{
  "abstract": "Introduction Carbapenem-resistant, Gram-negative bacteria (GNB) are a significant cause of neonatal sepsis, threatening survival. There is a scarcity of robust data on their burden and outcomes in low- and middle-income countries (LMICs). We aimed to describe clinical and microbiological characteristics, outcomes and mortality risk factors in neonates infected with GNB and assess the impact of carbapenem resistance.Methods Prospective observational cohort study from 1 February 2021 to 30 June 2023 conducted in a tertiary neonatal unit in Johannesburg, South Africa, in infants <90 days with culture-confirmed blood or cerebrospinal fluid infection with GNB. The primary outcome was mortality by day-28 post-sepsis diagnosis.Results Gram-negative sepsis incidence was 6.6/1000 patient-days. Among 353 infants enrolled (median birth weight 1465 g; gestational age 31 weeks), 173 (49%) had carbapenem-sensitive organisms (CSO), 152 (43%) had carbapenem-resistant organisms (CRO) and susceptibility was not reported in 28 (8%). There were 404 GNB isolated. Acinetobacter baumannii (156/404; 39%) and Klebsiella pneumoniae (127/404; 31%) were predominant. Of the 34 infants with early-onset sepsis caused by GNB, 13 (38%) were infected with CRO. Day-28 all-cause mortality was 23%. Infections with CRO were associated with higher crude 28-day mortality (31% vs 17%; OR 2.22, 95% CI 1.32 to 3.75; p=0.003), though this was not an independent association (p=0.552). Independent factors associated with mortality were the need for inotropes (adjusted OR (aOR) 6.09; 95% CI 3.05 to 12.15; p<0.001), metabolic acidosis (aOR 5.43, 95% CI 2.11 to 14.02; p<0.001), lethargy (aOR 3.20, 95% CI 1.46 to 7.02; p=0.004), glucose instability (aOR 2.31, 95% CI 1.22 to 4.36; p=0.010) and positive culture with A. baumannii (aOR 4.57, 95% CI 2.00 to 10.41; p<0.001) and K. pneumoniae (aOR 2.77, 95% CI 1.18 to 6.48; p=0.017).Conclusions There is a substantial burden of Gram-negative neonatal infections, particularly due to CRO, exceeding rates reported in other LMICs in Africa and globally. Although carbapenem resistance was not independently associated with mortality, infants with CRO had approximately two times higher crude mortality compared with those with CSO, emphasising the urgent need for antimicrobial stewardship and infection prevention interventions. Neonatal-specific trials are needed addressing prevention and optimal antibiotic treatment of CRO infections to improve outcomes.",
  "authors": [
    {
      "affiliations": [
        "School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa",
        "Department of Paediatrics, Chris Hani Baragwanath Academic Hospital, Johannesburg, South Africa"
      ],
      "name": "Reenu Thomas"
    },
    {
      "affiliations": [
        "St George’s University of London, London, UK"
      ],
      "name": "Michael Sharland"
    },
    {
      "affiliations": [
        "MRC Clinical Trials Unit at University College London, London, UK"
      ],
      "name": "Michelle Clements"
    },
    {
      "affiliations": [
        "School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa",
        "Department of Paediatrics, Chris Hani Baragwanath Academic Hospital, Johannesburg, South Africa"
      ],
      "name": "Sithembiso Christopher Velaphi"
    }
  ],
  "title": "Clinical features, risk factors and 28-day mortality in neonates with carbapenem-resistant sepsis or meningitis in a South African tertiary neonatal unit: a prospective cohort study",
  "uid": "f941b64d-30f3-5b93-b1f1-dac6afd2a786"
}