Incidence of infant Gram-negative invasive bacterial infections in England, 2011-2019: an observational study using population-wide surveillance data.

OBJECTIVE: Invasive bacterial infections account for an estimated 15% of infant deaths worldwide. We aimed to estimate the incidence and trends in invasive bacterial infections in infants caused by Gram-negative pathogens in England during 2011-2019. METHODS: Laboratory-confirmed invasive bacterial infections in infants (<1 year old) were identified in the UK Health Security Agency national laboratory surveillance data from April 2011 to March 2019. Polymicrobial infections were defined as two or more bacterial species from the same normally sterile sample site. Early-onset infections were defined as <7 days from birth and late-onset as ≥7 days (neonates 7-28 days; infants ≥29 days). Trend analyses were carried out using Poisson (for episodes/incidence) and beta (for proportions) regression. RESULTS: The annual incidence of invasive bacterial infections increased by 35.9%, from 189.8 to 258.0 cases per 100 000 live births (p<0.001). Late-onset infections in both neonates and infants increased substantially over the study period (p<0.001), whereas early-onset infections increased slightly (p=0.002). Escherichia coli was the most common Gram-negative pathogen isolated and accounted for 27.2% of the overall rise in Gram-negative infant disease incidence. Polymicrobial infections almost doubled, increasing from 29.2 to 57.7 per 100 000 live births (p<0.001), and mostly involved two species (81.3%, 1604/1974 episodes). CONCLUSIONS: The incidence of Gram-negative invasive bacterial infections in infants increased between 2011/2012 and 2018/2019 in England, driven mainly by an increase in late-onset infections. Further work is required to elucidate the risk factors and drivers of this increased incidence so that opportunities for prevention can be identified.

Enhanced nasopharyngeal infection and shedding associated with an epidemic lineage of emm3 group A Streptococcus.

BACKGROUND: A group A Streptococcus (GAS) lineage of genotype emm3, sequence type 15 (ST15) was associated with a 6 month upsurge in invasive GAS disease in the UK. The epidemic lineage (Lineage C) had lost 2 typical emm3 prophages, Φ315.1 and Φ315.2 associated with the superantigen ssa, but gained a different prophage (ΦUK-M3.1) associated with a different superantigen, speC and a DNAse spd1. METHODS AND RESULTS: The presence of speC and spd1 in Lineage C ST15 strains enhanced both in vitro mitogenic and DNase activities over non-Lineage C ST15 strains. Invasive disease models in Galleria mellonella and SPEC-sensitive transgenic mice, revealed no difference in overall invasiveness of Lineage C ST15 strains compared with non-Lineage C ST15 strains, consistent with clinical and epidemiological analysis. Lineage C strains did however markedly prolong murine nasal infection with enhanced nasal and airborne shedding compared with non-Lineage C strains. Deletion of speC or spd1 in 2 Lineage C strains identified a possible role for spd1 in airborne shedding from the murine nasopharynx. CONCLUSIONS: Nasopharyngeal infection and shedding of Lineage C strains was enhanced compared with non-Lineage C strains and this was, in part, mediated by the gain of the DNase spd1 through prophage acquisition.

Emerging trends in the epidemiology of invasive group B streptococcal disease in England and Wales, 1991-2010.

BACKGROUND: Few cross-population studies examining the epidemiology of invasive group B streptococcal (GBS) disease have been undertaken. To identify longitudinal trends in the burden and characteristics of infections, national surveillance data on diagnoses in England and Wales from 1991 to 2010 were analyzed. METHODS: A parallel review of laboratory-confirmed invasive GBS infection surveillance reports and isolates submitted to the national reference laboratory was undertaken. Cases were defined as GBS isolated from a normally sterile site. RESULTS: A total of 21 386 reports of invasive GBS infection were made between 1991 and 2010. The annual rate of reports doubled over the 20 years from 1.48 to 2.99 per 100 000 population. Significant increases were seen in all age groups but most pronounced in adults. Rates of early-onset (0-6 days) infant disease fluctuated but showed a general rise between 2000 and 2010 from 0.28 to 0.41 per 1000 live births. Rates of late-onset (7-90 days) disease increased steadily between 1991 and 2010 from 0.11 to 0.29 per 1000 live births. Resistance to erythromycin increased markedly from 2.5% in 1991 to 15% in 2010. The distribution of serotypes varied according to patient age and over time with type III increasing among early-onset cases and decreasing in adults. CONCLUSIONS: Although risk of invasive GBS infection remains highest within the first few days of life, the relative burden of disease is shifting toward adults. The rise in incidence and antibiotic resistance makes development of an effective and safe vaccine all the more pressing.

The contribution of infections to neonatal deaths in England and Wales.

This study used anonymized death certificate data to determine the contribution of specific infections to neonatal deaths in England and Wales between 2003 and 2005. Infection was recorded in 11% of deaths, with two-thirds occurring in premature neonates. Group B Streptococcus was indicated in 32% of death certificates that specified a bacterial infection and in 11% of all infection-related deaths.

Continuing impact of infectious diseases on childhood deaths in England and Wales, 2003-2005.

BACKGROUND: Data on the contribution of specific infections to childhood deaths in developed countries are limited. METHODS: Infection-related deaths in children aged 28 days to 14 years who died in England and Wales between 2003 and 2005 were identified from routine anonymized death certificate dataset provided by the Office for National Statistics to the Health Protection Agency, using predefined International Classification of Diseases codes for infection. RESULTS: There were 1368 infection-related deaths documented, constituting 20% of all childhood deaths. An underlying medical condition was recorded in 50% (676 cases), the most common being prematurity in infants (322/660, 52%), cerebral palsy in 1 to 4 year olds (46/190, 24%), and malignancy (46/163, 28%) in 5 to 14 year olds. Of the 837 deaths where a pathogen was coded, 494 (59%) specified bacterial infection, 256 (31%) viral infection, and 69 (8%) fungal infection. Among deaths with recorded bacterial infections, a lower proportion of meningococcal and pneumococcal infections (14% [22/155] vs. 60% [205/339], P < 0.0001) and a higher proportion of Gram-negative enteric bacilli (78/155 cases [50%] vs. 17/339 cases [5%], P < 0.0001) were reported in children with and without documented underlying medical conditions, respectively. CONCLUSIONS: Infections continue to make a major contribution to deaths in children, particularly among those with underlying conditions. Identification of the pathogens associated with childhood deaths should help prioritize the development of intervention strategies for reducing pediatric mortality. Linkage of death registrations to national infectious disease surveillance systems should be undertaken to strengthen monitoring of infectious deaths and evaluate the effect of interventions.

Predictors of death after severe Streptococcus pyogenes infection.

An evaluation of the relative importance of host and pathogen factors on the survival rate of patients with invasive Streptococcus pyogenes infection found a number of clinical and demographic factors to be associated with risk for death. Some evidence suggested a seasonal pattern to patient survival rate.

Epidemiology of severe Streptococcus pyogenes disease in Europe.

The past 2 decades have brought worrying increases in severe Streptococcus pyogenes diseases globally. To investigate and compare the epidemiological patterns of these diseases within Europe, data were collected through a European Union FP-5-funded program (Strep-EURO). Prospective population-based surveillance of severe S. pyogenes infection diagnosed during 2003 and 2004 was undertaken in 11 countries across Europe (Cyprus, the Czech Republic, Denmark, Finland, France, Germany, Greece, Italy, Romania, Sweden, and the United Kingdom) using a standardized case definition. A total of 5,522 cases were identified across the 11 countries during this period. Rates of reported infection varied, reaching 3/100,000 population in the northern European countries. Seasonal patterns of infection showed remarkable congruence between countries. The risk of infection was highest among the elderly, and rates were higher in males than in females in most countries. Skin lesions/wounds were the most common predisposing factor, reported in 25% of cases; 21% had no predisposing factors reported. Skin and soft tissue were the most common foci of infection, with 32% of patients having cellulitis and 8% necrotizing fasciitis. The overall 7-day case fatality rate was 19%; it was 44% among patients who developed streptococcal toxic shock syndrome. The findings from Strep-EURO confirm a high incidence of severe S. pyogenes disease in Europe. Furthermore, these results have identified targets for public health intervention, as well as raising awareness of severe S. pyogenes disease across Europe.

Severe Streptococcus pyogenes infections, United Kingdom, 2003-2004.

As part of a Europe-wide initiative to explore current epidemiologic patterns of severe disease caused by Streptococcus pyogenes, the United Kingdom undertook enhanced population-based surveillance during 2003-2004. A total of 3,775 confirmed cases of severe S. pyogenes infection were identified over 2 years, 3.33/100,000 population, substantially more than previously estimated. Skin/soft tissue infections were the most common manifestation (42%), followed by respiratory tract infections (17%). Injection drug use was identified as a risk factor for 20% of case-patients. One in 5 infected case-patients died within 7 days of diagnosis; the highest mortality rate was for cases of necrotizing fasciitis (34%). Nonsteroidal antiinflammatory drugs, alcoholism, young age, and infection with emm/M3 types were independently associated with increased risk for streptococcal toxic shock syndrome. Understanding the pattern of these diseases and predictors of poor patient outcome will help with identification and assessment of the potential effect of targeted interventions.

Susceptibility to moxifloxacin of pneumococci isolated in English hospitals participating in the European Antimicrobial Resistance Surveillance System (EARSS) in 2003.

Susceptibility to moxifloxacin, penicillin and erythromycin was determined for 592 invasive Streptococcus pneumoniae collected from 20 English hospitals participating in the European Antimicrobial Resistance Surveillance System (EARSS) during 2003. Resistance to moxifloxacin, penicillin and erythromycin was observed in 0.8%, 5.4% and 13% of the isolates, respectively. These results show that the large majority of pneumococci were susceptible to moxifloxacin in 2003, the year when it was licensed for clinical use in the UK.

Trends in MRSA in England and Wales: analysis of morbidity and mortality data for 1993-2002.

This article examines trends in infection and mortality from methicillin-resistant Staphylococcus aureus (MRSA) over the period 1993 to 2002. Trends in the number of deaths where MRSA was mentioned on the death certificate were compared with national reporting of microbiologically-confirmed bacteraemia to the Health Protection Agency Communicable Disease Surveillance Centre (CDSC). Alongside national trends, patterns in the place of death were examined. Both the number of deaths and number of laboratory reports increased substantially over the period examined. MRSA mortality rates increased over 15-fold during the period 1993 to 2002. Reporting rates for bacteraemia increased 24-fold.

Characterization of group B streptococci recovered from infants with invasive disease in England and Wales.

Group B streptococci (GBS) are a major cause of invasive disease in infants, with enhanced surveillance in England and Wales showing an incidence of 0.74 cases per 1000 live births and a mortality rate of 8%. Among 353 isolates obtained during enhanced surveillance, the predominant serotypes were III (48%), Ia (27%), and V (10%), and the remainder comprised Ib, II, IV, VI, and VII; 3% were not typable. Isolates from patients with early-onset disease had serotypes III (38%), Ia (32%), and V (13%), with late-onset disease having a higher incidence of type III (67%) strains. Patients infected with serotype III strains had a higher rate of meningitis, and those with type V strains had a higher mortality rate. Isolates were susceptible to penicillin and ampicillin, but 4% were resistant to erythromycin, and 91% were resistant to tetracycline. A trivalent vaccine containing capsular polysaccharides III, Ia, and V could theoretically provide coverage against 85% of the cases of GBS disease among infants in England and Wales.

Group B streptococcal disease in UK and Irish infants younger than 90 days.

The incidence, morbidity, and mortality of group B streptococcal disease in the UK and Republic of Ireland are largely unknown. Between Feb 1, 2000, and Feb 28, 2001, we identified cases of invasive group B streptococcal disease in infants younger than 90 days through surveillance involving paediatricians, microbiologists, and parents. 568 cases were identified, equivalent to a total incidence of 0.72 per 1000 live-births (95% CI 0.66-0.78); the incidence for early-onset disease (n=377) was 0.48 per 1000 (0.43-0.53), and for late-onset disease (n=191) was 0.24 per 1000 (0.21-0.28). Risk factors were identifiable for 218 (58%) cases of early-onset disease. 53 infants died (overall 9.7%). We have established the minimum current burden of group B streptococcal disease in UK and Irish infants. This information will assist in the formulation of guidelines for prevention of this disease.

Ciprofloxacin-resistant Escherichia coli from bacteraemias in England; increasingly prevalent and mostly from men.

OBJECTIVES: To assess ciprofloxacin resistance among Escherichia coli isolates from bacteraemia patients in England in relation to age, sex and Region. METHODS: Routine susceptibility data for bacteraemia isolates were collected from over 90% of hospitals in England. RESULTS: During 1995-2001, the prevalence of ciprofloxacin resistance trebled, from 2.1% to 6.5%. Isolates from men were more frequently resistant than those from women, possibly because infections in men more often involve nosocomial strains. Resistance was rare (<1.5%) in isolates from patients aged <1 year; among older patients, resistance was unrelated to age in isolates from women, but peaked in the 15-44 age group for men. CONCLUSIONS: The prevalence of ciprofloxacin resistance in E. coli from bacteraemia is strongly associated with sex and, to a lesser extent, age.

Increasing incidence of group A streptococcal infections amongst injecting drug users in England and Wales.

During 2000, the UK witnessed a sudden increase in severe infections and related deaths in injecting drug users (IDUs), sparking off a UK-wide investigation. A worrying upward trend in severe group A streptococcal (GAS) infections has recently been observed in IDUs based upon isolate referrals to the PHLS Respiratory and Systemic Infection Laboratory. Most cases were young male adults who presented with skin sepsis and bacteraemia. Serotyping revealed a diverse range of M types, with higher types predominating in some geographical areas. The data suggest that GAS invasive soft-tissue infections may present in an epidemic fashion among IDUs in the absence of a common source.