Eravacycline use in immunocompromised patients: multicenter evaluation of timely versus late initiation on clinical outcomes

Abstract

Infections from multidrug-resistant (MDR) bacteria lead to worse outcomes in immunocompromised patients. Eravacycline (ERV) is effective against MDR gram-negative and gram-positive bacteria, but its effects in immunocompromised populations remain unstudied. We aimed to evaluate clinical end points of immunocompromised patients receiving timely versus late ERV therapy. This multicenter, retrospective, observational study (October 2018 to September 2022) included adult immunocompromised patients hospitalized and treated with ERV for ≥72 h. The primary outcome was a composite of all-cause 30-day mortality, failure to improve clinically while on ERV, and/or microbial recurrence within 30 days of ERV initiation. Inverse probability of treatment weighting (IPTW) and Kaplan-Meier analyzes were used. Eighty-two patients from 17 US centers were included (median age 62 years; 59% male; intensive care unit admissions 57%). In the unadjusted cohort, timely ERV significantly reduced odds of clinical treatment failure (odds ratio [OR]: 0.321, 95% confidence interval [CI]: 0.129-0.800, P = 0.012) and microbial recurrence (OR: 0.545, 95% CI: 0.326-0.913, P = 0.034) compared to late ERV; in the IPTW-adjusted cohort, these associations remained significant with ORs of 0.675 (95% CI: 0.465-0.979, P = 0.029) for treatment failure and 0.384 (95% CI: 0.142-0.943, P = 0.041) for recurrence. Kaplan-Meier analysis showed a higher cumulative proportion of clinical treatment failure in the late ERV group (57%) compared to the timely ERV group (30%, P = 0.013), with a significantly longer time to clinical treatment failure in the timely ERV group (log-rank P = 0.034). Timely initiation of ERV in immunocompromised patients may improve clinical outcomes by reducing treatment failure and microbial recurrence compared to later initiation.IMPORTANCEThis multicenter, retrospective study evaluates the impact of timely versus late initiation of eravacycline (ERV) in immunocompromised patients with multidrug-resistant (MDR) bacterial infections. Immunocompromised patients face heightened risks of severe infections due to weakened immune defenses and limited treatment options, yet data on ERV use in this population are scarce. Our findings demonstrate that timely ERV initiation ≤72 h from index culture collection) significantly reduces clinical treatment failure and microbial recurrence compared to late initiation, with inverse probability of treatment weighting-adjusted odds ratios of 0.675 (P = 0.029) for treatment failure and 0.384 (P = 0.041) for recurrence. Kaplan-Meier analysis further confirms that delayed ERV therapy is associated with a higher cumulative incidence of clinical failure (57% vs 30%, P = 0.013). These results highlight the importance of early ERV initiation in optimizing outcomes for immunocompromised patients and addressing the growing challenge of MDR infections, emphasizing the need for further prospective studies to confirm these findings.

Keywords: antimicrobial stewardship; eravacycline; immunocompromised; multidrug-resistant.

Fig 1

Index cultured organisms treated with eravacycline. *Other: Citrobacter koseri, Klebsiella oxytoca, Morganella morganii, Proteus mirabilis, Serratia marcescens, and Streptococcus spp.

Fig 2

Kaplan-Meier curve for time to clinical treatment Failure. This Kaplan-Meier curve illustrates the probability of clinical treatment failure over time (measured in hours) in two groups: patients who received timely eravacycline (ERV) therapy (ERV = 1, green line) and those who received it later (ERV = 0, blue line). The y-axis represents the cumulative probability of clinical treatment failure, while the x-axis represents time in hours. Patients in the timely ERV group demonstrated a lower cumulative probability of clinical treatment failure compared to those in the late group. A statistically significant difference between the two groups was observed, as indicated by the log-rank test (P = 0.034). The median time to clinical treatment failure was 27 h (interquartile range [IQR], 15–60 hours) in the timely group versus 13 h (IQR, 6–20 h) in the late group, highlighting the association between earlier ERV initiation and delayed or reduced likelihood of treatment failure. Censored patients include those who had not yet experienced treatment failure based on the definition of the composite outcome.