Meropenem is a carbapenem antibacterial agent[1]. The MICs of meropenem was 0.03 mg/L against S. aureus and E. coli but > 256 mg/L against C. albicans[2]. It is stable to hydrolysis by most beta-lactamases produced by Gram-negative and Gram-positive bacteria, including penicillinases and cephalosporinases[1].
Meropenem, a carbapenem antibacterial agent, is stable to hydrolysis by most beta-lactamases produced by Gram-negative and Gram-positive bacteria, including penicillinases and cephalosporinases[1]. The MICs of meropenem was 0.03 mg/L against S. aureus and E. coli but > 256 mg/L against C. albicans[2].
In vitro, meropenem has the minimum inhibitory concentration (MIC) values is 128 µg/mL, but meropenem combined with vaborbactam reduced the minimum inhibitory concentration (MIC) values of meropenem by ≥ 64-fold against engineered strains and clinical isolates producing class A serine carbapenemases (e.g. KPC-2, KPC-3, SME-2, NMC-A)[3][4]. The minimum inhibitory concentrations of carvacrol and meropenem on carbapenem-resistant K. pneumoniae (CRKP) strains were detected within a range of 32-128 µg/mL using the broth microdilution method[5]. The MIC90 of meropenem (when tested with a fixed concentration of 8 µg/ml of vaborbactam) for isolates of KPC-positive Enterobacteriaceae was 1 µg/ml, and MIC values ranged from ≤0.03 to >32 µg/ml[6].
In vivo, in fully PTZ (pentylenetetrazol)-kindled mice, intravenous administration of meropenem (500 mg/kg) did not elicit any convulsions in the electroconvulsive shock test with low-intensity stimulus currents[7]. In vivo efficacy test shown that cats were administrated 10 mg/kg q12h meropenem is effected against bacteria with MIC values of 6 µg/ml, 7 µg/ml and 10 µg/ml for IV, IM and SC administration, respectively[8].
References:
[1]Zhanel GG, et al. Imipenem-relebactam and meropenem-vaborbactam: two novel carbapenem-beta-lactamase inhibitor combinations. Drugs. 2018;78(1):65-98.
[2]Yu L, et al. Synergetic Effects of Combined Treatment of Colistin With Meropenem or Amikacin on Carbapenem-Resistant Klebsiella pneumoniae in vitro. Front Cell Infect Microbiol. 2019 Dec 10;9:422.
[3]Hecker SJ, et al. Discovery of a cyclic boronic acid beta-lactamase inhibitor (RPX7009) with utility vs class A serine carbapenemases. J Med Chem. 2015;58(9):3682-3692.
[4]Lomovskaya O, et al. Vaborbactam: spectrum of beta-lactamase inhibition and impact of resistance mechanisms on activity in Enterobacteriaceae. Antimicrob Agents Chemother. 2017;61(11):e01443-17.
[5]KÖse EO. In vitro activity of carvacrol in combination with meropenem against carbapenem-resistant Klebsiella pneumoniae. Folia Microbiol (Praha). 2022 Feb;67(1):143-156.
[6]Hackel MA, et al. In Vitro Activity of Meropenem-Vaborbactam against Clinical Isolates of KPC-Positive Enterobacteriaceae. Antimicrob Agents Chemother. 2017 Dec 21;62(1):e01904-17.
[7]Suemaru K, et al. 5-Fluorouracil exacerbates cefepime-induced convulsions in pentylenetetrazol-kindled mice. Epilepsy Res. 2019 Nov;157:106195.
[8]Albarellos GA, et al. Pharmacokinetics of meropenem after intravenous, intramuscular and subcutaneous administration to cats. J Feline Med Surg. 2016 Dec;18(12):976-980.
美罗培南是一种碳青霉烯类抗菌剂[1]。它对金黄色葡萄球菌和大肠杆菌的 MIC 值为 0.03 mg/L,对白僵菌的 MIC 值大于 256 mg/L[2]。美罗培南对革兰氏阴性菌和革兰氏阳性菌产生的大多数β-内酰胺酶(包括青霉素酶和头孢菌素酶)的水解作用稳定[1]。
在体外,美罗培南的最低抑菌浓度(MIC)值为 128 µg/mL,但美罗培南与伐硼内酰胺联合使用,可使美罗培南对产生 A 类丝氨酸碳青霉烯酶(如 KPC-2、KPC-3、SME-2、NMC-A)的工程菌株和临床分离株的最低抑菌浓度(MIC)值降低≥64 倍[3][4]。使用肉汤微稀释法,检测到香芹酚和美罗培南对耐碳青霉烯类药物的肺炎克氏菌(CRKP)菌株的最小抑菌浓度在 32-128 µg/mL 范围内[5]。美罗培南对 KPC 阳性肠杆菌科细菌分离株的 MIC90(与固定浓度为 8 µg/ml 的伐博巴坦一起测试时)为 1 µg/ml,MIC 值范围从≤0.03 到 >32 µg/ml[6]。
在体内,对完全诱发 PTZ(戊四唑)的小鼠静脉注射美罗培南(500 毫克/千克),在低强度刺激电流的电休克试验中不会引起任何惊厥[7]。体内药效试验表明,给猫每 12 小时注射 10 毫克/千克美罗培南对细菌是有效的,静脉注射、口服和皮下注射的 MIC 值分别为 6 微克/毫升、7 微克/毫升和 10 微克/毫升[8]。