Mark Anthony

Incidence, Etiology, and Outcome of Bacterial Meningitis in Infants Aged <90 Days in the United Kingdom and Republic of Ireland: Prospective, Enhanced, National Population-Based Surveillance

BACKGROUND Bacterial meningitis remains a major cause of morbidity and mortality in young infants. Understanding the epidemiology and burden of disease is important. METHODS Prospective, enhanced, national population-based active surveillance was undertaken to determine the incidence, etiology, and outcome of bacterial meningitis in infants aged <90 days in the United Kingdom and Ireland. RESULTS During July 2010-July 2011, 364 cases were identified (annual incidence, 0.38/1000 live births; 95% confidence interval [CI], .35-.42). In England and Wales, the incidence of confirmed neonatal bacterial meningitis was 0.21 (n = 167; 95% CI, .18-.25). A total of 302 bacteria were isolated in 298 (82%) of the cases. The pathogens responsible varied by route of admission, gestation at birth, and age at infection. Group B Streptococcus (GBS) (150/302 [50%]; incidence, 0.16/1000 live births; 95% CI, .13-.18) and Escherichia coli (41/302 [14%]; incidence, 0.04/1000; 95% CI, .03-.06) were responsible for approximately two-thirds of identified bacteria. Pneumococcal (28/302 [9%]) and meningococcal (23/302 [8%]) meningitis were rare in the first month, whereas Listeria meningitis was seen only in the first month of life (11/302 [4%]). In hospitalized preterm infants, the etiology of both early- and late-onset meningitis was more varied. Overall case fatality was 8% (25/329) and was higher for pneumococcal meningitis (5/26 [19%]) than GBS meningitis (7/135 [5%]; P = .04) and for preterm (15/90 [17%]) compared with term (10/235 [4%]; P = .0002) infants. CONCLUSIONS The incidence of bacterial meningitis in young infants remains unchanged since the 1980s and is associated with significant case fatality. Prevention strategies and guidelines to improve the early management of cases should be prioritized.

The CovS/CovR Acid Response Regulator Is Required for Intracellular Survival of Group B Streptococcus in Macrophages

ABSTRACT Group B Streptococcus (GBS) is a leading cause of neonatal meningitis and septicemia. The ability of this organism to survive inside phagocytic cells is poorly understood but thought to be an important step for the establishment of disease in the host. Here, we demonstrate that GBS shows prolonged survival within J774 macrophages and that the capacity to survive is not significantly changed across a diverse range of strains representing different serotypes, multilocus sequence types (MLST), and sites of clinical isolation. Using staining for the lysosome-associated membrane protein (LAMP) and by pharmacological inhibition of phagosome acidification, we demonstrate that streptococci reside in a phagosome and that acidification of the phagosome is required for GBS to survive intracellularly. Moreover, we show that the GBS two-component system CovS/CovR, which is the major acid response regulator in this organism, is required for survival inside the phagosome.

Neonatal invasive fungal infection in England 2004-2010.

Rates of invasive fungal infection are highest among neonates, especially those of low birthweight. This study aimed to describe the current epidemiology of invasive neonatal fungal infections in a UK neonatal infection surveillance network. From 2004 to 2010 prospective multicentre surveillance was conducted by 14 neonatal units using a web-based database. Clinicians then completed a standardized pro forma for each positive fungal blood and/or cerebrospinal fluid culture. The overall incidence was 2.4/1000 neonatal unit admissions and was highest among babies <1000 g (extreme low birthweight, 18.8/1000). Only five infants (6%) were >1500 g. The majority of infections were caused by Candida albicans (59; 69%) and Candida parapsilosis (17; 20%); 33% of infants had received antifungal prophylaxis. Known risk factors (use of central venous catheter, parenteral nutrition, previous antibiotic use) were common among cases. The attributable case fatality rate was 21% (18/84). Extreme low birthweight infants remain at highest risk of invasive fungal infection and prophylaxis should be particularly considered for this group. The number needing to receive prophylaxis to prevent one case varies significantly among units, hence unit-specific decisions are required. Further research is still needed into the optimal empiric and therapeutic strategies.

Antibiotics for early onset neonatal infection

The National Institute for Health and Clinical Excellence (NICE) guidance, Antibiotics for early-onset neonatal infection ,1 published in August 2012, recommends stopping antibiotics at 36 h in term babies who have had a ‘septic screen’, provided there is no growth of a pathogen from blood cultures, low inflammatory markers including two C reactive proteins, and the baby is clinically well. This has been our practice since October 2010. We have audited 1 year of data (October 2010–September 2011) and consider it safe practice. The results are as follows: In this year, 952 blood cultures were taken from babies within our catchment area; 291 …

Rotavirus vaccination in preterm infants: a neonatal guidance chart to aid timely immunisation

Rotavirus infection causes 140 000 cases a year of diarrhoeal illness in children under the age of five; 1 in 10 requires hospital admission in the UK. In July 2013, the Department of Health and Public Health England introduced the monovalent human live attenuated rotavirus vaccine, Rotarix, into the childhood immunisation schedule. Preterm infants represent a vulnerable group, and these infants may miss or have …

Characterizing the burden of invasive Pseudomonas infection on neonatal units in the UK between 2005 and 2011

Concern about Pseudomonas infection in neonatal units has focused on outbreaks. This study analysed cases of invasive Pseudomonas infection in 18 UK neonatal units participating in the NeonIN Neonatal Infection Surveillance Network from January 2005 to December 2011. Forty-two cases were reported. The majority (35/42, 93%) of cases were late-onset (median 14 days, range 2-262 days), the highest incidence was seen in extremely-low-birthweight infants and all cases were sporadic. One-third of cases were known to be colonized prior to invasive disease. Attributable mortality was 18%. Opportunities for preventing invasive disease due to this important pathogen should be prioritized.

Transposon insertion in a serine-specific minor tRNA coding sequence affects intraperitoneal survival of Haemophilus influenzae in the infant rat model.

Due to its lifestyle as a commensal and occasional pathogen in the upper and lower respiratory tracts of humans, Haemophilus influenzae needs to protect itself from endogenously and exogenously generated reactive oxygen species. To better understand the oxygen radical resistance and to investigate a correlation with virulence, randomly generated paraquat-sensitive H. influenzae transposon mutants were analyzed in an infant rat model of infection. Among 25 different paraquat-sensitive mutants only one mutant harbouring a Tn-insertion within the tRNA-Ser1 gene specific for the rare serine codon UCC, was highly attenuated for intraperitoneal infectivity. Compared to the wild-type strain, the tRNA-Ser1 mutant was also more sensitive to neutrophil-mediated killing, deficient for DNA transformation but showed similar growth rates under laboratory conditions. However, by comparative analysis using an oxyR mutant strain, we could show that neutrophil-mediated killing might not be relevant for intraperitoneal infectivity. Therefore, the increased ROS sensitivity observed for tRNA-Ser1 mutant may not be directly responsible for the observed virulence deficiency in the intraperitoneal infection. We speculate that a reduced translation efficiency of several UCC containing mRNAs results in a delay of protein synthesis and consequently in the loss of cellular mechanisms which are necessary for ROS resistance and virulence.

Assessment of healthcare delivery in the early management of bacterial meningitis in UK young infants: an observational study

Objective To define early presenting features of bacterial meningitis in young infants in England and to review the adequacy of individual case management as compared with relevant national guidelines and an expert panel review. Design Retrospective medical case note review and parental recall using standardised questionnaires. Setting England and Wales. Participants Infants aged <90 days with bacterial meningitis diagnosed between July 2010 and July 2013. Results Of the 97 cases recruited across England and Wales, 66 (68%) were admitted from home and 31 (32%) were in hospital prior to disease onset. Almost all symptoms reported by parents appeared at the onset of the illness, with very few new symptoms appearing subsequently. Overall, 20/66 (30%) infants were assessed to have received inappropriate prehospital management. The median time from onset of first symptoms to first help was 5 hours (IQR: 2–12) and from triage to receipt of first antibiotic dose was 2.0 hours (IQR: 1.0–3.3), significantly shorter in infants with fever or seizures at presentation compared with those without (1.7 (IQR: 1.0–3.0) vs 4.2 (IQR: 1.8–6.3) hours, p=0.02). Overall, 26 (39%) infants had a poor outcome in terms of death or neurological complication; seizures at presentation was the only significant independent risk factor (OR, 7.9; 95% CI 2.3 to 207.0). For cases in hospital already, the median time from onset to first dose of antibiotics was 2.6 (IQR: 1.3–9.8) hours, and 12/31 (39%) of infants had serious neurological sequelae at hospital discharge. Hearing test was not performed in 23% and when performed delayed by ≥4 weeks in 41%. Conclusions In young infants, the non-specific features associated with bacterial meningitis appear to show no progression from onset to admission, whereas there were small but significant differences in the proportion of infants with more specific symptoms at hospital admission compared with at the onset of the illness, highlighting the difficulties in early recognition by parents and healthcare professionals alike. A substantial proportion of infants received inappropriate prehospital and posthospital management. We propose a targeted campaign for education and harmonisation of practice with evidence-based management algorithms.

P01 Bacterial meningitis in infants <90 days of age: Assessment of healthcare delivery

Background Bacterial meningitis in infants <90 days of age remains a significant cause of mortality and morbidity. Despite all the existing prevention and management strategies, recent UK study (2010–2011) showed that the incidence and case fatality rate has not changed over the last two decades. Data on the detailed early case management of bacterial meningitis in this age group is lacking. We therefore set out to assess in detail the healthcare delivery of the management of bacterial meningitis among this age group in order to formulate better management strategies to improve outcome. Methods We conducted a detailed review of the medical records of infants with bacterial meningitis whose parents consented to take part in England and Wales between September 2010 and June 2013. Parents completed a questionnaire with details of the timing of onset and progression of features. All stages of care, including pre-hospital management, initial hospital assessment and ongoing care, post admission follow up were assessed. Ethics approval was by Cambridgeshire 2 REC (Ref: 10/H0308/64). Results During the study period 103 parents consented and 97 were confirmed cases. 66 (68%) were admitted from home and 31 (32%) were already in hospital prior to the onset of the meningitis. The median age was14 days (IQR 3–25) and was higher in home admissions 17 days (11–34) compared to cases already in hospital 1 day (0–7), p = 0.0001. Most 52 (54%) were males and 73 (76%) were born at term. Amongst cases admitted from home, 38% encountered inappropriate pre-hospital management. The median time (IQR) from onset of symptoms to first help was 4.8 h (2–10), triage to first dose of antibiotics was 1.7 h (1.0–3.3) and 54% received empiric antibiotics that were not as per NICE bacterial meningitis guideline. For cases in hospital already, the median time from onset to first dose of antibiotics was 2.6 h (1.3–k8.5) whilst 54% received empiric antibiotics that were not as per NICE bacterial meningitis guideline. Discussion The quality of clinical care for bacterial meningitis in infants <90 days needs improvement. This study provides the first national data on the quality of care and provides rationale for developing targeted interventions to improve outcome.

Cross-species transfer of group B streptococcus via ingestion?

No abstract available