Subsequent infection with extended-spectrum β-lactamase-producing Enterobacteriaceae in patients with prior infection or fecal colonization
In clinical practice, there is a growing need to assess the impact of prior colonization or infection with extended-spectrum β-lactamase-producing Enterobacteriaceae (EPE) on new EPE infections. We have investigated the frequency of, and duration to, a subsequent EPE infection in patients with prior fecal carriage or infection with EPE. Culture data for 3272 EPE-positive patients in Western Sweden during 2004–2014 were evaluated. The median follow-up time was 3.7 years. The first recorded EPE-positive fecal screen, or clinical (urine, blood) culture, and subsequent EPE-positive clinical samples were analyzed, focusing on the first and last recurrence of EPE infection. ESBL Escherichia coli dominated (95%). Almost all (94%) patients initially positive in fecal screen (n = 1436) and 72 and 71% of those initially positive in urine (n = 1717) and blood (n = 119) had no further EPE clinical isolates. Subsequent EPE bacteremia was only detected in 0.7, 1.6, and 4.2% of the respective patient group. Recurrent EPE-positive urine cultures occurred in 27% (460/1717), most (75%) within 6 months, and rarely (13%) after 1 year. Repeated EPE-positive clinical samples were significantly (p < 0.01) more common in patients > 65 years and in men with ESBL Klebsiella pneumoniae. In our low-endemic setting, subsequent EPE infections in previously colonized patients were rare. On the other hand, in patients previously EPE-positive in urine or blood, subsequent EPE urinary tract infections were common, especially within 6 months and in patients > 65 years old.
KeywordsExtended-spectrum β-lactamases (ESBL) E. coli K. pneumoniae Fecal screening Urinary tract infection Bacteremia Recurrent infection
We thank the personnel at the Clinical Microbiology Laboratory at Sahlgrenska University Hospital for performing the bacterial culturing.
This work was supported by the Centre for Antibiotic Resistance Research (CARe), University of Gothenburg and by Region Västra Götaland, Sweden (VGFOUREG-660231).
Compliance with ethical standards
This study was conducted in accordance with the Declaration of Helsinki and national and institutional regulations.
The study was approved by the Regional Ethical Review Board in Gothenburg, Sweden (recordal: 170-17).
Conflict of interest
The authors declare that they have no conflict of interest.
No informed consent was required.
- 3.World Health Organization (2014) Antimicrobial resistance - Global report on surveillance. Available from: http://apps.who.int/iris/bitstream/10665/112642/1/9789241564748_eng.pdf?ua=1
- 5.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 Inf Secur 55:254–259Google Scholar
- 6.Tumbarello M, Spanu T, Di Bidino R, Marchetti M, Ruggeri M, Trecarichi EM, De Pascale G, Proli EM, Cauda R, Cicchetti A, Fadda G (2010) Costs of bloodstream infections caused by Escherichia coli and influence of extended-spectrum-beta-lactamase production and inadequate initial antibiotic therapy. Antimicrob Agents Chemother 54:4085–4091CrossRefPubMedPubMedCentralGoogle Scholar
- 7.Alevizakos M, Karanika S, Detsis M, Mylonakis E (2016) Colonisation with extended-spectrum beta-lactamase-producing Enterobacteriaceae and risk for infection among patients with solid or haematological malignancy: a systematic review and meta-analysis. Int J Antimicrob Agents 48:647–654CrossRefPubMedGoogle Scholar
- 9.Vodovar D, Marcade G, Rousseau H, Raskine L, Vicaut E, Deye N, Baud FJ, Megarbane B (2014) Predictive factors for extended-spectrum beta-lactamase producing Enterobacteriaceae causing infection among intensive care unit patients with prior colonization. Infection 42:743–748CrossRefPubMedGoogle Scholar
- 11.Rottier WC, Bamberg YR, Dorigo-Zetsma JW, van der Linden PD, Ammerlaan HS, Bonten MJ (2015) Predictive value of prior colonization and antibiotic use for third-generation cephalosporin-resistant enterobacteriaceae bacteremia in patients with sepsis. Clin Infect Dis 60:1622–1630CrossRefPubMedGoogle Scholar
- 13.Armand-Lefevre L, Angebault C, Barbier F, Hamelet E, Defrance G, Ruppe E, Bronchard R, Lepeule R, Lucet JC, El Mniai A, Wolff M, Montravers P, Plesiat P, Andremont A (2013) Emergence of imipenem-resistant gram-negative bacilli in intestinal flora of intensive care patients. Antimicrob Agents Chemother 57:1488–1495CrossRefPubMedPubMedCentralGoogle Scholar
- 14.European Committee on Antimicrobial Susceptibility Testing (EUCAST). Available from: http://www.eucast.org/clinical_breakpoints/
- 15.Karami N, Helldal L, Welinder-Olsson C, Ahren C, Moore ER (2013) Sub-typing of extended-spectrum-beta-lactamase-producing isolates from a nosocomial outbreak: application of a 10-loci generic Escherichia coli multi-locus variable number tandem repeat analysis. PLoS One 8:e83030CrossRefPubMedPubMedCentralGoogle Scholar
- 17.Martinez JA, Aguilar J, Almela M, Marco F, Soriano A, Lopez F, Balasso V, Pozo L, Mensa J (2006) Prior use of carbapenems may be a significant risk factor for extended-spectrum beta-lactamase-producing Escherichia coli or Klebsiella spp. in patients with bacteraemia. J Antimicrob Chemother 58:1082–1085CrossRefPubMedGoogle Scholar
- 18.Cornejo-Juarez P, Suarez-Cuenca JA, Volkow-Fernandez P, Silva-Sanchez J, Barrios-Camacho H, Najera-Leon E, Velazquez-Acosta C, Vilar-Compte D (2016) Fecal ESBL Escherichia coli carriage as a risk factor for bacteremia in patients with hematological malignancies. Support Care Cancer 24:253–259CrossRefPubMedGoogle Scholar
- 19.Arnan M, Gudiol C, Calatayud L, Linares J, Dominguez MA, Batlle M, Ribera JM, Carratala J, Gudiol F (2011) Risk factors for, and clinical relevance of, faecal extended-spectrum beta-lactamase producing Escherichia coli (ESBL-EC) carriage in neutropenic patients with haematological malignancies. Eur J Clin Microb Infect Dis 30:355–360CrossRefGoogle Scholar
- 22.Ejrnaes K, Sandvang D, Lundgren B, Ferry S, Holm S, Monsen T, Lundholm R, Frimodt-Moller N (2006) Pulsed-field gel electrophoresis typing of Escherichia coli strains from samples collected before and after pivmecillinam or placebo treatment of uncomplicated community-acquired urinary tract infection in women. J Clin Microbiol 44:1776–1781CrossRefPubMedPubMedCentralGoogle Scholar