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OBJECTIVE: We assessed the performance of influenza-like illness (ILI) case definitions by the Centers for Disease Control and Prevention (CDC), European Centers for Disease Control and Prevention and World Health Organization (WHO) in the tropics where seasonal patterns of respiratory viruses in acute upper respiratory tract infections (AURTIs) are ill-defined. METHODS: Clinical data and samples for respiratory multiplex polymerase chain reaction test were collected from 717 consecutive patients attending an emergency department in Singapore for uncomplicated AURTI in 2016-2018. RESULTS: Influenza (20.6%), rhinoviruses (14.4%), and coronaviruses (3.6%) were the most common viral pathogens identified. Biannual peaks with year-round activity were identified for influenza. Although higher rhinovirus activity was observed in inter-influenza seasonal periods, rhinoviruses and coronaviruses circulated year-round without distinct seasonal patterns. During high influenza activity months, the CDC and WHO ILI case definitions had moderate-to-high positive likelihood ratio (LR+) of 3.8-6.8 and 4.5-10.7, respectively, for ruling in influenza. They had moderately-high LR + of 3.3-3.8 and 3.9-4.6 for diagnosing influenza during other months. The ILI case definitions had high specificity (77.2%-85.4%) for rhinoviruses and coronaviruses. CONCLUSION: The CDC and WHO ILI case definitions can be applied to clinically diagnose influenza in the tropics, regardless of the time of the year.

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BACKGROUND: New Delhi metallo-ß-lactamase (bla NDM), a plasmid-borne carbapenemase gene associated with significant mortality and severely limited treatment options, is of global public health concern as it is found in extremely diverse Gram-negative bacterial strains. This study thus aims to genetically characterize local and global spread of bla NDM. METHODS: To investigate local transmission patterns in the context of a single hospital, whole genome sequencing data of the first 11 bla NDM-positive bacteria isolated in a local hospital were analyzed to: (1) identify and compare bla NDM-positive plasmids; and (2) study the phylogenetic relationship of the bacteria chromosomes. The global analysis was conducted by analyzing 2749 complete plasmid sequences (including 39 bla NDM-positive plasmids) in the NCBI database, where: (1) the plasmids were clustered based on their gene composition similarity; (2) phylogenetic study was conducted for each bla NDM-positive plasmid cluster to infer the phylogenetic relationship within each cluster; (3) gene transposition events introducing bla NDM into different plasmid backbones were identified; and (4) clustering pattern was correlated with the plasmids' incompatibility group and geographical distribution. RESULTS: Analysis of the first 11 bla NDM-positive isolates from a single hospital revealed very low bla NDM-positive plasmid diversity. Local transmission was characterized by clonal spread of a predominant plasmid with 2 sporadic instances of plasmid introduction. In contrast to the low diversity locally, global bla NDM spread involved marked plasmid diversity with no predominant bacterial clone. Thirty-nine (1.4 %) out of the 2749 complete plasmid sequences were bla NDM-positive, and could be resolved into 7 clusters, which were associated with plasmid incompatibility group and geographical distribution. The bla NDM gene module was witnessed to mobilize between different plasmid backbones on at least 6 independent occasions. CONCLUSIONS: Our analysis revealed the complex genetic pathways of bla NDM spread, with global dissemination characterized mainly by transposition of the bla NDM gene cassette into varied plasmids. Early local transmission following plasmid introduction is characterized by plasmid conjugation and bacterial spread. Our findings emphasize the importance of plasmid molecular epidemiology in understanding bla NDM spread.

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OBJECTIVE: Antibiotic computerized decision support systems (CDSSs) were developed to guide antibiotic decisions, yet prescriptions of CDSS-recommended antibiotics have remained low. Our aim was to identify predictors of patients' receipt of empiric antibiotic therapies recommended by a CDSS when the prescribing physician had an initial preference for using broad-spectrum antibiotics. METHODS: We conducted a prospective cohort study in a 1 500-bed tertiary-care hospital in Singapore. We included all patients admitted from October 1, 2011 through September 30, 2012, who were prescribed piperacillin-tazobactam or carbapenem for empiric therapy and auto-triggered to receive antibiotic recommendations by the in-house antibiotic CDSS. Relevant data on the patient, prescribing and attending physicians were collected via electronic linkages of medical records and administrative databases. To account for clustering, we used multilevel logistic regression models to explore factors associated with receipt of CDSS-recommended antibiotic therapy. RESULTS: One-quarter of the 1 886 patients received CDSS-recommended antibiotics. More patients treated for pneumonia (33.2%) than sepsis (12.1%) and urinary tract infections (7.1%) received CDSS-recommended antibiotic therapies. The prescribing physician - but not the attending physician or clinical specialty - accounted for some (13.3%) of the variation. Prior hospitalization (odds ratio [OR] 1.32, 95% CI, 1.01-1.71), presumed pneumonia (OR 6.77, 95% CI, 3.28-13.99), intensive care unit (ICU) admission (OR 0.38, 95% CI, 0.21-0.66), and renal impairment (OR 0.70, 95% CI, 0.52-0.93) were factors associated with patients' receipt of CDSS-recommended antibiotic therapies. CONCLUSIONS: We observed that ICU admission and renal impairment were negative predictors of patients' receipt of CDSS-recommended antibiotic therapies. Patients admitted to ICU and those with renal impairment might have more complex clinical conditions that require a physician's assessment in addition to antibiotic CDSS.

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Antibiotic computerised decision support systems (CDSSs) are shown to improve antibiotic prescribing, but evidence of beneficial patient outcomes is limited. We conducted a prospective cohort study in a 1500-bed tertiary-care hospital in Singapore, to evaluate the effectiveness of the hospital's antibiotic CDSS on patients' clinical outcomes, and the modification of these effects by patient factors. To account for clustering, we used multilevel logistic regression models. One-quarter of 1886 eligible inpatients received CDSS-recommended antibiotics. Receipt of antibiotics according to CDSS's recommendations seemed to halve mortality risk of patients (OR 0.54, 95% CI 0.26-1.10, P = 0.09). Patients aged ≤65 years had greater mortality benefit (OR 0.45, 95% CI 0.20-1.00, P = 0.05) than patients that were older than 65 (OR 1.28, 95% CI 0.91-1.82, P = 0.16). No effect was observed on incidence of Clostridium difficile (OR 1.02, 95% CI 0.34-3.01), and multidrug-resistant organism (OR 1.06, 95% CI 0.42-2.71) infections. No increase in infection-related readmission (OR 1.16, 95% CI 0.48-2.79) was found in survivors. Receipt of CDSS-recommended antibiotics reduced mortality risk in patients aged 65 years or younger and did not increase the risk in older patients. Physicians should be informed of the benefits to increase their acceptance of CDSS recommendations.

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Methicillin-resistant Staphylococcus aureus (MRSA) is a nosocomial pathogen that has become increasingly prominent in hospitals and the community. HIV-positive patients may be one of the most MRSA-susceptible populations because of their immunocompromised status. At the Communicable Disease Centre, Tan Tock Seng Hospital, Singapore, we implemented a universal MRSA screening program and performed a case-control study to identify risk factors for MRSA colonization among 294 HIV patients at admission from January 2009 to January 2010. Among 54 HIV-positive patients who were MRSA positive at hospital admission, 16 (29.6%) were positive at the nares/axilla/groin (NAG; one combined swab), 14 (25.9%) were NAG and perianal positive, 3 (5.6%) were NAG and throat positive, 10 (18.5%) were NAG, perianal, and throat positive, 6 (11.1%) were throat positive, and 5 (9.3%) were perianal positive. Upon multivariate analysis, we found that age [odds ratio (OR)=1.04, 95% confidence interval (CI): 1.01-1.07, p=0.006] and CD4 count <200/µl within the past 6 months (OR=4.29, 95% CI: 1.83-10.06, p=0.001) were significant risk factors for MRSA colonization. We generated a receiver operating characteristic curve using these two variables and found that the area under the curve was 0.69, indicating that age and CD4 count <200/µl performed moderately well in discriminating between those with MRSA colonization and those without. The results of our study indicate that HIV patients of older age and reduced CD4 count may have increased risk of MRSA colonization. These risk factors may serve as indicators for cohorting or isolating HIV patients at hospital admission.

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BACKGROUND: The United States FDA approved an over-the-counter HIV self-test, to facilitate increased HIV testing and earlier linkage to care. We assessed the accuracy of self-testing by untrained participants compared to healthcare worker (HCW) testing, participants' ability to interpret sample results and user-acceptability of self-tests in Singapore. METHODOLOGY/PRINCIPAL FINDINGS: A cross-sectional study, involving 200 known HIV-positive patients and 794 unknown HIV status at-risk participants was conducted. Participants (all without prior self-test experience) performed self-testing guided solely by visual instructions, followed by HCW testing, both using the OraQuick ADVANCE Rapid HIV 1/2 Antibody Test, with both results interpreted by the HCW. To assess ability to interpret results, participants were provided 3 sample results (positive, negative, and invalid) to interpret. Of 192 participants who tested positive on HCW testing, self-testing was positive in 186 (96.9%), negative in 5 (2.6%), and invalid in 1 (0.5%). Of 794 participants who tested negative on HCW testing, self-testing was negative in 791 (99.6%), positive in 1 (0.1%), and invalid in 2 (0.3%). Excluding invalid tests, self-testing had sensitivity of 97.4% (95% CI 95.1% to 99.7%) and specificity of 99.9% (95% CI: 99.6% to 100%). When interpreting results, 96%, 93.1% and 95.2% correctly read the positive, negative and invalid respectively. There were no significant demographic predictors for false negative self-testing or wrongly interpreting positive or invalid sample results as negative. Eighty-seven percent would purchase the kit over-the-counter; 89% preferred to take HIV tests in private. 72.5% and 74.9% felt the need for pre- and post-test counseling respectively. Only 28% would pay at least USD15 for the test. CONCLUSIONS/SIGNIFICANCE: Self-testing was associated with high specificity, and a small but significant number of false negatives. Incorrectly identifying model results as invalid was a major reason for incorrect result interpretation. Survey responses were supportive of making self-testing available.

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Understanding factors associated with de novo daptomycin-nonsusceptible Enterococcus (DNSE) infections will aid in better understanding the mechanisms of daptomycin nonsusceptibility. We conducted a case-control study to compare patients with DNSE infections who were daptomycin treatment naïve (n = 9) and those with DNSE infections who had exposure to daptomycin (n = 13). Less frequent exposure to antimicrobials, increased susceptibility to nitrofurantoin and gentamicin, and shorter duration of hospitalization were associated with de novo DNSE infection, suggesting a potential community reservoir.

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BACKGROUND: Pandemic influenza (H1N1) 2009 is susceptible to oseltamivir. There are few reports on its clinical and virologic response to oseltamivir. METHODS: During the pandemic containment response in Singapore, all patients with positive polymerase chain reaction (PCR) results for pandemic influenza (H1N1) 2009 were hospitalized, given oseltamivir for 5 days, and discharged when daily PCR results for combined nasal and throat swab samples became negative. Six patients had concurrent positive viral culture and PCR results. RESULTS: The median age of the first 70 consecutive patients was 26 years (interquartile range, 21-38 years); 60% were men, and 29% had comorbidity. The mean time (+/-SD) from illness onset to hospital admission was 3+/-2 days. Influenza-like illness was noted in 63% of patients. Fever occurred in 91%, cough in 88%, sore throat in 66%, and rhinorrhea in 53% of patients. The mean duration (+/-SD) of viral shedding from illness onset was day 6+/-2 days. Viral shedding persisted beyond 7 days in 37% of patients. Clinical features and viral shedding were similar between those with and without comorbidity, except the former had more cough and lower oxygen saturation. Patients receiving oseltamivir on days 1 to 3 of illness had significantly shorter viral shedding duration, compared with those treated from day 4 onwards (P < .05). The mean durations (+/-SD) of positive PCR and viral culture results were 5+/-8 and 4+/-18 days, respectively, for 6 patients with concurrent positive viral culture and PCR results. CONCLUSIONS: Prolonged viral shedding was noted in young immunocompetent adults with mild pandemic influenza (H1N1) 2009 despite receipt of oseltamivir. When prescribed during the first 3 days of illness, oseltamivir shortened the duration of viral shedding.

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BACKGROUND: Only a minority of probable SARS cases caused transmission. We assess if any epidemiological or clinical factors in SARS index patients were associated with increased probability of transmission. METHODS: We used epidemiological and clinical data on probable SARS patients admitted to Tan Tock Seng Hospital. Using a case-control approach, index patients who had probable SARS who subsequently transmitted the disease to at least one other patient were analysed as "cases" against patients with no transmission as "controls", using multivariate logistic regression analysis. RESULTS: 98 index patients were available for analysis (22 with transmission, 76 with no transmission). Covariates positively associated with transmission in univariate analysis at p < 0.05 included delay to isolation (Day 7 of illness or later), admission to a non-isolation facility, pre-existing chronic respiratory disease and immunosuppressive disease, need for oxygen, shortness of breath, vomiting, and higher lactate dehydrogenase levels and higher neutrophil counts. In the multivariate analysis, only three factors were significant: delay to isolation, admission to a non-isolation facility and higher lactate dehydrogenase levels of >650 IU/L (OR 6.4, 23.8 and 4.7 respectively). CONCLUSION: Clinical and epidemiological factors can help us to explain why transmission was observed in some instances but not in others.

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