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Resistance to imipenem in Pseudomonas aeruginosa: clinical experience and biochemical mechanisms
J P Quinn1, A E Studemeister, C A DiVincenzo
1Department of Medicine, Michael Reese Hospital, Chicago, Illinois 60616.
Abstract:
Emergence of resistance to imipenem during therapy for Pseudomonas aeruginosa infections is common and may result in treatment failure. Resistance emerges most often during therapy for lower respiratory tract infections. There are several unique features of this resistance to imipenem. First, cross-resistance to other beta-lactam agents is not observed. Second, the mechanism of resistance in most of the isolates studied to date appears to be related to a selective permeability barrier across the bacterial outer membrane, usually associated with discrete alterations in the electrophoretic profiles of outer membrane proteins. These data suggest that imipenem may traverse the outer membrane of P. aeruginosa via a specific porin protein that is not critical for penetration of other beta-lactam antibiotics.
Insights
Emergence of imipenem resistance in Pseudomonas aeruginosa is common, especially in respiratory infections. This resistance is unique, lacking cross-resistance to other beta-lactams and linked to outer membrane protein alterations affecting imipenem entry.
Area of Science:
- Microbiology
- Infectious Diseases
- Pharmacology
Background:
- Antibiotic resistance in Pseudomonas aeruginosa poses a significant clinical challenge.
- Imipenem is a crucial antibiotic for treating P. aeruginosa infections, but resistance can emerge during therapy.
- Understanding resistance mechanisms is vital for effective treatment strategies.
Purpose of the Study:
- To investigate the unique features of imipenem resistance in Pseudomonas aeruginosa.
- To elucidate the mechanism by which P. aeruginosa develops resistance to imipenem.
- To determine if specific porin proteins are involved in imipenem penetration.
Main Methods:
- Analysis of imipenem-resistant P. aeruginosa isolates from patients undergoing therapy.
- Assessment of cross-resistance patterns with other beta-lactam antibiotics.
- Examination of outer membrane protein profiles using electrophoresis.
- Investigation of potential porin involvement in antibiotic permeability.
Main Results:
- Resistance to imipenem frequently emerges during P. aeruginosa therapy, particularly for lower respiratory tract infections.
- Imipenem resistance did not exhibit cross-resistance to other beta-lactam agents.
- The primary mechanism identified involves a selective permeability barrier due to alterations in outer membrane proteins.
- Evidence suggests imipenem utilizes a specific porin for outer membrane traversal, distinct from those used by other beta-lactams.
Conclusions:
- Imipenem resistance in P. aeruginosa is a distinct phenomenon not associated with broad beta-lactam cross-resistance.
- Outer membrane protein alterations creating a permeability barrier are key to imipenem resistance.
- Specific porins likely mediate imipenem entry into P. aeruginosa, offering a potential target for future therapeutic strategies.