Evaluating Risks from Antibacterial Medication Therapy

ABSTRACT EVALUATING RISKS FROM ANTIBACTERIAL MEDICATION THERAPY USING AN OBSERVATIONAL PRIMARY CARE DATABASE Sharon B. Meropol Joshua P. Metlay Virtually everyone in the U.S. is exposed to antibacterial drugs at some point in their lives. It is important to understand the benefits and risks related to these medications with nearly universal public exposure. Most information on antibacterial drug-associated adverse events comes from spontaneous reports. Without an unexposed control group, it is impossible to know the real risks for treated vs. untreated patients. We used an electronic medical record database to select a cohort of office visits for non-bacterial acute respiratory tract infections (excluding patients with pneumonia, sinusitis, or acute exacerbations of chronic bronchitis), and compared outcomes of antibacterial drug-exposed vs. -unexposed patients. By limiting our assessment to visits with acute nonspecific respiratory infections, we promoted comparability between exposed and unexposed patients. To further control for confounding by indication and practice, we explored methods to promote further comparability between exposure groups. Our rare outcome presented an additional analytic challenge. Antibacterial drug prescribing for acute nonspecific respiratory infections decreased over the study period, but, in contrast to the U.S., broad spectrum antibacterial prescribing remained low. Conditional fixed effects linear regression provided stable estimates of exposure effects on rare outcomes; results were similar to those using more traditional methods for binary outcomes. Patients with acute nonspecific respiratory infections treated with antibacterial drugs were not at increased risk of severe adverse events compared to untreated patients. Patients with acute nonspecific respiratory infections exposed to antibacterials had a small decreased risk of pneumonia hospitalizations vs. unexposed patients. This very small measurable benefit of antibacterial drug therapy for acute nonspecific respiratory infections at the patient level must be weighed against the public health risk of emerging antibacterial resistance. Our data provide valuable point estimates of risks and benefits that can be used to inform future decision analysis and guideline recommendations for patients with acute nonspecific respiratory infections. Ultimately, improved point-of-care diagnostic testing may help direct antibacterial drugs to the subset of patients most likely to derive benefit. Degree Type Dissertation Degree Name Doctor of Philosophy (PhD) Graduate Group Epidemiology & Biostatistics First Advisor Joshua P. Metlay, MD, PhD This dissertation is available at ScholarlyCommons: http://repository.upenn.edu/edissertations/424