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Short-Course Adjunctive Gentamicin as Empirical Therapy in Patients With Severe Sepsis and Septic Shock: A
David S Y Ong1,2, Jos F Frencken2,3, Peter M C Klein Klouwenberg1,2
1Department of Medical Microbiology.
Background.:
Metaanalyses failed to demonstrate clinical benefits of beta lactam plus aminoglycoside combination therapy compared to beta lactam monotherapy in patients with sepsis. However, few data exist on the effects of short-course adjunctive aminoglycoside therapy in sepsis patients with organ failure or shock.
Methods.:
We prospectively enrolled consecutive patients with severe sepsis or septic shock in 2 intensive care units in the Netherlands from 2011 to 2015. Local antibiotic protocols recommended empirical gentamicin add-on therapy in only 1 of the units. We used logistic regression analyses to determine the association between gentamicin use and the number of days alive and free of renal failure, shock, and death, all on day 14.
Results.:
Of 648 patients enrolled, 245 received gentamicin (222 of 309 [72%] in hospital A and 23 of 339 [7%] in hospital B) for a median duration of 2 days (interquartile range, 1-3). The adjusted odds ratios associated with gentamicin use were 1.39 (95% confidence interval [CI], 1.00-1.94) for renal failure, 1.34 (95% CI, 0.96-1.86) for shock duration, and 1.41 (95% CI, 0.94-2.12) for day-14 mortality. Based on in vitro susceptibilities, inappropriate (initial) gram-negative coverage was given in 9 of 245 (4%) and 18 of 403 (4%) patients treated and not treated with gentamicin, respectively (P = .62).
Conclusions.:
Short-course empirical gentamicin use in patients with sepsis was associated with an increased incidence of renal failure but not with faster reversal of shock or improved survival in a setting with low prevalence of antimicrobial resistance.
Insights
Short-course gentamicin in sepsis patients increased renal failure risk without improving shock reversal or survival. This study highlights potential harms of empirical aminoglycoside use in critical illness.
Area of Science:
- Critical Care Medicine
- Infectious Diseases
- Pharmacology
Background:
- Previous meta-analyses found no benefit of beta-lactam/aminoglycoside combinations over monotherapy for sepsis.
- Limited data exist on short-course aminoglycoside therapy in sepsis patients with organ failure or shock.
Purpose of the Study:
- To investigate the association between short-course empirical gentamicin use and clinical outcomes in severe sepsis or septic shock.
- To assess the impact of gentamicin on renal failure, shock duration, and mortality at day 14.
Main Methods:
- Prospective enrollment of severe sepsis/septic shock patients in two Dutch ICUs (2011-2015).
- Logistic regression analysis to determine the association between gentamicin use and key outcomes.
- Comparison of outcomes between a unit with empirical gentamicin protocols and one without.
Main Results:
- 245 of 648 patients received gentamicin for a median of 2 days.
- Gentamicin use was associated with increased odds of renal failure (aOR 1.39) and shock duration (aOR 1.34).
- No significant improvement in day-14 survival was observed (aOR 1.41).
Conclusions:
- Short-course empirical gentamicin in sepsis patients was linked to higher renal failure incidence.
- Gentamicin did not accelerate shock reversal or improve survival in this low-resistance setting.
- Findings suggest caution with empirical aminoglycoside use in critically ill sepsis patients.
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