title: Impact of cotrimoxazole on carriage and antibiotic resistance of Streptococcus pneumoniae and Haemophilus influenzae in HIV-infected children in Zambia.
abstract: This is a substudy of a larger randomized controlled trial on HIV-infected Zambian children, which revealed that cotrimoxazole prophylaxis reduced morbidity and mortality despite a background of high cotrimoxazole resistance. The impact of cotrimoxazole on the carriage and antibiotic resistance of Streptococcus pneumoniae and Haemophilus influenzae as major causes of childhood mortality in HIV-infected children was investigated since these are unclear. Representative nasopharyngeal swabs were taken prior to randomization for 181 of 534 children (92 on cotrimoxazole and 89 on placebo). Bacterial identification and antibiotic susceptibility were performed by routine methods. Due to reduced mortality, prophylactic cotrimoxazole increased the median time from randomization to the last specimen from 48 to 56 months (P = 0.001). The carriage of H. influenzae was unaltered by cotrimoxazole. Carriage of S. pneumoniae increased slightly in both arms but was not statistically significant in the placebo arm. In S. pneumoniae switching between carriage and no carriage in consecutive pairs of samples was unaffected by cotrimoxazole (P = 0.18) with a suggestion that the probability of remaining carriage free was lower (P = 0.10). In H. influenzae cotrimoxazole decreased switching from carriage to no carriage (P = 0.02). Cotrimoxazole resistance levels were higher in postbaseline samples in the cotrimoxazole arm than in the placebo arm (S. pneumoniae, P < 0.0001; H. influenzae, P = 0.005). Cotrimoxazole decreased switching from cotrimoxazole resistance to cotrimoxazole sensitivity in S. pneumoniae (P = 0.002) and reduced the chance of H. influenzae remaining cotrimoxazole sensitive (P = 0.05). No associations were observed between the percentage of CD4 (CD4%), the change in CD4% from baseline, child age at date of specimen, child gender, or sampling month with carriage of either pathogen.
authors.affiliation: University Teaching Hospital, Lusaka, Zambia.
authors.forename: Darlington M
authors.initials: DM
authors.lastname: Mwenya
authors.forename: Bambos M
authors.initials: BM
authors.lastname: Charalambous
authors.forename: Patrick P J
authors.initials: PP
authors.lastname: Phillips
authors.forename: James C L
authors.initials: JC
authors.lastname: Mwansa
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Batt
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Nunn
authors.forename: Sarah
authors.initials: S
authors.lastname: Walker
authors.forename: Diana M
authors.initials: DM
authors.lastname: Gibb
authors.forename: Stephen H
authors.initials: SH
authors.lastname: Gillespie
mesh_terms: D000890:Anti-Infective Agents / Q000627:therapeutic use; D002675:Child, Preschool; D024881:Drug Resistance, Bacterial / Q000187:drug effects*; D005260:Female; D015658:HIV Infections / Q000382:microbiology*; D006192:Haemophilus Infections / Q000150:complications / Q000188:drug therapy / Q000382:microbiology*; D006193:Haemophilus influenzae / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008297:Male; D011008:Pneumococcal Infections / Q000150:complications / Q000188:drug therapy / Q000382:microbiology*; D013296:Streptococcus pneumoniae / Q000187:drug effects* / Q000502:physiology; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000627:therapeutic use*; D015024:Zambia
chemical_list: D000890:Anti-Infective Agents; D015662:Trimethoprim, Sulfamethoxazole Drug Combination