A recent analysis of antibiotic treatments suggests that prothrombin time (PT) prolongation and coagulation disorders may be more likely to occur with cefoperazone-sulbactam compared with treatment using cefoperazone-tazobactam or ceftazidime. The results of the analysis were published in Expert Opinion on Drug Safety.

This retrospective cohort study was based on data obtained from electronic medical records from January 2011 through June 2014 at West China Hospital at Sichuan University. Data were analyzed for 23,242 patients who had been given cefoperazone-sulbactam (15,094 patients), cefoperazone-tazobactam (4283 patients), or ceftazidime (3519 patients).

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Prolongation of PT, decreases in platelet count, and other variables related to bleeding or coagulation were used to evaluate risks associated with cefoperazone-sulbactam use.

Platelet decreases were reported in 15.7% of patients who received cefoperazone-sulbactam. Overall, 9.2% of patients on cefoperazone-sulbactam experienced coagulation disorders, with 6.7% having prolongation of activated partial thromboplastin time, 5.3% having PT prolongation, and 4.2% having bleeding.


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In propensity-score matching analyses, cefoperazone-sulbactam was significantly associated with greater odds of PT prolongation (adjusted odds ratio [aOR], 2.26; 95% CI, 1.61-3.18), coagulation disorders (aOR, 1.81; 95% CI, 1.43-2.30), and decreased platelets (aOR, 1.46; 95% CI, 1.25-1.72) compared with ceftazidime. The odds of PT prolongation were approximately 2-fold higher with cefoperazone-sulbactam than with ceftazidime. Bleeding risks did not significantly differ between these treatments.

Compared with cefoperazone-tazobactam, cefoperazone-sulbactam showed significantly higher odds of PT prolongation (aOR, 1.65; 95% CI, 1.21-2.25) and coagulation disorders (aOR, 1.63; 95% CI, 1.30-2.06) but similar odds of bleeding (aOR, 1.08; 95% CI, 0.85-1.37) and decreased platelets (aOR, 0.89; 95% CI, 0.78-1.02). Decreased platelets occurred in 18.8% of patients on cefoperazone-tazobactam.

“Clinicians should be aware that cefoperazone-containing antibiotics may increase the risk [for] coagulation disorders and should monitor patients receiving these drugs for these adverse events,” the researchers noted.

Reference

1.     Wang W, Liu Y, Yu C, et al. Cefoperazone-sulbactam and risk of coagulation disorders or bleeding: a retrospective cohort study [published online January 8, 2020]. Expert Opin Drug Saf. doi:10.1080/14740338.2020.1713090