A vitamin K deficiency- associated bleeding tendency during antibiotic therapy has recently become a serious problem, especially with the use of the new cephems. Broad spectrum antibiotics such as the cephems of the 2nd and 3rd generation may cause a marked change in the intestinal bacterial flora, leading to vitamin K deficiency in some patients. The changes of the intestinal bacterial flora and blood coagulation system including protein induced by vitamin K absence or antagonist (PIVKA II), an abnormal prothrombin which is demonstrated in patients with vitamin K deficiency, were investigated in children during antibiotic therapy. The influences of oral food intake and diarrhea, and the differences classified by antibiotics and age were also investigated.
Among the 160 patients, 37 patients (23%) showed the existence of PIVKA II and 24 patiens (15%) showed an abnormal prothrombin time (PT), activated partial thromboplastin time (APTT), hepaplastin test (HPT), and thrombotest (TT). Bleeding tendencies were noted in 11 patients (7%). PIVKA II became positive within 7 days after the initiation of antibiotics in 71% of the 37 patients, and returned negative with vitamin K administration.
PIVKA II was infrequently demonstrated in infants and frequently demonstrated in patients with sepsis, intrauterine infection, and central nervous system infection. None of patients with urinary tract infection were positive for PIVKA II. As for the relationship between the detection rate of PIVKA II and the antibiotics used, PIVKA II was frequently demonstrated in patients treated with latamoxef (LMOX), cefmetazole (CMZ), and cefoperazone (CPZ). None of the patients treated with cefotaxime (CTX), ceftazidime (CAZ), and ampicillin (ABPC) were positive for PIVKA II. LMOX, CMZ and CPZ have a 1-methyl-1-H-tetrazole-5-yl-thiomethyl group at position 3 of dihydrothiazine nucleus, and further investigation about the influences of this group to the vitamin K assosiated blood coagulation system is necessary.
The change of the intestinal bacterial flora was investigated for 124 of the 160 patients, and 83 of those (67%) showed a decrease of the intestinal bacterial flora. Twenty-three of the 83 patients (28%) were positive for PIVKA II. In 23 patients who had both a decrease of the intestinal bacterial flora and a decrease of oral food intake with or without diarrhea, 15 patients showed positive PIVKA II, a detection rate of 65%. This suggests that insufficient oral intake of vitamin K and the decrease of the intestinal bacterial flora play important roles in the etiology of the vitamin K deficiency during antibiotic therapy. A careful monitoring of the blood coagulation system, including PIVKA II, is necessary for patients receiving antibiotic therapy with broad spectrum agents such at the new cephems, and prophylactic use of vitamin K is indicated in newborn infants and patients with poor oral intake.