Outcomes of Empiric Antibiotic Therapy With Adjunctive Gentamicin in Patients With Septic Shock

Adding gentamicin to empiric antibiotic treatment regimens of patients with septic shock admitted to the intensive care unit (ICU) would have prevented inappropriate antibiotic treatment in 55% of cases, according to results of a prospective cohort study published in Infectious Diseases.

Investigators conducted a prospective cohort study among all patients with sepsis who were admitted to the ICU of a tertiary care hospital in the Netherlands since 2012, as well as a subset of patients admitted between 2012 and 2017 with septic shock due to 3 infectious foci including abdominal, urogenital, or unknown etiology.

Patients with sepsis were treated in accordance with local guidelines. The investigators randomly assigned patients to receive either monotherapy or combination therapy. Patients in the monotherapy group were treated with extended-spectrum penicillin/β-lactamase inhibitor combination (amoxicillin/clavulanate or piperacillin/tazobactam) and those in the combination therapy group received the same treatment with adjunctive gentamicin.

 The investigators analyzed Patients’ electronic health records to obtain demographic data and record clinical information, including results of microbiologic cultures, antibiotic treatment regimens, and antibiotic resistance patterns of the cultured micro-organisms within the first 5 days of ICU admission. The primary outcome was the occurrence of inappropriate antibiotic therapy, defined as an antibiotic prescription which did not cover bacteria present in cultures obtained within the first 5 days of ICU admission. Secondary outcomes were septic shock reversal and invasive fungal infection.

Of 203 patients with septic shock included in the final analysis, 115 (57%) received monotherapy and 88 (43%) received combination therapy. Patients in both treatment groups were predominantly men (62%), older than 65 years of age (56%), and invasively ventilated (79%). Abdominal focus was the cause of septic shock in 70% of patients.

Overall, inappropriate antibiotic therapy occurred in 14% of patients. A secondary analysis by treatment group showed that inappropriate antibiotic therapy occurred in 17% and 10% of patients in the monotherapy and combination therapy groups, respectively. The investigators noted that if patients in the monotherapy group had received adjunctive gentamicin, the rate of appropriate antibacterial therapy would have increased from 83% (95/115) to 92% (106/115).

Of note, gentamicin was found to be the only effective component of antibiotic therapy among 19% of patients in the combination therapy group due to antimicrobial resistance to the primary agent. Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Enterobacter cloacae were the most commonly cultured Gram-negative organisms resistant to the primary antibiotic. Among patients in the combination therapy group, inadequate therapy occurred in 14% of those treated with piperacillin/tazobactam/gentamicin and 10% of those treated with amoxicillin/clavulanate/gentamicin.

Fungal infection occurred among 22 (11%) patients in both groups (17/115, monotherapy group vs 5/88, combination therapy group). Mortality rates were not significantly different between the groups (P =.199).

Although the occurrence of septic shock reversal was significantly increased among patients who received monotherapy vs those who received combination therapy (P =.016), binomial logistic regression analysis showed that adjunctive gentamicin was not an associative factor (B, 1.578; 95% CI, 0.758-3.286; P =.223). However, the occurrence of septic shock reversal was associated with patients’ APACHE II scores (P =.003), highest lactate concentrations measured in the first 24 hours of ICU admission (P =.026), and norepinephrine doses administered at day 1 (P =.029).

The study was limited by its single-center setting and small sample size due to its highly selective patient population.

“In [patients] [with] unfavorable clinical courses [following] antibiotic monotherapy, lowering the threshold for administering adjunctive aminoglycoside and antifungal therapy should be considered,” the investigators concluded.

Reference

Driessen RGH, Groven RVM, van Koll J, et al. Appropriateness of empirical antibiotic therapy and added value of adjunctive gentamicin in patients with septic shock: a prospective cohort study in the ICU. Infect Dis (Lond). Published online June 22, 2021. doi:10.1080/23744235.2021.1942543