At the test-of-cure point, clinical response was similar in the combination and meropenem groups, both in clinical evidence (93% vs. 95%) and microbiological response (90% vs. 95%) At last follow-up, 100% of each group was clinically cured. The microbiological cure rates were 90% and 95%, respectively.
Success for complicated UTI
The complicated UTI study was likewise good news for CAZ-AVI, this time without metronidazole. This study included 95 children, mean age 6 years, in the same globally gathered cohorts. All of the children were hospitalized; they were randomized to CAZ-AVI at age-specific doses or cefepime, less than 2,000 mg/infusion for 72 hours. The test of cure was conducted at 8-15 days with a late follow-up at 20-36 days after the last infusion.
Most patients (83%) had acute pyelonephritis. About a quarter had at least one complicating factor, including obstructive uropathies due to functional or anatomic abnormalities of the urogenital tract, recurrent UTI, vesicoureteral reflex, or intermittent catheterization. About 20% of the group had a urological abnormality and 40% had been on a systemic antibiotic in the 2 weeks before study entry.
The most common infective organism was E. coli, (92%) followed by Klebsiella pneumoniae, Proteus mirabilis, and Enterobacter cloacae.
Again, about half of each group had at least one adverse event. Serious adverse events occurred in 12% of the combination group and 7% of the cefepime group. Three patients taking the combination discontinued because of the reaction.
There were eight serious events in the combination group, including abdominal pain, constipation, cystitis, acute pyelonephritis, UTI (not considered related to the study drug) viral infection, nervous system disorder, and nephrolithiasis. There were two serious adverse events in the cefepime group (cystitis and acute pyelonephritis).
Favorable clinical outcomes occurred in 89% of the combination group and 82.6% of the cefepime group. A microbiological cure was evident in 79.6% and 60.9%, respectively.
The combination was more effective than was cefepime at eradicating E. coli (79.6% vs. 59.1%), although no statistical analysis was presented. The other, less-frequent pathogens did not co-occur in both groups, so comparisons were not made. However, the combination eradicated P. mirabilis in both patients who had it, and 50% of K. pneumoniae infections.
A sustained clinical cure occurred in 81% of the combination group and 82.6% of the cefepime group.
Dr. Bradley said the University of California, San Diego, received fees from both Pfizer or AstraZeneca relating to the studies.
SOURCE: Bradley J et al. ECCMID 2018 oral abstracts O1123 and O1124.