Antibiotic Chemotherapy and the Hemorrhagic Tendency

The objective of the present research was to investigate the mechanism of the hemorrhagic tendency known to be associated with the administration of antibiotics. To do this from the viewpoints of the supply and utilization of vitamin K, studies were carried out in newborn infants and in germ‐free mice. The reasons for the selection of newborns were that their intestinal bacterial flora is easily changed by the administration of antibiotics and that it is easy to monitor their oral food intake. Germ‐free mice were selected because they do not have intestinal bacteria. Forty newborn infants were each given one of the antibiotics latamoxef (LMOX), cefmenoxime (CMX), cefotaxime (CTX) and ceftazidime (CAZ), and the establishment of most bacteria in the intestinal tract was delayed, with the exception of the enterococci, and sometimes S. epidermidis, which are insensitive to these antibiotics. PIVKA II, which is an indicator of vitamin K deficiency, was detected in 72% of the patients treated with LMOX and in 48% of the CMX‐treated patients. Conversely, all 16 patients who were treated with either CTX or CAZ were negative for PIVKA II. The correlation between the incidence of a positive result for PIVKA II and the oral food intake was investigated. It was found that 11 of 16 infants (68%) fed no milk or fed breast milk became positive for PIVKA II. In contrast, only 4 (16%) of 24 infants fed formula milk became positive for PIVKA II. The importance of the intestinal bacteria and the oral food intake was confirmed by the fact that the hepaplastin test value was prolonged when methyltetrazolyl‐thiomethyl (MTT) was administered to germ‐free mice and to normal mice on a vitamin‐K‐free diet. On the basis of these experimental findings, it is surmised that the association between antibiotic therapy and the development of a hemorrhagic tendency is a result of a complex interaction of various factors, i.e., a decrease in oral food intake, a decrease in the count of the normal bacterial flora of the intestinal tract, and the presence of an MTT group in the structure of the administered antibiotic.