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Introduction: Tuberculosis (TB) remains endemic in Singapore. Singapore's clinical practice guidelines for the management of tuberculosis were first published in 2016. Since then, there have been major new advances in the clinical management of TB, ranging from diagnostics to new drugs and treatment regimens. The National TB Programme convened a multidisciplinary panel to update guidelines for the clinical management of drug-susceptible TB infection and disease in Singapore, contextualising current evidence for local practice. Method: Following the ADAPTE framework, the panel systematically reviewed, scored and synthesised English-language national and international TB clinical guidelines published from 2016, adapting recommendations for a prioritised list of clinical decisions. For questions related to more recent advances, an additional primary literature review was conducted via a targeted search approach. A 2-round modified Delphi process was implemented to achieve consensus for each recommendation, with a final round of edits after consultation with external stakeholders. Results: Recommendations for 25 clinical questions spanning screening, diagnosis, selection of drug regimen, monitoring and follow-up of TB infection and disease were formulated. The availability of results from recent clinical trials led to the inclusion of shorter treatment regimens for TB infection and disease, as well as consensus positions on the role of newer technologies, such as computer-aided detectionartificial intelligence products for radiological screening of TB disease, next-generation sequencing for drugsusceptibility testing, and video observation of treatment. Conclusion: The panel updated recommendations on the management of drug-susceptible TB infection and disease in Singapore. [ABSTRACT FROM AUTHOR]

The global public health threat of antimicrobial resistance (AMR) has been accelerated by many interrelated factors spanning across One Health—human health, animal health, and the environment. Singapore launched its own National Strategic Action Plan (NSAP) on AMR in November 2017 with the aim of tackling the growing threat of AMR in Singapore through coordinated approaches. However, little is known about the policy process and development of the NSAP in Singapore. In this study, we analysed these aspects using an AMR governance framework. In-depth interviews were conducted with 20 participants across the One Health spectrum. The interviews were transcribed verbatim and analysed thematically. Areas that were well executed included (1) good coordination across various agencies, (2) a dedicated office to coordinate the work on the NSAP, and (3) a high level of governmental support. Areas that were lacking included (1) a lack of participation from certain sectors, (2) insufficient awareness around the AMR issue, (3) constraints in information sharing, and (4) a lack of ideal indicators to track the progress in addressing AMR. Improvements in these areas will provide a more holistic One Health engagement in support of the effective planning and implementation of the NSAP. [ABSTRACT FROM AUTHOR]

Antimicrobial resistance (AMR) is a global public health threat that affects humans, animals, and the environment across the One Health spectrum. Singapore launched its own National Strategic Action Plan (NSAP) on AMR in 2017 with the aim of tackling the growing threat of AMR in Singapore through coordinated approaches. However, little is known about the implementation of the NSAP. In this study, we analysed the implementation of the NSAP with guidance from an AMR governance framework. We conducted in-depth interviews with 20 participants across the One Health spectrum. The interviews were transcribed verbatim and analysed thematically. Overall, the implementation of activities against AMR was more advanced with respect to human health compared to other sectors such as (1) AMR and antimicrobial use (AMU) surveillance systems in hospitals; (2) the hospital antimicrobial stewardship (AMS) service and legislation to optimise AMU; (3) the national children and adults vaccination programme for IPC; (4) multiple avenues for education and awareness for both professionals and public; and (5) extensive research and collaboration networks with many sources of funding. Areas that were lacking presented problems including (1) an incomplete surveillance system for AMR and AMU across all sectors; (2) the need for better AMS and legislation in some sectors; (3) insufficient innovation in education for sustained behavioural modification; and (4) the need for more open research collaborations and the translation of research into policy outcomes. Improvements in these areas will enhance the overall implementation of the NSAP through a more holistic One Health approach. [ABSTRACT FROM AUTHOR]

Global sea level rise is a major environmental concern for many countries and cities, particularly for low-lying coastal areas where urban development is threatened by the combined effects of sea level rise and land subsidence. This study employed an improved two-layer network Persistent Scatterers Interferometric Synthetic Aperture Radar (PS-InSAR) technology to obtain high-precision land subsidence in Singapore from 2015 to 2019. Landsat images from 1973 to 2020 were also utilized to extract changes in Singapore's coastline. Geological, topographical, and global sea level rise data were integrated to investigate the causes and impacts of land subsidence in Singapore. The results indicate that the areas with severe subsidence coincide with land reclamation areas, where subsidence is mainly due to soil consolidation. Based on WorldDEM, land subsidence, and sea level rise data, the maximum inundation depth in Singapore by 2050 is estimated to be 1.24 m, with the Marina Bay area in Singapore's central business district being the most vulnerable to sea level rise. This study provides data support and a scientific basis for understanding the impact of land subsidence on Singapore's coastal areas under the influence of multiple factors using advanced InSAR technology. [ABSTRACT FROM AUTHOR]

Background: Antibiotic prescription practices in primary care in Singapore have received little scholarly attention. In this study, we ascertained prescription prevalence and identified care gaps and predisposing factors. Methods: A retrospective study was conducted on adults (>21 years old) at six public primary care clinics in Singapore. Prescriptions >14 days were excluded. Descriptive statistics were used to showcase the prevalence data. We used chi-square and logistic regression analyses to identify the factors affecting care gaps. Results: A total of 141,944 (4.33%) oral and 108,357 (3.31%) topical antibiotics were prescribed for 3,278,562 visits from 2018 to 2021. There was a significant reduction in prescriptions (p < 0.01) before and after the pandemic, which was attributed to the 84% reduction in prescriptions for respiratory conditions. In 2020 to 2021, oral antibiotics were most prescribed for skin (37.7%), genitourinary (20.2%), and respiratory conditions (10.8%). Antibiotic use in the "Access" group (WHO AWaRe classification) improved from 85.6% (2018) to 92.1% (2021). Areas of improvement included a lack of documentation of reasons for antibiotic use, as well as inappropriate antibiotic prescription for skin conditions. Conclusion: There was a marked reduction in antibiotic prescriptions associated with the onset of the COVID-19 pandemic. Further studies could address the gaps identified here and evaluate private-sector primary care to inform antibiotic guidelines and the local development of stewardship programs. [ABSTRACT FROM AUTHOR]

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. Carbapenemase-producing Enterobacterales cause healthcare-associated infections but modes of transmission are not well understood. Here, the authors find evidence of transmission without direct patient contact, indicating presence of undetected environmental reservoirs, whilst half of the transmission events are likely due to plasmid-mediated transmission. [ABSTRACT FROM AUTHOR]

Antimicrobial resistance (AMR) results in drug-resistant infections that are harder to treat, subsequently leading to increased morbidity and mortality. In 2008, we reviewed the problem of AMR in Singapore, limiting our discussion to the human healthcare sector. Ten years later, we revisit this issue again, reviewing current efforts to contain it in order to understand the progress made as well as current and emerging challenges. Although a significant amount of work has been done to control AMR and improve antibiotic prescribing in Singapore, most of it has focused on the hospital setting, with mixed impact. The role of antibiotic use and AMR in food animals and the environment - and the link to human health - is better understood today. This issue of AMR encompasses both human health as well as animal/food safety, and efforts to control it will need to continually evolve to maintain or improve on current gains. [ABSTRACT FROM AUTHOR]

There were 290 multidrug-resistant (MDR)-TB cases diagnosed in Singapore from 2006 to 2018. Eighty-one percent were foreign-born. Spoligotyping and MIRU-VNTR methods identified 108 patients in 24 clusters. The Beijing spoligotype accounted for 22 clusters. Whole genome sequencing (WGS) analysis reduced the number of clustered patients and clusters to 43 and nine respectively. One MIRU cluster was redefined into three WGS clusters. All the clusters had foreign-born source cases. Forty percent of local-born, versus 9% of foreign-born, MDR-TB cases belonged to WGS clusters. WGS more accurately elucidated potential MDR-TB transmission which was overestimated by conventional genotyping methods in Singapore. [ABSTRACT FROM AUTHOR]

Singapore's Antimicrobial Resistance (AMR) national strategic action plan includes inappropriate use of antimicrobials in food-producing animals as a specific priority. Although the use of antibiotics and other drugs are monitored by regulatory bodies, food fish farmers are allowed to buy and administer antimicrobials without a veterinary prescription. We conducted a qualitative study of Singaporean food fish farmers to understand patterns and determinants of antibiotic use, their knowledge of antibiotic resistance, as well as perceptions of on-farm infection prevention and control measures. During the interview, participants were asked about their farming processes, farm infrastructure, antibiotic use and any disease prevention measures. Thematic analysis of participants' interviews showed that antibiotic for growth promotion and infection prevention was uncommon among local food fish farmers. The following three main themes influenced participants' decisions to use antibiotics in their practice: 1) individual factors, 2) local regulatory factors as well as 3) market-related factors. Individual factors included their personal experience and knowledge both with antibiotics as well as with alternate options. In terms of local regulatory factors, we found that regular oversight was a strong deterrent in antibiotic use. Last, at the market level, the relatively high price of antibiotics in Singapore coupled with stiff competition was a strong disincentive for participants to use antibiotics in their farming practice. These factors were also influential in their relationships with local regulatory bodies as well as their counterparts. Although industries differ significantly across countries, lessons learnt from Singapore's food fish farming demonstrate the importance of an environment where multi-dimensional factors come together to discourage the irrational use of antibiotics in food animal production. In addition, our results allow greater insight into food fish farmers' perspectives on infection control and form a basis from which further research work can be undertaken. [ABSTRACT FROM AUTHOR]

The Asia Pacific region, home to two-thirds of the world's population and ten of the least developed countries, is considered a regional hot-spot for the emergence and spread of antimicrobial resistance (AMR). Despite this, there is a dearth of high-quality regional data on the extent of AMR. Recognising the urgency to close this gap, Singapore organised a meeting to discuss the problems in the region and frame a call for action. Representatives from across the region and beyond attended the meeting on the "Antimicrobial Resistance in the Asia Pacific & its impact on Singapore" held in November 2018. This meeting report is a summary of the discussions on the challenges and progress in surveillance, drivers and levers of AMR emergence, and the promising innovations and technologies that could be used to combat the increasing threat of AMR in the region. Enhanced surveillance and research to provide improved evidence-based strategies and policies are needed. The major themes that emerged for an action plan are working towards a tailored solution for the region by harnessing the One Health approach, enhancing inter-country collaborations, and collaboratively leverage upon new emerging technologies. A regionally coordinated effort that is target-driven, sustainable and builds on a framework facilitating communication and governance will strengthen the fight against AMR in the Asia Pacific region. [ABSTRACT FROM AUTHOR]

Background/aim: Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most common multidrug-resistant organisms in healthcare settings worldwide, but little is known about MRSA transmission outside of acute healthcare settings especially in Asia. We describe the methods for a prospective longitudinal study of MRSA prevalence and transmission.Methods: MRSA-colonized individuals were identified from MRSA admission screening at two tertiary hospitals and recruited together with their household contacts. Participants submitted self-collected nasal, axilla and groin (NAG) swabs by mail for MRSA culture at baseline and monthly thereafter for 6 months. A comparison group of households of MRSA-negative patients provided swab samples at one time point. In a validation sub-study, separate swabs from each site were collected from randomly selected individuals, to compare MRSA detection rates between swab sites, and between samples collected by participants versus those collected by trained research staff. Information on each participant's demographic information, medical status and medical history, past healthcare facilities usage and contacts, and personal interactions with others were collected using a self-administered questionnaire.Discussion/conclusion: Understanding the dynamics of MRSA persistence and transmission in the community is crucial to devising and evaluating successful MRSA control strategies. Close contact with MRSA colonized patients may to be important for MRSA persistence in the community; evidence from this study on the extent of community MRSA could inform the development of household- or community-based interventions to reduce MRSA colonization of close contacts and subsequent re-introduction of MRSA into healthcare settings. Analysis of longitudinal data using whole-genome sequencing will yield further information regarding MRSA transmission within households, with significant implications for MRSA infection control outside acute hospital settings. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the context of the ribosomal RNA methyltransferase gene armA in carbapenem-resistant global clone 2 (GC2) Acinetobacter baumannii isolates from Singapore.Methods: Antibiotic resistance was determined using disc diffusion; PCR was used to identify resistance genes. Whole genome sequences were determined and contigs were assembled and ordered using PCR. Resistance regions in unsequenced isolates were mapped.Results: Fifteen GC2 A. baumannii isolated at Singapore General Hospital over the period 2004-11 and found to carry the armA gene were resistant to carbapenems, third-generation cephalosporins, fluoroquinolones and most aminoglycosides. In these isolates, the armA gene was located in a third chromosomal resistance island, previously designated AbGRI3. In four isolates, armA was in a 19 kb IS 26 -bounded transposon, designated Tn 6180 . In three of them, a 2.7 kb transposon carrying the aphA1b gene, designated Tn 6179 , was found adjacent to and sharing an IS 26 with Tn 6180. However, in these four isolates a 3.1 kb segment of the adjacent chromosomal DNA has been inverted by an IS 26 -mediated event. The remaining 11 isolates all contained a derivative of Tn 6180 that had lost part of the central segment and only one retained Tn 6179 . The chromosomal inversion was present in four of these and in seven the deletion extended beyond the inversion into adjacent chromosomal DNA. AbGRI3 forms were found in available GC2 sequences carrying armA.Conclusions: In GC2 A. baumannii , the armA gene is located in various forms of a third genomic resistance island named AbGRI3. An aphA1b transposon is variably present in AbGRI3. [ABSTRACT FROM AUTHOR]

The Ministry of Health (MOH) has developed the clinical practice guidelines on Prevention, Diagnosis and Management of Tuberculosis to provide doctors and patients in Singapore with evidence-based treatment for tuberculosis. This article reproduces the introduction and executive summary (with recommendations from the guidelines) from the MOH clinical practice guidelines on Prevention, Diagnosis and Management of Tuberculosis, for the information of SMJ readers. The chapters and page numbers mentioned in the reproduced extract refer to the full text of the guidelines, which are available from the Ministry of Health website: http://www.moh.gov.sg/content/moh_web/healthprofessionalsportal/doctors/guidelines/cpg_medical.html. The recommendations should be used with reference to the full text of the guidelines. Following this article are multiple choice questions based on the full text of the guidelines. [ABSTRACT FROM AUTHOR]

A new national antimicrobial resistance surveillance program in Singapore public hospitals that uses WHONET detected high levels of methicillin resistance among Staphylococcus aureus (35.3%), carbapenem resistance among Acinetobacter spp. (49.6%), and third-generation cephalosporin resistance among Klebsiella pneumoniae (35.9%) hospital isolates in 2006. Antimicrobial drug resistance is a major problem in Singapore. [ABSTRACT FROM AUTHOR]

Background Limited information is available about seasonal influenza vaccine effectiveness ( VE) in tropical communities. Objectives Virus subtype-specific VE was determined for all military service personnel in the recruit camp and three other non-recruit camp in Singapore's Armed Forces from 1 June 2009 to 30 June 2012. Methods Consenting servicemen underwent nasal washes, which were tested with RT- PCR and subtyped. The test positive case and test negative control design was used to estimate the VE. To estimate the overall effect of the programme on new recruits, we used an ecological time series approach. Results A total of 7016 consultations were collected. The crude estimates for the VE of the triavalent vaccine against both influenza A( H1 N1)pdm09 and influenza B were 84% (95% CI 78-88%, 79-86%, respectively). Vaccine efficacy against influenza A( H3 N2) was markedly lower ( VE 33%, 95% CI −4% to 57%). An estimated 70% ( RR = 0·30; 95% CI 0·11-0·84), 39% ( RR = 0·61;0·25-1·43) and 75% ( RR = 0·25; 95% CI 0·11-0·50) reduction in the risk of influenza A( H1 N1)pdm09, influenza A( H3 N2) and influenza B infections, respectively, in the recruit camp during the post-vaccination period compared with during the pre-vaccination period was observed. Conclusions Overall, the blanket influenza vaccine programme in Singapore's Armed Forces has had a moderate to high degree of protection against influenza A( H1 N1)pdm09 and influenza B, but not against influenza A( H3 N2). Blanket influenza vaccination is recommended for all military personnel. [ABSTRACT FROM AUTHOR]

Background: Inappropriate prescription of antibiotics may contribute towards higher levels antimicrobial resistance. A key intervention for improving appropriate antibiotic prescription is surveillance of prescription. This paper presents the results of a longitudinal surveillance of broad-spectrum antibiotic prescription in 5 public-sector hospitals in Singapore from 2006 to 2010. Methodology/Principal Findings: Quarterly antibiotic prescription data were obtained and converted to defined daily doses (DDDs) per 1,000 inpatient-days. The presence of significant trends in antibiotic prescription over time for both individual and combined hospitals was tested by regression analysis and corrected for autocorrelation between time-points. Excluding fluoroquinolones, there was a significant increase in prescription of all monitored antibiotics from an average of 233.12 defined daily doses (DDD)/1,000 inpatient-days in 2006 to 254.38 DDD/1,000 inpatient-days in 2010 (Coefficient = 1.13, 95%CI: 0.16-2.09, p = 0.025). Increasing utilization of carbapenems, piperacillin/tazobactam, and Gram-positive agents were seen in the majority of the hospitals, while cephalosporins were less prescribed over time. The combined expenditure for 5 hospitals increased from USD9.9 million in 2006 to USD16.7 million in 2010. Conclusions/Significance: The rate of prescription of broad-spectrum antibiotics in Singaporean hospitals is much higher compared to those of European hospitals. This may be due to high rates of antimicrobial resistance. The increase in expenditure on monitored antibiotics over the past 5 years outstripped the actual increase in DDD/1,000 inpatient-days of antibiotics prescribed. Longitudinal surveillance of antibiotic prescription on a hospital and countrywide level is important for detecting trends for formulating interventions or policies. Further research is needed to understand the causes for the various prescription trends and to act on these where necessary. [ABSTRACT FROM AUTHOR]

ABSTRACT Background and objective: Streptococcus pneumoniae is an important cause of morbidity and mortality in both the paediatric and adult population. This study aimed to define pneumococcal colonization rates, and antibiotic resistance patterns across two periods a decade apart, and also assess the serotypes of colonizing strains in children in the era of early pneumococcal conjugate vaccine uptake in Singapore. Methods: Two cross-sectional prevalence surveys were carried out in 1997 and 2007-2008 on children attending day-care centres across Singapore. Nasopharyngeal swabs were obtained and cultured for S. pneumoniae, and antibiotic susceptibility testing was performed. Serotyping was also done in the 2007-2008 survey. Results: Three hundred and ninety-five children participated in the first survey in 1997, and 418 in the 2007-2008 survey. Pneumococcal colonization rates were 25.8 and 14.1%, respectively. There was a marked increase in antimicrobial non-susceptibility (penicillin 27.4% vs 69.5%; erythromycin 33.4% vs 78%; clindamycin 24.5% vs 45.8%, tetracycline 48% vs 67.8%), and multi-drug resistance (defined as non-susceptibility to three or more classes of antibiotics) increased from 33.3 to 74.6%. In the 2007-2008 survey, serotypes 6B (16.9%), 23F (11.9%) and 19F (10.2%) were most commonly observed. The projected coverage of the 7 and 13-valent conjugate pneumococcal vaccine for colonizing serotypes were 61.9 and 67%, respectively. Conclusions: S. pneumoniae antibiotic resistance has risen dramatically over the last 10 years in Singapore. Wider conjugate vaccine uptake and improved antibiotic stewardship should be made priorities. Surveillance of sentinel sites like day-care centres provides important data with respect to shifts in pneumococcal ecology. [ABSTRACT FROM AUTHOR]

Objective: Carbapenem-resistant Acinetobacter baumannii (CR-AB) is an emerging cause of nosocomial infections worldwide. Combination therapy may be the only viable option until new antibiotics become available. The objective of this study is to identify potential antimicrobial combinations against CR-AB isolated from our local hospitals. Methods: AB isolates from all public hospitals in Singapore were systematically collected between 2006 and 2007. MICs were determined according to CLSI guidelines. All CR-AB isolates were genotyped using a PCR-based method. Clonal relationship was elucidated. Time-kill studies (TKS) were conducted with polymyxin B, rifampicin and tigecycline alone and in combination using clinically relevant (achievable) unbound concentrations. Results: 31 CR AB isolates were identified. They are multidrug-resistant, but are susceptible to polymyxin B. From clonal typing, 8 clonal groups were identified and 11 isolates exhibited clonal diversity. In single TKS, polymyxin B, rifampicin and tigecycline alone did not exhibit bactericidal activity at 24 hours. In combination TKS, polymyxin plus rifampicin, polymyxin B plus tigecycline and tigecycline plus rifampicin exhibited bactericidal killing in 13/31, 9/31 and 7/31 isolates respectively at 24 hours. Within a clonal group, there may be no consensus with the types of antibiotics combinations that could still kill effectively. Conclusion: Monotherapy with polymyxin B may not be adequate against polymyxin B susceptible AB isolates. These findings demonstrate that in-vitro synergy of antibiotic combinations in CR AB may be strain dependant. It may guide us in choosing a pre-emptive therapy for CR AB infections and warrants further investigations. [ABSTRACT FROM AUTHOR]

Background: Methicillin-susceptible Staphylococcus aureus (MSSA) bacteraemia remains a condition associated with considerable morbidity and mortality worldwide. It is a common but little-studied problem outside of Europe and North America. Methods: A single-centre retrospective case series profiling all patients with community onset-MSSA bacteraemia presenting between March 2005 and February 2006 to a tertiary acute-care university hospital in Singapore. In addition to epidemiological and clinical data collection, risk factors for complicated bacteremia and attributable mortality were analysed. Results: A total of 100 patients met the case definition. Patients were more likely to be male (65%) and below 65 years of age (69%). Seventeen patients were intravenous drug abusers, while 38 had diabetes mellitus. There were 18 cases of endocarditis, with 11 occurring in intravenous buprenorphine abusers. Attributable mortality was 11%, and 46% of patients developed complicated bacteremia. On multivariate analysis, age > 65 years and presence of chronic pulmonary disease were the only significant risk factors for the former, while valvular heart disease was a significant risk factor for the latter. Conclusion: MSSA bacteraemia is associated with a significant risk of serious complications in Singapore. Other Asian cities should be alert to the risk factors for adverse outcomes for this important cause of morbidity and mortality. [ABSTRACT FROM AUTHOR]

Determines the frequency of drug resistance mutations among antiretroviral treatment-naive and -experienced patients infected with CRF01&95#;AE virus in Singapore. Factor that limits the long-term success of antiretroviral therapy; Pattern of development of resistance mutations; Results of socioeconomic factors or limitation in the development of health care infrastructure.

An outbreak of severe acute respiratory syndrome (SARS) occurred in Singapore in March 2003. To illustrate the problems in diagnosing and containing SARS in the hospital, we describe a case series and highlight changes in triage and infection control practices that have resulted. By implementing these changes, we have stopped the nosocomial transmission of the virus. [ABSTRACT FROM AUTHOR]

Describes the clinical features of index patient and initial contacts of severe acute respiratory syndrome (SARS) in Singapore. Occurrence of the index case; Demographic description of patients with SARS; Clinical course of SARS.

Antimicrobial resistance (AMR) is a global public health threat that warrants urgent attention. However, the multifaceted nature of AMR often complicates the development and implementation of comprehensive policies. In this study, we describe the policy context and explore experts' perspectives on the challenges, facilitators, and strategies for combating AMR in Singapore. We conducted semi-structured interviews with 21 participants. Interviews were transcribed verbatim and were analyzed thematically, adopting an interpretative approach. Participants reported that the Ministry of Health (MOH) has effectively funded AMR control programs and research in all public hospitals. In addition, a preexisting One Health platform, among MOH, Agri-Food & Veterinary Authority (restructured to form the Singapore Food Agency and the Animal & Veterinary Service under NParks in April 2019), National Environment Agency, and Singapore's National Water Agency, was perceived to have facilitated the coordination and formulation of Singapore's AMR strategies. Nonetheless, participants highlighted that the success of AMR strategies is compounded by various challenges such as surveillance in private clinics, resource constraints at community-level health facilities, sub-optimal public awareness, patchy regulation on antimicrobial use in animals, and environmental contamination. This study shows that the process of planning and executing AMR policies is complicated even in a well-resourced country such as Singapore. It has also highlighted the increasing need to address the social, political, cultural, and behavioral aspects influencing AMR. Ultimately, it will be difficult to design policy interventions that cater for the needs of individuals, families, and the community, unless we understand how all these aspects interact and shape the AMR response. [ABSTRACT FROM AUTHOR]

The article presents a study on the outbreak of multidrug-resistant tuberculosis (MDRTB) within two local area network (LAN) gaming centers in Singapore in 2012. The study examines five immunocompetent 19-28-year-old men via contact-tracing investigations, wherein their disease was resistant to ethionamide, isoniazid, rifampin and streptomycin. It notes the importance of whole-genome sequencing in developing a transmission chain.

A letter to the editor is presented in response to the article on multidrug-resistant tuberculosis (MDR TB) transmission in Singapore.

Background:Tuberculosis remains common in Singapore, increasing in incidence since 2008. We attempted to determine the molecular epidemiology of Mycobacterium tuberculosis complex (MTC) isolates locally, identifying major circulating genotypes and obtaining a glimpse of transmission dynamics. Methodology:Non-duplicate MTC isolates archived between 2006 and 2012 at the larger clinical tuberculosis laboratory in Singapore were sampled for spoligotyping and MIRU-VNTR typing, with case data obtained from the Singapore Tuberculosis Elimination Program registry database. Isolates between 2008 and 2012 were selected because of either multidrug-resistance or potential epidemiological linkage, whereas earlier isolates were randomly selected. Separate analyses were performed for the early (2006-2007) and later (2008-2012) study phases in view of potential selection bias. Principal Findings:A total of 1,612 MTC isolates were typed, constituting 13.1% of all culture-positive tuberculosis cases during this period. Multidrug-resistance was present in 91 (5.6%) isolates – higher than the national prevalence in view of selection bias. The majority of isolates belonged to the Beijing (45.8%) and EAI (22.8%) lineages. There were 347 (30.7%) and 133 (27.5%) cases clustered by combined spoligotyping and MIRU-VNTR typing from the earlier and later phases respectively. Patients within these clusters tended to be of Chinese ethnicity, Singapore resident, and have isolates belonging to the Beijing lineage. A review of prior contact investigation results for all patients with clustered isolates failed to reveal epidemiological links for the majority, suggesting either unknown transmission networks or inadequate specificity of the molecular typing methods in a country with a moderate incidence of tuberculosis. Conclusion:Our work demonstrates that Singapore has a large and heterogeneous distribution of MTC strains, and with possible cross-transmission over the past few years based on our molecular typing results. A universal MTC typing program coupled with enhanced contact investigations may be useful in further understanding the transmission dynamics of tuberculosis locally. [ABSTRACT FROM AUTHOR]

Background Bystander Cardio-Pulmonary Resuscitation (BCPR) can improve survival for Out-of-Hospital Cardiac Arrest (OHCA). This study aimed to investigate the geographic variation of BCPR provision and survival to discharge outcomes among residential OHCA cases, evaluate this variation with individual and population characteristics and identify high-risk residential areas with low relative risk (RR) of BCPR and high RR of OHCA at the development guide plan (DGP) census tract levels in Singapore. Methods This was a retrospective, secondary analysis of two prospectively-collected registries in Singapore from 2001 to 2011. We used Bayesian conditional autoregressive spatial models to examine predictors at the DGP level and calculate smoothed RR to identify high-risk areas. We used multi-level mixed-effects logistic regression models to examine the independent effects of individual and neighborhood factors. Results We found a total of 3942 OHCA with a BCPR rate of 20.3% and a survival to discharge rate of 1.9% and 3578 cases eligible for BCPR. After adjusting for age, witnessed status, presumed cardiac etiology and longer response time, the risk of BCPR provision significantly increased by 0.02% for every 1% increase in the proportion of household size 5 and above in the DGP area (odds ratio1.02, 95%CI = 1.002-1.038, p < 0.026). We identified 10 high-risk residential areas with low RR of BCPR and high RR of OHCA. Conclusion This study informed that neighborhood household size could have played a significant role in the provision of BCPR and occurrence of high-risk areas. It demonstrates the public health potential of combining geospatial and epidemiological analysis for improving health. [ABSTRACT FROM AUTHOR]

• 64% of residents in a SARS-CoV-2-affected dormitory were infected by July 2020 • < 0.2% of the Singapore general population were infected with SARS-CoV-2 in 2020 • SARS-CoV-2 spread can be suppressed with prompt, wide-ranging interventions • High-risk, crowded settings require special consideration in preparedness planning • Lowering densities in these settings is key to reducing vulnerability to outbreaks Since January 2020, Singapore has implemented comprehensive measures to suppress SARS-CoV-2. Despite this, the country has experienced contrasting epidemics, with limited transmission in the community and explosive outbreaks in migrant worker dormitories. To estimate SARS-CoV-2 infection incidence among migrant workers and the general population in Singapore. Prospective serological cohort studies. Two cohort studies — in a migrant worker dormitory and in the general population in Singapore. 478 residents of a SARS-CoV-2-affected migrant worker dormitory were followed up between May and July 2020, with blood samples collected on recruitment and after 2 and 6 weeks. In addition, 937 community-dwelling adult Singapore residents, for whom pre-pandemic sera were available, were recruited. These individuals also provided a serum sample on recruitment in November/December 2020. Exposure to SARS-CoV-2 in a densely populated migrant worker dormitory and in the general population. The main outcome measures were the incidences of SARS-CoV-2 infection in migrant workers and in the general population, as determined by the detection of neutralizing antibodies against SARS-CoV-2, and adjusting for assay sensitivity and specificity using a Bayesian modeling framework. No evidence of community SARS-CoV-2 exposure was found in Singapore prior to September 2019. It was estimated that < 2 per 1000 adult residents in the community were infected with SARS-CoV-2 in 2020 (cumulative seroprevalence: 0.16%; 95% CrI: 0.008–0.72%). Comparison with comprehensive national case notification data suggested that around 1 in 4 infections in the general population were associated with symptoms. In contrast, in the migrant worker cohort, almost two-thirds had been infected by July 2020 (cumulative seroprevalence: 63.8%; 95% CrI: 57.9–70.3%); no symptoms were reported in almost all of these infections. Our findings demonstrate that SARS-CoV-2 suppression is possible with strict and rapid implementation of border restrictions, case isolation, contact tracing, quarantining, and social-distancing measures. However, the risk of large-scale epidemics in densely populated environments requires specific consideration in preparedness planning. Prioritization of these settings in vaccination strategies should minimize the risk of future resurgences and potential spillover of transmission to the wider community. [ABSTRACT FROM AUTHOR]

Objective Between February 2012 and May 2016, six residents of an 11-storey apartment block were diagnosed with MDR-TB. Based on initial tests, all isolates had similar genotypic profiles, although there were no identifiable epidemiological transmission patterns between three cases. We present findings from the cluster investigation and results of a mass screening exercise. Design Free voluntary TB screening was offered to past and current residents of the apartment block, comprising an interview, Chest X-Ray, and Interferon Gamma Release Assay or Tuberculin skin test. Expected latent TB proportions were calculated using a reference population, and whole genome sequencing (WGS) was performed. Results The index case was involved in a separate gaming centre outbreak involving five patrons. 241 current (67.9% of 355 residents) and 18 past residents were screened. The latent TB proportion was 19.9%, which was at the higher end of the expected range. WGS confirmed relatedness of cases’ MDR-TB isolates– eight of 10 isolates were genetically identical, while the remaining two were one Single Nucleotide Polymorphism apart. Conclusion With WGS, TB clusters not apparent through regular activity-based contact tracing may be detected. Mass screening may help inform the extent of transmission, but is limited by participation and difficulties in interpretation. [ABSTRACT FROM AUTHOR]

Abstract: Data from an 800-bed hospital showed an increase in the incidence density of ceftriaxone-resistant Escherichia coli, from 13.1 to 21.7 per 100 000 inpatient days over a 4-year period. Detailed testing performed on 54 E. coli isolates showed bla CTX-M extended-spectrum β-lactamase (ESBL) genes (n = 37) and bla CMY-like ampC genes (n = 15). Typing data showed only limited clonal transmission in isolates with ESBL. [Copyright &y& Elsevier]

Methicillin-resistant Staphylococcus aureus (MRSA) has spread across countries and healthcare settings, with different clones occupying different ecological niches. It is crucial to understand the comparative epidemiology of MRSA clones between healthcare settings and independent factors associated with colonization of specific clones. We conducted annual cross-sectional surveillance studies in a network comprising an acute-care hospital and six closely-affiliated intermediate- and long-term care facilities in Singapore between June and July, 2014–2016; 5394 patients contributed 16 045 nasal, axillary and groin samples for culture and MRSA isolates for whole-genome sequencing. Multivariable multilevel multinomial regression models were constructed to assess independent factors associated with MRSA colonization. MRSA clonal complex (CC) 22 was more prevalent in the acute-care hospital (n = 256/493; 51.9%) and intermediate-care facilities (n = 348/634; 54.9%) than in long-term care (n = 88/351; 25.1%) facilities, with clones other than CC22 and CC45 being more prevalent in long-term care facilities (n = 144/351; 41.0%) (p < 0.001). Groin colonization with CC45 was six times that of nasal colonization (aOR 6.21, 95%CI 4.26–9.01). Prior MRSA carriage was associated with increased odds of current MRSA colonization in all settings, with a stronger association with CC22 (aOR 6.45, 95%CI 3.85–10.87) than CC45 (aOR 4.15, 95%CI 2.26–7.58). Colonization by MRSA clones differed between anatomical sites and across healthcare settings. With CC22 having a predilection for the nares and CC45 the groin, MRSA screening should include both sites. Prior MRSA carriage is a risk factor for colonization with predominant MRSA clones in the acute-care hospital and intermediate- and long-term care facilities. Contact precautions for prior MRSA carriers on admission to any healthcare facility could prevent intra- and inter-institutional MRSA transmission. [ABSTRACT FROM AUTHOR]

Introduction: Tuberculosis (TB) remains endemic in Singapore. Singapore's clinical practice guidelines for the management of tuberculosis were first published in 2016. Since then, there have been major new advances in the clinical management of TB, ranging from diagnostics to new drugs and treatment regimens. The National TB Programme convened a multidisciplinary panel to update guidelines for the clinical management of drug-susceptible TB infection and disease in Singapore, contextualising current evidence for local practice., Method: Following the ADAPTE framework, the panel systematically reviewed, scored and synthesised English-language national and international TB clinical guidelines published from 2016, adapting recommendations for a prioritised list of clinical decisions. For questions related to more recent advances, an additional primary literature review was conducted via a targeted search approach. A 2-round modified Delphi process was implemented to achieve consensus for each recommendation, with a final round of edits after consultation with external stakeholders., Results: Recommendations for 25 clinical questions spanning screening, diagnosis, selection of drug regimen, monitoring and follow-up of TB infection and disease were formulated. The availability of results from recent clinical trials led to the inclusion of shorter treatment regimens for TB infection and disease, as well as consensus positions on the role of newer technologies, such as computer-aided detection-artificial intelligence products for radiological screening of TB disease, next-generation sequencing for drug-susceptibility testing, and video observation of treatment., Conclusion: The panel updated recommendations on the management of drug-susceptible TB infection and disease in Singapore.

We estimated the annual bed days lost and economic burden of healthcare-associated infections to Singapore hospitals using Monte Carlo simulation. The mean (standard deviation) cost of a single healthcare-associated infection was S$1,809 (S$440) [or US$1,362 (US$331)]. This translated to annual lost bed days and economic burden of 55,978 (20,506) days and S$152.0 million (S$37.1 million) [or US$114.4 million (US$27.9 million)], respectively.

Objectives: The WHO's Global Action Plan on Antimicrobial Resistance (AMR) includes increasing overall public awareness of appropriate antibiotic use and resistance as a key priority area. We aimed to measure public knowledge, attitudes and practices of antibiotics and antibiotic resistance in Singapore, as well as their healthcare-seeking behaviours relating to respiratory illnesses, providing baseline data against which to measure the progress of future interventions., Design: A cross-sectional study., Setting: The general population in Singapore., Participants: Between May and June 2019, we conducted a survey via an online panel in Singapore with 706 respondents., Results: Our findings indicated common misconceptions surrounding antibiotic effectiveness and mechanisms of antibiotic resistance-most participants thought that resistance occurs when our bodies become resistant to antibiotics (62.5%) or when antibiotics become less powerful (48.5%). In multivariable analyses, better knowledge scores were associated with more favourable antibiotic attitudes (β=0.29; 95% CI 0.20 to 0.37). In addition, more favourable attitude scores were associated with lower odds of both expecting (OR: 0.84, 95% CI 0.72 to 0.99) and being prescribed antibiotics by a primary care doctor (OR: 0.76, 95% CI 0.63 to 0.90)., Conclusions: This study presents important information about population perceptions towards antibiotics and antibiotic resistance in Singapore. Results from this study emphasise the importance of effective public communication strategies to promote responsible antibiotic use locally and should be used to inform future implementation of programmes and activities as laid out in Singapore's National Strategic Action Plan on AMR., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Antimicrobial stewardship is a strategy to combat antimicrobial resistance in hospitals. Given the burden and impact of antimicrobial resistance in the Asia Pacific, it is important to document capacity and gaps in antimicrobial stewardship programmes (ASP). We aimed to understand existing capacities and practices, and define the resources needed to establish antimicrobial stewardship where it is lacking., Methods: An anonymous online survey, consisting of questions on antimicrobial control at country, hospital and programme levels, was circulated to healthcare providers in the field of infectious diseases and microbiology through Asian Network for Surveillance of Resistant Pathogens, ReAct Group and the Australasian Society for infectious Diseases., Results: 139 participants from 16 countries or regions completed the survey. The majority of participants were adult infectious diseases physicians (61/139, 43.9%) and microbiologists (31/139, 22.3%). Participants from 7 countries reported that antimicrobials can be obtained without prescriptions. Despite the high percentage (75.5%) of respondents working in large hospitals, only 22/139 participants (15.8%) from Australia, China, Singapore, Taiwan, Thailand and Vietnam reported having more than 10 infectious diseases physicians. Hospital empiric antimicrobial guidelines for common infections were available according to 110/139 (79.1%) participants. Pre-authorisation of antimicrobials was reported by 88/113 (77.9%) respondents while prospective audit and feedback was reported by 93/114 (81.6%). Automatic stop orders and culture-guided de-escalation were reported by only 52/113 (46.0%) and 27/112 (24.1%) respectively., Conclusion: The survey reveals a wide range of ASP development in Asia Pacific. Establishing national workgroups and guidelines will help advance antimicrobial stewardship in this diverse region., (Copyright © 2021 International Society for Antimicrobial Chemotherapy. Published by Elsevier Ltd. All rights reserved.)

We aimed to test the sensitivity of naso-oropharyngeal saliva and self-administered nasal (SN) swab compared to nasopharyngeal (NP) swab for COVID-19 testing in a large cohort of migrant workers in Singapore. We also tested the utility of next-generation sequencing (NGS) for diagnosis of COVID-19. Saliva, NP and SN swabs were collected from subjects who presented with acute respiratory infection, their asymptomatic roommates, and prior confirmed cases who were undergoing isolation at a community care facility in June 2020. All samples were tested using RT-PCR. SARS-CoV-2 amplicon-based NGS with phylogenetic analysis was done for 30 samples. We recruited 200 subjects, of which 91 and 46 were tested twice and thrice respectively. In total, 62.0%, 44.5%, and 37.7% of saliva, NP and SN samples were positive. Cycle threshold (Ct) values were lower during the earlier period of infection across all sample types. The percentage of test-positive saliva was higher than NP and SN swabs. We found a strong correlation between viral genome coverage by NGS and Ct values for SARS-CoV-2. Phylogenetic analyses revealed Clade O and lineage B.6 known to be circulating in Singapore. We found saliva to be a sensitive and viable sample for COVID-19 diagnosis.

Introduction: Primary healthcare providers play a crucial role in educating their patients on chronic disease self-management (CDSM). This study aims to evaluate CDSM competency and satisfaction in patients receiving their healthcare from public or private healthcare providers., Methods: A cross-sectional household study was conducted in a public housing estate using a standardised questionnaire to interview Singaporeans and permanent residents aged 40 years and above, who were diagnosed with at least 1 of these chronic diseases: hyperlipidaemia, hypertension or diabetes mellitus. CDSM competency was evaluated with the Partners In Health (PIH) scale and a knowledge based questionnaire. Satisfaction was evaluated using a satisfaction scale., Results: In general, the 420 respondents demonstrated good CDSM competency, with 314 followed up at polyclinics and 106 by general practitioners (GPs). There was no significant difference between patients of polyclinics and GPs in CDSM competency scores (mean PIH score 72.9 vs 75.1, P=0.563), hypertension knowledge scores (90.9 vs 85.4, P=0.16) and diabetes knowledge scores (84.3 vs 79.5, P=0.417), except for hyperlipidaemia knowledge scores (78.6 vs 84.7, P=0.043). However, respondents followed up by GPs had higher satisfaction rates than did those followed up at polyclinics (odds ratio 3.6, confidence interval 2.28-5.78). Favourable personality of the doctors and ideal consultation duration led to higher satisfaction in the GP setting. A longer waiting time led to lower satisfaction in the polyclinic group., Conclusion: Polyclinics and GPs provide quality primary care as evidenced by high and comparable levels of CDSM competency. Redistribution of patients from public to private clinics may result in improvements in healthcare service quality.

Objective: Methods that include the time-varying nature of healthcare-associated infections (HAIs) avoid biases when estimating increased risk of death and excess length of stay. We determined the excess mortality risk and length of stay associated with HAIs among inpatients in Singapore using a multistate model that accommodates the timing of key events., Design: Analysis of existing prospective cohort study data., Setting: Seven public acute-care hospitals in Singapore., Patients: Inpatients reviewed in a HAI point-prevalence survey (PPS) conducted between June 2015 and February 2016., Methods: We modeled each patient's admission over time using 4 states: susceptible with no HAI, infected, died, and discharged alive. We estimated the excess mortality risk and length of stay associated with HAIs, with adjustment for the baseline characteristics between the groups for mortality risk., Results: We included 4,428 patients, of whom 469 had ≥1 HAI. Using a multistate model, the expected excess length of stay due to any HAI was 1.68 days (95% confidence interval [CI], 1.15-2.21 days). Surgical site infections were associated with the longest excess length of stay of 4.68 days (95% CI, 2.60-6.76 days). After adjusting for baseline differences, HAIs were associated with increased hazards of in-hospital mortality (adjusted hazard ratio [aHR], 1.32; 95% CI, 1.09-1.65) and decreased hazards in being discharged (aHR, 0.75; 95% CI, 0.67-0.84)., Conclusions: HAIs are associated with increased length of hospital stay and mortality in hospitalized patients. Avoiding nosocomial infections can improve patient outcomes and free valuable bed days.

Background: To assess the genetic architecture of hypertrophic cardiomyopathy (HCM) in patients of predominantly Chinese ancestry., Methods: We sequenced HCM disease genes in Singaporean patients (n=224) and Singaporean controls (n=3634), compared findings with additional populations and White HCM cohorts (n=6179), and performed in vitro functional studies., Results: Singaporean HCM patients had significantly fewer confidently interpreted HCM disease variants (pathogenic/likely pathogenic: 18%, P <0.0001) but an excess of variants of uncertain significance (24%, P <0.0001), as compared to Whites (pathogenic/likely pathogenic: 31%, excess of variants of uncertain significance: 7%). Two missense variants in thin filament encoding genes were commonly seen in Singaporean HCM (TNNI3:p.R79C, disease allele frequency [AF]=0.018; TNNT2:p.R286H, disease AF=0.022) and are enriched in Singaporean HCM when compared with Asian controls (TNNI3:p.R79C, Singaporean controls AF=0.0055, P =0.0057, genome aggregation database-East Asian AF=0.0062, P =0.0086; TNNT2:p.R286H, Singaporean controls AF=0.0017, P <0.0001, genome aggregation database-East Asian AF=0.0009, P <0.0001). Both these variants have conflicting annotations in ClinVar and are of low penetrance (TNNI3:p.R79C, 0.7%; TNNT2:p.R286H, 2.7%) but are predicted to be deleterious by computational tools. In population controls, TNNI3:p.R79C carriers had significantly thicker left ventricular walls compared with noncarriers while its etiological fraction is limited (0.70 [95% CI, 0.35-0.86]) and thus TNNI3:p.R79C is considered variant of uncertain significance. Mutant TNNT2:p.R286H iPSC-CMs (induced pluripotent stem cells derived cardiomyocytes) show hypercontractility, increased metabolic requirements, and cellular hypertrophy and the etiological fraction (0.93 [95% CI, 0.83-0.97]) support the likely pathogenicity of TNNT2:p.R286H., Conclusions: As compared with Whites, Chinese HCM patients commonly have low penetrance risk alleles in TNNT2 or TNNI3 but exhibit few clinically actionable HCM variants overall. This highlights the need for greater study of HCM genetics in non-White populations.

Singapore, one of the first countries affected by COVID-19, adopted a national strategy for the pandemic which emphasised preparedness through a whole-of-nation approach. The pandemic was well contained initially until early April 2020, when there was a surge in cases, attributed to Singapore residents returning from hotspots overseas, and more significantly, rapid transmission locally within migrant worker dormitories. In this paper, we present the response of Singapore to the COVID-19 pandemic based on core dimensions of health system resilience during outbreaks. We also discussed on the surge in cases in April 2020, highlighting efforts to mitigate it. There was: (1) clear leadership and governance which adopted flexible plans appropriate to the situation; (2) timely, accurate and transparent communication from the government; (3) public health measures to reduce imported cases, and detect as well as isolate cases early; (4) maintenance of health service delivery; (5) access to crisis financing; and (6) legal foundation to complement policy measures. Areas for improvement include understanding reasons for poor uptake of government initiatives, such as the mobile application for contact tracing and adopting a more inclusive response that protects all individuals, including at-risk populations. The experience in Singapore and lessons learnt will contribute to pandemic preparedness and mitigation in the future., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Singapore, an island country with 5.6 million population and a large volume of tourists from mainland China, was one of the first countries to report imported COVID-19 cases and had the highest number of cases outside mainland China for a time in February 2020. The government responded with a series of broadscale public health measures and managed to contain this first wave of infection. Notwithstanding that, an evolving pandemic situation in other countries eventually triggered a second, and much larger, wave of infection. This case study narrates the developments, influencing factors, and outcomes related to events starting from Singapore's first response to COVID-19 and up to the point of its entry into Circuit Breaker. It serves as a reference for the understanding and analysis of developments in an evolving pandemic and a nation's response from a systems level perspective.

Antimicrobial resistance (AMR) results in drug-resistant infections that are harder to treat, subsequently leading to increased morbidity and mortality. In 2008, we reviewed the problem of AMR in Singapore, limiting our discussion to the human healthcare sector. Ten years later, we revisit this issue again, reviewing current efforts to contain it in order to understand the progress made as well as current and emerging challenges. Although a significant amount of work has been done to control AMR and improve antibiotic prescribing in Singapore, most of it has focused on the hospital setting, with mixed impact. The role of antibiotic use and AMR in food animals and the environment - and the link to human health - is better understood today. This issue of AMR encompasses both human health as well as animal/food safety, and efforts to control it will need to continually evolve to maintain or improve on current gains., (Copyright: © Singapore Medical Association.)