A comparison of the effects of mezlocillin and carbenicillin on haemostasis in volunteers

Copelan, Edward A.; Kusumi, Rodney K.; Miller, Linda; Fass, Robert J.

doi:10.1093/jac/11.suppl_c.43

Cited by 14 publications

(4 citation statements)

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“…In agreement with results of a previous study (2), moxalactam was found to inhibit ADP-induced aggregation; the effects were typical of those reported for other P-lactam antibiotics in healthy volunteers (1,2,4,5,7,17). Specifi (2) and indeed for other ,B-lactam antibiotics (5,7,17).…”

Section: Resultssupporting

confidence: 91%

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Effect of temocillin and moxalactam on platelet responsiveness and bleeding time in normal volunteers

Nunn¹,

Baird²,

Chamberlain³

1985

Antimicrob Agents Chemother

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The effects of temocillin and moxalactam on platelet responsiveness and bleeding time were examined in healthy male volunteers. In the first study, moxalactam (4 g intravenously every 12 h) was given to six subjects; template bleeding times were at least doubled in five subjects 12 to 14 h after 7 doses (P = 0.008) and in all six subjects 12 to 14 h after 13 doses (P = 0.004). ADP-induced primary aggregation was approximately halved after 7 (P = 0.026) and 13 doses (P = 0.008), and there was a markedly increased tendency toward disaggregation. Collagen-induced aggregation was also halved, but the effect only reached statistical significance after 13 doses (P = 0.008). There was essentially no effect on primary aggregation in response to the thromboxane receptor agonist U46619 or to platelet activating factor. Temocillin (4 g intravenously every 12h) was given to eight subjects, three of whom had participated in the moxalactam study 8 weeks earlier.Temocillin had no significant effect on template bleeding time 12 to 14 h after 7 or 13 doses. However, in four subjects, the endpoint may have been less abrupt. There was no significant effect on ADP-induced primary aggregation or responsiveness to collagen. Even after 13 doses of temocillin, secondary aggregation in response to normal concentrations of ADP was demonstrable in the platelet-rich plasma of all eight subjects. Neither antibiotic had any effect on prothrombin times. Thus, with methodology that readily detected the effects of moxalactam on hemostasis, we were unable to demonstrate any unequivocal deleterious effects of temocillin at its maximum recommended dose. Temocillin may therefore be particularly useful for the treatment of many gram-negative infections in patients at increased risk of clinical bleeding.Recent reports on bleeding complications in patients treated with cephalosporins have focused attention once again on the unwanted hematological effects of P-lactam antibiotics in general and new ones in particular (13, 16). Temocillin (BRL 17421) is a new semisynthetic P-lactam antibiotic that is exceptionally stable to a wide range of ,-lactamases and, unlike the majority of penicillins, has a relatively long half-life (3.5 to 5 h) in sera of normal subjects (3, 15). The study described here was designed to examine the effect of temocillin on platelet responsiveness and bleeding time in healthy volunteers when given intravenously at the maximum recommended dose for 7 days. However, it was preceded by a similar study of moxalactam for two reasons. First, we needed to establish that our methodology would detect the effects expected of a ,-lactam antibiotic. Moxalactam was selected for this because it has well-documented activity at doses similar to those to be used in the temocillin study (16 exclusion criteria included known history of penicillin allergy, gastrointestinal tract ulceration, or coagulation defects. All subjects denied having taken aspirin in the 10 days preceding each study. Alcohol and strenuous exercise were prohibited throughout the...

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Section: Resultssupporting

confidence: 91%

“…Specifi (2) and indeed for other ,B-lactam antibiotics (5,7,17). It should be noted that reduced responsiveness to collagen is not inconsistent with the ANTIMICROB.…”

Section: Resultsmentioning

confidence: 91%

Effect of temocillin and moxalactam on platelet responsiveness and bleeding time in normal volunteers

Nunn¹,

Baird²,

Chamberlain³

1985

Antimicrob Agents Chemother

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“…Their lower sodium content is an advantage in treating patients who are adversely affected by large sodium loads. Finally, mezlocillin (4,17) and possibly piperacillin (11) have less of a deleterious effect on platelet aggregation than do the a-carboxypenicillins and, therefore, may cause less bleeding.…”

Section: Discussionmentioning

confidence: 99%

Statistical comparison of the antibacterial activities of broad-spectrum penicillins against gram-negative bacilli

Fass¹

1983

Antimicrob Agents Chemother

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Minimal inhibitory concentrations (MICs) or two a-carboxypenicillins (carbenicillin and ticarcillin) and three acylaminopenicillins (azlocillin, mezlociliin, and piperacillin) for 300 aerobic and facultative gram-negative bacilli were determined by-a microdilution method and compared by parametric statistical tests. Within each group of penicillins, MICs were highly interrelated; MICs of one antibiotic were readily predictable based on knowledge of MICs of another antibiotic. Ticarcillin was consistently more active than carbenicillin by approximately one dilution step, but the relative activities of the acylaminopenicillins varied by bacterial species. The acylaminopenicillins were generally more active than the acarboxypenicillins, particularly against a-carboxypenicillin-resistant organisms. There were exceptions, however, and antibiotic MICs in one group were not readily predictable on the basis of the knowledge of antibiotic MICs in the other group. The enhanced antibacterial potencies and spectra of the acylaminopenicillins against gram-negative bacilli make these antibiotics potentially useful therapeutic agents. It is not necessary for clinical laboratories to routinely perform susceptibility tests with all five antibiotics.

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“…2). These penicillins have also demonstrated an ability to produce platelet dysfunction and clinical bleeding (Copeland et al 1983). …”

Section: Nomentioning

confidence: 99%

Adverse Effects of Newer Cephalosporins

Thompson

Jacobs

1993

Drug Safety

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While classifications into generations according to antimicrobial activity has helped clinicians incorporate the increasing number of cephalosporins into their pharmacological repertoire, adverse effects among the different agents fail to follow similar categories. In general, cephalosporins are fairly well tolerated antibiotics, and toxicity has been limited to specific agents. Subtle differences in chemical structure and pharmacokinetics can influence the potential for adverse effects. The route of administration may result in minor adverse reactions, including thrombophlebitis and pain. The most common adverse effects of cephalosporins are allergic reactions, occurring in 0.9 to 3.2% of patients. Cephalosporins have very rarely been associated with haematological toxicity (less than 1% of patients), but specific agents have been associated with neutropenia, hypoprothrombinaemia, haemolytic anaemia, and problems with platelet production and function. Other reactions include localised gastrointestinal disturbances, hepatotoxicity (e.g. biliary sludging), nephrotoxicity and mild central nervous system effects. The cephalosporins are generally well tolerated in the paediatric population. Very few interactions have been observed between cephalosporins and other drugs, largely because cephalosporins do not affect the microsomal P450 hepatic enzyme system. While cephalosporins are considered to be relatively 'safe' drugs, the introduction of newer members warrants continued careful observation for reporting of adverse drug reactions.

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A comparison of the effects of mezlocillin and carbenicillin on haemostasis in volunteers

Cited by 14 publications

References 0 publications

Effect of temocillin and moxalactam on platelet responsiveness and bleeding time in normal volunteers

Effect of temocillin and moxalactam on platelet responsiveness and bleeding time in normal volunteers

Statistical comparison of the antibacterial activities of broad-spectrum penicillins against gram-negative bacilli

Adverse Effects of Newer Cephalosporins

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