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Background Sepsis is a major contributor to neonatal mortality, particularly in low-income and middle-income countries (LMICs). WHO advocates ampicillin–gentamicin as first-line therapy for the management of neonatal sepsis. In the BARNARDS observational cohort study of neonatal sepsis and antimicrobial resistance in LMICs, common sepsis pathogens were characterised via whole genome sequencing (WGS) and antimicrobial resistance profiles. In this substudy of BARNARDS, we aimed to assess the use and efficacy of empirical antibiotic therapies commonly used in LMICs for neonatal sepsis. Methods In BARNARDS, consenting mother–neonates aged 0–60 days dyads were enrolled on delivery or neonatal presentation with suspected sepsis at 12 BARNARDS clinical sites in Bangladesh, Ethiopia, India, Pakistan, Nigeria, Rwanda, and South Africa. Stillborn babies were excluded from the study. Blood samples were collected from neonates presenting with clinical signs of sepsis, and WGS and minimum inhibitory concentrations for antibiotic treatment were determined for bacterial isolates from culture-confirmed sepsis. Neonatal outcome data were collected following enrolment until 60 days of life. Antibiotic usage and neonatal outcome data were assessed. Survival analyses were adjusted to take into account potential clinical confounding variables related to the birth and pathogen. Additionally, resistance profiles, pharmacokinetic–pharmacodynamic probability of target attainment, and frequency of resistance (ie, resistance defined by in-vitro growth of isolates when challenged by antibiotics) were assessed. Questionnaires on health structures and antibiotic costs evaluated accessibility and affordability. Findings Between Nov 12, 2015, and Feb 1, 2018, 36 285 neonates were enrolled into the main BARNARDS study, of whom 9874 had clinically diagnosed sepsis and 5749 had available antibiotic data. The four most commonly prescribed antibiotic combinations given to 4451 neonates (77·42%) of 5749 were ampicillin–gentamicin, ceftazidime–amikacin, piperacillin–tazobactam–amikacin, and amoxicillin clavulanate–amikacin. This dataset assessed 476 prescriptions for 442 neonates treated with one of these antibiotic combinations with WGS data (all BARNARDS countries were represented in this subset except India). Multiple pathogens were isolated, totalling 457 isolates. Reported mortality was lower for neonates treated with ceftazidime–amikacin than for neonates treated with ampicillin–gentamicin (hazard ratio [adjusted for clinical variables considered potential confounders to outcomes] 0·32, 95% CI 0·14–0·72; p=0·0060). Of 390 Gram-negative isolates, 379 (97·2%) were resistant to ampicillin and 274 (70·3%) were resistant to gentamicin. Susceptibility of Gram-negative isolates to at least one antibiotic in a treatment combination was noted in 111 (28·5%) to ampicillin–gentamicin; 286 (73·3%) to amoxicillin clavulanate–amikacin; 301 (77·2%) to ceftazidime–amikacin; and 312 (80·0%) to piperacillin–tazobactam–amikacin. A probability of target attainment of 80% or more was noted in 26 neonates (33·7% [SD 0·59]) of 78 with ampicillin–gentamicin; 15 (68·0% [3·84]) of 27 with amoxicillin clavulanate–amikacin; 93 (92·7% [0·24]) of 109 with ceftazidime–amikacin; and 70 (85·3% [0·47]) of 76 with piperacillin–tazobactam–amikacin. However, antibiotic and country effects could not be distinguished. Frequency of resistance was recorded most frequently with fosfomycin (in 78 isolates [68·4%] of 114), followed by colistin (55 isolates [57·3%] of 96), and gentamicin (62 isolates [53·0%] of 117). Sites in six of the seven countries (excluding South Africa) stated that the cost of antibiotics would influence treatment of neonatal sepsis. Interpretation Our data raise questions about the empirical use of combined ampicillin–gentamicin for neonatal sepsis in LMICs because of its high resistance and high rates of frequency of resistance and low probability of target attainment. Accessibility and affordability need to be considered when advocating antibiotic treatments with variance in economic health structures across LMICs. Funding The Bill & Melinda Gates Foundation.

Background: Little is known about the prevalence of co-infection with hepatitis B virus (HBV) and human immunodeficiency virus (HIV) in the post-conflict South-Kivu Province, Eastern Democratic Republic of the Congo. Therefore, we aimed to determine such data at Panzi Referral Hospital. Methods: We conducted a cross-sectional study of 198 HIV-positive patients seen in consultation from June to 31 November 2017. Socio-demographic and clinical data were collected by interview and clinical examination. Blood sample was taken for serological analyses. The presence of HBV serological markers was determined by enzyme linked immunoassay (ELISA) tests. CD4+ T cell counts were determined for all patients. Data analysis was done using the JMP 7.1 software. Proportions were compared using a Chi-square test or Fisher test. Results: Fourteen of 198 participants (7.07%, 95% confidence interval [CI]: 4.35 - 11.51) were HBsAg-positive. Overall, 33.33% of the subjects had been in contact with HBV and 36.87% were carriers of the immunization marker. Among co-infected patients, 28.57% had a chronic replicative viral B infection, 57.14% a chronic non-replicative infection and 14.29% were inactive carriers. No patient had an acute infection. Co-infection was higher in participants who were aged 55 and over (8.3%), men (12.90%, p = 0.0306), married (12.00%, p = 0.0063), or of Lega ethnicity (14.3%, p = 0.0100). Some clinical signs such as hepatomegaly and jaundice (p < 0.0001), fever (p = 0.0095), splenomegaly (p = 0.0007), ascites (p = 0.0173) and viral encephalitis (p ≤ 0.0001) were associated with co-infection. Severe immunosuppression (50.00%, p = 0.0110) and WHO clinical stage III/IV (10.64%; p = 0.0301) were associated with HIV/HBV co-infection. Conclusions: The relative high prevalence of HIV/HBV co-infection and chronic nature call for the need of integrating HBV screening programs into HIV routine care to reduce morbidity and mortality levels caused by HIV/HBV co-infection.