Predictors of mortality in culture-proven Burkholderia pseudomallei infections in a Singapore Tertiary Hospital.

Burkholderia pseudomallei is a pathogen expanding in geographic range. We performed a retrospective study analyzing the clinical, microbiologic features of culture-proven melioidosis, and predictors of mortality based on data from a Singapore tertiary hospital between 2006- 2016. We found ICU admission, bacteremia, and mechanical ventilation to be associated with mortality.

Nirmatrelvir/ritonavir treatment and risk for postacute sequelae of COVID-19 in older Singaporeans.

OBJECTIVES: Significant heterogeneity has been reported in cohort studies evaluating the impact of early oral antiviral treatment on preventing postacute sequelae after COVID-19. We evaluated the impact of early nirmatrelvir/ritonavir on risk of postacute cardiovascular, neurological, respiratory, and autoimmune diagnoses, as well as postacute symptoms amongst older Singaporeans. METHODS: National COVID-19 registries and healthcare claims databases were used to construct a retrospective population-based cohort enrolling all Singaporeans aged ≥60 years diagnosed with SARS-CoV-2 infection in primary care during Omicron transmission (18 March 2022-4 August 2023). The cohort was divided into nirmatrelvir/ritonavir-treated and untreated groups. Between-group differences in baseline characteristics were adjusted using overlap weighting. Risks of postacute cardiovascular, neurological, respiratory, and autoimmune diagnoses and postacute symptoms (31-180 days) after SARS-CoV-2 infection were contrasted in treated/untreated groups using competing risks regressions (adjusted for demographics/vaccination status/comorbidities). RESULTS: A total of 188 532 older Singaporeans were included; 5.8% (10 905/188 532) received nirmatrelvir/ritonavir. No significantly decreased risk of postacute sequelae (any sequelae: adjusted hazards ratio [aHR], 1.06; 0.94-1.19; cardiovascular sequelae: aHR, 1.01; 0.83-1.24; neurological sequelae: aHR, 1.09; 0.95-1.27; respiratory sequelae: aHR, 1.14; 0.84-1.55; autoimmune sequelae: aHR, 0.76; 0.53-1.09; or any postacute symptom: aHR, 0.97; 0.80-1.18) was observed up to 180 days post-infection in nirmatrelvir/ritonavir-treated individuals vs. untreated cases. Across all vaccination and age subgroups, no significantly decreased risk of any postacute diagnosis/symptom or any cardiovascular, neurological, respiratory, and autoimmune complications up to 180 days post-infection was observed. DISCUSSION: Early outpatient receipt of nirmatrelvir/ritonavir did not significantly reduce risk of postacute cardiovascular, neurological, respiratory, and autoimmune sequelae or the risk of postacute symptoms in a boosted cohort of older Singaporeans.

Climate change and its impact on infectious diseases in Asia.

ABSTRACT: Climate change, particularly increasing temperature, changes in rainfall, extreme weather events and changes in vector ecology, impacts the transmission of many climate-sensitive infectious diseases. Asia is the world's most populous, rapidly evolving and diverse continent, and it is already experiencing the effects of climate change. Climate change intersects with population, sociodemographic and geographical factors, amplifying the public health impact of infectious diseases and potentially widening existing disparities. In this narrative review, we outline the evidence of the impact of climate change on infectious diseases of importance in Asia, including vector-borne diseases, food- and water-borne diseases, antimicrobial resistance and other infectious diseases. We also highlight the imperative need for strategic intersectoral collaboration at the national and global levels and for the health sector to implement adaptation and mitigation measures, including responsibility for its own greenhouse gas emissions.

Predictors of disease severity in SARS-CoV-2 omicron variant XBB sublineages and variants of interest.

The Omicron variant has been reported to present with milder disease compared with Delta, although this may be due to immunity from vaccination and prior exposure. Predictors of severity with recent strains have not been well characterized. We retrospectively examined consecutive cases of moderate-to-severe COVID-19 (defined as requiring supplemental oxygenation, intensive care or mortality) admitted to seven tertiary hospitals across Singapore in April 2023. Whole genome sequencing was performed on each isolate to determine the sublineage, while baseline clinical, laboratory data and outcomes were tabulated. We reviewed 182 patients with moderate-to-severe illness and 466 controls hospitalized at the same time. Advanced age and presence of chronic kidney disease predicted adverse outcome. Previously reported markers such as radiographic evidence of pneumonia, elevated C-reactive protein and serum creatinine levels at presentation also correlated with adverse outcomes. There were no observable differences in outcomes with any specific Omicron XBB sublineage. We did not find any specific Omicron XBB sublineage that was associated with worse outcomes. Larger multinational studies would be important to track the clinical evolution of the virus in its current endemic state.

Coronavirus disease and home recovery: a Singapore perspective.

Objective: At the beginning of the coronavirus disease (COVID-19) pandemic in Singapore, the strategy initially involved aggressive ring-fencing of infections, before pivoting towards managing recurrent local interspersed outbreaks of COVID-19. A key feature of Singapore's efforts to preserve health-care capacity was the implementation of the nationwide Home Recovery Programme (HRP), whereby patients were allowed to recover at home as long as they met certain criteria. The programme was centrally coordinated by Singapore's Ministry of Health and was supported by telemedicine providers, primary care physicians and government agencies. This report aims to highlight Singapore's experience in coordinating and implementing the HRP, the challenges faced and the outcomes. Methods: Published and internal data from the Ministry of Health in Singapore, along with policy documents, were reviewed together with a brief literature review of similar programmes conducted globally. Results: Implementation of the HRP led to the majority of patients (98%) recovering from COVID-19 in the outpatient setting, with similar mortality rates to inpatient settings. Hospitalization rates for COVID-19 cases were reduced as compared to previously, alleviating strain on the health-care system. Discussion: The HRP was largely successful at preventing health-care capacities from being overwhelmed, while keeping fatalities to a minimum. Nonetheless, the risks of emergent variants of concern remain present, and heightened vigilance and potential modification of existing protocols based on fluctuations in virulence and infectivity are still needed.

ACORN (A Clinically-Oriented Antimicrobial Resistance Surveillance Network) II: protocol for case based antimicrobial resistance surveillance.

Background: Antimicrobial resistance surveillance is essential for empiric antibiotic prescribing, infection prevention and control policies and to drive novel antibiotic discovery. However, most existing surveillance systems are isolate-based without supporting patient-based clinical data, and not widely implemented especially in low- and middle-income countries (LMICs). Methods: A Clinically-Oriented Antimicrobial Resistance Surveillance Network (ACORN) II is a large-scale multicentre protocol which builds on the WHO Global Antimicrobial Resistance and Use Surveillance System to estimate syndromic and pathogen outcomes along with associated health economic costs. ACORN-healthcare associated infection (ACORN-HAI) is an extension study which focuses on healthcare-associated bloodstream infections and ventilator-associated pneumonia. Our main aim is to implement an efficient clinically-oriented antimicrobial resistance surveillance system, which can be incorporated as part of routine workflow in hospitals in LMICs. These surveillance systems include hospitalised patients of any age with clinically compatible acute community-acquired or healthcare-associated bacterial infection syndromes, and who were prescribed parenteral antibiotics. Diagnostic stewardship activities will be implemented to optimise microbiology culture specimen collection practices. Basic patient characteristics, clinician diagnosis, empiric treatment, infection severity and risk factors for HAI are recorded on enrolment and during 28-day follow-up. An R Shiny application can be used offline and online for merging clinical and microbiology data, and generating collated reports to inform local antibiotic stewardship and infection control policies. Discussion: ACORN II is a comprehensive antimicrobial resistance surveillance activity which advocates pragmatic implementation and prioritises improving local diagnostic and antibiotic prescribing practices through patient-centred data collection. These data can be rapidly communicated to local physicians and infection prevention and control teams. Relative ease of data collection promotes sustainability and maximises participation and scalability. With ACORN-HAI as an example, ACORN II has the capacity to accommodate extensions to investigate further specific questions of interest.

Evaluation of NG-Test CARBA 5 version 2, Cepheid Xpert Carba-R, and carbapenem inactivation methods in comparison to whole-genome sequencing for the identification of carbapenemases in non-fermenting Gram-negative bacilli.

NG-Test CARBA 5 (NG-Biotech) is a rapid in vitro multiplex immunoassay for the phenotypic detection and differentiation of the "big five" carbapenemase families (KPC, OXA-48-like, VIM, IMP, and NDM). Version 2 of this assay was evaluated alongside the Xpert Carba-R assay (Cepheid, Inc.), the modified carbapenem inactivation method (mCIM), and the CIMTris assay, with a collection of carbapenem-resistant non-fermenting Gram-negative bacilli comprising 138 Pseudomonas aeruginosa and 97 Acinetobacter baumannii isolates. Whole-genome sequencing (WGS) was used as the reference standard. For P. aeruginosa, NG-Test CARBA 5 produced an overall percentage agreement (OPA) with WGS of 97.1%, compared with 92.8% forXpert Carba-R and 90.6% for mCIM. For A. baumannii, as OXA-type carbapenemases (non-OXA-48) are not included, both the NG-Test CARBA 5 and Xpert Carba-R only had an OPA of 6.2%, while the CIMTris performed well with an OPA of 99.0%. The majority of A. baumannii isolates (95.9%) tested falsely positive for IMP on NG-Test CARBA 5; no IMP genes were found on WGS. No clear cause was found for this phenomenon; a cross-reacting protein antigen unique to A. baumannii is a possible culprit. NG-Test CARBA 5 performed well for carbapenemase detection in P. aeruginosa. However, results from A. baumannii isolates should be interpreted with caution.

Treatment outcomes with benzylpenicillin and non-benzylpenicillin antibiotics, and the performance of the penicillin zone-edge test versus molecular detection of blaZ in penicillin-susceptible Staphylococcus aureus (PSSA) bacteraemia.

OBJECTIVES: The blaZ gene encodes penicillinase, which inactivates penicillin. As there were reports on suboptimal sensitivity for the penicillin zone-edge test, a phenotypic method for blaZ detection, we investigated treatment outcomes in patients with penicillin-susceptible Staphylococcus aureus (PSSA) bacteraemia (phenotypically negative for penicillinase), subjecting isolates to molecular testing for blaZ retrospectively. PATIENTS AND METHODS: A retrospective cohort study was conducted on 121 patients with a first episode of PSSA bacteraemia from 1 January 2012 to 31 October 2015 at Tan Tock Seng Hospital (TTSH), Singapore. Patients were grouped into IV benzylpenicillin and non-benzylpenicillin groups. The primary outcome was overall treatment failure, defined as either 30 day all-cause mortality and/or 90 day relapse. The penicillin (P10) zone-edge test was repeated on archived PSSA isolates, concurrently with penicillin MIC determination via gradient diffusion and PCR for blaZ. RESULTS: Among 121 patients, 57 patients (47.1%) received IV benzylpenicillin as the predominant antibiotic. There was no significant difference in overall treatment failure between treatment with the benzylpenicillin [7/57 (12.3%)] versus non-benzylpenicillin groups [12/64 (18.8%)] (P = 0.33) or cloxacillin/cefazolin [6/37 (16.2%)] (P = 0.59). For 112 PSSA isolates available for testing, repeat penicillin zone-edge testing was negative for penicillinase production, corroborating previous results. A single PSSA isolate with a negative penicillin zone-edge test was found to be positive for blaZ. CONCLUSIONS: We found no differences in overall treatment failure between patients with PSSA bacteraemia treated with benzylpenicillin, anti-staphylococcal ß-lactams cefazolin/cloxacillin and other antimicrobials, when using the penicillin zone-edge test as the phenotypic method for blaZ screening.

Image-based real-time feedback control of magnetic digital microfluidics by artificial intelligence-empowered rapid object detector for automated in vitro diagnostics.

In vitro diagnostics (IVD) plays a critical role in healthcare and public health management. Magnetic digital microfluidics (MDM) perform IVD assays by manipulating droplets on an open substrate with magnetic particles. Automated IVD based on MDM could reduce the risk of accidental exposure to contagious pathogens among healthcare workers. However, it remains challenging to create a fully automated IVD platform based on the MDM technology because of a lack of effective feedback control system to ensure the successful execution of various droplet operations required for IVD. In this work, an artificial intelligence (AI)-empowered MDM platform with image-based real-time feedback control is presented. The AI is trained to recognize droplets and magnetic particles, measure their size, and determine their location and relationship in real time; it shows the ability to rectify failed droplet operations based on the feedback information, a function that is unattainable by conventional MDM platforms, thereby ensuring that the entire IVD process is not interrupted due to the failure of liquid handling. We demonstrate fundamental droplet operations, which include droplet transport, particle extraction, droplet merging and droplet mixing, on the MDM platform and show how the AI rectify failed droplet operations by acting upon the feedback information. Protein quantification and antibiotic resistance detection are performed on this AI-empowered MDM platform, and the results obtained agree well with the benchmarks. We envision that this AI-based feedback approach will be widely adopted not only by MDM but also by other types of digital microfluidic platforms to offer precise and error-free droplet operations for a wide range of automated IVD applications.

Rapid Screening of Urinary Tract Infection Using Microfluidic Inertial-Impedance Cytometry.

Urinary tract infection (UTI) diagnosis based on urine culture for bacteriuria analysis is time-consuming and often leads to wastage of hospital resources due to false-positive UTI cases. Direct cellular phenotyping (e.g., RBCs, neutrophils, epithelial cells) of urine samples remains a technical challenge as low cell concentrations, and urine characteristics (conductivities, pH, microbes) can affect the accuracy of cell measurements. In this work, we report a microfluidic inertial-impedance cytometry technique for label-free rapid (<5 min) neutrophil sorting and impedance profiling from urine directly. Based on size-based inertial focusing effects, neutrophils are isolated, concentrated, and resuspended in saline (buffer exchange) to improve consistency in impedance-based single-cell analysis. We first observed that both urine pH and the presence of bacteria can affect neutrophil high-frequency impedance measurements possibly due to changes in nucleus morphology as neutrophils undergo NETosis and phagocytosis, respectively. As a proof-of-concept for clinical testing, we report for the first time, rapid UTI testing based on multiparametric impedance profiling of putative neutrophils (electrical size, membrane properties, and distribution) in urine samples from non-UTI (n = 20) and UTI patients (n = 20). A significant increase in cell count was observed in UTI samples, and biophysical parameters were used to develop a UTI classifier with an area under the receiver operating characteristic curve of 0.84. Overall, the developed platform facilitates rapid culture-free urine screening which can be further developed to assess disease severity in UTI and other urologic diseases based on neutrophil electrical signatures.

Real-world effectiveness of nirmatrelvir/ritonavir against COVID-19 hospitalizations and severe COVID-19 in community-dwelling elderly Singaporeans during Omicron BA.2, BA.4/5, and XBB transmission.

OBJECTIVES: Real-world data on continued effectiveness of nirmatrelvir/ritonavir against hospitalization and severe COVID-19 in the context of widespread booster mRNA vaccine uptake and more immune-evasive Omicron sub-variants are lacking. We conducted a retrospective cohort study in adult Singaporeans aged ≥60 years presenting to primary care with SARS-CoV-2 infection, during waves of Omicron BA.2/4/5/XBB transmission. METHODS: Binary logistic regression was used to estimate the effect of treatment (receiving nirmatrelvir/ritonavir) on outcomes (hospitalization, severe COVID-19). Additional sensitivity analyses, including inverse-probability-of-treatment-weighting-adjusted analysis and adjustment using overlap weights, were performed to account for observed differences in baseline characteristics among treated/untreated cohorts. RESULTS: We included 3959 nirmatrelvir/ritonavir recipients and 139 379 untreated controls. Almost 95% received ≥3 doses of mRNA vaccines; 5.4% had preceding infection. Overall 26.5% of infections occurred during the Omicron XBB period and 1.7% were hospitalized. On multivariable logistic regression, receipt of nirmatrelvir/ritonavir was independently associated with lower odds of hospitalization (adjusted odds ratio [aOR] = 0.65, 95% CI = 0.50-0.85). Consistent estimates were obtained after inverse-probability-of-treatment-weighting adjustment (aOR for hospitalization = 0.60, 95% CI = 0.48-0.75) and adjustment using overlap weights (aOR for hospitalization = 0.64, 95% CI = 0.51-0.79). Although receipt of nirmatrelvir/ritonavir was associated with lower odds of severe COVID-19, it was not statistically significant. DISCUSSION: Outpatient usage of nirmatrelvir/ritonavir was independently associated with reduced odds of hospitalization amongst boosted older community-dwelling Singaporeans during successive waves of Omicron transmission, including Omicron XBB; however, it did not significantly reduce the already low risk of severe COVID-19 in a highly vaccinated population.

Compliance with face mask use during the COVID-19 pandemic: a community observational study in Singapore.

Introduction: Widespread mask use is an important intervention for control of the coronavirus disease 2019 pandemic. However, data on the factors affecting mask use are lacking. In this observational study, we evaluated the proportion of and factors influencing face mask use and related hygiene practices. Methods: We observed randomly selected members from the public in 367 venues across Singapore, and recorded the proportion of individuals with full compliance with mask use and mask hygiene (hand hygiene before and after touching the mask or face). Logistic regression analyses were used to determine variables associated with mask and hand hygiene compliance. Results: We made 3,821 observations - 2,149 (56.2%) females, 3,569 (93.4%) adults (≥21 years), 212 (5.5%) children (6-20 years) and 40 (1.0%) children (2-5 years). The overall full compliance rate (correct mask use), poor compliance rate (incorrect mask use) and absent mask use were 84.5%, 12.9% and 2.6%, respectively. The factors - male gender, fabric mask usage and crowded indoor venues - were associated with lower mask compliance. Face or mask touching behaviour was observed in 10.7% and 13.7% of individuals observed, respectively. Only one individual performed hand hygiene before and after touching the mask. Conclusion: The rate of mask compliance was high, probably due to legislation mandating mask usage. However, specific factors and crowded indoor venues associated with lower mask compliance were identified. We also noted an issue with the absence of hand hygiene before and after face or mask touching. These issues may benefit from targeted public health messaging.