An evaluation of the electronic reporting system for the enhanced surveillance of carbapenemase-producing Gram-negative bacteria in England.

BACKGROUND: An electronic reporting system (ERS) for the enhanced surveillance of carbapenemase-producing Gram-negative bacteria (CPGNB) was launched by Public Health England in May 2015. AIM: This evaluation aimed to assess uptake, timeliness and completeness of data provided and explore potential barriers and facilitators to adopting the system. METHODS: The evaluation comprised a retrospective analysis of surveillance data and semi-structured interviews with ERS users. FINDINGS: The proportion of organisms referred for investigation of carbapenem resistance via ERS increased over the first 12 months post-implementation from 35% to 73%; uptake varied widely across regions of England. Completeness of enhanced data fields was poor in 78% of submitted isolates. The median number of days to report confirmatory test results via ERS was 1 day for the regional service and nine days for the national reference laboratory, which additionally conducts phenotypic testing to confirm carbapenemase negativity. Hindrances to ERS utility included: a lack of designated, ongoing resource for system maintenance, technical support and development; uncertainty about how and when to use ERS and workload. Incomplete data prevented gaining a better understanding of important risk factors and transmission routes of CPGNB in England. CONCLUSION: The ERS is the only surveillance system in England with the potential to gather intelligence on important risk factors for CPGNB to inform public health measures to control their spread. Although the ERS captures more information on CPGNB than other surveillance systems, timeliness and completeness of the enhanced data require substantial improvements in order to deliver the desired health benefits.

Quantifying the Burden of Hospital-Acquired Bloodstream Infection in Children in England by Estimating Excess Length of Hospital Stay and Mortality Using a Multistate Analysis of Linked, Routinely Collected Data.

BACKGROUND: Hospital-acquired bloodstream infection (HA-BSI) is associated with substantial morbidity, mortality, and healthcare costs in all patient populations. Young children have been shown to have a high rate of healthcare-associated infections compared with the adult population. We aimed to quantify the excess mortality and length of stay in pediatric patients from HA-BSI. METHODS: We analyzed data collected retrospectively from a probabilistically linked national database of pediatric (aged 1 month-18 years) in-patients with a microbiologically confirmed HA-BSI in England between January and March 2009. A time-dependent Cox regression model was fit to determine the presence of any effect. Furthermore, a multistate model, adjusted for the time to onset of HA-BSI, was used to compare outcomes in patients with HA-BSI to those without HA-BSI. We further adjusted for patients' characteristics as recorded in hospital admission data. RESULTS: The dataset comprised 333 605 patients, with 214 cases of HA-BSI. After adjustment for time to HA-BSI and comorbidities, the hazard for discharge (dead or alive) from hospital for patients with HA-BSI was 0.9 times (95% confidence interval [CI], .8-1.1) that of noninfected patients. Excess length of stay associated with all-cause HA-BSI was 1.6 days (95% CI, .2-3.0), although this duration varied by pathogen. Patients with HA-BSI had a 3.6 (95% CI, 1.3-10.4) times higher hazard for in-hospital death than noninfected patients. CONCLUSIONS: Hospital-acquired bloodstream infection increased the length of stay and mortality of pediatric inpatients. The results of this study provide an evidence base to judge the health and economic impact of programs to prevent and control HA-BSI in children.

Timing of positive blood samples does not differentiate pathogens causing healthcare-associated from community-acquired bloodstream infections in children in England: a linked retrospective cohort study.

Paediatricians recognize that using the time-dependent community-acquired vs. hospital-acquired bloodstream infection (BSI) dichotomy to guide empirical treatment no longer distinguishes between causative pathogens due to the emergence of healthcare-associated BSIs. However, paediatric epidemiological evidence of the aetiology of BSIs in relation to hospital admission in England is lacking. For 12 common BSI-causing pathogens in England, timing of laboratory reports of positive paediatric (3 months to 5 years) bacterial blood isolates were linked to in-patient hospital data and plotted in relation to hospital admission. The majority (88·6%) of linked pathogens were isolated <2 days after hospital admission, including pathogens widely regarded as hospital acquired: Enterococcus spp. (67·2%) and Klebsiella spp. (88·9%). Neisseria meningitidis, Streptococcus pneumoniae, group A streptococcus and Salmonella spp. were unlikely to cause hospital-acquired BSI. Pathogens commonly associated with hospital-acquired BSI are being isolated <2 days after hospital admission alongside pathogens commonly associated with community-acquired BSI. We confirm that timing of blood samples alone does not differentiate between bacterial pathogens. Additional factors including clinical patient characteristics and healthcare contact should be considered to help predict the causative pathogen and guide empirical antibiotic therapy.

The changing antibiotic susceptibility of bloodstream infections in the first month of life: informing antibiotic policies for early- and late-onset neonatal sepsis.

This study describes the association between antibiotic resistance of bacteria causing neonatal bloodstream infection (BSI) and neonatal age to inform empirical antibiotic treatment guidelines. Antibiotic resistance data were analysed for 14 078 laboratory reports of bacteraemia in neonates aged 0-28 days, received by the Health Protection Agency's (now Public Health England) voluntary surveillance scheme for England and Wales between January 2005 and December 2010. Linear and restricted cubic splines were used in logistic regression models to estimate the nonlinear relationship between age and resistance; the significance of confounding variables was assessed using likelihood ratio tests. An increase in resistance in bacteria causing BSI in neonates aged <4 days was observed, which was greatest between days 2-3 and identified an age (4-8 days, depending on the antibiotic) at which antibiotic resistance plateaus to almost unchanging levels. Our results indicate important age-associated changes in antibiotic resistance and support current empirical treatment guidelines.

Community-acquired, healthcare-associated and hospital-acquired bloodstream infection definitions in children: a systematic review demonstrating inconsistent criteria.

BACKGROUND: Historically, bacterial infections were categorized as either community-acquired (CA) or hospital-acquired (HA). However, the CA/HA dichotomy no longer adequately reflects patterns of emerging healthcare-associated (HCA) infections in complex patients managed between hospital and the community. Studies trying to define this evolving epidemiology often excluded children. AIM: To identify what criteria have been used to distinguish between CA, HCA and HA bloodstream infections (BSIs) in children, and the proportional distribution of CA, HCA and HA among total BSIs and by organism. METHODS: We systematically reviewed published literature from PubMed, UK Department of Health and US Centers for Disease Control and Prevention websites. FINDINGS: Results from 23 studies and the websites highlighted the use of inconsistent criteria. There were 13 and 15 criteria variations for CA and HA BSI respectively, although a 48h cut-off for cultures sampled post admission was most commonly reported. Five studies used variable clinical criteria to define HCA. The mean proportion of paediatric CA BSI in nine studies was 50%. Only four BSI organisms from five studies were predominantly CA (Streptococcus pneumoniae, Salmonella spp.) or HA (coagulase-negative staphylococci, Enterococcus spp.), whereas Pseudomonas spp., Klebsiella spp. and Enterobacter spp. did not clearly fit into either category. CONCLUSIONS: Our study reveals inconsistent use of criteria, and a lack of evidence upon which to base them, to distinguish between CA, HCA and HA BSI in children. Criteria for CA, HCA and HA BSI need to be developed using population-based studies that consider patients' clinical characteristics, recent healthcare exposure as well as isolated organism species.

Empirical treatment of neonatal sepsis: are the current guidelines adequate?

OBJECTIVES: To use national laboratory surveillance data to determine whether pathogens responsible for neonatal bacteraemia were sensitive to nationally recommended antibiotic regimens. DESIGN: All reports of neonatal bacteraemia received by the Health Protection Agency's voluntary surveillance scheme in England and Wales from January 2006 until March 2008, were extracted from the database. Organisms were ranked by frequency, and proportions susceptible to antimicrobials recommended for empirical treatment of neonatal sepsis were determined. RESULTS: There were 1516 reports of bacteraemia for neonates <48 h old (early-onset) and 3482 reports for neonates 2-28 days old (late-onset). For early-onset bacteraemia, group B streptococcus (GBS) was the most frequent pathogen (31%) followed by coagulase-negative staphylococci (CoNS; 22%), non-pyogenic streptococci (9%) and Escherichia coli (9%). For late-onset bacteraemia, CoNS were isolated most frequently (45%), followed by Staphylococcus aureus (13%), Enterobacteriaceae (9%), E coli (7%) and GBS (7%). More than 94% of organisms (early-onset) were susceptible to regimens involving combinations of penicillin with either gentamicin or amoxicillin, amoxicillin combined with cefotaxime or cefotaxime monotherapy. More than 95% of organisms (late-onset) were susceptible to gentamicin with either flucloxacillin or amoxicillin and amoxicillin with cefotaxime, but only 79% were susceptible to cefotaxime monotherapy. CONCLUSIONS: Current guidelines for empirical therapy in neonates with sepsis are appropriate. However, gentamicin-based regimens should be used in preference to cefotaxime-based treatments, because of lower levels of susceptibility to cefotaxime and the need to avoid exerting selective pressure for resistance. Surveillance data linked to clinical data should further inform rational antibiotic prescribing in neonatal units.

Longitudinal study of meningococcal carrier rates in teenagers.

To gain actual information concerning the oropharyngeal carriage of Neisseria meningitidis among teenagers aged 15-18 years in Germany especially in a region with increased incidence of meningococal-related diseases prompted the study. Each teenager was swabbed three times with an interval of 2 months between the examinations. The 901 recovered N. meningitidis strains were characterized using serological (serogrouping, serotyping/serosubtyping) and molecular methods (PCR, PFGE) each. The results of the study demonstrate an overall average carrier rate of 18.8% for the three collection periods. There were, however, significant differences between the carrier rates within a given school and of different towns and counties. Of all isolates, 60.6% were not serogroupable. Serogroup B dominated (12.3%), followed by serogroup Y (9.0%) and serogroup C (3.6%). After PCR-based serogrouping of not serogroupable strains the percentages for serogroups enhanced to 18.8% for B, 10.8% for Y and 4.1% for C. Serotyping led to 305 different phenotypes with the most common being 29E:NT:P1.2,5 followed by Y:14:NST. In the 6 study towns the number of different N. meningitidis clones (PFGE types) isolated, varied between 30 and 87. In Wenden, where a prolonged outbreak had taken place, serogroup C (14.8%) was predominant. Only in this town C:2a isolates were found, all belonging to the ST-11/ET-37 complex and 12/13 matched identically to the ET-15 clone. Of the colonized teenagers, 26.7% were carriers over at least 23 weeks, 22.6% with the same strain, 36.0% were carrier for at least 15 weeks. Over all three collection periods 36.7% of the adolescents acquired a new strain. The highest acquisition rate was related to PFGE type 12.

Modelling hospital admissions for lower respiratory tract infections in the elderly in England.

Despite the importance of lower respiratory-tract infection (LRI) in causing hospitalizations in elderly patients (>or=65 years of age) and recent advances in vaccine development, a complete picture of the causative organisms is not available. All hospital discharge diagnoses (ICD-10 code) for LRI in elderly patients in England during 1995-1998 were reviewed. Using known seasonality in potential causative agents of LRI, the contribution of different respiratory pathogens to hospitalizations coded as 'unspecified LRI' was estimated by multiple linear regression analysis. Ninety-seven per cent of 551633 LRI-associated diagnoses had no specific organism recorded. From the statistical model the estimated proportions of admissions attributable to different pathogens were applied to calculate estimated hospitalization rates: 93.9 hospitalizations/10000 population aged >or=65 years due to S. pneumoniae, 22.9 to influenza virus, 22.3 to H. influenzae, 17.0 to whooping cough, and 12.8 to respiratory syncytial virus. There is enormous potential to improve health using existing vaccines and those under development.

Seroprevalence of herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) in former East and West Germany, 1997-1998.

The aim of this study was to investigate the seroprevalence of herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) in representative samples of the total former East German (FEG) and total former West German (FWG) populations. Type-specific testing with the HSV-1 (gG1) and HSV-2 (gG2) indirect ELISA was performed on an age- and sex-stratified random subsample of 3,792 sera collected during the 1997-1998 German National Health Survey. Weighted seroprevalence estimates were calculated for the total FEG and FWG populations. The overall age-standardised seroprevalence of HSV-1 was 82.6% in Germany, 85.5% (95%CI, 83.4-87.3%) in FEG and 81.8% (95%CI, 79.9-83.6%) in FWG. The overall seroprevalence of HSV-2 was 13.3% (95%CI, 11.8-14.9) in Germany, 16.5% (95%CI, 14.1-18.9) in FEG and 12.6% (95%CI, 10.7-14.5%) in FWG. The difference between FEG and FWG was largely due to the significantly higher age-adjusted seroprevalence of HSV-1 and HSV-2 in women (but not men) in FEG as compared to FWG. The HSV seroprevalence estimates in this study are consistent with results of previous less representative seroprevalence studies in Germany. Differences in HSV-2 seroprevalence between FEG and FWG suggest differences in sexual behaviour that warrant further investigation.

Contribution of RSV to bronchiolitis and pneumonia-associated hospitalizations in English children, April 1995-March 1998.

Estimates of the number of hospitalizations attributable to specific pathogens are required to predict the potential impact of vaccination. All hospital admissions for lower respiratory tract infection (LRI) in children < 5 years in England in 1995-8 were reviewed. Most admissions (76.8%) were not associated with specific organisms. Seasonality in pathogens that cause bronchiolitis and pneumonia was used to predict the proportion of cases with unspecified aetiology attributable to different organisms using multiple linear regression. Of 12,298 admissions for LRI, 17.5% were due to RSV infection. An estimated 74.8% (95% CI, 72.0-77.7%) of 'unspecified bronchiolitis' admissions and 16.3% (95% CI, 13.7-18.8%) of unspecified pneumonia' admissions were RSV related. The total mean annual incidence of hospital admissions attributable to RSV is 28.3/1000 children < 1 year of age, and 1.3/1000 children 1-4 years old. The greater burden of RSV infection than indicated through discharge data is revealed through applying simple statistical methods.