JAC Advance Access originally published online on January 14, 2003
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Journal of Antimicrobial Chemotherapy (2003) 51, 470-471
© 2003 The British Society for Antimicrobial Chemotherapy
Correspondence |
CTX-M extended-spectrum ß-lactamase arrives in the UK
1 Division of Microbiology, University of Leeds, Leeds LS2 9JT; 2 Antibiotic Resistance Monitoring and Reference Laboratory, Central Public Health Laboratory, London NW9 5HT; 3 Division of Immunity and Infection, University of Birmingham, Birmingham B15 2TT, UK
Keywords: extended-spectrum ß-lactamase, cefotaxime resistance
Sir,
The evolution and dispersal of extended-spectrum ß-lactamases (ESBLs) have compromised the clinical use of third-generation cephalosporins worldwide. Currently, most ESBLs belong to the TEM and SHV ß-lactamase families and have evolved by mutation to those plasmid-mediated enzyme types that have long caused transferable ampicillin resistance in, for example, Escherichia coli. Now, however, the members of a novel ESBL family, CTX-M, are increasingly being reported in Gram-negative bacilli worldwide. CTX-M enzymes have emerged via the genetic escape and mutation of chromosomal ß-lactamase genes from an obscure Gram-negative genus, Kluyvera. They preferentially hydrolyse and confer resistance to cefotaxime rather than ceftazidime—the opposite pattern to that for most TEM and SHV ESBLs.
CTX-M type ESBLs have become more prevalent than TEM and SHV ESBLs in the southern ‘cone’ of South America, and are also reported from Europe, Africa and the Far East, with major nosocomial outbreaks in Japan and Poland as well as South America.1–3
The appearance of novel resistance determinants in geographically separated regions is always worrying and, although CTX-M ß-lactamases may escape and evolve de novo, the transit of commensal bacteria carrying ESBL genes by travellers may be the most important route for their spread within and between countries. We now report here the first occurrence of a bacterium expressing the CTX-M ß-lactamase in the UK. This highlights the continuing global emergence of this new group of class A ß-lactamases.
During routine screening for the carriage of ESBL-producing isolates at the Paediatric Oncology Ward in St James’s University Hospital, Leeds, UK, a clinical isolate of Klebsiella oxytoca was recovered from a stool sample of a 6-year-old child in May 2000. The isolate was more resistant to cefotaxime than to ceftazidime by disc testing and gave a positive cephalosporin/co-amoxiclav synergy test, implying ESBL production. MICs were: cefotaxime 32 mg/L, ceftazidime 4 mg/L, ceftriaxone 32 mg/L and aztreonam 8 mg/L. PCR amplification of genomic DNA with blaCTX-M-specific primers was positive. Southern blotting and hybridization using a 604 bp PCR-generated probe from blaCTX-M-1 showed the gene to be located on a 130 kb plasmid. Attempts to transfer this plasmid to the laboratory strain E. coli UB1637 were unsuccessful. Nucleotide sequence analysis indicated the gene to be blaCTX-M-9, a variant previously found in both Spain4 and China.3 Analysis of the upstream region of the blaCTX-M-9 gene revealed the presence of part of a putative insertion sequence with 100% identity to IS Ecp1 (Stapleton, GenBank AJ242809). Work is ongoing to determine the prevalence of CTX-M-producing isolates in the hospital. It is a concern that diagnostic laboratories will fail to recognize CTX-M-positive strains as ESBL producers, as it is common practice to screen for ceftazidime resistance as an indicator of ESBLs, on the grounds that it tends to be the best indicator substrate for TEM and SHV variants. Ceftazidime is, however, a poor substrate for CTX-M types, and producers may appear moderately or fully susceptible. We would urge laboratories to test both ceftazidime and cefotaxime against nosocomial Enterobacteriaceae, and to suspect ESBLs (whether TEM/SHV or CTX-M types) in any isolates resistant to either agent. An alternative is to test cefpodoxime, which is degraded by both TEM/SHV and CTX-M ESBLs. In either case, ESBL production can then be confirmed using appropriate synergy tests.5 Failure to identify the CTX-M genes in isolates of bacteria will greatly hamper the control of spread of these clinically important resistance determinants.
Acknowledgements
We would like to thank Wyeth Laboratories, UK, for the support of this study.
Footnotes
* Corresponding author. Tel: +44-113-233-5597; Fax: +44-113-233-5649; E-mail: F.M'Zali{at}leeds.ac.uk 
References
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Baraniak, A., Fiett, J., Sulikowska, A., Hryniewicz, W. & Gniadkowski, M. (2002). Countrywide spread of CTX-M3 extended-spectrum ß-lactamase-producing microorganisms of the family Enterobacteriaceae in Poland. Antimicrobial Agents and Chemotherapy 46, 151–9.
2 . Bonnet, R., Sampaio, J. L. M., Labia, R., De Champ, C., Sirot, D., Chanal, C. et al. (2002). A novel CTX-M ß-lactamase (CTX-M-8) in cefotaxime-resistant Enterobacteriaceae isolated in Brazil. Antimicrobial Agents and Chemotherapy 46, 1936–42.
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Chanawong, A., M’Zali, F. H., Heritage, J., Xiong, J. & Hawkey, P. M. (2002). Three cefotaximases, CTX-M9, CTX-M13 and CTX-M14 among Enterobacteriaceae in the People’s Republic of China. Antimicrobial Agents and Chemotherapy 46, 630–7.
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Sabate, M., Tarrago, R., Navarro, F., Miro, E., Verges, C., Barbe, J. et al. (2000). Cloning and sequence of the gene encoding a novel cefotaxime-hydrolysing ß-lactamase (CTX-M-9) from Escherichia coli in Spain. Antimicrobial Agents and Chemotherapy 44, 1970–7.
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