Clinical Features and Treatment Outcomes of Bloodstream Infections Caused by Extended-Spectrum β-Lactamase-Producing Escherichia coli Sequence Type 131

Abstract

Despite the remarkable emergence of extended-spectrum β-lactamase (ESBL)-producing Escherichia coli sequence type 131 (ST131), the clinical features and outcomes of infections caused by ST131 remain poorly described. From 2011 to 2012, we collected ESBL-producing E. coli isolates from patients with bloodstream infections in 13 hospitals in Korea and compared clinical characteristics and outcomes between ST131 and non-ST131 clones. Of the 110 ESBL-producing isolates, the most common ST was ST131 (30.9%). Multivariate analysis showed that recent operation was the only variable associated with the ST131 clone; other comorbid conditions and clinical features were similar between ST131 and non-ST131 clones. CTX-M-14 and CTX-M-15 were the predominant types of ESBLs, and CTX-M-15 was significantly associated with ST131. The rate of nonsusceptibility to ciprofloxacin was higher in ST131 than in non-ST131 clones (94.1% vs. 75.0%). No significant differences in 30-day mortality rates were found between ST131 and non-ST131 clones. Multivariate analysis revealed that older age (odds ratio [OR]=5.39, 95% confidence interval [CI] 1.22–23.89; p=0.027), nosocomial infection (OR=4.81, 95% CI 1.15–20.15; p=0.032), and higher Pitt bacteremia score (OR=7.26, 95% CI 1.41–37.42; p=0.018) were independent risk factors for 30-day mortality. The ESBL-producing E. coli ST131 clone has emerged and disseminated in Korea. Our findings reveal similarities in clinical and demographic characteristics between ST131 and non-ST131 clones. Although a more resistant profile has been detected in ST131, patients with the ST131 clone did not exhibit a higher mortality rate.

Introduction

Since its initial description in 2008, Escherichia coli sequence type 131 (ST131), associated with the CTX-M-type extended-spectrum β-lactamases (ESBLs), has emerged as a pandemic clone causing community- and hospital-acquired infections worldwide.^6,15 This clone belongs to the serotype O25:H4 and the highly virulent phylogroup B2. Numerous studies have reported that ST131 strains are more likely to harbor a broader range of virulence and resistance genes than non-ST131 strains, suggesting that these characteristics might play an important role in the pandemic dissemination of ST131.^4,18,19 In addition, several more recent reports have described the reservoirs and transmission dynamics of ST131.^1,16

However, relatively little is known about the clinical features and treatment outcomes of infections caused by E. coli ST131, and most studies regarding clinical aspects of ST131 have focused on patients with urinary tract infections. This study was therefore performed to evaluate the clinical and microbiological characteristics of bacteremia caused by ESBL-producing E. coli ST131 and to assess the impact of ST131 on treatment outcomes.

Materials and Methods

Study design and data collection

A multicenter surveillance study for bacteremia was performed from June 2011 to December 2012 in 13 hospitals located in South Korea. Using this database, a post hoc analysis, including patients with bacteremia caused by ESBL-producing E. coli, was conducted. If the patients experienced more than one bacteremic episode, only the first episode was included. Patients with polymicrobial bacteremia were excluded. The following data were collected by reviewing the medical records: age; sex; underlying diseases; comorbid conditions and severity of underlying disease according to McCabe classification; epidemiological setting at the onset of bacteremia (hospital, healthcare-associated, or community-associated); severity of illness according to the Pitt bacteremia score; presence of severe sepsis or septic shock; antimicrobial use within 3 months before bacteremia; and the appropriateness of initial antimicrobial treatment. The main outcome measure was the 30-day mortality rate. Additionally, clinical response at 72 hr was also assessed. Clinical response was classified as complete response (resolution of fever, bacteremia, and all other signs of infection), partial response (improvement of the above, but not complete resolution), or failure (persistent fever or bacteremia, clinical deterioration, or death). This study was approved by the Institutional Review Board of Samsung Medical Center.

Definition

The sites of infection were determined by the patient's physician on the basis of isolation of organisms from the presumed portal of entry and by clinical evaluation. Nosocomial infection was defined as an infection that occurred more than 48 hr after admission to the hospital, whereas infections diagnosed within the first 48 hr of hospitalization were classified as community-onset infections. Episodes of community-onset bacteremia were further classified as healthcare-associated or community-associated infections, as defined in previous studies.⁷ Sepsis was defined as the presence of two or more systemic inflammatory response syndrome criteria in addition to a documented or presumed infection.² Severe sepsis was defined as sepsis with one or more clinical signs of organ dysfunction. Septic shock was defined as sepsis associated with evidence of organ hypoperfusion and a systolic blood pressure <90 or >30 mmHg lower than the baseline or a requirement for a vasopressor to maintain a normal blood pressure.

Initial empirical antimicrobial therapy was considered appropriate when administration of antibiotics, to which the isolated E. coli were susceptible in vitro, was initiated during the first 24 hr after the blood culture was obtained; otherwise, the initial therapy was considered inappropriate.

Microbiological analysis

Species identification and antimicrobial susceptibility testing were performed using standard identification cards with an automated system (GN card for identification and AST131 card for antimicrobial susceptibility testing, VITEK^®2, bioMérieux, Inc., Marcy l'Etoile, France; NC53 card, MicroScan^®, Siemens Healthcare Diagnostics, Deerfield, IL), according to the recommendations of the Clinical and Laboratory Standard Institute (CLSI). Minimum inhibitory concentrations of the antibiotics tested were determined by the broth agar microdilution method according to CLSI guidelines,⁵ and ESBL activity was confirmed by a double-disk synergy test using BBL Sensi-Discs™ (Becton Dickinson & Co., Sparks, MD).²² Escherichia coli ATCC 25922 and Pseudomonas aeruginosa ATCC 27853 were used as control strains. ESBL-related genes, such as bla_TEM, bla_SHV, and bla_CTX-M, were amplified by PCR and confirmed by sequencing of PCR fragments.¹¹ Multilocus sequence typing (MLST) was performed using the method described in a previous study.¹⁴

Statistical analyses

To compare the clinical characteristics between ST131 and non-ST131 isolates, Student's t-test and Mann–Whitney U-test were used to compare continuous variables, and the Chi-square test or Fisher's exact test was used to compare categorical variables. To evaluate the impact of ST131 clone on clinical outcomes and identify independent risk factors for 30-day mortality, a backward stepwise multivariate logistic regression analysis was used. Variables with a p-value<0.1 in the univariate analysis were candidates for multivariate analysis in addition to the main variable of interest (presence of the ST131 clone). A two-tailed p-value <0.05 was considered significant. SPSS Statistics, version 19.0 (IBM, Armonk, NY) was used for analyses.

Results

Study population

During the study period, a total of 851 cases with E. coli bacteremia were identified. Of these, 183 (21.5%) were identified as ESBL-producing E. coli. After excluding 73 cases because of unavailable clinical information (n=67) or polymicrobial bacteremia (n=6), a total of 110 cases with ESBL-producing E. coli bacteremia were included in the study (among 110 cases, 7 cases were also included in a previously reported study⁹).The mean age (±standard deviation) was 63.45±15.14 years, and 45.5% of patients were male. Forty-one cases (37.3%) were classified as hospital-onset infections and 69 as community-onset infections, including 36 cases (32.7%) of community-associated and 33 cases (30%) of healthcare-associated infections. Most of the patients (n=100, 90.9%) had at least one underlying disease, and the most common underlying disease was malignancy (50.9%). Among the total 110 isolates studied, MLST analysis identified 32 distinctive ST clones. The most prevalent clone was ST131 (n=34, 30.9%), followed by ST405 (n=13, 11.8%) and ST38 (n=11, 10.0%). The distribution of STs among the total 110 isolates studied is shown in Table 1.

Table 1.

Distribution of STs Among the Total 110 ESBL-Producing Escherichia coli Isolates

CC	ST (allelic profile ^a )	No. (%) of isolates
CC131	131 (53-40-47-13-36-28-29)	34 (30.9)
CC405	405 (35-37-29-25-4-5-73)	13 (11.8)
CC38	38 (4-26-2-25-5-5-19)	11 (10.0)
CC31	393 (18-106-17-6-5-5-4)	5 (4.5)
CC69	69 (21-35-27-6-5-5-4)	5 (4.5)
CC10	10 (10-11-4-8-8-8-2)	2 (1.8)
	44 (10-11-4-8-8-8-7)	1 (0.9)
	167 (10-11-4-8-8-13-2)	1 (0.9)
CC73	73 (36-24-9-13-17-11-25)	4 (3.6)
CC95	95 (37-38-19-37-17-11-26)	3 (2.7)
CC354	354 (85-88-78-29-59-58-62)	3 (2.7)
CC394	394 (21-35-61-52-5-5-4)	1 (0.9)
CC469	162 (9-65-5-1-9-13-6)	1 (0.9)
Singletons	68 (33-26-2-31-5-16-19)	1 (0.9)
	117 (20-45-41-43-5-32-2)	1 (0.9)
	224 (6-4-33-16-11-8-6)	1 (0.9)
	457 (101-88-97-108-26-79-2)	2 (1.8)
	539 (6-19-57-18-9-13-6)	1 (0.9)
	648 (92-4-87-96-70-58-2)	4 (3.6)
	744 (10-11-135-8-8-8-2)	1 (0.9)
	1177 (4-26-2-211-5-5-19)	4 (3.6)
	1193 (14-14-10-200-17-7-10)	1 (0.9)
	1584 (8-7-1-229-8-8-6)	1 (0.9)
	1642 (6-4-5-18-11-8-6)	1 (0.9)
	1832 (223-271-223-29-70-146-167)	1 (0.9)
	2003 (4-26-2-25-4-5-19)	1 (0.9)
	2522 (6-29-5-18-11-8-2)	1 (0.9)
	3177 (92-4-87-96-70-5-2)	1 (0.9)
	3943 (6-95-4-21-9-8-44)	1 (0.9)
	3944 (10-11-4-8-179-8-2)	1 (0.9)
	3945 (80-95-3-18-11-8-156)	1 (0.9)
	3946 (10-11-47-8-8-266)	1 (0.9)

Allelic profile, adk-fumC-gyrB-icd-mdh-purA-recA.

CC, clonal complex; ESBL, extended-spectrum β-lactamase; ST, sequence type.

Comparison of clinical characteristics between patients with ST131 and non-ST131 clones

Demographic and clinical characteristics were compared between patients with ST131 clones (n=34) and those with non-ST131 clones (n=76) (Table 2). The mean age (±standard deviation) of patients with ST131 clones and non-ST131 clones was 67.65±13.99 and 61.57±15.34 years, respectively (p=0.051). Neurologic disease was more frequent in patients with ST131 clones than those with non-ST131 clones (23.5% vs. 10.5%, p=0.086), although these data did not reach statistical significance, whereas underlying malignancy was more frequent in those with non-ST131 clones (59.2% vs. 32.4%, p=0.009). The urinary tract and hepatobiliary tract were the most common sites of infection in both patients with ST131 clones and those with non-ST131 clones; however, patients with non-ST131 clones were more likely to have primary bacteremia (21.1% vs. 5.9%, p=0.047). With respect to comorbid conditions, the presence of ST131 isolates was associated with recent operation (p=0.037), whereas the presence of non-ST131 isolates was associated with the central venous catheter (p=0.048). The presence of severe sepsis or septic shock at the onset of bacteremia and the incidence of previous antimicrobial use within 3 months before bacteremia were similar between the groups. In the multivariate analysis, recent operation within the previous 3 months (odds ratio [OR]=5.17, 95% confidence interval [CI] 1.52–17.58; p=0.009) was significantly associated with ST131 clones. The appropriateness of initial antimicrobial therapy and the rates of conversion from inappropriate empirical to appropriate definitive agents did not differ between ST131 clones and non-ST131 clones (52.9% vs. 48.7%, p=0.680 and 66.7% vs. 81.1%, p=0.236, respectively).

Table 2.

Clinical Characteristics of Patients with ST131 and Non-ST131 Clones in ESBL-Producing Escherichia coli Bacteremia

Clinical characteristics	ST131 (n=34)	Non-ST131 (n=76)	p-Value
Age (years) (mean±SD)	67.65±13.99	61.57±15.34	0.051
Male	15 (44.1)	35 (46.1)	0.851
Acquisition of bacteremia			0.990
Community-associated	11 (32.4)	25 (32.9)	0.955
Healthcare-associated	10 (29.4)	23 (30.3)	0.928
Nosocomial	13 (38.2)	28 (36.8)	0.889
Underlying disease
Malignancy	11 (32.4)	45 (59.2)	0.009
Cardiovascular disease	9 (26.5)	19 (25.0)	0.870
Neurologic disease	8 (23.5)	8 (10.5)	0.086
Liver disease	6 (17.6)	10 (13.2)	0.566
Renal disease	2 (5.9)	3 (3.9)	0.644
Lung disease	3 (8.8)	4 (5.3)	0.674
None	3 (8.8)	7 (9.2)	1.000
Severity of underlying disease (McCabe classification)
Rapidly fatal	3 (8.8)	10 (13.2)	0.553
None or nonrapidly fatal	31 (91.2)	66 (86.8)	0.751
Comorbid condition
Recent operation	9 (26.5)	7 (9.2)	0.037
Neutropenia	3 (8.8)	14 (18.4)	0.198
Corticosteroid use	2 (5.9)	1 (1.3)	0.225
Immunosuppressant use	0 (0)	4 (5.3)	0.309
Central venous catheterization	5 (14.7)	25 (32.9)	0.048
Indwelling urinary catheter	9 (26.5)	14 (18.4)	0.337
Nasogastric tube	2 (5.9)	9 (11.8)	0.498
Percutaneous tube	9 (26.5)	14 (18.4)	0.337
Invasive procedure within 72 hr	9 (26.5)	16 (21.1)	0.531
Prior receipt of antibiotics	19 (55.9)	39 (51.3)	0.658
Expanded-spectrum cephalosporins	12 (35.3)	28 (36.8)	0.876
Fluoroquinolones	7 (20.6)	11 (14.5)	0.423
β-Lactam+β-lactamase inhibitor	3 (8.8)	13 (17.1)	0.382
Carbapenems	5 (14.7)	5 (6.6)	0.279
Severe sepsis/septic shock	16 (47.1)	33 (43.4)	0.723
Pitt bacteremia score, ≥4 points	5 (14.7)	14 (18.4)	0.634
Site of infection
Urinary tract infection	17 (50.0)	36 (47.4)	0.799
Hepatobiliary tract infection	7 (20.6)	13 (17.1)	0.662
Intra-abdominal infection	2 (5.9)	6 (7.9)	1.000
Primary bacteremia	2 (5.9)	16 (21.1)	0.047
Pneumonia	4 (11.8)	6 (7.9)	0.495
Appropriate initial antibiotics	18 (52.9)	37 (48.7)	0.680
Complete response rate at 72 hr	11 (32.4)	41 (53.9)	0.360
30-day mortality	6 (17.6)	12 (15.8)	0.808

Data are n (%) of patients unless otherwise stated.

SD, standard deviation; ST131, sequence type 131.

Treatment outcomes of bacteremia caused by ESBL-producing E. coli ST131

When clinical response at 72 hr was assessed, the complete response rate was lower in the ST131 group than in the non-ST131 group (32.4% vs. 53.9%, respectively, p=0.36; Table 2). However, the 30-day mortality rate was similar between the two groups (17.6% vs. 15.8%, p=0.808). On univariate analysis, factors associated with higher 30-day mortality were older age, nosocomial infection, higher Pitt bacteremia score, severe sepsis or septic shock at presentation, hepatobiliary tract infection, and pneumonia. Multivariate analysis revealed that older age (OR=5.39, 95% CI 1.22–23.89; p=0.027), nosocomial infection (OR=4.81, 95% CI 1.15–20.15; p=0.032), and higher Pitt bacteremia score (OR=7.26, 95% CI 1.41–37.42; p=0.018) were independent risk factors for 30-day mortality (Table 3). However, the presence of the ST131 clone was not associated with 30-day mortality.

Table 3.

Factors Associated with 30-Day Mortality in Patients with ESBL-Producing Escherichia coli Bacteremia

Clinical characteristics	Survived (n=92)	Died (n=18)	p-Value	Multivariate analysis OR (95% CI)	p-Value
Age (years) (mean±SD)	61.73±14.82	72.22±14.01	0.007	5.39 (1.22–23.89)	0.027
Male	40 (43.5)	10 (55.6)	0.347
ST131 clone	28 (30.4)	6 (33.3)	0.808
Acquisition of bacteremia
Community-associated	33 (35.9)	3 (16.7)	0.112
Healthcare-associated	28 (30.4)	5 (27.8)	0.822
Nosocomial	31 (33.7)	10 (55.6)	0.079	4.81 (1.15–20.15)	0.032
Underlying disease
Malignancy	46 (50.0)	10 (55.6)	0.666
Cardiovascular disease	22 (23.9)	6 (33.3)	0.391
Diabetes mellitus	22 (23.9)	1 (5.6)	0.113
Neurologic disease	13 (14.1)	3 (16.7)	0.724
Liver disease	13 (14.1)	3 (16.7)	0.724
Renal disease	3 (3.3)	2 (11.1)	0.187
Lung disease	5 (5.4)	2 (11.1)	0.321
Severity of underlying disease
Rapidly fatal	9 (9.8)	4 (22.2)	0.222
None or nonrapidly fatal	83 (90.2)	14 (77.8)	0.222
Comorbid condition
Recent operation	15 (16.3)	1 (5.6)	0.463
Neutropenia	13 (14.1)	4 (22.2)	0.474
Solid organ transplantation	3 (3.3)	0 (0)	1.000
Corticosteroid use	3 (3.3)	0 (0)	1.000
Immunosuppressant use	4 (4.3)	0 (0)	1.000
Severe sepsis/septic shock	37 (40.2)	12 (66.7)	0.039
Pitt bacteremia score, ≥4	11 (12.0)	8 (44.4)	0.003	7.26 (1.41–37.42)	0.018
Site of infection
Urinary tract infection	47 (51.1)	6 (33.3)	0.168
Hepatobiliary tract infection	14 (15.2)	6 (33.3)	0.093
Intra-abdominal infection	7 (7.6)	1 (5.6)	1.000
Primary bacteremia	15 (16.3)	3 (16.7)	1.000
Pneumonia	5 (5.4)	5 (27.8)	0.010
Inappropriate initial antibiotics	47 (51.1)	8 (44.4)	0.606

Data are n (%) of patients unless otherwise stated.

CI, confidence interval; OR, odds ratio.

Antibiotic susceptibility and ESBL gene analysis

Regarding the antibiotic susceptibility of ST131 and non-ST131 clones, ST131 had a trend of greater nonsusceptibility to ciprofloxacin and ceftazidime compared with non-ST131 clones (94.1% vs. 75.0%, p=0.018 and 73.5% vs. 55.3%, p=0.070, respectively). However, no significant differences were found for piperacillin/tazobactam and carbapenems (Table 4). Among the 110 ESBL-EC isolates, 33 (30%) produced CTX-M-14 (CTX-M-14 alone [n=26], CTX-M-3 and CTX-M-14 [n=3], CTX-M-14 and CTX-M-55 [n=2],CTX-M-14 and CTX-M-57 [n=2]); 31 (28.2%) produced CTX-M-15 (CTX-M-15 alone [n=28] and CTX-M-15 and CTX-M-24 [n=3]); and 24 (21.8%) produced both CTX-M-14 and CTX-M-15. The remaining isolates produced CTX-M-24 alone (n=4), CTX-M-27 alone (n=3), CTX-M-57 alone (n=3), CTX-M-55 alone (n=2), CTX-M-3 alone (n=1) or CTX-M-24, and CTX-M-57 (n=2). Fifty-nine isolates (53.6%) also produced TEM-1 and 3 isolates (2.7%) also produced SHV-type β-lactamases (SHV-11, 2 isolates; SHV-1, 1 isolate) in addition to CTX-M-type ESBL. CTX-M-15-producing E. coli isolates showed a higher nonsusceptibility rate to ceftazidime than non CTX-M-15 E. coli isolates (74.5% vs. 47.3%, p=0.003). ST131 clones were strongly associated with CTX-M-15 production compared with non-ST131 clones, but there were no significant differences in the production of other types of ESBLs between ST131 and non-ST131 clones (Table 5).

Table 4.

Antibiotic Susceptibility of ESBL-Producing Escherichia coli Causing Bacteremia

	No. (%) of nonsusceptible isolates
Agent	ST131	Non-ST131	p-Value
Cefotaxime	34 (100)	74 (97.4)	0.569
Ceftazidime	25 (73.5)	42 (55.3)	0.070
Cefepime	29 (85.3)	58 (76.3)	0.285
Piperacillin/tazobactam	16 (47.1)	31 (40.8)	0.539
Ciprofloxacin	32 (94.1)	57 (75.0)	0.018
Ertapenem	4 (12.1)	9 (12.0)	1.000
Meropenem	1(2.9)	0 (0)	0.309

Table 5.

ESBL Types of ESBL-Producing Escherichia coli Causing Bacteremia

	No. (%) of isolates
ESBLs	ST131	Non-ST131	p-Value
CTX-M-14	8 (23.5)	25(32.9)	0.322
CTX-M-15	15 (44.1)	16 (21.1)	0.013
CTX-M-14+M-15	9 (26.5)	15 (19.7)	0.429

Discussion

This study investigated the clinical characteristics and treatment outcomes of bacteremia caused by ESBL-producing E. coli ST131. Previous studies of ESBL E. coli bacteremic isolates reported that the ST131 clone was more likely to cause community-onset infections, especially in patients with urinary tract infections, compared with non-ST131 clones.^18,19 However, in the present study, the ST131 clone was the most frequently observed clonal group in both hospital-onset and community-onset bacteremia caused by ESBL E. coli. With regard to the site of infection, urinary tract infections accounted for the majority of ST131 and non-ST131 clones, as expected. Additionally, 26.5% of cases with the ST131 clone had biliary tract infections or intra-abdominal infections. Data from the global Study for Monitoring Antimicrobial Resistance Trends (SMART) revealed that the prevalence of ESBL-producing E. coli isolates in patients with intra-abdominal infections is highest in countries in the Asia-Pacific region.⁸ However, the prevalence of the ST131 clone among these isolates has not been reported. Our findings suggest that intra-abdominal infection and biliary tract infection are common in patients with ESBL-producing E. coli ST131 in addition to urinary tract infection and that the increasing prevalence of intra-abdominal infections caused by ESBL-producing E. coli in the Asia-Pacific region might be closely associated with dissemination of the ST131 clone.

Recent studies have found that older age and residence in long-term care facilities (LTCFs) are predictors of ST131 infection.^1,16 Although the data did not show statistical significance, the patients in the present study with ST131 clones were older than those with non-ST131 clones and more likely to have underlying neurologic diseases. It is likely that extensive and frequent exposure to antibiotics and contact with colonized or infected patients in healthcare settings (including LTCFs or hospitals) contribute to the high prevalence of ST131 among patients with older age or underlying neurologic diseases. Our previous study on community-onset bacteremia caused by ESBL-producing E. coli did not reveal any significant differences in clinical characteristics in the ST131 group versus the non-ST131 group.⁹ Although recent surgery was significantly associated with ST131 clones, in the present study, other comorbid conditions and clinical features were similar between the groups. These findings suggest that the ESBL-producing ST131 clone has disseminated in both community and hospital settings in Korea.

A systematic review and meta-analysis showed that ESBL production is associated with increased mortality and a delay in effective therapy in Enterobacteriaceae bacteremia.²¹ However, there are very few studies focusing on treatment outcomes of bacteremia caused by ESBL-producing E. coli ST131. Despite the increased virulence factors and antibiotic resistance of ST131 clones, a recent study showed no differences in mortality between patients infected with ST131 and those infected with non-ST131 clones.³ Similarly, in the present study, ST131 and non-ST131 clones showed similar treatment outcomes. Although high virulence and multidrug resistance may contribute to a survival advantage and dissemination of ST131 clones, the impact of these factors on clinical outcome remains unclear. Moreover, increased mortality was not statistically associated with inappropriate empirical therapy. This finding might be explained by the influence of the site of infection on treatment efficacy. Initial inappropriate antibiotic therapy may be successful for the treatment of urinary tract infection because of the high antibiotic level achieved in the urine. In addition, in the case of biliary tract infection or intra-abdominal infection, the appropriate source control procedure to drain infected foci is an important component of the treatment in addition to antibiotic therapy, as we demonstrated in our previous study.¹⁰

The particular CTX-M enzyme type in ESBL-producing E. coli varies geographically. CTX-M-15, which belongs to the CTX-M-1 group, is the most prevalent CTX-M allele with a worldwide distribution.^19,20 CTX-M-14, which belongs to the CTX-M-9 group, is another common variant that is highly prevalent in some European and Asian countries.^13,17,23 In the present study, CTX-M-14 was the predominant type of ESBLs among both ST131 and non-ST131 clones, whereas CTX-M-15 was significantly associated with the ST131 clone. Despite the predominance of CTX-M-14, it is notable that the overall prevalence of CTX-M-15 was higher than that reported in earlier Korean studies.¹²

This study has several limitations. First, the medical chart review might be limited by the availability and completeness of a medical record as a result of the study's retrospective nature. In addition, because of the lack of detailed demographic features, such as travel abroad, food consumption, and LTCF residence, we do not know the reservoirs and transmission dynamics of ST131 clones. Second, because we used primers for only the CTX-M-1 group and CTX-M-9 group for detection of bla_CTX-M genes in the present study, we were unable to investigate the presence of other CTX-M groups, including CTX-M-2 and CTX-M-8. A more comprehensive survey, including these CTX-M groups, may be needed. Nevertheless, despite these limitations, this is the largest multicentre study comparing clinical characteristics and treatment outcomes between ST131 and non-ST131 clones. In conclusion, as in other parts of the world, the ESBL-producing E. coli ST131 clone has emerged and disseminated in both community and healthcare settings in Korea. Our findings reveal similarities in clinical and demographic characteristics between ST131 and non-ST131 clones in ESBL-producing E. coli bacteremia. Although a more resistant profile has been detected in ST131, the ST131 clone was not associated with a higher mortality than non-ST131 clones. Continuous surveillance and further investigations focusing on ST131 could help reduce infection-related morbidity and mortality.

Footnotes

Acknowledgments

The authors would like to thank all participating investigators in the KONSID: Jun Seong Son and Soo-Youn Moon (Kyung Hee University Hospital at Gangdong, Seoul, Korea); Choon Kwan Kim (Seoul Veterans Hospital, Seoul, Korea); Seung Soon Lee and Jeong-A Lee (Hallym University Sacred Heart Hospital, Seoul, Korea); Yeon-Sook Kim and Kyung Mok Sohn (Chungnam National University Hospital, Daejeon, Korea); Ji-Young Rhee (Dankook University Hospital, Cheonan, Korea); Sook-In Jung, Kyung Hwa Park, and Seung Ji Kang (Chonnam National University Hospital, Gwangju, Korea); Shin-Woo Kim and Hyun-Ha Chang (Kyungpook National University Hospital, Daegu, Korea); Seong Yeol Ryu and Hyun Ah Kim (Keimyung University Dongsan Medical Center, Daegu, Korea); Ki Tae Kwon (Daegu Fatima Hospital, Daegu, Korea); and Min Hee Lim (Changwon Fatima Hospital, Changwon, Korea).

This study was supported by the Basic Research Program through the National Research Foundation of Korea (NRF), funded by the Ministry of Education, Science and Technology (No. 2010-0021572).

Disclosure Statement

No competing financial interests exist.

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