Hypoprothrombinemia in Febrile, Neutropenic Patients with Cancer: Association with Antimicrobial Suppression of Intestinal Microflora

• Published in: The Journal of infectious diseases Vol. 150; no. 2; pp. 202 - 212
• Main Authors: Conly, J. M., Ramotar, K., Chubb, H., Bow, E. J., Louie, T. J.
• Format: Journal Article
• Language: English
• Published: Chicago, IL The University of Chicago Press 01.08.1984; University of Chicago Press
• Subjects: Anti-Bacterial Agents - adverse effects; Anti-Bacterial Agents - therapeutic use; Antibiotics; Antimicrobials; Bacterial Infections - complications; Bacterial Infections - drug therapy; Bacteroides; Bacteroides - growth & development; Biological and medical sciences; Bleeding; Disease susceptibility; Drug Therapy, Combination; Drug toxicity and drugs side effects treatment; Escherichia coli - growth & development; Feces - microbiology; Hemorrhagic Disorders - etiology; Homeostasis; Humans; Hypoprothrombinemias; Hypoprothrombinemias - etiology; Intestines - microbiology; Medical sciences; Microorganisms; Moxalactam - adverse effects; Neoplasms - complications; Neutropenia - complications; Original Articles; Pharmacology. Drug treatments; Platelets; Prothrombin Time; Ticarcillin - adverse effects; Tobramycin - adverse effects; Toxicity: blood; Vitamin K; Human; Antibiotic; Drug combination; Toxicity; Lactam; Tumor; Coagulopathy; Fever; Hypoprothrombinemia; Neutropenia
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1093/infdis/150.2.202

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 ⩾2 sec beyond control values (P < .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 ⩽ .05). Serial quantitative stool cultures revealed that both Escherichia coli and Bacteroides species were suppressed by ⩾5 log10, in eight of nine patients given M/T and in three of nine given T/T (P < .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.