Cefepime (hydrochloride)

Cefepime hydrochloride is a broad-spectrum, blood-brain barrier-permeable cephalosporin antibiotic with hPON1 inhibitory activity, with an IC₅₀ of 21.115 mM and a K_i of 35.092 mM. Cefepime hydrochloride inhibits hPON1 via a non-competitive mechanism and blocks GABA_A receptors. Cefepime hydrochloride penetrates the outer membrane of Gram-negative bacteria, inhibits the growth of Gram-positive and Gram-negative bacteria, and does not induce the production of β-lactamase^[1][2][3][4]. In Vitro:Hydrochloride of Cefepime (18 h) potently inhibits most isolates of Gram-negative aerobic bacteria. Among these pathogens, the MIC₉₀ value is ≤1 mg/L for most Enterobacteriaceae, 16 mg/L for Pseudomonas aeruginosa, and ≤0.12 mg/L for Haemophilus influenzae, Neisseria gonorrhoeae and Branhamella catarrhalis^[4].
Hydrochloride of Cefepime (18-48 h) inhibits Gram-positive bacterial isolates, with an MIC₉₀ value of ≤ 4 mg/L against staphylococci and an MIC₉₀ value of ≤ 0.25 mg/L against most streptococci, but shows limited activity against Enterococcus faecalis, Listeria monocytogenes and Bacteroides species^[4].
Cefepime hydrochloride exhibits stable in vitro activity across different culture media, pH values, and inoculum sizes. For most isolates, the difference between its MIC and MBC values is extremely small, but the MBC values of Pseudomonas aeruginosa and Staphylococcus aureus in human serum are higher^[4].
Hydrochloride of Cefepime (2-8×MIC; 2-24 h) exhibits concentration-dependent bactericidal activity against Enterobacter cloacae (with the strongest activity and no regrowth observed at 8×MIC), sustained bactericidal activity against Pseudomonas aeruginosa, but only limited transient activity against Methicillin (HY-121544)-resistant Staphylococcus aureus^[4].
1 mM Cefepime hydrochloride exhibits high stability against almost all tested plasmid-mediated and chromosome-mediated bacterial β-lactamases, and is only slightly hydrolyzed by the PSE-2 enzyme^[4].
Cefepime hydrochloride is a weak inhibitor of most bacterial β-lactamases, exhibiting only weak activity against Proteus vulgaris Ic enzyme and Pseudomonas aeruginosa Id enzyme, with an IC₅₀ value of > 400 mg/L against the key clinical β-lactamases TEM-1 and P99^[4].
The MIC values of Cefepime hydrochloride show only minor differences among permeability mutants of Escherichia coli, but an 8-fold difference among permeability mutants of Pseudomonas aeruginosa, indicating that its effect on enhancing permeability across bacterial cell walls is limited^[4]. In Vivo:Cefepime hydrochloride induces bacterial stasis in a neutropenic murine thigh infection model infected with Enterobacteriaceae and Klebsiella pneumoniae, under the condition that the unbound drug concentration remains above the MIC for 0-37.7% of the dosing interval^[2].
Hydrochloride of Cefepime (250-500 mg/kg; intravenous bolus) does not increase the susceptibility to pentylenetetrazol (PTZ)-induced convulsions in normal male ICR mice^[3].
Hydrochloride of Cefepime (250-500 mg/kg; intravenous bolus) significantly increases the average seizure grade to 3.3 in the low-current electroshock-induced seizure model of normal male ICR mice, while the 250 mg/kg dose increases the average seizure grade to 2.0^[3].
Hydrochloride of Cefepime (500 mg/kg; intravenous bolus) induces convulsions in 2 out of 3 normal male ICR mice, and elicits electroencephalogram spike waves in the parietal cortex of 1 mouse following low-current electroshock stimulation^[3].
Cefepime hydrochloride (500 mg/kg; intravenous bolus) significantly increases the average seizure grade induced by low-current electroconvulsive shock to 4.0 in cornea-kindled male ICR mice^[3].