Neonatal Infections; a hospital-based study in The Gambia examining aetiology and associated maternal Colonisation

An estimated 2.6 million newborns die each year, mostly from largely preventable causes – prematurity, intrapartum-related complications and infections. Data on neonatal infection aetiology and pathways of acquisition of infection are lacking particularly in sub-Saharan Africa (sSA), yet are essential to inform prevention. In a systematic review of neonatal infection aetiology studies in sSA, Klebsiella species, Escherichia coli, Staphylococcus aureus, Group B Streptococci, and Enterococcus were the top five reported bacterial pathogens across all regions. Application of the Strengthening the Reporting of Observational Studies in Epidemiology for Newborn Infection (STROBE-NI) checklist highlighted wide variation in clarity and completeness of reporting, impeding comparability and utility. A four-year audit of neonatal admissions and quality of care at The Gambia’s largest referral hospital showed that possible serious bacterial infection (pSBI) accounted for 44% (2166/4944) of admissions. There was a striking mismatch of high antibiotic use (95%) and low microbiological investigation for infection (1% blood culture and 2% lumbar puncture) was evident. A hospital-based matched case-control study was undertaken in the three main referral health facilities in The Gambia to describe neonatal infection aetiology, and evaluate the role of maternal bacterial colonisation. Sick newborn-mother pairs (n=203) and healthy newborn-mother pairs (n=203) were recruited. Pathogenic bacteria were isolated from blood cultures of 45% (91/202) of the sick newborns, and the most frequently identified isolates were S. aureus, Klebsiella, and Burkholderia cepacia. There was notable lack of GBS detected by culture but in the molecular sub-study, GBS was identified in 5% (2/42) of cases. Klebsiella demonstrated near universal resistance to WHO-recommended first- and second-line antibiotics. For 14 mother-infant pairs, the isolates from infant blood and maternal rectovaginal cultures matched suggesting possible vertical transmission This PhD shows that infections are a major problem among hospitalised newborns in The Gambia. Programmatic implications and priorities for research are outlined

Antibiotic use on paediatric inpatients in a teaching hospital in the Gambia, a retrospective study

Background: Antibiotics are useful but increasing resistance is a major problem. Our objectives were to assess antibiotic use and microbiology testing in hospitalized children in the Gambia. Methods: We conducted a retrospective analysis of paediatric inpatient data at The Edward Francis Small Teaching Hospital in Banjul, The Gambia. We extracted relevant data from the admission folders of all patients (aged >28 days to 15 years) admitted in 2015 (January-December), who received at least one antibiotic for 24 h. We also reviewed the microbiology laboratory record book to obtain separate data for the bacterial isolates and resistance test results of all the paediatric inpatients during the study period. Results: Over half of the admitted patients received at least one antibiotic during admission (496/917) with a total consumption of 670.7 Days of Antibiotic Therapy/1000 Patient-Days. The clinical diagnoses included an infectious disease for 398/496, 80.2% of the patients on antibiotics, pneumonia being the most common (184/496, 37.1%). There were 51 clinically relevant bacterial isolates, Klebsiella species being the most common (12/51, 23.5%), mainly from urine (11/12, 91.7%). Antibiotic resistance was mainly to ampicillin (38/51, 74.5%), mainly reported as Coliform species 11/51, 21.6%. Conclusions: More than half of the admitted patients received antibiotics. The reported antibiotic resistance was highest to the most commonly used antibiotics such as ampicillin. Efforts to maximize definitive antibiotic indication such as microbiological testing prior to start of antibiotics should be encouraged where possible for a more rational antibiotic use

Maternal colonisation and early-onset neonatal bacterial sepsis in The Gambia, West Africa: a genomic analysis of vertical transmission.

OBJECTIVES: To define bacterial aetiology of neonatal sepsis and estimate prevalence of neonatal infection from maternal genital tract bacterial carriage among mother-newborn pairs. METHODS: We carried out a cross-sectional study of newborns with clinical sepsis admitted to neonatal wards of three hospitals in The Gambia. Neonatal blood cultures and maternal genital swabs were obtained at recruitment. We used whole-genome sequencing (WGS) to explore vertical transmission for neonates with microbiologically confirmed bloodstream infection by comparing phenotypically matched paired neonatal blood culture and maternal genital tract bacterial isolates. RESULTS: We enrolled 203 maternal-newborn pairs. Two-thirds (67%; 137/203) of neonates presented with early-onset sepsis (days 0 - 6 after birth) of which 26% (36/137) were due to a clinically-significant bacterial pathogen. Blood culture isolates from newborns with early-onset sepsis due to Staphylococcus aureus (n=5), Klebsiella pneumonia (n=2), and Enterococcus faecalis (n=1), phenotypically matched their maternal genital tract isolates. Pairwise SNV comparisons showed differences of 12 - 52 SNVs only between maternal and newborn Staphylococcus aureus isolates, presumably representing vertical transmission with a transmission rate of 14% (5/36). CONCLUSIONS: We found low prevalence of vertical transmission of maternal genital tract colonisation in maternal-newborn pairs for early-onset neonatal sepsis in west African context. Identifying infection acquisition pathways among newborns is essential to prioritise preventive interventions, which could be targeted at mother or infection control in the hospital environment, depending on the major pathways of transmission

Should first-line empiric treatment strategies cover coagulase-negative staphylococcal infections in severely malnourished or HIV-infected children in Kenya?

BACKGROUND: Bloodstream infection is a common cause of morbidity in children aged andlt;5 years in developing countries. In studies reporting bacteremia in Africa, coagulase-negative Staphylococci (CoNS) are commonly isolated. However, it is currently unclear whether children who are highly susceptible to infection because of severe acute malnutrition (SAM) or HIV should be treated with antimicrobials specifically to cover CoNS. We aimed to determine the clinical significance of CoNS amongst children admitted to a rural hospital in Kenya in relation to nutritional and HIV status. METHODS: Systematically collected clinical and microbiological surveillance data from children aged 6-59 months admitted to Kilifi County Hospital (2007-2013) were analysed. Multivariable regression was used to test associations between CoNS isolation from blood cultures and SAM (MUAC andlt;11.5cm or nutritional oedema (kwashiorkor)), and HIV serostatus; and among children with SAM or HIV, associations between CoNS isolation and mortality, duration of hospitalization and clinical features. RESULTS: CoNS were isolated from blood culture in 906/13,315 (6.8%) children, of whom 135/906 (14.9%) had SAM and 54/906 (6.0%) were HIV antibody positive. CoNS isolation was not associated with SAM (MUACandlt;11.5cm (aOR 1.11, 95% CI 0.88-1.40) or kwashiorkor (aOR 0.84, 95% CI 0.48-1.49)), or a positive HIV antibody test (aOR 1.25, 95% CI 0.92-1.71). Among children with SAM or a positive HIV antibody test, CoNS isolation was not associated with mortality or prolonged hospitalization. CONCLUSION: In a large, systematic study, there was no evidence that antimicrobial therapy should specifically target CoNS amongst children with SAM or HIV-infection or exposure