Reconsidering Step-Down Therapy to ß-Lactams for Enterobacteriaceae Bacteremia?

Reviewed by Sonali Advani MBBS, MPH, Duke University School of Medicine

A recent systematic review and meta-analyses published in Open Forum Infectious Diseases compares oral fluoroquinolone (FQ), trimethoprim-sulfamethoxazole (TMP-SMX) and ß-lactams (BLs) as step-down therapy for enterobacteriaceae bacteremia. Eight retrospective studies met the inclusion criteria with data for 2289 patients, 65% of whom were transitioned to oral FQs, 7.7% to TMP-SMX, and 27.2% to BLs. The authors looked at all-cause mortality and recurrence of infection as primary end points. All-cause mortality was not significantly different between patients transitioned to either FQ/TMP-SMX or BLs (odds ratio [OR], 1.13; 95% confidence interval [CI], 0.69–1.87). Overall recurrence of infection occurred more frequently in patients transitioned to oral BLs vs FQs (OR, 2.05; 95% CI, 1.17–3.61), but this difference was not statistically significant when the analysis was limited to recurrent bacteremia alone.

The authors comment that higher recurrence in BL group could be attributed to suboptimal dosing or a class effect. However, there are other potential explanations for their findings. First, infection recurrence was defined as symptomatic infection with the same organism at the primary site of infection. Given heterogeneity of included studies in their definition of symptoms, it is possible some recurrences were misattributed. Given patients often receive BL in the presence of FQ or TMP-SMX resistance, it is possible patients in the BL group represent a group at higher underlying risk of recurrence. Additionally, the shortest effective duration of therapy for uncomplicated enterobacteriaceae is unknown; therefore, it is plausible the role of oral therapy after an up front course of intravenous therapy is negligible and the risk of recurrence seen is due to underlying host factors. Finally, the overall risk of infection recurrence is low in both groups (5.5% BL vs. 1.9% FQ) and should be taken into context when clinically applying findings from this study. While findings from this meta-analysis may not resoundingly support transition to BLs for step-down therapy in enterobacteriaceae bacteremia, we would caution readers from concluding that FQs are better and highlight there may be a role for narrower spectrum BLs in a subset of patients.


Chitra Punjabi, Vivian Tien, Lina Meng, Stan Deresinski, Marisa Holubar, Oral Fluoroquinolone or Trimethoprim-Sulfamethoxazole vs ß-Lactams as Step-Down Therapy for Enterobacteriaceae Bacteremia: Systematic Review and Meta-analysis, Open Forum Infectious Diseases, Volume 6, Issue 10, October 2019, ofz364, 

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