Lisa M McNally1, Prakash M Jeena2, Kavitha Gajee3, Stanley A Thula2, A Willem Sturm3, Sharon Cassol4, Andrew M Tomkins5, Hoosen M Coovadia6, David Goldblatt7. 1. Centre for International Child Health and Development, Institute of Child Health, University College London, London WC1N 1EH, UK; Department of Paediatrics and Child Health, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa. Electronic address: lisa.m.mc-nally@gskbio.com. 2. Department of Paediatrics and Child Health, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa. 3. Department of Medical Microbiology, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa. 4. MRC Unit for Inflammation and Immunity, Department of Immunology, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa. 5. Centre for International Child Health and Development, Institute of Child Health, University College London, London WC1N 1EH, UK. 6. Doris Duke Medical Research Institute, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa. 7. Immunobiology Unit, Institute of Child Health, University College London, London WC1N 1EH, UK.
Abstract
BACKGROUND: HIV-related pneumonia is the main cause of paediatric hospital admissions in southern Africa. We aimed to measure predictors of treatment failure and the cause of non-responsive pneumonia in children admitted to hospital with severe pneumonia in Durban, South Africa. METHODS: We investigated 358 children aged 1-59 months who presented with WHO-defined severe or very severe pneumonia. Children were recruited irrespective of HIV status and started on a standard antimicrobial regimen of benzylpenicillin and gentamicin. All infants also received high-dose trimethoprim-sulfamethoxazole. The primary outcome measure was treatment failure at 48 h. FINDINGS: 242 (68%) children were HIV infected, 41 (12%) HIV exposed, uninfected, and 75 (21%) HIV uninfected. Failure to respond by 48 h was predicted by age under 1 year (adjusted odds ratio 6.38, 95% CI 2.72-14.91, p<0.0001), very severe disease (2.47, 1.17-5.24, p=0.0181), HIV status (HIV infected 10.3, 3.26-32.51; HIV exposed, uninfected 6.02, 1.55-23.38; p=0.0003), and polymicrobial disease (one organism 2.06, 1.05-4.05; two organisms 10.75, 4.38-26.36; p<0.0001) on logistic regression analysis. All children with three organisms failed treatment. 72/110 treatment failures had at least two organisms isolated. Three of nine HIV-exposed, uninfected infants, 29/74 HIV-infected, but no HIV-uninfected infants who failed study therapy had Pneumocystis jirovecii pneumonia. INTERPRETATION: For children younger than 1 year, the WHO guidelines are inadequate and need to be revised since both HIV-infected and HIV-exposed, uninfected infants had more treatment failures than did HIV-uninfected infants. Polymicrobial disease is an important reason for treatment failure, and we need to identify rapid low-cost diagnostic methods to assist clinicians.
BACKGROUND: HIV-related pneumonia is the main cause of paediatric hospital admissions in southern Africa. We aimed to measure predictors of treatment failure and the cause of non-responsive pneumonia in children admitted to hospital with severe pneumonia in Durban, South Africa. METHODS: We investigated 358 children aged 1-59 months who presented with WHO-defined severe or very severe pneumonia. Children were recruited irrespective of HIV status and started on a standard antimicrobial regimen of benzylpenicillin and gentamicin. All infants also received high-dose trimethoprim-sulfamethoxazole. The primary outcome measure was treatment failure at 48 h. FINDINGS: 242 (68%) children were HIV infected, 41 (12%) HIV exposed, uninfected, and 75 (21%) HIV uninfected. Failure to respond by 48 h was predicted by age under 1 year (adjusted odds ratio 6.38, 95% CI 2.72-14.91, p<0.0001), very severe disease (2.47, 1.17-5.24, p=0.0181), HIV status (HIV infected 10.3, 3.26-32.51; HIV exposed, uninfected 6.02, 1.55-23.38; p=0.0003), and polymicrobial disease (one organism 2.06, 1.05-4.05; two organisms 10.75, 4.38-26.36; p<0.0001) on logistic regression analysis. All children with three organisms failed treatment. 72/110 treatment failures had at least two organisms isolated. Three of nine HIV-exposed, uninfected infants, 29/74 HIV-infected, but no HIV-uninfected infants who failed study therapy had Pneumocystis jirovecii pneumonia. INTERPRETATION: For children younger than 1 year, the WHO guidelines are inadequate and need to be revised since both HIV-infected and HIV-exposed, uninfected infants had more treatment failures than did HIV-uninfected infants. Polymicrobial disease is an important reason for treatment failure, and we need to identify rapid low-cost diagnostic methods to assist clinicians.
Authors: J Anthony G Scott; W Abdullah Brooks; J S Malik Peiris; Douglas Holtzman; E Kim Mulholland Journal: J Clin Invest Date: 2008-04 Impact factor: 14.808
Authors: Nazma Mansoor; Thomas J Scriba; Marwou de Kock; Michele Tameris; Brian Abel; Alana Keyser; Francesca Little; Andreia Soares; Sebastian Gelderbloem; Silvia Mlenjeni; Lea Denation; Anthony Hawkridge; W Henry Boom; Gilla Kaplan; Gregory D Hussey; Willem A Hanekom Journal: J Infect Dis Date: 2009-04-01 Impact factor: 5.226