Colistin levels not linked to clinical outcomes in XDR P. aeruginosa infections
Plasma concentrations of colistin do not appear to be associated with clinical cure and 30-day mortality in the treatment of infections caused by extremely drug-resistant (XDR) Pseudomonas aeruginosa, according to a Spanish prospective observational cohort study.
Although colistin has been available for decades, there is limited pharmacokinetic and pharmacodynamic data on this antimicrobial, which is often used as a “last-line” therapy against multidrug-resistant (MDR) Gram-negative bacteria. Moreover, the optimal dose or therapeutic level has yet to determined.
The study included a total of 91 adult patients with microbiologically documented and clinically defined infections due to colistin-susceptible XDR P. aeruginosa, and who had received treatment with intravenous colistimethate sodium (CMS) for at least 72 hours. Clinical data and steady-state colistin plasma levels (Css) were obtained.
The primary endpoint was clinical cure, defined as the resolution of signs and symptoms of infection, while the secondary endpoint was 30-day all-cause mortality, defined as death occurring within 30 days of starting CMS treatment.
As colistin carries a potential risk for nephrotoxicity, the serum creatinine level and glomerular filtration rate (GFR) were obtained to determine the presence of acute kidney injury (AKI) during CMS treatment.
Of the 91 patients, 72 (79 percent) achieved clinical cure with a mean Css of 1.49 mg/L vs 2.42 mg/L in those who did not achieve clinical cure (p=0.01).
Independent risk factors for clinical failure, defined as progression or worsening of signs and symptoms of infection, were male sex (odds ratio [OR], 5.88; p=0.039), APACHE II score (OR, 1.15; p=0.013) and the presence of nephrotoxicity at the end of treatment (EOT; OR, 9.13; p=0.004).For the endpoint of 30-day mortality, the rate was reported to be 30.8 percent. Risk factors for 30-day mortality included APACHE II score (OR, 1.98; p=0.046), McCabe score (OR, 2.49; p=0.021) and presence of AKI at the EOT (OR, 3.8; p=0.018).