The risk for recurrent bacteremia or death is not significantly higher with oral β-lactam antibiotics than with fluoroquinolones or trimethoprim-sulfamethoxazole (TMP-SMX), a new study finds.

“Oral β-lactam antibiotics are not routinely recommended as step-down therapy for Enterobacterales bacteremia owing to concern over subtherapeutic serum concentrations,” Jesse D. Sutton, PharmD, MS, of Veterans Affairs Salt Lake City Health Care System, in Salt Lake City, Utah, and colleagues noted.

In their study of 4089  hospitalized veterans (91.2% male; median age 71 years) with Escherichia coli, Klebsiella spp, or Proteus spp bacteremia from a suspected urine source, 955 received an oral β-lactam antibiotic and 3134 received fluoroquinolones or TMP-SMX after 1 to 5 days of parenteral antibiotics.

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A total of 4.4% of β-lactam antibiotic recipients and 3.0% of fluoroquinolones or TMP-SMX recipients experienced the primary composite endpoint of all-cause mortality and/or recurrent bacteremia within 30 days. But no significant difference in mortality was observed between treatment groups (3.0% vs 2.6%, respectively), Dr Sutton’s team reported in JAMA Network Open. Additionally, the relative risk of recurrent bacteremia within 30 days was not significantly higher with oral β-lactam antibiotics (eg, amoxicillin-clavulanate potassium, cephalexin) compared with fluoroquinolones (eg, ciprofloxacin, levofloxacin) or TMP-SMX (1.5% vs 0.4%, respectively), and the absolute risk and risk difference were less than 3% and, according to the investigators, probably not clinically meaningful. The number of recurrent bacteremia events was low, so the results need to be validated by future studies. Few patients experienced a repeat hospitalization with urinary tract infection (UTI) within 30 days: 1.5% vs 0.7%, respectively.

“These data suggest that oral β-lactam antibiotics are a reasonable step-down treatment option in the setting of Enterobacterales bacteremia from a urine source after initial parenteral antibiotics, primarily when alternative treatments are limited by antibiotic resistance or potential adverse effects,” Dr Sutton and his collaborators wrote. The results do not apply to other sources of bacteremia, other Enterobacterales species, and oral β-lactam antibiotics used alone without preceding parenteral antibiotics, they noted.

The study population comprised older men so the findings may not pertain to younger men, who have higher renal clearance of β-lactam antibiotics. “Involvement of infectious diseases and antimicrobial stewardship programs should be considered to optimize patient selection,” according to the investigators.


Sutton JD, Stevens VW, Chang N-C N, Khader K, Timbrook TT, Spivak ES. Oral β-lactam antibiotics vs fluoroquinolones or trimethoprim-sulfamethoxazole for definitive treatment of Enterobacterales bacteremia from a urine source. JAMA Netw Open. doi:10.1001/jamanetworkopen.2020.20166