Medical Microbiology, University of Edinburgh Medical School, Teviot Place, Edinburgh EH8 9AG, Scotland, UK
![]() |
Abstract |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Keywords: ESBLs , emergence , TEM , CTX-M
![]() |
Introduction |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
![]() |
How does the situation in the UK compare with other European countries? |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Extended-spectrum cephalosporins (cefoperazone, cefuroxime, cefalonium, and the third and forth-generation cephalosporins, ceftiofur and cefquinone) are prescription-only medicines approved in the UK for the treatment of diseases such as mastitis in dairy cattle, respiratory diseases in ruminants (cattle, sheep, goats) and cattle foot rot.5 Extended-spectrum cephalosporins are also licensed for the treatment of bacterial diseases in poultry, such as necrotic enteritis and colisepticaemia. Commonly the only practical method of treating these problematic diseases is mass oral medication.5 Extended-spectrum ß-lactamases (ESBLs) are most often found in Escherichia coli and Klebsiella pneumoniae,6 but have been detected in non-typhoidal salmonellae in France and Italy since 1989 and 1990, respectively.7,8 However, it was not until 14 years later that the first ESBL was actually reported in a salmonella isolate from the UK, a TEM-52 ß-lactamase-containing strain isolated in Glasgow.9 Recently, Batchelor et al.10 retrospectively studied the reference laboratory collection of human clinical and food salmonellae from England and Wales for the presence of CTX-M-type enzymes. Of interest is that the isolates analysed in this study had been collected during 19922003, yet no isolates containing CTX-M enzymes were present in this extensive collection of 278 308 isolates until September 1997.
![]() |
Why would resistance development vary between countries? |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Countries differ in the quantity of cephalosporins used, and the dosage and route of administration, as well as the duration of usage in that country. However, it has proved extremely difficult to obtain data on cephalosporin use in European countries. Many countries monitor sales of veterinary antibiotics, but comparison of sales between countries is confounded by differences in data collection and numbers of food-animal species per country.
In addition to differences in cephalosporin usage, countries may differ in the methods used to detect ESBL producers. In the UK, many laboratories use only ceftazidime resistance as an indicator of ESBL production.10 This may result in cefotaxime-resistant organisms, for which the ceftazidime MIC is in the susceptible range, being missed during ESBL screening tests, and is exemplified by the work of Batchelor et al.10 Similarly, screening for AmpC-type enzymes (which confer a broader spectrum of resistance than the ESBLs) is not routinely performed in the UK. As a result, the first identification of a salmonella isolate from the UK harbouring an AmpC-type enzyme was identified following a retrospective study on isolates collected during 19932003.11 These important studies indicate that we may be missing the opportunity to identify new resistance genes. According to Liebana et al.,11 there should be routine surveillance to identify emerging genes which may present a threat to the treatment of invasive pathogens.
The tendency of salmonellae to develop or acquire resistance mechanisms also depends on the particular serovar and sometimes phage type; antibiotic resistance is, for instance, relatively uncommon in Salmonella Enteritidis.1 During 19962000, the overall incidence of multidrug resistance (resistance to four or more antibiotics) in this serovar was <1% in England and Wales.1 In contrast, multidrug-resistant Salmonella Typhimurium, identified in the UK in 1964, has been responsible for several epidemics. These were caused by definitive phage type (DT) 29 in the late 1960s,12 DT 204 and DT 193 from 1975 until the mid-1980s,13 and DT 104 in the early 1990s.14 Therefore, differences in salmonella resistance between countries will also depend on the prevalence of specific serovars and phage types.
ESBL-harbouring salmonellae are frequently isolated from hospitals in North African countries, India and in South Korea. Travel from these areas has been linked with outbreaks of ESBL-harbouring salmonellae in France.15,16 A study in the UK of 41 906 human isolates of non-typhoidal salmonellae isolated during 19981999 also found a link between travel to developing countries and resistance to third-generation cephalosporins, although the presence of ESBLs in resistant isolates was not confirmed. However, only six of the 14 retrospective cases described by Batchelor et al.10 in 2005 were associated with travel abroad and there was no link between foreign travel and the outbreak of salmonellosis reported in Glasgow in 2004.9
![]() |
Development of ESBL-harbouring salmonellae in the UK |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Fortunately, ESBLs from Salmonella spp. in the UK have not yet been categorically identified to be of veterinary origin. Surveillance of antibiotic resistance in 5214 salmonellae isolated from animals and their environment in 2003 revealed that none was resistant to the third-generation cephalosporin ceftazidime.18 Food-producing animals are the primary reservoirs of salmonella, and so these results suggest that the presence of ESBLs in the UK clinical isolates arose by some other method, such as nosocomial acquisition from other Enterobacteriacae. In Madrid, a nosocomial outbreak caused by a Salmonella Othmarschen was found to involve the dissemination of a single TEM-27-encoding plasmid among E. coli and Enterobacter cloacae.19
Although the epidemiology of the recent reports of ESBL-harbouring salmonellae in the UK is not clear, the detection of three different ESBL types in Britain means that we can no longer be complacent in the face of this serious human health issue. Continued surveillance of the presence of ESBLs in Enterobacteriacae, and rapid elucidation of the mode of spread of these resistance genes in Salmonella spp., is essential to minimize the risks to future treatment that their widespread dissemination would create.
![]() |
References |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
2. Hohmann EL. Nontyphoidal salmonellosis. Clin Infect Dis 2001; 32: 2639.[CrossRef][ISI][Medline]
3. Hammami A, Arlet G, Ben Redjeb S et al. Nosocomial outbreak of acute gastroenteritis in a neonatal intensive care unit in Tunisia caused by multiply drug resistant Salmonella wien producing SHV-2 ß-lactamase. Eur J Clin Microbiol Infect Dis 1991; 10: 6416.[ISI][Medline]
4. Health Protection Agency. Report: Salmonella in humans (excluding S. Typhi and S. Paratyphi), England and Wales, 19812003. http://www.hpa.org.uk/infections/topics_az/salmonella/data_human.htm (4 March 2005, date last accessed).
5. Hornish RE, Kotarski SF. Cephalosporins in veterinary medicine ceftiofur use in food animals. Curr Top Med Chem 2002; 2: 71731.[CrossRef][Medline]
6.
Bradford PA. Extended-spectrum ß-lactamases in the 21st century: characterization, epidemiology, and detection of this important resistance threat. Clin Microbiol Rev 2001; 14: 93351.
7. Garbarg-Chenon A, Vu Thien H, Labia R et al. Characterization of a plasmid coding for resistance to broad-spectrum cephalosporins in Salmonella typhimurium. Drugs Exp Clin Res 1991; 15: 14550.
8.
Villa L, Mammina C, Miriagou V et al. Multidrug and broad-spectrum cephalosporin resistance among Salmonella enterica serotype Enteritidis clinical isolates in southern Italy. J Clin Microbiol 2002; 40: 26625.
9.
Yates CM, Brown DJ, Edwards GF et al. Detection of TEM-52 in Salmonella enterica serovar Enteritidis isolated in Scotland. J Antimicrob Chemother 2004; 53: 4078.
10.
Batchelor M, Hopkins K, Threlfall EJ et al. blaCTX-M genes in clinical Salmonella isolates recovered from humans in England and Wales from 1992 to 2003. Antimicrob Agents Chemother 2005; 49: 13191322.
11.
Liebana E, Batchelor M, Clifton-Hadley FA et al. First report of Salmonella isolates with the DHA-1 AmpC ß-lactamase in the United Kingdom. Antimicrob Agents Chemother 2004; 48: 4492.
12. Anderson ES. Drug resistance in Salmonella typhimurium and its implications. Br Med J 1968; 3: 3339.[ISI][Medline]
13. Rowe B, Threlfall EJ. Drug resistance in gram-negative aerobic bacilli. Br Med Bull 1984; 40: 6876.[ISI][Medline]
14. Threlfall EJ, Frost JA, Ward LR et al. Epidemic in cattle and humans of Salmonella typhimurium DT 104 with chromosomally integrated multiple drug resistance. Vet Rec 1994; 134: 577.[ISI][Medline]
15. Poupart MC, Chanal C, Sirot D et al. Identification of CTX-2, a novel cefotaximase from a Salmonella mbandaka isolate. Antimicrob Agents Chemother 1991; 35: 14981500.[ISI][Medline]
16.
Weill FX, Demartin M, Tande D et al. SHV-12-like extended-spectrum-ß-lactamase-producing strains of Salmonella enterica serotypes Babelsberg and Enteritidis isolated in France among infants adopted from Mali. J Clin Microbiol 2004; 42: 24327.
17.
Munday CJ, Whitehead GM, Todd NJ et al. Predominance and genetic diversity of community- and hospital-acquired CTX-M extended-spectrum ß-lactamases in York, UK. J Antimicrob Chemother 2004; 54: 62833.
18. DEFRA. Salmonella in livestock production in GB 2003. http://www.defra.gov.uk/corporate/vla/science/science-salm-rep03.htm (4 March 2005, date last accessed).
19. Morosini MI, Blazquez J, Negri MC et al. Characterization of a nosocomial outbreak involving an epidemic plasmid encoding for TEM-27 in Salmonella enterica subspecies enterica serotype Othmarschen. J Infect Dis 1996; 174: 101520.[ISI][Medline]
|