Abstract
Beta-lactam antibiotics have been discussed as options for the treatment of infections caused by multiresistant extended-spectrum beta-lactamase (ESBL)-producing bacteria if the minimum inhibitory concentration (MIC) is low. The objective of this study was to investigate the in vitro activity of different beta-lactam antibiotics against CTX-M-producing Escherichia coli. A total of 198 isolates of E. coli with the ESBL phenotype were studied. Polymerase chain reaction (PCR) amplification of CTX-M genes and amplicon sequencing were performed. The MICs for amoxicillin–clavulanic acid, aztreonam, cefepime, cefotaxime, ceftazidime, ceftibuten, ertapenem, imipenem, mecillinam, meropenem, piperacillin–tazobactam, and temocillin were determined with the Etest. Susceptibility was defined according to the breakpoints of the European Committee on Antimicrobial Susceptibility Testing (EUCAST). MIC50 and MIC90 values were calculated. Isolates from CTX-M group 9 showed higher susceptibility to the beta-lactam antibiotics tested than isolates belonging to CTX-M group 1. More than 90% of the isolates belonging to CTX-M group 9 were susceptible to amoxicillin–clavulanic acid, ceftazidime, ceftibuten, piperacillin–tazobactam, and temocillin. The susceptibility was high to mecillinam, being 91%, regardless of the CTX-M group. All isolates were susceptible to imipenem and meropenem, and 99% to ertapenem. This study shows significant differences in susceptibility to different beta-lactam antibiotics among the CTX-M-producing E. coli isolates and a significant difference for many antibiotics tested between the CTX-M-producing groups 1 and 9. The good in vitro activity of other beta-lactam antibiotics compared to carbapenems indicate that clinical studies are warranted in order to examine the potential role of these beta-lactam antibiotics in the treatment of infections caused by multiresistant ESBL-producing E. coli.
Similar content being viewed by others
References
Alsterlund R, Carlsson B, Gezelius L et al (2009) Multiresistant CTX-M-15 ESBL-producing Escherichia coli in southern Sweden: description of an outbreak. Scand J Infect Dis 41(6–7):410–415
Fang H, Ataker F, Hedin G et al (2008) Molecular epidemiology of extended-spectrum beta-lactamases among Escherichia coli isolates collected in a Swedish hospital and its associated health care facilities from 2001 to 2006. J Clin Microbiol 46(2):707–712
Kjerulf A, Hansen DS, Sandvang D et al (2008) The prevalence of ESBL-producing E. coli and Klebsiella strains in the Copenhagen area of Denmark. APMIS 116(2):118–124
Lytsy B, Sandegren L, Tano E et al (2008) The first major extended-spectrum beta-lactamase outbreak in Scandinavia was caused by clonal spread of a multiresistant Klebsiella pneumoniae producing CTX-M-15. APMIS 116(4):302–308
Naseer U, Natås OB, Haldorsen BC et al (2007) Nosocomial outbreak of CTX-M-15-producing E. coli in Norway. APMIS 115(2):120–126
Nyberg SD, Osterblad M, Hakanen AJ et al (2007) Detection and molecular genetics of extended-spectrum beta-lactamases among cefuroxime-resistant Escherichia coli and Klebsiella spp. isolates from Finland, 2002–2004. Scand J Infect Dis 39(5):417–424
Jacoby G, Bush K.OXA-type β-lactamases. Available online at: http://www.lahey.org/Studies/other.asp#table1. Last date accessed 9 August 2010
Bonnet R (2004) Growing group of extended-spectrum beta-lactamases: the CTX-M enzymes. Antimicrob Agents Chemother 48(1):1–14
European Antimicrobial Resistance Surveillance System (EARSS) (2005) EARSS manual 2005. Available online at: http://www1.szu.cz/cem/earss/docs/Earss_manual_2005.pdf. Last date accessed 2 February 2011
European Committee on Antimicrobial Susceptibility Testing (EUCAST) (2008) Expert rules in antimicrobial susceptibility testing. Available online at: http://www.srga.org/eucastwt/EUCAST%20Expert%20rules%20final%20April_20080407.pdf. Last date accessed 9 August 2010
European Committee on Antimicrobial Susceptibility Testing (EUCAST) (2008) Expert rules. Home page at: http://www.eucast.org/expert_rules/. Last date accessed 9 August 2010
Melzer M, Petersen I (2007) Mortality following bacteraemic infection caused by extended spectrum beta-lactamase (ESBL) producing E. coli compared to non-ESBL producing E. coli. J Infect 55(3):254–259
Schwaber MJ, Carmeli Y (2007) Mortality and delay in effective therapy associated with extended-spectrum beta-lactamase production in Enterobacteriaceae bacteraemia: a systematic review and meta-analysis. J Antimicrob Chemother 60(5):913–920
Cordery RJ, Roberts CH, Cooper SJ et al (2008) Evaluation of risk factors for the acquisition of bloodstream infections with extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella species in the intensive care unit; antibiotic management and clinical outcome. J Hosp Infect 68(2):108–115
Gudiol C, Calatayud L, Garcia-Vidal C et al (2010) Bacteraemia due to extended-spectrum beta-lactamase-producing Escherichia coli (ESBL-EC) in cancer patients: clinical features, risk factors, molecular epidemiology and outcome. J Antimicrob Chemother 65(2):333–341
Ortega M, Marco F, Soriano A et al (2009) Analysis of 4758 Escherichia coli bacteraemia episodes: predictive factors for isolation of an antibiotic-resistant strain and their impact on the outcome. J Antimicrob Chemother 63(3):568–574
Rodríguez-Baño J, Navarro MD, Romero L et al (2006) Bacteremia due to extended-spectrum beta-lactamase-producing Escherichia coli in the CTX-M era: a new clinical challenge. Clin Infect Dis 43(11):1407–1414
Tumbarello M, Sanguinetti M, Montuori E et al (2007) Predictors of mortality in patients with bloodstream infections caused by extended-spectrum-beta-lactamase-producing Enterobacteriaceae: importance of inadequate initial antimicrobial treatment. Antimicrob Agents Chemother 51(6):1987–1994
Tumbarello M, Sali M, Trecarichi EM et al (2008) Bloodstream infections caused by extended-spectrum-beta-lactamase-producing Escherichia coli: risk factors for inadequate initial antimicrobial therapy. Antimicrob Agents Chemother 52(9):3244–3252
Song KH, Jeon JH, Park WB et al (2009) Clinical outcomes of spontaneous bacterial peritonitis due to extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella species: a retrospective matched case–control study. BMC Infect Dis 9:41
Bin C, Hui W, Renyuan Z et al (2006) Outcome of cephalosporin treatment of bacteremia due to CTX-M-type extended-spectrum beta-lactamase-producing Escherichia coli. Diagn Microbiol Infect Dis 56(4):351–357
Lagacé-Wiens PR, Nichol KA, Nicolle LE et al (2006) Treatment of lower urinary tract infection caused by multidrug-resistant extended-spectrum-beta-lactamase-producing Escherichia coli with amoxicillin/clavulanate: case report and characterization of the isolate. J Antimicrob Chemother 57(6):1262–1263
Nicolle LE, Mulvey MR (2007) Successful treatment of ctx-m ESBL producing Escherichia coli relapsing pyelonephritis with long term pivmecillinam. Scand J Infect Dis 39(8):748–749
Rodríguez-Baño J, Alcalá JC, Cisneros JM et al (2008) Community infections caused by extended-spectrum beta-lactamase-producing Escherichia coli. Arch Intern Med 168(17):1897–1902
Gupta ND, Smith RE, Balakrishnan I (2009) Clinical efficacy of temocillin. J Antimicrob Chemother 64(2):431–433
Monstein HJ, Tärnberg M, Nilsson LE (2009) Molecular identification of CTX-M and blaOXY/K1 beta-lactamase genes in Enterobacteriaceae by sequencing of universal M13-sequence tagged PCR-amplicons. BMC Infect Dis 9:7
European Committee on Antimicrobial Susceptibility Testing (EUCAST) (2010) Breakpoint tables for interpretation of MICs and zone diameters. Available online at: http://www.eucast.org/fileadmin/src/media/PDFs/EUCAST_files/Disk_test_documents/EUCAST_breakpoints_v1.1.pdf. Last date accessed 9 August 2010
British Society for Antimicrobial Chemotherapy (BSAC) (2010) BSAC methods for antimicrobial susceptibility testing. Available online at: http://www.bsac.org.uk/Resources/BSAC/Version_9.1_March_2010_final.pdf. Last date accessed 2 February 2011
Livermore DM, Hope R, Mushtaq S et al. (2008) Orthodox and unorthodox clavulanate combinations against extended-spectrum beta-lactamase producers. Clin Microbiol Infect 14(Suppl 1):189–193
Rodriguez-Villalobos H, Malaviolle V, Frankard J et al (2006) In vitro activity of temocillin against extended spectrum beta-lactamase-producing Escherichia coli. J Antimicrob Chemother 57(4):771–774
Tofteland S, Haldorsen B, Dahl KH et al (2007) Effects of phenotype and genotype on methods for detection of extended-spectrum-beta-lactamase-producing clinical isolates of Escherichia coli and Klebsiella pneumoniae in Norway. J Clin Microbiol 45(1):199–205
Liao CH, Sheng WH, Wang JT et al (2006) In vitro activities of 16 antimicrobial agents against clinical isolates of extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae in two regional hospitals in Taiwan. J Microbiol Immunol Infect 39(1):59–66
Thomas K, Weinbren MJ, Warner M et al (2006) Activity of mecillinam against ESBL producers in vitro. J Antimicrob Chemother 57(2):367–368
Livermore DM, Hope R, Fagan EJ et al (2006) Activity of temocillin against prevalent ESBL- and AmpC-producing Enterobacteriaceae from south-east England. J Antimicrob Chemother 57(5):1012–1014
Sorlózano A, Gutiérrez J, Romero JM et al (2007) Activity in vitro of twelve antibiotics against clinical isolates of extended-spectrum beta-lactamase producing Escherichia coli. J Basic Microbiol 47(5):413–416
Hoban DJ, Bouchillon SK, Johnson BM et al (2005) In vitro activity of tigecycline against 6792 Gram-negative and Gram-positive clinical isolates from the global Tigecycline Evaluation and Surveillance Trial (TEST Program, 2004). Diagn Microbiol Infect Dis 52(3):215–227
Oteo J, Navarro C, Cercenado E et al (2006) Spread of Escherichia coli strains with high-level cefotaxime and ceftazidime resistance between the community, long-term care facilities, and hospital institutions. J Clin Microbiol 44(7):2359–2366
Prakash V, Lewis JS 2nd, Herrera ML et al (2009) Oral and parenteral therapeutic options for outpatient urinary infections caused by enterobacteriaceae producing CTX-M extended-spectrum beta-lactamases. Antimicrob Agents Chemother 53(3):1278–1280
Colodner R, Samra Z, Keller N et al (2007) First national surveillance of susceptibility of extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella spp. to antimicrobials in Israel. Diagn Microbiol Infect Dis 57(2):201–205
Sader HS, Hsiung A, Fritsche TR et al (2007) Comparative activities of cefepime and piperacillin/tazobactam tested against a global collection of Escherichia coli and Klebsiella spp. with an ESBL phenotype. Diagn Microbiol Infect Dis 57(3):341–344
Gavin PJ, Suseno MT, Thomson RB Jr et al (2006) Clinical correlation of the CLSI susceptibility breakpoint for piperacillin–tazobactam against extended-spectrum-beta-lactamase-producing Escherichia coli and Klebsiella species. Antimicrob Agents Chemother 50(6):2244–2247
Peterson LR (2008) Antibiotic policy and prescribing strategies for therapy of extended-spectrum beta-lactamase-producing Enterobacteriaceae: the role of piperacillin–tazobactam. Clin Microbiol Infect 14(Suppl 1):181–184
Hernández JR, Velasco C, Romero L et al (2006) Comparative in vitro activity of ertapenem against extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae isolated in Spain. Int J Antimicrob Agents 28(5):457–459
Kiremitci A, Dinleyici EC, Erben N et al (2008) In vitro activity of ertapenem and other carbapenems against extended-spectrum beta-lactamase producing Escherichia coli and Klebsiella pneumoniae clinical isolates in a tertiary care center in Turkey. Expert Opin Pharmacother 9(9):1441–1449
Funding
This work was supported by the Medical Research Council of Southeast Sweden.
Transparency declaration
Nothing to declare.
Author contributions
MT, ÅÖB, H-JM, AH, HH, and LEN participated in the conception, design, and drafting of the manuscript, and final approval of the version to be published. MT was responsible for the laboratory work, analysis, statistical calculations, and interpretations. MT, ÅÖB, and LEN were responsible for the clinical strain collection.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Tärnberg, M., Östholm-Balkhed, Å., Monstein, HJ. et al. In vitro activity of beta-lactam antibiotics against CTX-M-producing Escherichia coli . Eur J Clin Microbiol Infect Dis 30, 981–987 (2011). https://doi.org/10.1007/s10096-011-1183-4
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10096-011-1183-4