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Cefepime: overview of activity in vitro and in vivo
1Istituto di Malattie Respiratoire, Cattedra di Chemio terapia, Pavia, Italy.
Abstract:
Cefepime is a novel methoxyimino-aminothiazolyl cephalosporin with a quaternized N-methyl-pyrrolidine moiety at the 3' position conferring zwitterionic properties. Because of this the molecule penetrates the outer cell membrane of Gram-negative bacteria rapidly. In addition it is resistant to degradation by several plasmid and chromosomally-mediated beta-lactamases, for which it also shows very low affinity and no inducing capacity. It has good affinity for PBPs 2 and 3 of Escherichia coli and for PBP 3 of Pseudomonas aeruginosa. Its broad-spectrum of activity includes Gram-positive and Gram-negative pathogens. It is more active than cefotaxime or ceftazidime, against Enterobacteriaceae. The MIC90 for P. aeruginosa is higher than that of ceftazidime, but lower than those of cefpirome, cefoperazone and latamoxef. Other Gram-negative organisms, Haemophilus influenzae, Neiserria meningitidis, Neiserria gonorrhoeae, Moraxella catarrhalis are highly susceptible to cefepime. Among Gram-positive species methicillin-susceptible Staphylococcus aureus and coagulase-negative staphylococci, whether beta-lactamase producers or not, Streptococcus pneumoniae and Streptococcus pyogenes are susceptible. Cefepime is active against cefotaxime- and/or ceftazidime-resistant Enterobacteriaceae. Only strains of P. aeruginosa producing large amounts of beta-lactamase may be resistant to both ceftazidime and cefepime. In experimental infections such as meningitis, induced with various bacterial species in neonatal rats and chronic staphylococcal osteomyelitis in rabbits, cefepime has shown good efficacy.
Insights
Cefepime, a novel cephalosporin antibiotic, demonstrates broad-spectrum activity against Gram-positive and Gram-negative bacteria, including resistant strains. Its unique properties allow rapid bacterial cell penetration and resistance to beta-lactamases, showing efficacy in experimental infections.
Area of Science:
- Microbiology
- Pharmacology
- Infectious Diseases
Background:
- Cefepime is a fourth-generation cephalosporin antibiotic.
- It possesses a unique zwitterionic structure due to a quaternized N-methyl-pyrrolidine moiety.
- This structure facilitates rapid penetration of the outer cell membrane in Gram-negative bacteria.
Purpose of the Study:
- To characterize the antimicrobial spectrum and properties of cefepime.
- To evaluate its efficacy against various bacterial pathogens, including those resistant to other beta-lactam antibiotics.
- To assess its affinity for penicillin-binding proteins (PBPs) and resistance to beta-lactamases.
Main Methods:
- In vitro susceptibility testing against a range of Gram-positive and Gram-negative bacteria.
- Evaluation of resistance to plasmid and chromosomally-mediated beta-lactamases.
- Determination of affinity for key penicillin-binding proteins (PBPs) in *Escherichia coli* and *Pseudomonas aeruginosa*.
- Assessment of efficacy in experimental infection models, including meningitis and osteomyelitis.
Main Results:
- Cefepime exhibits broad-spectrum activity against Gram-positive and Gram-negative pathogens.
- It demonstrates enhanced activity against Enterobacteriaceae compared to cefotaxime and ceftazidime.
- The antibiotic is effective against cefotaxime- and/or ceftazidime-resistant Enterobacteriaceae.
- High susceptibility was observed for *Haemophilus influenzae*, *Neisseria meningitidis*, *Neisseria gonorrhoeae*, and *Moraxella catarrhalis*.
- Methicillin-susceptible *Staphylococcus aureus*, coagulase-negative staphylococci, *Streptococcus pneumoniae*, and *Streptococcus pyogenes* are susceptible.
- Cefepime shows good efficacy in experimental meningitis and osteomyelitis models.
Conclusions:
- Cefepime is a potent cephalosporin with a broad antimicrobial spectrum and favorable pharmacokinetic properties.
- Its resistance to beta-lactamases and ability to penetrate bacterial membranes contribute to its efficacy.
- Cefepime represents a valuable therapeutic option for treating infections caused by susceptible Gram-positive and Gram-negative bacteria, including resistant strains.