Cefepime microbiology
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Abdurahman Khalil, M.D. [2]
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:
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 |
Diffusion Techniques Quantitative methods that require measurement of zone diameters also provide reproducible estimates of the susceptibility of bacteria to antimicrobial compounds. One such standardized procedure2 requires the use of standardized inoculum concentrations. This procedure uses paper disks impregnated with 30 mcg of cefepime to test the susceptibility of microorganisms to cefepime. Interpretation is identical to that stated above for results using dilution techniques.
Reports from the laboratory providing results of the standard single-disk susceptibility test with a 30-mcg cefepime disk should be interpreted according to the following criteria:
Microorganism | Susceptible(S)mm | Intermediate(I)mm | Resistant(R)mm |
Microorganisms other than Haemophilus spp.* and S. pneumoniae* |
≥18 | 15 to 17 | ≤14 |
Haemophilus spp.* | ≥26 | —* | —* |
**NOTE: Isolates from these species should be tested for susceptibility using specialized diffusion testing methods.2 Isolates of Haemophilus spp. with zones smaller than 26 mm should be considered equivocal and should be further evaluated. Isolates of S. pneumoniae should be tested against a 1-mcg oxacillin disk; isolates with oxacillin zone sizes larger than or equal to 20 mm may be considered susceptible to cefepime.
As with standardized dilution techniques, diffusion methods 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. For the diffusion technique, the 30 mcg cefepime disk should provide the following zone diameters in these laboratory test quality control strains.
Microorganism | ATCC | Zone Size Range (mm) |
Escherichia coli | 25922 | 29 to 35 |
Staphylococcus aureus | 25923 | 23 to 29 |
Pseudomonas aeruginosa | 27853 | 24 to 30 |
Haemophilus influenzae | 49247 | 25 to 31 |