Incidence and aetiology of infant Gram-negative bacteraemia and meningitis: systematic review and meta-analysis.

BACKGROUND: One in six infant deaths worldwide are caused by invasive bacterial infections, of which a substantial but unquantified proportion are caused by Gram-negative bacteria. METHODS: We conducted a systematic review of studies published from 31 May 2010 to 1 June 2020 indexed in MEDLINE, Embase and Global Health databases. We performed meta-analyses of the incidence of Gram-negative bacteraemia and of individual Gram-negative species as proportions of all infant bacteraemia, stratified by onset (early vs late) and country income (low/middle vs high). RESULTS: 152 studies from 54 countries were included, 60 in high-income countries (HIC) and 92 in low-income/middle-income countries (LMIC). Gram-negatives represented a higher proportion (53%, 95% CI 49% to 57%) of all infant bacteraemia in LMIC compared with HIC (28%, 95% CI 25% to 32%). Incidence of infant Gram-negative bacteraemia was 2.01 (95% CI 1.15 to 3.51) per 1000 live births; it was five times higher in LMIC (4.35, 95% CI 2.94 to 6.43) compared with HIC (0.73, 95% CI 0.39 to 7.5). In HIC, Escherichia coli was the leading Gram-negative pathogen, representing 19.2% (95% CI 15.6% to 23.4%) of early and 7.3% (95% CI 5.3% to 10.1%) of all late-onset bacteraemia; Klebsiella spp were the next most common cause (5.3%) of late-onset bacteraemia. In LMIC, Klebsiella spp caused 16.4% (95% CI 11.5% to 22.7%) of early and 15.0% (95% CI 10.1% to 21.8%) of late-onset bacteraemia, followed by E. coli (early-onset 7.50%, 95% CI 4.98% to 11.1%; late-onset 6.53%, 95% CI 4.50% to 9.39%) and Pseudomonas spp (early-onset 3.93%, 95% CI 2.04% to 7.44%; late-onset 2.81%, 95% CI 1.99% to 3.95%). CONCLUSION: E. coli, Klebsiella and Pseudomonas spp cause 20%-28% of early-onset infant bacteraemia and 14% cases of infant meningitis worldwide. Implementation of preventive measures could reduce the high incidence of Gram-negative bacteraemia in LMIC. PROSPERO REGISTRATION NUMBER: CRD42020191618.

Prospective genomic surveillance of methicillin-resistant Staphylococcus aureus (MRSA) associated with bloodstream infection, England, 1 October 2012 to 30 September 2013.

BackgroundMandatory reporting of methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections (BSI) has occurred in England for over 15years. Epidemiological information is recorded, but routine collection of isolates for characterisation has not been routinely undertaken. Ongoing developments in whole-genome sequencing (WGS) have demonstrated its value in outbreak investigations and for determining the spread of antimicrobial resistance and bacterial population structure. Benefits of adding genomics to routine epidemiological MRSA surveillance are unknown.AimTo determine feasibility and potential utility of adding genomics to epidemiological surveillance of MRSA.MethodsWe conducted an epidemiological and genomic survey of MRSA BSI in England over a 1-year period (1 October 2012--30 September 2013).ResultsDuring the study period, 903 cases of MRSA BSI were reported; 425 isolates were available for sequencing of which, 276 (65%) were clonal complex (CC) 22. Addition of 64 MRSA genomes from published outbreak investigations showed that the study genomes could provide context for outbreak isolates and supported cluster identification. Comparison to other MRSA genome collections demonstrated variation in clonal diversity achieved through different sampling strategies and identified potentially high-risk clones e.g. USA300 and local expansion of CC5 MRSA in South West England.ConclusionsWe demonstrate the potential utility of combined epidemiological and genomic MRSA BSI surveillance to determine the national population structure of MRSA, contextualise previous MRSA outbreaks, and detect potentially high-risk lineages. These findings support the integration of epidemiological and genomic surveillance for MRSA BSI as a step towards a comprehensive surveillance programme in England.

Descriptive epidemiology of Escherichia coli bacteraemia in England, April 2012 to March 2014.

We determined the incidence, risk factors and antimicrobial susceptibility associated with Escherichia coli bacteraemia in England over a 24 month period. Case data were obtained from the national mandatory surveillance database, with susceptibility data linked from LabBase2, a voluntary national microbiology database. Between April 2012 and March 2014, 66,512 E. coli bacteraemia cases were reported. Disease incidence increased by 6% from 60.4 per 100,000 population in 2012-13 to 63.5 per 100,000 population in 2013-14 (p < 0.0001). Rates of E. coli bacteraemia varied with patient age and sex, with 70.5% (46,883/66,512) of cases seen in patients aged ≥ 65 years and 52.4% (33,969/64,846) of cases in females. The most common underlying cause of bacteraemia was infection of the genital/urinary tract (41.1%; 27,328/66,512), of which 98.4% (26,891/27,328) were urinary tract infections (UTIs). The majority of cases (76.1%; 50,617/66,512) had positive blood cultures before or within two days of admission and were classified as community onset cases, however 15.7% (10,468/66,512) occurred in patients who had been hospitalised for over a week. Non-susceptibility to ciprofloxacin, third-generation cephalosporins, piperacillin-tazobactam, gentamicin and carbapenems were 18.4% (8,439/45,829), 10.4% (4,256/40,734), 10.2% (4,694/46,186), 9.7% (4,770/49,114) and 0.2% (91/42,986), respectively. Antibiotic non-susceptibility was higher in hospital-onset cases than for those presenting from the community (e.g. ciprofloxacin non-susceptibility was 22.1% (2,234/10,105) for hospital-onset vs 17.4% (5,920/34,069) for community-onset cases). Interventions to reduce the incidence of E. coli bacteraemia will have to target the community setting and UTIs if substantial reductions are to be realised.