Serratia marcescens in the neonatal intensive care unit: A cluster investigation using molecular methods.

BACKGROUND: Serratia marcescens (S. marcescens) is associated with nosocomial infections with significant morbidity and mortality in the neonatal intensive care units (NICU). We describe the control of a multi-clonal S. marcescens infections outbreak in our tertiary-level NICU and the application of molecular typing using repetitive element palindromic PCR (rep-PCR) and next generation sequencing (NGS) in the investigation. METHODS: Outbreak investigation was performed where clinical, spatial and epidemiologic links were established. Screening of all infants in the NICU and the environment was performed. Rep-PCR and NGS methods were used to identify potential environmental sources of infections and clustering among cases. RESULTS: Eleven cases were detected during the outbreak period: mean gestational age 27 weeks (range: 24-32), predominantly male (82%), mean age of infection 24 days (range: 6-51). Six infants were treated for conjunctivitis and one for bacteraemia. Identification of colonized infant via a point prevalence survey and cohorting of all infected/colonized patients were implemented. We performed environmental swabbing of surfaces, water outlets, chlorhexidine hand wash solutions and hand hygiene hand rubs. Both rep-PCR and NGS classified the 11 case isolates into 5 types. No point source was identified except for a single positive environmental isolate from a sink which was clonally distinct from the cases. CONCLUSION: Identification and cohorting of infected/colonized patient was important in the control of S. marcescens outbreak in the NICU. The utility of rep-PCR was comparable to NGS in providing molecular information to develop S. marcescens outbreak control strategies.

Pragmatic and evidence-based approach to paediatric cerebrospinal fluid reference limits for white cell count and concentrations of total protein and glucose.

BACKGROUND: It is often impractical for each laboratory to establish its own paediatric reference intervals. This is particularly true for specimen types collected using invasive procedures, for example, cerebrospinal fluid (CSF). METHODS: Published CSF reference intervals for white cell count, and concentrations of total protein and glucose were reviewed by stakeholders in a paediatric hospital. Consensus reference intervals for the three CSF parameters were then subjected to verification using guidelines from the Clinical Laboratory Standards Institute and residual CSF specimens. RESULTS: Consensus paediatric reference intervals adapted from published studies with minor modifications were locally verified as follows. White cell count (x106 cells/L): 0-20 (<1 month); 0-10 (1-2 months); 0-5 (>2 months). Total protein (g/L): 0.3-1.2 (<1 month); 0.2-0.6 (1-3 months); 0.1-0.4 (>3 months). Glucose (mmol/L): 2.0-5.6 (<6 months); 2.4-4.3 (6 months or older).

Prevalence of Healthcare-Associated Infections and Antimicrobial Use Among Adult Inpatients in Singapore Acute-Care Hospitals: Results From the First National Point Prevalence Survey.

BACKGROUND: We conducted a national point prevalence survey (PPS) to determine the prevalence of healthcare-associated infections (HAIs) and antimicrobial use (AMU) in Singapore acute-care hospitals. METHODS: Trained personnel collected HAI, AMU, and baseline hospital- and patient-level data of adult inpatients from 13 private and public acute-care hospitals between July 2015 and February 2016, using the PPS methodology developed by the European Centre for Disease Prevention and Control. Factors independently associated with HAIs were determined using multivariable regression. RESULTS: Of the 5415 patients surveyed, there were 646 patients (11.9%; 95% confidence interval [CI], 11.1%-12.8%) with 727 distinct HAIs, of which 331 (45.5%) were culture positive. The most common HAIs were unspecified clinical sepsis (25.5%) and pneumonia (24.8%). Staphylococcus aureus (12.9%) and Pseudomonas aeruginosa (11.5%) were the most common pathogens implicated in HAIs. Carbapenem nonsusceptibility rates were highest in Acinetobacter species (71.9%) and P. aeruginosa (23.6%). Male sex, increasing age, surgery during current hospitalization, and presence of central venous or urinary catheters were independently associated with HAIs. A total of 2762 (51.0%; 95% CI, 49.7%-52.3%) patients were on 3611 systemic antimicrobial agents; 462 (12.8%) were prescribed for surgical prophylaxis and 2997 (83.0%) were prescribed for treatment. Amoxicillin/clavulanate was the most frequently prescribed (24.6%) antimicrobial agent. CONCLUSIONS: This survey suggested a high prevalence of HAIs and AMU in Singapore's acute-care hospitals. While further research is necessary to understand the causes and costs of HAIs and AMU in Singapore, repeated PPSs over the next decade will be useful to gauge progress at controlling HAIs and AMU.

Gestational age-specific reference intervals for serum thyroid hormone levels in a multi-ethnic population.

BACKGROUND: Thyroid disorders are common during pregnancy. To date, a limited number of studies have reported differences in serum thyroid hormone concentrations between different ethnic groups. We sought to establish gestational age-specific reference intervals for serum levels of thyroid hormones in a multi-ethnic population and investigate whether separate reference intervals should be used for different ethnic groups. METHODS: A total of 926 pregnant women from multiple ethnic groups attended four separate study visits spanning the three trimesters. Venous blood samples were taken at 9 to 14 weeks, 18 to 22 weeks, 28 to 32 weeks, and 34 to 39 weeks of gestation. Serum concentrations of thyroid-stimulating hormone (TSH), free thyroxine (T4), free triiodothyronine (T3), total T4, total T3, thyroid peroxidase antibody and thyroglobulin antibody were measured using Abbott Architect immunoassays. A total of 562 women with singleton pregnancies were found to be negative for both thyroid autoantibodies at all four study visits and thus included in the reference sample group for the establishment of reference intervals (2.5th to 97.5th percentiles). RESULTS: Reference intervals for serum thyroid hormones at 9-14 weeks of gestation derived from the combined group of pregnant women are as follows: TSH, 0.01-2.39 mIU/L; free T4, 11.4-19.5 pmol/L; free T3, 4.23-6.69 pmol/L; total T4, 77.8-182.4 nmol/L; total T3, 1.39-2.97 nmol/L. No differences in the five thyroid parameters' reference intervals are detectable among the ethnic groups except that at study visit 3 (28-32 weeks of gestation), the upper reference limit of total T3 in Malays (3.20 nmol/L; 90% CI, 2.99-3.76 nmol/L) is slightly higher than that in Chinese (2.86 nmol/L; 90% CI, 2.70-2.98 nmol/L). CONCLUSIONS: The findings from this study on a multi-ethnic cohort highlight the importance of establishing locally derived and gestational age-specific reference intervals for the five thyroid hormone parameters.

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

BACKGROUND: 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. MATERIALS AND METHODS: 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. RESULTS: 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). CONCLUSION: 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.

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.

INTRODUCTION: 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. MATERIALS AND METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Evidence for the interaction of the human metapneumovirus G and F proteins during virus-like particle formation.

BACKGROUND: Human metapneumovirus (HMPV) is now a major cause of lower respiratory infection in children. Although primary isolation of HMPV has been achieved in several different cell lines, the low level of virus replication and the subsequent recovery of low levels of infectious HMPV have hampered biochemical studies on the virus. These experimental methodologies usually require higher levels of biological material that can be achieved following HMPV infection. In this study we demonstrate that expression of the HMPV F, G and M proteins in mammalian cells leads to HMPV virus-like particles (VLP) formation. This experimental strategy will serve as a model system to allow the process of HMPV virus assembly to be examined. METHODS: The HMPV F, G and M proteins were expressed in mammalian cell lines. Protein cross-linking studies, sucrose gradient centrifugation and in situ imaging was used to examine interactions between the virus proteins. VLP formation was examined using sucrose density gradient centrifugation and electron microscopy analysis. RESULTS: Analysis of cells co-expressing the F, G and M proteins demonstrated that these proteins interacted. Furthermore, in cells co-expression the three HMPV proteins the formation VLPs was observed. Image analysis revealed the VLPs had a similar morphology to the filamentous virus morphology that we observed on HMPV-infected cells. The capacity of each protein to initiate VLP formation was examined using a VLP formation assay. Individual expression of each virus protein showed that the G protein was able to form VLPs in the absence of the other virus proteins. Furthermore, co-expression of the G protein with either the M or F proteins facilitated their incorporation into the VLP fraction. CONCLUSION: Co-expression of the F, G and M proteins leads to the formation of VLPs, and that incorporation of the F and M proteins into VLPs is facilitated by their interaction with the G protein. Our data suggests that the G protein plays a central role in VLP formation, and further suggests that the G protein may also play a role in the recruitment of the F and M proteins to sites of virus particle formation during HMPV infection.

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

INTRODUCTION: 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). MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Teacher led school-based surveillance can allow accurate tracking of emerging infectious diseases - evidence from serial cross-sectional surveys of febrile respiratory illness during the H1N1 2009 influenza pandemic in Singapore.

BACKGROUND: Schools are important foci of influenza transmission and potential targets for surveillance and interventions. We compared several school-based influenza monitoring systems with clinic-based influenza-like illness (ILI) surveillance, and assessed the variation in illness rates between and within schools. METHODS: During the initial wave of pandemic H1N1 (pdmH1N1) infections from June to Sept 2009 in Singapore, we collected data on nation-wide laboratory confirmed cases (Sch-LCC) and daily temperature monitoring (Sch-DTM), and teacher-led febrile respiratory illness reporting in 6 sentinel schools (Sch-FRI). Comparisons were made against age-stratified clinic-based influenza-like illness (ILI) data from 23 primary care clinics (GP-ILI) and proportions of ILI testing positive for pdmH1N1 (Lab-ILI) by computing the fraction of cumulative incidence occurring by epidemiological week 30 (when GP-ILI incidence peaked); and cumulative incidence rates between school-based indicators and sero-epidemiological pdmH1N1 incidence (estimated from changes in prevalence of A/California/7/2009 H1N1 hemagglutination inhibition titers ≥ 40 between pre-epidemic and post-epidemic sera). Variation in Sch-FRI rates in the 6 schools was also investigated through a Bayesian hierarchical model. RESULTS: By week 30, for primary and secondary school children respectively, 63% and 79% of incidence for Sch-LCC had occurred, compared with 50% and 52% for GP-ILI data, and 48% and 53% for Sch-FRI. There were 1,187 notified cases and 7,588 episodes in the Sch-LCC and Sch-DTM systems; given school enrollment of 485,723 children, this represented 0.24 cases and 1.6 episodes per 100 children respectively. Mean Sch-FRI rate was 28.8 per 100 children (95% CI: 27.7 to 29.9) in the 6 schools. We estimate from serology that 41.8% (95% CI: 30.2% to 55.9%) of primary and 43.2% (95% CI: 28.2% to 60.8%) of secondary school-aged children were infected. Sch-FRI rates were similar across the 6 schools (23 to 34 episodes per 100 children), but there was widespread variation by classrooms; in the hierarchical model, omitting age and school effects was inconsequential but neglecting classroom level effects led to highly significant reductions in goodness of fit. CONCLUSIONS: Epidemic curves from Sch-FRI were comparable to GP-ILI data, and Sch-FRI detected substantially more infections than Sch-LCC and Sch-DTM. Variability in classroom attack rates suggests localized class-room transmission.

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

INTRODUCTION: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Decline in Clostridium difficile-associated disease rates in Singapore public hospitals, 2006 to 2008.

BACKGROUND: Clostridium difficile is the major cause of pseudomembranous colitis associated with antibiotic use, and the spread of the hypervirulent epidemic ribotype 027/NAP-1 strain across hospitals worldwide has re-focused attention on this nosocomial pathogen. The overall incidence and trend of C. difficile-associated disease (CDAD) in Singapore is unknown, and a surveillance program to determine these via formal laboratory-based reporting was established. FINDINGS: Laboratory and pharmacy data were collated from one tertiary and two secondary hospitals on a quarterly basis between 2006 and 2008. All hospitals tested for C. difficile using Immunocard Toxins A&B (Meridian Bioscience Inc., Cincinnati, OH) during this period. Duplicate positive C. difficile results within a 14-day period were removed. The CDAD results were compared with trends in hospital-based prescription of major classes of antibiotics.Overall CDAD incidence-density decreased from 5.16 (95%CI: 4.73 - 5.62) cases per 10,000 inpatient-days in 2006 to 2.99 (95%CI: 2.67 to 3.33) cases per 10,000 inpatient-days in 2008 (p < 0.001), while overall rates for C. difficile testing increased significantly (p < 0.001) within the same period. These trends were mirrored at the individual hospital level. Evaluation of antibiotic prescription data at all hospitals showed increasing use of carbapenems and fluoroquinolones, while cephalosporin and clindamycin prescription remained stable. CONCLUSIONS: Our results demonstrate a real decline of CDAD rates in three large local hospitals. The cause is unclear and is not associated with improved infection control measures or reduction in antibiotic prescription. Lack of C. difficile stool cultures as part of routine testing precluded determination of the decline of a major clone as a potential explanation. For more accurate epidemiological trending of CDAD and early detection of epidemic clones, data collection will have to be expanded and resources set in place for reference laboratory culture and typing.

Pandemic (H1N1) 2009 infection in adult solid organ transplant recipients in Singapore.

BACKGROUND: Influenza can produce significant complications in immunocompromised persons. METHODS: We studied the effects of the pandemic (H1N1) 2009 (pH1N1) infection on solid organ transplant recipients in our hospital, with emphasis on clinical information, duration of viral culture positivity, polymerase chain reaction positivity, effects of oseltamivir therapy, and graft status at 6 months of follow-up. RESULTS: Twenty-two cases of pH1N1 infection involving 18 renal, two lung, one heart, and one liver transplant recipients were seen from July 14 to September 8, 2009. Their median age was 50.5 years (range 20-70 years); 64% were women, and median time posttransplant was 40 months (range 6-204 months). Common symptoms were fever (86%), cough (77%), sore throat (55%), phlegm (32%), and myalgia (27%). The median duration of symptoms (n=21) and duration of polymerase chain reaction positivity (n=15) were 7 (range 4-13 days) and 8 days (range 4-16 days), respectively. Mean (± SD) duration of symptom resolution (7.4 ± 3.0 vs. 7.8 ± 3.0 days, P=0.76) and viral culture positivity (5.3 ± 2.8 vs. 4.3 ± 3.2 days, P=0.65) did not differ between those who received a 5-day (n=9) or 10-day (n=12) course of oseltamivir. Five patients (22.7%) developed pneumonia with three needing intensive care. Mortality rate was 4.5% (1/22). At 6 months, three graft rejections involving two renal and one lung developed. CONCLUSIONS: Our findings indicate that the pH1N1 infection in solid organ transplant recipients is associated with some degree of morbidity and may affect the function of the transplanted organ. In this nonrandomized comparison, patients treated with 5 days of oseltamivir did not fare worse compared with those who received 10 days.

Comparison of the incidence of influenza in relation to climate factors during 2000-2007 in five countries.

Relatively few international comparisons of the incidence of influenza related to climate parameters have been performed, particularly in the Eastern hemisphere. In this study, the incidence of influenza and climate data such as temperature, relative humidity, and rainfall, from cities at different latitudes with contrasting climates: Singapore, Hong Kong (China), Ulaanbaatar (Mongolia), Vancouver (Canada), and three Australian cities (Brisbane, Melbourne and Sydney) were examined to determine whether there was any overall relationship between the incidence of influenza and climate. Applying time-series analyses to the more comprehensive datasets, it was found that relative humidity was associated with the incidence of influenza A in Singapore, Hong Kong, Brisbane, and Vancouver. In the case of influenza B, the mean temperature was the key climate variable associated with the incidence of influenza in Hong Kong, Brisbane, Melbourne, and Vancouver. Rainfall was not significantly correlated with the incidence of influenza A or B in any of these cities.

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

INTRODUCTION: Influenza A H1N1 (2009) pandemic has affected countries worldwide including Singapore. Data on obstetric outcomes of women with H1N1 (2009) in pregnancy are lacking. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: Our study suggested that obstetric outcomes were not adversely affected by influenza A H1N1 (2009) infection.

The increased role of non-albicans species in candidaemia: results from a 3-year surveillance study.

Various studies have documented a shift in species distribution in Candida bloodstream infections (BSI), but there are little data from Southeast Asia. This study was performed to determine the species epidemiology and antifungal susceptibilities of Candida species BSI in Singapore. Candida spp. from BSI were collected from a tertiary and secondary referral hospital, and an obstetrics/paediatric hospital over a 3-year period. The most common isolates were Candida albicans (36%), Candida tropicalis (27%), Candida glabrata (16%) and Candida parapsilosis (16%). Candida parapsilosis and C. albicans were predominant in the paediatric hospital, and C. albicans and C. tropicalis predominant in the other two institutions. Candida tropicalis temporarily replaced C. albicans as the predominant strain from BSI in 2006. Overall, 87.3% of Candida isolates were susceptible to fluconazole, and 10.4% classified as susceptible-dose-dependent. Fluconazole resistance was detected in C. tropicalis (3.6%), C. parapsilosis (2.1%) and C. glabrata (4.0%). Candida albicans is the predominant species isolated from BSI in Singapore. However, non-albicans species accounted for nearly two-thirds of all cases of candidaemia and the relative increase in C. tropicalis infections deserves further investigation. Resistance to fluconazole was uncommon.

The incidence of human bocavirus infection among children admitted to hospital in Singapore.

Human bocavirus (HBoV) is a parvovirus, belonging to the genus Bocavirus. The virus was identified recently in Sweden, and has now been detected in several different countries. Although it is associated with lower respiratory tract infections in pediatric patients, the incidence of HBoV infection in a developed country in South East Asia, has not been examined. The objective of this study was to determine the importance of HBoV as a cause of lower respiratory tract infections among children admitted to hospital in Singapore. Five hundred nasopharyngeal swabs were collected from anonymized pediatric patients admitted to the Kandang Kerbau Women's and Children's Hospital for acute respiratory infections. The specimens were tested for the presence of HBoV using polymerase chain reactions. HBoV was detected in 8.0% of the patients tested, and a majority of these HBoV patients exhibited lower respiratory tract infections. A significant level of coinfection with respiratory syncytial viruses and rhinoviruses was also observed in these HBoV patients. The data suggest that HBoV is an important cause of lower respiratory tract infections among children admitted to hospital in Singapore, and is the first study examining the incidence of HBoV infection in a developed country in South East Asia.

Antibiotic resistance in gram-negative bacilli: a Singapore perspective.

INTRODUCTION: 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. MATERIALS AND METHODS: 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). RESULTS: 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. CONCLUSION: 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.

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

INTRODUCTION: 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. MATERIALS AND METHODS: 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). RESULTS: 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. CONCLUSION: 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.