Continuous Infusion Ceftolozane/Tazobactam Could Be an Option for Treating MDR Infections

A new study suggests that continuous infusion dosing of ceftolozane/tazobactam (C/T) is a safe, well-tolerated, and convenient way to treat infections caused by multidrug-resistant (MDR) Pseudomonas aeruginosa.

Current dosing regimens for the use of C/T at 8-hour intervals make outpatient delivery impractical, but the once-daily continuous infusion option could help patients avoid hospital admission.

The retrospective chart review, published in Open Forum Infectious Diseases, included 7 patients evaluated from August 2016 through January 2018 who received either 4.5 g or 9 g of continuous infusion C/T every 24 hours in the outpatient setting. The study showed that 6 out of 7 had symptom resolution, and 3 out of 3 had microbiologic resolution.

“Pseudomonas aeruginosa, including strains that are multidrug-resistant, is a problem for most health systems,” study author Bruce M. Jones, Pharm.D., BCPS, infectious diseases clinical pharmacy specialist at St. Joseph's/Candler Health System, Inc. and clinical adjunct assistant professor at the University of Georgia College of Pharmacy told Contagion^®. “There are limited oral treatment options available and many of the current intravenous options are dosed multiple times per day, leading to difficulties in transitioning patients to outpatient therapy. Specifically looking at ceftolozane/tazobactam, being able to give once daily at an outpatient infusion center instead of every 8 hours has helped with transitions of care in our patient population.”

The patients had various infectious diagnoses, with some having transitioned to outpatient C/T after inpatient treatment with other antimicrobials.

“We expected to see a majority of our patients with complicated urinary tract infections, but infectious diagnoses were fairly broad and included pneumonia, discitis, and bacteremia,” Jones and Christopher M. Bland, PharmD, FCCP, FIDSA, BCPS, clinical associate professor at the University of Georgia College of Pharmacy and clinical pharmacy specialist at St. Joseph’s/Candler Health System, told Contagion^®.

No adverse effects were reported. Patient satisfaction surveys indicated that patients agreed or strongly agreed that continuous infusion with daily visits to an infusion center was a better alternative to hospitalization.

“There is a need for safe and effective intravenous antimicrobials that can be given outpatient, especially for difficult to treat or resistant infections,” Jones and Bland told Contagion^®. “Having the option to avoid an admission or decrease length of stay in a patient that only requires intravenous antimicrobials would be beneficial.”

Research into the use of continuous infusion of C/T is limited, and this study included a limited number of patients with varying diagnoses and treatment histories.

“More research regarding safety and efficacy for [continuous infusion] C/T should be performed,” Bland told Contagion^®. “Additionally, more research is needed regarding stability and efficacy/safety for other intravenous agents used in the treatment of multidrug-resistant pathogens in the outpatient setting. Many of these infections don’t have an amenable oral option, could potentially be treated outside of the hospital, and potentially increase patient quality of life by facilitating treatment in the outpatient setting.”

The combination of C/T was found to be safe and effective for patients with drug-resistant Pseudomonas aeruginosa when compared with polymyxins or aminoglycosides, according to a study published last year. That study showed that 81% of patients who took C/T were clinically cured and acute kidney injury rates (6%) were lower than for patients who received polymyxin/aminoglycoside (34%).

The treatment also did well for immunocompromised patients with multidrug-resistant Pseudomonas infections, according to a retrospective cohort study of patients from 15 United States institutions. That study showed a 69% rate of clinical cure and a 19% rate of 30-day all-cause mortality.