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Effect of resistance to third-generation cephalosporins on morbidity and mortality from bloodstream infections in Blantyre, Malawi: a prospective cohort study.
Lester, Rebecca; Musicha, Patrick; Kawaza, Kondwani; Langton, Josephine; Mango, James; Mangochi, Helen; Bakali, Winnie; Pearse, Oliver; Mallewa, Jane; Denis, Brigitte; Bilima, Sithembile; Gordon, Stephen B; Lalloo, David G; Jewell, Christopher P; Feasey, Nicholas A.
Afiliação
  • Lester R; Malawi-Liverpool Wellcome Research Programme, Kamuzu University of Health Sciences, Blantyre, Malawi; Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, UK. Electronic address: rebecca.lester@lstmed.ac.uk.
  • Musicha P; Malawi-Liverpool Wellcome Research Programme, Kamuzu University of Health Sciences, Blantyre, Malawi; Parasites and Microbes Programme, Wellcome Sanger Institute, Hinxton, UK.
  • Kawaza K; Department of Paediatrics and Child Health, Kamuzu University of Health Sciences, Blantyre, Malawi.
  • Langton J; Department of Paediatrics and Child Health, Kamuzu University of Health Sciences, Blantyre, Malawi.
  • Mango J; Malawi-Liverpool Wellcome Research Programme, Kamuzu University of Health Sciences, Blantyre, Malawi.
  • Mangochi H; Malawi-Liverpool Wellcome Research Programme, Kamuzu University of Health Sciences, Blantyre, Malawi.
  • Bakali W; Malawi-Liverpool Wellcome Research Programme, Kamuzu University of Health Sciences, Blantyre, Malawi.
  • Pearse O; Malawi-Liverpool Wellcome Research Programme, Kamuzu University of Health Sciences, Blantyre, Malawi; Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, UK.
  • Mallewa J; Department of Medicine, Kamuzu University of Health Sciences, Blantyre, Malawi; Department of Medicine, Queen Elizabeth Central Hospital, Blantyre, Malawi.
  • Denis B; Malawi-Liverpool Wellcome Research Programme, Kamuzu University of Health Sciences, Blantyre, Malawi.
  • Bilima S; Malawi-Liverpool Wellcome Research Programme, Kamuzu University of Health Sciences, Blantyre, Malawi.
  • Gordon SB; Malawi-Liverpool Wellcome Research Programme, Kamuzu University of Health Sciences, Blantyre, Malawi; Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, UK.
  • Lalloo DG; Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, UK.
  • Jewell CP; Centre for Health Informatics, Computing and Statistics, Lancaster University, Lancaster, UK.
  • Feasey NA; Malawi-Liverpool Wellcome Research Programme, Kamuzu University of Health Sciences, Blantyre, Malawi; Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, UK.
Lancet Microbe ; 3(12): e922-e930, 2022 12.
Article em En | MEDLINE | ID: mdl-36335953
BACKGROUND: 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. METHODS: 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. FINDINGS: 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. INTERPRETATION: 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. FUNDING: Wellcome Trust and Wellcome Asia and Africa Programme.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Bacteriemia / Sepse Tipo de estudo: Etiology_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Humans País como assunto: Africa Idioma: En Ano de publicação: 2022 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Bacteriemia / Sepse Tipo de estudo: Etiology_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Humans País como assunto: Africa Idioma: En Ano de publicação: 2022 Tipo de documento: Article