title: Comparison of atovaquone and azithromycin with trimethoprim-sulfamethoxazole for the prevention of serious bacterial infections in children with HIV infection.
abstract: BACKGROUND
  Trimethoprim-sulfamethoxazole (TMP-SMZ) has been used extensively for the prevention of Pneumocystis carinii (also referred to as "Pneumocystis jiroveci") pneumonia (PCP) and other opportunistic infections in human immunodeficiency virus (HIV)-infected children. Because the efficacy of TMP-SMZ for treatment of bacterial infections is limited, it is sometimes poorly tolerated, and there is risk of emergence of drug-resistant strains associated with widespread use, we evaluated a regimen that included atovaquone and azithromycin.
  
  
  METHODS
  A randomized, double-blind, placebo-controlled trial was designed to determine whether atovaquone-azithromycin had equivalent efficacy to TMP-SMZ for the prevention of serious bacterial infections and to compare the long-term tolerance, PCP breakthrough rates, and nonserious bacterial infection rates among HIV-infected children aged 3 months to 19 years. Children qualified for PCP prophylaxis (on the basis of Centers for Disease Control and Prevention recommendations) were randomized to receive atovaquone-azithromycin or TMP-SMZ daily for >or=2 years.
  
  
  RESULTS
  Data from 366 of the 369 eligible patients (median duration of follow-up, 3 years) showed that the estimated rates of serious bacterial infection-related events were lower among atovaquone-azithromycin recipients than among TMP-SMZ recipients (17.3 vs. 24.2 events per 100 patient-years; difference, 6.9 events per 100 patient-years; 95% confidence interval [CI], -0.22 to 14.12). Rates for all end points (serious bacterial infection, PCP, Mycobacterium avium complex infection, and serious and nonserious bacterial infection-related deaths) were 19.7 and 27.7 events per 100 patient-years, respectively (difference, 7.9 events per 100 patient-years; 95% CI, -0.28 to 15.54 events per 100 patient-years). The results marginally favored atovaquone-azithromycin therapy statistically. Atovaquone-azithromycin and TMP-SMZ therapies had similar adverse event profiles.
  
  
  CONCLUSIONS
  We conclude that, in HIV-infected children, atovaquone-azithromycin is as effective as TMP-SMZ for the prevention of serious bacterial infections and is similarly tolerated.
authors.affiliation: Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN 38105-2794, USA. Walter.hughes@stjude.org
authors.forename: Walter T
authors.initials: WT
authors.lastname: Hughes
authors.forename: Wayne M
authors.initials: WM
authors.lastname: Dankner
authors.forename: Ram
authors.initials: R
authors.lastname: Yogev
authors.forename: Sharon
authors.initials: S
authors.lastname: Huang
authors.forename: Mary E
authors.initials: ME
authors.lastname: Paul
authors.forename: Midnela Acevedo
authors.initials: MA
authors.lastname: Flores
authors.forename: Mark W
authors.initials: MW
authors.lastname: Kline
authors.forename: Lee-Jen
authors.initials: LJ
authors.lastname: Wei
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000517:prevention & control*; D000293:Adolescent; D053626:Atovaquone; D017963:Azithromycin / Q000627:therapeutic use*; D001424:Bacterial Infections / Q000517:prevention & control*; D002648:Child; D002675:Child, Preschool; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000150:complications*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009285:Naphthoquinones / Q000627:therapeutic use*; D011020:Pneumonia, Pneumocystis / Q000517:prevention & control; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000627:therapeutic use
chemical_list: D009285:Naphthoquinones; D015662:Trimethoprim, Sulfamethoxazole Drug Combination; D017963:Azithromycin; D053626:Atovaquone