Impact of prolonged co-trimoxazole prophylaxis on colonization with antibiotic resistant bacteria in persons newly diagnosed with HIV-infection: CoTrimResist-a randomized placebo-controlled trial.

Abstract

Objective: To assess whether prolonged co-trimoxazole prophylaxis for people with HIV in sub-Saharan Africa increases colonization with antibiotic-resistant bacteria.

Methods: The CoTrimResist trial (NCT03087890) randomized newly diagnosed Tanzanian adults with HIV and CD4 counts >350/µL to daily co-trimoxazole or placebo for 1 year. Clinical data, rectal and nasopharyngeal/nasal swabs were collected at enrolment, 2 weeks, 6 months, and 1 year. Primary outcomes were carriage of extended-spectrum beta-lactamase-producing Escherichia coli (ESBL-EC) and Klebsiella species (ESBL-K), methicillin-resistant Staphylococcus aureus (MRSA), and penicillin-non-susceptible pneumococci (PNSP).

Results: Among 537 participants (median age 37 years; 77% female), 259 received co-trimoxazole, and 278 placebo. Co-trimoxazole temporarily reduced nasal S. aureus carriage at 2 weeks (risk difference -7.3%; 95% confidence interval [CI] -12.0% to -2.6%) and 6 months (-7.6%; 95% CI -13.9% to -1.3%), and MRSA at 2 weeks (-4.5%; 95% CI -8.0% to -1.1%). ESBL-EC colonization increased more rapidly with co-trimoxazole. At 1 year, there were no between-group differences in colonization rates, mortality or serious adverse events. Intercurrent use of other antibiotics was associated with increased carriage of ESBL-EC.

Conclusion: Prolonged co-trimoxazole prophylaxis leads to transient reductions in S. aureus and MRSA and early increase in ESBL-EC, but shows no persistent effect on colonization with antimicrobial-resistant bacteria at 1 year.