Buscar en
Enfermedades Infecciosas y Microbiología Clínica
Toda la web
Inicio Enfermedades Infecciosas y Microbiología Clínica Association of blaOXA-1, and aac(6′)-Ib-cr with ST405 K. pneumoniae clone
Información de la revista
Vol. 37. Núm. 6.
Páginas 417-418 (Junio - Julio 2019)
Descargar PDF
Más opciones de artículo
Vol. 37. Núm. 6.
Páginas 417-418 (Junio - Julio 2019)
Scientific letter
DOI: 10.1016/j.eimc.2018.06.001
Acceso a texto completo
Association of blaOXA-1, and aac(6′)-Ib-cr with ST405 K. pneumoniae clone
Asociación de los genes blaOXA-1 y aac(6′)-Ib-cr con el clon ST405 de K. pneumoniae
P. Luque-Gonzáleza, L. López-Cererob,
Autor para correspondencia

Corresponding author.
, P. Díaz-de-Albab, J.M. Rodríguez-Martíneza
a Departamento de Microbiologia, Facultad de Medicina, Seville, Spain
b Unidad Clínica de Enfermedades Infecciosas, Microbiología y Medicina Preventiva, Hospital Universitario Virgen Macarena/CSIC/Departamento de Microbiología, Universidad de Sevilla/Instituto de Biomedicina de Sevilla (IBiS), Seville, Spain
Información del artículo
Texto completo
Descargar PDF
Texto completo

In recent years, various plasmid-mediated resistance mechanisms that confer low-level resistance to quinolones (PMQR) have been described. These include enzymatic modification by the acetyltransferase AAC(6’)-Ib-cr, QepA active efflux pumps, and qnr genes, which have been associated with genes blaOXA-1, blaCTX-M-15 and blaTEM-1 genes.1 These determinants have frequently been found to be related to successful clones producing blaCTX-M-15 and blaOXA-48, such as sequence type (ST) 4052,3 or ST15 K. pneumoniae.4 In unsuccessful clones, an association of these determinants can also be found, such as an 3 years-outbreak in a hospital in Barcelona caused by ST14 K. pneumoniae.5 Nevertheless, the prevalence of these genes in non-extended-spectrum beta-lactamases (ESBL) or carbapenemases-producing isolates is unknown.

A previous study carried out by Rodríguez-Martínez et al.6 described a phenotypic detection algorithm for PMQR, which was validated in a collection of 99 isolates of Enterobacteriales of clinical origin from the University Hospital Virgen Macarena. Fifty-one isolates (51%) had at least one PMQR mechanism: qnrS, the most prevalent, appeared in 25 (49%) isolates, qnrB in 20 (39%) isolates, aac(6′)-Ib-cr in 9 (18%) isolates, oqxAB in 6 (12%) isolates, qnrA in 2 (4%) isolates and qnrD in 2 (4%) isolates. The phenotype compatible with the production of blaOXA-1 consists of an intermediate sensitivity or resistance to amoxicillin/clavulanic acid, decreased sensitivity to piperacillin/tazobactam according to CLSI breakpoints and synergy by disc diffusion between clavulanic and cefepime in the absence of ESBL enzymes. In order to estimate the frequency of the association between PMQR determinants and blaOXA-1 and blaTEM-1, 37 (37.3%) isolates with MIC values >8/4μg/ml to amoxicillin/clavulanic acid and >2μg/ml to cefepime were selected from the same collection. Screening of OXA-1 was performed by examining the synergy between discs of the amoxicillin/clavulanic and cefepime, and also by PCR, using specific primers for the blaOXA-1 gene.7 Twelve (32.4%) isolates were positive for blaOXA-1, including 8 (66.7%) K. pneumoniae (6 of them qnrB), 3 (25%) E. coli (1 qnrA and 1 qnrS) and 1 (8.3%) E. cloacae (qnrA). XbaI PFGE was used to study the clonal relatedness of K. pneumoniae isolates was studied by. Six isolates (75%) formed a cluster (less than 6 difference bands, 86% similarity using the Dice index) and shared the following determinants of resistance: all of them possessed aac(6′)Ib-cr and blaOXA-1; 5 (83%) also have qnrB, and 2 of them (33%) also carried blaCTX-M-15 and blaTEM-1. Two isolates from this group were selected for MLST (one isolate carrying blaOXA-1, qnrB1, aac(6′)-Ib-cr, and blaTEM-1; and the other isolate carrying blaOXA-1, qnrB1, aac(6′)-Ib-cr, blaTEM-1, and blaCTX-M-15) were assigned ST405. When these were also compared with the genetic profiles held at the Andalusian Reference Laboratory for molecular typing, they were found to share 85% similarity with isolates belonging to the same clone from other areas of Spain.

This clone with the genetic profile blaTEM-1, blaCTX-M-15 and blaOXA-1 was described for the first time in Casablanca (Morocco) in isolates collected between February 2007 and March 2008.8 The first description of ST405 with OXA-48 production was in Belgium (between January 2010 to April 2011) 4 isolates. These isolates also involved blaTEM-1 and blaCTX-M-15, and 3 of them additionally carried aac(6′)-Ib-cr and qnrB1.9 The largest single-centre outbreak to date, in the Hospital La Paz, Madrid,10 was caused by a ST405 producer of OXA-48 that also carried qnrB1 and aac(6′)-Ib-cr.2 The same clone was associated with two outbreaks in neonatology units in Andalusian hospitals (in the South of Spain) caused by isolated producers of CTX-M-15, but not of OXA-48.3

ST405 shares a series of determinants in every location where it has been detected: blaOXA-1, blaTEM-1 and aac(6′)-Ib-cr, even in non-ESBL or non carbapenemase-producing isolates, as well as having the characteristics of a successful clone. The dissemination of this clone seems to be associated with acquisition of determinants of low resistance to amoxicillin/clavulanic acid and quinolones, with acquisition of ESBL or carbapenemase genes occurring later. This clone could be more widely disseminated than initially thought, since there are few data available on cephalosporin- and carbapenems-susceptible isolates. In a recent study in our country, this was one of the 5 most important clones in the dissemination of carbapenemases in Spain, accounting for 13.5% of carbapenemases producers,11 and only 2 of the five non-carbapenemases-producers ST405 were susceptible to third-generation cephalosporins. It would be of interest to find out the real prevalence of this clone in resistant and wild type isolates in order to study the selective forces that drive its dissemination.


This work was supported by Plan Nacional de I+D+i 2013–2016 and Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Economía, Industria y Competitividad, Spanish Network for Research in Infectious Diseases (REIPI; RD16/0016/0001)-co-financed by European Development Regional Fund “A way to achieve Europe”, Operative Program Intelligent Growth 2014–2020.

N. Filippa, A. Carricajo, F. Grattard, P. Fascia, F. El Sayed, J.P. Defilippis, et al.
Outbreak of multidrug-resistant Klebsiella pneumoniae carrying qnrB1 and blaCTX-M-15 in a French intensive care unit.
Ann Intensive Care, 3 (2013), pp. 18
J.M. Rodríguez Martínez, P. Díaz-de Alba, Lopez-Cerero, G. Ruiz-Carrascoso, R. Gomez-Gil, A. Pascual.
Presence of quinolone resistance to qnrB1 genes and blaOXA-48 carbapenemase in clinical isolates of Klebsiella pneumoniae in Spain.
Enferm Infect Microbiol Clin, 32 (2014), pp. 441-442
J. Machuca, L. López-Cerero, F. Fernández-Cuenca, I. Gracia-Ahufinger, G. Ruiz-Carrascoso, F. Rodríguez-López, et al.
Characterization of an outbreak due to CTX-M-15-producing Klebsiella pneumoniae lacking the blaOXA-48 gene belonging to clone ST405 in a neonatal unit in southern Spain.
J Antimicrob Chemother, 71 (2016), pp. 2353-2355
E. Ruiz, Y. Sáenz, M. Zarazaga, R. Rocha-Gracia, L. Martínez-Martínez, G. Arlet, et al.
qnr, aac(6′)-Ib-cr and qepA genes in Escherichia coli and Klebsiella spp.: genetic environments and plasmid and chromosomal location.
J Antimicrob Chemother, 67 (2012), pp. 886-897
M. Cubero, L. Calatayud, J. Ayats, C. Peña, R. Martín, J. Liñares, et al.
Clonal spread of Klebsiella pneumoniae producing OXA-1 betalactamase in a Spanish hospital.
Int Microbiol, 16 (2013), pp. 227-233
J.-M. Rodríguez-Martínez, L. López-Cerero, P. Díaz-de-Alba, F.J. Chamizo-López, J. Polo-Padillo, Á. Pascual.
Assessment of a phenotypic algorithm to detect plasmid-mediated quinolone resistance in Enterobacteriaceae.
J Antimicrob Chemother, 71 (2016), pp. 845-847
E. Torres, L. López-Cerero, J.M. Rodríguez-Martínez, Á. Pascual.
Reduced susceptibility to cefepime in clinical isolates of Enterobacteriaceae producing OXA-1 beta-lactamase.
Microb Drug Resist, 22 (2016), pp. 141-146
S. Breurec, N. Guessennd, M. Timinouni, T.T.H. Le, V. Cao, A. Ngandjio, et al.
Klebsiella pneumoniae resistant to third-generation cephalosporins in five African and two Vietnamese major towns: multiclonal population structure with two major international clonal groups, CG15 and CG258.
Clin Microbiol Infect, 19 (2013), pp. 349-355
Y. Glupczynski, T.-D. Huang, W. Bouchahrouf, R. Rezende de Castro, C. Bauraing, M. Gérard, et al.
Rapid emergence and spread of OXA-48-producing carbapenem-resistant Enterobacteriaceae isolates in Belgian hospitals.
J Antimicrob Chemother, 39 (2012), pp. 168-172
J.R. Paño-Pardo, G. Ruiz-Carrascoso, C. Navarro-San Francisco, R. Gómez-Gil, M. Mora-Rillo, M.P. Romero-Gómez, et al.
Infections caused by OXA-48-producing Klebsiella pneumoniae in a tertiary hospital in Spain in the setting of a prolonged, hospital-wide outbreak.
J Antimicrob Chemother, 68 (2013), pp. 89-96
A. Esteban-Cantos, B. Aracil, V. Bautista, A. Ortega, N. Lara, D. Saez, et al.
The carbapenemase-producing Klebsiella pneumoniae population is distinct and more clonal than the carbapenem-susceptible population.
Antimicrob Agents Chemother, 61 (2017), pp. e02520-e2616
Copyright © 2018. Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica
Opciones de artículo
es en pt

¿Es usted profesional sanitario apto para prescribir o dispensar medicamentos?

Are you a health professional able to prescribe or dispense drugs?

Você é um profissional de saúde habilitado a prescrever ou dispensar medicamentos

es en pt
Política de cookies Cookies policy Política de cookies
Utilizamos cookies propias y de terceros para mejorar nuestros servicios y mostrarle publicidad relacionada con sus preferencias mediante el análisis de sus hábitos de navegación. Si continua navegando, consideramos que acepta su uso. Puede cambiar la configuración u obtener más información aquí. To improve our services and products, we use "cookies" (own or third parties authorized) to show advertising related to client preferences through the analyses of navigation customer behavior. Continuing navigation will be considered as acceptance of this use. You can change the settings or obtain more information by clicking here. Utilizamos cookies próprios e de terceiros para melhorar nossos serviços e mostrar publicidade relacionada às suas preferências, analisando seus hábitos de navegação. Se continuar a navegar, consideramos que aceita o seu uso. Você pode alterar a configuração ou obter mais informações aqui.