Ceftazidime–avibactam well tolerated in children with complicated UTI

Stephen Padilla
27 Aug 2019
Ceftazidime–avibactam well tolerated in children with complicated UTI

A phase II randomized, controlled trial has recently reaffirmed the safety profile of ceftazidime–avibactam in children with complicated urinary tract infection (cUTI), which is consistent with that of adults and of ceftazidime monotherapy.

Ceftazidime–avibactam also “appeared effective in the treatment of pediatric cUTI caused by Gram-negative pathogens, with favourable clinical and microbiologic response rates observed against the predominant cUTI pathogen, including ceftazidime-nonsusceptible isolates,” the researchers said.

“Ceftazidime–avibactam may … offer physicians a valuable treatment option in the initial treatment of children with cUTI caused by susceptible pathogens in an era of increasing prevalence of multidrug-resistant Gram-negative pathogens,” the researchers said.

Children aged ≥3 months to <18 years with cUTI were randomized 3:1 to receive intravenous (IV) ceftazidime–avibactam or cefepime for ≥72 hours, with subsequent optional oral switch, for 7–14 days. Safety assessment was the primary objective, while secondary objectives included descriptive efficacy and pharmacokinetics.

A blinded observer ascertained adverse event (AE) causality and clinical outcomes up to the late follow-up visit at 20–36 days following the last dose of IV/oral therapy.

Of the 95 children who received ≥1 dose of IV treatment, 67 were given ceftazidime–avibactam and 28 cefepime. Escherichia coli was the predominant (92.2 percent) baseline Gram-negative uropathogen. [Pediatr Infect Dis J 2019;38:920-928]

AEs occurred in 53.7 percent of patients in the ceftazidime–avibactam group and 53.6 percent in the cefepime group. Serious AEs occurred in 11.9 percent and 7.1 percent of patients, respectively, of which one was considered drug-related.

Microbiologic intent-to-treat analysis showed favourable clinical response rates >95 percent for both groups at end-of-IV, which was sustained in 88.9 percent of patients in the ceftazidime–avibactam group and in 82.6 percent in the cefepime group at test-of-cure. Favourable per-patient microbiologic response at test-of-cure was 79.6 percent and 60.9 percent, respectively.

“While this study was not powered for inferential statistical comparisons between treatment groups, the high clinical/microbiologic response rates observed were consistent with studies of ceftazidime–avibactam conducted in adult patients with cUTI,” the researchers said. [Clin Infect Dis 2016;63:754-762; Lancet Infect Dis 2016;16:661-673; Curr Med Res Opin 2012;28:1921-1931]

The finding regarding E. coli as the most common pathogen was consistent with expectations for patients with cUTI, they added. [J Pediatr Urol 2018;14:176.e1-176.e5; Front Cell Infect Microbiol 2015;5:45; Int J Pediatr 2014;2014:126142]

Furthermore, there was an 86.5-percent favourable per-pathogen microbiologic response at test-of-cure for ceftazidime–avibactam-treated patients with an E. coli isolate at baseline, including those with ceftazidime- and cefepime-nonsusceptible pathogens. These findings are consistent with those from adult patients with cUTI. [Clin Infect Dis 2016;63:754-776; Lancet Infect Dis 2016;16:661-673]

“Of note, there were no cases of Pseudomonas in the study,” the researchers said. “This suggests that the infections were predominantly community acquired in healthy individuals who had not received extensive antibiotic pretreatment.” [J Urol 2012;187:260-264]

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