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Risk of bleeding and hypoprothrombinaemia associated with NMTT side chain antibiotics: using cefoperazone as a test
B L Strom1, R Schinnar, G A Gibson
1Center for Clinical Epidemiology and Biostatistics and Department of Biostatistics and Epidemiology, University of Pennsylvania School of Medicine, Philadelphia, 19104-6021, USA. Bstrom@cceb.med.upenn.edu
Abstract:
A retrospective cohort study was performed to determine the incidence of hypoprothrombinaemia and bleeding in patients receiving cefoperazone, a third-generation cephalosporin that contains an NMTT side chain. 374 patients receiving cefoperazone from February 1983 to March 1986 at a teaching hospital in Philadelphia were compared with 497 patients receiving either ceftizoxime or cefotaxime during the same period, and with 476 patients receiving ceftazidime from April 1985 to December 1987. Adverse events (any bleeding episodes, decrease in haemoglobin, prolongation of prothrombin time (PT), and prolongation of partial thromboplastin times (PTT)) were evaluated, if occurring during the period from the start of cephalosporin therapy, or the start of therapy with one of the two control drugs, for 14 days after the last date of the first course of therapy were recorded. An increased risk of hypoprothrombinaemia was associated with the use of cefoperazone: the prothrombin time was prolonged by 5 s or more in 12.3% of patients receiving cefoperazone vs. 5.8% of patients receiving ceftizoxime or cefotaxime, and vs. 5.8% receiving ceftazidime; the adjusted odds ratios (95% CIs) were 3.6 (1.7-7.4) and 3.8 (1.8-7.8), respectively, and these increased at higher doses of cephalosporin. No protection was apparent from the administration of vitamin K prior to or during the course of cephalosporin. No overall increased risks were observed for bleeding (adjusted odds ratios (95% CIs) were 1.1 (0.8-1.4) vs. ceftizoxime or cefotaxime, and 0.9 (0.6-1.2) vs. ceftazidime), decrease in haemoglobin, or increased partial thromboplastin time. In subgroup analyses, increased risks of bleeding were observed with high dose cefoperazone use [2.8 (1.5-5.5) vs. ceftizoxime or cefotaxime, and 2.3 (1.1-4.6) vs. ceftazidime]. Patients receiving NMTT side chain antibiotics should be monitored for hypoprothrombinaemia, but any increase in bleeding is likely to be small, and prophylactic vitamin K is probably not warranted.
Insights
Cefoperazone, an NMTT side chain cephalosporin, increases hypoprothrombinaemia risk. While bleeding risk is not significantly elevated overall, high doses of cefoperazone may increase bleeding. Monitor patients for hypoprothrombinaemia, but prophylactic vitamin K is not recommended.
Area of Science:
- Pharmacology
- Clinical Medicine
- Drug Safety
Background:
- Cefoperazone is a third-generation cephalosporin containing an NMTT side chain.
- Hypoprothrombinaemia and bleeding are potential adverse events associated with certain antibiotics.
Purpose of the Study:
- To determine the incidence of hypoprothrombinaemia and bleeding in patients receiving cefoperazone.
- To compare the safety profile of cefoperazone with other cephalosporins (ceftizoxime, cefotaxime, ceftazidime) regarding these adverse events.
Main Methods:
- Retrospective cohort study comparing 374 patients on cefoperazone with control groups on ceftizoxime/cefotaxime (n=497) and ceftazidime (n=476).
- Adverse events including bleeding, decreased hemoglobin, and prolonged prothrombin time (PT)/partial thromboplastin time (PTT) were evaluated for 14 days post-therapy.
- Statistical analysis using adjusted odds ratios (95% CIs) to assess risk.
Main Results:
- Cefoperazone use was associated with a significantly increased risk of hypoprothrombinaemia (PT prolonged by ≥5s): 12.3% vs. 5.8% in controls (aORs 3.6-3.8).
- This risk increased with higher doses of cefoperazone.
- No overall increased risk of bleeding, decreased hemoglobin, or increased PTT was observed.
- Subgroup analysis showed increased bleeding risk with high-dose cefoperazone (aORs 2.3-2.8).
Conclusions:
- Patients receiving cefoperazone, particularly at high doses, face an elevated risk of hypoprothrombinaemia.
- While bleeding risk is not significantly increased overall, caution is advised with high-dose cefoperazone.
- Routine monitoring for hypoprothrombinaemia is recommended, but prophylactic vitamin K administration is likely not warranted.
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