Gram-Negative Infections Successfully Treated with Ceftazidime-Avibactam

Ceftazidime-avibactam was safe and effective for patients with a variety of gram-negative bacterial infections, according to an abstract planned for presentation at the European Congress of Clinical Microbiology and Infectious Diseases (ECCMID) 2020 Meeting this year.

Investigators from the US, Germany, Spain, and the UK reviewed 5 randomized, controlled, multi-center phase 3 trials in adults with complicated intra-abdominal infection (cIAI), complicated urinary tract infection (cUTI), hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) — all infections caused by ceftazidime non-susceptible and multidrug-resistant gram-negative bacteria.

According to the US Centers for Disease Control and Prevention (CDC), Gram-negative bacteria can cause infections, are resistant to multiple drugs, and are increasingly resistant to most available antibiotics. Additionally, they can pass along genetic material that can allow other bacteria to also become resistant to drugs. The agency believes their “aggressive recommendations” can prevent the spread of gram-negatives.

In each of the trials the study authors reviewed, patients were randomized to receive either intravenous ceftazidime-avibactam or comparators for between 5-21 days. The treatment durations varied in each of the studies. In a majority of the studies, the comparators were carbapenems; the patients with cIAI were treated with ceftazidime-avibactam plus metronidazole.

The investigators measured efficacy using clinical and microbiological responses at a test-of-cure visit, which was timed according to the protocols of each of the 5 studies. They examined the safety outcomes as well, including adverse events and clinical lab assessments through the last patient visit. If a patient received 1 or more dose of study treatment, they were included in the analysis, the study authors explained.

All 5 studies contained a total population of 3172 patients, of which 1855 received ceftazidime-avibactam and 1857 received comparators. The study authors also said 54 patients were in the gram-negative extended microbiologically evaluable (GNeME) subset and treated with ceftazidime-avibactam, while 47 GNeME patients received comparators. The most common primary diagnoses (acute pyelonephritis and VAP) and the most frequently isolated pathogens (Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa, among the top 3) were consistent across the studies, investigators wrote.

Patients treated with ceftazidime-avibactam had a “generally similar” microbiological response rates at test-of-cure visit to those who received comparators. For example:

• 9 of 11 patients treated with ceftazidimeavibactam plus metronidazole for cIAI reached a clinical cure while 9 out of 10 on the comparator did.
• 28 of 28 cUTI patients reached clinical cure, while 25 of 29 given the comparator did.
• 10 of 15 HAP and VAP patients reached clinical cure, while 5 of 8 given the comparator did.
• 43 of 54 patients treated with ceftazidimeavibactam and metronidazole were found to have a favorable microbiological response compared to 32 of 47 patients treated with the comparator.

The investigators also found a favorable microbiological response for those patients with ceftazidime-susceptible isolates. They wrote that about half of the patients treated with ceftazidime-avibactam and about half of those treated with comparators were treated successfully.

Both groups had similar adverse events and they were consistent with the known safety profile of ceftazidime-avibactam, investigators.

The study was sponsored by Pfizer.