Novel antibiotic combo good alternative to carbapenems for complicated UTI

India: Researchers from India have developed CSE -- a novel combination of ceftriaxone, sulbactam, and disodium EDTA -- that can be used as an alternative to carbapenems for the patients suffering from complicated urinary tract infections (cUTI/AP) caused by resistant gram-negative pathogens, according to a randomized non-inferiority trial conducted in India. The findings are published in the Open Forum Infectious Diseases journal.CSE has activity against multidrug-resistant gram-negative pathogens.

The addition of sulbactam and disodium EDTA (a known metal chelator) have been shown to expand the in vitro activity of ceftriaxone against beta-lactamase-producing bacteria. CSE has been shown to demonstrate efficacy in animal infection models.

The primary objective of the trial conducted by Saransh Chaudhary, Venus Medicine Research Centre, Baddi, HP, India, and colleagues was to show the noninferiority of CSE to meropenem in the microbiologic modified intent-to-treat (mMITT) population at the test-of-cure visit, with a non-inferiority margin of 10 percentage points.

The phase 3 trial included 230 adults at 17 sites with a diagnosis of cUTI, including acute pyelonephritis. They were randomized in the ratio 1:1 to receive either intravenous CSE or intravenous meropenem.

The mMITT population consisted of 143 patients, with 74 receiving CSE and 69 receiving meropenem. Ceftriaxone non-susceptible pathogens were identified in 140 patients (97.9%), extended-spectrum beta-lactamase-producing pathogens in 119 (83.2%), and multidrug-resistant pathogens in 100 (69.9%).

Noninferiority of CRE to meropenem was demonstrated for both of the US Food and Drug Administration–defined co-primary endpoints.

Key findings include:

• Seventy-one of 74 patients (95.9%) in the CSE group showed symptomatic resolution at test-of-cure, compared with 62 of 69 patients (89.9%) in the meropenem group (treatment difference, 6 percentage points), and 70 of 74 patients (94.6%) in the CSE group showed both symptomatic resolution and microbiologic eradication at test-of-cure, compared with 60 of 69 (87.0%) patients (treatment difference, 7.6 percentage points)


• Non-inferiority was also demonstrated for the European Medicine Agency primary endpoint (microbiologic eradication at test-of-cure).


• The safety profile of CSE was consistent with that of ceftriaxone alone.

"The results support the use of CSE as a potential alternative to carbapenems in the treatment of patients with cUTI or acute pyelonephritis, including infections caused by extended-spectrum beta-lactamase-producing gram-negative bacteria," concluded the authors.

The bottom line is -- CSE can be used in place of carbapenems for the treatment of cUTI caused by multidrug-resistant gram-negative pathogens.

To read the complete study log on to https://doi.org/10.1093/ofid/ofz373