Cefotan (Page 2 of 6)

Microbiology

Mechanism of Action

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 microorganisms both in vitro and in clinical infections (see INDICATIONS AND USAGE).

Gram-Negative Bacteria

Escherichia coli

Haemophilus influenza

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

Susceptibility Testing

For specific information regarding susceptibility test interpretive criteria and associated test methods and quality control standards recognized by FDA for this drug, please see: https://www.fda.gov/STIC.

INDICATIONS AND USAGE

To reduce the development of drug-resistant bacteria and maintain the effectiveness of CEFOTAN^® and other antibacterial drugs, CEFOTAN^® should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.

Treatment

CEFOTAN^® (cefotetan for Injection, USP) is indicated for the therapeutic treatment of the following infections when caused by susceptible strains of the designated organisms:

Urinary Tract Infections caused by E. coli, Klebsiella spp (including K. pneumoniae ), Proteus mirabilis, Proteus vulgaris , Providencia rettgeri , and Morganella morganii ).

Lower Respiratory Tract Infections caused by Streptococcus pneumoniae , Staphylococcus aureus(methicillin-susceptible), Haemophilus influenzae , Klebsiella species (including K. pneumoniae ), E. coli , Proteus mirabilis , and Serratia marcescens.*

Skin and Skin Structure Infections due to Staphylococcus aureus (methicillin-susceptible), Staphylococcus epidermidis (methicillin susceptible), Streptococcus pyogenes , Streptococcus species, Escherichia coli , Klebsiella pneumoniae , Peptococcus niger *, Peptostreptococcus species.

Gynecologic Infections caused by Staphylococcus aureus (methicillin susceptible), Staphylococcus epidermidis (methicillin susceptible, Streptococcus species, Streptococcus agalactiae , E. coli , Proteus mirabilis , Neisseria gonorrhoeae , Bacteroides fragilis, Prevotella melaninogenica Bacteroides vulgatus , Fusobacterium species*, and gram- positive anaerobic cocci (including Peptococcus niger and Peptostreptococcus species).

Cefotetan, like other cephalosporins, has no activity against Chlamydia trachomatis. Therefore, when cephalosporins are used in the treatment of pelvic inflammatory disease, and C. trachomatis is one of the suspected pathogens, appropriate antichlamydial coverage should be added.

Intra-abdominal lnfections caused by E. coli , Klebsiella species (including K. pneumoniae), Streptococcus species, Bacteroides fragilis, Prevotella melaninogenica, Bacteroides vulgatus and Clostridium species (other than Clostridium difficile [see WARNINGS])*.

Bone and Joint Infections caused by Staphylococcus aureus (methicillin susceptible)*.

* Efficacy for this organism in this organ system was studied in fewer than ten infections in clinical studies

Specimens for bacteriological examination should be obtained in order to isolate and identify causative organisms and to determine their susceptibilities to cefotetan. Therapy may be instituted before results of susceptibility studies are known; however, once these results become available, the antibiotic treatment should be adjusted accordingly.

In cases of confirmed or suspected gram-positive or gram-negative sepsis or in patients with other serious infections in which the causative organism has not been identified, it is possible to use CEFOTAN^® concomitantly with an aminoglycoside. Cefotetan combinations with aminoglycosides have been shown to be synergistic in vitro against many Enterobacteriaceae and also some other gram- negative bacteria. The dosage recommended in the labeling of both antibiotics may be given and depends on the severity of the infection and the patient’s condition.

NOTE: Increases in serum creatinine have occurred when CEFOTAN^® was given alone. If CEFOTAN^® and an aminoglycoside are used concomitantly, renal function should be carefully monitored, because nephrotoxicity may be potentiated.