title: A retrospective study on the effects of colistin therapy in children with multidrug-resistant Gram-negative bacterial pathogens: impact of HIV status on outcome.
abstract: BACKGROUND
  Nosocomially acquired multidrug-resistant (MDR) Gram-negative bacteria are important contributors to paediatric intensive care unit (PICU) mortality and morbidity, with limited treatment options.
  
  
  OBJECTIVE
  To investigate the outcomes of all children treated with colistin for infection with MDR Gram-negative bacteria while admitted to PICU.
  
  
  METHODS
  Retrospective observational study of 19 months. Primary endpoints were all-cause intensive care unit mortality and safety. Secondary endpoints evaluated clinical and microbiological outcomes. Cases were stratified according to HIV status.
  
  
  RESULTS
  Twenty-seven children received 30 colistin courses during the study period. Eight patients (29.6%) were HIV infected, six (22.2%) were HIV uninfected but exposed, and 11 (40.7%) were HIV uninfected and unexposed. Common MDR Gram-negative bacteria cultured were: Acinetobacter species (n=22, 81.5%), Pseudomonas aeruginosa (n=11, 40.7%) and Klebsiella pneumoniae (n=7, 25.9%). Mortality was 37%, with no significant difference between HIV strata. No adverse drug reactions were noted. A composite clinical improvement was noted in 16 courses (53.3%) of colistin. Only 30% of colistin courses used in HIV-infected children resulted in an improved clinical assessment as compared with 83.3% of courses in HIV-uninfected/unexposed children (p=0.04). In HIV-infected children, five of 10 (50%) courses of colistin showed bacteriological clearance compared to the HIV uninfected/unexposed group where all cases showed bacterial eradication (p=0.02).
  
  
  CONCLUSIONS
  HIV-infected children had poorer clinical and bacteriological responses to colistin treatment than HIV uninfected/unexposed. These results require confirmation with prospective studies to determine whether findings are due to poor microbial response, immunodeficiency or repeated reinfections.
authors.affiliation: Department of Paediatrics and Child Health, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Inkosi Albert Luthuli Central Hospital, , Durban, , KwaZulu-Natal, South Africa.
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Dimitriades
authors.forename: Brenda May
authors.initials: BM
authors.lastname: Morrow
authors.forename: Prakash
authors.initials: P
authors.lastname: Jeena
mesh_terms: D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D046688:Child Mortality; D002675:Child, Preschool; D003091:Colistin / Q000627:therapeutic use*; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects*; D005260:Female; D006090:Gram-Negative Bacteria / Q000187:drug effects*; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy*; D015658:HIV Infections / Q000150:complications* / Q000382:microbiology; D006801:Humans; D007223:Infant; D015278:Intensive Care Units, Pediatric; D008297:Male; D012189:Retrospective Studies; D013019:South Africa; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D003091:Colistin
keywords: Colistin; HIV; Multidrug resistant gram negative bacteria; Outcome