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N-methyl-thio-tetrazole (NMTT) has been proposed as a causative factor in antibiotic-associated coagulopathy. To evaluate this hypothesis, a nationwide surveillance program was initiated to determine the relative frequency of antibiotic-associated coagulopathy and the importance of specific risk factors. A total of 970 patients were studied, with 491 being treated for infections and 479 receiving antimicrobial surgical prophylaxis. The NMTT-containing antibiotic cefotetan was compared with non-NMTT-containing antibiotics, for example, cefoxitin and cefazolin (prophylaxis only), and an aminoglycoside-antianaerobic (AG + AA) combination. Prothrombin time (PT) and partial thromboplastin time (PTT) were measured for each patient prior to the start of antibiotics and within 24-96 hours after the conclusion of drug administration. The patient population was relatively young [mean (SD) age 51.0 (20) yrs] with good nutritional status. The overall frequency of hypoprothrombinemia (4.5%) and bleeding (1.7%) was very low, and was highest with the use of AG + AA (p less than 0.05). No statistical differences were observed for the remaining antibiotic regimens in either the prophylaxis or treatment group. Logistic regression analysis identified treatment with the AG + AA combination, presence of liver disease, and renal dysfunction as factors associated with an increased risk of hypoprothrombinemia. In conclusion, this study suggests that the frequency of antibiotic-associated coagulopathy is low, regardless of antibiotic, in patients who are not critically ill and not malnourished.

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The chemistry, pharmacology, microbiology, pharmacokinetics, clinical efficacy, and adverse effects of sulbactam are reviewed. Sulbactam is a competitive, irreversible beta-lactamase inhibitor. Its binding to penicillin-binding proteins imparts weak intrinsic antibacterial activity. Synergy of sulbactam with beta-lactam antibiotics is most marked in bacterial species in which beta lactamase is a major mechanism of resistance. Sulbactam sodium is available in combination with ampicillin sodium for injection in a 1:2 ratio of sulbactam to ampicillin. Sultamicillin, an oral prodrug that is hydrolyzed to equimolar amounts of ampicillin and sulbactam, is in clinical trials. Ampicillin and sulbactam have similar pharmacokinetic properties. Sulbactam-ampicillin appears to be most useful for the treatment of polymicrobial aerobic or anaerobic infections and uncomplicated gonorrhea. Persistence, relapse, and superinfections have been reported after sulbactam-ampicillin treatment of urinary-tract and respiratory-tract infections. The combination is not effective against pseudomonal infections. Sulbactam-ampicillin is generally well tolerated. By restoring or expanding the activity of older, well-established beta-lactam antibiotics, sulbactam offers a new approach to the management of bacterial infections; the minimal toxicity of sulbactam-ampicillin makes the combination appealing for the treatment of gram-negative nonpseudomonal and anaerobic infections.

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The management of anticoagulant therapy for hospitalized patients by seven certified pharmacist prescribers and one physician was compared. Eighty-one consecutive patients referred to the anticoagulation service were randomly assigned to two groups. For patients in the pharmacist-prescriber group, the physician independently monitored laboratory results and simulated heparin and warfarin doses. The roles of pharmacist and physician were reversed for patients in the physician-prescriber group. According to an established protocol, adjustments in heparin sodium infusion rate were based on activated partial thromboplastin time (PTT); warfarin sodium dosage was adjusted using a proconvertin and prothrombin (P&P) method. Heparin doses, warfarin doses, and clotting-test results were compared for patients in the two prescriber groups; simulated and actual doses also were compared. Patients were observed for complications of anticoagulant therapy. There were no significant differences in the mean heparin and warfarin doses administered to patients in the two prescribed groups. Similarly, PTT and number of days to reach therapeutic P&P were not significantly different. Within each group, the mean prescribed and simulated heparin doses were not significantly different. There were no episodes of major bleeding, but four patients in the pharmacist-prescriber group had minor bleeding. While the results are not applicable to all pharmacists or all settings, the certified pharmacist prescribers in this study adjusted anticoagulant therapy as well as an experienced physician.

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