Cephalosporins Bleeding disorders: incidence study

Bleeding disorders with extended thromboplastin times have been reported in patients receiving cephalosporin s with a N-methylthlotetrazole (NMTT) side chain: in most cases blood clotting was normalised wi th IV phy tomenadione [vitamin Kd . This pilot study compared the adverse effects of treatment wi th latamoxef [moxalactam] , cefoperazone o r NMT' cephalosponns, with those of cefotaxime, a NMTT-free cephalosporin, on blood clotting and phytomenadione levels in elderly patients .

Patients, aged 62-91 (median 78) years , with urinary tract infections received IV cefotaxime 2g tid (n = 6) IV cefoperazone 2g bid (5) or IV latamoxef 2g bid (5) for 7 days. Duri treatment. pat ients with a Quick vall of < 50% ( n = 1) received IV phytomenadlone 10mg.

Two cefotaxlme recipients were excluded because of cefotaxime­resistant pathoQe_ns and absence of leucocytes in urine, respectively . No patient had signs of infection after treatment but 1 cefoperazone recipient and 1 latamoxef recipient had a reinfection 3 days after the end of treatment.

Two cefoperazone recipients experienced a marked reduction in Quick value, from 68 to 39% and from 79 to 41 %, respectively . In these 2 patients the phytomenadione-epoxide values after treatment were elevated vs pretreatment values : phytomenadione-epoxide values were generally unchanged in the remaining patients . These 2 patients had prothrombin induced in the absence of phytomenadione. After treatment, mean Quick values were significan tly higher in latamoxef recipients than in cefotaxime recipients . Phytomenadione-epoxide was present after treatment in 4 of 5 patients receiving cefoperazone and in 3 of 5 patients receiving latomoxef vs 0 of 6 patients receiving cefotaxime. Phytomenadione-epoxide levels and thrombocyte levels were significantly higher in cefoperazone recipients than in cefotaxime recipients.

The concentration and weight of free-circulating NMTT side chain was significantly higher in latamoxef recipients than in cefoperazone recipients . No correlation was found between NMTT concentration , clotting parameters , age or initial phytomenadione levels. AST levels were significantly higher in cefoperazone and latamoxef recipients than in cefotaxime recipients .

Thus , NMTT-cephalosporins were found to cause a clotting disorder in 2 of 10 elderly patients . An increased risk for Quick value reduction appears to exist in patients with a previously existing disorder of hepatic phytomenadione metabolism, indicated by PIVKA II or phytomenadione­epoxide levels . Schafer H, Naber K. Adam D Haemoslasls disorders under Irea lment With cephatosporlns With a N ·methyl lhlotetrazole side chain A randomlsed pilot study Arznelmillel Forschung Drug Research 39 t 156-1162, Sep 1989 [Translated from Ihe original published In German] .,.