key: cord-0936443-5uusko1g authors: Denny, Sarah; Abdolrasouli, Alireza; Elamin, Tamador; Gonzalo, Ximena; Pallett, Scott; Charani, Esmita; Patel, Aatish; Donaldson, Hugo; Hughes, Stephen; Armstrong-James, Darius; Moore, Luke SP; Mughal, Nabeela title: A retrospective multicenter analysis of candidaemia among COVID-19 patients during the first UK pandemic wave date: 2021-02-18 journal: J Infect DOI: 10.1016/j.jinf.2021.02.020 sha: 40a2af0b31f1d0364a84228514b89d442987411d doc_id: 936443 cord_uid: 5uusko1g nan 19. An increased incidence of candidaemia has been noted in patients with COVID-19 and although patient characteristics, investigations and antifungal therapies have been described (2) , to our knowledge, compliance with candidaemia management bundles has not (3). Here, we present a retrospective review of candidaemias in adult patients (>17 years) with PCR proven COVID-19 between 1 st March 2020 -31 st May 2020 across six acute London hospitals. All yeasts isolated from blood cultures were identified by matrix assisted laser desorption/ionisation-time-of-flight (MALDI-TOF) mass spectroscopy (Bruker Daltonik GmbH, Bremen, Germany). Antifungal susceptibility testing was carried out using broth micro-dilution in accordance with EUCAST guidelines (4) . An episode of candidaemia was defined as blood culture growth of any Candida species. Eleven patients with concurrent candidaemia and PCR-proven COVID-19 were identified during the study period; ten were male (90.9%), mean age 62 (33-77 years). Underlying comorbidities were predominantly cardiovascular (10/11). Two patients were immunosuppressed (see Table 1 ), but neutropenia was not identified. Ten patients (90.9%) were admitted to an intensive care unit (ICU) prior to their candidaemia diagnosis. Of the ICU patients (n=10), all were intubated and ventilated, had an intravascular and urinary catheter and received inotropes. The non-ICU patient also had a urinary catheter. Nine (90%) of the ICU patients received haemofiltration. None of the patients in our cohort received total parenteral nutrition. All eleven patients received broad-spectrum antibacterials. One patient received prior antifungal treatment in hospital with topical clotrimazole and oral terbinafine for a tinea infection. The average number of days from PCR-proven COVID-19 to candidaemia was 14.8 days and from ICU admission to candidaemia, 15.5 days (range 6-24 days). Seven out of eleven candidaemias (63.6%) were C.albicans, two (18.2%) C.parapsilosis, one (9.1%) C. glabrata and one (9.1%) C.dubliniensis. All isolates were fluconazole susceptible, except one (Candida glabrata), which showed intermediate susceptibility, although the patient was successfully treated with azole therapy through dose-optimisation. An echinocandin was commenced for ten patients, as per local guidelines, pending susceptibility testing. One patient died prior to blood culture positivity and treatment. Four out of ten (40%) patients were switched to fluconazole to complete treatment. In line with recommended practice (3) six out of eleven patients (54.5%) had repeat blood cultures within 48 hours of treatment, eight (72.7%) patients had an echocardiogram, but only one (9.1%) had fundoscopy. Serum (1-3)-β-D-glucan(BDG) testing was performed in 54.4% (6/11) of patients; three were positive(see Table 1 ). Intravascular catheters were removed for nine out of ten patients (90%), the last patient dying prior to candidaemia notification. Seven out of nine patients had line tips sent for culture; two were positive for yeasts. One line tip confirmed an identical Candida spp., and hence constituted a line infection, but no further identification was available for the second. Four patients had prior colonization with yeasts; one with the same species as their candidaemia, no further identification was available for the remaining three. Five patients were not colonized and two had an unknown status following transfer from other secondary care providers, developing candidaemia shortly after transfer. In concordance with Mastrangelo et al (1), there was a high 30-day mortality of 54.4% (6/11) in our patient cohort. The four surviving patients (36.6%) were discharged; average total length of stay 58 days (range 31-78 days). One patient was stepped down after nine weeks in ICU but remained an inpatient until the end of our study period. Given the high mortality rate, it is important to identify and address modifiable risk factors in an attempt to prevent the occurrence of candidaemia. Firstly, all our patients received broad-spectrum antibacterials, a recognized risk factor for candidaemia (5, 6) . A recent study from Hughes et al (7) Secondly, intravascular catheters are a well-recognised risk factor for candidaemia (5) and over 90% of our patients had these. The incidence of candidaemia observed warrants further consideration, and whilst not compared to pre-COVID-19 incidence (2), may potentially reflect pandemic unique challenges. Examples include increased ICU capacity, redeployment of less-experienced staff to ICU, challenges to aseptic technique with personal protective equipment (PPE), and patients requiring re-positioning to improve oxygenation, thus increasing possibility of line displacement/contamination. Improved aseptic intravascular catheter training focusing on PPE may be beneficial. In addition, although we were unable to identify urinary catheters as a source in our cohort, they are a recognized risk factor for candidaemia (6) and all patients in our cohort had these. One patient died prior to candidaemia notification. Time to blood culture positivity may be delayed, particularly for non-albicans candidaemias (8) , and delay in treatment is known to increase mortality (9), therefore, non-culture-based diagnostics such as galactomannan antigen and BDG should be combine with clinical data to aid diagnosis (10). 54.4% (n=6) of the patients were tested for BDG, and of those, 50% (n=3) were positive. Although not possible to demonstrate in this patient cohort, an early positive BDG may herald invasive fungal infection, enabling timely initiation of empirical antifungal therapy. Guidelines for management of candidaemia recommend a care bundle, including repeat blood cultures at 48 hours, echocardiogram, and fundoscopy to identify Ethical approval was not required for this service evaluation and audit of practice. SD, AR and NM designed the study methodology. SD, TE and XG collated the data. SD drafted the initial manuscript with all authors contributing significantly to revising this for submission. All authors agreed on the final version for submission to the journal. This research did not receive any grant from funding agencies in the public or commercial sectors. SC has received a research grants from the Scientific Exploration Society. EC has been paid for consultancy fees by bioMerieux. All other authors have no conflicts of interest to declare. The data analysed during the current study and further details on the assays are available from the corresponding author (SD; sarahdenny1@nhs.net) on reasonable request, as long as this meets local ethical and research governance criteria. Co-infection of Chlamydia pneumoniae and Mycoplasma pneumoniae with SARS-CoV-2 is associated with more severe features. The Journal of infection Candidemia in COVID-19 patients: incidence and characteristics in a prospective cohort compared to historical non-COVID-19 controls. 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