Is A Shorter Duration Of Antibiotic Therapy Paradoxically Associated With More Resistant Secondary Infection In Randomized, Controlled Trials?
BACKGROUND: One theoretical benefit of shortening duration of antibiotic therapy for hospital-managed infections is decreased risk of resistant superinfections. We hypothesized that a review of randomized trials of duration of antibiotic therapy would demonstrate a lower rate of resistant secondary infections in patients with a shorter duration versus a longer duration of treatment.
METHODS: PubMed was searched for all clinical, controlled trials where randomization was used to determine duration of antimicrobial therapy in a population of hospital-managed infections. Resistant superinfections were defined as a documented resistant infection, other than the initial infection being treated, that occurred during or immediately after each study's designated treatment period.
RESULTS: Thirteen studies met criteria. Pneumonia was the most common infection, followed by intra-abdominal infections. A total of 5437 patients were included, 2685 in a short duration arm and 2752 in a long duration arm. Mean days of therapy were 6.7 days in the short duration arm and 10.5 days in the long duration arm. Despite receiving, on average, 3.8 fewer days of therapy, the short duration patients had increased resistant superinfections, 322/2685 patients (11.99%) versus 271/2752 patients (9.85%), p = 0.011 by chi-square analysis.
CONCLUSIONS: A shorter duration of antibiotic treatment in randomized, controlled trials unexpectedly appeared to be associated with a higher rate of resistant superinfections. It is possible that damage to the host microbiome occurs within the first few days of therapy and future emphasis should be placed on avoiding the initiation of any antibiotics where unnecessary rather than shortening therapeutic courses.