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[Penetration of meropenem in gram-negative bacilli. Differences in activity with imipenem]
J García de Lomas1, D Navarro, C Gimeno
1Departamento de Microbiología, Hospital Clínico Universitario, Facultad de Medicina, Valencia.
Abstract:
The outer membrane of gramnegative bacteria cell-wall contain channels formed by proteins known as porins, which facilitate the penetration of molecules into the cell. Imipenem and meropenem possess an important intrinsic activity against most gramnegative bacteria due to their high affinity for the penicillin-binding proteins PBP-2 and/or PBP-3. Meropenem is slightly more active against certain species of Enterobacteriaceae, Pseudomonas aeruginosa and nonfermenters bacilli. In this sense the differences in the activity between the two carbapenems may be attributable to differences in their affinity for PBPs, differences in their resistance to beta-lactamases hydrolysis, or to the differences in the capacity to employ certain porin channels. OprF is the main porin channel involved in the beta-lactam penetration of bacteria, though OprC and OprD2 may also contribute to the penetration of carbapenems into P. aeruginosa. However, evidences suggest that although impenem requires the presence of OprD2, meropenem may use other pathways for penetration. In Escherichia coli both carbapenems use ompF and ompC, and no specific porin channels have been detected. Only in the case of Enterobacter cloacae may exceptions exists among Enterobacteriaceae.
Insights
Imipenem and meropenem are carbapenem antibiotics effective against Gram-negative bacteria. Their differing effectiveness may stem from how they utilize bacterial porin channels for entry.
Area of Science:
- Microbiology
- Bacterial Cell Wall Structure
- Antibiotic Resistance
Background:
- Gram-negative bacteria possess an outer membrane with porin channels essential for molecule transport.
- Imipenem and meropenem exhibit potent activity against Gram-negative bacteria by targeting penicillin-binding proteins (PBPs).
Purpose of the Study:
- To investigate the differential mechanisms of imipenem and meropenem penetration into Gram-negative bacteria.
- To explore the role of specific porin channels in the activity of these carbapenems.
Main Methods:
- Comparative analysis of imipenem and meropenem activity against various Gram-negative bacteria.
- Examination of porin channel involvement in carbapenem uptake, focusing on Pseudomonas aeruginosa and Escherichia coli.
Main Results:
- Meropenem shows slightly enhanced activity against certain Enterobacteriaceae, Pseudomonas aeruginosa, and nonfermenter bacilli compared to imipenem.
- While imipenem requires the OprD2 porin for entry into P. aeruginosa, meropenem appears to utilize alternative pathways.
- Both carbapenems utilize OmpF and OmpC porins in Escherichia coli, with no specific porin identified for their entry.
Conclusions:
- Differences in carbapenem activity are influenced by PBP affinity, beta-lactamase stability, and porin channel utilization.
- Meropenem exhibits greater flexibility in bacterial entry mechanisms compared to imipenem, potentially contributing to its broader spectrum of activity in certain species.