Cefotaximases (CTX-M-ases), an expanding family of extended-spectrum β-lactamases

Walther-Rasmussen, Jan; Høiby, Niels

doi:10.1139/w03-111

Cited by 86 publications

(73 citation statements)

References 111 publications

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“…Other worldwide studies have documented similar findings (6,30). This increase has been attributed to the rising prevalence of the CTX-M family of ESBLs that has emerged as an important and rapidly developing problem worldwide (1,9,25).…”

Section: Discussionsupporting

confidence: 56%

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Spread of Escherichia coli Strains with High-Level Cefotaxime and Ceftazidime Resistance between the Community, Long-Term Care Facilities, and Hospital Institutions

et al. 2006

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A total of 151 Escherichia coli strains resistant to cefotaxime and ceftazidime were isolated during a prospective surveillance study. These strains were characterized by clinical, microbiological, and molecular analyses and were distributed into four clusters of 103, 11, 6, and 5 isolates, along with 25 unrelated strains. The principal cluster was isolated from urine, wound, blood, and other samples in three hospitals, eight nursing homes, and a community healthcare center. This cluster was associated with both nosocomial (65%) and community-acquired (35%) infections. Most strains were resistant to ciprofloxacin, gentamicin, tobramycin, cefepime, amoxicillin-clavulanic acid, and trimethoprim-sulfamethoxazole but were susceptible to imipenem. All isolates from the four clusters expressed the extended-spectrum ␤-lactamase (ESBL) CTX-M-15. This enzyme was also present in 8 (30.8%) of the 26 unrelated isolates. The other ESBLs, CTX-M-14 and CTX-M-32, were detected in five and seven cases, respectively, but they were detected in individual E. coli isolates only. In three clusters, bla CTX-M-15 alleles were linked to an ISEcp1-like element, while in eight strains of cluster II an IS26 element preceded the bla CTX-M-15 allele. An additional pool of resistance genes included tetA, drfA14 or dfrA17, sul1 or sul2, aac(6)Ib, and aac(3)IIb. All except one of the 27 isolates tested for genetic virulence markers harbored the same three virulence genes: iutA and fyuA (siderophores), and traT (serum survival factor). Epidemic or occasional isolates of cefotaxime-and ceftazidime-resistant E. coli can spread between distinct health facilities including hospitals, community health centers, and long-term care centers.

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Section: Discussionsupporting

confidence: 56%

“…In recent years, ESBL production in Enterobacteriaceae, particularly Escherichia coli, has significantly increased in several countries, including Spain (6,21,30). This increase is primarily due to the spread of CTX-M-type ESBLs (25).…”

mentioning

confidence: 99%

Spread of Escherichia coli Strains with High-Level Cefotaxime and Ceftazidime Resistance between the Community, Long-Term Care Facilities, and Hospital Institutions

et al. 2006

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“…It is conceivable that the Salmonella strains in Kuwait and UAE could have acquired the gene encoding this enzyme from E. coli and Klebsiella in the community, and then it spread among the various species and serotypes of Salmonella. This speculation is supported by the fact that the mobile genetic element ISEcpI, a single copy insertion sequence responsible for mobilization of bla genes and identified upstream of several bla CTX-M genes (Walther-Rasmussen & Høiby, 2004), was found in association with about 72 % of our isolates. The only other ESBL found in Salmonella in the Middle East is SHV-2 type, which was first reported during a nosocomial outbreak of acute gastroenteritis due to 'Salmonella wien' in a neonatal intensive care unit in Tunisia (Hammami et al, 1991).…”

Section: Discussionmentioning

confidence: 53%

Emergence of CTX-M-15 type extended-spectrum β-lactamase-producing Salmonella spp. in Kuwait and the United Arab Emirates

Rotimi

Jamal

Pal

et al. 2008

Journal of Medical Microbiology

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Cephalosporins are major antimicrobials used to treat serious Salmonella infections. However, their effectiveness is being compromised by the emergence of extended-spectrum b-lactamases (ESBLs). The genetic determinants encoding ESBL in Salmonella spp. isolated from patients in Kuwait and United Arab Emirates (UAE) were studied over a 2 year period. Out of a total of 407 isolates, 116 isolates possessed the resistance phenotypes consistent with possible ESBL production. Of these, 69 (59.5 %) were ESBL positive. PCR and sequencing were used to determine the genetic determinant(s) responsible for ESBL phenotypes. A total of 14 (12.1 %) and 29 (24.6 %) isolates were CTX-M-15 ESBL producers and TEM producers, respectively. Ten CTX-M-15 producers carried the insertion sequence ISEcpI gene. PFGE analysis revealed identical profiles in 4 of the 13 Kuwaiti strains. This study reports the presence of the bla CTX-M-15 gene in Salmonella spp. and Salmonella enterica serotype Typhi from Kuwait and UAE for what is believed to be the first time. This is of great concern as the gene is also found in association with the ISEcpI gene, which may easily facilitate its spread. These isolates originated mostly from nonKuwaiti Arabs rather than from people of Asian origin. INTRODUCTIONSalmonella spp. are an important cause of enteric fever and gastroenteritis in humans worldwide. The organisms are transmitted by contaminated food and inadequate hygiene. Typhoidal and serious invasive non-typhoidal Salmonella spp. infections are usually treated with antimicrobial agents. Fluoroquinolones and b-lactams are the drugs of choice for invasive salmonella infections. However, resistance has emerged to various classes of antibiotics in many parts of the world with the spread of resistant strains. Both health care-associated outbreaks and community outbreaks have been reported (Arlet et al., 2006).In Salmonella, resistance to cephalosporins is largely due to production of extended-spectrum b-lactamases (ESBLs). Most ESBLs in Salmonella are derivatives of TEM and SHV b-lactamase families. Other groups, including PER and CTX-M types, have been described recently (Bonnet, 2004;Bradford, 2001). Also, b-lactamases belonging to either Ambler class B (metallo-b-lactamase) or class A, such as KPC-2, able to hydrolyse carbapenems, have been described (Miriagou et al., 2003).CTX-M type ESBLs or cefotaximases, belong to class A blactamases and are encoded by bla CTX-M genes located in a plasmid or on the chromosome (Rodriguez et al., 2004). Different elements may be involved in the mobilization of bla CTX-M genes. Studies with plasmids have confirmed the potential involvement of the insertion sequence ISEcp1 in the mobility of bla CTX-M (Cao et al., 2002). CTX-M enzymes comprise a rapidly growing family of enzymes disseminated in several parts of the world (Bonnet, 2004). A concern is the fact that CTX-M type ESBLs display a level of resistance to cefotaxime (Ctx) and ceftriaxone (Cro) significantly higher than that to ceftazidime (Caz) (Bradford, 2001),...

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“…Also, in the same study, and belonging to CTX-M group 9, we found bla CTX-M17-18 in several Salmonella serotypes (2). CTX-M group 9 enzymes are also the most common group found in other countries in Europe (28). However, it has recently become apparent that the predominant enzyme in the United Kingdom in humans seems to be CTX-M-15 (16).…”

Section: Discussionmentioning

confidence: 99%

Longitudinal Farm Study of Extended-Spectrum β-Lactamase-Mediated Resistance

Liébana

Batchelor

Hopkins³

et al. 2006

J Clin Microbiol

110

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Extended-spectrum ␤-lactamase (ESBL)-mediated resistance is of considerable importance in human medicine. Recently, such enzymes have been reported in bacteria from animals. We describe a longitudinal study of a dairy farm suffering calf scour with high mortality rates. In November 2004, two Escherichia coli isolates with resistance to a wide range of ␤-lactams (including amoxicillin-clavulanate and cefotaxime) were isolated from scouring calves. Testing by PCR and sequence analysis confirmed the isolates as being both bla CTX-M14/17 and bla TEM-35 (IRT-4) positive. They had indistinguishable plasmid and pulsed-field gel electrophoresis (PFGE) profiles. Transferability studies demonstrated that bla CTX-M was located on a conjugative 65-MDa IncK plasmid. Following a farm visit in December 2004, 31/48 calves and 2/60 cows were positive for E. coli with bla CTX-M . Also, 5/48 calf and 28/60 cow samples yielded bla CTX -and bla TEM -negative E. coli isolates that were resistant to cefotaxime, and sequence analysis confirmed that these presented mutations in the promoter region of the chromosomal ampC gene. Fingerprinting showed 11 different PFGE types (seven in bla CTX-Mpositive isolates). Six different PFGE clones conjugated the same bla CTX-M -positive IncK plasmid. One clone carried a different-sized, bla CTX-M -positive, transformable plasmid. This is the first report of bla CTX-M from livestock in the United Kingdom, and this report demonstrates the complexity of ESBL epidemiology. Results indicate that horizontal plasmid transfer between strains as well as horizontal gene transfer between plasmids have contributed to the spread of resistance. We have also shown that some clones can persist for months, suggesting that clonal spread also contributes to the perpetuation of resistance.Cefotaximases (CTX-M) are class A ␤-lactamases produced by a wide range of bacteria of clinical significance and in general present higher levels of hydrolytic activity against cefotaxime than against ceftazidime. CTX-M enzymes comprise a genetically diverse (five groups designated 1, 2, 8, 9, and 25 have been described) and rapidly growing family. These are the predominant extended-spectrum ␤-lactamases (ESBL) in human infections in parts of Eastern Europe, South America, and Japan. In the United Kingdom, the first report of a CTX-M enzyme was in a human clinical isolate of Klebsiella oxytoca with bla CTX-M9 in 2000 (1). Since then, CTX-M-producing Escherichia coli has emerged as a significant and developing problem, occurring in patients in the community as well as in those with recent hospital contact (16,19).In spite of this human situation, worldwide, there have been only a few recent reports of CTX-M-producing bacteria in animals (3,4,10,11,25,29). It is unclear whether it is primarily human or veterinary use of antibiotics that has provided the selective pressures necessary for this situation. In a recent letter, we described the first reported isolation of CTX-Mproducing E. coli from cattle in the United Kingdom. These resist...

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Cefotaximases (CTX-M-ases), an expanding family of extended-spectrum β-lactamases

Cited by 86 publications

References 111 publications

Spread of Escherichia coli Strains with High-Level Cefotaxime and Ceftazidime Resistance between the Community, Long-Term Care Facilities, and Hospital Institutions

Spread of Escherichia coli Strains with High-Level Cefotaxime and Ceftazidime Resistance between the Community, Long-Term Care Facilities, and Hospital Institutions

Emergence of CTX-M-15 type extended-spectrum β-lactamase-producing Salmonella spp. in Kuwait and the United Arab Emirates

Longitudinal Farm Study of Extended-Spectrum β-Lactamase-Mediated Resistance

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