Risk Factors for Cefoperazone/Sulbactam-Induced Coagulation Disorder

Abstract

Purpose

Cefoperazone/sulbactam is a β-lactam/β-lactamase inhibitor combination effective against intra-abdominal, urinary tract, and respiratory infections. Although some studies have suggested that cefoperazone/sulbactam is associated with coagulation disorders, it remains debatable whether the combination of cefoperazone/sulbactam with tigecycline or valproic acid increases the risk of bleeding, as both drugs can lead to coagulation disorders. This study aimed to explore the risk factors of cefoperazone/sulbactam-induced coagulopathy.

Patients and Methods

This was a single-center, retrospective, nested case-control study. The sample groups were derived from individuals registered at the Department of Neurosurgery, Shanxi Provincial People’s Hospital. Propensity score matching (PSM) was used to adjust for demographic data. Conditional logistic regression was used to estimate the matched odds ratios representing the odds of cefoperazone/sulbactam-induced coagulopathy (CIC), and a receiver operating characteristic curve was used to determine the optimal cut-off conditions.

Results

After PSM, 155 and 56 patients were included in the control and case groups, respectively. Multivariate analysis revealed that advanced age, treatment duration, and total dose were independent risk factors of cefoperazone/sulbactam-induced coagulation disorders. Concomitant use of vitamin K was an independent protective factor against CIC. The optimal cut-off for the length of treatment was 5 d, and the cut-off for the total dose was 48 g.

Conclusion

Tigecycline and valproic acid were not associated with CIC. Advanced age and long treatment duration are risk factors for CIC. Supplementation with vitamin K during cefoperazone/sulbactam treatment was associated with a reduced risk.

Keywords:

• cefoperazone/sulbactam
• coagulopathy
• tigecycline
• valproic acid

Abbreviations

APTT, activated partial thromboplastin time; AUC, area under the curve; CI, confidence interval; CIC, cefoperazone/sulbactam-induced coagulopathy; CRAB, carbapenem-resistant Acinetobacter baumannii; g, gram; ICU, intensive care unit; IQR, interquartile range; INR, international normalized ratio; PSM, propensity score matching; PT, prothrombin time; ROC, receiver operating characteristic; VPA, valproic acid.

Data Sharing Statement

The data that support the findings of this study are available from the corresponding author (Professor Jinlin Guo) upon reasonable request.

Ethical Approval Statement

The study protocol was approved by the Ethics Committee of Shanxi Provincial People’s Hospital (201936) and was conducted following the legal requirements and tenets of the Declaration of Helsinki and its subsequent amendments. Written informed consent was waived by the Ethics Committee of Shanxi Provincial People’s Hospital because this was a retrospective study, and the clinical data collected were only for the purpose of scientific research, with no additional burden on patients.

Disclosure

The authors report no conflicts of interest in this work.