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Outbreak of Candida auris infection in a COVID-19 hospital in Mexico

2021; Elsevier BV; Volume: 27; Issue: 5 Linguagem: Inglês

10.1016/j.cmi.2020.12.030

1469-0691

Hiram Villanueva-Lozano, Rogelio de J. Treviño‐Rangel, Gloria M. González, María Teresa Ramírez-Elizondo, Reynaldo Lara-Medrano, Mary Cruz Alemán-Bocanegra, Claudia Elena Guajardo-Lara, Natalia Gaona-Chávez, Fernando Castilleja‐Leal, Guillermo Torre‐Amione, Michel F. Martínez‐Reséndez,

Parasitic Diseases Research and Treatment

Since its emergence in December 2019, the rapid spread of coronavirus disease 2019 (COVID-19) has necessitated the expansion and transformation of healthcare facilities worldwide to accommodate the constantly increasing numbers of patients. This situation has provided a potential ground for the transmission of nosocomial infections [[1]Auerbach A. O'Leary K.J. Greysen S.R. Harrison J.D. Kripalani S. Ruhnke G.W. et al.Hospital ward adaptation during the covid-19 pandemic: a national survey of academic medical centers.J Hosp Med. 2020; 15: 483-488Crossref PubMed Scopus (39) Google Scholar]. Candida auris is a multidrug-resistant fungal pathogen with the capability for nosocomial transmission. Some studies have suggested an increased risk for Candida sp. in COVID-19 patients, resulting in poor outcomes [[2]Al-Hatmi A.M. Mohsin J. Al-Huraizi A. Khamis F. Covid-19 associated invasive candidiasis.J Infect. 2020; (S0163-4453:30539-9)Abstract Full Text Full Text PDF Scopus (46) Google Scholar,[3]Lone S.A. Ahmad A. Candida auris—the growing menace to global health.Mycoses. 2019; 62: 620-637Crossref PubMed Scopus (128) Google Scholar]. Here we describe an outbreak of C. auris which started in a non-COVID-19 patient at the end of May 2020 (reported previously [[4]Ayala-Gaytán J.J. Montoya A.M. Martínez-Resendez M.F. Guajardo-Lara C.E. Treviño-Rangel RdJ. Salazar-Cavazos L. et al.First case of Candida auris isolated from the bloodstream of a Mexican patient with serious gastrointestinal complications from severe endometriosis.Infection. 2020; : 1-3PubMed Google Scholar]). This occurred during the transition of the hospital to an exclusive COVID-19 facility; the infection later spread to 12 patients in the intensive care unit (ICU). We collected the clinical data of all the patients admitted to the hospital from April 2020 to the present date. Characteristics of the patients with a diagnosis of C. auris infection were analysed. This study was approved by the Research Ethics Committee of the Hospital San José Tec-Salud (registration number: P000353-COVID-19-TecSalud-CS001). C. auris strains from 12 patients and three environmental isolates from their bedrooms were identified by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry (Bruker Daltonics, MALDI Biotyper) and confirmed by multilocus sequence typing of the ITS1-5.8S-ITS2, D1/D2, RPB1 and RPB2 regions. Sequences were aligned and analysed by MEGA v.7.0.26 and a dendrogram was delineated. Antifungal susceptibility testing for amphotericin B (AMB), fluconazole (FLU), voriconazole (VRC), posaconazole (POS), itraconazole (ITC), isavuconazole (ISA), anidulafungin (ANF) and caspofungin (CAS) was performed using the Clinical and Laboratory Standards Institute (CLSI) broth microdilution method M27-A3/S4. Our team reported the first case of C. auris infection in May 2020. At that time the hospital was transitioning from a general hospital to an exclusive COVID-19 facility which included expansion of the ICU to four areas with 60 beds; this was completed as the last non-COVID-19 patient was discharged. Three months later an outbreak of COVID-19-associated Candida auris infections started in three of the ICUs, affecting 12 patients. All the affected patients were under mechanical ventilation, had peripherally inserted central lines (PICCs), urinary catheters and prolonged hospital stay (20–70 days). C. auris was isolated from blood in six patients (6/12; 50%), from urine in eight (8/12; 66.6%), and from both sites in two (2/12; 16.6%). Mortality was 83.3% (5/6) among the patients with candidaemia (Table 1A).Table 1(A) Clinical characteristics of 12 patients with C. auris infection and COVID-19 pneumonia. (B) MLST and antifungal susceptibility results of the C. auris isolates from the patients and surface sampling from an infusion pump (13) and bed rails (14 and 15)A. Clinical characteristics of 12 patients with C. auris infection and COVID-19 pneumonia.No. Patient123456789101112Age515455516464546058366646SexMMMMMMFFMMMMCo-infectionsPseudomonas aeruginosaPseudomonas aeruginosa,Klebsiella pneumoniaePseudomonas aeruginosa, Candida glabrataPseudomonas aeruginosa, Candida glabrata, Enterococcus faecalisPseudomonas aeruginosaCandida glabrataNonePseudomonas aeruginosaPseudomonas aeruginosaCytomegalovirusPseudomonas aeruginosa,Stenotropho-monas maltofiliaNoneRisk factorsHBP, DM2, ObesityHBP, DM2, Obesity, AsthmaHBP, DM2,CADObesityAKIHBP, Smoking, Obesity, HipothyroidismHBP, Obesity.ObesityHBP, ObesityDM2, ObesityHBP, DM2, CAD, VHDObesityAntibioticsCTR, CAZ/ABI, MEM, LZDMEM, LZD, VAN, TZP, VAN,CTZ/TAZOCRO, MEM, LZD, CAZ/ABICRO, MEM, LZD, CTZ/TZP, CSTCRO, LZD, CAZ, MEM, CAZ/ABICRO, CAZ,TZPAZM, LZD, CRO, VAN, CTZ/TZPCRO, LZD, CAZ, CAZ/ABI, VANCTZ/TZP, VAN, CRO, CSTCRO, LZD, CAZ, MEM, VGVTZP, MEM, CTZ/TZP, METROCRO, MEM, CAZ/ABI, LZDSARS-CoV-2 treatmentLPV/RTV, RBV, BARI, PLASMALPV/RTV, RBV, BARILPV/RTV, RBV, BARILPV/RTV, RBV, BARI, PLASMALPV/RTV, RBV, BARILPV/RTV, RBV, BARI, TOCI, PLASMALPV/RTV, RBV, BARI,LPV/RTV, RBV, BARI, PLASMALPV/RTV, RBV, BARILPV/RTV, RBV, BARI, TOCI, PLASMALPV/RTV, RBV, BARILPV/RTV, RBV, BARISteroidsDex 6mg QDHidro 100mg BIDDex 6mg QDMetil 60mg BIDDex 6mg QDHidro 100 BIDDex 6mg QDMetil 40mg BIDMetil40mg BIDDex 6mgQDMetil 125mg BIDHidro100mgTIDMetil 60mg BIDHidro 100mg TIDDex 6mg QDMetil 60mg BIDDex 6mg QDMetil 60mg BIDCumulative dose of steroids (mg prednisone)1480mg15801360144013001000124050002025255013203280AntifungalsCAS, ANFISA, CASANFISA, ANFCAS, VRC, AMB (intravesical)ANF, ISAAMB, CAS, VRCCAS, ANF, VRCANFCASVRC, CASVRC, CASInterleukin 6 (pg/mL)270.5NA89.56192.29.2944.13798.3NA235.9203.6NANAD dimer (ng/mL)83138325420005516150211714316,11144828084Ferritin (ng/mL)15633187170111,0074163369411996582235329220301307CultureBloodUrineBloodUrineBlood and UrineBlood, PIC line and UrineBloodUrineUrineUrineUrineBlood∗Number of days elapsed from hospital admission to the first positive culture for C. auris.Days to 1st. positive culture371729361310311627221127OutcomeDiedSurvivedDiedDiedDiedDiedDiedDiedDiedSurvived (Hospital transfer)SurvivedSurvivedB. MLST and antifungal susceptibility results of the C. auris isolates from the patients and surface sampling from an infusion pump (13) and bed rails (14 and 15).No. IsolateGenBank accession numbers (ITS-D1/D2-RPB1-RPB2)ST clusterMIC (μg/mL)AMBFLCVRCPOSITCISAANFCAS1MW087107-MW089312-MW091400- MW113720IV46410.520.5112MW087108-MW089313-MW091401- MW113721IV4160.25<0.030.250.06113MW087109-MW089314-MW091402- MW113722IV216<0.03<0.030.50.250.50.54MW087110-MW089315-MW091403- MW113723IV2160.50.0620.5115MW087111-MW089316-MW091404- MW113724IV2640.250.060.1250.1250.516MW087112-MW089317-MW091405- MW113725IV2160.1250.030.25110.57MW087113-MW089318-MW091406- MW113726IV4640.50.510.50.518MW087114-MW089319-MW091407- MW113727IV2320.250.030.50.1250.519MW087115-MW089320-MW091408- MW113728IV46410.1250.500.1250.5110MW087116-MW089321-MW091409- MW113729IV4320.1250.1250.1250.060.5111MW087117-MW089322-MW091410- MW113730IV480.06<0.030.060.12540.512MW087118-MW089323-MW091411- MW113731IV280.125<0.030.060.1250.5113MW087119-MW089324-MW091412- MW113732IV4320.060.060.1250.251214MW087120-MW089325-MW091413- MW113733IV4160.1250.060.1250.2520.515MW087121-MW089326-MW091414- MW113734IV4320.1250.250.50.511CTR: ceftaroline; CAZ: ceftazidime; CAZ/ABI: ceftazidime/abivactam; CRO: ceftriaxone; CTZ/TZP: ceftolozane/tazobactam; CST: colistin; AZM: azithromycin; VAN: vancomycin; MEM: meropenem; MTZ: metronidazole; TZP: piperacillin/tazobactam; ISA: isavuconazol; ANF: anidulafungin; CAS: caspofungin; AMB: amphotericin B; VRC: voriconazole; LPV/RTV: lopinavir/ritonavir; VGV: valgancyclovir; Metil: methylprednisolone; Hidro: hydrocortisone, DEX: dexametasone; BARI: baricitinib; TOCI: tocilizumab; CAD: coronary artery disease; VHD: valvular heart disease; HBP: high blood pressure; DM2: diabetes mellitus type 2; AKI: acute kidney injury; NA: not available; PIC: peripherally inserted central catheter.AMB: amphotericin B; FLC: fluconazole; VRC: voriconazole; POS: posaconazole; ITC: itraconazole; ISA: isavuconazole; ANF: anidulafungin; CAS: caspofungin; MIC: minimal inhibitory concentration; ST: sequence typing.∗ Number of days elapsed from hospital admission to the first positive culture for C. auris. Open table in a new tab CTR: ceftaroline; CAZ: ceftazidime; CAZ/ABI: ceftazidime/abivactam; CRO: ceftriaxone; CTZ/TZP: ceftolozane/tazobactam; CST: colistin; AZM: azithromycin; VAN: vancomycin; MEM: meropenem; MTZ: metronidazole; TZP: piperacillin/tazobactam; ISA: isavuconazol; ANF: anidulafungin; CAS: caspofungin; AMB: amphotericin B; VRC: voriconazole; LPV/RTV: lopinavir/ritonavir; VGV: valgancyclovir; Metil: methylprednisolone; Hidro: hydrocortisone, DEX: dexametasone; BARI: baricitinib; TOCI: tocilizumab; CAD: coronary artery disease; VHD: valvular heart disease; HBP: high blood pressure; DM2: diabetes mellitus type 2; AKI: acute kidney injury; NA: not available; PIC: peripherally inserted central catheter. AMB: amphotericin B; FLC: fluconazole; VRC: voriconazole; POS: posaconazole; ITC: itraconazole; ISA: isavuconazole; ANF: anidulafungin; CAS: caspofungin; MIC: minimal inhibitory concentration; ST: sequence typing. Sequences of the genes used for the 15 C. auris isolates clustered together in the dendrogram performed with the sequence previously reported from a non-COVID-19 patient, which belonged to the Clade IV (South American) [[4]Ayala-Gaytán J.J. Montoya A.M. Martínez-Resendez M.F. Guajardo-Lara C.E. Treviño-Rangel RdJ. Salazar-Cavazos L. et al.First case of Candida auris isolated from the bloodstream of a Mexican patient with serious gastrointestinal complications from severe endometriosis.Infection. 2020; : 1-3PubMed Google Scholar], suggesting a very close relationship. Antifungal susceptibility testing showed that all the isolates (15/15) were resistant to AMB (MIC ≥2 μg/mL), just one isolate was resistant to ANF (MIC ≥4 μg/mL), one to CAS (MIC ≥2 μg/mL) and eight isolates (8/15; 53.3%) were resistant to FLU (MIC ≥32 μg/mL). Eight isolates were multidrug-resistant (resistance to two major classes of antifungals) (Table 1B). Numerous reports have described COVID-19 co-infections by fungal pathogens, especially in critically ill patients. As stated in the work of Arasthefar et al. [[5]Arastehfar A. Carvalho A. Nguyen M.H. Hedayati M.T. Netea M.G. Perlin D.S. et al.Covid-19-associated candidiasis (CAC): an underestimated complication in the absence of immunological predispositions?.J Fungi. 2020; 6: 211Crossref Scopus (137) Google Scholar], classic risk factors commonly found in these patients include diabetes mellitus, use of multiple antibiotics, renal failure, and use of central venous catheters, but other factors specifically associated with COVID-19—such as excessive corticosteroid use, which has an immunosuppressive effect on neutrophils and macrophages—might also contribute to this problem. Nonetheless, a lot of interest still exists in elucidating a relationship between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immune response and predisposition to Candida infection [[2]Al-Hatmi A.M. Mohsin J. Al-Huraizi A. Khamis F. Covid-19 associated invasive candidiasis.J Infect. 2020; (S0163-4453:30539-9)Abstract Full Text Full Text PDF Scopus (46) Google Scholar]. In our report 12 patients have presented COVID-19-associated C. auris infection, and so far only three environmental samples have yielded this pathogen. The prolonged lag between the first case 3 months ago and current cases is thought to be due to measures taken during the transformation process from a general hospital to a COVID-19-exclusive facility, such as reinforcement of hand washing compliance and use of personal protective equipment (PPE). Chowdhary et al. [[6]Chowdhary A. Tarai B. Singh A. Sharma A. Multidrug-resistant Candida auris infections in critically ill coronavirus disease patients, India, April–July 2020.Emerg Infect Dis. 2020; 26: 2694-2696Crossref PubMed Scopus (175) Google Scholar] theorized that transmission of COVID-19-associated C. auris by health personnel is unlikely because of the use of PPE. The 15 isolates of C. auris were non-susceptible to AMB and FLU, which are the main antifungal drugs used in most of the hospitals in Mexico. This study has some limitations as it was conceived as a description of an outbreak; as such, there is no control group, and findings may not be generalizable to other populations. Nonetheless mortality in patients with COVID-19-associated C. auris bloodstream infection was exceedingly high, five of six patients died even with antifungal treatment; strict control of risk factors, such as central line care bundles, corticosteroids and antibiotic stewardship, must therefore be implemented to avoid the lethal combination of these two emergent infectious threats. HV-L, RJT-R and GMG contributed to drafting and revising the article, as well as in the conception and design of the study. RL-M, MTR-E and NG-Ch contributed to the acquisition and interpretation of data. FC-L, MCA-B, CEG-L and GT-A contributed to revision and final approval of the report. MFM-R participated in the analysis and interpretation of data, drafting and final approval of the version to be submitted. All authors declare no conflicts of interest. This work was supported by internal resources of the department. We thank all the health personnel involve in the attention and care of these patients, specially to Mauricio Sánchez-Rodríguez MD and Alvaro E. Camero-Garza MD. We also thank Gerald Martin Rhoades-Torres MD for his review of the manuscript prior to submission.