Department of General Medicine, Juntendo University School of Medicine, Tokyo, Japan.
Department of Emergency and Disaster Medicine, Juntendo University School of Medicine, Tokyo, Japan.
Am J Case Rep. 2022 Jul 27;23:e936712. doi: 10.12659/AJCR.936712.
BACKGROUND Cefmetazole (CMZ), containing an N-methyl-tetrazole-thiol (NMTT) side chain, is a therapeutic option for diverticulitis in Japan. Cephems containing an NMTT, a methyl-thiadiazol, and a thiadiazolethiol side chain are known to induce coagulation disorders. CASE REPORT A 76-year-old woman developed hypoprothrombinemia after receiving oral levofloxacin (LVFX) 250 mg q24h for 2 days followed by intravenous CMZ 2 g q8h for sigmoid diverticulitis. On day 5 of CMZ administration (after 12 doses in total), black stool was observed. On the following day (after 14 doses), prothrombin time (PT) prolongation was noted; PT and international normalized ratio (INR) were 37.1 s and 2.47, respectively. We diagnosed the patient with hypoprothrombinemia because of vitamin K deficiency caused by markedly elevated protein levels induced by vitamin K absence or antagonist-II on day 6 of CMZ administration. Intravenous vitamin K administration and CMZ cessation rapidly restored PT and led to the disappearance of black stool. CONCLUSIONS The causes of vitamin K deficiency were considered to be an impaired vitamin K cycle due to CMZ and decreased vitamin K intake because of malnutrition. These findings are consistent with CMZ's reported adverse effects. Decreased vitamin K production due to alterations in the gut bacterial flora by LVFX and CMZ was also postulated as a cause. If a bleeding tendency is noted during diverticulitis treatment with NMTT-containing cephems, switching to intravenous quinolones or carbapenems is recommended. It remains unclear how this reaction can be avoided; however, prudent monitoring of bleeding signs and PT-INR is recommended.
头孢美唑（CMZ）含有 N-甲基四唑硫醇（NMTT）侧链，是日本治疗憩室炎的一种治疗选择。含有 NMTT、甲基噻二唑和噻二唑硫醇侧链的头孢菌素已知会引起凝血障碍。
一名 76 岁女性因乙状结肠憩室炎接受左氧氟沙星（LVFX）250mg q24h 口服治疗 2 天后，改为 CMZ 2g q8h 静脉滴注，之后出现低凝血酶原血症。在 CMZ 给药的第 5 天（总共 12 剂后），观察到黑便。第二天（总共 14 剂后），发现凝血酶原时间（PT）延长；PT 和国际标准化比值（INR）分别为 37.1s 和 2.47。由于 CMZ 给药第 6 天显著升高的蛋白水平引起的维生素 K 缺乏或拮抗剂-II 导致维生素 K 缺乏，我们诊断该患者为低凝血酶原血症。静脉内给予维生素 K 和停止 CMZ 迅速恢复了 PT，并导致黑便消失。
维生素 K 缺乏的原因被认为是由于 CMZ 导致维生素 K 循环受损，以及由于营养不良导致维生素 K 摄入减少。这些发现与 CMZ 报告的不良反应一致。LVFX 和 CMZ 改变肠道细菌菌群导致维生素 K 产生减少也被认为是一个原因。如果在含有 NMTT 的头孢菌素治疗憩室炎时出现出血倾向，建议改用静脉用喹诺酮类或碳青霉烯类药物。目前尚不清楚如何避免这种反应；然而，建议谨慎监测出血迹象和 PT-INR。
