Hostname: page-component-cd9895bd7-fscjk Total loading time: 0 Render date: 2024-12-22T22:07:38.333Z Has data issue: false hasContentIssue false

Clinical and Molecular Epidemiology of Healthcare-Associated Infections Due to Extended-Spectrum β-Lactamase (ESBL)–Producing Strains of Escherichia coli and Klebsiella pneumoniae That Harbor Multiple ESBL Genes

Published online by Cambridge University Press:  02 January 2015

Anucha Apisarnthanarak*
Affiliation:
Division of Infectious Diseases, Faculty of Medicine, Thammasart University Hospital, Pratumthani, Thailand
Pattarachai Kiratisin
Affiliation:
Department of Microbiology, Faculty of Medicine, Siriraj Hospital, Bangkok, Thailand
Linda M. Mundy
Affiliation:
Saint Louis University School of Public Health, Saint Louis, Missouri
*
Division of Infectious Diseases, Faculty of Medicine, Thammasart University Hospital, Pratumthani, Thailand12121 ([email protected])

Abstract

Objectives.

To characterize healthcare-associated infections due to extended-spectrum β-lactamase (ESBL)-producing strains of Escherichia coli and Klebsiella pneumoniae that harbor multiple ESBL genes, as opposed to a single ESBL gene.

Methods.

All patients with a confirmed healthcare-associated infection due to an ESBL-producing strain of E. coli or K. pneumoniae were enrolled in the study. Molecular typing of isolates was performed, and the comparative risks and outcomes of patients were analyzed.

Results.

Among 71 patients with healthcare-associated infection due to an ESBL-producing strain of E. coli or K. pneumoniae, the gene for CTX-M, with or without other ESBL genes, was identified in all 51 (100%) of the patients infected with an E. coli strain and in 18 (90%) of the 20 patients infected with a K. pneumoniae strain. Of these 71 patients, 17 (24%) met the definition of healthcare-associated infection due to an ESBL-producing strain that harbored multiple genes; in multivariate analysis, previous exposure to 3 or more classes of antibiotics (adjusted odds ratio, 4.5 [95% confidence interval, 1.7-75.2]) was the sole risk factor for healthcare-associated infection due to an ESBL-producing strain that harbored multiple ESBL genes. Isolates recovered from patients with healthcare-associated infection due to an ESBL-producing strain that harbored multiple ESBL genes were more resistant to various antibiotic classes, and, compared with patients with healthcare-associated infection due to an ESBL-producing strain that harbored a single ESBL gene, they were more likely to have ineffective initial empirical antimicrobial therapy (52% vs 94%; odds ratio, 5.1 [95% confidence interval, 1.04-14.5]).

Conclusions.

CTX-M ESBL is highly prevalent in Thailand. Patients with healthcare-associated infection due to an ESBL-producing strain that harbored multiple ESBL genes were more likely to have had ineffective initial empirical antimicrobial therapy, and, given that antibiotic selection pressure was the only associated risk, we suggest focused antimicrobial stewardship programs to limit the emergence and spread of healthcare-associated infection due to ESBL-producing strains in this middle-income country.

Type
Original Article
Copyright
Copyright © The Society for Healthcare Epidemiology of America 2008

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1.Rice, LB, Willey, SH, Papanicolaou, GA, et al.Outbreak of ceftazidime resistance caused by extended-spectrum β-lactamases at a Massachusetts chronic-care facility. Antimicrob Agents Chemother 1990;34:22002209.CrossRefGoogle Scholar
2.Burwen, DR, Banerjee, SN, Gaynes, RP. Ceftazidime resistance among selected nosocomial gram-negative bacilli in the United States. The National Nosocomial Infections Surveillance System. J Infect Dis 1994;170:16221625.CrossRefGoogle ScholarPubMed
3.Itokazu, GS, Quinn, JP, Bell-Dixon, C, Kahan, FM, Weinstein, RA. Antimicrobial resistance rates among aerobic gram-negative bacilli recovered from patients in intensive care units: evaluation of a national postmarketing surveillance program. Clin Infect Dis 1996;23:779784.CrossRefGoogle ScholarPubMed
4.Nijssen, S, Florijn, A, Bonten, MJM, Schmitz, FJ, Verhoef, J, Fluit, AC. β-Lactam susceptibilities and prevalence of ESBL-producing isolates among more than 5000 European Enterobacteriaceae isolates. Int J Antimicrob Agents 2004;24:585591.CrossRefGoogle ScholarPubMed
5.Lautenbach, E, Patel, JB, Bilker, WB, Edelstein, PH, Fishman, NO. Extended-spectrum β-lactamase-producing Escherichia coli and Klebsiella pneumoniae, risk factors for infection and impact of resistance on outcomes. Clin Infect Dis 2001;32:11621171.CrossRefGoogle ScholarPubMed
6.Paterson, DL, Ko, WC, Von Gottberg, A, et al.International prospective study of Klebsiella pneumoniae bacteremia: implications of extended-spectrum beta-lactamase production in nosocomial infections. Ann Intern Med 2004;140:2632.CrossRefGoogle ScholarPubMed
7.Hyle, EP, Lipworth, AD, Zaoutis, TE, et al.Risk factors for increasing multidrug resistance among extended-spectrum β-lactamase-producing Escherichia coli and Klebsiella pneumoniae. Clin Infect Dis 2005;40:13171324.CrossRefGoogle Scholar
8.Cordery, RJ, Roberts, CH, Cooper, SJ, Bellinghan, G, Shetty, N. Evaluation of risk factors for the acquisition of bloodstream infections with extended-spectrum β-lactamase-producing Escherichia coli and Klebsiella species in the intensive care unit; antibiotic management and clinical outcome. J Hosp Infect 2008;68:108115.Google Scholar
9.Cosgrove, SE. The relationship between antimicrobial resistance and patient outcomes: mortality, length of hospital stay, and health care costs. Clin Infect Dis 2006;42(Suppl 2):S82S89.Google Scholar
10.Lautenbach, E, Strom, BL, Bilker, WB, Patel, JB, Edelstein, PH, Fishman, NO. Epidemiological investigation of fluoroquinolone resistance in infections due to extended-spectrum β-lactamase-producing Escherichia coli and Klebsiella pneumoniae. Clin Infect Dis 2001;33:12881294.CrossRefGoogle ScholarPubMed
11.Skippen, I, Shemko, M, Turton, J, Kaufmann, ME, Palmer, C, Shetty, N. Epidemiology of infections caused by extended-spectrum β-lactamase-producing Escherichia coli and Klebsiella spp.: a nested case-control study from a tertiary hospital in London. J Hosp Infect 2006;64:115123.CrossRefGoogle Scholar
12.Peña, C, Gudiol, C, Tubau, F, et al.Risk-factors for acquisition of extended-spectrum β-lactamase-producing Escherichia coli among hospitalized patients. Clin Microbiol Infect 2006;12:279284.CrossRefGoogle Scholar
13.Tumbarello, M, Spanu, T, Sanguinetti, M, et al.Bloodstream infections caused by extended-spectrum-/3-lactamase-producing Klebsiella pneumoniae, risk factors, molecular epidemiology, and clinical outcome. Antimicrob Agents Chemother 2006;50:498504.CrossRefGoogle ScholarPubMed
14.Apisarnthanarak, A, Mundy, LM. Prevalence, treatment, and outcome of infection due to extended-spectrum β-lactamase-producing microorganisms. Infect Control Hosp Epidemiol 2006;27:326327.CrossRefGoogle ScholarPubMed
15.Kang, CI, Kira, SH, Kim, DM, et al.Risk factors for and clinical outcomes of bloodstream infections caused by extended-spectrum β-lactamase-producing Klebsiella pneumoniae. Infect Control Hosp Epidemiol 2004;25:860867.CrossRefGoogle ScholarPubMed
16.Lin, MF, Huang, ML, Lai, SH. Risk factors in the acquisition of extended-spectrum β-lactamase Klebsiella pneumoniae, a case-control study in a district teaching hospital in Taiwan. J Hosp Infect 2003;53:3945.CrossRefGoogle Scholar
17.Apisarnthanarak, A, Kiratisin, P, Saifon, P, Kitphati, R, Dejsirilert, S, Mundy, LM. Risk factors for and outcomes of healthcare-associated infection due to extended-spectrum β-lactamase-producing Escherichia coli or Klebsiella pneumoniae in Thailand. Infect Control Hosp Epidemiol 2007;28:873876.CrossRefGoogle ScholarPubMed
18.Apisarnthanarak, A, Danchaivijitr, S, Khawcharoenporn, T, et al.Effectiveness of education and an antibiotic-control program in a tertiary care hospital in Thailand. Clin Infect Dis 2006;42:768775.CrossRefGoogle Scholar
19.Dejsirilert, S, Apisarnthanarak, A, Kitphati, R, et al. The status of antimicrobial resistance in Thailand among gram-negative pathogens in bloodstream infections: NARST data, 2000-2003 [abstract FP-A-3]. In: Program and abstracts of the 9th Western Pacific Congress on Chemotherapy and Infectious Diseases (Bangkok). Bangkok: Medinfo GD, 2004:185.Google Scholar
20.Garner, JS, Jarvis, WR, Emori, TG, Horan, TC, Hughes, JM. CDC definitions for nosocomial infections, 1988. Am J Infect Control 1988;16:128140.CrossRefGoogle ScholarPubMed
21.Kollef, MH. Inadequate antimicrobial treatment: an important determinant of outcome for hospitalized patients. Clin Infect Dis 2000;31 (Suppl 4):S131S138.CrossRefGoogle ScholarPubMed
22.Rodriguez-Bano, J, Navarro, MD, Romero, L, et al.Bacteremia due to extended-spectrum /?-lactamase-producing Escherichia coli in the CTX-M era: a new clinical challenge. Clin Infect Dis 2006;43:14071414.Google Scholar
23.CLSI. Performance standards for antimicrobial susceptibility testing: 17th informational supplement. CLSI document. Wayne, PA: CLSI, 2007: M100-S17.Google Scholar
24.Coque, TM, Oliver, A, Perez-Diaz, JC, et al.Genes encoding TEM-4, SHV-2, and CTX-M-10 extended-spectrum β-lactamases are carried by multiple Klebsiella pneumoniae clones in a single hospital (Madrid, 1989 to 2000). Antimicrob Agents Chemother 2002;46:500510.CrossRefGoogle Scholar
25.Oliver, A, Perez-Diaz, JC, Coque, TM, et al.Nucleotide sequence and characterization of a novel cefotaxime-hydrolyzing β-lactamases (CTX-M-10). Antimicrob Agents Chemother 2001;45:612620.CrossRefGoogle ScholarPubMed
26.Tenover, FC, Arbeit, RD, Goering, RV, et al.Interpreting chromosomal DNA restriction patterns produced by pulsed-field gel electrophoresis: criteria for bacterial strain typing. J Clin Microbiol 1995;33:22332239.CrossRefGoogle ScholarPubMed
27.Colodner, R, Rock, W, Chazan, B, et al.Risk factors for the development of extended-spectrum β-lactamase-producing bacteria in nonhospitali-zed patients. Eur J Clin Microbiol Infect Dis 2004;23:163167.CrossRefGoogle ScholarPubMed
28.Calbo, E, Romaní, V, Xercavins, M, et al.Risk factors for community-onset urinary tract infections due to Escherichia colt harboring extended-spectrum β-lactamases. J Antimicrob Chemother 2006;57:780783.CrossRefGoogle Scholar
29.Apisarnthanarak, A, Kiratisin, P, Saifon, P, Kitphati, R, Dejsirilert, S, Mundy, LM. Clinical and molecular epidemiology of community-onset, extended-spectrum β-lactamase-producing Escherichia coli infections in Thailand: a case-case-control study. Am J Infect Control 2007;35:606612.CrossRefGoogle ScholarPubMed
30.Paterson, DL, Hujer, KM, Hujer, AM, et al.Extended-spectrum β-lactamases in Klebsiella pneumonia bloodstream isolates from seven countries: dominance and widespread prevalence of SHV-and CTX-M-type β-lactamases. Antimicrob Agents Chemother 2003;47:35543560.CrossRefGoogle Scholar
31.Mehrgan, H, Rahbar, M. Prevalence of extended-spectrum β-lactamase-producing Escherichia coli in a tertiary care hospital in Tehran, Iran. Int J Antimicrob Agents 2008;31:147151.CrossRefGoogle Scholar
32.Lavilla, S, González-López, JJ, Sabaté, M, et al.Prevalence of qnr genes among extended-spectrum β-lactamase-producing enterobacterial isolates in Barcelona, Spain. J Antimicrob Chemother 2008;61:291295.CrossRefGoogle ScholarPubMed
33.Wu, JJ, Chen, HM, Ko, WC, Wu, HM, Tsai, SH, Yan, JJ. Prevalence of extended-spectrum β-lactamases in Proteus mirabilis in a Taiwanese university hospital, 1999 to 2005: identification of a novel CTX-M enzyme (CTX-M-66). Diagn Microbiol Infect Dis 2008;60:169175.CrossRefGoogle Scholar
34.Chanawong, A, M'Zali, FH, Heritage, J, Lulitanond, A, Hawkey, PM. SHV-12, SHV-5, SHV-2a and VEB-1 extended-spectrum β-lactamases in Gram-negative bacteria isolated in a university hospital in Thailand. J Antimicrob Chemother 2001;48:839852.CrossRefGoogle Scholar
35.Girlich, D, Poirel, L, Leelaporn, A, et al.Molecular epidemiology of the integron-located VEB-1 extended-spectrum β-lactamase in nosocomial enterobacterial isolates in Bangkok, Thailand. J Clin Microbiol 2001;39:175182.CrossRefGoogle ScholarPubMed
36.Kiratisin, P, Apisarnthanarak, A, Saifon, P, Laesripa, C, Kitphati, R, Mundy, LM. The emergence of a novel ceftazidime-resistant CTX-M extended-spectrum β-lactamase, CTX-M-55, in both community-onset and hospital-acquired infections in Thailand. Diagn Microbiol Infect Dis 2007;58:349355.Google Scholar
37.Moubareck, C, Daoud, Z, Hakime, NI, et al.Countrywide spread of community-and hospital-acquired extended-spectrum β-lactamase (CTX-M-15)-producing Enterobacteriaceae in Lebanon. J Clin Microbiol 2005;43:33093313.CrossRefGoogle ScholarPubMed
38.Ben-Ami, R, Schwaber, MJ, Navon-Venezia, S, et al.Influx of extended-spectrum β-lactamase-producing Enterobacteriaceae into the hospital. Clin Infect Dis 2006;42:925934.CrossRefGoogle ScholarPubMed
39.Safdar, N, Maki, DG. The commonality of risk factors for nosocomial colonization and infection with antimicrobial-resistant Staphylococcus aureus, Enterococcus, gram-negative bacilli, Clostridium difficile, and Candida. Ann Intern Med 2002;136:834844.CrossRefGoogle ScholarPubMed
40.Rodriguez-Bano, J, Navarro, MD, Romero, L, et al.Clinical and molecular epidemiology of extended-spectrum β-lactamase-producing Escherichia coli as a cause of nosocomial infection or colonization: implication for control. Clin Infect Dis 2006;42:3745.CrossRefGoogle ScholarPubMed
41.Moriguchi, N, Itahashi, Y, Tabata, N, et al.Outbreak of CTX-M-3-type extended-spectrum β-lactamase-producing Enterobacter cloacae in a pediatric ward. J Infect Chemother 2007;13:263264.CrossRefGoogle Scholar
42.Lavollay, M, Mamlouk, K, Frank, T, et al.Clonal dissemination of a CTX-M-15 β-lactamase-producing Escherichia coli strain in the Paris area, Tunis, and Bangui. Antimicrob Agents Chemother 2006;50:24332438.Google Scholar
43.Pai, H, Kim, MR, Seo, MR, Choi, TY, Oh, SH. A nosocomial outbreak of Escherichia coli producing CTX-M-15 and OXA-30 β-lactamase. Infect Control Hosp Epidemiol 2006;27:312314.CrossRefGoogle ScholarPubMed
44.Harris, AD, Perencevich, EN, Johnson, JK, et al.Patient-to-patient transmission is important in extended-spectrum β-lactamase-producing Klebsiella pneumoniae acquisition. Clin Infect Dis 2007;45:13471350.CrossRefGoogle ScholarPubMed
45.Paterson, DL, Yu, VL. Extended-spectrum β-lactamases: a call for improved detection and control. Clin Infect Dis 1999;29:14191422.CrossRefGoogle Scholar
46.Lavigne, JP, Marchandin, H, Delmas, J, et al.CTX-M β-lactamase-producing Escherichia coli in French hospitals: prevalence, molecular epidemiology, and risk factors. J Clin Microbiol 2007;45:620626.CrossRefGoogle ScholarPubMed