Empiric Antibiotic Therapy in Suspected Sepsis: Impact of Gentamicin-Based Regimens on Incident Renal Failure and Mortality

Abstract

Background: The efficacy and safety of administering a narrow-spectrum β-lactam and gentamicin as empirical therapy for community-acquired sepsis has been questioned. We compared the efficacy and safety of this combination with that of broad-spectrum β-lactams (cefotaxime, piperacillin-tazobactam, or meropenem) in patients with suspected sepsis.

Methods: In this retrospective study, we included patients initiated on narrow-spectrum β-lactam/gentamicin or broad-spectrum β-lactams for suspected sepsis between January 2017 and December 2022. Patients without baseline creatinine and at least 1 subsequent creatinine measurement were excluded. We compared the impact of antibiotic regimens using a 5-level ordinal outcome scale ranging from no acute kidney injury (AKI) to all-cause death during 30-day follow-up.

Results: Among 1917 patients, 33.1% received narrow-spectrum β-lactam/gentamicin, and 66.9% received broad-spectrum β-lactams. Patients initiated on broad-spectrum β-lactams had more comorbidities, had lower estimated glomerular filtration rate on admission, and more frequently required treatment with noradrenaline, respiratory support, and admission to the intensive care and medical intermediate care units. Therapy with broad-spectrum β-lactams was associated with a higher posttreatment stage of AKI or death (adjusted odds ratio, 1.61 [95% confidence interval, 1.27-2.04]). We found no significant association between cumulative dose of gentamicin and peak creatinine value. For patients treated with gentamicin experiencing AKI, creatinine normalized during 30-day follow-up.

Conclusions: In patients with suspected sepsis, empirical treatment with narrow-spectrum β-lactam/gentamicin was not associated with an increased risk of AKI or death. If local antimicrobial resistance patterns permit, narrow-spectrum β-lactam/gentamicin may reduce broad-spectrum β-lactam usage, addressing a key element of antibiotic stewardship.

Keywords: antibiotics; antimicrobial stewardship; mortality; nephrotoxicity; sepsis.

Figure 1.

Flow diagram of study inclusion (study period from 1 January 2017 to 31 December 2022). ¹Narrow-spectrum β-lactams include benzylpenicillin and ampicillin. ²Broad-spectrum β-lactams include cefotaxime, piperacillin-tazobactam, and meropenem.

Figure 2.

Adjusted probabilities of clinical outcomes according to antibiotic regimen. Probabilities derived from ordinal logistic regression. Adjusted for age, sex, Charlson Comorbidity Index score, kidney function (estimated glomerular filtration rate), time to first dose of antibiotics, and markers of disease severity including National Early Warning Score 2, noradrenaline, respiratory support, and admission to intensive care unit or medical intermediate care unit. Abbreviation: AKI, acute kidney injury.

Figure 3.

Changes in creatinine values during 30 days after admission for patients receiving broad-spectrum β-lactams. Patients with no creatinine increase compared to patients with ≥1.5 times increase in creatinine within 30 days after admission according to empiric antibiotic regimen. Adjusted for age, sex, Charlson Comorbidity Index score, renal replacement therapy, time to first dose of antibiotics, and markers of disease severity including National Early Warning Score 2, noradrenaline, respiratory support, and admission to intensive care unit or medical intermediate care unit.

Figure 4.

Changes in creatinine values during 30 days after admission for patients receiving narrow-spectrum β-lactam/gentamicin. Patients with no creatinine increase compared to patients with ≥1.5 times increase in creatinine within 30 days after admission according to empiric antibiotic regimen. Adjusted for age, sex, Charlson Comorbidity Index score, renal replacement therapy, time to first dose of antibiotics, and markers of disease severity including National Early Warning Score 2, noradrenaline, respiratory support, and admission to intensive care unit or medical intermediate care unit.