Ceftolozane-Tazobactam Safe for Acute Bacterial Infections

Ceftolozane-tazobactam could be a useful treatment for acute bacterial infections, but also might increase the risk of Clostridioides difficile infections (CDI).

A team, led by Li-Ting Wang, Department of Internal Medicine, Chi-Mei Hospital, assessed the clinical safety of ceftolozane-tazobactam for treating acute bacterial infections for adults.

Ceftolozane-tazobactam is a combination of the broad-spectrum cephalosporin and a ß-lactamase inhibitor, in which ceftolozane, an oxyimino-aminothiazolyl cephalosporin, is structurally similar to ceftazidime and tazobactam, a β-lactam sulfone, is a potent β-lactamase inhibitor of most common class A and C β-lactamases

The Study

In the study, the researchers searchers various databases from inception until May 2020 for randomized controlled trials evaluating the risk of adverse events for ceftolozane-tazobactam and comparative treatments for acute bacterial infections in adult patients.

The team identified 4 trials that fit the criteria involving 2924 total patients, 1475 of which were treated with ceftolozane-tazobactam and 1449 patients in the control group.

The investigators sought primary outcomes of the risk of adverse events, including treatment-emergent adverse events (TEAE), treatment-related adverse events, serious adverse events, discontinuation of the study drug due to an adverse events, and all-cause mortality.

Adverse Events

The overall rate of treatment-emergent adverse events (TEAE) was 51.3% (n = 748) in the treatment group, compared to 49.9% (n = 714) in the placebo control group (OR, 1.06; 95% CI, 0.91-1.25; I² = 0%).

There was also no difference observed in the risk of serious adverse events between the 2 groups (OR, 1.22l 95% CI, 0.93-1.61; I² = 15.5%). This was also true for the risk of discontinuing ceftolozane-tazobactam because of adverse events (OR, 0.85; 95% CI, 0.55-1.33; I² = 0%).

Another positive for the study drug was that the rate of all-cause mortality did not significantly differ between the 2 groups (OR, 1.11; 95% CI, 0.82-1.50; I² = 0%).

However, there was 1 troubling trend in regard to Clostridiodes difficile colitis.

The researchers found ceftolozane-tazobactam treatment was linked to a significantly higher risk of all-cause mortality (0.72%; n = 10) compared to the control group (0.14%; n = 2) (OR, 3.84; 95% CI, 1.23-11.97; I² = 0%).

“Ceftolozane-tazobactam treatment is as tolerable as comparative treatment options for acute bacterial infections in adult patients, however it has an increased risk of C. difficile infection,” the authors wrote. “As a novel broad-spectrum antibiotic, ceftolozane-tazobactam could be a safe therapeutic option for use in common clinical practice.”

The Need for Antimicrobial Resistance Plans

Countries have begun to craft national plans optimizing and narrowing the use of antibiotics without requiring substantial resources could be effective in the fight against antimicrobial resistance.

For example, Japan has set goals of reducing the use of oral cephalosporins, quinolones, and macrolides per day per 1000 inhabitants in 2020 by 50% from the levels found in 2013.

The Japanese government created a national plan in 2016 after finding that approximately 90% of antimicrobials consumed in Japan are oral medications, which are prescribed to patients over an extensive age range.

The study, “The safety of ceftolozane-tazobactam for the treatment of acute bacterial infections: a systemic review and meta-analysis,” was published online by Therapeutic Advances in Drug Safety.