Impact of COVID-19 pandemic on carbapenem-resistant Enterobacterales incidence in the South-East Asia region: an observational study.

The COVID-19 pandemic led to an initial increase in the incidence of carbapenem-resistant Enterobacterales (CRE) from clinical cultures in South-East Asia hospitals, which was unsustained as the pandemic progressed. Conversely, there was a decrease in CRE incidence from surveillance cultures and overall combined incidence. Further studies are needed for future pandemic preparedness.

Whole genome sequencing reveals hidden transmission of carbapenemase-producing Enterobacterales.

Carbapenemase-producing Enterobacterales (CPE) infection control practices are based on the paradigm that detected carriers in the hospital transmit to other patients who stay in the same ward. The role of plasmid-mediated transmission at population level remains largely unknown. In this retrospective cohort study over 4.7 years involving all multi-disciplinary public hospitals in Singapore, we analysed 779 patients who acquired CPE (1215 CPE isolates) detected by clinical or surveillance cultures. 42.0% met putative clonal transmission criteria, 44.8% met putative plasmid-mediated transmission criteria and 13.2% were unlinked. Only putative clonal transmissions associated with direct ward contact decreased in the second half of the study. Both putative clonal and plasmid-mediated transmission associated with indirect (no temporal overlap in patients' admission period) ward and hospital contact did not decrease during the study period. Indirect ward and hospital contact were identified as independent risk factors associated with clonal transmission. In conclusion, undetected CPE reservoirs continue to evade hospital infection prevention measures. New measures are needed to address plasmid-mediated transmission, which accounted for 50% of CPE dissemination.

Preparation and consideration for establishment of an isolation maternity unit in a tertiary hospital during COVID-19 pandemic.

The SARS-CoV-2 pandemic is rapidly evolving and remains a major health challenge worldwide. With an increase in pregnant women with COVID-19 infection, we recognized an urgent need to set up a multidisciplinary taskforce to provide safe and holistic care for this group of women. In this review of practice in a tertiary hospital in Singapore, we discuss the key considerations in setting up an isolation maternity unit and our strategies for peripartum and postpartum care. Through teleconsultation, we involve these women and their families in the discussion of timing and mode of birth, disposition of babies after birth and safety of breastfeeding to enable them to make informed decisions and individualize their care.

Low incidence of venous thrombosis but high incidence of arterial thrombotic complications among critically ill COVID-19 patients in Singapore.

BACKGROUND: Arterial and venous thrombosis are reported to be common in critically ill COVID-19 patients. METHOD AND RESULTS: This is a national multicenter retrospective observational study involving all consecutive adult COVID-19 patients who required intensive care units (ICU) admission between 23 January 2020 and 30 April 2020 in Singapore. One hundred eleven patients were included and the venous and arterial thrombotic rates in ICU were 1.8% (n = 2) and 9.9% (n = 11), respectively. Major bleeding rate was 14.8% (n = 16). CONCLUSIONS: Critically ill COVID-19 patients in Singapore have lower venous thromboembolism but higher arterial thrombosis rates and bleeding manifestations than other reported cohorts.

A comparative study on the clinical features of COVID-19 with non-SARS-CoV-2 respiratory viral infections.

During this coronavirus disease 2019 (COVID-19) pandemic, physicians have the important task of risk stratifying patients who present with acute respiratory illnesses. Clinical presentation of COVID-19, however, can be difficult to distinguish from other respiratory viral infections. Thus, identifying clinical features that are strongly associated with COVID-19 in comparison to other respiratory viruses can aid risk stratification and testing prioritization especially in situations where resources for virological testing and resources for isolation facilities are limited. In our retrospective cohort study comparing the clinical presentation of COVID-19 and other respiratory viral infections, we found that anosmia and dysgeusia were symptoms independently associated with COVID-19 and can be important differentiating symptoms in patients presenting with acute respiratory illness. On the other hand, laboratory abnormalities and radiological findings were not statistically different between the two groups. In comparing outcomes, patients with COVID-19 were more likely to need high dependency or intensive care unit care and had a longer median length of stay. With our findings, we emphasize that epidemiological risk factors and clinical symptoms are more useful than laboratory and radiological abnormalities in differentiating COVID-19 from other respiratory viral infections.

Cohort study to evaluate the effect of vitamin D, magnesium, and vitamin B12 in combination on progression to severe outcomes in older patients with coronavirus (COVID-19).

OBJECTIVES: The aim of this study was to determine clinical outcomes of older patients with coronavirus (COVID-19) who received a combination of vitamin D, magnesium, and vitamin B12 (DMB) compared with those who did not. We hypothesized that fewer patients administered this combination would require oxygen therapy, intensive care support, or a combination of both than those who did not. METHODS: This was a cohort observational study of all consecutive hospitalized patients ≥50 y of age with COVID-19 in a tertiary academic hospital. Before April 6, 2020, no patients received the (DMB) combination. After this date, patients were administered 1000 IU/d oral vitamin D3, 150 mg/d oral magnesium, and 500 mcg/d oral vitamin B12 upon admission if they did not require oxygen therapy. Primary outcome was deterioration leading to any form of oxygen therapy, intensive care support, or both. RESULTS: Between January 15 and April 15, 2020, we identified 43 consecutive patients ≥50 y of age with COVID-19. Seventeen patients received DMB before onset of primary outcome and 26 patients did not. Baseline demographic characteristics between the two groups were significantly different by age. In univariate analysis, age and hypertension had a significant influence on outcome. After adjusting for age or hypertension separately in a multivariate analysis, the intervention group retained protective significance. Fewer treated patients than controls required initiation of oxygen therapy during hospitalization (17.6 vs 61.5%, P = 0.006). DMB exposure was associated with odds ratios of 0.13 (95% confidence interval [CI], 0.03-0.59) and 0.20 (95% CI, 0.04-0.93) for oxygen therapy, intensive care support, or both on univariate and multivariate analyses, respectively. CONCLUSIONS: A vitamin D / magnesium / vitamin B12 combination in older COVID-19 patients was associated with a significant reduction in the proportion of patients with clinical deterioration requiring oxygen support, intensive care support, or both. This study supports further larger randomized controlled trials to ascertain the full benefit of this combination in ameliorating the severity of COVID-19.

Experience of a Tertiary Hospital in Singapore with Management of a Dual Outbreak of COVID-19 and Dengue.

During the COVID-19 pandemic, distinguishing dengue from cases of COVID-19 in endemic areas can be difficult. In a tertiary hospital contending with COVID-19 during a dengue epidemic, a triage strategy of routine COVID-19 testing for febrile patients with viral prodromes was used. All febrile patients with viral prodromes and no epidemiologic risk for COVID-19 were first admitted to a designated ward for COVID-19 testing, where enhanced personal protective equipment was used by healthcare workers until COVID-19 was ruled out. From January to May 2020, 11,086 admissions were screened for COVID-19; 868 cases of COVID-19 were diagnosed in our institution, along with 380 cases of dengue. Only 8.5% (943/11,086) of suspected COVID-19 cases were concurrently tested for dengue serology due to a compatible overlapping clinical syndrome, and dengue was established as an alternative diagnosis in 2% (207/10,218) of suspected COVID-19 cases that tested negative. There were eight COVID-19 cases with likely false-positive dengue serology and one probable COVID-19/dengue coinfection. From April to May 2020, 251 admissions presenting as viral prodromes with no respiratory symptoms were screened; of those, 15 cases had COVID-19, and 2/15 had false-positive dengue IgM. Epidemiology investigations showed no healthcare-associated transmission. In a dengue epidemic season coinciding with a COVID-19 pandemic, dengue was established as an alternative diagnosis in a minority of COVID-19 suspects, likely due to early availability of basic diagnostics. Routine screening of patients with viral prodromes during a dual outbreak of COVID-19 and dengue enabled containment of COVID-19 cases masquerading as dengue with false-positive IgM.

Subacute thyroiditis associated with COVID-19.

We report a case of a hospitalised patient with COVID-19 who developed subacute thyroiditis in association with SARS-COV-2 infection. The patient presented with tachycardia, anterior neck pain and thyroid function tests revealing hyperthyroidism together with consistent ultrasonographic evidence suggesting subacute thyroiditis. Treatment with corticosteroids resulted in rapid clinical resolution. This case illustrates that subacute thyroiditis associated with viruses such as SARS-CoV-2 should be recognised as a complication of COVID-19 and considered as a differential diagnosis when infected patients present with tachycardia without evidence of progression of COVID-19 illness.

Antimicrobial stewardship programme: a vital resource for hospitals during the global outbreak of coronavirus disease 2019 (COVID-19).

Healthcare resources are being diverted for the containment and control of coronavirus disease 2019 (COVID-19). During this outbreak, it is cautioned that antibiotic misuse may be increased, especially for respiratory tract infections. With stewardship interventions, the duration of antibiotic therapy and length of stay of hospitalized patients can be reduced significantly. Antibiotic stewardship programmes should continually engage and educate prescribers to mitigate antibiotic misuse during the COVID-19 pandemic.

Acquisition of Plasmid with Carbapenem-Resistance Gene blaKPC2 in Hypervirulent Klebsiella pneumoniae, Singapore.

The convergence of carbapenem-resistance and hypervirulence genes in Klebsiella pneumoniae has led to the emergence of highly drug-resistant superbugs capable of causing invasive disease. We analyzed 556 carbapenem-resistant K. pneumoniae isolates from patients in Singapore hospitals during 2010-2015 and discovered 18 isolates from 7 patients also harbored hypervirulence features. All isolates contained a closely related plasmid (pKPC2) harboring blaKPC-2, a K. pneumoniae carbapenemase gene, and had a hypervirulent background of capsular serotypes K1, K2, and K20. In total, 5 of 7 first patient isolates were hypermucoviscous, and 6 were virulent in mice. The pKPC2 was highly transmissible and remarkably stable, maintained in bacteria within a patient with few changes for months in the absence of antimicrobial drug selection pressure. Intrapatient isolates were also able to acquire additional antimicrobial drug resistance genes when inside human bodies. Our results highlight the potential spread of carbapenem-resistant hypervirulent K. pneumoniae in Singapore.

Antecedent Carbapenem Exposure as a Risk Factor for Non-Carbapenemase-Producing Carbapenem-Resistant Enterobacteriaceae and Carbapenemase-Producing Enterobacteriaceae.

Carbapenem-resistant Enterobacteriaceae (CRE) can be mechanistically classified into carbapenemase-producing Enterobacteriaceae (CPE) and non-carbapenemase-producing carbapenem nonsusceptible Enterobacteriaceae (NCPCRE). We sought to investigate the effect of antecedent carbapenem exposure as a risk factor for NCPCRE versus CPE. Among all patients with CRE colonization and infection, we conducted a case-control study comparing patients with NCPCRE (cases) and patients with CPE (controls). The presence of carbapenemases was investigated with phenotypic tests followed by PCR for predominant carbapenemase genes. We included 843 unique patients with first-episode CRE, including 387 (45.9%) NCPCRE and 456 (54.1%) CPE. The resistance genes detected in CPEs were blaNDM (42.8%), blaKPC (38.4%), and blaOXA-48-like (12.1%). After adjusting for confounders and clustering at the institutional level, the odds of prior 30-day carbapenem exposure was three times higher among NCPCRE than CPE patients (adjusted odds ratio [aOR], 3.48; 95% confidence interval [CI], 2.39 to 5.09; P < 0.001). The odds of prior carbapenem exposure and NCPCRE detection persisted in stratified analyses by Enterobacteriaceae species (Klebsiella pneumoniae and Escherichia coli) and carbapenemase gene (blaNDM and blaKPC). CPE was associated with male gender (aOR, 1.45; 95% CI, 1.07 to 1.97; P = 0.02), intensive care unit stay (aOR, 1.84; 95% CI, 1.24 to 2.74; P = 0.003), and hospitalization in the preceding 1 year (aOR, 1.42; 95% CI, 1.01 to 2.02; P = 0.05). In a large nationwide study, antecedent carbapenem exposure was a significant risk factor for NCPCRE versus CPE, suggesting a differential effect of antibiotic selection pressure.

Clinical and microbiological characteristics of non-tuberculous mycobacteria diseases in Singapore with a focus on pulmonary disease, 2012-2016.

BACKGROUND: Information on non-tuberculosis mycobacterial (NTM) diseases remains limited in Singapore and other Southeast Asian countries. This study aimed to delineate epidemiological and clinical features of pulmonary NTM disease. METHODS: A retrospective review was performed on all NTM isolates identified in Singapore General Hospital from 2012 to 2016 using the 2007 ATS/IDSA diagnostic criteria. RESULTS: A total of 2026 NTM isolates from 852 patients were identified. M. abscessus-chelonae group (1010, 49.9%) was the most commonly isolated and implicated in pulmonary NTM disease. Pulmonary cases (352, 76%) had the highest prevalence among patients diagnosed with NTM diseases (465/852, 54.6%) with no gender difference. Male patients were older (68.5 years, P = 0.014) with a higher incidence of chronic obstructive pulmonary disease (COPD) (23.6%, P < 0.001) and recurrent cough with phlegm production (51.6%, P = 0.035). In contrast, more female patients had bronchiectasis (50%, P < 0.001) and haemoptysis (37.6%, P = 0.042). Age and COPD were associated with multiple NTM species isolation per patient. CONCLUSIONS: M. abscessus-chelonae group was the commonest NTM species isolated in Singapore. Pulmonary NTM infection has the highest frequency with male and female patients associated with a higher incidence of COPD and bronchiectasis respectively. Age and COPD were associated with multiple NTM species isolation per patient.

Clinical and Molecular Epidemiology of Carbapenem-Resistant Enterobacteriaceae Among Adult Inpatients in Singapore.

BACKGROUND: Since 2010, the incidence of carbapenem-resistant Enterobacteriaceae (CRE) has been increasing in Singapore. We analyzed the clinical and molecular epidemiology of CRE among adult inpatients in Singapore. METHODS: Quarterly incidence of unique subjects (per 100000 patient-days) with positive clinical and surveillance cultures for CRE were estimated based on mandatory data submitted to the National Public Health Laboratory by public hospitals between 2010 and 2015. CRE-positive adult inpatients were prospectively recruited from 6 public sector hospitals between December 2013 and April 2015. Subjects answered a standardized epidemiologic questionnaire and provided samples for this study. Further clinical information was extracted from subjects' electronic medical records. Whole-genome sequencing was performed on study isolates to determine transmission clusters. RESULTS: Incidence of CRE clinical cultures among adult inpatients plateaued from 2013 (range: 7.73 to 10.32 per 100000 patient-days) following an initial increase between 2010 and end-2012. We prospectively recruited 249 subjects. Their median age was 65 years, 108 (43%) were female, and 161 (64.7%) had carbapenemase-producing Enterobacteriaceae (CPE). On multivariate analysis, prior carbapenem exposure (OR: 3.23; 95% CI: 1.67-6.25) and hematological malignancies (OR: 2.85; 95% CI: 1.10-7.41) were associated with non-carbapenemase-producing CRE (NCPE) (n = 88) compared with CPE (n = 161) subjects. Among 430 CRE isolates from the 249 subjects, 307(71.3%) were CPE, of which 154(50.2%) were blaKPC-positive, 97(31.6%) blaNDM-positive, and 42 (13.7%) blaOXA-positive. Klebsiella pneumoniae (n = 180, 41.9%), Escherichia coli (n = 129, 30.0%) and Enterobacter cloacae (n = 62, 14.4%) were the main Enterobacteriaceae species. WGS (n = 206) revealed diverse bacterial strain type (STs). The predominant blaKPC-positive plasmid was pHS102707 (n = 62, 55.4%) and the predominant blaNDM-positive plasmid was pNDM-ECS01 (n = 46, 48.9%). Five transmission clusters involving 13 subjects were detected. CONCLUSIONS: Clinical CRE trend among adult inpatients showed stabilization following a rapid rise since introduction in 2010 potentially due to infection prevention measures and antimicrobial stewardship. More work is needed on understanding CPE transmission dynamics.