A sub-analysis of results from a multicenter, observational study shows that ceftolozane-tazobactam (C/T Zerbaxa, Merck) was well tolerated and effective in people living with cystic fibrosis (CF), even in those who may be allergic to penicillin. The findings offer a potential new antibiotic for this patient population (Open Forum Infect Dis 2024;11[8]:ofae391).
“While ceftolozane-tazobactam is not approved for use in people with cystic fibrosis exacerbations, it is definitely effective in patients both without lung transplantation and post-lung transplantation with gram-negative bacterial infection. It’s really a new tool for fighting cystic fibrosis exacerbations,” said Pierre-RÉgis Burgel, MD, PhD, the author of the study and a professor of respiratory medicine at the Paris-CitÉ University and HÔpital Cochin.
Cystic fibrosis disrupts the normal flow of salt water to the goblet cells, resulting in thick mucus and an environment that encourages bacterial growth, with Pseudomonas aeruginosa and Staphylococcus aureus being the most common organisms seen.
“The lung is not supposed to be a place where there are trillions of bacteria. The immune system is at a baseline—not really able to deal with it—and then on top of that, there are immune defects that are caused by cystic fibrosis itself,” said As Paul Planet, PhD, MD, an attending physician in the Division of Infectious Diseases at Children’s Hospital of Philadelphia.
C/T is a fixed-dose combination antibiotic that pairs a cephalosporin with a beta-lactamase inhibitor. It is approved in both the United States and European Union for urinary tract infections and is on the WHO Model Lists of Essential Medicines. Because of its high effectiveness and the ability of gram-negative bacteria to develop resistance, Dr. Planet uses it as a last resort.
“When I have multidrug-resistant bacteria and I won’t have any other options, that’s what I reach for,” he said.
The CONDUCT study was designed initially to evaluate how C/T was used, along with associated outcomes in French hospital settings. Researchers across 30 sites in France enrolled 260 patients between October 2018 and December 2019. Of those patients, 63 were living with CF and 12 had previously received a lung transplant, with a median age of 34 years.
“This is phenomenal because cystic fibrosis is a very rare disease in France,” Dr. Burgel said. “We have almost 68 million inhabitants, and we have 7,700 patients with cystic fibrosis, which means that is one ten-thousandth of the French population.”
The sub-analysis found that P. aeruginosa was the most frequently isolated pathogen, and 91.5% of the test strains were susceptible to C/T. The other isolated strains were Escherichia coli, Citrobacter koseri, Proteus mirabilis and Serratia marcescens, and were also susceptible to the antibiotic.
In addition, 56 of the 63 patients (88.9%) benefited from C/T, and the main reasons for stopping treatment were planned end of therapy and improvement in condition. Included in that majority were patients with historical beta-lactam hypersensitivity, an immune-mediated reaction to beta-lactam antibiotics such as penicillin that affects about 10% of the population. Only two patients experienced an adverse event that forced them to stop treatment.
“Approximately 70% of the people treated had a previous history of drug allergy to other treatments, so if you look at the safety profile of ceftolozane-tazobactam, it is very good. Most people were able to resume a full IV course of antibiotics, which means usually 14 days, with/without adverse effects,” Dr. Burgel said.
Dr. Planet also agrees that the study provides a rationale for using C/T in CF, especially after the bacteria become resistant to other drugs.
“There is a desperate need for new antibiotics in cystic fibrosis because there are a lot of kids who run out of options. I feel that we did not previously have good evidence base for using ceftolozane-tazobactam in cystic fibrosis, but now we can point to this study and say that it is safe and effective,” he said.
In the United States, C/T is indicated to treat adults (=18 years of age) with hospital-acquired and ventilator-associated pneumonia caused by susceptible organisms.
Dr. Burgel received institutional research funding from GSK and Vertex Pharmaceuticals, and advisory boards/lecture funding from AstraZeneca, Chiesi, GSK, Insmed, Merck, Vertex, Viatris and Zambon. Dr. Planet reported no relevant financial disclosures.
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This article is from the October 2024 print issue.