Influence of Cephalosporin Antibiotics on Blood Coagulation and Platelet Function

Moxalactam, a potent new f8-lactam antibiotic with a relatively wide spectrum of activity against facultative and anaerobic gram-negative bacilli, was evaluated in vitro and in 28 patients with a variety of severe infections with moxalactamsusceptible organisms (minimum inhibitory concentration c31 .tg/ml). Although therapy was successful in most of these patients, caution is suggested because of the development of resistance on therapy in one patient, persistence of Bacteroides fragilis endocarditis in another, and for certain organisms, a significant inoculum effect on the minimum inhibitory concentration and minimum bactericidal concentration of moxalactam. in serum and urine were determined in patients receiving 0.5 to 1.0 g of this drug on days 2 to 27 of therapy. Serum specimens were drawn at various intervals from 0.5 to 11.5 h after the end of a 20-min intravenous (i.v.) infusion of moxalactam. Urine specimens were obtained by having the patient void before receiving a dose of moxalactam and collecting urine voided over the dosage interval. One patient with renal failure was hemodialyzed with a Travenol RSP (Travenol Laboratories, Inc.). Serum and urine were stored (usually for less than 1 week) at -20°C until the time of assay. The concentrations of moxalactam in urine and serum were determined by the agar diffusion method with paper disks (7).The serum half-life (t12) was defined as the log, divided by the slope of the f3 phase of the serum decay curve beginning at 1 h after the end of the 20-min i.v.

Section: Methodsmentioning

confidence: 52%

In vitro activity, efficacy, and pharmacology of moxalactam, a new beta-lactam antibiotic

Snepar¹,

Poporad²,

Romano³

et al. 1981

“…Pineo and colleagues have suggested that hypoprothrombinemia is a frequent concomitant condition in the malnourished, often severely debilitated population for whom extended-spectrum cephalosporins are most commonly used and that the apparent increased incidence of coagulopathy reflects the selection bias inherent in the use of these agents in patients with a dietary deficiency of vitamin K (21). Others have proposed a direct inhibition of fibrin formation by ,-lactam antibiotics through the inhibition of the final steps of blood coagulation (6,14). Conly and colleagues have recently proposed that the broad antimicrobial spectrum of the newer cephalosporins eliminates the menaquinone-producing bacteria in the intestinal lumen, thereby facilitating the development of vitamin K deficiency and hypoprothrombinemia in hosts already so predisposed because of pre-existing malnutrition and general debilitation (3,22).…”

Section: Resultsmentioning

confidence: 99%

“…The mechanisms whereby these agents cause this reaction and the actual incidence of hypoprothrombinemia associated with their therapeutic use are controversial (2,12,14; N. V. Bang, A. Dwyer, S. S. Campbell, C. A. Marks, and R. 0.…”

mentioning

confidence: 99%

Coagulopathy associated with extended-spectrum cephalosporins in patients with serious infections

Nichols¹,

Wikler²,

McDevitt³

et al. 1987

Patients enrolled in two double-blind multicenter studies were evaluated for the development of hypoprothrombinemia during treatment with cephalosporins. Patients with pneumonia or peritonitis received ceftizoxime, cefotaxime, or moxalactam. The incidence of hypoprothrombinemia was greater in patients with peritonitis (12 of 49) than in those with pneumonia (5 of 96; P < 0.05). Overall, moxalactam was associated with a higher incidence of hypoprothrombinemia (13 of 52) than either ceftizoxime (1 of 43; P < 0.05) or cefotaxime (3 of 50; P < 0.05), and moxalactam patients incurred the highest average increase in prothrombin time (3.7 s) as compared with either ceftizoxime (0.5 s; P < 0.05) or cefotaxime (0.9 s; P < 0.05) patients. The occurrence of hypoprothrombinemia in moxalactam patients with peritonitis was not related to dosage, duration of therapy, age, sex, race, or renal or hepatic function. The degree of ileus was, however, strongly related to the development of coagulopathy in moxalactam-treated patients only.

“…DISCUSSION Antibiotic-induced platelet dysfunction has been reported most frequently with carbenicillin and penicillin (2,4). However, other penicillins and some cephalosporins, including a few of the newer agents (e.g., piperacillin and moxalactam), have been shown to produce platelet dys- function at various concentrations (3,6,8,13,14). The cases presented here suggest that nafcillin can also induce a hemostatic defect attributable to platelet dysfunction.…”

mentioning

confidence: 88%

“…These defects, however, can result in clinically evident bleeding episodes that may be accentuated by the underlying disease of the patients or by other administered drugs. The time course for the appearance of abnormalities in platelet function and of prolonged bleeding time is from 30 min to 3 days after therapy is started (4,11,13), with the maximum defect in platelet function occurring between 1 and 10 days (3,10). The duration of the platelet function abnormalities is variable but may be prolonged in certain individuals.…”

mentioning

confidence: 99%

Nafcillin-induced platelet dysfunction and bleeding

Alexander¹,

Russo²,

Fohrman³

et al. 1983

This paper describes two cases of nafcillin-induced platelet dysfunction, with positive rechallenge data for one patient. Nafcillin resulted in abnormal bleeding times in both patients and a clinically apparent bleeding episode in one of the cases. Platelet function tests were performed on one patient during the initial therapy and after rechallenge with nafcillin. Platelet aggregation showed abnormal responses to ADP, collagen, and epinephrine. Platelet count and morphology were normal. Nafcillin should be recognized as another antibiotic which causes platelet function abnormalities and clinical bleeding episodes. sites, but the hematocrit did not decrease. At this time, debridement with possible grafting was planned for the leg ulcers. The preoperative laboratory screen revealed a template bleeding time of greater than 25 min (normal, 6 to 9 min), and the procedure was cancelled. The partial thromboplastin time and platelet count were normal. Platelet morphology was also normal. The prothrombin time was 15.6 s with a control of 13.6 s and was corrected with normal plasma. Liver function tests were normal, although 1 week earlier mild elevations of serum glutamic oxalacetic transaminase and serum glutamic pyruvic transaminase had been present. The patient's medications included prednisone (40 mg daily), double-strength trimethoprim-sulfamethoxazole (twice daily), sulindac (Clinoril; 200 mg twice daily), amitriptyline (50 mg at bedtime), and nafcillin as described above. All medications except prednisone and nafcillin were discontinued, and the bleeding time was repeated at 48 and 72 h. Platelet function tests revealed abnormal aggregation (see Table 1). Surgery was deferred, nafcillin was discontinued, and the patient was discharged. A bleeding time repeated 9 days later was normal (6.5 min).The patient was readmitted 1 month later for surgical repair of the extensor tendons on the right hand. The only medication at that time was prednisone (30 mg daily). The platelet count, prothrombin time, and partial thromboplastin time were normal, and the bleeding time was 6.5 min. The tendon repair was accomplished without excessive bleeding, and consent of the patient to rechallenge her with nafcillin was obtained. During this period, fat-containing foods were not allowed after 10 p.m., to prevent lipemic blood samples. No blood samples were drawn other than those done for coagulation 59