Inoculum effect with cefazolin among clinical isolates of methicillin-susceptible Staphylococcus aureus: frequency and possible cause of cefazolin treatment failure.

Methicillin (meticillin)-susceptible Staphylococcus aureus (MSSA) strains producing large amounts of type A beta-lactamase (Bla) have been associated with cefazolin failures, but the frequency and impact of these strains have not been well studied. Here we examined 98 MSSA clinical isolates and found that 26% produced type A Bla, 15% type B, 46% type C, and none type D and that 13% lacked blaZ. The cefazolin MIC(90) was 2 microg/ml for a standard inoculum and 32 microg/ml for a high inoculum, with 19% of isolates displaying a pronounced inoculum effect (MICs of >or=16 microg/ml with 10(7) CFU/ml) (9 type A and 10 type C Bla producers). At the high inoculum, type A producers displayed higher cefazolin MICs than type B or C producers, while type B and C producers displayed higher cefamandole MICs. Among isolates from hemodialysis patients with MSSA bacteremia, three from the six patients who experienced cefazolin failure showed a cefazolin inoculum effect, while none from the six patients successfully treated with cefazolin showed an inoculum effect, suggesting an association between these strains and cefazolin failure (P = 0.09 by Fisher's exact test). In summary, 19% of MSSA clinical isolates showed a pronounced inoculum effect with cefazolin, a phenomenon that could explain the cases of cefazolin failure previously reported for hemodialysis patients with MSSA bacteremia. These results suggest that for serious MSSA infections, the presence of a significant inoculum effect with cefazolin could be associated with clinical failure in patients treated with this cephalosporin, particularly when it is used at low doses.

[Coagulation abnormalities after total hip prosthesis (THP), a rare cause: antibiotic prophylaxis]. / Anomalies de la coagulation après prothèse totale de hanche (PTH), une cause rare: l'antibioprophylaxie.

A 87-year-old patient developed coagulation abnormality following hip surgery related to the prophylactic use of cefamandole. Cefamandole as others cephalosporins with a methyl-tetrazol-thiol lateral chain interferes with the vitamin K regeneration cycle as do oral anticoagulants. Therefore, the use of others antibiotics or systematic vitamin K1 supplementation or single dose of cefamandole is recommended for patients with renal failure or with malnutrition. Vitamin K1 supplementation is a simple method resulting in complete resolution of the coagulation disorder.

The impact of penicillinase on cefamandole treatment and prophylaxis of experimental endocarditis due to methicillin-resistant Staphylococcus aureus.

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.

In vitro study of the potential role of quinupristin/dalfopristin in the treatment of catheter-related staphylococcal infections.

The susceptibility of clinical isolates of methicillin-susceptible and -resistant staphylococci from cancer patients with central venous catheter bacteremia to quinupristin/dalfopristin, a semisynthetic streptogramin, was determined in vitro. Susceptibility of these isolates to nine other antistaphylococcal antibiotics was also determined for comparison. A total of 197 staphylococcal strains were tested from 1983 to 1992. Quinupristin/dalfopristin was bactericidal against all isolates, independent of their resistance to methicillin. Its activity was similar to that of vancomycin but superior to that of teicoplanin. Quinupristin/dalfopristin may prove to be an important addition to our armamentarium against catheter-related staphylococcal infections.

Comparative multicentre evaluation of the safety and efficacy of ceftazidime versus cefamandole for pneumonia.

Ceftazidime and cefamandole were compared in a randomized multicentre trial in hospitalized patients with pneumonia. Of 290 patients enrolled, 92 patients in the ceftazidime group and 71 patients in the cefamandole group were evaluable. Geometric mean MICs of organisms isolated and tested to ceftazidime were within achievable therapeutic serum concentrations of ceftazidime. Satisfactory clinical responses were observed in 91% (84/92) of ceftazidime-treated patients and 83% (59/71) of cefamandole-treated patients (P greater than 0.05). Superinfection occurred in one (1%) ceftazidime-treated patient and in five (7%) cefamandole-treated patients. Side effects were infrequent with either treatment. Ceftazidime is as safe and effective as cefamandole for the treatment of pneumonia due to a variety of Gram-positive and Gram-negative pathogens.

[Treatment of urologic infections with cefamandole (Pharmachim)--the microbiological and clinical results]. / Lechenie na uroinfektsiite c tsefamandol (Farmakhim)--mikrobiologichni i klinichni rezultati.

The authors study the possibilities of cephalosporin antibiotic cefamandol, new for our clinical practice, in the treatment of uroinfections. The microbiological study on a total of 2301 bacterial strains, isolated from patients with uroinfections, reveals that cefamandol excels in its action against gram-positive microorganisms, all beta-lactam antibiotics, used in our country. As regards E. coli, Citrobacter, Klebsiella, Enterobacter, P. mirabilis and indole positive pro cefamandol is better than ampicillin, carbencillin and cefalotin. A resistance to the preparation showed the majority of the isolates of Enterococcus, Serratia, Acinebacter and Pseudomonas aeruginosa. Excellent result was attained in 60% of all the 35 patients with uroinfections treated, manifested in "sterilization" of urine and in 5.71% bacteruiria became insignificant. In parallel, the clinical and laboratory symptoms of uroinfection were favourably influenced. The preparation has a good tolerance. Finally it should be underlined that this antibiotic must be introduced in the routine clinical practice for the treatment of adequate forms of uroinfections.