Clinical and Economic Consequences of Failure of Initial Antibiotic Therapy for Hospitalized Patients With Complicated Skin and Skin-Structure Infections

Objective. To estimate the consequences of failure of initial antibiotic therapy for patients with complicated skin and skin-structure infections. Design. Retrospective cohort study. Setting. Large US multihospital database. Patients. We identified a total of 47,219 patients (age 18 years or older) who were admitted to the hospital for complicated skin and skin-structure infections from April 1, 2003, through March 31, 2004, and who received intravenous antibiotics during the first 2 hospital-days (ie, initial antibiotic therapy). Failure of therapy was defined as drainage, debridement, or receipt of other intravenous antibiotics at any subsequent time (except for changes to narrower-spectrum agents or any therapy change immediately before discharge). Predictors of failure of antibiotic therapy and mortality were examined using multivariate logistic regression. Analysis of covariance was used to estimate the impact of treatment failure on duration of intravenous antibiotic therapy, length of stay, and total inpatient charges. Results. For 10,782 admitted patients (22.8%), there was evidence of failure of initial antibiotic therapy. In multivariate analyses, treatment failure was associated with receipt of vasoactive medications during the first 2 hospital-days (odds ratio [OR], 1.66 [95% confidence interval {CI}, 1.19-2.31]), initiation of antibiotic therapy in the intensive care unit (OR, 1.53 [95% CI, 1.28-1.84]), and the patient's Charlson comorbidity index (OR per 1-point increase, 1.06 [95% CI, 1.04-1.08]); treatment failure was also was associated with a 3-fold increase in mortality (OR, 2.91 [95% CI, 2.34-3.62]). Compared with patients for whom initial treatment was successful, patients who experienced treatment failure received intravenous antibiotic therapy for a mean of 5.7 additional days, were hospitalized for a mean of 5.4 additional days, and incurred a mean of $5,285 (in 2003 dollars) in additional inpatient charges (all P <.01). Conclusion. Failure of initial antibiotic therapy in the treatment of complicated skin and skin-structure infections is associated with significantly worse clinical and economic outcomes.