Oral β-Lactam Antibiotics vs Fluoroquinolones or Trimethoprim-Sulfamethoxazole for Definitive Treatment of Enterobacterales Bacteremia From a Urine Source

JAMA Netw Open. 2020 Oct 1;3(10):e2020166. doi: 10.1001/jamanetworkopen.2020.20166.


Importance: Oral β-lactam antibiotics are traditionally not recommended to treat Enterobacterales bacteremia because of concerns over subtherapeutic serum concentrations, but there is a lack of outcomes data, specifically after initial treatment with parenteral antibiotics. Given the limited data and increasing limitations of fluoroquinolones or trimethoprim-sulfamethoxazole (TMP-SMX), oral β-lactam antibiotics may be a valuable additional treatment option.

Objective: To compare definitive therapy with oral β-lactam antibiotics vs fluoroquinolones or TMP-SMX for Enterobacterales bacteremia from a suspected urine source.

Design, setting, and participants: A retrospective cohort study was conducted from January 1, 2007, to September 30, 2015, at 114 Veterans Affairs hospitals among 4089 adults with Escherichia coli, Klebsiella spp, or Proteus spp bacteremia and matching urine culture results. Additional inclusion criteria were receipt of active parenteral antibiotic(s) followed by conversion to an oral antibiotic. Exclusion criteria were previous Enterobacterales bacteremia, urologic abscess, or chronic prostatitis. Data were analyzed from April 15, 2019, to July 26, 2020.

Exposures: Conversion of therapy to an oral β-lactam antibiotic vs fluoroquinolones or TMP-SMX after 1 to 5 days of parenteral antibiotics.

Main outcomes and measures: The main outcome was a composite of either 30-day all-cause mortality or 30-day recurrent bacteremia. Propensity-based overlap weights were used to adjust for differences between groups. Log binomial regression models were used to estimate adjusted relative risks (aRRs) and adjusted risk differences (aRDs).

Results: Of the 4089 eligible patients (3731 men [91.2%]; median age, 71 years [interquartile range, 63-81 years]), 955 received an oral β-lactam antibiotic, and 3134 received fluoroquinolones or TMP-SMX. The primary outcome occurred for 42 patients (4.4%) who received β-lactam antibiotics and 94 patients (3.0%) who received fluoroquinolones or TMP-SMX (aRD, 0.99% [95% CI, -0.42% to 2.40%]; aRR, 1.31 [95% CI, 0.87-1.95]). Mortality rates were 3.0% (n = 29) for patients receiving β-lactam antibiotics vs 2.6% (n = 82) for those receiving fluoroquinolones or TMP-SMX (aRD, 0.06% [95% CI, -1.13% to 1.26%]; aRR, 1.02 [95% CI, 0.67-1.56]). Recurrent bacteremia rates were 1.5% (n = 14) among those receiving β-lactam antibiotics vs 0.4% (n = 12) among those receiving fluoroquinolones or TMP-SMX (aRD, 1.03% [95% CI, 0.24%-1.82%]; aRR, 3.43 [95% CI, 0.42-27.90]).

Conclusions and relevance: In this cohort study of adults with E coli, Klebsiella spp, or Proteus spp bacteremia from a suspected urine source, the relative risk of recurrent bacteremia was not significantly higher with β-lactam antibiotics compared with fluoroquinolones or TMP-SMX, and the absolute risk and risk difference were small (ie, <3%). No significant difference in mortality was observed. Oral β-lactam antibiotics may be a reasonable step-down treatment option, primarily when alternative options are limited by resistance or adverse effects. Further study is needed because statistical power was limited owing to a low number of recurrent bacteremia events.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Anti-Bacterial Agents / therapeutic use*
  • Anti-Infective Agents, Urinary / therapeutic use*
  • Cohort Studies
  • Drug Resistance, Multiple, Bacterial
  • Enterobacteriaceae Infections / drug therapy*
  • Enterobacteriaceae Infections / microbiology
  • Female
  • Humans
  • Male
  • Middle Aged
  • Retrospective Studies
  • Trimethoprim, Sulfamethoxazole Drug Combination / therapeutic use*
  • Urinary Tract Infections / drug therapy*
  • Urinary Tract Infections / microbiology
  • beta-Lactams / therapeutic use*


  • Anti-Bacterial Agents
  • Anti-Infective Agents, Urinary
  • beta-Lactams
  • Trimethoprim, Sulfamethoxazole Drug Combination