Cefepime microbiology

Microbiology

Cefepime is a bactericidal agent that acts by inhibition of bacterial cell wall synthesis. Cefepime has a broad spectrum of in vitro activity that encompasses a wide range of Gram-positive and Gram-negative bacteria. Cefepime has a low affinity for chromosomally-encoded beta-lactamases. Cefepime is highly resistant to hydrolysis by most beta-lactamases and exhibits rapid penetration into Gram-negative bacterial cells. Within bacterial cells, the molecular targets of cefepime are the penicillin binding proteins (PBP).

Susceptible organisms

Aerobic Gram-Negative Microorganisms:

• Enterobacter
• Escherichia coli
• Klebsiella pneumoniae
• Proteus mirabilis
• Pseudomonas aeruginosa

Aerobic Gram-Positive Microorganisms:

• Staphylococcus aureus (methicillin-susceptible isolates only)
• Streptococcus pneumoniae
• Streptococcus pyogenes (Lancefield’s Group A streptococci)
• Viridans group streptococci.

The following in vitro data are available, but their clinical significance is unknown. Cefepime has been shown to have in vitro activity against most isolates of the following microorganisms; however, the safety and effectiveness of cefepime in treating clinical infections due to these microorganisms have not been established in adequate and well-controlled trials.
Aerobic Gram-Positive Microorganisms:

• Staphylococcus epidermidis (methicillin-susceptible isolates only)
• Staphylococcus saprophyticus
• Streptococcus agalactiae (Lancefield’s Group B streptococci)

NOTE: Most isolates of enterococci, eg, Enterococcus faecalis, and methicillin-resistant staphylococci are resistant to cefepime.
Aerobic Gram-Negative Microorganisms:

• Acinetobacter lwoffii
• Citrobacter diversus
• Citrobacter freundii
• Enterobacter agglomerans
• Haemophilus influenzae (including beta-lactamase producing isolates)
• Hafnia alvei
• Klebsiella oxytoca
• Moraxella catarrhalis (including beta-lactamase producing isolates)
• Morganella morganii
• Proteus vulgaris
• Providencia rettgeri
• Providencia stuartii
• Serratia marcescens

Microorganism	Susceptible (S) (MIC; mcg/mL)	Intermediate (I) (MIC; mcg/mL)	Resistant (R) (MIC; mcg/mL)
Microorganisms other than Haemophilus spp.* and Streptococcus pneumoniae*	≤8	16	≥32
Haemophilus spp.*	≤2	—*	—*
S. pneumoniae*	≤0.5	1	≥2

^* NOTE: Isolates from these species should be tested for susceptibility using specialized dilution testing methods.1
Also, isolates of Haemophilus spp. with MICs greater than 2 mcg/mL should be considered equivocal and should be further evaluated

A report of “Susceptible” indicates that the pathogen is likely to be inhibited if the antimicrobial compound in the blood reaches the concentrations usually achievable. A report of “Intermediate” indicates that the result should be considered equivocal, and, if the microorganism is not fully susceptible to alternative, clinically feasible drugs, the test should be repeated. This category implies possible clinical applicability in body sites where the drug is physiologically concentrated or in situations where high dosage of drug can be used. This category also provides a buffer zone which prevents small uncontrolled technical factors from causing major discrepancies in interpretation. A report of “Resistant” indicates that the pathogen is not likely to be inhibited if the antimicrobial compound in the blood reaches the concentrations usually achievable; other therapy should be selected.

Standardized susceptibility test procedures require the use of laboratory control microorganisms to control the technical aspects of the laboratory procedures. Laboratory control microorganisms are specific strains of microbiological assay organisms with intrinsic biological properties relating to resistance mechanisms and their genetic expression within bacteria; the specific strains are not clinically significant in their current microbiological status. Standard cefepime powder should provide the following MIC values when tested against the designated quality control strains:

Microorganism	ATCC	MIC (mcg/mL)
Escherichia coli	25922	0.016 to 0.12
Staphylococcus aureus	29213	1 to 4
Pseudomonas aerugino	27853	1 to 4
Haemophilus influenzae	49247	0.5 to 2
Streptococcus pneumoniae	49619	0.06 to 0.25