Detection and characterisation of a sixth Candida auris clade in Singapore: a genomic and phenotypic study.

BACKGROUND: The emerging fungal pathogen Candida auris poses a serious threat to global public health due to its worldwide distribution, multidrug resistance, high transmissibility, propensity to cause outbreaks, and high mortality. We aimed to characterise three unusual C auris isolates detected in Singapore, and to determine whether they constitute a novel clade distinct from all previously known C auris clades (I-V). METHODS: In this genotypic and phenotypic study, we characterised three C auris clinical isolates, which were cultured from epidemiologically unlinked inpatients at a large tertiary hospital in Singapore. The index isolate was detected in April, 2023. We performed whole-genome sequencing (WGS) and obtained hybrid assemblies of these C auris isolates. The complete genomes were compared with representative genomes of all known C auris clades. To provide a global context, 3651 international WGS data from the National Center for Biotechnology Information (NCBI) database were included in a high-resolution single nucleotide polymorphism (SNP) analysis. Antifungal susceptibility testing was done and antifungal resistance genes, mating-type locus, and chromosomal rearrangements were characterised from the WGS data of the three investigated isolates. We further implemented Bayesian logistic regression models to classify isolates into known clades and simulate the automatic detection of isolates belonging to novel clades as their WGS data became available. FINDINGS: The three investigated isolates were separated by at least 37 000 SNPs (range 37 000-236 900) from all existing C auris clades. These isolates had opposite mating-type allele and different chromosomal rearrangements when compared with their closest clade IV relatives. The isolates were susceptible to all tested antifungals. Therefore, we propose that these isolates represent a new clade of C auris, clade VI. Furthermore, an independent WGS dataset from Bangladesh, accessed via the NCBI Sequence Read Archive, was found to belong to this new clade. As a proof-of-concept, our Bayesian logistic regression model was able to flag these outlier genomes as a potential new clade. INTERPRETATION: The discovery of a new C auris clade in Singapore and Bangladesh in the Indomalayan zone, showing a close relationship to clade IV members most commonly found in South America, highlights the unknown genetic diversity and origin of C auris, particularly in under-resourced regions. Active surveillance in clinical settings, along with effective sequencing strategies and downstream analysis, will be essential in the identification of novel strains, tracking of transmission, and containment of adverse clinical effects of C auris infections. FUNDING: Duke-NUS Academic Medical Center Nurturing Clinician Researcher Scheme, and the Genedant-GIS Innovation Program.

Rapid management of Serratia marcescens outbreak in neonatology unit in Singapore: Risk factors and infection control measures.

BACKGROUND: We describe the investigations for control of two consecutive Serratia marcescens outbreaks in neonatology unit of Singapore General Hospital. METHODS: Epidemiological investigations, environmental sampling and risk-factors analysis were performed to guide infection control measures. Active surveillance sampling of nasopharyngeal aspirate and/or stool from neonates was conducted during both outbreaks. Whole-genome-sequencing was done to determine clonal links. Retrospective case-control study was conducted for second outbreak to identify risk factors for S marcescens acquisition. RESULTS: In 2022, two genetically unrelated S marcescens outbreaks were managed involving five neonates in March 2022 (outbreak 1) and eight neonates in November 2022 (outbreak 2). A link to positive isolates from sinks in intensive care units and milk preparation room was identified during outbreak 1. Neonatal jaundice (aOR, 16.46; p-value= 0.023) and non-formula milk feeding (aOR, 13.88; p-value= 0.02) were identified as risk factors during second outbreak. Multiple interventions adopted were cohorting of positive cases, carriage-screening, enhanced environmental cleaning, and emphasis on alcohol-based handrubs for hand-hygiene. CONCLUSION: The two outbreaks were likely due to infection prevention practices lapses and favourable environmental conditions. Nosocomial S marcescens outbreaks in neonatology units are difficult to control and require multidisciplinary approach with strict infection prevention measures to mitigate risk factors.

Environmental contamination and evaluation of healthcare-associated SARS-CoV-2 transmission risk in temporary isolation wards during the COVID-19 pandemic.

BACKGROUND: Temporary isolation wards have been introduced to meet demands for airborne-infection-isolation-rooms (AIIRs) during the COVID-19 pandemic. Environmental sampling and outbreak investigation was conducted in temporary isolation wards converted from general wards and/or prefabricated containers, in order to evaluate the ability of such temporary isolation wards to safely manage COVID-19 cases over a period of sustained use. METHODS: Environmental sampling for SARS-CoV-2 RNA was conducted in temporary isolation ward rooms constructed from pre-fabricated containers (N = 20) or converted from normal-pressure general wards (N = 47). Whole genome sequencing (WGS) was utilized to ascertain health care-associated transmission when clusters were reported amongst HCWs working in isolation areas from July 2020 to December 2021. RESULTS: A total of 355 environmental swabs were collected; 22.4% (15/67) of patients had at least one positive environmental sample. Patients housed in temporary isolation ward rooms constructed from pre-fabricated containers (adjusted-odds-ratio, aOR = 10.46, 95% CI = 3.89-58.91, P = .008) had greater odds of detectable environmental contamination, with positive environmental samples obtained from the toilet area (60.0%, 12/20) and patient equipment, including electronic devices used for patient communication (8/20, 40.0%). A single HCW cluster was reported amongst staff working in the temporary isolation ward constructed from pre-fabricated containers; however, health care-associated transmission was deemed unlikely based on WGS and/or epidemiological investigations. CONCLUSION: Environmental contamination with SARS-CoV-2 RNA was observed in temporary isolation wards, particularly from the toilet area and smartphones used for patient communication. However, despite intensive surveillance, no healthcare-associated transmission was detected in temporary isolation wards over 18 months of prolonged usage, demonstrating their capacity for sustained use during succeeding pandemic waves.

Healthcare-associated multispecies outbreaks of OXA-48-positive carbapenemase-producing Enterobacteriaceae in a Singapore tertiary-care hospital.

OBJECTIVE: To describe OXA-48-like carbapenem-producing Enterobacteriaceae (CPE) outbreaks at Singapore General Hospital between 2018 and 2020 and to determine the risk associated with OXA-48 carriage in the 2020 outbreak. DESIGN: Outbreak report and case-control study. SETTING: Singapore General Hospital (SGH) is a tertiary-care academic medical center in Singapore with 1,750 beds. METHODS: Active surveillance for CPE is conducted for selected high-risk patient cohorts through molecular testing on rectal swabs or stool samples. Patients with CPE are isolated or placed in cohorts under contact precautions. During outbreak investigations, rectal swabs are repeated for culture. For the 2020 outbreak, a retrospective case-control study was conducted in which controls were inpatients who tested negative for OXA-48 and were selected at a 1:3 case-to-control ratio. RESULTS: Hospital wide, the median number of patients with healthcare-associated OXA-48 was 2 per month. In the 3-year period between 2018 and 2020, 3 OXA-48 outbreaks were investigated and managed, involving 4 patients with Klebsiella pneumoniae in 2018, 55 patients with K. pneumoniae or Escherichia coli in 2019, and 49 patients with multispecies Enterobacterales in 2020. During the 2020 outbreak, independent risk factors for OXA-48 carriage on multivariate analysis (49 patients and 147 controls) were diarrhea within the preceding 2 weeks (OR, 3.3; 95% CI, 1.1-10.7; P = .039), contact with an OXA-48-carrying patient (OR, 8.7; 95% CI, 1.9-39.3; P = .005), and exposure to carbapenems (OR, 17.2; 95% CI, 2.2-136; P = .007) or penicillin (OR, 16.6; 95% CI, 3.8-71.0; P < .001). CONCLUSIONS: Multispecies OXA-48 outbreaks in our institution are likely related to a favorable ecological condition and selective pressure exerted by antimicrobial use. The integration of molecular surveillance epidemiology of the healthcare environment is important in understanding the risk of healthcare-associated infection to patients.

Linking sporadic hospital clusters during a community surge of the severe acute respiratory coronavirus virus 2 (SARS-CoV-2) B.1.617.2 delta variant: The utility of whole-genome sequencing.

Sporadic clusters of healthcare-associated coronavirus disease 2019 (COVID-19) occurred despite intense rostered routine surveillance and a highly vaccinated healthcare worker (HCW) population, during a community surge of the severe acute respiratory coronavirus virus 2 (SARS-CoV-2) B.1.617.2 δ (delta) variant. Genomic analysis facilitated timely cluster detection and uncovered additional linkages via HCWs moving between clinical areas and among HCWs sharing a common lunch area, enabling early intervention.

Unintended consequences of infection prevention and control measures during COVID-19 pandemic.

BACKGROUND: In the current COVID-19 pandemic, aggressive Infection Prevention and Control (IPC) measures have been adopted to prevent health care-associated transmission of COVID-19. We evaluated the impact of a multimodal IPC strategy originally designed for the containment of COVID-19 on the rates of other hospital-acquired-infections (HAIs). METHODOLOGY: From February-August 2020, a multimodal IPC strategy was implemented across a large health care campus in Singapore, comprising improved segregation of patients with respiratory symptoms, universal masking and heightened adherence to Standard Precautions. The following rates of HAI were compared pre- and postpandemic: health care-associated respiratory-viral-infection (HA-RVI), methicillin-resistant Staphylococcus aureus, and CP-CRE acquisition rates, health care-facility-associated C difficile infections and device-associated HAIs. RESULTS: Enhanced IPC measures introduced to contain COVID-19 had the unintended positive consequence of containing HA-RVI. The cumulative incidence of HA-RVI decreased from 9.69 cases per 10,000 patient-days to 0.83 cases per 10,000 patient-days (incidence-rate-ratio = 0.08; 95% confidence interval [CI] = 0.05-0.13, P< .05). Hospital-wide MRSA acquisition rates declined significantly during the pandemic (incidence-rate-ratio = 0.54, 95% CI = 0.46-0.64, P< .05), together with central-line-associated-bloodstream infection rates (incidence-rate-ratio = 0.24, 95% CI = 0.07-0.57, P< .05); likely due to increased compliance with Standard Precautions. Despite the disruption caused by the pandemic, there was no increase in CP-CRE acquisition, and rates of other HAIs remained stable. CONCLUSIONS: Multimodal IPC strategies can be implemented at scale to successfully mitigate health care-associated transmission of RVIs. Good adherence to personal-protective-equipment and hand hygiene kept other HAI rates stable even during an ongoing pandemic where respiratory infections were prioritized for interventions.

Early Recognition of Coronavirus 2019 Disease (COVID-19) Infection in Surgical Inpatients: The Importance of a Risk-Stratified Approach for Early Testing and Isolation.

Background: In the ongoing coronavirus disease 2019 (COVID-19) pandemic, resuming provision of surgical services poses a challenge given that patients may have acute surgical pathologies with concurrent COVID-19 infection. We utilized a risk-stratified approach to allow for early recognition and isolation of potential COVID-19 infection in surgical patients, ensuring continuity of surgical services during a COVID-19 outbreak. Patients and Methods: Over a four-month period from January to April 2020, surgical patients admitted with concurrent respiratory symptom, infiltrates on chest imaging, or suspicious travel/epidemiologic history were placed in a dedicated ward in which they were tested for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). If emergency operations were necessary prior to the exclusion of COVID-19, patients were managed as per suspected cases of COVID-19, with appropriate precautions and full personal protective equipment (PPE). Results: From January through April 2020, a total of 8,437 patients were admitted to our surgical department; 5.9% (498/8437) required peri-operative testing for SARS-CoV-2. Because testing was in-house with turnaround within 24 hours, only a small number of emergency operations (n = 10) were conducted for suspected COVID-19 cases prior to results; none tested positive. The testing yield was lower in surgical inpatients compared with medical inpatients (odds ratio [OR] = 0.20, 95% confidence interval [CI], 0.12-0.32, p < 0.001). Three operations were conducted in known COVID-19 cases; all healthcare workers (HCWs) used full PPE. A risk-stratified testing strategy picked up previously unsuspected COVID-19 in six cases; 66.7% (4/6) were asymptomatic at presentation. Although 48 HCWs were exposed to these six cases, delayed diagnosis was averted and no evidence of spread to patients or HCWs was detected. Conclusion: A risk-stratified approach allowed for early recognition, testing, and isolation of potential COVID-19 infection in surgical patients, ensuring continuity of surgical services.

Containing COVID-19 outside the isolation ward: The impact of an infection control bundle on environmental contamination and transmission in a cohorted general ward.

BACKGROUND: During an ongoing outbreak of COVID-19, unsuspected cases may be housed outside of dedicated isolation wards. AIM: At a Singaporean tertiary hospital, individuals with clinical syndromes compatible with COVID-19 but no epidemiologic risk were placed in cohorted general wards for COVID-19 testing. To mitigate risk, an infection control bundle was implemented comprising infrastructural enhancements, improved personal protective equipment, and social distancing. We assessed the impact on environmental contamination and transmission. METHODS: Upon detection of a case of COVID-19 in the dedicated general ward, patients and health care workers (HCWs) contacts were identified. All patient and staff close-contacts were placed on 14-day phone surveillance and followed up for 28 days; symptomatic contacts were tested. Environmental samples were also obtained. FINDINGS: Over a 3-month period, 28 unsuspected cases of COVID-19 were contained in the dedicated general ward. In 5 of the 28 cases, sampling of the patient's environment yielded SARS-CoV-2; index cases who required supplemental oxygen had higher odds of environmental contamination (P = .01). A total of 253 staff close-contacts and 45 patient close-contacts were identified; only 3 HCWs (1.2%, 3/253) required quarantine. On 28-day follow-up, no patient-to-HCW transmission was documented; only 1 symptomatic patient close-contact tested positive. CONCLUSIONS: Our institution successfully implemented an intervention bundle to mitigate COVID-19 transmission in a multibedded cohorted general ward setting.

Healthcare workers' beliefs, attitudes and compliance with mobile phone hygiene in a main operating theatre complex.

BACKGROUND: Phone hygiene is increasingly recognized in infection prevention. We aimed to explore the beliefs, attitudes and performance of phone hygiene amongst healthcare workers (HCWs) in the major operation theatre (MOT) complex of a Singapore tertiary acute care hospital. We also monitored the impact of phone hygiene stations, introduced to improve phone hygiene. METHODS: We sent two online anonymous surveys to the Departments of Anaesthesia and MOT Nurses one month before and after we set up phone hygiene stations. Four phone hygiene stations displaying visual phone hygiene reminders and Mikrozid® sensitive wipes were set up at MOT entrances. RESULTS: A total of 205 and 91 HCWs responded to the first and second surveys respectively. In the first survey, 11.5% cleaned their phones daily while 9.4% never cleaned their phones. These changed to 16.9% and 3.8% respectively after the introduction of phone hygiene stations. 80.0% in the first survey said they would clean their phones more often if there were a readily accessible disinfection method in the MOT. A majority believed phones are a source of healthcare associated infection. Common reasons for not cleaning phones were 'lack of available resources' and 'I don't think about it.' Senior doctors were the least compliant to phone hygiene. CONCLUSION: Phone hygiene is easily overlooked during our busy workday. Besides increasing awareness of phone hygiene, having a readily available disinfection method in the MOT complex is important to improve phone hygiene. We suggest HCWs clean their phones before entering and/or after leaving the MOT daily.

Risk factors for acquisition of carbapenem resistant Enterobacteriaceae in an acute tertiary care hospital in Singapore.

BACKGROUND: Carbapenem resistant Enterobacteriaceae (CRE) is increasingly reported worldwide. A similar increase is seen in Singapore since identification of its first case in 2008. The aim of this study was to identify local risk factors for carriage of CRE in patients from an acute tertiary care hospital in Singapore. METHOD: A matched case-control study was conducted on inpatients treated from January 1, 2011 till December 31, 2013. Two hundred and three cases of CRE infection or colonization were matched with 203 controls. CRE types were identified by PCR. Statistical analysis of data including a multivariate logistic regression analysis was done using SPSS 21.0. RESULTS: CREs were commonly seen in Klebsiella pneumoniae (42.2 %), Escherichia coli (24.3 %) and Enterobacter cloacae complex (17.2 %) in the 268 isolates. NDM-1 was the commonest CRE type seen (44.4 %), followed by KPC (39.9 %) whilst OXA-48 only constituted (7.8 %). Univariate analysis identified key risk factors associated with CRE as history of previous overseas hospitalization (OR: 33.667; 95 % CI: 4.539-259.700), admission to ICU (OR: 11.899; 95 % CI: 4.986-28.399) and HD/ICA (OR: 6.557; 95 % CI: 4.057-10.596); whilst a multivariate analysis revealed exposure to antibiotics penicillin (OR: 4.640; 95 % CI: 1.529-14.079] and glycopeptide (OR: 5.162; 95 % CI: 1.377-19.346) and presence of central line device (OR: 3.117; 95 % CI: 1.167-8.330) as significant independent predictors. CONCLUSIONS: The identification of risk factors amongst our local population helped to refine the criteria used for target active surveillance screening for CRE amongst inpatients at time of hospital admission.

Active surveillance testing and decontamination strategies in intensive care units to reduce methicillin-resistant Staphylococcus aureus infections.

BACKGROUND: Active surveillance testing (AST) and decontamination strategies (DS) using a topical methicillin-resistant Staphylococcus aureus (MRSA) cleansing agent was introduced in July 2007 in a medical intensive care unit (MICU) and a surgical ICU (SICU) of a tertiary care hospital to reduce the incidence of MRSA infection. METHODS: Data on ICU admissions between July 1, 2007, and June 30, 2008, was analyzed. All subjects, excluding known MRSA status, had an ICU length of stay (LOS) of more than 24 hours and nasal swabs performed on ICU admission, every 7 days during the ICU stay, and on discharge. MICU and SICU specimens were sent for culture and in-house real-time polymerase chain reaction, respectively. MRSA-colonized (MRSAc) patients were subjected to contact isolation precautions and DS for 5 days or until ICU discharge. Data recorded included demographics, LOS, and antibiotic use. Results were analyzed using SPSS. Control charts were used to determine special cause variation. RESULTS: Of 653 eligible patients admitted to the ICU, 85 (13%) were determined to be MRSAc on ICU admission. A further 15% (52 of 351) were determined to be MRSAc during the ICU stay or at discharge. Thus, AST detected MRSA in at least 137 of the 653 patients (21.0%). In contrast, clinical cultures for MRSA were positive in only 12 patients (1.8%). Compared with noncolonized patients, MRSAc patients at any screening point had a longer pre-ICU LOS (P =.001), received more antibiotics (P = .004), and had a longer ICU LOS (P = .003). Compared with the preintervention period of July 2006 to June 2007, there was no significant reduction in mean MRSA infection incidence rate in both ICUs (3.8 to 3.0 per 1000 patient-days [P = .057] in the SICU and 1.4 to 1.7 per 1000 patient-days in the MICU) following intervention. CONCLUSIONS: In ICUs, AST detected 11 times more MRSA than clinical cultures. The lack of reduction in MRSA infection rates in the ICUs does not negate the roles of AST and DS, but does argue for better study design and outcome measures like MRSA transmission incidence, which perhaps would have demonstrated a true benefit of AST and DS.