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Important and emerging beta-lactamase-mediated resistances in hospital-based pathogens: the Amp C enzymes
1Department of Pathology, University of Iowa College of Medicine, Iowa City 52242, USA.
Abstract:
Resistance to third-generation cephalosporins mediated by beta-lactamases is an increasing problem for clinical therapeutics. A wide range of Enterobacteriaceae produce these AmpC enzymes (Bush-Jacoby-Medeiros group 1), including Enterobacter spp., Citrobacter freundii, Morganella morganii, Providencia spp., and Serratia marcescens. Resistance via this mechanism has been shown to be statistically correlated with the use of some third-generation cephalosporins, and the infections caused by these stably derepressed enzyme-producing species seem to occur most frequently in the seriously ill. More recently the genes encoding this enzyme have been documented on plasmids capable of transfer into other species such as Klebsiella pneumoniae. Fourth-generation cephalosporins, with stability and low affinity for the Amp C beta-lactamases and the ability to penetrate rapidly into the periplasmic space of Gram-negative organisms, offer a viable alternative in the treatment of these infections or as empiric regimens. Furthermore, these compounds (example: cefpirome) possess greater potency against the frequently occurring Gram-positive cocci such as oxacillin-susceptible staphylococci and the streptococci (including some penicillin-resistant strains) as compared to previously used anti-pseudomonal cephalosporias, ceftazidime.
Insights
AmpC beta-lactamase resistance to third-generation cephalosporins is rising, particularly in sick patients. Fourth-generation cephalosporins offer a promising alternative for treating these infections.
Area of Science:
- Microbiology
- Clinical Therapeutics
- Antimicrobial Resistance
Background:
- Resistance to third-generation cephalosporins is a growing clinical challenge.
- AmpC beta-lactamases, produced by various Enterobacteriaceae, mediate this resistance.
- This resistance is linked to third-generation cephalosporin use and affects seriously ill patients.
Purpose of the Study:
- To highlight the increasing problem of AmpC beta-lactamase-mediated resistance.
- To discuss the role of fourth-generation cephalosporins as an alternative treatment.
- To compare the efficacy of fourth-generation cephalosporins against Gram-positive cocci.
Main Methods:
- Literature review on beta-lactamase resistance mechanisms.
- Analysis of clinical data correlating cephalosporin use and resistance.
- Pharmacological comparison of fourth-generation cephalosporins with older agents.
Main Results:
- AmpC beta-lactamase production is a significant mechanism of resistance in Enterobacteriaceae.
- Genes encoding AmpC enzymes can be plasmid-mediated, facilitating interspecies transfer.
- Fourth-generation cephalosporins demonstrate stability against AmpC beta-lactamases and enhanced Gram-positive activity.
Conclusions:
- Fourth-generation cephalosporins represent a viable therapeutic option for infections caused by AmpC-producing Enterobacteriaceae.
- These agents offer a valuable alternative for empiric treatment regimens.
- Cefpirome and similar compounds show improved potency against common Gram-positive pathogens.