Access to COVID-19 vaccination by socio-economic status in older Singaporean adults: a population-based cohort study.

OBJECTIVES: Socio-economic status (SES) disparities exist in the uptake of COVID-19 vaccination; however, most studies were conducted during the initial pandemic wave when vaccination was less discretionary, limiting generalizability. We aimed to determine whether differences in vaccination uptake across SES strata widened after the removal of vaccination-differentiated measures prior to the rollout of the second boosters, in a nationwide cohort of older Singaporeans at higher risk of severe-COVID-19. STUDY DESIGN: Retrospective population-based cohort study. METHODS: Retrospective population-based cohort study of all Singaporeans aged ≥60 years from 22nd February 2021-14th February 2023. Cox regression models controlling for demographics and comorbidities were used to estimate hazard-ratios (HRs) for the uptake of primary vaccination as well as first/second boosters, as recorded in the national vaccination registry, according to SES (housing type). RESULTS: 836,170 individuals were included for completion of a primary vaccine series; 784,938 individuals for completion of the first booster and 734,206 individuals for the completion of the second booster. Differences in vaccination uptake by SES strata were observed (e.g. vaccination uptake in lowest-SES [1-2 room public-housing] versus highest-SES [private housing]: second booster, 47.6% vs. 58.1%; first booster, 93.9% vs. 98.0%). However, relative differences did not markedly widen during second booster rollout when vaccination was more discretionary (e.g. amongst those aged 60-69 years: 0.75 [95% CI = 0.73-0.76] for the first booster; 0.81 [95% CI = 0.79-0.84] for the second booster). CONCLUSION: While differences in vaccination uptake across SES strata by housing type persisted during the rollout of primary vaccination and subsequent boosters in a nationwide cohort of older Singaporeans, differences did not widen substantially when vaccination was made more discretionary.

Association Between Minimum Inhibitory Concentration, Beta-lactamase Genes and Mortality for Patients Treated With Piperacillin/Tazobactam or Meropenem From the MERINO Study.

INTRODUCTION: This study aims to assess the association of piperacillin/tazobactam and meropenem minimum inhibitory concentration (MIC) and beta-lactam resistance genes with mortality in the MERINO trial. METHODS: Blood culture isolates from enrolled patients were tested by broth microdilution and whole genome sequencing at a central laboratory. Multivariate logistic regression was performed to account for confounders. Absolute risk increase for 30-day mortality between treatment groups was calculated for the primary analysis (PA) and the microbiologic assessable (MA) populations. RESULTS: In total, 320 isolates from 379 enrolled patients were available with susceptibility to piperacillin/tazobactam 94% and meropenem 100%. The piperacillin/tazobactam nonsusceptible breakpoint (MIC >16 mg/L) best predicted 30-day mortality after accounting for confounders (odds ratio 14.9, 95% confidence interval [CI] 2.8-87.2). The absolute risk increase for 30-day mortality for patients treated with piperacillin/tazobactam compared with meropenem was 9% (95% CI 3%-15%) and 8% (95% CI 2%-15%) for the original PA population and the post hoc MA populations, which reduced to 5% (95% CI -1% to 10%) after excluding strains with piperacillin/tazobactam MIC values >16 mg/L. Isolates coharboring extended spectrum ß-lactamase (ESBL) and OXA-1 genes were associated with elevated piperacillin/tazobactam MICs and the highest risk increase in 30-day mortality of 14% (95% CI 2%-28%). CONCLUSIONS: After excluding nonsusceptible strains, the 30-day mortality difference from the MERINO trial was less pronounced for piperacillin/tazobactam. Poor reliability in susceptibility testing performance for piperacillin/tazobactam and the high prevalence of OXA coharboring ESBLs suggests that meropenem remains the preferred choice for definitive treatment of ceftriaxone nonsusceptible Escherichia coli and Klebsiella.

Administrative data is as good as medical chart review for comorbidity ascertainment in patients with infections in Singapore.

The Charlson comorbidity index (CCI) is widely used for control of confounding from comorbidities in epidemiological studies. International Classification of Diseases (ICD)-coded diagnoses from administrative hospital databases is potentially an efficient way of deriving CCI. However, no studies have evaluated its validity in infectious disease research. We aim to compare CCI derived from administrative data and medical record review in predicting mortality in patients with infections. We conducted a cross-sectional study on 199 inpatients. Correlation analyses were used to compare comorbidity scores from ICD-coded administrative databases and medical record review. Multivariable regression models were constructed and compared for discriminatory power for 30-day in-hospital mortality. Overall agreement was fair [weighted kappa 0·33, 95% confidence interval (CI) 0·23-0·43]. Kappa coefficient ranged from 0·17 (95% CI 0·01-0·36) for myocardial infarction to 0·85 (95% CI 0·59-1·00) for connective tissue disease. Administrative data-derived CCI was predictive of CCI ⩾5 from medical record review, controlling for age, gender, resident status, ward class, clinical speciality, illness severity, and infection source (C = 0·773). Using the multivariable model comprising age, gender, resident status, ward class, clinical speciality, illness severity, and infection source to predict 30-day in-hospital mortality, administrative data-derived CCI (C = 0·729) provided a similar C statistic as medical record review (C = 0·717, P = 0·8548). In conclusion, administrative data-derived CCI can be used for assessing comorbidities and confounding control in infectious disease research.

Can intra-articular therapies prior to total knee arthroplasty increase the risk of periprosthetic infection?

Intra-articular therapies, such as steroid injection, viscosupplement injection and acupuncture, are common non-surgical options for patients with osteoarthritis of the knee. With any intra-articular injection or acupuncture procedure, there is a potential for inoculation with bacteria leading to possible knee infection. The authors report a patient who incurred an acute infection found after a total knee arthroplasty attributed to prior acupuncture procedure done as part of conservative treatment.

Empowerment of nurses in antibiotic stewardship: a social ecological qualitative analysis.

BACKGROUND: Inappropriate antibiotics use and antimicrobial resistance (AMR) are increasingly becoming global health issues of great concern. Despite the established antibiotic stewardship programmes (ASPs) in many countries, limited efforts have been made to engage nurses and clearly define their roles in ASPs. AIM: An exploratory qualitative study was conducted to understand the facilitators and barriers that impact nurses' involvement and empowerment in antibiotic stewardship. METHODS: Focus group discussions (FGDs) were conducted with purposively sampled nurses from three major public hospitals in Singapore. FGDs were audio-recorded and transcribed verbatim. Data were analysed using Applied Thematic Analysis and interpreted using the Social Ecological Model. FINDINGS: At the intrapersonal level, nurses felt empowered in carrying out their roles in antibiotic administration. They saw themselves as gatekeepers to ensure that the prescribed antibiotics were administered appropriately. However, nurses felt they lacked the knowledge and expertise in antibiotic use and AMR prevention. At the interpersonal level, this deficit in knowledge and expertise in antibiotic use impacted how they were perceived by patients and caregivers as well as their interactions with the primary care team when voicing outpatient safety concerns and antibiotic administration suggestions. At the organizational level, nurses relied on drug administration guidelines to ensure appropriate antibiotic administration and as a safety net when physicians questioned their clinical practice. At the community level, nurses felt there was a lack of awareness and knowledge on antibiotic use among the general population. CONCLUSION: These findings provide important insights to harness the contributions of nurses, and to formally acknowledge and enlarge their roles in ASPs.

Decision tree algorithm in deciding hospitalization for adult patients with dengue haemorrhagic fever in Singapore.

OBJECTIVES: To develop a simple decision tree for clinicians to decide between hospitalization and outpatient monitoring of adult dengue patients. METHOD: Retrospective cohort study on all laboratory-diagnosed dengue patients admitted in 2004 to Tan Tock Seng Hospital, Singapore. Demographic, clinical, laboratory and radiological data were collected, and cases classified as dengue fever (DF) or dengue haemorrhagic fever (DHF) using World Health Organization criteria. To develop the decision tree, we used chi-squared automatic interaction detector (CHAID) with bi-way and multi-way splitting. The resulting trees were pruned to achieve the highest sensitivity with the shortest tree. RESULTS: In 2004, 1973 probable and confirmed adult dengue patients were admitted; DF comprised 1855 (94.0%) and DHF 118 (6.0%) of the cases. The best decision tree prediction had three branches, consisting of a history of clinical bleeding, serum urea, and serum total protein. This decision tree had a sensitivity of 1.00, specificity of 0.46, positive predictive value of 7.5%, and negative predictive value of 100%. The overall accuracy of the decision tree was 48.1%. The test sensitivity and specificity compared favourably with other predictive probability equations and sophisticated laboratory tests, and would prevent 43.9% of mild DF cases from hospitalization. CONCLUSIONS: A simple decision tree is effective in predicting DHF in the clinical setting for adult dengue infection.

Risk factors and treatment outcomes of severe Clostridioides difficile infection in Singapore.

Severe Clostridioides difficile infection (CDI) is associated with poorer outcomes. We aimed to identify risk factors and treatment outcomes of severe CDI. This was a retrospective cohort study. Eligible patients from January to December 2012 were recruited. Severity definitions were in accordance with SHEA/IDSA 2010 guideline. Treatment outcomes were (1) diarrhoea persistence, (2) CDI recurrence, (3) major complications despite treatment and (4) 30-day mortality. Two hundred and seventy-two patients were included and 40% had severe CDI. High APACHE II score (aOR 1.112, 95% CI 1.014-1.219; p < 0.05), high C-reactive protein (aOR 1.011; 95% CI 1.004-1.019; p < 0.01) and carbapenem usage in past 90 days (aOR 3.259; 95% CI 1.105-9.609; p < 0.05) were independent risk factors of severe CDI. Majority received oral metronidazole as sole treatment (92.6% for mild-moderate, 83.9% for severe, 77% for severe-complicated). Diarrhoea persistence was 32% versus 50% (p < 0.01), CDI recurrence 16.6% versus 16.5% (p > 0.05), major complications 1.2% versus 11% (p < 0.001) and 30-day mortality 7.4% versus 20.2% (p < 0.01) in mild-moderate CDI and severe CDI groups respectively. Oral metronidazole for severe CDI was associated with persistent diarrhoea, major complications and mortality. Risk factors for severe CDI can guide doctors in diagnosing severe CDI earlier and instituting oral vancomycin treatment to improve outcomes from severe CDI.

Diagnostic lumbar puncture: minimizing complications.

Diagnostic lumbar puncture (LP) is essential to the diagnosis of central nervous system infections and subarachnoid haemorrhage. Life or limb-threatening adverse events due to the procedure are rare, but less severe complications may be common. Clinical practice in diagnostic LP is often not evidenced based. The aim of the study was to use best available published evidence to address questions on minimizing complications associated with diagnostic LP. We searched PubMed for studies in the English language using key words relevant to the complications of diagnostic LP. We emphasized randomized controlled trials and systematic reviews enrolling adult patients undergoing diagnostic LP. Uncontrolled studies and studies involving children or spinal anaesthesia were considered when no other evidence was available. There were nine prospective studies and three systematic reviews on reducing complications from LP. Recommendations on interventions to minimize complications of LP are graded based on the quality and strength of evidence.

Ertapenem for the treatment of extended-spectrum beta-lactamase-producing Gram-negative bacterial infections.

Ertapenem is indicated for complicated intra-abdominal, skin and skin-structure, urinary tract and acute pelvic infections as well as community-acquired pneumonia, for which there are cheaper and more narrow-spectrum antibiotics. It is active against extended-spectrum beta-lactamase (ESBL)-producing Gram-negative bacteria, but report of its clinical efficacy is lacking. We evaluated our experience with the use of ertapenem for ESBL-producing Gram-negative bacterial infections over 13 months. Forty-seven patients were treated with 50 courses of ertapenem. Thirty-nine courses were for ESBL-producing Gram-negative bacterial infections, 33% of which were bacteraemia. The clinical response rate was 92% and survival to hospital discharge was 94%. We propose that ertapenem has a role in the first-line treatment of these infections.

Proposed primary endpoints for use in clinical trials that compare treatment options for bloodstream infection in adults: a consensus definition.

OBJECTIVES: To define standardized endpoints to aid the design of trials that compare antibiotic therapies for bloodstream infections (BSI). METHODS: Prospective studies, randomized trials or registered protocols comparing antibiotic therapies for BSI, published from 2005 to 2016, were reviewed. Consensus endpoints for BSI studies were defined using a modified Delphi process. RESULTS: Different primary and secondary endpoints were defined for pilot (small-scale studies designed to evaluate protocol design, feasibility and implementation) and definitive trials (larger-scale studies designed to test hypotheses and influence clinical practice), as well as for Staphylococcus aureus and Gram-negative BSI. For pilot studies of S. aureus BSI, a primary outcome of success at day 7 was defined by: survival, resolution of fever, stable/improved Sequential Organ Failure Assessment (SOFA) score and clearance of blood cultures, with no microbiologically confirmed failure up to 90 days. For definitive S. aureus BSI studies, a primary outcome of success at 90 days was defined by survival and no microbiologically confirmed failure. For pilot studies of Gram-negative BSI, a primary outcome of success at day 7 was defined by: survival, resolution of fever and symptoms related to BSI source, stable or improved SOFA score and negative blood cultures. For definitive Gram-negative BSI studies, a primary outcome of survival at 90 days supported by a secondary outcome of success at day 7 (as previously defined) was agreed. CONCLUSIONS: These endpoints provide a framework to aid future trial design. Further work will be required to validate these endpoints with respect to patient-centred clinical outcomes.

Practical management of avian influenza in humans.

There has been much alarm about avian influenza and its potential for a global pandemic ever since the current epidemic of avian influenza infections in humans began in 2003. While there have been a number of published reports on the clinical features of avian influenza, there are few guidelines on the practical management of patients with avian influenza. A symposium organised by the Society of Infectious Disease (Singapore), Society of Intensive Care Medicine and the Singapore General Hospital was held in Singapore to gather the views of experts from Turkey, Thailand, Vietnam and Indonesia who collectively had first-hand experience of the management of the majority (more than 100 of 192) of cases of avian influenza worldwide. The experts emphasised the importance of adapting international guidelines to the practicalities of situations on the ground. There was stress on wide screening using clinical criteria primarily, molecular diagnostic techniques (with reference laboratory confirmation) for diagnosis, and rational use of antiviral prophylaxis as well as infection control using at least surgical masks, gowns and gloves. A detailed analysis of data from a pooled database from these and other affected countries is critical to building up the evidence base for practical internationally applicable guidelines.

Implementation hurdles of an interactive, integrated, point-of-care computerised decision support system for hospital antibiotic prescription.

Antimicrobial stewardship is used to combat antimicrobial resistance. In Singapore, a tertiary hospital has integrated a computerised decision support system, called Antibiotic Resistance Utilisation and Surveillance-Control (ARUSC), into the electronic inpatient prescribing system. ARUSC is launched either by the physician to seek guidance for an infectious disease condition or via auto-trigger when restricted antibiotics are prescribed. This paper describes the implementation of ARUSC over three phases from 1 May 2011 to 30 April 2013, compared factors between ARUSC launches via auto-trigger and for guidance, examined factors associated with acceptance of ARUSC recommendations, and assessed user acceptability. During the study period, a monthly average of 9072 antibiotic prescriptions was made, of which 2370 (26.1%) involved ARUSC launches. Launches via auto-trigger comprised 48.1% of ARUSC launches. In phase 1, 23% of ARUSC launches were completed. This rose to 38% in phase 2, then 87% in phase 3, as escapes from the ARUSC programme were sequentially disabled. Amongst completed launches for guidance, 89% of ARUSC recommendations were accepted versus 40% amongst completed launches via auto-trigger. Amongst ARUSC launches for guidance, being from a medical department [adjusted odds ratio (aOR)=1.20, 95% confidence interval (CI) 1.04-1.37] and ARUSC launch during on-call (aOR=1.81, 95% CI 1.61-2.05) were independently associated with acceptance of ARUSC recommendations. Junior physicians found ARUSC useful. Senior physicians found ARUSC reliable but admitted to having preferences for antibiotics that may conflict with ARUSC. Hospital-wide implementation of ARUSC encountered hurdles from physicians. With modifications, the completion rate improved.

Rapidly growing mycobacteria in Singapore, 2006-2011.

Nontuberculous mycobacteria infection is a growing global concern, but data from Asia are limited. This study aimed to describe the distribution and antibiotic susceptibility profiles of rapidly growing mycobacterium (RGM) isolates in Singapore. Clinical RGM isolates with antibiotic susceptibility tests performed between 2006 and 2011 were identified using microbiology laboratory databases and minimum inhibitory concentrations of amikacin, cefoxitin, clarithromycin, ciprofloxacin, doxycycline, imipenem, linezolid, moxifloxacin, sulfamethoxazole or trimethoprim-sulfamethoxazole, tigecycline and tobramycin were recorded. Regression analysis was performed to detect changes in antibiotic susceptibility patterns over time. A total of 427 isolates were included. Of these, 277 (65%) were from respiratory specimens, 42 (10%) were related to skin and soft tissue infections and 36 (8%) were recovered from blood specimens. The two most common species identified were Mycobacterium abscessus (73%) and Mycobacterium fortuitum group (22%), with amikacin and clarithromycin being most active against the former, and quinolones and trimethoprim-sulfamethoxazole against the latter. Decreases in susceptibility of M. abscessus to linezolid by 8.8% per year (p 0.001), M. fortuitum group to imipenem by 9.5% per year (p 0.023) and clarithromycin by 4.7% per year (p 0.033) were observed. M. abscessus in respiratory specimens is the most common RGM identified in Singapore. Antibiotic options for treatment of RGM infections are increasingly limited.

The impact of multidrug resistance in healthcare-associated and nosocomial Gram-negative bacteraemia on mortality and length of stay: cohort study.

Multidrug-resistant Gram-negative bacteria (MDR-GNB) are an emerging public health threat. Accurate estimates of their clinical impact are vital for justifying interventions directed towards preventing or managing infections caused by these pathogens. A retrospective observational cohort study was conducted between 1 January 2007 and 31 July 2009, involving subjects with healthcare-associated and nosocomial Gram-negative bacteraemia at two large Singaporean hospitals. Outcomes studied were mortality and length of stay post-onset of bacteraemia in survivors (LOS). There were 675 subjects (301 with MDR-GNB) matching study inclusion criteria. On multivariate analysis, multidrug resistance was not associated with 30-day mortality, but it was independently associated with longer LOS in survivors (coefficient, 0.34; 95% CI, 0.21-0.48; p < 0.001). The excess LOS attributable to multidrug resistance after adjustment for confounders was 6.1 days. Other independent risk factors for higher mortality included male gender, higher APACHE II score, higher Charlson comorbidity index, intensive care unit stay and presence of concomitant pneumonia. Concomitant urinary tract infection and admission to a surgical discipline were associated with lower risk of mortality. Appropriate empirical antibiotic therapy was neither associated with 30-day mortality nor LOS, although the study was not powered to assess this covariate adequately. Our study adds to existing evidence that multidrug resistance per se is not associated with higher mortality when effective antibiotics are used for definitive therapy. However, its association with longer hospitalization justifies the use of control efforts.

Acute HIV infection in Singapore: predominance of men who have sex with men.

INTRODUCTION: The incidence of human immunodeficiency virus (HIV) infection in Singapore is on the rise. We aimed to study the clinical epidemiology of acute HIV infection in Singapore. METHODS: All patients that fulfilled the criteria for definite and probable acute HIV infection were prospectively identified from January 1, 2003 to June 30, 2006. Demographic, clinical and laboratory data were recorded. RESULTS: A total of 16 out of 34 patients had definite acute HIV infection, and 68 percent of the entire cohort comprised men who have sex with men (MSM). Ten percent of the patients were co-infected with hepatitis B and C viruses, while 27 percent were infected with syphilis. Signs and symptoms were nonspecific, with fever, rash and diarrhoea being the three most common symptoms. Only 35 percent of the patients required hospitalisation. CONCLUSION: Men who have sex with men account for the majority of patients with acute HIV infections in Singapore, many of them also being co-infected with syphilis. Safer sex campaign among MSM should be implemented or intensified.

The benign nature of acute dengue infection in hospitalized older adults in Singapore.

OBJECTIVES: In Singapore, dengue primarily affects adults. This study aimed to determine if older dengue patients in Singapore have greater morbidity and mortality. METHODS: All laboratory diagnosed dengue patients admitted to Tan Tock Seng Hospital in 2004 were retrospectively reviewed. Cases were re-classified into dengue fever and dengue hemorrhagic fever based on World Health Organization criteria. Demographic, clinical, laboratory, and outcome data of patients aged > or = 60 years and <60 years were collected. RESULTS: Of 1971 laboratory confirmed dengue cases, 66 were aged > or = 60 years. Older patients were significantly less likely to be male (44% vs. 64%), and more likely to have diabetes (17% vs. 2%), hypertension (48% vs. 4%), ischemic heart disease (6% vs. 0.1%), hyperlipidemia (18% vs. 1%), and secondary dengue infections (64% vs. 34%). Clinical features were similar except older patients were significantly less likely to report fever (92% vs. 99%), or have leukopenia (32% vs. 51%) or hemoconcentration (0 vs. 5%) on admission. Older patients had similar dengue hemorrhagic fever, bleeding, hypotension, severe thrombocytopenia, and elevated transaminase rates. Length of hospital stay, risk of intensive care unit admission, and outcome of death were not statistically different. CONCLUSIONS: Despite greater co-morbidity and secondary dengue infection, older dengue patients in Singapore did not have greater morbidity or mortality.

New influenza A (H1N1) 2009 in Singapore: the first ten adult imported cases.

INTRODUCTION: Since late March 2009, a novel influenza H1N1 strain emerged in humans in Mexico and the United States. It has rapidly spread to many countries on different continents, prompting unprecedented activation of pandemic preparedness plans. Singapore has adopted a containment strategy with active screening of febrile travellers with respiratory symptoms from affected countries since April 27, 2009. METHODS: All cases with new influenza A (H1N1) confirmed on polymerase chain reaction assay on combined nasal and throat swabs and who were admitted to the Communicable Disease Centre, were included in a prospective evaluation of clinical characteristics of new influenza A (H1N1). RESULTS: From May 26 to June 3, 2009, there were ten patients with a mean age of 27.6 years, seven of whom were female. All but one travelled from the United States, six of whom travelled from New York; the last one travelled from the Philippines. Clinical illness developed within a mean of 1.4 days after arrival in Singapore, and presentation to the emergency department at a mean of 2.7 days from illness onset. Fever occurred in 90 percent, cough 70 percent, coryza 40 percent, sore throat and myalgia/arthralgia 30 percent; none had diarrhoea. The fever lasted a mean of 2.1 days. All were treated with oseltamivir. The clinical course was uncomplicated in all cases. CONCLUSION: Clinical features of new influenza A (H1N1) appeared mild, and ran an uncomplicated course in immunocompetent patients.