Ceftolozane/tazobactam potential new treatment for serious nosocomial pneumonia: Lancet

Delhi: Ceftolozane/tazobactam (Zerbaxa) is well tolerated and efficient for the treatment of gram-negative nosocomial pneumonia in mechanically ventilated patients, a high-risk, critically ill population, shows a recent study. The antibiotic was shown to be non-inferior to meropenem in the treatment of this serious condition in this phase 3 trial published in The Lancet Infectious Diseases journal.

Zerbaxa is antibiotic approved in 2014 for the treatment of urinary tract and intra-abdominal infections. Meropenem (Merrem) is a broad-spectrum antibiotic used for the treatment of a variety of bacterial infections.

Hospital-acquired pneumonia (HAP), or nosocomial pneumonia is defined as pneumonia that occurs 48 hours or more after hospital admission and not incubating at the admission time. HAP due to antimicrobial-resistant pathogens is associated with high mortality.

Marin H Kollef, Washington University School of Medicine, St Louis, MO, USA, and colleagues assessed the efficacy and safety of the combination antibacterial drug ceftolozane–tazobactam versus meropenem for treatment of Gram-negative nosocomial pneumonia.

The randomized, controlled trial was conducted across 263 hospitals in 34 countries. It involved 726 patients with severe nosocomial pneumonia: 71% had ventilator-associated pneumonia, and 92% required intensive care. 362 received 3 grams of ceftolozane–tazobactam and 364 received 1 gram meropenem. Both the antibiotics were administered every 8 hours for 8 to 14 days.

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Key findings include:

• At 28 days, 87 (24·0%) patients in the ceftolozane–tazobactam group and 92 (25·3%) in the meropenem group had died.


• At the test-of-cure visit 197 (54%) patients in the ceftolozane–tazobactam group and 194 (53%) in the meropenem group were clinically cured.


• Ceftolozane–tazobactam was thus non-inferior to meropenem in terms of both 28-day all-cause mortality and clinical cure at the test of cure.


• Treatment-related adverse events occurred in 38 (11%) of 361 patients in the ceftolozane–tazobactam group and 27 (8%) of 359 in the meropenem group.


• Eight (2%) patients in the ceftolozane–tazobactam group and two (1%) in the meropenem group had serious treatment-related adverse events.


• There were no treatment-related deaths.

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"High-dose ceftolozane-tazobactam can be used to treat nosocomial pneumonia caused by P aeruginosa (including multidrug-resistant strains), Enterobacteriaceae (including producers of extended-spectrum β-lactamases), and other Gram-negative pathogens," wrote the authors.

"Ceftolozane–tazobactam is a combination treatment comprising a β-lactamase inhibitor (tazobactam), which can inhibit common class A extended-spectrum β-lactamases (ESBLs), and a novel cephalosporin (ceftolozane), which has certain characteristics that make it active against Pseudomonas aeruginosa. These characteristics include a high affinity for some penicillin-binding proteins, stability in the presence of chromosomal AmpC-β-lactamases, and robustness against OprD deficiency and efflux systems," experts from the United States and Brazil point out in an accompanying editorial.

"These features render the combination an appealing option for some multidrug-resistant Gram-negative bacteria. Ceftolozane–tazobactam has been approved for the treatment of complicated urinary tract and intra-abdominal infections. Use of ceftolozane–tazobactam to treat nosocomial pneumonia caused by multidrug-resistant P aeruginosa has been reported in retrospective series, but data from a randomised clinical trial are awaited."

To read the complete study log on to https://doi.org/10.1016/S1473-3099(19)30403-7