After intramuscular administration of a 500-mg dose of cefamandole to normal volunteers, the mean peak serum concentration was 13 µg/mL. After a 1-g dose, the mean peak concentration was 25 µg/mL. These peaks occurred at 30 to 120 minutes. Following intravenous doses of 1, 2, and 3 g, serum concentrations were 139, 240, and 533 mcg/mL respectively at 10 minutes. These concentrations declined to 0.8, 2.2, and 2.9 mcg/mL at 4 hours. Intravenous administration of 4-g doses every 6 hours produced no evidence of accumulation in the serum. The half-life after an intravenous dose is 32 minutes; after intramuscular administration, the half-life is 60 minutes.

Sixty-five percent to 85% of cefamandole is excreted by the kidneys over an 8-hour period, resulting in high urinary concentrations. Following intramuscular doses of 500 mg and 1 g, urinary concentrations averaged 254 and 1,357 mcg/mL respectively. Intravenous doses of 1 and 2 g produced urinary levels averaging 750 and 1,380 mcg/mL respectively. Probenecid slows tubular excretion and doubles the peak serum level and the duration of measurable serum concentrations.

The antibiotic reaches therapeutic levels in pleural and joint fluids and in bile and bone.

Microbiology The bactericidal action of cefamandole results from inhibition of cell-wall synthesis. Cephalosporins have in vitro activity against a wide range of gram-positive and gram-negative organisms. Cefamandole is usually active against the following organisms in vitro and in clinical infections:

Gram-positive

Staphylococcus aureus, including penicillinase- and non-penicillinase-producing strains

Staphylococcus epidermidis

(beta)-hemolytic and other streptococci (Most strains of enterococci, eg, Enterococcus faecalis [formerly Streptococcus faecalis ], are resistant.)

Streptococcus pneumoniae

Gram-negative

Escherichia coli

Klebsiella spp.

Enterobacter spp. (Initially susceptible organisms occasionally may become resistant during therapy.)

Haemophilus influenzae

Proteus mirabilis

Providencia rettgeri (formerly Proteus rettgeri )

Morganella morganii (formerly Proteus morganii )

Proteus vulgaris (Some strains of P. vulgaris have been shown by in vitro tests to be resistant to cefamandole and certain other cephalosporins.)

Anaerobic organisms

Gram-positive and gram-negative cocci (including Peptococcus and Peptostreptococcus spp.)

Gram-positive bacilli (including Clostridium spp.)

Gram-negative bacilli (including Bacteroides and Fusobacterium spp.). Most strains of Bacteroides fragilis are resistant.

Pseudomonas, Acinetobacter calcoaceticus (formerly Mima and Herellea   spp.), and most Serratia strains are resistant to cefamandole and certain other cephalosporins. Cefamandole is resistant to degradation by (beta)-lactamases from certain members of the Enterobacteriaceae.

Susceptibility Tests  Quantitative methods that require measurement of zone diameters give the most precise estimates of antibiotic susceptibility. One such procedure ¹ has been recommended for use with disks to test susceptibility to cefamandole. Interpretation involves correlation of the diameters obtained in the disk test with minimal inhibitory concentration (MIC) values for cefamandole.

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