Trimethoprim-Sulfamethoxazole Versus Levofloxacin for Stenotrophomonas maltophilia Infections: A Retrospective Comparative Effectiveness Study of Electronic Health Records from 154 US Hospitals

Background Trimethoprim-sulfamethoxazole (TMP-SMX) is considered first-line therapy for Stenotrophomonas maltophilia infections based on observational data from small studies. Levofloxacin has emerged as a popular alternative due to tolerability concerns related to TMP-SMX. Data comparing levofloxacin to TMP-SMX as targeted therapy are lacking. Methods Adult inpatient encounters January 2005 through December 2017 with growth of S maltophilia in blood and/or lower respiratory cultures were identified in the Cerner Healthfacts database. Patients included received targeted therapy with either levofloxacin or TMP-SMX. Overlap weighting was used followed by downstream weighted regression. The primary outcome was adjusted odds ratio (aOR) for in-hospital mortality or discharge to hospice. The secondary outcome was number of days from index S maltophilia culture to hospital discharge. Results Among 1581 patients with S maltophilia infections, levofloxacin (n = 823) displayed statistically similar mortality risk (aOR, 0.76 [95% confidence interval {CI}, .58-1.01]; P = .06) compared to TMP-SMX (n = 758). Levofloxacin (vs TMP-SMX) use was associated with a lower aOR of death in patients with lower respiratory tract infection (n = 1452) (aOR, 0.73 [95% CI, .54-.98]; P = .03) and if initiated empirically (n = 89) (aOR, 0.16 [95% CI, .03-.95]; P = .04). The levofloxacin cohort had fewer hospital days between index culture collection and discharge (weighted median [interquartile range], 7 [4-13] vs 9 [6-16] days; P < .0001). Conclusions Based on observational evidence, levofloxacin is a reasonable alternative to TMP-SMX for the treatment of bloodstream and lower respiratory tract infections caused by S maltophilia. Our findings suggest that mortality outcomes are similar comparing levofloxacin and trimethoprim-sulfamethoxazole (TMP-SMX) treatment of Stenotrophomonas maltophilialower respiratory tract and bloodstream infections. Until trial data are available, levofloxacin appears to be a reasonable alternative to TMP-SMX for these infections.