Ceftazidime-avibactam (CAZ-AVI) was found to be a viable option for the treatment of Klebsiella pneumoniae carbapenemase-producing K pneumonia (KPC-Kp) infections, according to the results of a retrospective, observational multicenter study published in Clinical Infectious Diseases.

Patients (N=577) treated with CAZ-AVI for KPC-Kp infections at 22 hospitals in Italy from June 2018 to January 2020 were included in this analysis. Infection details and clinical outcomes were assessed.

The median age of patients was 66 years (interquartile range [IQR], 56-76), 66.9% were men, 85.1% acquired their infection while hospitalized, 31.2% had an INCREMENT score higher than 8, 17.3% had septic shock, and 23.7% were transferred to the intensive care unit. The patients were stratified by bacterial (n=391) and nonbacterial (n=186) infection status. Most of the patients with bacterial infections were men (P =.003); more had hematologic malignancy (P =.004), neutropenia (P =.001), and a central venous catheter (P =.001); and fewer were hospitalized for surgery (P =.01) or had dementia (P =.005).


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The median duration of treatment with CAZ-AVI was 12 days (IQR, 8-16), and most (53.9%) started therapy within 48 hours of infection and were given another active antimicrobial drug (66.1%).

All-cause mortality at 30 days was 26.3% and 23.1% for patients with and without a bacterial infection, respectively; 10.7% and 11.3% had infection relapse; 3.6% and 3.2% developed CAZ-AVI resistance; and 3.3% and 3.8% had adverse reactions, respectively.

Stratified by nonbacterial infection type, mortality (37.3%) was highest among patients with lower respiratory tract infections, followed by intra-abdominal infections (20.0%) and complicated urinary tract infections (18.3%). Infection relapse was highest among patients with intra-abdominal infections (20.0%), followed by those with lower respiratory tract infections (13.6%). Mortality was lowest among patients who had complicated urinary tract infections (7.1%).

In a multivariate analysis, after propensity matching, 30-day mortality was associated with neutropenia (odds ratio [OR], 6.86; 95% CI, 2.55-18.42; P <.001), septic shock (OR, 2.59; 95% CI, 1.37-4.89; P =.003), lower respiratory tract infection (OR, 2.48; 95% CI, 1.26-4.86; P =.008), high INCREMENT score (OR, 2.23; 95% CI, 1.27-3.91; P =.005), and CAZ-AVI dose adjustment for renal function (OR, 2.01; 95% CI, 1.15-3.48; P =.01). Patients who received prolonged CAZ-AVI infusion were at decreased risk for mortality (OR, 0.54; 95% CI, 0.34-0.83; P =.006).

These findings may have been biased by the retrospective observational study design and would require confirmation in a clinical trial setting.

The study authors concluded that CAZ-AVI for the treatment of KCP-Kp infections as either monotherapy or in combination with other therapies was a viable treatment option, especially for individuals with complicated urinary tract or intra-abdominal infections. Further study of prolonged infusions and their effect on increased survival is warranted.

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.

Reference

Tumbarello M, Raffaelli F, Giannella M, et al. Ceftazidime-avibactam use for KPC-Kp infections: a retrospective observational multicenter study. Clin Infect Dis. Published online February 22, 2021. doi:10.1093/cid/ciab176