Effects of antibiotic resistance, drug target attainment, bacterial pathogenicity and virulence, and antibiotic access and affordability on outcomes in neonatal sepsis: an international microbiology and drug evaluation prospective substudy (BARNARDS)

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

Systematic media review: A novel method to assess mass-trauma epidemiology in absence of databases—A pilot-study in Rwanda

Objective Surge capacity refers to preparedness of health systems to face sudden patient inflows, such as mass-casualty incidents (MCI). To strengthen surge capacity, it is essential to understand MCI epidemiology, which is poorly studied in low- and middle-income countries lacking trauma databases. We propose a novel approach, the "systematic media review", to analyze mass-trauma epidemiology; here piloted in Rwanda. Methods A systematic media review of non-academic publications of MCIs in Rwanda between January 1(st), 2010, and September 1(st), 2020 was conducted using NexisUni, an academic database for news, business, and legal sources previously used in sociolegal research. All articles identified by the search strategy were screened using eligibility criteria. Data were extracted in a RedCap form and analyzed using descriptive statistics. Findings Of 3187 articles identified, 247 met inclusion criteria. In total, 117 MCIs were described, of which 73 (62.4%) were road-traffic accidents, 23 (19.7%) natural hazards, 20 (17.1%) acts of violence/terrorism, and 1 (0.09%) boat collision. Of Rwandas 30 Districts, 29 were affected by mass-trauma, with the rural Western province most frequently affected. Road-traffic accidents was the leading MCI until 2017 when natural hazards became most common. The median number of injured persons per event was 11 (IQR 5-18), and median on-site deaths was 2 (IQR 1-6); with natural hazards having the highest median deaths (6 [IQR 2-18]). Conclusion In Rwanda, MCIs have decreased, although landslides/floods are increasing, preventing a decrease in trauma-related mortality. By training journalists in "mass-casualty reporting", the potential of the "systematic media review" could be further enhanced, as a way to collect MCI data in settings without databases

Challenges and opportunities to improve efficiency and quality of prehospital emergency care using an mHealth platform: Qualitative study in Rwanda

Introduction: Prompt, high-quality pre-hospital emergency medical services (EMS) can significantly reduce morbidity and mortality. The goal of this study was to identify factors that compromise efficiency and quality of pre-hospital emergency care in Rwanda, and explore the opportunities for a mobile health (mHealth) tool to address these challenges. Methods: In-depth interviews were conducted with 21 individuals representing four stakeholder groups: EMS dispatch staff, ambulance staff, hospital staff, and policymakers. A semi-structured interview guide explored participants’ perspectives on all aspects of the pre-hospital emergency care continuum, from receiving a call at dispatch to hospital handover. Participants were asked how the current system could be improved, and the potential utility of an mHealth tool to address existing challenges. Interviews were audio-recorded, and transcripts were thematically analyzed using NVivo. Results: Stakeholders identified factors that compromise the efficiency and quality of care across the prehospital emergency care continuum: triage at dispatch, dispatching the ambulance, locating the emergency, coordinating patient care at scene, preparing the receiving hospital, and patient handover to the hospital. They identified four areas where an mHealth tool could improve care: efficient location of the emergency, streamline communication for decision making, documentation with real-time communication, and routine data for quality improvement. While stakeholders identified advantages of an mHealth tool, they also mentioned challenges that would need to be addressed, namely: limited internet bandwidth, capacity to maintain and update software, and risks of data security breaches that could lead to stolen or lost data. Conclusion: Despite the success of Rwanda's EMS system, this study highlights factors across the care continuum that could compromise quality and efficiency of prehospital emergency care. Mobile health tools hold great promise to address these challenges, but contextual issues need to be considered to ensure sustainability of use

Building Trauma and EMS Systems Capacity in Rwanda: Lessons and Recommendations

Background: Surgical capacity building has gained substantial momentum. However, care at the hospital level depends on improved access to emergency services. There is no established model for facilitating trauma and EMS system capacity in LMIC settings. This manuscript describes our model for multi-disciplinary collaboration to advance trauma and EMS capacity in Rwanda, along with our lessons and recommendations. Methods: After high-level meetings at the Ministry of Health in Rwanda (MOH), in 2016, a capacity building plan focusing on improved clinical services, quality improvement/research and leadership capacity across prehospital and emergency settings. The main themes for the collaborative model included for empowerment of staff, improving clinical service delivery, and investing in systems and infrastructure. Funding was sought and incorporated into the Sector Wide Approaches to Planning process at the Ministry of Health of Rwanda. Findings: A shared mental model was created through a fully funded immersion program for Rwandese leaders from emergency medicine, nursing, prehospital care, and injury policy. Prehospital care delivery was standardized within Kigali through a train-the-trainers program with four new context-appropriate short courses in trauma, medical, obstetric/neonatal, and pediatric emergencies and expanded across the country to reach \u3e600 staff at district and provincial hospitals. Forty-two protocols and checklists were implemented to standardize prehospital care across specialties. The WHO Trauma Registry was instituted across four major referral centers in the country capturing over 5,000 injured patients. Long-term research capacity development included Masters\u27 Degree support for 11 staff. Conclusions and recommendations: This collaboration was highly productive in empowering staff and leadership, standardizing clinical service delivery in EMS, and investing in systems and infrastructure. This can be a useful model for trauma and EMS system capacity development in other LMICs