Oral Fluoroquinolone or Trimethoprim-sulfamethoxazole vs. ß-lactams as Step-Down Therapy for Enterobacteriaceae Bacteremia: Systematic Review and Meta-analysis

Open Forum Infect Dis. 2019 Aug 14;6(10):ofz364. doi: 10.1093/ofid/ofz364. Online ahead of print.

Abstract

Background: Using published data, we sought to compare outcomes in patients transitioned to either oral fluoroquinolones (FQ) or trimethoprim-sulfamethoxazole (TMP-SMX) versus ß-lactams (BL's) after an initial intravenous (IV) course for gram-negative rod (GNR) bacteremia.

Methods: We conducted a systematic review of PubMed and EMBASE and published IDWeek abstracts. We included studies that reported all-cause mortality and/or infection recurrence in patients transitioned to oral FQ/TMP-SMX and BL's.

Results: Eight retrospective studies met inclusion criteria with data for 2,289 patients, of whom 65% were transitioned to oral FQ, 7.7% to TMP-SMX, and 27.2% to BL's. Follow up periods ranged from 21 to 90 days. All-cause mortality was not significantly different between patients transitioned to either FQ/TMP-SMX or BL's (OR 1.13; 95%CI, 0.69-1.87). Overall recurrence of infection, either bacteremia or the primary site, occurred more frequently in patients transitioned to oral BL's vs. FQ's (OR 2.05, 95% CI 1.17 to 3.61). Analysis limited to recurrent bacteremia was similarly suggestive although limited by small numbers (OR 2.32, 95% CI 0.99 to 5.44). However, based on known pharmacokinetics/pharmacodynamics, prescribed ß-lactam dosing regimens were frequently suboptimal.

Conclusions: In the step-down IV to oral treatment of GNR bacteremia, we found insufficient data regarding outcomes after oral TMP-SMX; however, selection of a FQ over commonly utilized ß-lactam regimens may reduce chances of infection recurrence. While this may be a class effect, it may simply be the result of inadequate dosing of ß-lactams. Additional investigations are warranted to determine outcomes with TMP-SMX and optimized oral ß-lactam dosing regimens.