Comparison of atovaquone and azithromycin with trimethoprim- sulfamethoxazole for the prevention of serious bacterial infections in children with HIV infection

Walter T. Hughes, Wayne M. Dankner, Ram Yogev, Sharon Huang, Mary E. Paul, Midnela Acevedo Flores, Mark W. Kline, Lee Jen Wei

Research output: Contribution to journalArticle

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 ≥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.

Original languageEnglish (US)
Pages (from-to)136-145
Number of pages10
JournalClinical Infectious Diseases
Volume40
Issue number1
DOIs
StatePublished - Jan 1 2005
Externally publishedYes

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Atovaquone
Azithromycin
Sulfamethoxazole Drug Combination Trimethoprim
Virus Diseases
Bacterial Infections
HIV
Pneumocystis carinii
Confidence Intervals
Mycobacterium avium Complex
Pneumocystis Pneumonia
Opportunistic Infections
Centers for Disease Control and Prevention (U.S.)
Therapeutics
Placebos

ASJC Scopus subject areas

  • Immunology

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Comparison of atovaquone and azithromycin with trimethoprim- sulfamethoxazole for the prevention of serious bacterial infections in children with HIV infection. / Hughes, Walter T.; Dankner, Wayne M.; Yogev, Ram; Huang, Sharon; Paul, Mary E.; Flores, Midnela Acevedo; Kline, Mark W.; Wei, Lee Jen.

In: Clinical Infectious Diseases, Vol. 40, No. 1, 01.01.2005, p. 136-145.

Research output: Contribution to journalArticle

Hughes, Walter T. ; Dankner, Wayne M. ; Yogev, Ram ; Huang, Sharon ; Paul, Mary E. ; Flores, Midnela Acevedo ; Kline, Mark W. ; Wei, Lee Jen. / Comparison of atovaquone and azithromycin with trimethoprim- sulfamethoxazole for the prevention of serious bacterial infections in children with HIV infection. In: Clinical Infectious Diseases. 2005 ; Vol. 40, No. 1. pp. 136-145.
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AU - Huang, Sharon

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AU - Wei, Lee Jen

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N2 - 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 ≥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.

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