SHV-derived Extended-spectrum Beta-lactamases Research Articles

Extended-spectrum β-lactamases in non-typhoidal Salmonella spp. isolated in the UK are now a reality: why the late arrival?

In February 2004, we reported the first recognition of the presence of an extended-spectrum beta-lactamase (ESBL) in non-typhoidal Salmonella spp. in the UK; the beta-lactamase was TEM-52. Six months later, an SHV-derived ESBL (SHV-12) was detected in a salmonella strain isolated in York and 6 months after that we have just identified CTX-M-type beta-lactamases in Scottish isolates of Salmonella enterica subsp. enterica serovar Typhimurium and Salmonella Virchow (unpublished results). A very recent retrospective study of UK isolates suggests that they may have been in the population for some years but have gone undetected. Even so, compared with reports of ESBLs in Salmonella spp. elsewhere, these results are suggestive of a delayed emergence of the ESBL phenotype in non-typhoidal Salmonella spp. in the UK. Should the British congratulate themselves on warding off the emergence of these important resistance mechanisms in Salmonella spp., or is the sudden revelation of three of the major ESBL types a cause for concern?

Treatment options for extended-spectrum beta-lactamase-producers.

A review of antibiotic options for the treatment of infections caused by extended-spectrum beta-lactamase-producing isolates is presented. The use of the third-generation cephalosporin, cefotaxime, for infections caused by isolates producing ceftazidimase-type extended-spectrum beta-lactamases is controversial, despite in vitro susceptibility to the antibiotic in many instances. The fourth-generation cephalosporin, cefipime, although active against most extended-spectrum beta-lactamases, is reported to show a marked inoculum effect. The cephamycins, such as cefoxitin. are generally effective against Enterobacteriaceae producing TEM- and SHV-derived extended-spectrum beta-lactamases, but Klebsella pneumoniae strains are prone to cephamycin resistance as a result of porin loss. The use of beta-lactamase inhibitor combinations is variable. Sulbactam is less effective than clavulanate for the inhibition of SHV-derived extended-spectrum beta-lactamases and a marked inoculum effect has been noted, while the efficacy of tazobactam against SHV-derived extended-spectrum beta-lactamase producers is controversial. Furthermore, extended-spectrum beta-lactamases are often encoded by multi-resistant plasmids carrying genes conferring resistance to aminoglycosides, chloramphenicol, sulfonamides, trimethoprim and other antimicrobials, severely limiting even alternative therapies. Extensive susceptibility testing before the institution of antibiotic therapy is thus vital.

A preliminary survey of extended-spectrum beta-lactamases (ESBLs) in clinical isolates of Klebsiella pneumoniae and Escherichia coli in Japan.

We conducted a survey of extended-spectrum beta-lactamases (ESBLs) among 16805 Escherichia coli and 9794 Klebsiella pneumoniae clinical isolates recovered from 196 separate medical institutions during the period January 1997 to January 1998. Using the criteria for minimal inhibitory concentrations (MICs) of oxyimino-cephalosporins of >/=8 microg ml(-1) and confirmation by double-disk test, we detected 15 E. coli and 34 K. pneumoniae isolates producing ESBLs. Genotypes of ESBLs determined by PCR with type-specific primers included one TEM-derived and 24 SHV-derived ESBLs, in addition to 24 Toho-1-type ESBLs, one of the major types of ESBLs reported in Japan. Nucleotide sequence analysis of SHV-specific PCR products revealed that SHV-12 was the dominant type of SHV-derived ESBL. In addition, we also identified TEM-26 and SHV-2. This is the first report characterizing TEM- and SHV-derived ESBLs in Japan.

Repeated epidemics caused by extended-spectrum beta-lactamase-producing Serratia marcescens strains.

An outbreak of Serratia marcescens involving 42 patients admitted to the general intensive care unit of the Hospital of Varese, Italy, occurred from March 1994 to August 1995. The causative strains were resistant to oxyimino-cephalosporins and monobactams due to their production of an extended-spectrum beta-lactamase. Another outbreak caused by Serratia marcescens strains had occurred in the same unit a few months earlier, from February to October 1993, with the strains involved producing a novel TEM-derived extended-spectrum beta-lactamase. In order to verify whether there were any relationships between isolates from the two epidemics, the strains and their enzymes were characterized. Biochemical data and gene amplification experiments showed that the isolates of the second outbreak harbored a non-conjugative plasmid of approximately 48 kb, codifying for the production of an SHV-derived extended-spectrum beta-lactamase with pI 8.2. Restriction fragment length polymorphism analysis of total genomic DNA by pulsed-field gel electrophoresis of Serratia marcescens isolates unambiguously identified two different bacterial clones responsible for the two epidemics. Epidemiological and microbiological investigations demonstrated the long persistence of Serratia marcescens strains and their circulation in other hospital wards, thus suggesting their possible role as a long-term reservoir for further epidemic spread.

TEM- and SHV-derived extended-spectrum beta-lactamases: relationship between selection, structure and function.

The later-generation cephalosporins were developed to overcome beta-lactamases which conferred resistance to earlier beta-lactam drugs. Within two years of their clinical introduction, the ubiquitous TEM and SHV plasmid-encoded beta-lactamase genes underwent simple point mutations that changed key amino acids around the active site of the protein and enabled the enzyme to bind and hydrolyse these new drugs. Successive mutations interacted in concert, radically increasing the enzymes' abilities to bind and confer resistance to later-generation cephalosporins. These modified enzymes have been classified in three groups, based on activity, and altered functions have been correlated with changes in the enzyme structure.