The CTX-M β-lactamase pandemic

In the past decade CTX-M enzymes have become the most prevalent extended-spectrum beta-lactamases, both in nosocomial and in community settings. The insertion sequences (ISs) ISEcp1 and ISCR1 (formerly common region 1 [CR1] or orf513) appear to enable the mobilization of chromosomal beta-lactamase Kluyvera species genes, which display high homology with bla(CTX-Ms). These ISs are preferentially linked to specific genes: ISEcp1 to most bla(CTX-Ms), and ISCR1 to bla(CTX-M-2) or bla(CTX-M-9). The bla(CTX-M) genes embedded in class 1 integrons bearing ISCR1 are associated with different Tn402-derivatives, and often with mercury Tn21-like transposons. The bla(CTX-M) genes linked to ISEcp1 are often located in multidrug resistance regions containing different transposons and ISs. These structures have been located in narrow and broad host-range plasmids belonging to the same incompatibility groups as those of early antibiotic resistance plasmids. These plasmids frequently carry aminoglycoside, tetracycline, sulfonamide or fluoroquinolone resistance genes [qnr and/or aac(6')-lb-cr], which would have facilitated the dissemination of bla(CTX-M) genes because of co-selection processes. In Escherichia coli, they are frequently carried in well-adapted phylogenetic groups with particular virulence-factor genotypes. Also, dissemination has been associated with different clones (CTX-M-9 or CTX-M-14 producers) or epidemic clones associated with specific enzymes such as CTX-M-15. All these events might have contributed to the current pandemic CTX-M beta-lactamase scenario.