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: INTRODUCTION: Data on HIV treatment outcomes in people who inject drugs (PWID) in the Asia‐Pacific are sparse despite the high burden of drug use. We assessed immunological and virological responses, AIDS‐defining events and mortality among PWID receiving antiretroviral therapy (ART). METHODS: We investigated HIV treatment outcomes among people who acquired HIV via injecting drug use in the TREAT Asia HIV Observational Database (TAHOD) between January 2003 and March 2019. Trends in CD4 count and viral suppression (VS, HIV viral load RESULTS: Of 622 PWID from 12 countries in the Asia‐Pacific, 93% were male and the median age at ART initiation was 31 years (IQR, 28 to 34). The median pre‐ART CD4 count was 71 cells/µL. CD4 counts increased over time, with a mean difference of 401 (95% CI, 372 to 457) cells/µL at year‐10 (n = 78). Higher follow‐up HIV viral load and pre‐ART CD4 counts were associated with smaller increases in CD4 counts. Among 361 PWID with ≥1 viral load after six months on ART, proportions with VS were 82%, 88% and 93% at 2‐, 5‐ and 10‐years following ART initiation. There were 52 new AIDS‐defining events and 50 deaths during 3347 person‐years of follow‐up (PYS) (incidence 3.05/100 PYS, 95% CI, 2.51 to 3.70). Previous AIDS or TB diagnosis, lower current CD4 count and adherence CONCLUSIONS: Despite improved outcomes over time, our findings highlight the need for rapid ART initiation and adherence support among PWID within Asian settings., INTRODUCTION Globally, injecting drug use is a major public health concern leading to substantial health burden and transmission risk of blood‐borne infections from injecting equipment sharing behaviours. In a multi‐stage [...]

: Introduction: Cotrimoxazole (CTX) is recommended as prophylaxis against Pneumocystis jiroveci pneumonia, malaria and other serious bacterial infections in HIV‐infected patients. Despite its in vitro activity against Mycobacterium tuberculosis, the effects of CTX preventive therapy on tuberculosis (TB) remain unclear. Methods: Adults living with HIV enrolled in a regional observational cohort in Asia who had initiated combination antiretroviral therapy (cART) were included in the analysis. Factors associated with new TB diagnoses after cohort entry and survival after cART initiation were analysed using Cox regression, stratified by site. Results: A total of 7355 patients from 12 countries enrolled into the cohort between 2003 and 2016 were included in the study. There were 368 reported cases of TB after cohort entry with an incidence rate of 0.99 per 100 person‐years (/100 pys). Multivariate analyses adjusted for viral load (VL), CD4 count, body mass index (BMI) and cART duration showed that CTX reduced the hazard for new TB infection by 28% (HR 0.72, 95% CI l 0.56, 0.93). Mortality after cART initiation was 0.85/100 pys, with a median follow‐up time of 4.63 years. Predictors of survival included age, female sex, hepatitis C co‐infection, TB diagnosis, HIV VL, CD4 count and BMI. Conclusions: CTX was associated with a reduction in the hazard for new TB infection but did not impact survival in our Asian cohort. The potential preventive effect of CTX against TB during periods of severe immunosuppression should be further explored., Introduction Cotrimoxazole (CTX) has been recommended as prophylaxis against Pneumocystis jiroveci pneumonia (PJP), toxoplasmosis, malaria and other serious bacterial infections in adults with severe or advanced HIV clinical disease, with [...]

Objectives: We conducted a longitudinal cohort analysis to evaluate the association of pre‐treatment body mass index (BMI) with CD4 recovery, virological failure (VF) and cardiovascular risk disease (CVD) markers among people living with HIV (PLHIV). Methods: Participants who were enrolled between January 2003 and March 2019 in a regional Asia HIV cohort with weight and height measurements prior to antiretroviral therapy (ART) initiation were included. Factors associated with mean CD4 increase were analysed using repeated‐measures linear regression. Time to first VF after 6 months on ART and time to first development of CVD risk markers were analysed using Cox regression models. Sensitivity analyses were done adjusting for Asian BMI thresholds. Results: Of 4993 PLHIV (66% male), 62% had pre‐treatment BMI in the normal range (18.5–25.0 kg/m2), while 26%, 10% and 2% were underweight (< 18.5 kg/m2), overweight (25–30 kg/m2) and obese (> 30 kg/m2), respectively. Both higher baseline and time‐updated BMI were associated with larger CD4 gains compared with normal BMI. After adjusting for Asian BMI thresholds, higher baseline BMIs of 23–27.5 and > 27.5 kg/m2 were associated with larger CD4 increases of 15.6 cells/µL [95% confidence interval (CI): 2.9–28.3] and 28.8 cells/µL (95% CI: 6.6–50.9), respectively, compared with normal BMI (18.5–23 kg/m2). PLHIV with BMIs of 25–30 and > 30 kg/m2 were 1.27 times (95% CI: 1.10–1.47) and 1.61 times (95% CI: 1.13–2.24) more likely to develop CVD risk factors. No relationship between pre‐treatment BMI and VF was observed. Conclusions: High pre‐treatment BMI was associated with better immune reconstitution and CVD risk factor development in an Asian PLHIV cohort. [ABSTRACT FROM AUTHOR]

Objectives: To assess second‐line antiretroviral therapy (ART) virological failure and HIV drug resistance‐associated mutations (RAMs), in support of third‐line regimen planning in Asia. Methods: Adults > 18 years of age on second‐line ART for ≥ 6 months were eligible. Cross‐sectional data on HIV viral load (VL) and genotypic resistance testing were collected or testing was conducted between July 2015 and May 2017 at 12 Asia‐Pacific sites. Virological failure (VF) was defined as VL > 1000 copies/mL with a second VL > 1000 copies/mL within 3–6 months. FASTA files were submitted to Stanford University HIV Drug Resistance Database and RAMs were compared against the IAS‐USA 2019 mutations list. VF risk factors were analysed using logistic regression. Results: Of 1378 patients, 74% were male and 70% acquired HIV through heterosexual exposure. At second‐line switch, median [interquartile range (IQR)] age was 37 (32–42) years and median (IQR) CD4 count was 103 (43.5–229.5) cells/µL; 93% received regimens with boosted protease inhibitors (PIs). Median duration on second line was 3 years. Among 101 patients (7%) with VF, CD4 count > 200 cells/µL at switch [odds ratio (OR) = 0.36, 95% confidence interval (CI): 0.17–0.77 vs. CD4 ≤ 50) and HIV exposure through male–male sex (OR = 0.32, 95% CI: 0.17–0.64 vs. heterosexual) or injecting drug use (OR = 0.24, 95% CI: 0.12–0.49) were associated with reduced VF. Of 41 (41%) patients with resistance data, 80% had at least one RAM to nonnucleoside reverse transcriptase inhibitors (NNRTIs), 63% to NRTIs, and 35% to PIs. Of those with PI RAMs, 71% had two or more. Conclusions: There were low proportions with VF and significant RAMs in our cohort, reflecting the durability of current second‐line regimens. [ABSTRACT FROM AUTHOR]

Objectives: Early mortality among those still initiating antiretroviral therapy (ART) with advanced stages of HIV infection in resource‐limited settings remains high despite recommendations for universal HIV treatment. We investigated risk factors associated with early mortality in people living with HIV (PLHIV) starting ART at low CD4 levels in the Asia‐Pacific. Methods: PLHIV enrolled in the Therapeutics, Research, Education and AIDS Training in Asia (TREAT Asia) HIV Observational Database (TAHOD) who initiated ART with a CD4 count < 100 cells/μL between 2003 and 2018 were included in the study. Early mortality was defined as death within 1 year of ART initiation. PLHIV in follow‐up for > 1 year were censored at 12 months. Competing risk regression was used to analyse risk factors with loss to follow‐up as a competing risk. Results: A total of 1813 PLHIV were included in the study, of whom 74% were male. With 73 (4%) deaths, the overall first‐year mortality rate was 4.27 per 100 person‐years (PY). Thirty‐eight deaths (52%) were AIDS‐related, 10 (14%) were immune reconstituted inflammatory syndrome (IRIS)‐related, 13 (18%) were non‐AIDS‐related and 12 (16%) had an unknown cause. Risk factors included having a body mass index (BMI) < 18.5 [sub‐hazard ratio (SHR) 2.91; 95% confidence interval (CI) 1.60–5.32] compared to BMI 18.5–24.9, and alanine aminotransferase (ALT) ≥ 5 times its upper limit of normal (ULN) (SHR 6.14; 95% CI 1.62–23.20) compared to ALT < 5 times its ULN. A higher CD4 count (51–100 cells/μL: SHR 0.28; 95% CI 0.14–0.55; and > 100 cells/μL: SHR 0.12; 95% CI 0.05–0.26) was associated with reduced hazard for mortality compared to CD4 count ≤ 25 cells/μL. Conclusions: Fifty‐two per cent of early deaths were AIDS‐related. Efforts to initiate ART at CD4 counts > 50 cell/μL are associated with improved short‐term survival rates, even in those with late stages of HIV disease. [ABSTRACT FROM AUTHOR]

Objectives: Diabetes is a growing cause of morbidity and mortality in people living with HIV (PLHIV) receiving antiretroviral therapy (ART). We investigated the association between fasting plasma glucose (FPG) levels and mortality, and factors associated with FPG monitoring rates in Asia. Methods: Patients from the Therapeutics Research, Education, and AIDS Training in Asia (TREAT Asia) HIV Observational Database Low Intensity Transfer (TAHOD‐LITE) cohort were included in the present study if they had initiated ART. Competing risk and Poisson regression were used to analyse the association between FPG and mortality, and assess risk factors for FPG monitoring rates, respectively. FPG was categorized as diabetes (FPG ≥ 7.0 mmol/L), prediabetes (FPG 5.6–6.9 mmol/L) and normal FPG (FPG < 5.6 mmol/L). Results: In total, 33 232 patients were included in the analysis. Throughout follow‐up, 59% had no FPG test available. The incidence rate for diabetes was 13.7 per 1000 person‐years in the 4649 patients with normal FPG at ART initiation. Prediabetes [sub‐hazard ratio (sHR) 1.32; 95% confidence interval (CI) 1.07–1.64] and diabetes (sHR 1.90; 95% CI 1.52–2.38) were associated with mortality compared to those with normal FPG. FPG monitoring increased from 0.34 to 0.78 tests per person‐year from 2012 to 2016 (P < 0.001). Male sex [incidence rate ratio (IRR) 1.08; 95% CI 1.03–1.12], age > 50 years (IRR 1.14; 95% CI 1.09–1.19) compared to ≤ 40 years, and CD4 count ≥ 500 cells/μL (IRR 1.04; 95% CI 1.00–1.09) compared to < 200 cells/μL were associated with increased FPG monitoring. Conclusions: Diabetes and prediabetes were associated with mortality. FPG monitoring increased over time; however, less than half of our cohort had been tested. Greater resources should be allocated to FPG monitoring for early diabetic treatment and intervention and to optimize survival. [ABSTRACT FROM AUTHOR]

Objectives: With earlier antiretroviral therapy (ART) initiation, time spent in HIV care is expected to increase. We aimed to investigate loss to follow‐up (LTFU) in Asian patients who remained in care 5 years after ART initiation. Methods: Long‐term LTFU was defined as LTFU occurring after 5 years on ART. LTFU was defined as (1) patients not seen in the previous 12 months; and (2) patients not seen in the previous 6 months. Factors associated with LTFU were analysed using competing risk regression. Results: Under the 12‐month definition, the LTFU rate was 2.0 per 100 person‐years (PY) [95% confidence interval (CI) 1.8–2.2 among 4889 patients included in the study. LTFU was associated with age > 50 years [sub‐hazard ratio (SHR) 1.64; 95% CI 1.17–2.31] compared with 31–40 years, viral load ≥ 1000 copies/mL (SHR 1.86; 95% CI 1.16–2.97) compared with viral load < 1000 copies/mL, and hepatitis C coinfection (SHR 1.48; 95% CI 1.06–2.05). LTFU was less likely to occur in females, in individuals with higher CD4 counts, in those with self‐reported adherence ≥ 95%, and in those living in high‐income countries. The 6‐month LTFU definition produced an incidence rate of 3.2 per 100 PY (95% CI 2.9–3.4 and had similar associations but with greater risks of LTFU for ART initiation in later years (2006–2009: SHR 2.38; 95% CI 1.93–2.94; and 2010–2011: SHR 4.26; 95% CI 3.17–5.73) compared with 2003–2005. Conclusions: The long‐term LTFU rate in our cohort was low, with older age being associated with LTFU. The increased risk of LTFU with later years of ART initiation in the 6‐month analysis, but not the 12‐month analysis, implies that there was a possible move towards longer HIV clinic scheduling in Asia. [ABSTRACT FROM AUTHOR]

Background: An increased incidence of Pseudomonas aeruginosa in microbiological surveillance (MS) cultures from gastrointestinal endoscopes was detected between March 2020 and March 2023 in Tan Tock Seng Hospital Singapore., Aim: To describe the use of whole-genome sequencing (WGS) in this investigation., Methods: WGS was performed for all P. aeruginosa isolates with pairwise comparison of isolates to assess for genomic linkage. Comprehensive review of reprocessing practices and environmental sampling was performed., Findings: Twenty-two P. aeruginosa isolates were detected from endoscopic MS cultures. Fifteen (68%) isolates were available for WGS. Eighteen pairwise comparisons of isolates were made, of which 10 were found to be genomically linked. One endoscope had P. aeruginosa repeatedly cultured from subsequent MS that were genomically linked and persistent despite repeat endoscopic reprocessing, establishing the persistence of biofilm that could not be eradicated with routine reprocessing. All P. aeruginosa isolates cultured from other different endoscopes were genetically distinct. Investigation into reprocessing practices revealed the use of air/water valves connected to endoscopes during clinical use. Inspection of these valves revealed the presences of cracks and tears. All other environmental samples were negative., Conclusion: The WGS findings helped to deprioritize common source contamination and supported the hypothesis of biofilm build-up within endoscopes, leading to repeatedly positive MS cultures that were genomically linked. This was possibly related to incomplete reprocessing of the damaged air/water valves, resulting in biofilm build-up. All faulty valves were changed and subsequently cleaned separately with ultrasonic cleaning followed by sterilization which resolved this incident., (Copyright © 2024 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.)

Background: The spread of Carbapenemase-producing Organisms (CPO) remains a major threat globally. Within clinical settings, the existing method of determining gene load involves traditional culture to determine bacterial load and polymerase-chain-reaction-based Xpert Carba-R Assay to determine carbapenemase gene type. However, there is a need for a fast and accurate method of quantifying CPO colonisation to study the risk of persistent CPO carriage., Objective: This study evaluated the accuracy of Xpert Carba-R Ct value in estimating carbapenamase producing bacterial loads in stool samples., Methods: Stool samples were obtained from an ongoing study investigating the household transmission of CPO in Singapore. Stool samples lacking carbapenemase producing organisms were spiked with organism carrying a single carbapenemase gene (blaKPC, blaNDM, blaVIM, blaOXA-48(-like) or blaIMP-1) and serially diluted before being subjected to Xpert Carba-R assay and traditional culture. Standard curves with regression lines showing correlation between Ct values and plate counts were generated. The standard curves were validated with stool samples collected from patients., Results: The limit of detection of blaNDM, blaKPC, and blaOXA-48 was approximately 103 cfu/mL, while that of blaIMP-1 and blaVIM was approximately 104 cfu/mL. Validation of the blaNDM and blaOXA-48 curves revealed average delta values of 0.56 log(cfu/mL) (95% CI 0.24-0.88) and 0.80 log(cfu/mL) (95% CI 0.53-1.07), respectively., Conclusions: Our validation data for stool positive for blaNDM and blaOXA-48-type suggests that bacterial loads can be estimated within a reasonable range of error., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Chua et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

This study investigates the genetic traits and transmission mechanisms of cephalosporin-resistant Escherichia coli in tropical aquatic environments in Singapore. From 2016 to 2020, monthly samples were collected from wastewater treatment plants, marine niches, community sewage, beaches, reservoirs, aquaculture farms, and hospitals, yielding 557 isolates that were analyzed for antimicrobial resistance genes (ARGs) and mobile genetic elements (MGEs) using genomic methods. Findings reveal significant genotypic similarities between environmental and hospital-derived strains, particularly the pandemic E. coli ST131. Environmental strains exhibited high levels of intrinsic resistance mechanisms, including mutations in porins and efflux pumps, with key ARGs such as CMY-2 and NDM-9 predominantly carried by MGEs, which facilitate horizontal gene transfer. Notably, pathogenic EPEC and EHEC strains were detected in community sewage and aquaculture farms, posing substantial public health risks. This underscores the critical role of these environments as reservoirs for multidrug-resistant pathogens and emphasizes the interconnectedness of human activities and environmental health., Competing Interests: Declaration of Competing Interest We confirmed that there are no competing interests in this study., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: Toxoplasma gondii can cause symptomatic toxoplasmosis in immunodeficient hosts, including in people living with human immunodeficiency virus (PLWH), mainly because of the reactivation of latent infection. We assessed the prevalence of toxoplasmosis and its associated risk factors in PLWH in the Asia-Pacific region using data from the TREAT Asia Human Immunodeficiency Virus (HIV) Observational Database (TAHOD) of the International Epidemiology Databases to Evaluate AIDS (IeDEA) Asia-Pacific., Methods: This study included both retrospective and prospective cases of toxoplasmosis reported between 1997 and 2020. A matched case-control method was employed, where PLWH diagnosed with toxoplasmosis (cases) were each matched to two PLWH without a toxoplasmosis diagnosis (controls) from the same site. Sites without toxoplasmosis were excluded. Risk factors for toxoplasmosis were analyzed using conditional logistic regression., Results: A total of 269/9576 (2.8%) PLWH were diagnosed with toxoplasmosis in 19 TAHOD sites. Of these, 227 (84%) were reported retrospectively and 42 (16%) were prospective diagnoses after cohort enrollment. At the time of toxoplasmosis diagnosis, the median age was 33 years (interquartile range 28-38), and 80% participants were male, 75% were not on antiretroviral therapy (ART). Excluding 63 out of 269 people without CD4 values, 192 (93.2%) had CD4 ≤200 cells/μL and 162 (78.6%) had CD4 ≤100 cells/μL. By employing 538 matched controls, we found that factors associated with toxoplasmosis included abstaining from ART (odds ratio [OR] 3.62, 95% CI 1.81-7.24), in comparison to receiving nucleoside reverse transcriptase inhibitors plus non-nucleoside reverse transcriptase inhibitors, HIV exposure through injection drug use (OR 2.27, 95% CI 1.15-4.47) as opposed to engaging in heterosexual intercourse and testing positive for hepatitis B virus surface antigen (OR 3.19, 95% CI 1.41-7.21). Toxoplasmosis was less likely with increasing CD4 counts (51-100 cells/μL: OR 0.41, 95% CI 0.18-0.96; 101-200 cells/μL: OR 0.14, 95% CI 0.06-0.34; >200 cells/μL: OR 0.02, 95% CI 0.01-0.06), when compared to CD4 ≤50 cells/μL. Moreover, the use of prophylactic cotrimoxazole was not associated with toxoplasmosis., Conclusions: Symptomatic toxoplasmosis is rare but still occurs in PLWH in the Asia-Pacific region, especially in the context of delayed diagnosis, causing advanced HIV disease. Immune reconstitution through early diagnosis and ART administration remains a priority in Asian PLWH., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Lee et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

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., Competing Interests: The authors declare no competing interests., (© The Author(s) 2023.)

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., (© 2023 Wiley Periodicals LLC.)

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., Competing Interests: The authors declare no conflict of interest.

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., Competing Interests: No competing interests were disclosed., (Copyright: © 2023 Mo Y et al.)

Pseudomonas aeruginosa ST308 clone has been reported to carry carbapenemase genes such as bla IMP and bla VIM but has been rarely associated with bla NDM-1 . A total of 199 P. aeruginosa ST308 clinical and environmental isolates obtained between April 2019 and November 2020 from a tertiary-care hospital in Singapore were characterized using whole-genome sequencing. In addition, 71 bla NDM-1 -positive ST308 whole-genome sequences from two other local tertiary-care hospitals in Singapore and 83 global bla NDM-1 -negative ST308 whole-genome sequences in public databases were included to assess phylogenetic relationships and perform genome analyses. Phylogenetic analysis and divergent time estimation revealed that bla NDM-1 -positive P. aeruginosa ST308 was introduced into Singapore in 2005 (95 % highest posterior density: 2001 to 2008). Core genome, resistome, and analyses of all local bla NDM-1 -positive ST308 isolates showed chromosomal integration of multiple antibiotic resistance genes (ARGs) [ aac(3)-Id , aac(6')-Il , aadA6 , aadA11 , dfrB5 , msr ( E ), floR , sul2 , and qnrVC1 ], which was absent in global bla NDM-1 -negative ST308 sequences. Most ARGs and virulence genes were conserved across isolates originating from the three different local hospitals. Close genetic relatedness of the bla NDM-1 -positive ST308 clinical and environmental isolates suggests cocirculation between the hospital environment and human hosts with the hospital environment as a potential reservoir. Core genome single nucleotide polymorphism analyses revealed possible clonal transmission of bla NDM-1 -positive ST308 isolates between the three hospitals over 7 years. Bloodstream isolates accounted for six of 95 (6.3%) clinical isolates. This study reports the introduction of a pathogenic bla NDM-1 -positive P. aeruginosa ST308 more than a decade ago in Singapore and warrants surveillance for wider dissemination. IMPORTANCE P. aeruginosa is a Gram-negative opportunistic pathogen ubiquitously found in the environment and a major cause of nosocomial infections. While the P. aeruginosa ST308 clone has been known to bear bla IMP and bla VIM among global isolates, reports of bla NDM-1 -positive P. aeruginosa ST308 are rare. The local bla NDM-1 -positive P. aeruginosa ST308 isolates detected in this study appear to be unique to this region, with evidence of chromosomal acquisition of multiple ARGs compared to global bla NDM-1 -negative P. aeruginosa ST308 isolates. Surveillance in Singapore and beyond for dissemination is essential to determine whether existing measures are sufficient to control the spread of this ST308 clone., Competing Interests: The authors declare no conflict of interest.

We conducted a prospective environmental surveillance study to investigate the air, surface, dust, and water contamination of a room occupied by a patient infected with mpox virus (MPXV) at various stages of the illness. The patient tested positive for MPXV from a throat swab and skin lesions. Environmental sampling was conducted in a negative pressure room with 12 unidirectional high efficiency particulate air filter (HEPA) air changes per hour and daily cleaning of the surfaces. A total of 179 environmental samples were collected on days 7, 8, 13, and 21 of illness. Among the days of sampling, air, surface, and dust contamination showed the highest contamination rates on day 7 and 8 of illness, with a gradual decline to the lowest contamination level by day 21. Viable MPXV was isolated from surfaces and dust samples and no viable virus was isolated from the air and water samples., Competing Interests: Declaration of competing interest The authors have no competing interests to declare., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

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., Competing Interests: None

Serological testing of Singaporeans who received childhood smallpox vaccination found anti-vaccinia IgG binding and neutralizing activity indicating long-term humoral immunity. There was correlation between IgG and neutralizing titers indicating IgG could be used as a surrogate marker for humoral immunity. In 2019, Singapore experienced a case of imported monkeypox. As with smallpox, disease can be prevented through vaccination, which was mandatory for Singaporean infants until 1981. However, the degree of residual immunity in older vaccinated Singaporeans remains unknown. Sera from individuals born 1946-1984 were therefore tested and those born prior to 1981 were found to have higher anti-vaccinia IgG and neutralizing activity titers. This suggests that protective humoral immunity remains, which could reduce disease severity in an orthopoxvirus outbreak. Correlation between IgG and neutralizing titers was observed indicating that serology could be used as a surrogate marker for immunity., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: In our center, previous infection prevention and control (IPC) resources were concentrated on multidrug-resistant organisms other than CRAB because the rate of CRAB was stable with no evidence of outbreaks. Triggered by an increase in the baseline rate of CRAB isolated in clinical cultures, we investigated horizontal transmission of CRAB to guide targeted IPC actions., Methods: We prospectively collected clinical data of patients with positive CRAB cultures. We identified genetic relatedness of CRAB isolates using whole-genome sequencing. Findings were regularly presented to the IPC committee, and follow-up actions were documented., Results: During the study period, 66 CRAB isolates were available for WGS. Including 12 clinical isolates and 10 environmental isolates from a previous study, a total of 88 samples were subjected to WGS, of which 83 were successfully sequenced and included in the phylogenetic analysis. We identified 5 clusters involving 44 patients. Genomic transmissions were explained by spatiotemporal overlap in 12 patients and by spatial overlap only in 12 patients. The focus of transmission was deduced to be the intensive care units. One cluster was related to a retrospective environmental isolate, suggesting the environment as a possible route of transmission. Discussion of these findings at multidisciplinary IPC meetings led to implementation of measures focusing on environmental hygiene, including hydrogen peroxide vapor disinfection in addition to terminal cleaning for rooms occupied by CRAB patients., Conclusions: We showed that WGS could be utilized as a "tool of persuasion" by demonstrating the presence of ongoing transmission of CRAB in an endemic setting, and by identifying actionable routes of transmission for directed IPC interventions.

Background: Non-Asian body mass index (BMI) classifications are commonly used as a risk factor for high fasting blood glucose (FBG). We investigated the incidence and factors associated with high FBG among people living with HIV in the Asia-Pacific region, using a World Health Organization BMI classification specific to Asian populations., Methods: This study included people living with HIV enrolled in a longitudinal cohort study from 2003 to 2019, receiving antiretroviral therapy (ART), and without prior tuberculosis. BMI at ART initiation was categorized using Asian BMI classifications: underweight (<18.5 kg/m 2 ), normal (18.5-22.9 kg/m 2 ), overweight (23-24.9 kg/m 2 ), and obese (≥25 kg/m 2 ). High FBG was defined as a single post-ART FBG measurement ≥126 mg/dL. Factors associated with high FBG were analyzed using Cox regression models stratified by site., Results: A total of 3939 people living with HIV (63% male) were included. In total, 50% had a BMI in the normal weight range, 23% were underweight, 13% were overweight, and 14% were obese. Median age at ART initiation was 34 years (interquartile range 29-41). Overall, 8% had a high FBG, with an incidence rate of 1.14 per 100 person-years. Factors associated with an increased hazard of high FBG included being obese (≥25 kg/m 2 ) compared with normal weight (hazard ratio [HR] = 1.79; 95% confidence interval [CI] 1.31-2.44; p < 0.001) and older age compared with those aged ≤30 years (31-40 years: HR = 1.47; 95% CI 1.08-2.01; 41-50 years: HR = 2.03; 95% CI 1.42-2.90; ≥51 years: HR = 3.19; 95% CI 2.17-4.69; p < 0.001)., Conclusion: People living with HIV with BMI >25 kg/m 2 were at increased risk of high FBG. This indicates that regular assessments should be performed in those with high BMI, irrespective of the classification used., (© 2022 British HIV Association.)

Competing Interests: Declaration of competing interest None of the authors have any financial or commercial conflict of interest.

Purpose: This report aims to present a case of dengue-related myopic shift., Methods: This is a case report of a patient with dengue-related transient myopia, and demonstrates possible underlying pathophysiology., Results: A 38-year-old gentleman presented with bilateral blurring of vision with an unaided visual acuity (VA) of 6/120 bilaterally. He had a refractive error of -2.50 dioptres in the right eye, and -3.50 dioptres in the left eye. Ultrasound biomicroscopy (UBM) revealed suprachoroidal effusion with anterior displacement of the lens-iris complex bilaterally. Biometry performed showed lens thickness (LT) of 4.47 mm in the right eye, and 4.65 mm in the left eye. His unaided VA was noted to be 6/6 bilaterally 4 days later., Conclusions: Dengue-related myopic shift was likely secondary to two mechanisms. Firstly, suprachoroidal effusion resulted in an anterior displacement of the lens-iris complex. Secondly, there was an increase in the antero-posterior diameter of the lens, resulting in index myopia.

Long-term colonization of the gut microbiome by carbapenemase-producing Enterobacteriaceae (CPE) is a growing area of public health concern as it can lead to community transmission and rapid increase in cases of life-threatening CPE infections. Here, leveraging the observation that many subjects are decolonized without interventions within a year, we used longitudinal shotgun metagenomics (up to 12 timepoints) for detailed characterization of ecological and evolutionary dynamics in the gut microbiome of a cohort of CPE-colonized subjects and family members (n = 46; 361 samples). Subjects who underwent decolonization exhibited a distinct ecological shift marked by recovery of microbial diversity, key commensals and anti-inflammatory pathways. In addition, colonization was marked by elevated but unstable Enterobacteriaceae abundances, which exhibited distinct strain-level dynamics for different species (Escherichia coli and Klebsiella pneumoniae). Finally, comparative analysis with whole-genome sequencing data from CPE isolates (n = 159) helped identify substrain variation in key functional genes and the presence of highly similar E. coli and K. pneumoniae strains with variable resistance profiles and plasmid sharing. These results provide an enhanced view into how colonization by multi-drug-resistant bacteria associates with altered gut ecology and can enable transfer of resistance genes, even in the absence of overt infection and antibiotic usage., (© 2022. The Author(s).)

Background: In Singapore, quarantine of all close contacts with entry and exit polymerase chain reaction testing enabled evaluation of the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination and pediatric age on transmission of the Delta variant., Methods: This retrospective cohort study included all household close contacts between 1 March 2021 and 31 August 2021., Results: Among 8470 Delta variant-exposed contacts linked to 2583 indices, full-vaccination of the index with BNT162b2 or mRNA-1273 was associated with reduction in acquisition by contacts (adjusted odds ratio [aOR], 0.56; 95% robust confidence interval [RCI], .44-.71 and aOR, 0.51; 95% RCI, .27-.96, respectively). Compared with young adults (aged 18-29 years), children (aged 0-11 years) were significantly more likely to transmit (aOR, 2.37; 95% RCI, 1.57-3.60) and acquire (aOR, 1.43; 95% RCI, 1.07-1.93) infection, vaccination considered. Longer duration from vaccination completion among contacts was associated with decline in protection against acquisition (first-month aOR, 0.42; 95% RCI, .33-.55; fifth-month aOR, 0.84; 95% RCI, .55-.98; P < .0001 for trend) and symptomatic disease (first-month aOR, 0.30; 95% RCI, .23-.41; fifth-month aOR, 0.62; 95% RCI, .38-1.02; P < .0001 for trend). Contacts immunized with mRNA-1273 had significant reduction in acquisition (aOR, 0.73; 95% RCI, .58-.91) compared with BNT162b2., Conclusions: Among household close contacts, vaccination prevented onward SARS-CoV-2 transmission and there was in-creased risk of SARS-CoV-2 acquisition and transmission among children compared with young adults. Time after completion of vaccination and vaccine type affected SARS-CoV-2 acquisition., (© The Author(s) 2022. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Given the spasmodic increment in antimicrobial resistance (AMR), world is on the verge of "post-antibiotic era". It is anticipated that current SARS-CoV2 pandemic would worsen the situation in future, mainly due to the lack of new/next generation of antimicrobials. In this context, nanoscale materials with antimicrobial potential have a great promise to treat deadly pathogens. These functional materials are uniquely positioned to effectively interfere with the bacterial systems and augment biofilm penetration. Most importantly, the core substance, surface chemistry, shape, and size of nanomaterials define their efficacy while avoiding the development of AMR. Here, we review the mechanisms of AMR and emerging applications of nanoscale functional materials as an excellent substitute for conventional antibiotics. We discuss the potential, promises, challenges and prospects of nanobiotics to combat AMR., (© 2022. The Author(s).)

Importance: Assessing booster effectiveness of COVID-19 mRNA vaccine and inactivated SARS-CoV-2 vaccine over longer time intervals and in response to any further SARS-CoV-2 variants is crucial in determining optimal COVID-19 vaccination strategies., Objective: To determine levels of protection against severe COVID-19 and confirmed SARS-CoV-2 infection by types and combinations of vaccine boosters in Singapore during the Omicron wave., Design, Setting, and Participants: This cohort study included Singapore residents aged 30 years or more vaccinated with either at least 2 doses of mRNA COVID-19 vaccines (ie, Pfizer-BioNTech BNT162b2 or Moderna mRNA-1273) or inactivated SARS-CoV-2 vaccines (Sinovac CoronaVac or Sinopharm BBIBP-CorV) as of March 10, 2022. Individuals with a known SARS-CoV-2 infection prior to December 27, 2021, an infection on or before the date of their second vaccine dose, or with reinfection cases were excluded., Exposures: Two or 3 doses of Pfizer-BioNTech BNT162b2, Moderna mRNA-1273, Sinovac CoronaVac, or Sinopharm BBIBP-CorV., Main Outcomes and Measures: Notified infections from December 27, 2021, to March 10, 2022, adjusted for age, sex, race, housing status, and calendar days. Estimated booster effectiveness, defined as the relative incidence-rate reduction of severe disease (supplemental oxygen, intensive care, or death) or confirmed infection following 3-dose vaccination compared with 5 months after second mRNA dose, was determined using binomial regression., Results: Among 2 441 581 eligible individuals (1 279 047 [52.4%] women, 846 110 (34.7%) aged 60 years and older), there were 319 943 (13.1%) confirmed SARS-CoV-2 infections, of which 1513 (0.4%) were severe COVID-19 cases. mRNA booster effectiveness against confirmed infection 15 to 60 days after boosting was estimated to range from 31.7% to 41.3% for the 4 boosting combinations (homologous BNT162b2, homologous mRNA-1273, 2-dose BNT162b2/mRNA-1273 booster, and 2-dose mRNA-1273/BNT162b2 booster). Five months and more after boosting, estimated booster effectiveness against confirmed infection waned, ranging from -2.8% to 14.6%. Against severe COVID-19, estimated mRNA booster effectiveness was 87.4% (95% CI, 83.3%-90.5%) 15 to 60 days after boosting and 87.2% (95% CI, 84.2%-89.7%) 5 to 6 months after boosting, with no significant difference comparing vaccine combinations. Booster effectiveness against severe COVID-19 15 days to 330 days after 3-dose inactivated COVID-19 vaccination, regardless of combination, was estimated to be 69.6% (95% CI, 48.7%-81.9%)., Conclusions and Relevance: Booster mRNA vaccine protection against severe COVID-19 was estimated to be durable over 6 months. Three-dose inactivated SARS-CoV-2 vaccination provided greater protection than 2-dose but weaker protection compared with 3-dose mRNA.

Dissemination of carbapenemase-encoding plasmids by horizontal gene transfer in multidrug-resistant bacteria is the major driver of rising carbapenem-resistance, but the conjugative mechanics and evolution of clinically relevant plasmids are not yet clear. We performed whole-genome sequencing on 1,215 clinical Enterobacterales isolates collected in Singapore during 2010-2015. We identified 1,126 carbapenemase-encoding plasmids and discovered pKPC2 is becoming the dominant plasmid in Singapore, overtaking an earlier dominant plasmid, pNDM1. pKPC2 frequently conjugates with many Enterobacterales species, including hypervirulent Klebsiella pneumoniae, and maintains stability in vitro without selection pressure and minimal adaptive sequence changes. Furthermore, capsule and decreasing taxonomic relatedness between donor and recipient pairs are greater conjugation barriers for pNDM1 than pKPC2. The low fitness costs pKPC2 exerts in Enterobacterales species indicate previously undetected carriage selection in other ecological settings. The ease of conjugation and stability of pKPC2 in hypervirulent K. pneumoniae could fuel spread into the community.