Intestinal Carriage of ESBL-producing gram-negative bacilli in hospitalised neonates <2000g in The Gambia (Feasibility Study Results).

This week’s spotlight focuses on a feasibility study conducted by Dr Helen Brotherton (LSHTM, Faculty of EPH, Research Degree Student – supervised by Professor Joy Lawn, Professor Simon Cousens and Dr Anna Roca) conducting a clinical trial into effects of early Kangaroo Mother Care (KMC) (<24 hours of admission) on the mortality, clinical and microbiological outcomes in unstable preterm babies in The Gambia, based at MRC Unit The Gambia at London School of Hygiene and Tropical Medicine (LSHTM).

Over half of all births in Sub-Saharan Africa are in health facilities and hospital born neonates are up-to 21 times more likely to develop a health-care associated infection (HAI) than neonates in high-income countries. Preterm and low-birth weight neonates are at increased risk of both acquiring HAI and have higher mortality risk, contributing to unacceptably high global neonatal mortality rates. Over half of all neonatal HAI are caused by gram-negative bacteria and multi-drug resistant organisms such as extended spectrum β-lactamase producing gram-negative bacilli (ESBL-GNB) are an important cause. Intestinal carriage of MDR-GNB is a pre-curser for invasive disease, with carriage occurring in as many as 86% of neonates in resource-limited neonatal units. Developing and evaluating low cost, feasible methods of breaking the chain of ESBL-GNB transmission is urgently needed to impact on the important public health challenge of neonatal MDR infections.

Kangaroo mother care (KMC) is a low-tech, high-impact intervention consisting of continuous skin-to-skin contact (>18h/day) between baby and caregiver. KMC is recommended by WHO as standard care for stable babies <2000g and reduces HAI at discharge (or term) in stable babies by 65% compared to incubator care in resource limited settings. (Cochrane 2016) However, intestinal ESBL-GNB colonisation occurs rapidly after hospital admission and interventions within the first 24 hours are urgently needed to prevent infections and improve survival.

This formative work was part of a mixed methods feasibility study for a randomised controlled trial comparing early kangaroo mother care versus standard care in hospitalised unstable babies <2000g in The Gambia (eKMC). The prospective observational cohort study was conducted at Edward Francis Small Teaching Hospital, the national neonatal unit in The Gambia, from April to August 2017. A cohort of hospitalised neonates <2000g and <20 hours old had peri-anal swabs taken at day 0 of admission and weekly until 28 days old (or discharge). Paired maternal recto-vaginal swabs were collected within 24h of neonatal admission. Samples were cultured at MRC Unit The Gambia Clinical Laboratory (ISO 15189 accredited) by standard methods on MacConkey and Chrome Agar with API testing for species identification. Antibiotic sensitivity testing was by Kirby Bauer Diffusion Method with Double Disc Synergy Test for ESBL detection.

35 neonates were recruited (mean weight 1300g, 33+1 weeks gestation) providing 130 samples with 57 Gram-negative isolates and mixed growth in 33%. All neonates received ampicillin/gentamicin on admission, with 14% (5/35) also receiving 3rd generation cephalosporin antibiotics during hospitalisation.

44% (25/57) of GNB were ESBL-producing with 32% of ESBL-GNB resistant to all antibiotics tested and 12% sensitivity to gentamicin.  Interestingly, neonatal intestinal ESBL-GNB carriage at admission was 6% (2/35) increasing to 58% (7/12) at day 7 of life. Klebsiella species was the most common ESBL-GNB identified from neonates and no paired mothers had ESBL-Klebsiella spp. carriage with 9% (2/23) having recto-vaginal ESBL-E coli carriage.

To conclude, this small feasibility study found that more than half of hospitalised preterm neonates alive at day 7 of life had intestinal ESBL-GNB carriage, predominantly ESBL-Klebsiella spp. This has led to further planned research to explore transmission of ESBL-GNB and impact of early KMC on carriage and invasive disease.