CTX-M-Type Extended-Spectrum β-Lactamases in Italy: Molecular Epidemiology of an Emerging Countrywide Problem

Abstract

A nationwide survey of extended-spectrum ␤-lactamase (ESBL) production among Enterobacteriaceae, carried out in 2003, showed that CTX-M-type enzymes have achieved a sizeable prevalence among ESBL producers in Italy, mostly in Escherichia coli and, to a lesser extent, in Klebsiella pneumoniae. In this work, we report on the molecular epidemiology of the CTX-M-producing isolates from that survey and on the mechanisms of dissemination of these emerging resistance determinants. The CTX-M-producing isolates were detected in 10 of the 11 participating centers distributed across the Italian national territory, although at remarkably variable rates in different centers (1.2 to 49.5% of the ESBL producers). All CTX-M determinants were of group 1, with CTX-M-15 and CTX-M-1 being the most prevalent variants (60% and 35%, respectively) and CTX-M-32 carried by a minority (5%) of isolates. Each variant was detected both in E. coli and in K. pneumoniae. Genotyping of the CTX-M-producing isolates by random amplification of polymorphic DNA revealed a notable diversity, especially among those producing CTX-M-1, while clonal expansion was evident with some CTX-M-15-producing strains. Mating experiments revealed a higher overall transferability of bla CTX-M-1 and bla CTX-M-32 than of bla CTX-M-15 . Coresistance to quinolones and aminoglycosides was overall higher with the CTX-M-15-producing isolates. The present results indicate that CTX-M-producing strains are now widespread across the Italian territory and underscore the emerging role of these ESBL determinants in the European setting. They also reveal notable differences in the dissemination mechanisms of genes encoding different CTX-M variants of the same lineage.

High Prevalence and Significant Association of ESBL and QNR Genes in Pathogenic Klebsiella pneumoniae Isolates of Patients from Kolkata, India

“…K. pneumoniae ATCC 700603 and E. coli ATCC 25922 were used as positive and negative controls respectively in each phenotypic ESBL test [10]. K. pneumoniae B1 was used as quinolone drug resistant positive control [11].…”

Extended-Spectrum β-Lactamases of the CTX-M Type Now in Switzerland

“…The antibiotic susceptibility of enterobacterial clinical isolates was determined with the Vitek2 Advance Expert System (bioMerieux) and by the disk diffusion method on Mueller-Hinton (MH) agar plates with ␤-lactam and non-␤-lactam antibioticcontaining disks (Sanofi Diagnostics Pasteur, Marnes-La-Coquette, France), according to the Clinical and Laboratory Standards Institute guidelines (7). The double-disk synergy test was performed with ceftriaxone, ceftazidime, aztreonam, cefpodoxime, and amoxicillin-clavulanic acid disks using different disk spacings (20,25,30, and 40 mm) on MH agar plates, and the results were interpreted as described previously (11). The Etest strips containing cefepime plus clavulanic acid (AB Biodisk, Solna, Sweden) were also used.…”

“…Most of the CTX-Ms hydrolyze cefotaxime better than ceftazidime. However, several CTX-Ms including CTX-M-15 (2, 12, 25), which is now the most widespread CTX-M enzyme worldwide (6), hydrolyze ceftazidime efficiently (25).Since those CTX-Ms are reported increasingly in France (8,15,17,26), Italy (4,20), and recently Austria (9), it was interesting to search for those enzymes in Switzerland, a country known to have a strict policy of antibiotic prescription and to have an overall low level of multidrug resistance in bacteria (10).The aim of the present study was to estimate the prevalence and the type of the ESBLs produced by enterobacterial isolates among nonrepetitive clinical isolates over an 18-month period from January 2004 to June 2005 at the University Hospital of Lausanne, Switzerland. …”

“…Since those CTX-Ms are reported increasingly in France (8,15,17,26), Italy (4,20), and recently Austria (9), it was interesting to search for those enzymes in Switzerland, a country known to have a strict policy of antibiotic prescription and to have an overall low level of multidrug resistance in bacteria (10).…”

EPIDEMIOLOGICAL OBSERVATORY: spreading of ESBL and carbapenemase positive strains in the period between January 2007 - June 2012, at the Hospital - University Campus - Hospital “Luigi Sacco” in Milan

“…Inoltre una rapida identificazione di ESBL e carbapenemasi permette l'immediata applicazione di tutte le misure di prevenzione atte al contenimento e alla diffusione dell'infezione (20) (isolamento dei pazienti, controlli programmati sui Reparti a rischio etc…), nonché la possibilità di instaurare una corretta terapia farmacologica per evitare l'insorgere di nuove e più temibili resistenze (7,23). Nell'ultimo decennio anche in Italia la prevalenza delle ESBL ed enzimi correlati ha raggiunto livelli preoccupanti, secondo numerosi studi, infatti siamo passati dalla percentuale di Enterobacteriaceae produttrici di ESBL che nel 2003 si attestava intorno al 7% con una prevalenza del tipo CTX-M di circa il 60% (dato nazionale) (15,18), a dati più recenti del 16.9% di ceppi ESBL produttori che hanno confermato la tendenza all'aumento e ad un drastico incremento del tipo CTX-M, che ha raggiunto una prevalenza del 73% (9, 22).…”