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. 2021 Mar 30;7(4):259.
doi: 10.3390/jof7040259.

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

Danilo Y Thomaz  1 , João N de Almeida Jr  1   2   3 , Odeli N E Sejas  4 , Gilda M B Del Negro  1 , Gabrielle O M H Carvalho  1 , Viviane M F Gimenes  1 , Maria Emilia B de Souza  4 , Amir Arastehfar  3 , Carlos H Camargo  5 , Adriana L Motta  2 , Flávia Rossi  2 , David S Perlin  3 , Maristela P Freire  4 , Edson Abdala  4 , Gil Benard  1
Affiliations

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

Danilo Y Thomaz et al. J Fungi (Basel). .

Abstract

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.

Keywords: Candida parapsilosis; ERG11 mutations; antifungal agents; azole-resistant; candidemia; clonal outbreak; drug resistance mechanisms; environmental reservoirs; horizontal transmission; microsatellite typing.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Candida parapsilosis isolates per 100 positive blood cultures at the cancer referral center. The red dashed trend line shows the marked increase from October 2017 to April 2020.
Figure 2
Figure 2
Candidemia cases by azole-resistant C. parapsilosis (ARCP) or non-ARCP in the adult oncology intensive care unit (ICU) from January 2019 to April 2020. The red arrows indicate the two decontamination efforts of the ICU environment with quaternary ammonium disinfectant.
Figure 3
Figure 3
Circular tree generated from 112 C. parapsilosis sensu stricto isolates obtained from the adult oncology intensive care unit in 2019. The small colored circles indicate the isolate source. ARCP = azole-resistant C. parapsilosis.
Figure 4
Figure 4
Dendrogram showing the clustering of the 112 C. parapsilosis sensu stricto isolates and the ATCC22019 strain based on microsatellite analysis. The black square indicates the presence of an amplification product, the red square indicates the azole-resistant isolates, and the green square indicates the non-azole-resistant ones. FLC = fluconazole, VRC = voriconazole, and MIC = minimum inhibitory concentration.
Figure 5
Figure 5
Kaplan–Meier curve for 30-day survival of candidemia patients infected with azole-resistant C. parapsilosis (ARCP) vs. non-ARCP (p = 0.025). The curve was constructed and compared with the log-rank test.
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References

    1. McCarthy M.W., Walsh T.J. Candidemia in the cancer patient: Diagnosis, treatment, and future directions. Expert Rev. Anti-Infect. Ther. 2018;16:849–854. doi: 10.1080/14787210.2018.1536546. - DOI - PubMed
    1. Alves J., Palma P., Azevedo D., Rello J. Candidemia in the patient with malignancy. Hosp. Pract. 2018;46:246–252. doi: 10.1080/21548331.2018.1508290. - DOI - PubMed
    1. Colombo A.L., Agnelli C., Kontoyiannis D.P. Knowledge gaps in candidaemia/invasive candidiasis in haematological cancer patients. J. Antimicrob. Chemother. 2020 doi: 10.1093/jac/dkaa446. - DOI - PubMed
    1. Logan C., Martin-Loeches I., Bicanic T. Invasive candidiasis in critical care: Challenges and future directions. Intensive Care Med. 2020 doi: 10.1007/s00134-020-06240-x. - DOI - PubMed
    1. Gamaletsou M.N., Walsh T.J., Sipsas N.V. Invasive Fungal Infections in Patients with Hematological Malignancies: Emergence of Resistant Pathogens and New Antifungal Therapies. Turk. J. Haematol. 2018;35:1–11. doi: 10.4274/tjh.2018.0007. - DOI - PMC - PubMed

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