Evaluating the Risk of Coagulopathy in Cephalosporins with Different Side Chains: A Propensity Score-Weighted Study

Background and Objectives: Cephalosporins containing N-hydroxyethyltetrazolethiol (HTT) or N-methylthiotetrazole (NMTT) side chains, such as flomoxef and cefoperazone, have been linked to coagulation abnormalities. Cefazolin, which contains an N-methylthiadiazolethiol (MTD) side chain, may also interfere with vitamin K metabolism. However, comparative clinical evidence remains limited. This study evaluated the associations between selected cephalosporins and coagulopathy risk. Materials and Methods: We conducted a retrospective cohort study using a comprehensive clinical database. Patients receiving cefazolin, flomoxef, or cefoperazone-sulbactam were compared with those receiving reference antibiotics. Coagulopathy was defined as either a ≥25% increase in prothrombin time (PT) from baseline or a PT exceeding the upper limit of normal by more than 3 s within three days before or after antibiotic cessation. Inverse probability of treatment weighting based on propensity scores was applied. Weighted logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Results: After weighting, no significant association with coagulopathy was observed for cefazolin (OR, 1.05; 95% CI, 0.86-1.29), flomoxef (OR, 1.00; 95% CI, 0.77-1.29), or cefoperazone-sulbactam (OR, 0.88; 95% CI, 0.67-1.15). Although international normalized ratio >1.2 was more frequent with cefoperazone-sulbactam, the risk of bleeding events showed a marginal increase compared with the reference group (OR, 1.06; 95% CI, 1.00-1.11). Conclusions: Cefoperazone-sulbactam was associated with more frequent laboratory INR elevation and a borderline increase in bleeding risk. Given the observational design, these findings should be interpreted cautiously, and close clinical monitoring may be considered when prescribing cefoperazone-sulbactam.