scholarly journals Clonal Candidemia Outbreak by Candida parapsilosis Carrying Y132F in Turkey: Evolution of a Persisting Challenge

2021 ◽  
Vol 11 ◽  
Author(s):  
Amir Arastehfar ◽  
Suleyha Hilmioğlu-Polat ◽  
Farnaz Daneshnia ◽  
Weihua Pan ◽  
Ahmed Hafez ◽  
...  
Keyword(s):  
Candida Parapsilosis ◽  
Control Strategies ◽  
Antifungal Susceptibility ◽  
Therapeutic Failure ◽  
University Hospital ◽  
Antifungal Stewardship ◽  
Major Health ◽  
Major Cluster ◽  
Echinocandin Resistance ◽  
Clinical Profiles

As the second leading etiological agent of candidemia in Turkey and the cause of severe fluconazole-non-susceptible (FNS) clonal outbreaks, Candida parapsilosis emerged as a major health threat at Ege University Hospital (EUH). Evaluation of microbiological and pertinent clinical profiles of candidemia patients due to C. parapsilosis in EUH in 2019–2020. Candida parapsilosis isolates were collected from blood samples and identified by sequencing internal transcribed spacer ribosomal DNA. Antifungal susceptibility testing was performed in accordance with CLSI M60 protocol and ERG11 and HS1/HS2-FKS1 were sequenced to explore the fluconazole and echinocandin resistance, respectively. Isolates were typed using a multilocus microsatellite typing assay. Relevant clinical data were obtained for patients recruited in the current study. FNS C. parapsilosis isolates were recovered from 53% of the patients admitted to EUH in 2019–2020. Y132F was the most frequent mutation in Erg11. All patients infected with C. parapsilosis isolates carrying Y132F, who received fluconazole showed therapeutic failure and significantly had a higher mortality than those infected with other FNS and susceptible isolates (50% vs. 16.1%). All isolates carrying Y132F grouped into one major cluster and mainly recovered from patients admitted to chest diseases and pediatric surgery wards. The unprecedented increase in the number of Y132F C. parapsilosis, which corresponded with increased rates of fluconazole therapeutic failure and mortality, is worrisome and highlights the urgency for strict infection control strategies, antifungal stewardship, and environmental screening in EUH.

Genetically related micafungin-resistant Candida parapsilosis blood isolates harbouring novel mutation R658G in hotspot 1 of Fks1p: a new challenge?

2020 ◽  
Author(s):  
Amir Arastehfar ◽  
Farnaz Daneshnia ◽  
Süleyha Hilmioglu-Polat ◽  
Macit Ilkit ◽  
Melike Yasar ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Candida Parapsilosis ◽  
Genetic Relatedness ◽  
Novel Mutation ◽  
Antifungal Susceptibility ◽  
Underlying Mechanism ◽  
Therapeutic Failure ◽  
Paediatric Surgery ◽  
Echinocandin Resistance

Abstract Background Echinocandin resistance rarely occurs in clinical Candida parapsilosis isolates and the underlying mechanism is unknown. Objectives To determine the prevalence of echinocandin resistance and the underlying mechanism for a large collection of C. parapsilosis blood isolates and to determine whether the echinocandin-resistant isolates were clonally related. Methods C. parapsilosis blood isolates (n = 213) were subjected to antifungal susceptibility testing (CLSI M27), for micafungin, anidulafungin, amphotericin B and, if appropriate, caspofungin. Hotspot (HS) 1 and HS2 of FKS1 were sequenced for all isolates (n = 213) and microsatellite typing was performed for echinocandin-resistant isolates. Results All isolates were susceptible to amphotericin B and two isolates were intermediate to anidulafungin (MIC = 4 mg/L), while micafungin resistance was noted in four isolates (MIC >8 mg/L); three of which were also fluconazole resistant and therefore were MDR. Interestingly, micafungin-resistant isolates, but not those intermediate to anidulafungin, carried novel mutation R658G in HS1 of Fks1p; three of which also harboured Y132F+K143R in Erg11. The first isolate (MICR1) was recovered in November 2017 from a patient admitted to paediatric gastroenterology who showed therapeutic failure under caspofungin treatment. MICR2–MICR4 were collected during 2018–19 and were recovered from three echinocandin-naive paediatric-surgery patients; the isolates shared the same genotype. Conclusions Herein, for the first time (to the best of our knowledge), we identified micafungin-resistant C. parapsilosis blood isolates harbouring a novel mutation in HS1 of FKS1, which was likely attributable to in vitro micafungin resistance and in vivo caspofungin therapeutic failure. The acquisition of micafungin-resistant C. parapsilosis isolates in echinocandin-naive patients likely implicates clonal expansion, as supported by the close genetic relatedness of MICR2–MICR4.

scholarly journals Candida parapsilosis Candidemia Resistance Patterns and Treatment Outcomes: An Opportunity for Antifungal Stewardship

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S86-S86
Author(s):  
Gary Fong ◽  
Kim Ngo ◽  
Hannah Russo ◽  
Nicholas Beyda
Keyword(s):  
Combination Therapy ◽  
Treatment Outcomes ◽  
Candida Parapsilosis ◽  
Medical Center ◽  
Antifungal Susceptibility ◽  
Antifungal Stewardship ◽  
Resistance Patterns ◽  
Fluconazole Therapy ◽  
The Impact ◽  
Research Grant

Abstract Background Candida parapsilosis has emerged as an important fungal pathogen with mortality rates up to 30%. Recent studies show no difference in treatment outcomes for patients treated both empirically and definitively with either echinocandins or fluconazole. However, the impact of antifungal susceptibility testing and opportunities for antifungal stewardship are less clear in this patient population. The purpose of this study was to assess antifungal susceptibility rates, treatment patterns, and outcomes among patients with C. parapsilosis candidemia. Methods This was a single-center, retrospective cohort review of adult patients with a positive blood culture for C. parapsilosis hospitalized at Baylor St. Luke’s Medical Center, between 2006 and 2016. Patients with mixed or breakthrough candidemia were excluded as well as patients who expired within 3 days of candidemia onset. Results Eighty patients with C. parapsilosis candidemia were identified of which 48 met inclusion criteria. Nine patients had infections caused by fluconazole non-susceptible isolates (19%). The most common empiric treatment choice was an echinocandin (33/48, 69%), followed by fluconazole (9/48, 19%), and combination therapy (6/48, 13%). Of the 39 patients with fluconazole susceptible isolates, only 17 were treated with fluconazole definitively (44%). Among patients who received empiric echinocandin vs. fluconazole therapy, there was no difference in 14-day mortality (9% vs. 11%, P = 1.00) or in-hospital mortality (12% vs. 11%, P = 1.00). Empiric combination therapy was the only independent risk factor for treatment failure (OR, 13.8; 95% CI, 1.4–138.3; P = 0.03). Conclusion Treatment outcomes for patients receiving echinocandins were similar for those receiving fluconazole. At our institution, the increased incidence of fluconazole non-susceptible isolates warrants the use of echinocandins empirically. Patients were more likely to remain on echinocandin therapy even when fluconazole susceptible isolates were identified. This study reinforces the guideline suggestion that neither echinocandins nor fluconazole treatment leads to superior outcomes, but also identifies a cohort of patients in need of antifungal stewardship. Disclosures N. Beyda, Astellas: Grant Investigator and Scientific Advisor, Research grant

scholarly journals Environmental Clonal Spread of Azole-Resistant Candida parapsilosis with Erg11-Y132F Mutation Causing a Large Candidemia Outbreak in a Brazilian Cancer Referral Center

2021 ◽  
Vol 7 (4) ◽  
pp. 259 ◽  
Author(s):  
Danilo Y. Thomaz ◽  
João N. de Almeida ◽  
Odeli N. E. Sejas ◽  
Gilda M. B. Del Negro ◽  
Gabrielle O. M. H. Carvalho ◽  
...  
Keyword(s):  
Mortality Rate ◽  
Candida Parapsilosis ◽  
Susceptibility Testing ◽  
Antifungal Susceptibility ◽  
Reference Method ◽  
Blood Cultures ◽  
Environmental Niche ◽  
Referral Center ◽  
Major Cluster ◽  
Environmental Decontamination

Clonal outbreaks due to azole-resistant Candida parapsilosis (ARCP) isolates have been reported in numerous studies, but the environmental niche of such isolates has yet to be defined. Herein, we aimed to identify the environmental niche of ARCP isolates causing unremitting clonal outbreaks in an adult ICU from a Brazilian cancer referral center. C. parapsilosis sensu stricto isolates recovered from blood cultures, pericatheter skins, healthcare workers (HCW), and nosocomial surfaces were genotyped by multilocus microsatellite typing (MLMT). Antifungal susceptibility testing was performed by the EUCAST (European Committee for Antimicrobial Susceptibility Testing) broth microdilution reference method and ERG11 was sequenced to determine the azole resistance mechanism. Approximately 68% of isolates were fluconazole-resistant (76/112), including pericatheter skins (3/3, 100%), blood cultures (63/70, 90%), nosocomial surfaces (6/11, 54.5%), and HCW’s hands (4/28, 14.2%). MLMT revealed five clusters: the major cluster contained 88.2% of ARCP isolates (67/76) collected from blood (57/70), bed (2/2), pericatheter skin (2/3), from carts (3/7), and HCW’s hands (3/27). ARCP isolates were associated with a higher 30 day crude mortality rate (63.8%) than non-ARCP ones (20%, p = 0.008), and resisted two environmental decontamination attempts using quaternary ammonium. This study for the first time identified ARCP isolates harboring the Erg11-Y132F mutation from nosocomial surfaces and HCW’s hands, which were genetically identical to ARCP blood isolates. Therefore, it is likely that persisting clonal outbreak due to ARCP isolates was fueled by environmental sources. The resistance of Y132F ARCP isolates to disinfectants, and their potential association with a high mortality rate, warrant vigilant source control using effective environmental decontamination.

Epidemiology and Antifungal Susceptibility in Patients with Candidemia in a University Hospital, Thailand

2020 ◽  
Vol 103 (10) ◽  
pp. 1048-1056
Keyword(s):  
Antifungal Susceptibility ◽  
Underlying Disease ◽  
Outcome Data ◽  
Adult Patients ◽  
Antifungal Treatment ◽  
University Hospital ◽  
Fluconazole Resistance ◽  
Fluconazole Therapy ◽  
Fluconazole Resistant ◽  
High Level

Background: Candidemia is the most common nosocomial invasive fungal infection that causes high mortality. Emergence of drug-resistant Candida is reported worldwide but there are few studies in Thailand. Objective: To determine the epidemiology, antifungal susceptibility of Candida, and outcomes among adult patients with candidemia. Materials and Methods: A prospective, observational study in adult patients with candidemia was conducted in 2015 at a university hospital. Demographic, microbiological, and outcome data were recorded. Results: Fifty-two patients with candidemia were identified, of whom 76.9% had an underlying disease and 69.2% had risks for candidemia. Sixty-four percent of candidemia patients contracted non-albicans Candida and 36% had Candida albicans. C. tropicalis was the most common non-albicans Candida species isolated (35%), followed by C. parapsilosis (19%), and C. glabrata (10%). Fluconazole resistance was found in 12.5% of C. albicans and in 11.1% of C. parapsilosis isolates. Reduced fluconazole susceptibility or high-level fluconazole resistance was found in 68.7% of C. tropicalis isolates. All except C. parapsilosis had excellent susceptibility to echinocandins. Seventy-three percent (38/52) of patients received antifungal treatment, of whom, 78.9% received empiric fluconazole therapy, and 89.7% were started on antifungal treatment 24 hours after the isolation of Candida. The overall mortality rate was 51.9%. Conclusion: Fluconazole-resistant Candida became more prevalent particularly in C. tropicalis, which was the predominant species among non-albicans Candida causing candidemia. Empiric treatment with either amphotericin B or echinocandins would be appropriate in high-risk patients with suspected candidemia. Trial registration: Thai Clinical Trials Registry, TCTR20150605001 Keywords: Candida, Fluconazole, Resistant, Thailand

Malaria among migrants in a university hospital in Colombia during 2018: A case series

2020 ◽  
pp. 004947552098130
Author(s):  
Fabián R Carreño-Almánzar ◽  
Adán Coronado-Galán ◽  
Sonia A Cala-Gómez ◽  
Agustín Vega-Vera
Keyword(s):  
Latin American ◽  
Previous History ◽  
Case Series ◽  
Cross Sectional Study ◽  
Imported Malaria ◽  
University Hospital ◽  
Sectional Study ◽  
Cross Sectional ◽  
History Of ◽  
Clinical Profiles

Imported malaria has increased in Colombia since 2015 and has been attributed to migrants coming from Venezuela. We present a series of malaria cases, nested in a retrospective cross-sectional study between 2017 and 2018, aimed at calculating the prevalence of medical diseases among immigrants in a University Hospital in Colombia. Among 154 immigrants admitted for medical causes between 2017 and 2018, 8 were diagnosed with malaria, all due to Plasmodium vivax. Of these, seven had uncomplicated malaria, five had a previous history of malaria, one was critically ill, but none died. We highlight that, similar to other case series of imported malaria, Latin American migrants were young, with similar clinical profiles, having a low proportion of severe cases, and P. vivax was the most frequent cause.

scholarly journals A Statewide Assessment of Antifungal Stewardship Activities in Acute-Care Hospitals in Connecticut

2020 ◽  
Vol 41 (S1) ◽  
pp. s105-s105
Author(s):  
Romina Bromberg ◽  
Vivian Leung ◽  
Meghan Maloney ◽  
Anu Paranandi ◽  
David Banach
Keyword(s):  
Infectious Diseases ◽  
Acute Care ◽  
Antifungal Therapy ◽  
Antibiotic Stewardship ◽  
Susceptibility Testing ◽  
Antifungal Susceptibility ◽  
Acute Care Hospitals ◽  
Antifungal Susceptibility Testing ◽  
Antifungal Stewardship ◽  
Infectious Diseases Consultation

Background: Morbidity and mortality associated with invasive fungal infections and concerns of emerging antifungal resistance have highlighted the importance of optimizing antifungal therapy among hospitalized patients. Little is known about antifungal stewardship (AFS) practices among acute-care hospitals. We sought to assess AFS activities within Connecticut and to identify opportunities for improvement. Methods: An electronic survey assessing AFS practices was distributed to infectious disease physicians or pharmacy antibiotic stewardship program leaders in Connecticut hospitals. Survey questions evaluated AFS activities based on antibiotic stewardship principles, including several CDC Core Elements. Questions assessed antifungal restriction, prospective audit and feedback practices, antifungal utilization measurements, and the perceived utility of a local or statewide antifungal antibiogram. Results: Responses were received from 15 respondents, which represented 20 of 31 hospitals (65%); these hospitals made up the majority of the acute-care hospitals in Connecticut. Furthermore, 18 of these hospitals (58%) include antifungals in their stewardship programs. Also, 16 hospitals (52%) conduct routine review of antifungal ordering and provide feedback to providers for some antifungals, most commonly for amphotericin B, voriconazole, micafungin, isavuconazole, and flucytosine. All hospitals include guidance on intravenous (IV) to oral (PO) conversions, when appropriate. Only 14 of hospitals (45%) require practitioners to document indication(s) for systemic antifungal use. Most hospitals (17, 55%) provide recommendations for de-escalation of therapy in candidemia, though only 4 (13%) have institutional guidelines for candidemia treatment, and only 11 hospital mandates an infectious diseases consultation for candidemia. Assessing outcomes pertaining to antifungal utilization is uncommon; only 8 hospitals (26%) monitor days of therapy and 5 (16%) monitor antifungal expenditures. Antifungal susceptibility testing on Candida bloodstream isolates is performed routinely at 6 of the hospitals (19%). Most respondents (19, 95%) support developing an antibiogram for Candida bloodstream isolates at the statewide level. Conclusions: Although AFS interventions occur in Connecticut hospitals, there are opportunities for enhancement, such as providing institutional guidelines for candidemia treatment and mandating infectious diseases consultation for candidemia. The Connecticut Department of Public Health implemented statewide Candida bloodstream isolate surveillance in 2019, which includes antifungal susceptibility testing. The creation of a statewide antibiogram for Candida bloodstream infections is underway to support empiric antifungal therapy.Funding: NoneDisclosures: None

scholarly journals Prevalence, distribution and antifungal susceptibility profiles of Candida parapsilosis, Candida orthopsilosis and Candida metapsilosis bloodstream isolates

2012 ◽  
Vol 61 (7) ◽  
pp. 1003-1008 ◽  
Author(s):  
Lucas Xavier Bonfietti ◽  
Marilena dos Anjos Martins ◽  
Maria Walderez Szeszs ◽  
Sandra Brasil Stolf Pukiskas ◽  
Sonia Ueda Purisco ◽  
...  
Keyword(s):  
Candida Parapsilosis ◽  
Antifungal Susceptibility ◽  
Candida Metapsilosis ◽  
Candida Orthopsilosis ◽  
Susceptibility Profiles

scholarly journals Candidemia by Candida parapsilosis in a neonatal intensive care unit: human and environmental reservoirs, virulence factors, and antifungal susceptibility

2020 ◽  
Vol 51 (3) ◽  
pp. 851-860
Author(s):  
Ralciane de Paula Menezes ◽  
Sávia Gonçalves de Oliveira Melo ◽  
Meliza Arantes Souza Bessa ◽  
Felipe Flávio Silva ◽  
Priscila Guerino Vilela Alves ◽  
...  
Keyword(s):  
Intensive Care Unit ◽  
Intensive Care ◽  
Neonatal Intensive Care Unit ◽  
Virulence Factors ◽  
Neonatal Intensive Care ◽  
Candida Parapsilosis ◽  
Antifungal Susceptibility

scholarly journals Molecular Analysis of Resistance and Detection of Non-Wild-Type Strains Using Etest Epidemiological Cutoff Values for Amphotericin B and Echinocandins for Bloodstream Candida Infections from a Tertiary Hospital in Qatar

2018 ◽  
Vol 62 (9) ◽  
Author(s):  
Saad J. Taj-Aldeen ◽  
Husam Salah ◽  
Winder B. Perez ◽  
Muna Almaslamani ◽  
Mary Motyl ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Hot Spot ◽  
Antifungal Susceptibility ◽  
Tertiary Hospital ◽  
Wild Type ◽  
Content Type ◽  
Cutoff Values ◽  
Echinocandin Resistance ◽  
Candida Infections ◽  
Type Strains

ABSTRACT A total of 301 Candida bloodstream isolates collected from 289 patients over 5 years at a tertiary hospital in Qatar were evaluated. Out of all Candida infections, 53% were diagnosed in patients admitted to the intensive care units. Steady increases in non-albicans Candida species were reported from 2009 to 2014 (30.2% for Candida albicans versus 69.8% for the other Candida species). Etest antifungal susceptibility testing was performed on all recovered clinical isolates to determine echinocandin (micafungin and anidulafungin) and amphotericin B susceptibilities and assess non-wild-type (non-WT) strains (strains for which MICs were above the epidemiological cutoff values). DNA sequence analysis was performed on all isolates to assess the presence of FKS mutations, which confer echinocandin resistance in Candida species. A total of 3.9% of isolates (12/301) among strains of C. albicans and C. orthopsilosis contained FKS hot spot mutations, including heterozygous mutations in FKS1. For C. tropicalis, the Etest appeared to overestimate strains non-WT for micafungin, anidulafungin, and amphotericin B, as 14%, 11%, and 35% of strains, respectively, had values above the epidemiological cutoff value. However, no FKS mutations were identified in this species. For all other species, micafungin best reported the echinocandin non-WT strains relative to the FKS genotype, as anidulafungin tended to overestimate non-wild-type strains. Besides C. tropicalis, few strains were classified as non-WT for amphotericin B.

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