title: Effect of presumptive co-trimoxazole prophylaxis on pneumococcal colonization rates, seroepidemiology and antibiotic resistance in Zambian infants: a longitudinal cohort study.
abstract: OBJECTIVE
  To ascertain the microbiological consequences of WHO's recommendation for presumptive co-trimoxazole prophylaxis for infants with perinatal HIV exposure.
  
  
  METHODS
  Using a longitudinal cohort design, we followed HIV-exposed and HIV-unexposed infants trimonthly for up to 18 months per infant. HIV-exposed infants received daily co-trimoxazole prophylaxis from 6 weeks to > or = 12 months of age. Using Streptococcus pneumoniae as our sentinel pathogen, we measured how co-trimoxazole altered nasopharyngeal colonization, pneumococcal resistance to antibiotics and serotype distribution as a function of co-trimoxazole exposure.
  
  
  RESULTS
  From 260 infants followed for 3096 patient-months, we detected pneumococci in 360/1394 (25.8%) samples. HIV-exposed infants were colonized more frequently than HIV-unexposed infants (risk ratio, RR: 1.4; 95% confidence interval, CI: 1.0-1.9, P = 0.04). Co-trimoxazole prophylaxis reduced colonization by ca 7% but increased the risk of colonization with co-trimoxazole-resistant pneumococci within 6 weeks of starting prophylaxis (RR: 3.2; 95% CI: 1.3-7.8, P = 0.04). Prophylaxis with co-trimoxazole led to a small but statistically significant increase of nasopharyngeal colonization with pneumococci not susceptible to clindamycin (RR: 1.6; 95% CI: 1.0-2.6, P = 0.04) but did not increase the risk of non-susceptibility to penicillin (RR: 1.1; 95% CI: 0.7-1.7), erythromycin (RR: 1.0; 95% CI: 0.6-1.7), tetracycline (RR: 0.9; 95% CI: 0.6-1.5) or chloramphenicol (RR: 0.8; 95% CI: 0.3-2.3). Co-trimoxazole prophylaxis did not cause the prevailing pneumococcal serotypes to differ from those that are targeted by the 7-valent conjugate pneumococcal vaccine (RR: 1.0; 95% CI: 0.7-1.6).
  
  
  CONCLUSIONS
  Co-trimoxazole prophylaxis modestly suppresses pneumococcal colonization but accelerates infant acquisition of co-trimoxazole- and clindamycin-resistant pneumococci. Co-trimoxazole prophylaxis appears unlikely to compromise the future efficacy of conjugate vaccines.
authors.affiliation: Department of International Health, Boston University School of Public Health, Boston, MA, United States of America. cgill@bu.edu
authors.forename: C J
authors.initials: CJ
authors.lastname: Gill
authors.forename: V
authors.initials: V
authors.lastname: Mwanakasale
authors.forename: M P
authors.initials: MP
authors.lastname: Fox
authors.forename: R
authors.initials: R
authors.lastname: Chilengi
authors.forename: M
authors.initials: M
authors.lastname: Tembo
authors.forename: M
authors.initials: M
authors.lastname: Nsofwa
authors.forename: V
authors.initials: V
authors.lastname: Chalwe
authors.forename: L
authors.initials: L
authors.lastname: Mwananyanda
authors.forename: D
authors.initials: D
authors.lastname: Mukwamataba
authors.forename: B
authors.initials: B
authors.lastname: Malilwe
authors.forename: D
authors.initials: D
authors.lastname: Champo
authors.forename: W B
authors.initials: WB
authors.lastname: Macleod
authors.forename: D M
authors.initials: DM
authors.lastname: Thea
authors.forename: D H
authors.initials: DH
authors.lastname: Hamer
mesh_terms: D000890:Anti-Infective Agents / Q000627:therapeutic use*; D019072:Antibiotic Prophylaxis; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects*; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008137:Longitudinal Studies; D008297:Male; D008826:Microbial Sensitivity Tests; D011008:Pneumococcal Infections / Q000188:drug therapy* / Q000453:epidemiology; D016036:Seroepidemiologic Studies; D013296:Streptococcus pneumoniae / Q000187:drug effects; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000627:therapeutic use*; D015024:Zambia / Q000453:epidemiology
chemical_list: D000890:Anti-Infective Agents; D015662:Trimethoprim, Sulfamethoxazole Drug Combination