Beyond the target pathogen: ecological effects of the hospital formulary

Abstract

Antibiotic therapy has the potential for intended as well as unintended consequences due to ecological effects that extend beyond the target pathogen. This review examines some of the collateral damage and collateral benefit that may occur when using antibiotic therapy. Antibiotics excreted in the gastrointestinal tract cause alterations of the indigenous flora. Such disruptions may increase the risk of colonization and overgrowth of pathogenic bacteria, including resistant species, with the potential for serious infection for an individual patient as well as possible hospital-wide dissemination resulting in local outbreaks of infection. For example, Clostridium difficile infection (CDI), and particularly associated diarrhea and colitis, is a potentially serious and growing problem in hospitals worldwide, and is associated with disruption of gut flora through use of broad-spectrum antibiotics, especially those with antianaerobic activity. Infection control measures and improved antibiotic stewardship are key measures for CDI prevention. Another example is the risk of intestinal colonization and overgrowth with resistant bacteria, which is heightened in surgical patients requiring antimicrobial therapy for intraabdominal infections. Results from two Optimizing Intra-Abdominal Surgery with Invanz studies (OASIS-I and OASIS-II) suggested emergence of resistant Enterobacteriaceae was less likely in these patients treated with ertapenem than in those treated with ceftriaxone/metronidazole or piperacillin/tazobactam. Finally, recent studies have reported that increased use of a nonpseudomonal carbapenem such as ertapenem does not reduce the susceptibility of Pseudomonas aeruginosa to pseudomonal carbapenems, for example, imipenem or meropenem. In fact, data from one study showed increased ertapenem/decreased imipenem use was associated with improved susceptibility of P. aeruginosa to imipenem, probably due to decreased selective pressure for resistant species. Improper antibiotic use can be associated with detrimental effects related to the ecological impacts of these drugs. Improved antibiotic stewardship and appropriate infection control measures are key to minimization of the collateral damage associated with antibiotic therapy and may even have collateral benefits.