Ceftolozane/tazobactam on par with meropenem in children with complicated UTI

Combination therapy with ceftolozane and tazobactam demonstrates a favourable safety profile in children with complicated urinary tract infection (cUTI) similar to that of meropenem and to the previously reported safety profile in adults with cUTI, a study has shown.

In addition, treatment with ceftolozane/tazobactam delivers high rates of clinical cure as well as microbiologic eradication.

“Thus, ceftolozane/tazobactam is a safe and effective new treatment option active against antimicrobial-resistant Gram-negative bacteria for children, including neonates and young infants with cUTI,” the researchers said.

This phase II study compared ceftolozane/tazobactam with meropenem for the treatment of cUTI in children from birth to <18 years of age. Safety and tolerability were the primary objectives, while secondary endpoints included clinical cure and per-participant microbiologic response rates at end of treatment (EOT) and test of cure (TOC) visits.

Ninety-five children were included in the microbiologic modified intent-to-treat population, of whom 71 received ceftolozane/tazobactam and 24 meropenem. [Pediatr Infect Dis J 2023;42:292-298]

Pyelonephritis (ceftolozane/tazobactam, 84.5 percent; meropenem, 79.2 percent) and Escherichia coli (ceftolozane/tazobactam, 74.6 percent; meropenem, 87.5 percent) were the most common diagnosis and pathogen, respectively. Moreover, 5.7 percent (ceftolozane/tazobactam) and 4.8 percent (meropenem) of E. coli isolates were extended-spectrum β-lactamase-producers.

Adverse events occurred at a similar rate between treatment groups (any: ceftolozane/tazobactam, 59.0 percent vs meropenem, 60.6 percent; drug-related: 14.0 percent vs 15.2 percent; serious: 3.0 percent vs 6.1 percent).

No new safety concerns arose with ceftolozane/tazobactam therapy. Likewise, these findings were consistent with previously reported results about the safety of ceftolozane/tazobactam in adults. [Lancet 2015;385:1949-1956]

Cure rates

Furthermore, clinical cure rates for ceftolozane/tazobactam and meropenem were 94.4 percent and 100 percent at EOT and 88.7 percent and 95.8 percent at TOC, respectively. The corresponding microbiologic eradication rates were 93.0 percent and 95.8 percent at EOT and 84.5 percent and 87.5 percent at TOC.

“While this study was not powered for comparison of between-group efficacy outcomes, the high clinical and microbiologic response rates observed were consistent with studies of ceftolozane/tazobactam in adults with cUTI,” the researchers said. [Lancet 2015;385:1949-1956; J Antimicrob Chemother 2017;72:268-272; J Antimicrob Chemother 2016;71:2014-2021]

The current study was limited by its small sample size, which is common in paediatric studies. However, it included not only adolescents and children, but also participants aged 3 months to 2 years and those  from birth to 3 months of age.

Ceftolozane/tazobactam, a cephalosporin-β-lactamase inhibitor combination, is an approved treatment for cUTI, including pyelonephritis, complicated intra-abdominal infection‚ and nosocomial pneumonia in adults. [Clin Infect Dis 2016;63:234-241]

UTI commonly occurs in the paediatric population, with prevalence rates of 7.0 percent among febrile infants ≤24 months of age and 7.8 percent among those aged <19 years with urinary symptoms or fever. [Pediatr Infect Dis J 2008;27:302-308]

Children with cUTI are more likely to have complications such as bacteraemia, renal scarring, and chronic abdominal pain. [J Pediatr Gastroenterol Nutr 2015;60:214-216; Am J Emerg Med 2017;35:36-38; Pediatrics 2010;126:1084-1091]