Title : Clinical outcomes of full-dose vs. renally adjusted oral beta-lactams in gram-negative bloodstream infections
Authors : Sadaf Gharibi, PharmD; Sarah Valiante, PharmD, BCIDP; Samantha Stewart, PharmD, BCOP; Antoinette Acbo, PharmD, BCIDP
Objective: Assess the effect of oral beta-lactam dosing on 90-day all-cause mortality and other clinical outcomes in patients with gram-negative bloodstream infections (GN BSI)
Self assessment question:
- Which of the following patients would be the best candidate for transition from intravenous therapy to oral cefuroxime for gram-negative bloodstream infections?
- A) In the ICU on norepinephrine drip
- B) Clinically stable after > 48 hours of IV antibiotic, tolerating oral intake
- C) Intra-abdominal abscess without source control
- D) ESBL-producing organisms not susceptible to available oral beta-lactams
Background: Studies suggest that the higher recurrence with oral beta-lactams (BL) in treating GN BSI may be due to suboptimal dosing and preserved renal function. This study evaluates the effect of oral (PO) BL dosing on clinical outcomes.
Methods: This single center retrospective study was conducted from January 2025 to June 2025. The primary outcome was 90-day all-cause mortality in patients with GN BSIs treated with full dose versus renally adjusted PO BL. Secondary outcomes included 90-day hospital readmission, relapse of bloodstream infection at 90 days, total intravenous (IV) and PO antibiotic days, and length of hospital stay. Patients included were adults with GN BSI treated with PO step down BL following at least 48 hours of empiric IV therapy. Exclusion criteria included complicated infections requiring prolonged IV therapy, concomitant use of non-BL PO antibiotics active against the index isolate, received PO BL to which the index organism in blood or other culture was not susceptible, and expiration within 48 hours of appropriate therapy. PO antibiotic use trends were also evaluated.
Results:
Among the 237 included patients (Median age: 74, 123 male (51.9%), 202 patients had good renal function and 37 patients had bad renal function. The primary outcome (90-day all-cause mortality) occurred in 5 patients with good and 5 patients with bad renal function, and good renal function was associated with significantly lower odds of 90-day all-cause mortality compared with bad renal function (OR:0.10, 95% CI 0.01-0.73, p=0.025). No significant association was observed for 90-day readmission (OR 0.51, 95% CI 0.20-1.26, p=0.145) or recurrence (OR 0.91, 95% CI 0.13-7.89, p=0.921). Antibiotic dosing strategy (dose-adjusted vs. full dose) was not significantly associated with any of the outcomes.
Conclusion:
In this retrospective study of adults with GN BSI treated with PO step down BL, the odds of 90-day all cause mortality was significantly lower in patients with good renal function. No significant difference was observed in the rate of 90-day readmission or recurrence among groups. Collectively, the result of the study suggested that dosing strategy of PO BLs (full dose vs renally dose adjusted), may have no impact on 90-day mortality, hospitalization and recurrence in patients with GN BSI.
