Ceftazidime-avibactam safe, effective in babies with bacterial infections

Treatment with single or multiple doses of ceftazidime-avibactam (CAZ-AVI) results in favourable clinical outcomes and is well tolerated in hospitalized neonates and young infants with suspected or confirmed bacterial infections, according to a phase IIa study presented at IDWeek 2023.

In addition, treatment-emergent adverse events (TEAEs) are mostly mild or moderate in severity, with no new safety issues occurring. Furthermore, plasma concentrations of CAZ and AVI following single and multiple doses are comparable to those seen in previous paediatric studies.

The current phase IIa study was conducted in two parts at 39 sites in nine countries to assess the pharmacokinetics (PK), safety, and efficacy of CAZ-AVI in hospitalized neonates and young infants (from 26 weeks gestation up to 3 months of age) with suspected or confirmed infections due to Gram-negative pathogens requiring intravenous (IV) antibiotic treatment.

Patients received either single (part A) or multiple doses (part B) of IV CAZ-AVI. The researchers then evaluated the PK, safety, and efficacy of the said treatment. They used descriptive methods to summarize all data. Of note, the study was not designed for inferential statistical analysis.

Forty-six patients (aged 2 to 89 days and 31 to ≥37 weeks gestation) received CAZ-AVI. The most common primary infections diagnosed were sepsis (39.1 percent) and urinary tract infection (15.2 percent). [IDWeek 2023, abstract 2890]

In part B, most of the baseline pathogens isolated were Escherichia coli (60 percent), and the median duration of CAZ-AVI treatment was 7.0 days.

Adverse events

Fifty percent of the patients (n=23) developed TEAEs, and most were either mild or moderate in severity. Eight serious AEs and two deaths occurred. The deaths were caused by necrotizing enterocolitis in one and septic shock in the other, both of which were not related to the antibiotic treatment.

“Half the patients had TEAEs. However, they were pretty much all mild or moderate, and none were considered treatment-related in the multidose part B,” according to presenting author Richard England from Pfizer, Inc., Groton, Connecticut, US.

“In part A, there was one treatment-related oxygen desaturation that occurred half an hour after finishing the infusion. The investigators felt that might be related,” he said.

Notably, neonates and young infants administered CAZ-AVI demonstrated favourable clinical outcomes and microbiological response at test of cure.

“Plasma concentrations after single and multiple doses are very similar to what we’ve seen in the other paediatric studies,” England said.

“Single and multiple doses of CAZ-AVI were safe, were well tolerated in young infants and neonates. The majority of adverse events were mild or moderate and considered unrelated [to CAZ-AVI by the investigators], and there were no new safety concerns [identified], he added.”

“Antibiotic resistance in paediatrics, including neonates and infants, is increasing globally. CAZ-AVI is approved for use in paediatric patients (age ≥ 3 months) with Gram-negative bacterial infections,” according to the investigators.