Risk Factors for Infection or Colonization with CTX-M Extended-
Spectrum-?-Lactamase-Positive Escherichia coli
Jennifer H. Han,aKei Kasahara,bPaul H. Edelstein,cWarren B. Bilker,d,eand Ebbing Lautenbacha,d,e
Division of Infectious Diseases, Department of Medicine,aDepartment of Pathology and Laboratory Medicine,cDepartment of Biostatistics and Epidemiology,dand
Center for Clinical Epidemiology and Biostatistics,eUniversity of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA, and Center for Infectious Diseases,
Nara Medical University, Kashihara, Japanb
Therehasbeenasignificantincreaseintheprevalenceof Enterobacteriaceae thatproduceCTX-M-typeextended-spectrum
richia coli. A case-control study was conducted within a university system from 1 January 2007 to 31 December 2008. All patients
with clinical cultures with E. coli demonstrating resistance to extended-spectrum cephalosporins were included. Case patients
were designated as those with cultures positive for CTX-M-positive E. coli, and control patients were designated as those with
non-CTX-M-producing E. coli. Multivariable logistic regression analyses were performed to evaluate risk factors for CTX-M-
positive isolates. A total of 83 (56.8%) of a total of 146 patients had cultures with CTX-M-positive E. coli. On multivariable anal-
yses, there was a significant association between infection or colonization with CTX-M-type ?-lactamase-positive E. coli and
an increased risk of colonization or infection with CTX-M-positive E. coli. Future studies will need to focus on outcomes associ-
ated with infections due to CTX-M-positive E. coli, as well as infection control strategies to limit the spread of these increasingly
ESBL-producing Enterobacteriaceae are associated with increased
morbidity, mortality, and health care costs (19, 42). In the past
decade, there has been a significant increase in the prevalence of
Given the increased mortality associated with delay in appro-
priate treatment for ESBL-associated infections (41), early recog-
ing E. coli is critical for selection of empirical antibiotic therapy
Risk factors such as severity of illness, instrumentation, and prior
teriaceae in general (4, 5, 19). However, despite emerging data
suggesting that the epidemiology of CTX-M-producing isolates is
are few published studies specifically evaluating risk factors for
CTX-M-producing Enterobacteriaceae (7, 20, 26, 37, 39, 46). Fur-
thermore, these have been limited by small sample sizes (20, 26,
37, 46) and restricted to select patient populations or types of
studies evaluating risk factors for CTX-M-producing E. coli in
the United States, where the epidemiologies of infections asso-
ciated with CTX-M-type ?-lactamases may be different due to
variation in antibiotic prescription and infection control prac-
tices. Finally, to our knowledge, our study is the first to inves-
tigate risk factors for CTX-M production in E. coli using a
?-lactamase (ESBL)-producing Gram-negative organisms
control group selected from non-CTX-M-producing Entero-
bacteriaceae demonstrating resistance, as opposed to suscepti-
bility, to extended-spectrum cephalosporins. Elucidating risk
other ESBLs) is critical, since prior work suggests that the epi-
demiologies of various resistance mechanisms among Entero-
bacteriaceae, including risk factors for isolation, may be differ-
ent (18). Therefore, we conducted the present study to evaluate
risk factors for infection or colonization with CTX-M-positive
E. coli, with the hypothesis that prior antibiotic use is a signif-
icant risk factor for isolation of CTX-M-positive E. coli.
MATERIALS AND METHODS
Study design and setting. This case-control study was conducted at two
hospitals in the University of Pennsylvania Health System (UPHS) in
Philadelphia: the Hospital of the University of Pennsylvania (HUP), a
725-bed academic tertiary care medical center, and Penn Presbyterian
Study population. All adult inpatients and outpatients with clinical
Received 30 May 2012 Returned for modification 17 July 2012
Accepted 7 August 2012
Published ahead of print 13 August 2012
Address correspondence to Jennifer H. Han, email@example.com.
Copyright © 2012, American Society for Microbiology. All Rights Reserved.
November 2012 Volume 56 Number 11Antimicrobial Agents and Chemotherapyp. 5575–5580aac.asm.org
30. Pena C, et al. 2006. Risk-factors for acquisition of extended-spectrum
beta-lactamase-producing Escherichia coli among hospitalized patients.
Clin. Microbiol. Infect. 12:279–284.
31. Pitout JD, Hamilton N, Church DL, Nordmann P, Poirel L. 2007.
Development and clinical validation of a molecular diagnostic assay to
detect CTX-M-type beta-lactamases in Enterobacteriaceae. Clin. Micro-
biol. Infect. 13:291–297.
32. Pitout JD, Hanson ND, Church DL, Laupland KB. 2004. Population-
based laboratory surveillance for Escherichia coli-producing extended-
spectrum beta-lactamases: importance of community isolates with
blaCTX-Mgenes. Clin. Infect. Dis. 38:1736–1741.
33. Pitout JD, Laupland KB, Church DL, Menard ML, Johnson JR. 2005.
Virulence factors of Escherichia coli isolates that produce CTX-M-type
extended-spectrum beta-lactamases. Antimicrob. Agents Chemother. 49:
34. Quan H, et al. 2005. Coding algorithms for defining comorbidities in
ICD-9-CM and ICD-10 administrative data. Med. Care 43:1130–1139.
35. Rodriguez-Bano J, et al. 2008. Community infections caused by extend-
ed-spectrum beta-lactamase-producing Escherichia coli. Arch. Intern.
36. Rodriguez-Bano J, et al. 2004. Epidemiology and clinical features of
infections caused by extended-spectrum beta-lactamase-producing Esch-
erichia coli in nonhospitalized patients. J. Clin. Microbiol. 42:1089–1094.
37. Rodriguez-Bano J, et al. 2006. Clinical and molecular epidemiology of
extended-spectrum beta-lactamase-producing Escherichia coli as a cause
of nosocomial infection or colonization: implications for control. Clin.
Infect. Dis. 42:37–45.
38. Rodriguez-Bano J, Paterson DL. 2006. A change in the epidemiology of
infections due to extended-spectrum beta-lactamase-producing organ-
isms. Clin. Infect. Dis. 42:935–937.
39. Rodriguez-Bano J, et al. 2010. Community-onset bacteremia due to
extended-spectrum beta-lactamase-producing Escherichia coli: risk fac-
tors and prognosis. Clin. Infect. Dis. 50:40–48.
40. Rossolini GM, D’Andrea MM, Mugnaioli C. 2008. The spread of CTX-
M-type extended-spectrum beta-lactamases. Clin. Microbiol. Infect.
41. Schwaber MJ, Carmeli Y. 2007. Mortality and delay in effective therapy
associated with extended-spectrum beta-lactamase production in Entero-
bacteriaceae bacteraemia: a systematic review and meta-analysis. J. Anti-
microb. Chemother. 60:913–920.
42. Schwaber MJ, et al. 2006. Clinical and economic impact of bacteremia
with extended-spectrum-beta-lactamase-producing Enterobacteriaceae.
Antimicrob. Agents Chemother. 50:1257–1262.
43. Sidjabat HE, et al. 2009. Molecular epidemiology of CTX-M-producing
Escherichia coli isolates at a tertiary medical center in western Pennsylva-
nia. Antimicrob. Agents Chemother. 53:4733–4739.
44. Skippen I, et al. 2006. Epidemiology of infections caused by extended-
spectrum beta-lactamase-producing Escherichia coli and Klebsiella spp.: a
nested case-control study from a tertiary hospital in London. J. Hosp.
45. Woodford N, et al. 2004. Community and hospital spread of Escherichia
coli producing CTX-M extended-spectrum beta-lactamases in the UK. J.
Antimicrob. Chemother. 54:735–743.
46. Wu UI, Wang JL, Chen WC, Chang SC, Chen YC. 2010. Risk factors and
outcomes of Escherichia coli bacteremia caused by strains that produce
Microbiol. Infect. Dis. 30:33–39.
Han et al.
aac.asm.org Antimicrobial Agents and Chemotherapy