Hypoprothrombinemia in febrile, neutropenic patients with cancer: association with antimicrobial suppression of intestinal microflora.
Serial, twice-weekly prothrombin times were determined in 108 febrile, granulocytopenic patients with cancer who were prospectively randomized to receive empiric antimicrobial therapy with moxalactam plus ticarcillin (M/T) or tobramycin plus ticarcillin (T/T). Thirty of 54 patients given M/T and 13 of 54 patients given T/T developed prothrombin times that were greater than or equal to 2 sec beyond control values (P less than .001) after a mean of 6.5 days of antimicrobial therapy. Serious bleeding episodes were more frequent in the group given M/T than in that given T/T (10 and two patients, respectively; P less than or equal to .05). Serial quantitative stool cultures revealed that both Escherichia coli and Bacteroides species were suppressed by greater than or equal to 5 log10 in eight of nine patients given M/T and in three of nine given T/T (P less than .05, Fisher's exact test). A significant reduction of the population of E. coli and Bacteroides fragilis, organisms that are major producers of bacterially synthesized menaquinones, was associated with a high incidence of hypoprothrombinemia. These observations support the hypothesis that menaquinones may play an important physiological role in the maintenance of blood coagulation during episodic dietary deficiency of phylloquinone.
D000900:Anti-Bacterial Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001424:Bacterial Infections / Q000150:complications / Q000188:drug therapy; D001439:Bacteroides / Q000254:growth & development*; D004359:Drug Therapy, Combination; D004926:Escherichia coli / Q000254:growth & development*; D005243:Feces / Q000382:microbiology; D006474:Hemorrhagic Disorders / Q000209:etiology; D006801:Humans; D007020:Hypoprothrombinemias / Q000209:etiology*; D007422:Intestines / Q000382:microbiology*; D009070:Moxalactam / Q000009:adverse effects; D009369:Neoplasms / Q000150:complications*; D009503:Neutropenia / Q000150:complications; D011517:Prothrombin Time; D013982:Ticarcillin / Q000009:adverse effects; D014031:Tobramycin / Q000009:adverse effects
D000900:Anti-Bacterial Agents; D013982:Ticarcillin; D009070:Moxalactam; D014031:Tobramycin