Ceftolozane/Tazobactam Effective in Treating Some ESBL-E Infections

Ceftolozane/tazobactam (C/T) could be an effective treatment for some patients with severe extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E) infections, according to a recent study in Italy.

The multicenter, retrospective study, published in Open Forum Infectious Diseases, reviewed C/T treatment in 153 patients whose diagnoses included hospital-acquired pneumonia (n = 46 [30%]) and complicated urinary tract infections (n = 34 [22.2%]). Favorable clinical outcomes—resolution of symptoms and lack of microbiological evidence of infection—were observed in 128 (83.7%) patients.

“This study reports the largest clinical experience with C/T therapy for the treatment of serious ESBL-E infection, published so far,” the study noted. “We showed that C/T is an effective drug for treating different types of ESBL-E infections.”

The study, funded by a research grant from Merck & Co., showed an increased risk of failure among patients with a higher Charlson comorbidity index, presentation of septic shock and continuous renal replacement therapy (CRRT). Sepsis was reported in 38.6% of patients, and septic shock in 27.5% of patients.

“Clinicians should be aware of the risk of clinical failure with C/T therapy in septic patients receiving CRRT,” the study noted.

The study involved patients treated at 12 centers with a median age of 69. Along with pneumonia and UTIs, diagnoses in the study included acute bacterial skin and skin-structure infections, complicated intra-abdominal infections and concomitant bloodstream infection. Pathogens included Escherichia coli in 48.3% of cases, Klebsiella pneumoniae in 29.4% and and Enterobacter spp in 14.4%.

C/T was administered for a median duration of 14 days as monotherapy in 83% of patients and in combination in 17% with no statistically significant difference in outcomes between mono and combo treatments. Successful clinical outcomes were reported in 128 patients, including 100% of patients treated with empiric therapy, 83.8% of targeted therapy and 66.7% of rescue therapy.

Clinical failure was reported in 25 patients, including lack of clinical response in 4, recurrence of infection in 6, and mortality in 15. Resistance to C/T developed during therapy in 3 patients.

Limitation of the study included that it was a retrospective study unable to control for variables; C/T was administered as a second- or third-line therapy and it is unclear how prior therapies may have affected outcomes; molecular analysis of antibiotic resistance was unavailable; and antibiotic blood levels weren’t performed.

Carbapenems are a first choice for treatment of ESBL-E infections, which are associated with high rates of treatment failure and mortality. But an increase in carbapenem-resistant Enterobacterales strains has sparked a move toward other treatments. This study is in line with previous studies, including the recently published paper ASPECT-NP.

Hospitals have made progress in efforts to reduce multi-drug resistant infections, but ESBL infections remain a growing challenge. A recent study found decreases in 4 of 6 pathogens at 890 U.S. hospitals from 2012 through 2017, but the incidence of carbapenem-resistant Enterobacteriaceae remained steady and ESBL infections increased by 53.3% during that time.

Preventing ESBL-E infections has been an area of focus. A recent study examined contact isolation precautions at 20 hospitals in Germany, the Netherlands, Spain, and Switzerland and found that in non-critical care units contact isolation revealed no benefits when used in addition to standard precautions.