Is a shorter duration of antibiotic therapy associated with more resistant secondary infections?

Author(s):
Cole Kircher; Robert Sawyer

Background:

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 published, randomized trials of duration of antibiotic therapy would demonstrate a lower rate of resistant secondary infections in patients randomized to a shorter duration versus a longer duration of treatment.

Methods:

Methods: PubMed was searched for all human, 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.  The definition of resistant was that used by the investigators in the original studies.

Results:

Results: Thirteen studies met inclusion criteria.  Pneumonia was the most common infection studied, followed by intra-abdominal infections and urinary tract infections. In 5 studies, duration of therapy was pre-designated, in 5 studies duration was determined by changes in procalcitonin levels, and in 3 studies one arm had a fixed duration of therapy and was compared to one determined by biological parameters.  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 numbers of resistant superinfections, 322/2685 patients (11.99%) versus 271/2752 patients (9.85%), p = 0.011 by chi-square analysis.

Conclusions:

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.