[Beta-lactamases of Gram negative bacteria: never-ending clockwork!].
The acquired resistance against the wide-spectrum and highly stable beta-lactams including third-generation cephalosporins (3GC) and carbapenems is constinuously increasing and widespead with the discovery of various plasmid-encoded, or genes cassette or integrons coding for a novel beta-lactamase, always a major mechanism of resistance. To explain resistance against 3GC, with the continuing story with TEM and SHV mutated enzymes, several types of ESBL (class A) emerge the CTX-M type, at least CTX-M-40, but also other non predominant types intitled BES, GES, PLA, PER, VEB. The wider resistance including 3GC, cephamycins and beta-lactamase inhibitor is correlated to synthesis of transferable cephalosporinases (class C) usually located in the chromosome but mobilized from Enterobacter spp., Citrobacter freundii, Hafnia alvei, Morganella morganii, Aeromonas caviae. Such genes encoded the following types: ACC-1, ACT-1, CFE-1, CMY group, DHA-1, FOX group, MIR-1, MOX-1. Finally the resistance against carbapemens e.g. imipenem originally restricted to Pseudomonas aeruginosa, then to Acinetobacter baumannii and finally to enterobacteria is related to production of novel enzymes (classes B, D and A) denominated IMP, VIM SME, GIM, OXA, KPC. A striking exemple of evolution towards more and more resistance is given by Salmonella, even from animal origins, a great threat fo public health. So far it appears necessary to perform molecular approaches to identify such enzymatic production. Finally because the absence of real new drugs, the discovery of some progenitors of the gene beta-lactamase, a strict control of beta-lactam antibiotics must be provide not only in medecine or veterinary field but also in agriculture, including aquaculture for example.
Philippon
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A
Service de bactériologie, CHU Cochin, AP-HP, Paris. alain.philippon@cch.ap-hop-paris
Arlet
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D000818:Animals; D024881:Drug Resistance, Bacterial; D006090:Gram-Negative Bacteria / Q000187:drug effects / Q000201:enzymology*; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy*; D006801:Humans; D008997:Monobactams / Q000494:pharmacology / Q000627:therapeutic use*; D012480:Salmonella Infections / Q000188:drug therapy; D015047:Zoonoses; D001618:beta-Lactamases / Q000378:metabolism*
D008997:Monobactams; D001618:beta-Lactamases