Risk Factors for Severe Adenovirus Infection in Children during an Outbreak in Singapore

<p><b>BACKGROUND</b>Human adenoviruses (HAdVs) can cause a variety of human illnesses, with associated temporal and geographic changes in disease incidence. We report the emergence of an outbreak of HAdV infections in Singapore, presumably caused by a change of the predominating type to HAdV-7. We examined the clinical features of children admitted with HAdV infection to 1 institution and the risk factors for severe infection.</p><p><b>MATERIALS AND METHODS</b>This is a retrospective case-control study of all HAdV-infected children admitted during weeks 1 to 19 in 2013, as identified from laboratory records. A descriptive retrospective analysis of epidemiology, clinical data and the outcome of these children was also performed. Patients with severe infections were defined as cases, those with non-severe infections as controls, and the 2 groups were compared to find possible independent risk factors.</p><p><b>RESULTS</b>Eighty-five patients with HAdV infection were studied, including 11 (12.9%) cases and 74 (87.1%) controls. Binary logistic regression showed that cases were more likely to be <2 years old (adjusted OR 10.6, 95% CI, 1.8 to 63.2) and to have significant comorbidities (adjusted OR 19.9, 95% CI, 3.4 to 116.1) compared to controls. The predominant type in 2013 was HAdV-7, which differed from 2011 and 2012, when HAdV-3 was more common. There was a trend towards pneumonia being more common in patients infected with HAdV-7 than in patients infected with other types, although this did not reach statistical significance (OR 2.8, 95% CI, 0.9 to 8.7).</p><p><b>CONCLUSION</b>The emergence of HAdV-7 in a population where other HAdV types had circulated previously may have caused the outbreak in Singapore, and this was associated with more serious infections in children. Young age (<2 years) and significant comorbidities were associated with more severe HAdV infection.</p>

Systemic Candidiasis in Extremely Low Birthweight (ELBW) Neonates Despite the Routine Use of Topical Miconazole Prophylaxis: Trends, Risk Factors and Outcomes over an 11-Year Period

<p><b>INTRODUCTION</b>This study aims to determine the incidence, trends of systemic candidiasis and meningitis in extremely low birthweight (ELBW) neonates (<1000 gms) despite the routine use of topical miconazole prophylaxis and to compare the risk factors, adverse outcomes and comorbidities with controls.</p><p><b>MATERIALS AND METHODS</b>Retrospective cohort study of ELBW neonates with systemic candidiasis and meningitis over an 11-year period (1997 to 2007). Matched case control analyses were performed to determine the risk factors and comorbidities which were severe intraventricular haemorrhage (IVH), severe retinopathy of prematurity (ROP), patent ductus arteriosus (PDA) requiring treatment, necrotising enterocolitis (NEC), chronic lung disease (CLD) and cholestatic jaundice. Mortality and end organ involvement secondary to systemic candidiasis were identified as adverse outcomes.</p><p><b>RESULTS</b>Of the 757 ELBW neonates, 51 (6.7%) had evidence of systemic candidiasis with a significant 3-fold increase in trend noted in 2007 as compared against 1997 (12.1% vs 3.8%) (RR 1.2, 95% CI, 1.06 to 1.36, P <0.001). This corresponds to a significant increasing trend of preceding or co-existent bacterial blood stream infections (BSI) in neonates with systemic candidiasis (0% in 1997 vs 7.1% in 2007, RR 1.40, 95% CI, 1.04 to 1.25, P = 0.005). On logistic regression analysis, decreasing gestational age was an independent risk factor for systemic candidiasis (OR 2.0, 95% CI, 1.52 to 2.63, P <0.001). Candida meningitis was detected in 4/38 (10.5%) and end organ involvement in 17 (33%). The organisms isolated were Candida parapsilosis 31 (61%), Candida albicans 17 (33%) and Candida glabrata 3 (5.8%). Significantly higher mortality was seen in cases when compared to controls 10/51 (19.6%) vs 76/706 (10.7%) (OR 2.02, 95% CI, 1.02 to 4.40, P <0.001).</p><p><b>CONCLUSION</b>Increasing trend in the incidence of systemic candidiasis despite routine use of topical miconazole prophylaxis is of concern and future studies comparing the use of systemic fl uconazole versus oral nystatin may need to be considered.</p>

Risk Factors for Complicated Influenza A (H1N1) 2009 Disease in Children

<p><b>INTRODUCTION</b>Singapore had its first case of pandemic influenza A (H1N1) 2009 on 26 May 2009. As of 3 August 2009, 440 children with confirmed H1N1were admitted to KK Women's and Children's Hospital (KKH).</p><p><b>MATERIALS AND METHODS</b>This is a retrospective case control study of children admitted from 26 May 2009 to 19 July 2009 with H1N1infection. Cases and controls were first differentiated by whether they were complicated or non-complicated in nature, and subsequently analysed with regards to possible independent risk factors.</p><p><b>RESULTS</b>We analysed 143 admitted children; 48 cases and 95 controls (1: 2 ratio). Significant comorbidity was found in 20.3% (n = 29) of patients with the majority having asthma (n = 18, 12.6 %) followed by obesity (n = 7, 4.9%). Binary logistic regression analysis showed risk factors for complicated disease were comorbidity (adjusted OR 6.0, 95% CI, 2.5 to 14.6, P < 0.0001) and age <2 years (adjusted OR 9.8, 95% CI, 2.4 to 40, P = 0.001). Age less than 5 years was not found to be a risk factor.</p><p><b>CONCLUSION</b>In the early stages of an evolving influenza epidemic when oseltamivir stocks are low, oseltamivir treatment for influenza can be streamlined and offered to those at highest risk who are under 2 years old or have significant comorbidity to prevent complicated disease.</p>

Vancomycin-resistant Enterococci in Singaporean hospitals: 5-year results of a multi-centre surveillance programme

<p><b>INTRODUCTION</b>Vancomycin-resistant enterococci (VRE) have emerged as one of the major nosocomial antimicrobial-resistant pathogens globally. In this article, we describe the epidemiology of VRE in Singaporean public hospitals in the 5 years following the major local VRE outbreak in 2005.</p><p><b>MATERIALS AND METHODS</b>A passive laboratory surveillance programme identified non-duplicate VRE isolates from 7 hospitals from 2006 to 2010. Descriptive statistics and time-series analysis was performed on all clinical VRE isolates for each individual hospital as well as for the combined dataset.</p><p><b>RESULTS</b>There were a total of 418 VRE isolates over 5 years, of which 102 isolates (24.4%) were from clinical cultures. Between 0.4% and 0.7% of all clinical enterococcal isolates were resistant to vancomycin. The overall incidence-density of VRE did not change over time in Singapore despite 2 separate outbreaks in tertiary hospitals in 2009 and 2010. Incidence-density of clinical VRE cases fell in 2 secondary hospitals, while another 2 hospitals experienced no significant VRE infections after 2008.</p><p><b>CONCLUSION</b>The prevalence of VRE clinical isolates remains low in Singaporean public sector hospitals. However, the presence of at least 2 outbreaks in separate hospitals over the past 5 years indicates the need for continued vigilance in order to prevent any further increase in VRE prevalence locally.</p>

Obstetric outcomes of influenza A H1N1 (2009) infection in pregnancy--experience of a Singapore tertiary hospital

<p><b>INTRODUCTION</b>Influenza A H1N1 (2009) pandemic has affected countries worldwide including Singapore. Data on obstetric outcomes of women with H1N1 (2009) in pregnancy are lacking.</p><p><b>MATERIALS AND METHODS</b>This was an observational study analysing the obstetric outcomes of pregnant women with influenza A H1N1 (2009) infection who had delivered at a viable gestation (24 weeks or more) in our centre.</p><p><b>RESULTS</b>Between 23 June 2009 and 30 September 2009, 235 pregnant women were diagnosed with influenza A H1N1 (2009) at our centre, with 42 having delivered and comprising the study cohort. Median age was 27.5 years (range, 16 to 42). Multiparous women comprised 59.5% (25/42) whilst 40.5% (17/42) were primiparous. In terms of ethnicity, 61.9% were Malays, 26.2% Chinese, 4.8% Indians and 7.1% Others. All women received oseltamivir. All had shown recovery from the acute influenza infection. There were no respiratory complications. Twenty-nine women (69.0%) delivered at term. Twenty-fi ve women (59.5%) had spontaneous labour whilst 15 (35.7%) had labour induction. Two women (4.8%) did not labour. Thirty-six women (85.7%) had vaginal delivery, of whom 3 were instrumental deliveries. Apgar scores of greater than 8 at 1 min and 5 min were documented in babies of 95.2% (40/42) women, respectively. Thirty-two women (76.2%) delivered babies with birthweights greater than 2500 g. Compared with historical data from 2008, the H1N1 cohort had comparable mean birthweight and average gestational age at delivery of 38 weeks.</p><p><b>CONCLUSION</b>Our study suggested that obstetric outcomes were not adversely affected by influenza A H1N1 (2009) infection.</p>

The efficacy of influenza vaccination in healthcare workers in a tropical setting: a prospective investigator blinded observational study

<p><b>INTRODUCTION</b>Influenza vaccine has been shown to be highly effective in temperate regions with well-defined seasonal influenza. Healthcare workers (HCWs) are advised to receive regular influenza vaccination to protect themselves and their patients. However, there are limited data on the efficacy of influenza vaccine in HCWs in the tropics.</p><p><b>MATERIALS AND METHODS</b>In this observational, investigator blinded cohort study, bi-monthly questionnaires recording influenza-like illness (ILI) episodes and medical leave were administered to 541 HCWs at the Singapore National University Hospital and KK Women's and Children's Hospital from 2004 to 2005. ILI was defined according to a standard symptom score.</p><p><b>RESULTS</b>Baseline characteristics were comparable in both the vaccinated and non-vaccinated groups. Overall, the relative risk of self-reported ILI in vaccinated HCWs was 1.13 [95% confidence interval (CI), 0.98-1.13; P=0.107]; medical leave taken was lower in the vaccinated group [mean 0.26+/-0.6 days per visit, compared with 0.30+/-0.5 days in the non-vaccinated group (P=0.40)]. Because of the reported Northern Hemisphere 2003/04 vaccine mismatch, we stratified the cohort and determined that the group which received a matched vaccine had a relative risk of ILI of 0.49 (95% CI, 0.37-0.66; P<0.001), achieving a vaccine efficacy of 51%. Mean medical leave decreased significantly in HCWs who received the matched vaccine, compared with those who did not receive vaccination (0.13+/-0.3 vs 0.30+/-0.5; P<0.001) and with HCWs vaccinated with mismatched strains (0.13+/-0.3 vs 0.39+/-0.9; P=0.01).</p><p><b>CONCLUSIONS</b>A well-matched influenza vaccine is effective in preventing ILI and reducing sickness absence in healthcare workers in tropical settings. Efforts need to be made to increase influenza vaccination rates and to improve the currently available vaccines.</p>

Antibiotic resistance in gram-negative bacilli: a Singapore perspective

<p><b>INTRODUCTION</b>Antibiotic resistance in gram-negative bacilli is an area of increasing importance. This prospective study was performed to survey antibiotic resistance in Escherichia coli (E. coli), Klebsiella spp., Pseudomonas aeruginosa and Acinetobacter spp. over a 1-year period.</p><p><b>MATERIALS AND METHODS</b>Non-duplicate isolates of E. coli, Klebsiella spp., P. aeruginosa and Acinetobacter spp. were collected from participating Singapore hospitals during defined collection periods in 2006 and 2007. Confirmatory identification and antibiotic susceptibility testing were performed at Changi General Hospital. Minimum inhibitory concentrations (MIC) to a defined panel of antibiotics were determined using microbroth dilution methods. The presence of extended-spectrum beta lactamases and AmpC beta-lactamases in Enterobacteriaceae was determined by phenotypic methods, and susceptibility results were defined using current breakpoints from the Clinical Laboratory Standards Institute (CLSI).</p><p><b>RESULTS</b>Seven hundred and forty-six gram-negative bacilli were received for testing. Resistance to extended-spectrum cephalosporins was present in a third of Enterobacteriaceae isolates, and extended-spectrum beta-lactamases (ESBL) carriage was present in 19.6% and 30.1% of E. coli and Klebsiella pneumoniae, respectively. AmpC enzymes were also detected in 8.5% and 5.6% of E. coli and K. pneumoniae isolates respectively. All Enterobacteriaceae were susceptible to imipenem and meropenem. The most active antibiotics against P. aeruginosa were amikacin, meropenem and piperacillin-tazobactam. A third of P. aeruginosa showed reduced susceptibility to polymyxin B. Carbapenem resistance was significantly higher in Acinetobacter baumannii (70.5%) than in other Acinetobacter species (25.0%). The most active antibiotic against A. baumannii was polymyxin B.</p><p><b>CONCLUSION</b>Antibiotic resistance is prevalent in gram-negative bacilli isolated from Singapore hospitals. The MIC testing surveillance programme complemented susceptibility data from wider laboratory-based surveillance, and has revealed emerging mechanisms of antibiotic resistance.</p>

A retrospective analysis of antifungal susceptibilities of Candida bloodstream isolates from Singapore hospitals

<p><b>INTRODUCTION</b>Worldwide, Candida albicans is the most common Candida species implicated in bloodstream infections. However, the proportion of non-albicans bloodstream infections is increasing. Fluconazole resistance is known to be more common in non-albicans species, but is also reported in C. albicans. This retrospective study was performed to determine the species epidemiology of Candida bloodstream infections in Singapore hospitals, and to perform susceptibility testing to a range of antifungal drugs.</p><p><b>MATERIALS AND METHODS</b>Candida spp. isolated from bloodstream infections from October 2004 to December 2006 were collected from 3 participating hospitals: a tertiary referral hospital (Singapore General Hospital), a secondary referral hospital (Changi General Hospital) and an obstetrics/paediatric hospital [KK Women's and Children's Hospital (KKWCH)]. Isolate collection was also retrospectively extended to January 2000 for KKWCH because of the limited number of cases from this hospital. Isolates were identified by a common protocol, and antifungal susceptibility testing was performed by microbroth dilution (Sensititre One, Trek Diagnostics, United Kingdom).</p><p><b>RESULTS</b>The most common isolates were C. albicans (37%), C. tropicalis (27%) and C. glabrata (16%). There were differences in species distribution between institutions, with C. parapsilosis and C. albicans predominant in KKWCH, and C. albicans and C. tropicalis predominant in the other 2 institutions. Fluconazole resistance was detected in 3.2% of all Candida spp., and 85.3% were classified as susceptible. All C. albicans and C. parapsilosis were susceptible to fluconazole and voriconazole, while susceptibility to fluconazole was much more variable for C. glabrata and C. krusei.</p><p><b>CONCLUSION</b>This study shows that C. albicans remains the predominant Candida species isolated from bloodstream infections in the 3 participating hospitals. However, non-albicans species accounted for nearly two-thirds of all cases of candidaemia. Resistance to fluconazole was uncommon, and was generally confined to C. krusei and C. glabrata.</p>