Spanish Multicenter Study of the Epidemiology and Mechanisms of Amoxicillin-Clavulanate Resistance in Escherichia coli

Spanish Multicenter Study of the Epidemiology and Mechanisms of Amoxicillin-Clavulanate Resistance in Escherichia coli

1. Adriana Ortega^a,
2. Jesús Oteo^a,
3. Maitane Aranzamendi-Zaldumbide^b,
4. Rosa M. Bartolomé^c,
5. Germán Bou^d,
6. Emilia Cercenado^e,
7. M. Carmen Conejo^f,
8. Juan José González-López^c,
9. Mercedes Marín^e,
10. Luis Martínez-Martínez^b,^g,
11. María Merino^d,
12. Ferran Navarro^h,ⁱ,
13. Antonio Oliver^j,
14. Álvaro Pascual^f,^k,
15. Alba Rivera^h,
16. Jesús Rodríguez-Baño^k,^l,
17. Irene Weber^j,
18. Belén Aracil^a and
19. José Campos^a,^m

+ Author Affiliations

1. ^aLaboratorio de Antibióticos, Bacteriología, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain
2. ^bServicio de Microbiología, Hospital Universitario Marqués de Valdecilla-IFIMAV, Santander, Spain
3. ^cServei de Microbiologia, Hospital Vall d'Hebrón, Universitat Autònoma de Barcelona, Barcelona, Spain
4. ^dServicio de Microbiología-INIBIC, Complejo Hospitalario Universitario A Coruña, Galicia, Spain
5. ^eServicio de Microbiología, Hospital General Universitario Gregorio Marañón, Madrid, Spain
6. ^fDepartamento de Microbiología, Universidad de Sevilla, Seville, Spain
7. ^gDepartamento de Biología Molecular, Universidad de Cantabria, Santander, Spain
8. ^hServei de Microbiologia, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
9. ⁱDepartament de Genètica i de Microbiología, Universitat Autònoma de Barcelona, Institut d′Investigacions Biomèdiques Sant Pau, Barcelona, Spain
10. ^jServicio de Microbiología, Hospital Son Espases, Palma de Mallorca, Spain
11. ^kUnidad Clínica de Enfermedades Infecciosas y Microbiología, Hospital Universitario Virgen Macarena, Seville, Spain
12. ^lDepartamento de Medicina, Universidad de Sevilla, Seville, Spain
13. ^mConsejo Superior de Investigaciones Científicas, Madrid, Spain

ABSTRACT

We conducted a prospective multicenter study in Spain to characterize the mechanisms of resistance to amoxicillin-clavulanate (AMC) in Escherichia coli. Up to 44 AMC-resistant E. coli isolates (MIC ≥ 32/16 μg/ml) were collected at each of the seven participant hospitals. Resistance mechanisms were characterized by PCR and sequencing. Molecular epidemiology was studied by pulsed-field gel electrophoresis (PFGE) and by multilocus sequence typing. Overall AMC resistance was 9.3%. The resistance mechanisms detected in the 257 AMC-resistant isolates were OXA-1 production (26.1%), hyperproduction of penicillinase (22.6%), production of plasmidic AmpC (19.5%), hyperproduction of chromosomic AmpC (18.3%), and production of inhibitor-resistant TEM (IRT) (17.5%). The IRTs identified were TEM-40 (33.3%), TEM-30 (28.9%), TEM-33 (11.1%), TEM-32 (4.4%), TEM-34 (4.4%), TEM-35 (2.2%), TEM-54 (2.2%), TEM-76 (2.2%), TEM-79 (2.2%), and the new TEM-185 (8.8%). By PFGE, a high degree of genetic diversity was observed although two well-defined clusters were detected in the OXA-1-producing isolates: the C1 cluster consisting of 19 phylogroup A/sequence type 88 [ST88] isolates and the C2 cluster consisting of 19 phylogroup B2/ST131 isolates (16 of them producing CTX-M-15). Each of the clusters was detected in six different hospitals. In total, 21.8% of the isolates were serotype O25b/phylogroup B2 (O25b/B2). AMC resistance in E. coli is widespread in Spain at the hospital and community levels. A high prevalence of OXA-1 was found. Although resistant isolates were genetically diverse, clonality was linked to OXA-1-producing isolates of the STs 88 and 131. Dissemination of IRTs was frequent, and the epidemic O25b/B2/ST131 clone carried many different mechanisms of AMC resistance.

FOOTNOTES

• Received 21 December 2011.
• Returned for modification 15 January 2012.
• Accepted 31 March 2012.
• Address correspondence to Jesús Oteo, jesus.oteo@isciii.es.
• Published ahead of print 9 April 2012

• Copyright © 2012, American Society for Microbiology. All Rights Reserved.