Cefepime (hydrochloride)

Cefepime (BMY-28142) 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 exhibits high affinity for PBPs, inhibits the growth of both Gram-positive and Gram-negative bacteria, and does not induce the production of β-lactamases^[1][2][3][4]. In Vitro:Cefepime (18 h) hydrochloride 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].
Cefepime (18-48 h) hydrochloride 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].
Cefepime (2-8×MIC; 2-24 h) hydrochloride 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].
Cefepime (1 mM) 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].
Cefepime hydrochloride exhibited only marginal differences in MIC values among Escherichia colipermeability mutants, whereas an 8-fold difference was observed among Pseudomonas aeruginosapermeability mutants, indicating that its ability to enhance bacterial cell wall penetration 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].
Cefepime (250-500 mg/kg; intravenous bolus) hydrochloride does not increase the susceptibility to pentylenetetrazol (PTZ)-induced convulsions in normal male ICR mice^[3].
Cefepime (250-500 mg/kg; intravenous bolus) hydrochloride 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].
Cefepime (500 mg/kg; intravenous bolus) hydrochloride 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 (500 mg/kg; intravenous bolus) hydrochloride significantly increases the average seizure grade induced by low-current electroconvulsive shock to 4.0 in cornea-kindled male ICR mice^[3].