title: Effect of age, polymicrobial disease, and maternal HIV status on treatment response and cause of severe pneumonia in South African children: a prospective descriptive study.
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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.affiliation: 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.
authors.forename: Lisa M
authors.initials: LM
authors.lastname: McNally
authors.affiliation: Department of Paediatrics and Child Health, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa.
authors.forename: Prakash M
authors.initials: PM
authors.lastname: Jeena
authors.affiliation: Department of Medical Microbiology, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa.
authors.forename: Kavitha
authors.initials: K
authors.lastname: Gajee
authors.affiliation: Department of Paediatrics and Child Health, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa.
authors.forename: Stanley A
authors.initials: SA
authors.lastname: Thula
authors.affiliation: Department of Medical Microbiology, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa.
authors.forename: A Willem
authors.initials: AW
authors.lastname: Sturm
authors.affiliation: MRC Unit for Inflammation and Immunity, Department of Immunology, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa.
authors.forename: Sharon
authors.initials: S
authors.lastname: Cassol
authors.affiliation: Centre for International Child Health and Development, Institute of Child Health, University College London, London WC1N 1EH, UK.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Tomkins
authors.affiliation: Doris Duke Medical Research Institute, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa.
authors.forename: Hoosen M
authors.initials: HM
authors.lastname: Coovadia
authors.affiliation: Immunobiology Unit, Institute of Child Health, University College London, London WC1N 1EH, UK.
authors.forename: David
authors.initials: D
authors.lastname: Goldblatt
mesh_terms: D000367:Age Factors; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D002675:Child, Preschool; D005260:Female; D006679:HIV Seropositivity; D015497:HIV-1; D017052:Hospital Mortality; D006801:Humans; D007223:Infant; D016015:Logistic Models; D008297:Male; D008429:Maternal Welfare; D011014:Pneumonia / Q000150:complications / Q000188:drug therapy* / Q000382:microbiology; D011446:Prospective Studies; D012720:Severity of Illness Index; D013019:South Africa; D017211:Treatment Failure
chemical_list: D000900:Anti-Bacterial Agents