Search

The burden of antimicrobial resistance is a major threat to global health; however, prospective clinical outcome data from Africa are scarce. In Malawi, third-generation cephalosporins are the antibiotics of choice in patients admitted to hospital despite a rapid proliferation of resistance to these drugs. We aimed to quantify the effect of resistance to third-generation cephalosporins on mortality and length of hospital stay among patients with bloodstream infections.We did a prospective cohort study of patients admitted to Queen Elizabeth Central Hospital in Blantyre, Malawi. Patients of all ages who had positive blood cultures for Enterobacterales were included, with the exception of those from the genus Salmonella, and were followed up for 180 days. We characterised blood culture isolates using whole-genome sequencing and used Cox regression models to estimate the effect of resistance to third-generation cephalosporins on length of hospital stay, in-hospital mortality, and survival.Between Jan 31, 2018, and Jan 13, 2020, we recruited 326 patients, from whom 220 (68%) of 326 isolates were resistant to third-generation cephalosporins. The case fatality proportion was 45% (99 of 220) in patients with bloodstream infections that were resistant to third-generation cephalosporins, and 34% (36 of 106) in patients with bloodstream infections that were sensitive to third-generation cephalosporins. Resistance to third-generation cephalosporins was associated with an increased probability of in-hospital mortality (hazard ratio [HR] 1·44, 95% CI 1·02-2·04), longer hospital stays (1·5 days, 1·0-2·0) and decreased probability of discharge alive (HR 0·31, 0·22-0·45). Whole-genome sequencing showed a high diversity of sequence types of both Escherichia coli and Klebsiella pneumoniae. Although isolates associated with death were distributed across clades, we identified three E coli clades (ST410, ST617, and ST648) that were isolated from 14 patients who all died.Resistance to third-generation cephalosporins is associated with increased mortality and longer hospital stays in patients with bloodstream infections in Malawi. These data show the urgent need for allocation of resources towards antimicrobial resistance mitigation strategies in Africa.Wellcome Trust and Wellcome Asia and Africa Programme.

Background: Neonatal sepsis is responsible for a considerable burden of morbidity and mortality in sub-Saharan African countries. Outcomes from neonatal sepsis are worsening due to increasing rates of antimicrobial resistance. Sub-optimal Infection Prevention and Control (IPC) practices of health care workers and caregivers are important drivers of infection transmission. The Chatinkha Neonatal Unit at Queen Elizabeth Central Hospital, Blantyre, Malawi has experienced multiple outbreaks of neonatal sepsis, associated with drug resistant Klebsiella pneumoniae. We aimed to understand the barriers to implementation of optimal IPC focusing on hand hygiene practice. Methods: We used a qualitative research methodology to meet the study aim. Combining participant observation (PO) over a seven-month period with semi structured interviews (SSI) to provide an in-depth understanding of activities relating to hygiene and IPC existing on the ward. Results: While most staff and some caregivers, had a good understanding of ideal IPC and understood the importance of good handwashing practices, they faced substantial structural limitations, and scarce resources (both material and human) which made implementation challenging. For staff, the overwhelming numbers of patients meant the workload was often unmanageable and practicing optimal IPC was challenging. Caregivers lacked access to basic amenities, including linen and chairs, meaning that it was almost impossible for them to maintain good hand hygiene. Limited access to soap and the erratic water supply for both caregivers and healthcare workers further worsened the situation. Communication challenges between different cadres of staff and with patient caregivers meant that those handling neonates and cleaning the wards were often unaware of outbreaks of drug resistant infection. Conclusion: For IPC to be improved, interventions need to address the chronic shortages of material resources and create an enabling environment for HCWs and patient caregivers.

BackgroundPeople with recurrent or drug-resistant TB require long courses of intramuscular injections. We evaluate a novel system in which patient-nominated lay carers were trained to deliver intramuscular injections to patients in their own homes.MethodsA pragmatic, individually randomised non-inferiority trial was conducted at two hospitals in Malawi. Adults starting TB retreatment were recruited. Patients randomised to the intervention received home-based care from patient-nominated lay people trained to deliver intramuscular streptomycin. Patients receiving standard care were admitted to hospital for 2 months of streptomycin. The primary outcome was successful treatment (alive and on treatment) at the end of the intervention.ResultsOf 456 patients screened, 204 participants were randomised. The trial was terminated early due to futility. At the end of the intervention, 97/101 (96.0%) in the hospital arm were still alive and on treatment compared with 96/103 (93.2%) in the home-based arm (risk difference −0.03 (95% CI −0.09 to 0.03); p value 0.538). There were no differences in the proportion completing 8 months of anti-TB treatment; or the proportion experiencing 2-month sputum culture conversion. The mean cost of hospital-based management was US$1546.3 per person, compared to US$729.2 for home-based management. Home-based care reduced risk of catastrophic household costs by 84%.ConclusionsAlthough this trial failed to meet target recruitment, the available data demonstrate that training patient-nominated lay people has potential to provide a feasible solution to the operational challenges associated with delivering long-term-injectable drugs to people with recurrent or drug-resistant TB in resource-limited settings, and substantially reduce costs. Further data under operational conditions are required.Trial registration numberISRCTN05815615.