In the Journals

Phase 2 study shows Avycaz is safe, effective in kids with cUTIs

Photo of John Bradley
John S. Bradley

Children with complicated UTIs were safely and effectively treated with the combination antibiotic Avycaz compared with cefepime, according to findings from a phase 2 study published in The Pediatric Infectious Disease Journal.

“We are always looking for better therapy for complicated UTIs,” study researcher John S. Bradley, MD, director of the division of infectious diseases at Rady Children’s Hospital-San Diego, told Infectious Diseases in Children.

Avycaz (ceftazidime-avibactam, Forest Pharmaceuticals) was approved in 2015 for the treatment of adults with complicated urinary tract infections (cUTIs), including kidney infections. The drug is also indicated for complicated intra-abdominal infections (cIAIs) and nosocomial pneumonia. This year, the label was expanded to include pediatric patients aged 3 months and older with cUTIs and cIAIs.

“The most common bacterial pathogen for complicated UTI is Escherichia coli, and about 50% of community isolates are resistant to ampicillin, which was commonly used as first-line therapy 30 years ago, with ceftriaxone subsequently being the most active antibiotic until the emergence of extended spectrum beta-lactamases,” Bradley explained. “Now, we are seeing the slow emergence of E. coli and Klebsiella that are resistant to meropenem and that are often also resistant to ciprofloxacin and gentamicin. We need therapy for these emerging strains for both hospitalized children who may develop nosocomial infections and for the inevitable spread of these multidrug-resistant pathogens to the community.”

In the phase 2 study, children aged 3 months to 18 years with cUTIs were randomly assigned to receive IV ceftazidime-avibactam (n = 67) or cefepime (n = 28) for at least 72 hours. Then, the children had the option to switch to an oral regimen, which resulted in a treatment duration that ranged between 7 and 14 days.

The predominant uropathogen at baseline was Escherichia coli (92.2%), according to the researchers. The rate of adverse events associated with ceftazidime-avibactam and cefepime were comparable (53.7% vs. 53.6%). Serious adverse events occurred in 11.9% of the ceftazidime-avibactam group and 7.1% of the cefepime group. Only one serious event — which occurred in the ceftazidime-avibactam group — was deemed drug related.

In the microbiological intent-to-treat analysis, favorable clinical response rates exceeded 95% in both groups at the end of IV treatment and remained elevated at the test-of-cure (88.9% for ceftazidime-avibactam and 82.6% for cefepime). The favorable microbiological response rate at the test-of-cure was 79.6% for ceftazidime-avibactam and 60.9% for cefepime.

“We knew that ceftazidime was safe, but this study documented that avibactam, a new beta-lactamase inhibitor with a unique chemical structure, in combination with ceftazidime was as safe as cefepime,” he said. “We are not planning on using this antibiotic for all kids with kidney infections, but it is quite reassuring to know that we now have an FDA-approved antibiotic for complicated UTI in children in case we need it.” – by Katherine Bortz

Disclosures: Bradley reports that his institution received funds from AstraZeneca and Pfizer to conduct and consult on this study. He reports that he received no funds for the creation of the manuscript. Please see the study for all other authors' relevant financial disclosures.

Photo of John Bradley
John S. Bradley

Children with complicated UTIs were safely and effectively treated with the combination antibiotic Avycaz compared with cefepime, according to findings from a phase 2 study published in The Pediatric Infectious Disease Journal.

“We are always looking for better therapy for complicated UTIs,” study researcher John S. Bradley, MD, director of the division of infectious diseases at Rady Children’s Hospital-San Diego, told Infectious Diseases in Children.

Avycaz (ceftazidime-avibactam, Forest Pharmaceuticals) was approved in 2015 for the treatment of adults with complicated urinary tract infections (cUTIs), including kidney infections. The drug is also indicated for complicated intra-abdominal infections (cIAIs) and nosocomial pneumonia. This year, the label was expanded to include pediatric patients aged 3 months and older with cUTIs and cIAIs.

“The most common bacterial pathogen for complicated UTI is Escherichia coli, and about 50% of community isolates are resistant to ampicillin, which was commonly used as first-line therapy 30 years ago, with ceftriaxone subsequently being the most active antibiotic until the emergence of extended spectrum beta-lactamases,” Bradley explained. “Now, we are seeing the slow emergence of E. coli and Klebsiella that are resistant to meropenem and that are often also resistant to ciprofloxacin and gentamicin. We need therapy for these emerging strains for both hospitalized children who may develop nosocomial infections and for the inevitable spread of these multidrug-resistant pathogens to the community.”

In the phase 2 study, children aged 3 months to 18 years with cUTIs were randomly assigned to receive IV ceftazidime-avibactam (n = 67) or cefepime (n = 28) for at least 72 hours. Then, the children had the option to switch to an oral regimen, which resulted in a treatment duration that ranged between 7 and 14 days.

The predominant uropathogen at baseline was Escherichia coli (92.2%), according to the researchers. The rate of adverse events associated with ceftazidime-avibactam and cefepime were comparable (53.7% vs. 53.6%). Serious adverse events occurred in 11.9% of the ceftazidime-avibactam group and 7.1% of the cefepime group. Only one serious event — which occurred in the ceftazidime-avibactam group — was deemed drug related.

In the microbiological intent-to-treat analysis, favorable clinical response rates exceeded 95% in both groups at the end of IV treatment and remained elevated at the test-of-cure (88.9% for ceftazidime-avibactam and 82.6% for cefepime). The favorable microbiological response rate at the test-of-cure was 79.6% for ceftazidime-avibactam and 60.9% for cefepime.

“We knew that ceftazidime was safe, but this study documented that avibactam, a new beta-lactamase inhibitor with a unique chemical structure, in combination with ceftazidime was as safe as cefepime,” he said. “We are not planning on using this antibiotic for all kids with kidney infections, but it is quite reassuring to know that we now have an FDA-approved antibiotic for complicated UTI in children in case we need it.” – by Katherine Bortz

Disclosures: Bradley reports that his institution received funds from AstraZeneca and Pfizer to conduct and consult on this study. He reports that he received no funds for the creation of the manuscript. Please see the study for all other authors' relevant financial disclosures.