Ceftolozane/tazobactam effective against complicated UTI in children

Ceftolozane and tazobactam (Zerbaxa; Merck Sharp) have similar safety and efficacy to meropenem (Merrem; Pfizer) in treating neonates and children with complicated urinary tract infection (cUTI), according to a recent study.

UTI presents in 7% of infants aged under 24 months and 7.8% of children aged under 19 years, leading to urinary symptoms and fever in these infants and children. In children with cUTI, risks of bacteremia, renal scarring‚ and chronic abdominal pain rise.

Among the rising need for antibacterial agents approved for adults to be available for neonatal and pediatric patients, ceftolozane and tazobactam have been approved for treating CUTI in adults, showing safety and efficacy in a phase 3 trial. Recently, ceftolozane and tazobactamwere approved for use in pediatric patients aged under 18 years in the United States.

While 1 pharmacokinetic study showed similar safety and efficacy of ceftolozane in children as in adults, data on the drug in this age group remains limited. To assess to the safety and efficacy of ceftolozane for treating cUTI in pediatric patients, investigators compared the drug to meropenem in a phase 2, randomized, double-blind study.

Participants included male and female children aged under 18 years with a birth over 32 weeks gestational age and 7 or more days postnatal. Participants also underwent intravenous (IV) antibacterial therapy for treating cUTI. 

A pretreatment baseline urine culture specimen was obtained for each patient within 48 hours prior to receiving the first dose. Clinical signs of cUTI were present in participants, with clinical diagnosis decided by the investigators.

Participants were randomized into a ceftolozane group or a meropenem group. In the ceftolozane group, patients aged 0 to under 12 years received 20 mg/kg ceftolozane and 10 mg/kg tazobactam, while those aged 12 to under 18 years received 1.0 g ceftolozane and 0.5 g tazobactam.

In the meropenem group, participants of all ages were given 20 mg/kg meropenem, with a maximum of 1 g per dose. For patients aged 14 days to under 3 months, dosing could reach 30 mg/kg at the investigator’s discretion.

Treatment lasted for 7 to 14 days with optional oral step-down therapy available after 3 days of treatment. Within 48 hours prior to the first dosage, a baseline urine sample was collected.

At end of treatment (EOT) visits, participants underwent clinical and microbiologic assessments. Adverse events (AEs) and changes in laboratory values and vital signs were measured as the primary endpoints of the study. 

Evaluation of AEs occurred from the first dose of treatment to the last evaluation performed. Rates of clinical success and per-participant microbiologic eradication were also measured as secondary endpoints.

There were 133 patients randomized 3:1 into a ceftolozane/tazobactam group and a meropenem group. Baseline characteristics were similar between the 2 groups. 

Common underlying issues with cUIT were recurring UIT, congenital abnormalities of the urogenital tract, and anatomic abnormalities of the urogenital tract. Most patients had monomicrobial infections.

IV treatment lasted 6.1 days on average for the ceftolozane/tazobactam group and 5.7 days on average for the meropenem group. In the ceftolozane/tazobactam group, about 70% patients transitioned to optional oral step-down therapy, compared to about 83% in the meropenem group.

Similar rates of AE incidence, serious AEs (SAEs), and discontinuing because of AEs were seen between the ceftolozane/tazobactam group and the meropenem group. AEs leading to death, drug-related SAEs‚ or discontinuations because of drug-related AEs or SAEs were not seen in either group.

At test of cure visits, ceftolozane/tazobactam had a clinical cure rate of 88.7%, while meropenem had an efficacy of 95.8%. At EOT visits, the clinical cure rate of ceftolozane/tazobactam was 94.4% and meropenem 100%.

Ceftolozane and tazobactam showed high rates of efficacy, along with a favorable safety profile. These results were similar to meropenem, showing ceftolozane and tazobactam are safe and effective in children with cUTI.

Reference

Roilides E, Ashour N, Bradley J, Johnson M, Lonchar J, Su F. Safety and efficacy of ceftolozane/tazobactam versus meropenem in neonates and children with complicated urinary tract infection, including pyelonephritis: aphase 2, randomized clinical trial. The Pediatric Infectious Disease Journal. 2023. doi:10.1097/INF.0000000000003832