OBJECTIVES: Data from adverse drug reactions case reports have led to concerns about the safety profile of cefoperazone/sulbactam. We conducted a retrospective database study to investigate the association between cefoperazone/sulbactam and the risk of coagulation disorders, thrombocytopenia and bleeding.

METHODS: A cohort of patients who received either cefoperazone/sulbactam, cefoperazone/tazobactam or ceftazidime were generated from West China Hospital from 1 January 2011 and 30 June 2014. Information including demographic characteristics, the doctor's advice, laboratory test, surgical and diagnostic information were extracted. We used propensity score matching to assess whether cefoperazone/sulbactam increased the risk of coagulation disorders and bleeding, and multivariate regression to evaluating the potential influencing factors.

RESULTS: Our cohort included 25297 patients, of whom 16574 patients received cefoperazone/sulbactam, 4550 received cefoperazone/tazobactam, and 3816 received ceftazidime. The proportion of prolonged PT, thrombocytopenia and bleeding among patients recieved cefoperazone/sulbactam were 5.6%, 16.8% and 4.4%, respectively. Results from propensity score matching showed, compared to cefoperazone/tazobactam, the risk of prolonged PT, coagulation disorders (prolonged PT, APTT or TT) and bleeding was increased (P< 0.05). Compared to ceftazidime, cefoperazone/sulbactam was associated with increased risk of prolonged PT, coagulation disorders and thrombocytopenia (P< 0.05). Multiple logistic analysis showed malignant tumor (aOR 1.29, 95% CI 1.08-1.54), hepatic disease (aOR 1.73, 95% CI 1.43-2.09), CKD (aOR 3.42, 95% CI 2.86-4.08), anticoagulant drugs (aOR 3.34, 95% CI 2.86-4.08), discharged from surgery (aOR 2.20, 95% CI 1.83-2.65) and ICU (aOR 4.33, 95% CI 3.53-5.30), daily dose 3-6g (aOR 1.38, 95% CI 1.11-1.71) and ≥ 6g (aOR 1.47, 95% CI 1.07-2.02) increased the risk of prolonged PT.

CONCLUSIONS: Compared to ceftazidime and cefoperazone/tazobactam, cefoperazone/sulbactam may associated with increased risk of coagulation disorders, which indicated that sulbactam may have effect on hypoprothrombinaemia. Combined with liver and kidney disease, anticoagulant drugs, daily dose ≥3g, discharged from surgery and ICU may increase the risk of developing hypoprothrombinaemia.