cefamandole and Endocarditis

140 cases of patients requiring sternotomy incisions were divided into two groups receiving Penicillin/Flucloxacillin and Cefamandole prophylaxis. Pre- and post-operative and bypass circuit bacteriology was performed to determine the extent of contamination and infection with each regime after operations lasting 7 or more hours. Unexpectedly high contamination of the respiratory tract was observed in patients receiving Penicillin/Flucloxacillin prophylaxis. Significantly higher Slesser Intensive Therapy Unit stays were observed in 8 of these patients, 3 of whom succumbed to chest infection associated pathology. The 50% resistant organism rate in the Cefa group (Table IV) suggests that short sharp course prophylaxis (i.e. less than 48 hours) using wide spectrum antibiotics is effective and does not necessarily promote emergence of resistant organisms over or above that of any narrow spectrum antibiotic prophylaxis. Acceptably low wound infection rates in both groups suggests that wound healing (aided by iodine sprays topically before closure) is more dependent on closing technique than on type of antibiotic prophylaxis. The very similar bacteriaemia rates, with odd organisms, in both groups in the immediate post-operative period suggests that vigilance and frequent post-operative blood cultures are a surer policy in the prevention and treatment of early endocarditis than faith in any particular antibiotic prophylaxis.

Topics: Bacterial Infections; Cardiac Surgical Procedures; Cefamandole; Cephalosporins; Clinical Trials as Topic; Endocarditis; Floxacillin; Humans; Penicillins; Surgical Wound Infection

Beta-lactams active against methicillin-resistant Staphylococcus aureus (MRSA) must resist penicillinase hydrolysis and bind penicillin-binding protein 2A (PBP 2A). Cefamandole might share these properties. When tested against 2 isogenic pairs of MRSA that produced or did not produce penicillinase, MICs of cefamandole (8-32 mg/L) were not affected by penicillinase, and cefamandole had a > or =40 times greater PBP 2A affinity than did methicillin. In rats, constant serum levels of 100 mg/L cefamandole successfully treated experimental endocarditis due to penicillinase-negative isolates but failed against penicillinase-producing organisms. This suggested that penicillinase produced in infected vegetations might hydrolyze the drug. Indeed, cefamandole was slowly degraded by penicillinase in vitro. Moreover, its efficacy was restored by combination with sulbactam in vivo. Cefamandole also uniformly prevented MRSA endocarditis in prophylaxis experiments, a setting in which bacteria were not yet clustered in the vegetations. Thus, while cefamandole treatment was limited by penicillinase, the drug was still successful for prophylaxis of experimental MRSA endocarditis.

Topics: Animals; Anti-Bacterial Agents; Bacterial Proteins; Carrier Proteins; Cefamandole; Cephalosporins; Endocarditis; Hexosyltransferases; Methicillin Resistance; Microbial Sensitivity Tests; Muramoylpentapeptide Carboxypeptidase; Penicillin-Binding Proteins; Penicillinase; Peptidyl Transferases; Rats; Staphylococcal Infections; Staphylococcus aureus