed: 01/09/2023]
Abstract
The rise of antimicrobial-resistant phenotypes and the spread of the global pandemic of COVID-19 are worsening the outcomes of hospitalized patients for invasive fungal infections. Among them, candidiases are seriously worrying, especially since the currently available drug armamentarium is extremely limited. We recently reported a new class of macrocyclic amidinoureas bearing a guanidino tail as promising antifungal agents. Herein, we present the design and synthesis of a focused library of seven derivatives of macrocyclic amidinoureas, bearing a second phenyl ring fused with the core. Biological activity evaluation shows an interesting antifungal profile for some compounds, resulting to be active on a large panel of Candida spp. and C. neoformans. PAMPA experiments for representative compounds of the series revealed a low passive diffusion, suggesting a membrane-based mechanism of action or the involvement of active transport systems. Also, compounds were found not toxic at high concentrations, as assessed through MTT assays.
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Changing Trends of Candida Species and Antifungal Susceptibility Profile of Candida Bloodstream Isolates: A 5-Year Retrospective Survey. Jundishapur J Microbiol 2022. [DOI: 10.5812/jjm.120801] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
Background: Candida species have emerged as one of the most common causes of bloodstream infections (BSIs). There are limited data on the distribution of Candida spp. and susceptibility by year. Objectives: In this study, we analyzed changes in the distribution of Candida spp. and their antifungal susceptibility profiles from blood cultures. Methods: Records from January 2016 to December 2020 were obtained from the microbiology laboratory in Istanbul. Antifungal susceptibility tests were performed using the VITEK 2 compact system and evaluated according to EUCAST breakpoints. A total of 241 unique candidemia episodes were included in this study. Results: Candida albicans was the predominant pathogen (n = 95, 39.42%), followed by C. parapsilosis (n = 82, 34.02%), C. glabrata (n = 18, 7.47%), C. tropicalis (n = 17, 7.05%), C. krusei (n = 15, 6.22%), and other Candida spp. (n = 14, 5.79%). There was no statistically significant difference in the percentage of episodes of Candida spp. After data analysis, a tendency to shift from C. albicans to C. parapsilosis was observed in the period analyzed in this study. Candida albicans was the most common species in intensive care units (ICUs), hematology and hemopoietic stem cell transplantation units, and surgical clinics, with C. parapsilosis predominant in medical clinics. In general, micafungin susceptibility was the highest, and fluconazole was the lowest. There was reduced sensitivity to fluconazole and voriconazole for C. albicans and C. parapsilosis over 5 years. Conclusions: Detecting changes in the distribution of Candida spp. and antifungal susceptibility over time will lead to the selection of appropriate empirical therapy and monitor phenomena of antifungal resistance. Empirical treatment with antifungal agents is associated with high costs, toxicities, and risk of antifungal resistance. Therefore, it is mandatory to determine and monitor Candida spp. and antifungal susceptibility testing to select appropriate antifungal agents.
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Al-Khairallah HA, Al-Yasiri MH. MOLECULAR DETECTION OF THE TWO VIRULENCE GENES HWP1 AND ALS1 IN CANDIDA SPECIES ISOLATED FROM ONYCHOMYCOSIS. WIADOMOSCI LEKARSKIE (WARSAW, POLAND : 1960) 2022; 75:1295-1298. [PMID: 35758446 DOI: 10.36740/wlek202205211] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/15/2023]
Abstract
OBJECTIVE The aim: This article was aimed to assess the prevalence of Candida species causing nail infections and to investigate the most important virulence genes that cause adhesion. PATIENTS AND METHODS Materials and methods: Samples were collected from General Hospital and the outpatient's clinics in Thi-Qar Province, southern Iraq, during the period from January 2021 to May 2021. Samples were inoculated on Sabouraud Dextrose Agar plates containing 0.5 mg chloramphenicol, then Petri dishes were incubated at 30°C under aerobic conditions and observed for Candida species growth for 24-72 hrs. All isolates were identified by morphologic and chromatic properties on CHROMagar and by Api Candida. RESULTS Results: Twenty five isolates were obtained from hundred samples, which belong to five species of the genus Candida, distributed in percentage 9(36%), 4(16%), 4(16%), 4(16%) and 3(12%) of C. glabrata, C. krusei, C. albicans, C. famata and C. tropicalis consecutively and one isolate was not identified. Monoplex PCR technique was used to detect virulence genes (hwp1 and als1) of Candida species. Four Candida albicans isolates (16%) were carried of both hwp1 and als1 genes. CONCLUSION Conclusions: The virulence gene (hwp1) can be relied upon in molecular detection as a special diagnostic tool of Candida albicans species except other types causing Candidal onychomycosis.
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Shukla M, Chandley P, Kaur H, Ghosh AK, Rudramurthy SM, Rohatgi S. Expression and Purification along with Evaluation of Serological Response and Diagnostic Potential of Recombinant Sap2 Protein from C. parapsilosis for Use in Systemic Candidiasis. J Fungi (Basel) 2021; 7:jof7120999. [PMID: 34946982 PMCID: PMC8708535 DOI: 10.3390/jof7120999] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2021] [Revised: 11/19/2021] [Accepted: 11/22/2021] [Indexed: 11/22/2022] Open
Abstract
Systemic candidiasis is the fourth most common bloodstream infection in ICU patients worldwide. Although C. albicans is a predominant species causing systemic candidiasis, infections caused by non-albicans Candida (NAC) species are increasingly becoming more prevalent globally along with the emergence of drug resistance. The diagnosis of systemic candidiasis is difficult due to the absence of significant clinical symptoms in patients. We investigated the diagnostic potential of recombinant secreted aspartyl proteinase 2 (rSap2) from C. parapsilosis for the detection of Candida infection. The rSap2 protein was successfully cloned, expressed and purified using Ni-NTA chromatography under denaturing conditions using an E. coli-based prokaryotic expression system, and refolded using a multi-step dialysis procedure. Structural analysis by CD and FTIR spectroscopy revealed the refolded protein to be in its near native conformation. Immunogenicity analysis demonstrated the rSap2 protein to be highly immunogenic as evident from significantly high titers of Sap2-specific antibodies in antigen immunized Balb/c mice, compared to sham-immunized controls. The diagnostic potential of rSap2 protein was evaluated using immunoblotting and ELISA assays using proven candidiasis patient serum and controls. Immunoblotting results indicate that reactivity to rSap2 was specific to candidiasis patient sera with no cross reactivity observed in healthy controls. Increased levels of anti-Sap2-specific Ig, IgG and IgM antibodies were observed in candidiasis patients compared to controls and was similar in sensitivity obtained when whole Candida was used as coating antigen. In summary, the rSap2 protein from C. parapsilosis has the potential to be used in the diagnosis of systemic candidiasis, providing a rapid, convenient, accurate and cost-effective strategy.
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Affiliation(s)
- Manisha Shukla
- Department of Biosciences and Bioengineering, Indian Institute of Technology Roorkee, Roorkee 247667, India; (M.S.); (P.C.)
| | - Pankaj Chandley
- Department of Biosciences and Bioengineering, Indian Institute of Technology Roorkee, Roorkee 247667, India; (M.S.); (P.C.)
| | - Harsimran Kaur
- Department of Medical Microbiology, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India; (H.K.); (A.K.G.); (S.M.R.)
| | - Anup K. Ghosh
- Department of Medical Microbiology, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India; (H.K.); (A.K.G.); (S.M.R.)
| | - Shivaprakash M. Rudramurthy
- Department of Medical Microbiology, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India; (H.K.); (A.K.G.); (S.M.R.)
| | - Soma Rohatgi
- Department of Biosciences and Bioengineering, Indian Institute of Technology Roorkee, Roorkee 247667, India; (M.S.); (P.C.)
- Correspondence:
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M El-Ganiny A, E Yossef N, A Kamel H. Prevalence and antifungal drug resistance of nosocomial Candida species isolated from two university hospitals in Egypt. Curr Med Mycol 2021; 7:31-37. [PMID: 34553095 PMCID: PMC8443875 DOI: 10.18502/cmm.7.1.6181] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2020] [Revised: 02/17/2021] [Accepted: 04/07/2021] [Indexed: 11/24/2022] Open
Abstract
Background and Purpose: There is a significant rise in morbidity and mortality of infections caused by Candida. Candida spp. infections are currently ranked fourth among nosocomial infections which are difficult
to diagnose and refractory to therapy. Given the differences in susceptibility among various spp., identification of Candida spp. is an important step that leads to the selection of a suitable antifungal. Materials and Methods: A prevalence study was conducted on 122 Candida isolates. The Candida spp. were identified using Chromogenic agar and polymerase chain reaction (PCR).
The antifungal susceptibility (AFS) of Candida spp. to amphotericin B, fluconazole, voriconazole, and caspofungin was determined by the disc diffusion method. Results: In total, 122 Candida clinical isolates were investigated in this study. Candida albicans with 57.4% (70 isolates) had the highest prevalence rate,
while 52 isolates (42.6%) were non-albicansCandida species (NAC). The NAC include Candida krusei (20.4%), Candida tropicalis (6.5%), Candida parapsilolsis (5.7%),
Candida dubliniensis (4.9%), and Candida glabrata (4.9%). The AFS showed that the resistance rates of Candida spp. to fluconazole and voriconazole were 13.1% (16 isolates)
and 9.8% (12 isolates), respectively. Moreover, only five isolates (4.1%) were resistant to caspofungin. Furthermore, there was no resistance against amphotericin B. The spp.
that showed the highest resistance were C. glabrata and C. tropicalis, while the lowest resistance was observed in C. albicans and C. dubliniensis. Conclusion: In conclusion, rapid identification of clinical Candida isolates and standard AFS are essential procedures for controlling the rise of resistant NAC spp. in clinical settings.
Usage of fluconazole should be restricted, especially in patients with recurrent Candida infections.
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Affiliation(s)
- Amira M El-Ganiny
- Microbiology and Immunology Department, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt
| | - Nehal E Yossef
- Microbiology and Immunology Department, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt
| | - Hend A Kamel
- Microbiology and Immunology Department, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt.,Microbiology Department, Faculty of Pharmacy and Pharmaceutical Industries, Sinai University, Kantara, Egypt
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