Cefotetan

Cefotetan is a bactericidal agent that acts by inhibition of bacterial cell wall synthesis. Cefotetan has activity in the presence of some beta-lactamases, both penicillinases and cephalosporinases, of gram-negative and gram-positive bacteria.

Resistance

Resistance to cefotetan is primarily through hydrolysis by some beta-lactamases, alteration of penicillin–binding proteins (PBPs) and decreased permeability.

Antimicrobial Activity

Cefotetan has been shown to be active against most isolates of the following microoranisms both in vitro and in clinical infections.

Gram-Negative Bacteria:

Escherichia coli
Haemophilus influenzae
Klebsiella species (including K. pneumoniae)
Morganella morganii
Neisseria gonorrhoeae
Proteus mirabilis
Proteus vulgaris
Providencia rettgeri
Serratia marcescens

Gram-Positive Bacteria:

Staphylococcus aureus (methicillin-susceptible isolates only)
Staphylococcus epidermidis (methicillin-susceptible isolates only)
Streptococcus agalactiae
Streptococcus pneumoniae
Streptococcus pyogenes
Streptococcus species

Anaerobes:

Prevotella bivia
Prevotella disiens
Bacteroides fragilis
Prevotella melaninogenica
Bacteroides vulgatus
Fusobacterium species
Clostridium species
Peptococcus niger
Peptostreptococcus species

The following in vitro data are available but their clinical significance is unknown. At least 90 percent of the following bacteria exhibit an in vitro minimum inhibitory concentration (MIC) less than or equal to the susceptible breakpoint for cefotetan against isolates of similar genus or organism group. However, the efficacy of cefotetan in treating clinical infections caused by these bacteria has not been established in adequate and well-controlled clinical trials.

Gram-Negative Bacteria:

Citrobacter species (including C. koseri and C. freundii)
Moraxella catarrhalis
Salmonella species
Serratia species
Shigella species
Yersinia enterocolitica

Anaerobes:

Porphyromonas asaccharolytica
Prevotella oralis
Bacteroides splanchnicus
Propionibacterium species
Veillonella species

High plasma levels of cefotetan are attained after intravenous and intramuscular administration of single doses to normal volunteers.

Plasma concentrations after 1 gram intravenous^a or intramuscular dose:

^a 30-minute infusion

Plasma concentrations after 2 gram intravenous^a or intramuscular dose:

^a Injected over 3 minutes
^b Concentrations estimated from regression line

Repeated administration of cefotetan does not result in accumulation of the drug in normal subjects.

Distribution

Cefotetan is 88% plasma protein bound.

Therapeutic concentrations of cefotetan are achieved in many body tissues and fluids including:

Metabolism and Excretion

The plasma elimination half-life of cefotetan is 3 to 4.6 hours after either intravenous or intramuscular administration.

No active metabolites of cefotetan have been detected; however, small amounts (less than 7%) of cefotetan in plasma and urine may be converted to its tautomer, which has antimicro bial activity similar to the parent drug.

In normal patients, from 51% to 81% of an administe re d dose of cefotetan is excreted unchanged by the kidneys over a 24-hour period, which results in high and prolonged urinary concentrations. Following intravenous doses of 1 gram and 2 g rams, urinary concentrations are highest during the first hour and reach concentrations of approximately 1700 and 3500 mcg/mL, respectively.

Specific Populations

Patients with Renal impairment

In volunteers with reduced renal function, the plasma half-life of cefotetan is prolonged. The mean terminal half-life incre ases with declining renal function, from approximately 4 hours in volunteers with normal renal function to about 10 hours in those with mo derate renal impairment. There is a linear correlation between the systemic clearance of cefotetan and creatinine clearanc e. When renal function is impaired, a reduced dosing schedule based on creatinine clearance must be used.

Geriatric patients

In pharmac o kine tic studies of eight elderly patients (greater than 65 years) with normal renal function and six healthy volunteers (aged 25 to 28 years), mean±SD) Total Body Clearance (1.8±0.1 vs. 1.8±0.3 L/h) and mean±SD Vo lume of Distribution (10.4±1.2 vs. 10.3±1.6 L) were similar fo llo wing administration of a one gram intravenous bolus dose.