Study of the Effects of Ticarcillin on Blood Coagulation and Platelet Function

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Administration of cephalothin to normal volunteers in maximal doses of 300 mg/kg per day resulted in a combined defect of platelet function and blood coagulation. No such abnormalities were evident after infusion of cefazolin or cephapirin at a maximal dosage of 200 mg/kg per day. The observed thrombocytopathy was similar to but less severe than that induced by carbenicillin or ticarcillin and was not reflected by a prolonged bleeding time test or impaired prothrombin consumption. Moreover, it was not a consistent finding in those persons receiving cephalothin. A separate defect involving blood coagulation appeared to result from delayed fibrinogen-fibrin polymerization and was evidenced by extended values of the activated partial thromboplastin and thrombin time tests. It remains uncertain whether the abnormalities described may constitute clinically important hemostatic disorders in patients with normal renal function receiving large doses of cephalosporin antibiotics.

Section: Discussionmentioning

confidence: 36%

“…Recent studies have confirmed that a specific hemostatic defect may be induced by administration of certain penicillin derivatives (2,3). Cephalosporins are closely related in chemical structure to penicillin and have also been implicated as causative of coagulation abnormalities (6).…”

mentioning

confidence: 99%

Influence of Cephalosporin Antibiotics on Blood Coagulation and Platelet Function

Natelson

Brown

Bradshaw

et al. 1976

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“…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.…”

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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

“…We found ticarcillin to be two to four times more active than carbenicillin against all organisms tested except S. epidermidis and enterococci, suggesting that perhaps lower doses of ticarcillin, as compared with the usual doses of carbenicillin might be clinically effective. Pharmacologically, carbenicillin and ticarcillin seem to be comparable (3,4,6,11), and early clinical studies have shown promise (9,10,15). Therefore, ticarcillin would seem to merit further laboratory and clinical investigation to ascertain whether it offers a real advantage over carbenicillin in terms of cost, clinical effectiveness, and side effects.…”

Section: Discussionmentioning

confidence: 99%

Comparative Activity In Vitro of Ticarcillin, BL-P1654, and Carbenicillin

Eickhoff

Ehret

1976

The activity of ticarcillin, BL-P1654, and carbenicillin was compared in vitro using a microtiter tube dilution test in Mueller-Hinton broth against 50 recent clinical isolates each of Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, Klebsiella species, Enterobacter species, Proteus species, and Pseudomonas aeruginosa. Bactericidal end points were determined using a modified Steers replicator. Ticarcillin was generally two to four times more active against all organisms tested except S. epidermidis against which BL-P1654 was most active. Median minimum inhibitory concentrations in micrograms per milliliter were for S. aureus: ticarcillin (6.2), carbenicillin (12.5), BL-P1654 (25); for S. epidermidis: BL-P1654 (1.6), ticarcillin (3.2), carbenicillin (3.2); for E. coli: ticarcillin (3.2), BL-P1654 (6.2), carbenicillin (6.2); for Klebsiella sp.: >100 for all three drugs; for Enterobacter sp.: ticarcillin (3.2), carbenicillin (6.2), BL-P1654 (12.5); for Proteus sp.: ticarcillin (1.6), carbenicillin (1.6), BL-P1654 (3.2); for P. aeruginosa: ticarcillin (31), BL-P1654 (62), carbenicillin (125). Bactericidal end points were dependent on both the drug and the species but were in general no more than twofold more than the minimum inhibitory concentration with the exception of BL-P1654 against P. aeruginosa. BL-P1654 was bactericidal for only 60% of the strains tested at a concentration of 500 gg/ml.Carbenicillin has been found, in the years since its introduction, to be a remarkably useful drug in certain patients with infections caused by Pseudomonas aeruginosa, Serratia marcescens, and other selected susceptible pathogens. However, the emergence of carbenicillin-resistant strains and the risk of electrolyte and coagulation problems associated with high-dose therapy of sytemic infections have limited its clinical use.BL-P1654 is the sodium salt of 3-guanylureido-phenyl-acetamino-penicillanic acid, with a spectrum similar to that of carbenicillin. BRL-2288, ticarcillin, is the disodium salt of a-carboxy-3-thienylmethyl penicillin, also with a spectrum similar to that of carbenicillin. We compared the in vitro activity of these three drugs against a number of recent clinical isolates.MATERIALS AND METHODS Fifty isolates each of Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, Klebsiella species, Enterobacter species, Proteus species, Pseudomonas aeruginosa, and 10 isolates of enterococci were studied. The organisms were isolated in the Clinical Microbiology Laboratory of Colorado General Hospital, University of Colorado Medical Center, having been recovered from specimens of blood, urine, sputum, and other infected sites submitted from patients and were identified by standard methods under the direction of L. Barth Reller. Minimum inhibitory concentrations were carried out using microtiter tube dilution tests in Mueller-Hinton broth, adding 0.05 ml of a 10-4 dilution of an overnight Mueller-Hinton broth culture of each organism to be tested to 0.05 ml of diluted antibiotic in a micr...