Community-based antibiotic delivery for possible serious bacterial infections in neonates in low- and middle-income countries.

BACKGROUND: The recommended management for neonates with a possible serious bacterial infection (PSBI) is hospitalisation and treatment with intravenous antibiotics, such as ampicillin plus gentamicin. However, hospitalisation is often not feasible for neonates in low- and middle-income countries (LMICs). Therefore, alternative options for the management of neonatal PSBI in LMICs needs to be evaluated.

OBJECTIVES: To assess the effects of community-based antibiotics for neonatal PSBI in LMICs on neonatal mortality and to assess whether the effects of community-based antibiotics for neonatal PSBI differ according to the antibiotic regimen administered.

SEARCH METHODS: We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL 2018, Issue 3), MEDLINE via PubMed (1966 to 16 April 2018), Embase (1980 to 16 April 2018), and CINAHL (1982 to 16 April 2018). We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomised controlled trials (RCTs) and quasi-randomised trials.

SELECTION CRITERIA: We included randomised, quasi-randomised and cluster-randomised trials. For the first comparison, we included trials that compared antibiotics which were initiated and completed in the community to the standard hospital referral for neonatal PSBI in LMICs. For the second comparison, we included trials that compared simplified antibiotic regimens which relied more on oral antibiotics than intravenous antibiotics to the standard regimen of seven to 10 days of injectable penicillin/ampicillin with an injectable aminoglycoside delivered in the community to treat neonatal PSBI.

DATA COLLECTION AND ANALYSIS: We extracted data using the standard methods of the Cochrane Neonatal Group. The primary outcomes were all-cause neonatal mortality and sepsis-specific neonatal mortality. We used the GRADE approach to assess the quality of evidence.

MAIN RESULTS: For the first comparison, five studies met the inclusion criteria. Community-based antibiotic delivery for neonatal PSBI reduced neonatal mortality when compared to hospital referral only (typical risk ratio (RR) 0.82, 95% confidence interval (CI) 0.68 to 0.99; 5 studies, n = 125,134; low-quality evidence). There was, however, a high level of statistical heterogeneity (I² = 87%) likely, due to the heterogenous nature of the study settings as well as the fact that four of the studies provided various co-interventions in conjunction with community-based antibiotics. Community-based antibiotic delivery for neonatal PSBI showed a possible effect on reducing sepsis-specific neonatal mortality (typical RR 0.78, 95% CI 0.60 to 1.00; 2 studies, n = 40,233; low-quality evidence).For the second comparison, five studies met the inclusion criteria. Using a simplified antibiotic approach resulted in similar rates of neonatal mortality when compared to the standard regimen of seven days of injectable procaine benzylpenicillin and injectable procaine benzylpenicillin and injectable gentamicin delivered in community-settings for neonatal PSBI (typical RR 0.81, 95% CI 0.44 to 1.50; 3 studies, n = 3476; moderate-quality evidence). In subgroup analysis, the simplified antibiotic regimen of seven days of oral amoxicillin and injectable gentamicin showed no difference in neonatal mortality (typical RR 0.84, 95% CI 0.47 to 1.51; 3 studies, n = 2001; moderate-quality evidence). Two days of injectable benzylpenicillin and injectable gentamicin followed by five days of oral amoxicillin showed no difference in neonatal mortality (typical RR 0.88, 95% CI 0.29 to 2.65; 3 studies, n = 2036; low-quality evidence). Two days of injectable gentamicin and oral amoxicillin followed by five days of oral amoxicillin showed no difference in neonatal mortality (RR 0.67, 95% CI 0.24 to 1.85; 1 study, n = 893; moderate-quality evidence). For fast breathing alone, seven days of oral amoxicillin resulted in no difference in neonatal mortality (RR 0.99, 95% CI 0.20 to 4.91; 1 study, n = 1406; low-quality evidence). None of the studies in the second comparison reported the effect of a simplified antibiotic regimen on sepsis-specific neonatal mortality.

AUTHORS' CONCLUSIONS: Low-quality data demonstrated that community-based antibiotics reduced neonatal mortality when compared to the standard hospital referral for neonatal PSBI in resource-limited settings. The use of co-interventions, however, prevent disentanglement of the contribution from community-based antibiotics. Moderate-quality evidence showed that simplified, community-based treatment of PSBI using regimens which rely on the combination of oral and injectable antibiotics did not result in increased neonatal mortality when compared to the standard treatment of using only injectable antibiotics. Overall, the evidence suggests that simplified, community-based antibiotics may be efficacious to treat neonatal PSBI when hospitalisation is not feasible. However, implementation research is recommended to study the effectiveness and scale-up of simplified, community-based antibiotics in resource-limited settings.