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The global rise of carbapenem-resistant Enterobacterales (CRE) infections is posing a grave challenge to hospital systems worldwide (1). Carbapenemase genes usually are located on plasmids that can transmit vertically along [...]

This study in Singapore analysed the incubation periods of the following SARS-CoV-2 variants: Wuhan-Hu-1, Delta, and Omicron. Three pandemic waves were examined: Wuhan-Hu-1 (January 2020–March 2021), Delta (May–October 2021), and Omicron (January–June 2022). Data from the SingHealth COVID-19 registry, covering patients from 23 January 2020 to 10 June 2022, were used to calculate incubation periods during the three time periods. The study found median incubation periods of 11 days for Wuhan-Hu-1, 3 days for Delta, and 3 days for Omicron (p-value: <0.001). This study highlighted the impact of different containment measures and the importance of robust EMR systems for tracking and managing infectious diseases. Key challenges included accurate contact tracing and IT infrastructure capabilities. The findings support the use of EMR data for future infectious disease preparedness in Singapore. [ABSTRACT FROM AUTHOR]

The rise of multidrug-resistant (MDR) Enterobacteriaceae prompted the World Health Organization to classify carbapenem-resistant Enterobacteriaceae, of which Klebsiella is the most common genus, on the global priority list of antibiotic-resistant [...]

Human adenoviruses (HAdVs) are classified into >50 types and are associated with clinical manifestations that include respiratory, gastrointestinal, ocular, genitourinary, and neurologic disease (1). HAdV infections have been estimated to [...]

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

Introduction: Healthcare workers (HCWs) are a critical resource in the effort to control the COVID-19 pandemic. They are also a sentinel surveillance population whose clinical status reflects the effectiveness of the hospital's infection prevention measures in the pandemic.Methods: This was a retrospective cohort study conducted in Singapore General Hospital (SGH), a 1,822-bed tertiary hospital. Participants were all HCWs working in SGH during the study period. HCW protection measures included clinical workflows and personal protective equipment developed and adapted to minimise the risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission. HCW monitoring comprised staff contact logs in high-risk locations, twice-daily temperature monitoring, assessment of HCWs with acute respiratory illnesses (ARIs) in the staff clinic and, in the event of an exposure, extensive contact tracing, detailed risk assessment and risk-based interventions. HCW surveillance utilised monitoring data and ARI presentations and outcomes.Results: In the ten-week period between 6 January 2020 and 16 March 2020, 333 (17.1%) of 1,946 HCWs at risk of occupational COVID-19 presented with ARI. 32 (9.6%) screened negative for SARS-CoV-2 from throat swabs. Five other HCWs developed COVID-19 attributed to non-clinical exposures. From the nine COVID-19 exposure episodes investigated, 189 HCW contacts were identified, of whom 68 (36.2%) were placed on quarantine and remained well.Conclusion: Early in an emerging infectious disease outbreak, close monitoring of frontline HCWs is essential in ascertaining the effectiveness of infection prevention measures. HCWs are at risk of community disease acquisition and should be monitored and managed to prevent onward transmission. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

• Epidemiological investigation and sequencing identified B.1.617.2 hospital clusters. • Despite high vaccination rates and N95 usage, sporadic transmission occurred. • Unvaccinated and immunocompromised patients remain at-risk. • More transmissible severe-acute-respiratory-syndrome-coronavirus-2 variants challenge containment efforts. Sporadic clusters of health care-associated COVID-19 infection occurred in a highly vaccinated health care-workers and patient population, over a 3-month period during ongoing community transmission of the B.1.617.2 variant. Enhanced infection-prevention measures and robust surveillance systems, including routine-rostered-testing of all inpatients and staff and usage of N95-respirators in all clinical areas, were insufficient in achieving zero health care-associated transmission. The unvaccinated and immunocompromised remain at-risk and should be prioritized for enhanced surveillance. [ABSTRACT FROM AUTHOR]

The complete picture regarding transmission modes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is unknown. This review summarises the available evidence on its transmission modes, our preliminary research findings and implications for infection control policy, and outlines future research directions. Environmental contamination has been reported in hospital settings occupied by infected patients, and is higher in the first week of illness. Transmission via environmental surfaces or fomites is likely, but decontamination protocols are effective in minimising this risk. The extent of airborne transmission is also unclear. While several studies have detected SARS-CoV-2 ribonucleic acid in air samples, none has isolated viable virus in culture. Transmission likely lies on a spectrum between droplet and airborne transmission, depending on the patient, disease and environmental factors. Singapore's current personal protective equipment and isolation protocols are sufficient to manage this risk. [ABSTRACT FROM AUTHOR]

The International Health Regulations—State Party Annual Reporting (IHR-SPAR) index and the Global Health Security Index (GHSI) have been developed to aid in strengthening national capacities for pandemic preparedness. We examined the relationship between country-level rankings on these two indices, along with two additional indices (the Universal Health Coverage Service Coverage Index and World Bank Worldwide Governance Indicator (n  = 195)) and compared them to the country-level reported coronavirus disease (COVID-19) cases and deaths (Johns Hopkins University COVID-19 Dashboard) through 17 June 2020. Ordinary least squares regression models were used to compare weekly reported COVID-19 cases and death rates per million in the first 12 weeks of the pandemic between countries classified as low, middle and high ranking on each index while controlling for country socio-demographic information. Countries with higher GHSI and IHR-SPAR index scores experienced fewer reported COVID-19 cases and deaths but only for the first 8 weeks after the country's first case. For the GHSI, this association was further limited to countries with populations below 69.4 million. For both the GHSI and IHR-SPAR, countries with a higher sub-index score in human resources for pandemic preparedness reported fewer COVID-19 cases and deaths in the first 8 weeks after the country's first reported case. The Universal Health Coverage Service Coverage Index and Worldwide Governance Indicator country-level rankings were not associated with COVID-19 outcomes. The associations between GHSI and IHR-SPAR scores and COVID-19 outcomes observed in this study demonstrate that these two indices, although imperfect, may have value, especially in countries with a population under 69.4 million people for the GHSI. Preparedness indices may have value; however, they should continue to be evaluated as policy makers seek to better prepare for future global public health crises. [ABSTRACT FROM AUTHOR]

To the Editor: During the past decade, enterobacteria that produce Klebsiella pneumoniae carbapenemase (KPC) have become established in the United States and countries in South America and Europe (1). In [...]

• It is feasible to use EHR to create a surveillance system to identify ARI clusters. • This requires combination of clinical and geospatial variables mapped over time. • This may aid surveillance efforts during the COVID-19 pandemic. Since December 2019, COVID-19 has caused a worldwide pandemic and Singapore has seen escalating cases with community spread. Aggressive contact tracing and identification of suspects has helped to identify local community clusters, surveillance being the key to early intervention. Healthcare workers (HCWs) have contracted COVID-19 infection both at the workplace and community. We aimed to create a prototype staff surveillance system for the detection of acute respiratory infection (ARI) clusters amongst our HCWs and describe its effectiveness. A prototypical surveillance system was built on existing electronic health record infrastructure. Over a 10-week period, we investigated 10 ARI clusters amongst 7 departments. One of the ARI clusters was later determined to be related to COVID-19 infection. We demonstrate the feasibility of syndromic surveillance to detect ARI clusters during the COVID-19 outbreak. The use of syndromic surveillance to detect ARI clusters amongst HCWs in the COVID-19 pandemic may enable early case detection and prevent onward transmission. It could be an important tool in infection prevention within healthcare institutions. [ABSTRACT FROM AUTHOR]

COVID-19 is an infectious disease caused by a novel β-coronavirus, belonging to the same subgenus as the Severe Acute Respiratory Syndrome (SARS) virus. Remdesivir, an investigational broad-spectrum antiviral agent has previously demonstrated in vitro activity against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), and in vivo efficacy against other related coronaviruses in animal models. Its safety profile has been tested in a compassionate use setting for patients with COVID-19. The current therapeutic studies demonstrate clinical effectiveness of remdesivir in COVID-19 patients by shortening time to clinical recovery, and hospital stay. In this review, we critically analyze the current evidence of remdesivir against COVID-19 and dissect the aspects over its safety and efficacy. Based on existing data, remdesivir can be regarded as a potential therapeutic agent against COVID-19. Further large-scale, randomized placebo-controlled clinical trials are, however, awaited to validate these findings. [ABSTRACT FROM AUTHOR]

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

Low incidence of non-COVID-19 community respiratory viral infections amongst adults with haematological malignancies during the COVID-19 pandemic Since then studies have reported a significant reduction in non-COVID-19 CA-RVIs in vulnerable patient populations, such as those with pre-existing respiratory diseases. Keywords: COVID-19; haematological malignancies; mask-wearing; public health measures; respiratory viral infections EN COVID-19 haematological malignancies mask-wearing public health measures respiratory viral infections 244 246 3 01/21/22 20220201 NES 220201 Dear Editor, Community acquired respiratory viral infections (CA-RVIs) are a significant cause of morbidity and mortality in patients with haematological malignancies [1,2]. [Extracted from the article]

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

Objectives: Patients with COVID‐19 may present with respiratory syndromes indistinguishable from common viruses. This poses a challenge for early detection during triage in the emergency department (ED). Over a 3‐month period, our ED aimed to minimize nosocomial transmission by using broader suspect case criteria for better detection and using appropriate personal protective equipment (PPE) for health care workers (HCWs). Methods: All ED admissions with respiratory syndromes over a 3‐month period were tested for COVID‐19. The sensitivity and specificity of screening criteria in detecting COVID‐19 were assessed. A risk‐stratified approach was adopted for PPE usage in the ED, based on high‐risk "fever areas" and lower‐risk zones. When a case of COVID‐19 was confirmed, surveillance was conducted for potentially exposed patients and HCWs. Results: A total of 1,841 cases presenting with respiratory syndromes required admission over the study period. Among these, 70 cases of COVID‐19 were subsequently confirmed. The majority (84.2%, 59/70) were detected at ED triage because they fulfilled suspect case criteria. Of these, 34 met the official screening criteria; an additional 25 were detected by the broader internal screening criteria. Over the 12‐week period, the cumulative sensitivity of internal screening criteria was 84.3% (95% confidence interval [CI] = 73.6% to 91.9%), whereas the sensitivity of the official screening criteria was 48.6% (95% CI = 36.4% to 60.8%). Given the broadened internal criteria, the preexisting ED "fever area" was insufficient and had to be expanded. However, there were no cases of nosocomial transmission from intra‐ED exposure, despite extensive surveillance. Conclusion: Frontline physicians need to be given leeway to decide on the disposition of cases based on clinical suspicion during an ongoing outbreak of COVID‐19. If a broader criterion is used at ED triage, ED facilities and isolation facilities need to be readied to accommodate a surge of suspect cases. Usage of appropriate PPE is essential in minimizing nosocomial transmission. [ABSTRACT FROM AUTHOR]

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

Objectives: bla OXA-23 is a class D carbapenemase-encoding gene typical of the Acinetobacter genus. However, its occurrence in the Enterobacteriaceae is uncommon. Here we provide the genome characterization of blaOXA-23-positive Proteus mirabilis.Methods: In Singapore, a national surveillance of carbapenem non-susceptible clinical Enterobacteriaceae has enabled the collection of OXA-23 bearing isolates. Three clinical P. mirabilis were whole-genome sequenced using Oxford Nanopore MinION and Illumina platforms. The sequence accuracy of MinION long-read contigs was enhanced by polishing with Illumina-derived short-read data.Results: In two P. mirabilis genomes, blaOXA-23 was detected as two copies, present on the chromosome and on a 60018 bp plasmid. blaOXA-23 was associated with the classic Acinetobacter composite transposon Tn2006, bounded by two copies of ISAba1 bracketing the carbapenemase gene. The Tn2006 itself was embedded within an Acinetobacter baumannii AbaR4 resistance island. In the chromosome, the AbaR4 was found integrated into the comM gene, which is also the preferred 'hotspot' in A. baumannii. In the plasmid, AbaR4 integrated into a putative colicin gene.Conclusions: Our description of an A. baumannii AbaR4 encoding blaOXA-23 in P. mirabilis is to our knowledge the first description of an Acinetobacter resistance island in Proteus and suggests that P. mirabilis may be a reservoir for this class D carbapenemase gene. [ABSTRACT FROM AUTHOR]

Objectives: To describe the population structure, molecular epidemiology and genetic context of blaKPC-2-bearing Klebsiella pneumoniae.Methods: Isolates (n = 157) were retrospective, phenotypically carbapenem-resistant blaKPC-positive K. pneumoniae, collected from public hospitals. WGS was performed on the Illumina platform. Phylogenomic analysis, screening of resistance and virulence genes, and comparison of the genetic environment of blaKPC were carried out.Results: Based on core-tree phylogeny, 67.5% of the isolates were K. pneumoniae and the remainder comprised Klebsiella quasipneumoniae. No Klebsiella variicola strains were observed. Only a single K. pneumoniae carbapenemase (KPC) variant type, blaKPC-2, was seen. MLSTs were diverse and did not comprise the 'traditional' KPC clonal group (CG) 258. blaKPC-2 was associated with a non-Tn4401 element (NTE) in >99% of genomes. Screening for four key virulence loci: yersiniabactin (ybt), aerobactin (iuc), salmochelin (iro) and colibactin (clb) as well as ICEKp (virulence-associated integrative conjugative element of K. pneumoniae), revealed the lack of virulence factors and ICEKp within K. quasipneumoniae. Amongst the K. pneumoniae, there were 32 ybt+ isolates (32/106, 30.2%) and, of these, 8 isolates were also clb+ (7.5%). K. pneumoniae serotypes K1 and K2, the majority of capsular serotype seen in patients with invasive liver abscess syndrome, were detected at 4.5% (7/157).Conclusions: Results suggest that dissemination of blaKPC-2 is driven by NTEKPC in non-ST258 isolates. The detection of blaKPC-2K. pneumoniae serotypes K1/K2 carrying virulence factors, albeit in low numbers, reflects the worrisome convergence of carbapenem resistance and hypervirulence in K. pneumoniae. [ABSTRACT FROM AUTHOR]

Invasive pneumococcal infection is a major cause of morbidity and mortality worldwide despite the availability of pneumococcal vaccines. The aim of this study was to re-evaluate the clinical syndromes, prognostic factors and outcomes for pneumococcal disease in adults and children in Singapore during the period before and after the introduction of the pneumococcal vaccine. We retrospectively analyzed a large cohort of patients admitted to the four main public hospitals in Singapore with S. pneumoniae infection between 1997 and 2013. A total of 889 (64% of all isolates identified in the clinical laboratories) cases were included in the analysis; 561 (63.1%) were adult (≥16 years) cases with a median age of 62 years and 328 (36.9%) were paediatric cases with a median age of 3 years. Bacteraemic pneumonia was the most common syndrome in both groups (69.3% vs. 44.2%), followed by primary bacteraemia without pneumonia (14.3% vs. 13.4%), meningitis (6.4% vs. 7.6%) and non-bacteraemic pneumonia (5.2% vs. 21%). The major serotypes in adults were 3, 4, 6B, 14, 19F and 23F whereas in children they were 14, 6B and 19F, accounting both for nearly half of pneumococcal disease cases. No particular serotype was associated with mortality or severity of the pneumococcal disease. Overall mortality rate was 18.5% in adults and 3% in children. Risk factors for mortality included acute cardiac events in adults, meningitis in children and critical illness and bilateral pulmonary infiltrates in both adults and children. Penicillin resistance was not associated with increased mortality. Our results agree with global reports that the course of pneumococcal disease and its clinical outcome were more severe in adults than in children. The main serotypes causing invasive disease were mostly covered by the vaccines in use. The high mortality rates reflect an urgent need to increase vaccination coverage in both adults and children to tackle this vaccine-preventable infection. [ABSTRACT FROM AUTHOR]

Objectives: MDR Pseudomonas aeruginosa is a serious global threat to healthcare institutions. The mechanism by which drug resistance can be acquired is variable, but acquired carbapenemase production has been reported in P. aeruginosa. An investigation was performed to determine the rate and genomic epidemiology of New Delhi MBL (NDM) in β-lactam-non-susceptible isolates.Methods: P. aeruginosa isolates from a tertiary hospital in Singapore between January 2015 and February 2018 were investigated for the presence of NDM genes.Results: Out of 298 pan-β-lactam-non-susceptible isolates, 31 were found to be NDM positive (10.4%). WGS demonstrated that all 31 NDM-positive isolates were clonal, belonging to ST-308. blaNDM was chromosomally inserted within an integrative and conjugative element (ICE), ICETn43716385. The NDM-P. aeruginosa isolates possessed an extensive repertoire of both cell-associated [flagella, pili, alginate/biofilm, LPS, type III secretion system (T3SS) and type VI secretion system (T6SS)] and secreted virulence factors. Antibiograms revealed higher rates of drug resistance in NDM-positive isolates compared with their non-NDM counterparts. The NDM isolates remained 100% susceptible only to colistin.Conclusions: The combination of chromosomal mutations, acquired resistance genes and virulence factors likely facilitated the persistent and ongoing spread of the ST-308 clade of P. aeruginosa within the hospital. Our study illustrates the particular threat of NDM-positive P. aeruginosa in a tertiary hospital setting in the era of antimicrobial resistance. [ABSTRACT FROM AUTHOR]

Introduction: Osteoporosis is the main cause of fractures among women after menopause. This study aimed to evaluate the efficacy and safety of denosumab compared to bisphosphonates in treating postmenopausal osteoporosis.Methods: Databases including PubMed and the Cochrane Central Register of Controlled Trials were systematically searched for randomised controlled trials (RCTs) that directly compared denosumab and bisphosphonates. RCTs that studied both denosumab and bisphosphonates in postmenopausal women with osteoporosis and had a Jadad score ≥ 3 were included.Results: Nine studies were eligible for inclusion. They were further categorised into six cohort groups. All studies had denosumab with oral bisphosphonates as the active comparator. Four out of six cohort studies showed significant improvements in bone strength (p < 0.001) at the distal radius, tibia, total hip, femoral neck, lumbar spine and trochanter at 12 months for patients on denosumab compared to the bisphosphonate group. Serum C-telopeptide of cross-linked collagen, a bone turnover marker, was consistently lower in the denosumab group in all studies. There were no significant differences in hypocalcaemia, atypical fractures, fragility fractures, osteonecrosis of the jaw, all infections (including fever or influenza-like symptoms), gastrointestinal side effects or dermatological conditions in all studies, except for one that did not document side effects.Conclusion: Denosumab can be used both as a first-line agent and an alternative to bisphosphonate in the treatment of postmenopausal osteoporosis. There is currently insufficient data to show that denosumab is not inferior to bisphosphonates in fracture prevention. [ABSTRACT FROM AUTHOR]

Objectives: Owing to gene transposition and plasmid conjugation, New Delhi metallo-β-lactamase (NDM) is typically identified among varied Enterobacteriaceae species and STs. We used WGS to characterize the chromosomal and plasmid molecular epidemiology of NDM transmission involving four institutions in Singapore.Methods: Thirty-three Enterobacteriaceae isolates (collection years 2010-14) were sequenced using short-read sequencing-by-synthesis and analysed. Long-read single molecule, real-time sequencing (SMRTS) was used to characterize genetically a novel plasmid pSg1-NDM carried on Klebsiella pneumoniae ST147.Results: In 20 (61%) isolates, blaNDM was located on the pNDM-ECS01 plasmid in the background of multiple bacterial STs, including eight K. pneumoniae STs and five Escherichia coli STs. In six (18%) isolates, a novel blaNDM-positive plasmid, pSg1-NDM, was found only in K. pneumoniae ST147. The pSg1-NDM-K. pneumoniae ST147 clone (Sg1-NDM) was fully sequenced using SMRTS. pSg1-NDM, a 90 103 bp IncR plasmid, carried genes responsible for resistance to six classes of antimicrobials. A large portion of pSg1-NDM had no significant homology to any known plasmids in GenBank. pSg1-NDM had no conjugative transfer region. Combined chromosomal-plasmid phylogenetic analysis revealed five clusters of clonal bacterial NDM-positive plasmid transmission, of which two were inter-institution clusters. The largest inter-institution cluster involved six K. pneumoniae ST147-pSg1-NDM isolates. Fifteen patients were involved in transmission clusters, of which four had ward contact, six had hospital contact and five had an unknown transmission link.Conclusions: A combined sequencing-by-synthesis and SMRTS approach can determine effectively the transmission clusters of blaNDM and genetically characterize novel plasmids. Plasmid molecular epidemiology is important to understanding NDM spread as blaNDM-positive plasmids can conjugate extensively across species and STs. [ABSTRACT FROM AUTHOR]

Background: The seroprevalence of varicella in Southeast Asia is not well described especially in healthcare workers (HCW) in the region. We report the varicella seroprevalence among healthcare workers from a diverse range of countries working in a tertiary care hospital in Singapore. Methods: We audited the results of annual HCW health screening, which included a varicella assay, from the years 2009 to 2014. During this period, there was a change in hospital policy mandating varicella immunity for all newly employed healthcare workers. The serological data were reviewed with employment records on occupation and nationality. Seroprevalence rates were determined by standard commercial enzyme linked immunosorbent assays for each year of testing. Odds of being immune in 2014 were compared by means of multiple logistic regression. Results: A total of 10,585 samples were obtained from 6668 unique individuals over four separate cross-sections of the hospital workforce. A peak seroprevalence of 92.8 % (95 % CI 92.0-93.5) was recorded in 2014. Younger employees had a lower seroprevalence than their older colleagues. In a consolidated sample of 4875 members of the active workforce in October 2014, we identified that Indian nationals were less likely to be immune than their Singaporean national colleagues, odds ratio (OR) 0.26 (95 % CI 0.17-0.43, p < 0.001), while Chinese nationals were more likely to be immune, OR 4.34 (95 % CI 1.61-12.2, p = 0.004), after controlling for year of screening, gender, age-group and vocation. In 2014, being employed as administrative staff, OR 0.43 (95 % CI 0.29-0.64, p < 0.001) or contract service provider, OR 0.30 (95 % CI 0.19-0.47, p < 0.001), was also associated with a lower odds of being immune than being employed as a nurse. Conclusions: There remain a small number of healthcare workers who are non-immune to varicella in our tertiary hospital. A new pre-employment policy of mandatory screening and vaccination may have increased rates of immunity but more needs to be done to ensure that all of our employees are immune to varicella to protect our vulnerable patients. [ABSTRACT FROM AUTHOR]

Background: Early diagnosis of human immunodeficiency virus (HIV) allows for appropriately timed interventions with improved outcomes, but HIV screening among asymptomatic persons and the general population in Singapore remains low. In 2008, Singapore’s Ministry of Health implemented HIV voluntary opt-out screening (VOS) for hospitalised adults. We evaluated the outcome of VOS and surveyed reasons for its low uptake in our institution. Methods: We assessed the outcomes of the VOS programme from January 2010 to December 2013 at National University Hospital, a 1081-bed tertiary hospital in Singapore. We also examined reasons for opting-in and opting-out using an interviewer–administered structured questionnaire in a representative sample in January 2013. Results: 107,523 patients fulfilled VOS criteria and were offered HIV screening, of which 5215 (4.9%) agreed to testing. 4850 (93.1%) of those who opted-in had an HIV test done. Three (0.06%) tested positive for HIV. 238 patients (14.2%) were surveyed regarding reasons for opting-in or out of VOS. 21 (8.8%) had opted-in. Patients who opted-in were likely to be younger, more educated and reported having more regular sexual partners. Type of housing, number of casual sexual partners, sexual orientation, intravenous drug use, condom use and previous sexually transmitted infection were not associated with deciding to opt-in/out. Patients’ most common reasons for opting-out were: belief that they were at low risk (50.2%), belief that they were too old (26.8%), cost (6.9%) and aversion to venepuncture (6.5%). The most common reason for opting-in was desire to know their HIV status (47.6%). Conclusion: The success of an HIV-VOS program is largely determined by test uptake. Our study showed that the majority of eligible VOS patients opted-out of HIV screening. Given the considerable cost and low yield of this programme, more needs to be done to better equip patients in self-risk assessment and opting in to testing. [ABSTRACT FROM AUTHOR]

Hospitalisations for acute exacerbations of COPD (AECOPD) carry significant morbidity and mortality. Respiratory viral infections (RVIs) are the most common cause of AECOPD and are associated with worse clinical outcomes. During the COVID-19 pandemic, public health measures, such as social distancing and universal masking, were originally implemented to reduce transmission of SARS-CoV-2; these public health measures were subsequently also observed to reduce transmission of other common circulating RVIs. In this study, we report a significant and sustained decrease in hospital admissions for all AECOPD as well as RVI-associated AECOPD, which coincided with the introduction of public health measures during the COVID-19 pandemic. [ABSTRACT FROM AUTHOR]