Changing Epidemiology of Extended Spectrum Beta-Lactamases ... · Changing Epidemiology of Extended Spectrum Beta-Lactamases Pathogen of Urinary Tract Taesoo Choi, Koo Han Yoo, Sun-Ju

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ReviewISSN 2465-8243(Print) / ISSN 2465-8510(Online)

http://dx.doi.org/10.14777/uti.2015.10.2.74Urogenit Tract Infect 2015;10(2):74-83

Changing Epidemiology of Extended Spectrum Beta-Lactamases Pathogen of Urinary Tract

Taesoo Choi, Koo Han Yoo, Sun-Ju Lee

Department of Urology, Kyung Hee University School of Medicine, Seoul, Korea

This review covers the recent findings on extended spectrum beta-lactamases (ESBL) pathogens, focusing on the epidemiology of infection due to this pathogen. Use of ESBL is growing rapidly and widely. CTX-M-15 producing ESBL Escherichia coli is the most commonly encountered in clinical practice. In general, ESBL infections are represented by urinary tract infections, but they can also cause fatal infections involving the vascular system and central nervous system. Because E. coli is a common colonizer of normal intestine, increasing prevalence of ESBL-producing pathogens is particularly troublesome. In a situation where ESBLs are disseminated in the community, the ideal control of this multidrug-resistant pathogen will be challenging. Precise data on the prevalence and risk factors of ESBL-producing microorganism are still undetermined. More epidemiological studies are needed for the question to be answered. In order to maximize efficiency of treatment, information on the trend of increasing numbers of ESBLs is also needed on persistence of ESBLs in carriers as well as better understanding of how antibiotic treatment and other risk factors affect their persistence and further dissemination. The global emergence of multidrug-resistant ESBL pathogen has recently led to critical treatment problems. Early detection, adequate antibiotic therapy, and effective prevention are necessary for achievement of a safe community.

Keywords: Beta-lactamases; Epidemiology; Pathogen; Uropathogenic Escherichia coli

Copyright 2015, Korean Association of Urogenital Tract Infection and Inflammation. All rights reserved. This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits

unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Received: 30 June, 2015Revised: 27 July, 2015Accepted: 27 July, 2015

Correspondence to: Koo Han Yoo http://orcid.org/0000-0001-7952-7902

Department of Urology, Kyung Hee University Hospital at Gangdong, 892 Dongnam-ro, Gangdong- gu, Seoul 05278, KoreaTel: +82-2-440-7735, Fax: +82-2-440-7744E-mail: [email protected]

INTRODUCTION

Extended spectrum beta-lactamases (ESBLs) are the

enzymes that have been produced by microorganisms,

which weaken the effect of beta-lactam antibiotics with

broad-spectrum [1]. Beta-Lactams are one of common

regimen for the management of infections including urinary

tract infections (UTI) and pneumonia, as well as for fatal

state such as bacteremia. Beta-Lactams are also frequently

used to prevent infections perioperatively. The ESBL-producing

organism was historically first reported in 1983. The cha-

racteristics of beta-lactamase in strains of Klebsiella pneu-

moniae were described as being capable of hydrolyzing

extended-spectrum cephalosporins in Germany [2]. Recently,

ESBL-producing organisms are considered as important

cause of nosocomial and community acquired infections

[3]. The outbreak of ESBLs happens from TEM-1, TEM-2,

or SHV-1 genes by mutation, which are commonly found

in Enterobacteriaceae family [4]. The enzymes are found

in Klebsiella species and Escherichia coli mostly; however,

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Taesoo Choi, et al. Current Trend of ESBL Epidemiology Worldwide 75

Urogenit Tract Infect Vol. 10, No. 2, October 2015

they have also been reported in other Enterobacteriaceae

family including Citrobacter, Serratia, Proteus, Providencia,

Shigella, Salmonella, and Enterobacter [5]. The prevalence

of isolates expressing ESBLs varies region by region with

low rates of 3-8% in Sweden, Japan, and Singapore

compared to much higher rates of 30-60% in Portugal, Italy,

New York, Latin American countries, and Turkey [1]. In

the Arabian Peninsula, ESBL detection rates range from

8.5-38.5% in Saudi Arabia and 31.7% in Kuwait [6,7]. This

diversity may be due to the fact that the studies focused

on biased study group or specific sites of infection.

The major types of beta-lactamases are below; TEM, SHV,

CTX-M, and OXA beta-lactamases. CTX-M ESBLs have

appeared as the most common and significant type of ESBL

worldwide, their incidence markedly exceeding those of

TEM, SHV, and OXA ESBLs. According to recent studies,

the most widely distributed CTX-M enzyme is CTX-M-15,

which was first reported in E. coli from India in 2001 [8].

CTX-M-15 producing E. coli with multidrug-resistant is

emerging globally as a virulent pathogen causing hospital

and community acquired infections since 2003 [9,10].

ESBL-producing members of the family Enterobacteriaceae

are clinically important due to the fact that they play a

role of inflammation and infections in urinary tract, central

nervous system, lower respiratory tract and bloodstream,

but are also familiar colonizers of digestive system. These

microorganisms form a heterogeneous group that enables

hydrolytic reaction against the beta-lactams while remaining

sensitive to inhibition by beta-lactamase inhibitors. This

is critical because ESBLs are resistant to common antibiotics

including penicillins, broad-spectrum cephalosporins, and

aztreonam [11]. ESBL-producing organisms are also resistant

to quinolones, aminoglycosides, and trimethoprim-sulfa-

methoxazole [1].

Previous large-scale studies demonstrate that ESBL-pro-

ducing E. coli and K. pneumonia isolates are susceptible

to carbapenems generally [12]. Nevertheless, antibiotic

resistance in gram-negative bacilli (GNB) is spreading

worldwide with variety of regional resistance. So, we need

to monitor susceptibility trends in every corner of the world

over time to understand those trends so that effective

treatments can be accomplished to meet national social

needs. We have reviewed the recent findings on epi-

demiology of ESBL-producing organisms, based on the

comparison with prior surveys.

METHODS

A systemic literature review was performed on PubMed

and Google Scholar. Keywords included “epidemiology”, “ESBL” and “ST131 E. coli”. Original articles, related articles

and their references were considered, and a summary of

each data was reorganized based on clinical basis.

THE CHARACTERISTICS OF ESCHERICHIA COLI ST131 CLONE

E. coli sequence type 131 (ST131) is a multidrug-resistant

and highly virulent clone that was first reported in 2008

and has been reported in various regions globally [13].

It is associated with numerous community and hospital

acquired infections particularly UTIs [14]. The prevalence

of ST131 isolates varies from region to region and host

population, ranging from 12.5-40% [15,16]. Generally, ST131

is resistant to fluoroquinolone, and CTX-M-15 enzyme [10],

whereas other beta-lactamases including TEM, SHV are less

likely to be [13]. Both ESBL and non-ESBL-producing E.

coli ST131 isolates are resistant to fluoroquinolones, which

may play a role as marker for ST131-positive E. coli [17].

The ways to manage E. coli ST131 infections are similar

to those of other types of E. coli [13]. Carbapenem alone

or combination therapy with amikacin has been used to

eradicate infections associated with CTX-M-producing E.

coli isolates. And the trial has become a huge success [18].

The diagnosis of ESBLs in the laboratory is not simple.

Since the ESBL has emerged as important pathogen, specific

guidelines for ESBL detection were proposed in 1999 by

the National Committee for Clinical Laboratory Standards

(NCCLS). We can suspect the existence of ESBL in case that

bacterial growth is present despite 1 g/ml of broad-spectrum

cephalosporins (ceftazidime, ceftriaxone, or cefotaxime),

or aztreonam, or growth occurs despite the use of 4 g/ml

of cefpodoxime. Multiple antibiotics for screening improve

the sensitivity of ESBLs detection. Confirmatory tests include

the supplement of clavulanic acid to both ceftazidime and

cefotaxime. Double disk approximation test, three-dimen-

sional test, E-test and Vitek automated susceptibility system

(bioMérieux, Marcy l’Etoile, France) has been applied to

detect ESBLs in clinical isolates. The superiority of one

test over the other is not clear in respect of sensitivity

and technically challenging.

76 Taesoo Choi, et al. Current Trend of ESBL Epidemiology Worldwide


Table 1. The prevalence rates of ESBL worldwide

Location First author, year ESBL (+)/total clinical samples in strains Total number (%) of ESBL (+) pathogen

Australia [26] Hawser, 2009 A (1/13), B (0/3), C (0/0) 1 (6.3)Benin [27] Ahoyo, 2007 A (31/143) 31 (21.7)Central African Republic [28] Bercion, 2009 A (29/357), B (17/57), F (3/3), G (1/1) 50 (12.0)China [29] Hawkey, 2008 A (158/287), B (25/91), C (1/4) 184 (48.2)Egypt [30,31] Fam, 2011 A (55/291), B (23/165) 78 (17.1)

Saied, 2011 A (9/23), B (130/162) 139 (75.1)Hong Kong [29] Hawkey, 2008 A (8/45), B (0/0), C (0/0) 8 (17.8)India [32] Varaiya, 2008 A (264/334), B (77/111), C (15/15) 356 (77.4)Kenya [33] Kohli, 2010 A (10/69), B (5/38) 15 (14.0)Morocco [34,35] Barguigua, 2013 B (34/453) 34 (7.5)

Barguigua, 2011 A (10/767), B (2/36) 12 (1.5)New Zealand [26] Hawser, 2009 A (3/94), B (1/14), C (1/5) 5 (4.4)Nigeria [36,37] Aibinu, 2012 A (14/109) 14 (12.8)

Ogbolu, 2011 A (7/28), B (8/63), D (3/11), F (2/2), G (2/3), H (1/1) 23 (21.3)Philippines [26] Hawser, 2009 A (9/53), B (8/20), C (0/2) 17 (22.7)Senegal [38] Sire, 2007 A (38/1,010) 38 (3.8)Singapore [26] Hawser, 2009 A (17/51), B (12/32), C (0/1) 29 (34.5)South Africa [39-43] Keddy, 2012 E (4/263) 4 (1.5)

Bamford, 2012 A (29,066/358,843) 29,066 (8.1)Brink, 2012 A (43/566), B (59/171), D (8/71) 110 (13.6)Habte, 2009 A (84/482), B (30/239), D (8/85) 122 (15.1)Brink, 2007 A (1,420/28,412), B (1,954/7,514), F (484/4,031) 3,858 (9.7)

South Korea [44] Ko, 2008 A (10/44), B (12/37), C (1/4) 23 (27.1)Taiwan [45] Chambers, 2005 A (33/260), B (30/164), C (2/14) 65 (14.8)Tanzania [46] Blomberg, 2005 A (9/36), B (9/52), C (1/37) 19 (15.2)Thailand [29] Hawkey, 2008 A (33/65), B (15/33), C (0/2) 48 (48.0)Tunisia [47] Ben Haj Khalifa, 2012 B (40/198) 40 (20.2)Vietnam [48] Jones, 2006 A (42/122), B (9/23), C (2/4) 53 (35.6)

ESBL: extended spectrum beta-lactamases, A: Escherichia coli, B: Klebsiella pneumoniae, C: Klebsiella oxytoca, D: Proteus mirabilis, E: Shigella, F: Enterobacter spp., G: Morganella morganii, H: Serratia odorifera.

A few recent studies using multilocus sequencing typing

identified a single clone of ST131 from several countries

in Europe (Spain, France, Portugal, and Switzerland), North

America (Canada), and Asia (Lebanon, India, Kuwait, and

Korea) [9,10]. Serogroup O25 is associated with it. Clone

ST131 belongs to phylogenetic group B2 which is highly

virulent, and harbors multidrug-resistant incompatibility

group FII plasmids. These previous studies proved that

CTX-M-15 producing ST131 have also been emerged in

various countries. ST131 isolates have also been associated

with other types of beta-lactamases, as well as ciprofloxacin

resistant E. coli isolates that do not have ESBLs [19-21].

It is not obvious what has facilitated ST131 to spread

so widely and rapidly. ST131 is clearly more extensively

antibiotic-resistant than other types of E. coli and contains

a plenty of virulence factors. It may have a tendency to

be transmitted from host to colonize the intestine followed

by UTI [22,23]. The risk factors for intestinal colonization

with ST131 in different populations, possible differences

between colonizing and clinical ST131 isolates, and the

reservoirs and transmission courses have not been closely

surveyed [16]. The possible reservoirs of ST131 have been

evaluated for decades, which included food or water

sources, travel history from nations with a high prevalence

of the clone, long-term care facilities, and commercial

animals [24,25].

THE EMERGENCE AND DISTRIBUTION OF ESBLs BY REGIONAL GROUPS

Until 1990s, enterobacteria, mainly K. pneumoniae, produ-

cing SHV and TEM types of ESBLs have traditionally been

causative of serious nosocomial infections. This trend has

changed significantly, and E. coli producing CTX-M

beta-lactamases has emerged and cause of community-onset

infections, mostly UTIs. Most infections caused by ESBL-pro-

ducing E. coli or K. pneumoniae had mostly been described

as nosocomially acquired or nursing home related. These



outbreaks are usually clonal, the strains are mainly spread

through cross-transmission, and the risk factors are similar

to those found for other multidrug-resistant pathogens. Each

ESBL genotypes have different specificities for the various

beta-lactam antibiotics. Some recent data suggest that

infections related to ESBL-producing organisms might be

a critical problem in outpatients worldwide, but detailed

epidemiological data were not collected in most studies

(Table 1) [26-48].

ESBLs were first reported in 1983 from Germany and

England, in Europe [2]. Most ESBL-producing Klebsiella

isolates harbored enzymes belonging to the TEM and SHV

families. And the prevalence of ESBLs differs with countries.

In Netherlands, below 1% of E. coli and K. pneumoniae

were identified as ESBL-producing pathogens [49]. In France

and Italy, up to 40% of ESBL producing K. pneumoniae

has been reported [50]. The studies on the genotypes of

ESBLs also have been undertaken actively. In Sweden,

50-60% of ESBL-producing E. coli harbor CTX-M-15

followed by 10-15% of CTX-M-14 [51]. About 50% of

genotypes in Norway and 20% in Denmark proved to be

CTX-M-15 and CTX-M-14 [52,53]. In Finland, predominance

of CTX-M-1 group (including CTX-M-15) was reported

[54,55]. The different genotypes are found in other parts

of Europe. In Spain, high prevalence of CTX-M-14 and

CTX-M-9 is remarkable, and in Poland, CTX-M-3 has been

frequently reported, which is similar to several countries

in eastern Europe [56,57].

The first emergence of ESBL pathogen in USA was

reported in 1988 [58]. Its prevalence rate ranges from 0-25%

with average 3% [59]. In previous study of intensiive care

unit patients in USA, the rate of E. coli resistant to

broad-spectrum cephalosporin increased 48% compared

with that in the past 5 years. A recent study from the USA

presents results from the SENTRY surveillance program

including 26 hospitals from 20 states. The resistance levels

to cephalosporins and/or aztreonam in invasive Entero-

bacteriaceae was 6.4%. CTX-M-15 is the most frequent and

increasing in USA and Canada, where SHV phenotypes

used to be the most common [60]. A Canadian study reported

ESBL-production in almost 5% of the E. coli population−numbers similar to northern Europe. In Latin America, it

seems that ESBLs are more common than other continents.

The 8.5% of E. coli and 45% of K. pneumoniae were ESBL

positive in large scaled, multicenter study [61]. South

America stands out with a wide distribution of the CTX-M-2.

Also the CTX-M-8 is found in South America which is rare

on the outermost regions [62,63]. In the Africa and Australia,

CTX-M-15 is predominant [63].

There are also several reports on the epidemiology of

ESBL pathogens in Asia. Various differences are observed

between Asian countries. The rate of multiresistant E. coli

was 5% in Korea compared with 23.3% in Indonesia [64].

Contrastively, the rate of multiresistant K. pneumoniae

was 48.8% in Korea and 20-40% in China and Japan. A

single center study of 493 isolates in South Korea of

Enterobacter, Serratia marcescens, Citrobacter freundii, and

Morganella morganii revealed rates of ESBL-positive isolates

of 12.8%, 12.4%, 4.9%, and 0%, respectively [65]. Some

authors in South Korea described 22.4% of K. pneumoniae

isolates and 10.2% of E. coli isolates as ESBL producers

[44]. In Thailand, up to 52% of health workers carrying

ESBL pathogen has been reported. In a recent study from

Taiwan, 28.4% of K. pneumoniae from various body sites

proved to be ESBL positive. A study in Vietnam reported

that, of 350 isolates from specimens, 87.4% were GNB.

The 88.9% of them were Enterobacteriaceae, of which 14.7%

were ESBL positive [48]. In India, the reports are also

alarming with high numbers seen among patients. A study

from two hospitals in India collected isolates from patients

with abscesses, UTI, blood and found ESBL pathogen in

69% of E. coli. Another study from India, the rate of

ESBL-positive isolates was similarly elevated with 23.1%

of ESBL positive [32]. Of the isolates, 48.4% were E. coli

and 51.6% were K. pneumoniae. In Japan, the CTX-M-9

is dominant and in China, CTX-M-14 is more commonly

reported [66,67]. In India, CTX-M-15 is exclusively found

[68]. Notably, all of the ESBL-producing isolates were

consistently susceptible to carbapenems. Asia is almost

certainly a part of the world in which ESBLs have emerged,

with early antimicrobial resistance studies showing elevated

levels of ESBL phenotypes, particularly among Klebsiella

isolates and particularly in China, South Korea, Japan, and

India [29].

THE DISSEMINATION OF ESBL-PRODU-CING PATHOGENS VIA VARIOUS FACTORS

ESBL-producing E. coli is spreading extensively and

quickly in our community. Although a reliable explanation



Table 2. Outbreaks of infection due to ESBL-producing Enterobacteriaceae

High risk patient Intensive care units 　 History of transplantation　 Long-term care facilitiesRisk factor Severity of disease　 Length of hospital/intensive care units stay　 Arterial/central venous catheter　 Infusion of total parenteral nutrition　 Mechanical ventilator　 Feeding tube　 Urethral catheter　 Age　 Hemodialysis　 Bedsore　 Altered nutrition　 Premature baby　 Previous antibiotics treatment; fluoroquinolones,

broad-spectrum cephalosporins, aztreonam, aminoglycosides, metronidazole

Reservoir Hospital workers hand　 Medical devices; thermometers, ultrasound gel,

oxygen probes, liquid soap

ESBL: extended spectrum beta-lactamases.

is not yet known, different factors may explain this spread

such as acquisition of ESBL-producing E. coli by food [69,70],

person-to-person transmission from fecal carriers [71-73],

dissemination of ESBL-producing E. coli in the environment

[74], carriage by domestic [70,75,76] and wild animals [77-79],

and the existence of reservoirs like long-term care facilities

(Table 2) [80,81]. Sewage sludge is also a reservoir of

ESBL-producing E. coli [74]. In 141 healthy individuals in

Thailand, 51.8% had ESBL-producing E. coli in stool samples

[82]. In China, the fecal colonization rate of ESBL-producing

E. coli was 7% among 270 elderly people [71]. Seven of

105 healthy humans (6.7%) from Spain were carriers of

ESBL-producing E. coli [72]. In healthy children from

Portugal, the carriage rate was 2.7% [73]. In another study,

the fecal carriage of ESBL-producing E. coli in patients

with UTI caused by these pathogens was 67%, but the

household members and the non-household relatives of

these patients also had ESBL-producing E. coli in fecal

samples, 27.4% and 15.6% respectively, while in healthy

unrelated controls the fecal carriage rate was 7.4% [83].

Long-term care centers may also represent a significant

reservoir for multi-resistant ESBL-producing E. coli isolates,

and infection control efforts must be addressed in these

settings. Among 294 nursing home residents in Northern

Ireland, 119 nursing home residents (40.5%) were gut

carriers of ESBL-producing E. coli [80], a carriage rate about

40 times higher than that for community patients with acute

diarrhea in the same area; fluoroquinolones use and

previous UTI were the risk factors for ESBL-producing E.

coli carriage [80]. In Italy, 41.4% of residents and 11.6%

of staff members in a long-term care facility were colonized

with ESBL-producing E. coli [81].

RISK FACTORS OF ESBL-PRODUCING ESCHERICHIA COLI INFECTION

Treatment options for multi-resistant ESBL-producing

pathogens are restrictive and initial empirical antibiotic

therapy is occasionally inappropriate. As a result, the

information of risk factors for ESBL-related infections is

important for early detection and adequate initial treatment.

In hospitalized cancer patients, 17 of 135 bacteremia caused

by E. coli were ESBL-producing E. coli; several factors

including female sex, hematological malignancy and previous

antibiotic therapy were found to be remarkable for ESBL

acquisition [84]. One control study in Switzerland found

that previous antibiotic treatment and mechanical ventilation

were risk factors for ESBL-related infection [85]. Typically,

the most common risks factors for community acquired

ESBL-producing E. coli infections are correlated to healthcare

centers including recent admission history, residence in a

long-term care facility, urethral catheterization. Other signifi-

cant factors include recent use of antibiotics, older age,

and diabetes mellitus. However, considerable cases of

infections due to ESBL-producing E. coli occur without

obvious risk factors [86]. This may be induced by increasing

incidence of healthy carriers. One survey has reported the

risk factors for ESBL-producing E. coli infections in 890

non-hospitalized patients. Remarkable risk factors were

recent antibiotic use, residence in long-term care facilities,

recent admission history, older age, and male sex [87].

Some studies on community acquired infections have

been undertaken in Spanish hospitals [86]. The risk factors

included older age, female sex, diabetes mellitus, recurrent

UTIs, previous invasive procedures of urinary tract such

as catheterization, and previous antibiotic use including

cephalosporins, and fluoroquinolones. In the other study

on community acquired bacteremia [86], long-term care

facilities, urethral catheter, and previous antibiotic use (es-

pecially fluoroquinolones) were risks factors of ESBL-producing

E. coli bacteremia [86]. Mostly, community-acquired ESBL-pro-

ducing E. coli infections are originated in urinary tract;



in a recent study, over three UTI episodes in the last year,

use of a beta-lactam antibiotic in the past 3 months and

the history of prostatic disease were found to be associated

with ESBL-producing E. coli [88]. The history of international

travel as a risk factor for ESBL-producing E. coli has been

reported in previous studies. In Switzerland, the beginning

of symptoms, or recent antibiotic treatment in foreign

country, proved to be a risk factor for ESBL-producing E.

coli infection [85]. In Calgary, 44% of patients with community

acquired ESBL-producing E. coli infection had a history

of trip abroad. Journey to India was the most dangerous

factor [89]. In New Zealand, considerable patients suffered

with UTIs by CTX-M-15producing E. coli had a history

of travel or recent emigration from India [90].

CONCLUSIONS

The current epidemiology of ESBL-producing organisms

is complex. Several species of the Enterobacteriaceae family

with different types of enzymes are causing troublesome

infections in patients in the hospital and outside of the

hospital. The dominant subtype of ESBL organism is

changing from SHV, TEM to CTX-M recently. Infection

related to ESBLs occurs more commonly in Southern Asia

than Eastern Asia, Southern Europe and Northern Europe

in order. The cumulative effect of antibiotics on the disse-

mination and persistence of resistant bacteria should not

be underestimated. To use appropriate antibiotics as far

as possible, we need to understand how resistance arises

and all the factors that influence dissemination, which allows

practitioners to identify high-risk patients and avoid inap-

propriate empirical antibiotic therapy consequentially.

Finally, there is an obvious goal to investigate the epi-

demiological aspect of the influx of ESBL-producing

organisms in order to plan adequate infection management.

CONFLICT OF INTEREST

No potential conflict of interest relevant to this article

was reported.

REFERENCES

1. Paterson DL, Bonomo RA. Extended-spectrum beta-lacta-mases: a clinical update. Clin Microbiol Rev 2005;18:657-86.

2. Knothe H, Shah P, Krcmery V, Antal M, Mitsuhashi S. Transferable resistance to cefotaxime, cefoxitin, cefamandole and cefuroxime in clinical isolates of Klebsiella pneumoniae and Serratia marcescens. Infection 1983;11:315-7.

3. Pitout JD. Extraintestinal pathogenic Escherichia coli: an update on antimicrobial resistance, laboratory diagnosis and treatment. Expert Rev Anti Infect Ther 2012;10:1165-76.

4. Rawat D, Nair D. Extended-spectrum β-lactamases in Gram negative bacteria. J Glob Infect Dis 2010;2:263-74.

5. Kiratisin P, Henprasert A. Resistance phenotype-genotype correlation and molecular epidemiology of Citrobacter, Entero-bacter, Proteus, Providencia, Salmonella and Serratia that carry extended-spectrum β-lactamases with or without plasmid- mediated AmpC β-lactamase genes in Thailand. Trans R Soc Trop Med Hyg 2011;105:46-51.

6. El-Khizzi NA, Bakheshwain SM. Prevalence of extended- spectrum beta-lactamases among Enterobacteriaceae isolated from blood culture in a tertiary care hospital. Saudi Med J 2006;27:37-40.

7. Babay HA. Detection of extended-spectrum b-lactamases in members of the family enterobacteriaceae at a teaching hospital, Riyadh, Kingdom of Saudi Arabia. Saudi Med J 2002;23: 186-90.

8. Karim A, Poirel L, Nagarajan S, Nordmann P. Plasmid-mediated extended-spectrum beta-lactamase (CTX-M-3 like) from India and gene association with insertion sequence ISEcp1. FEMS Microbiol Lett 2001;201:237-41.

9. Coque TM, Novais A, Carattoli A, Poirel L, Pitout J, Peixe L, et al. Dissemination of clonally related Escherichia coli strains expressing extended-spectrum beta-lactamase CTX-M-15. Emerg Infect Dis 2008;14:195-200.

10. Nicolas-Chanoine MH, Blanco J, Leflon-Guibout V, Demarty R, Alonso MP, Caniça MM, et al. Intercontinental emergence of Escherichia coli clone O25:H4-ST131 producing CTX-M-15. J Antimicrob Chemother 2008;61:273-81.

11. Bush K, Jacoby GA, Medeiros AA. A functional classification scheme for beta-lactamases and its correlation with molecular structure. Antimicrob Agents Chemother 1995;39:1211-33.

12. Lee NY, Lee CC, Huang WH, Tsui KC, Hsueh PR, Ko WC. Carbapenem therapy for bacteremia due to extended-spec-trum-β-lactamase-producing Escherichia coli or Klebsiella pneumoniae: implications of ertapenem susceptibility. Antimicrob Agents Chemother 2012;56:2888-93.

13. Rogers BA, Sidjabat HE, Paterson DL. Escherichia coli O25b- ST131: a pandemic, multiresistant, community-associated strain. J Antimicrob Chemother 2011;66:1-14.

14. Peirano G, van Greune CH, Pitout JD. Characteristics of infections caused by extended-spectrum β-lactamase-producing Escherichia coli from community hospitals in South Africa. Diagn Microbiol Infect Dis 2011;69:449-53.

15. Banerjee R, Johnston B, Lohse C, Porter SB, Clabots C, Johnson JR. Escherichia coli sequence type 131 is a dominant, anti-



microbial-resistant clonal group associated with healthcare and elderly hosts. Infect Control Hosp Epidemiol 2013;34: 361-9.

16. Nicolas-Chanoine MH, Bertrand X, Madec JY. Escherichia coli ST131, an intriguing clonal group. Clin Microbiol Rev 2014; 27:543-74.

17. Johnson JR, Johnston B, Clabots C, Kuskowski MA, Castanheira M. Escherichia coli sequence type ST131 as the major cause of serious multidrug-resistant E. coli infections in the United States. Clin Infect Dis 2010;51:286-94.

18. Vigil KJ, Johnson JR, Johnston BD, Kontoyiannis DP, Mulanovich VE, Raad II, et al. Escherichia coli Pyomyositis: an emerging infectious disease among patients with hematologic malig-nancies. Clin Infect Dis 2010;50:374-80.

19. Clermont O, Dhanji H, Upton M, Gibreel T, Fox A, Boyd D, et al. Rapid detection of the O25b-ST131 clone of Escherichia coli encompassing the CTX-M-15-producing strains. J Antimicrob Chemother 2009;64:274-7.

20. Johnson JR, Menard M, Johnston B, Kuskowski MA, Nichol K, Zhanel GG. Epidemic clonal groups of Escherichia coli as a cause of antimicrobial-resistant urinary tract infections in Canada, 2002 to 2004. Antimicrob Agents Chemother 2009; 53:2733-9.

21. Oteo J, Diestra K, Juan C, Bautista V, Novais A, Pérez-Vázquez M, et al; Spanish Network in Infectious Pathology Project (REIPI). Extended-spectrum beta-lactamase-producing Esche-richia coli in Spain belong to a large variety of multilocus sequence typing types, including ST10 complex/A, ST23 complex/A and ST131/B2. Int J Antimicrob Agents 2009; 34:173-6.

22. Moreno E, Andreu A, Pérez T, Sabaté M, Johnson JR, Prats G. Relationship between Escherichia coli strains causing urinary tract infection in women and the dominant faecal flora of the same hosts. Epidemiol Infect 2006;134:1015-23.

23. Banerjee R, Johnson JR. A new clone sweeps clean: the enigmatic emergence of Escherichia coli sequence type 131. Antimicrob Agents Chemother 2014;58:4997-5004.

24. Zhang H, Zhou Y, Guo S, Chang W. Multidrug resistance found in extended-spectrum beta-lactamase-producing Enterobac-teriaceae from rural water reservoirs in Guantao, China. Front Microbiol 2015;6:267.

25. Del Rosario-Quintana C, Tosco-Núñez T, Lorenzo L, Martín- Sánchez AM, Molina-Cabrillana J. Prevalence and risk factors of multi-drug resistant organism colonization among long-term care facilities in Gran Canaria (Spain). Rev Esp Geriatr Gerontol 2015;50:232-6.

26. Hawser SP, Bouchillon SK, Hoban DJ, Badal RE, Hsueh PR, Paterson DL. Emergence of high levels of extended-spec-trum-beta-lactamase-producing gram-negative bacilli in the Asia-Pacific region: data from the Study for Monitoring Antimicrobial Resistance Trends (SMART) program, 2007. Antimicrob Agents Chemother 2009;53:3280-4.

27. Ahoyo AT, Baba-Moussa L, Anago AE, Avogbe P, Missihoun TD, Loko F, et al. Incidence of infections dues to Escherichia coli strains producing extended spectrum betalactamase, in the Zou/Collines Hospital Centre (CHDZ/C) in Benin. Med Mal Infect 2007;37:746-52.

28. Bercion R, Mossoro-Kpinde D, Manirakiza A, Le Faou A. Increasing prevalence of antimicrobial resistance among Enterobacteriaceae uropathogens in Bangui, Central African Republic. J Infect Dev Ctries 2009;3:187-90.

29. Hawkey PM. Prevalence and clonality of extended-spectrum beta-lactamases in Asia. Clin Microbiol Infect 2008;14 Suppl 1:159-65.

30. Fam N, Leflon-Guibout V, Fouad S, Aboul-Fadl L, Marcon E, Desouky D, et al. CTX-M-15-producing Escherichia coli clinical isolates in Cairo (Egypt), including isolates of clonal complex ST10 and clones ST131, ST73, and ST405 in both community and hospital settings. Microb Drug Resist 2011;17:67-73.

31. Saied T, Elkholy A, Hafez SF, Basim H, Wasfy MO, El-Shoubary W, et al. Antimicrobial resistance in pathogens causing nosocomial bloodstream infections in university hospitals in Egypt. Am J Infect Control 2011;39:e61-5.

32. Varaiya AY, Dogra JD, Kulkarni MH, Bhalekar PN. Extended- spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae in diabetic foot infections. Indian J Pathol Microbiol 2008;51:370-2.

33. Kohli R, Omuse G, Revathi G. Antibacterial susceptibility patterns of blood stream isolates in patients investigated at the Aga Khan University Hospital, Nairobi. East Afr Med J 2010;87:74-80.

34. Barguigua A, El Otmani F, Talmi M, Reguig A, Jamali L, Zerouali K, et al. Prevalence and genotypic analysis of plasmid-mediated β-lactamases among urinary Klebsiella pneumoniae isolates in Moroccan community. J Antibiot (Tokyo) 2013;66:11-6.

35. Barguigua A, El Otmani F, Talmi M, Bourjilat F, Haouzane F, Zerouali K, et al. Characterization of extended-spectrum β- lactamase-producing Escherichia coli and Klebsiella pneumo-niae isolates from the community in Morocco. J Med Microbiol 2011;60:1344-52.

36. Aibinu I, Odugbemi T, Koenig W, Ghebremedhin B. Sequence type ST131 and ST10 complex (ST617) predominant among CTX-M-15-producing Escherichia coli isolates from Nigeria. Clin Microbiol Infect 2012;18:E49-51.

37. Ogbolu DO, Daini OA, Ogunledun A, Alli AO, Webber MA. High levels of multidrug resistance in clinical isolates of Gram-negative pathogens from Nigeria. Int J Antimicrob Agents 2011;37:62-6.

38. Sire JM, Nabeth P, Perrier-Gros-Claude JD, Bahsoun I, Siby T, Macondo EA, et al. Antimicrobial resistance in outpatient Escherichia coli urinary isolates in Dakar, Senegal. J Infect Dev Ctries 2007;1:263-8.

39. Keddy KH, Sooka A, Crowther-Gibson P, Quan V, Meiring S, Cohen C, et al; Group for Enteric, Respiratory, and Meningeal



Disease Surveillance in South Africa (GERMS-SA). Systemic shigellosis in South Africa. Clin Infect Dis 2012;54:1448-54.

40. Bamford C, Bonorchis K, Ryan A, Hoffmann R, Naicker P, Nana T, et al. Antimicrobial susceptibility patterns of Escherichia coli strains isolated from urine samples in South Africa from 2007-2011. South Afr J Epidemiol Infect 2012;27:46-52.

41. Brink AJ, Botha RF, Poswa X, Senekal M, Badal RE, Grolman DC, et al. Antimicrobial susceptibility of gram-negative pathogens isolated from patients with complicated intra-abdominal infections in South African hospitals (SMART Study 2004- 2009): impact of the new carbapenem breakpoints. Surg Infect (Larchmt) 2012;13:43-9.

42. Habte TM, Dube S, Ismail N, Hoosen AA. Hospital and community isolates of uropathogens at a tertiary hospital in South Africa. S Afr Med J 2009;99:584-7.

43. Brink A, Moolman J, da Silva MC, Botha M; National Antibiotic Surveillance Forum. Antimicrobial susceptibility profile of selected bacteraemic pathogens from private institutions in South Africa. S Afr Med J 2007;97:273-9.

44. Ko KS, Lee MY, Song JH, Lee H, Jung DS, Jung SI, et al. Prevalence and characterization of extended-spectrum beta- lactamase-producing Enterobacteriaceae isolated in Korean hospitals. Diagn Microbiol Infect Dis 2008;61:453-9.

45. Chambers HF. Beta-lactam antibiotics and other inhibitors of cell wall synthesis. In: Katzung BG, Masters SB, Trevor AJ, editors. Basic & clinical pharmacology. Boston, MA: McGraw- Hill; 2005. p. 734-53.

46. Blomberg B, Jureen R, Manji KP, Tamim BS, Mwakagile DS, Urassa WK, et al. High rate of fatal cases of pediatric septicemia caused by gram-negative bacteria with extended-spectrum beta-lactamases in Dar es Salaam, Tanzania. J Clin Microbiol 2005;43:745-9.

47. Ben Haj Khalifa A, Khedher M. Epidemiological study of Klebsiella spp. uropathogenic strains producing extended- spectrum β-lactamase in a Tunisian university hospital, 2009. Pathol Biol (Paris) 2012;60:e1-5.

48. Jones SL, Nguyen VK, Nguyen TM, Athan E. Prevalence of multiresistant Gram-negative organisms in a surgical hospital in Ho Chi Minh City, Vietnam. Trop Med Int Health 2006;11: 1725-30.

49. Stobberingh EE, Arends J, Hoogkamp-Korstanje JA, Goessens WH, Visser MR, Buiting AG, et al. Occurrence of extended- spectrum betalactamases (ESBL) in Dutch hospitals. Infection 1999;27:348-54.

50. Branger C, Lesimple AL, Bruneau B, Berry P, Lambert- Zechovsky N. Long-term investigation of the clonal dissemi-nation of Klebsiella pneumoniae isolates producing extended- spectrum beta-lactamases in a university hospital. J Med Microbiol 1998;47:201-9.

51. Brolund A, Edquist PJ, Mäkitalo B, Olsson-Liljequist B, Söderblom T, Wisell KT, et al. Epidemiology of extended- spectrum β-lactamase-producing Escherichia coli in Sweden

2007-2011. Clin Microbiol Infect 2014;20:O344-52.52. Naseer U, Haldorsen B, Tofteland S, Hegstad K, Scheutz F,

Simonsen GS, et al; Norwegian ESBL Study Group. Molecular characterization of CTX-M-15-producing clinical isolates of Escherichia coli reveals the spread of multidrug-resistant ST131 (O25:H4) and ST964 (O102:H6) strains in Norway. APMIS 2009;117:526-36.

53. Olesen B, Hansen DS, Nilsson F, Frimodt-Møller J, Leihof RF, Struve C, et al. Prevalence and characteristics of the epidemic multiresistant Escherichia coli ST131 clonal group among extended-spectrum beta-lactamase-producing E. coli isolates in Copenhagen, Denmark. J Clin Microbiol 2013;51:1779-85.

54. Forssten SD, Kolho E, Lauhio A, Lehtola L, Mero S, Oksaharju A, et al. Emergence of extended-spectrum beta-lactamase-pro-ducing Escherichia coli and Klebsiella pneumoniae during the years 2000 and 2004 in Helsinki, Finland. Clin Microbiol Infect 2010;16:1158-61.

55. Nyberg SD, Osterblad M, Hakanen AJ, Huovinen P, Jalava J, Resistance TF. Detection and molecular genetics of extended- spectrum beta-lactamases among cefuroxime-resistant Esche-richia coli and Klebsiella spp. isolates from Finland, 2002-2004. Scand J Infect Dis 2007;39:417-24.

56. Baraniak A, Fiett J, Sulikowska A, Hryniewicz W, Gniadkowski M. Countrywide spread of CTX-M-3 extended-spectrum beta- lactamase-producing microorganisms of the family Entero-bacteriaceae in Poland. Antimicrob Agents Chemother 2002; 46:151-9.

57. Livermore DM, Canton R, Gniadkowski M, Nordmann P, Rossolini GM, Arlet G, et al. CTX-M: changing the face of ESBLs in Europe. J Antimicrob Chemother 2007;59:165-74.

58. Jacoby GA. Extended-spectrum beta-lactamases and other enzymes providing resistance to oxyimino-beta-lactams. Infect Dis Clin North Am 1997;11:875-87.

59. Bradford PA. Extended-spectrum beta-lactamases in the 21st century: characterization, epidemiology, and detection of this important resistance threat. Clin Microbiol Rev 2001;14:933- 51, table of contents.

60. Doi Y, Park YS, Rivera JI, Adams-Haduch JM, Hingwe A, Sordillo EM, et al. Community-associated extended-spectrum β-lacta-mase-producing Escherichia coli infection in the United States. Clin Infect Dis 2013;56:641-8.

61. Winokur PL, Canton R, Casellas JM, Legakis N. Variations in the prevalence of strains expressing an extended-spectrum beta- lactamase phenotype and characterization of isolates from Europe, the Americas, and the Western Pacific region. Clin Infect Dis 2001;32 Suppl 2:S94-103.

62. Cantón R, Coque TM. The CTX-M beta-lactamase pandemic. Curr Opin Microbiol 2006;9:466-75.

63. Naseer U, Sundsfjord A. The CTX-M conundrum: dissemination of plasmids and Escherichia coli clones. Microb Drug Resist 2011;17:83-97.

64. Jones RN. Summation: beta-lactam resistance surveillance in



the Asia-Western Pacific region. Diagn Microbiol Infect Dis 1999;35:333-8.

65. Choi SH, Lee JE, Park SJ, Kim MN, Choo EJ, Kwak YG, et al. Prevalence, microbiology, and clinical characteristics of exten-ded-spectrum beta-lactamase-producing Enterobacter spp., Serratia marcescens, Citrobacter freundii, and Morganella morganii in Korea. Eur J Clin Microbiol Infect Dis 2007;26: 557-61.

66. Chong Y, Shimoda S, Yakushiji H, Ito Y, Miyamoto T, Kamimura T, et al. Community spread of extended-spectrum β-lacta-mase-producing Escherichia coli, Klebsiella pneumoniae and Proteus mirabilis: a long-term study in Japan. J Med Microbiol 2013;62:1038-43.

67. Xia S, Fan X, Huang Z, Xia L, Xiao M, Chen R, et al. Dominance of CTX-M-type extended-spectrum β-lactamase (ESBL)-pro-ducing Escherichia coli isolated from patients with community- onset and hospital-onset infection in China. PLoS One 2014; 9:e100707.

68. Muzaheed, Doi Y, Adams-Haduch JM, Endimiani A, Sidjabat HE, Gaddad SM, et al. High prevalence of CTX-M-15-producing Klebsiella pneumoniae among inpatients and outpatients with urinary tract infection in Southern India. J Antimicrob Chemother 2008;61:1393-4.

69. Ben Slama K, Jouini A, Ben Sallem R, Somalo S, Sáenz Y, Estepa V, et al. Prevalence of broad-spectrum cephalosporin-resistant Escherichia coli isolates in food samples in Tunisia, and charac-terization of integrons and antimicrobial resistance mechanisms implicated. Int J Food Microbiol 2010;137:281-6.

70. Machado E, Coque TM, Cantón R, Sousa JC, Peixe L. Antibiotic resistance integrons and extended-spectrum {beta}-lactamases among Enterobacteriaceae isolates recovered from chickens and swine in Portugal. J Antimicrob Chemother 2008;62:296- 302.

71. Tian SF, Chen BY, Chu YZ, Wang S. Prevalence of rectal carriage of extended-spectrum beta-lactamase-producing Escherichia coli among elderly people in community settings in China. Can J Microbiol 2008;54:781-5.

72. Vinué L, Sáenz Y, Martínez S, Somalo S, Moreno MA, Torres C, et al. Prevalence and diversity of extended-spectrum beta-lac-tamases in faecal Escherichia coli isolates from healthy humans in Spain. Clin Microbiol Infect 2009;15:954-7.

73. Guimarães B, Barreto A, Radhouani H, Figueiredo N, Gaspar E, Rodrigues J, et al. Genetic detection of extended-spectrum beta-lactamase-containing Escherichia coli isolates and van-comycin-resistant enterococci in fecal samples of healthy children. Microb Drug Resist 2009;15:211-6.

74. Reinthaler FF, Feierl G, Galler H, Haas D, Leitner E, Mascher F, et al. ESBL-producing E. coli in Austrian sewage sludge. Water Res 2010;44:1981-5.

75. Costa D, Vinué L, Poeta P, Coelho AC, Matos M, Sáenz Y, et al. Prevalence of extended-spectrum beta-lactamase-producing Escherichia coli isolates in faecal samples of broilers. Vet

Microbiol 2009;138:339-44.76. Yuan L, Liu JH, Hu GZ, Pan YS, Liu ZM, Mo J, et al. Molecular

characterization of extended-spectrum beta-lactamase-pro-ducing Escherichia coli isolates from chickens in Henan Province, China. J Med Microbiol 2009;58:1449-53.

77. Bonnedahl J, Drobni M, Gauthier-Clerc M, Hernandez J, Granholm S, Kayser Y, et al. Dissemination of Escherichia coli with CTX-M type ESBL between humans and yellow-legged gulls in the south of France. PLoS One 2009;4:e5958.

78. Poeta P, Radhouani H, Pinto L, Martinho A, Rego V, Rodrigues R, et al. Wild boars as reservoirs of extended-spectrum beta- lactamase (ESBL) producing Escherichia coli of different phylogenetic groups. J Basic Microbiol 2009;49:584-8.

79. Literak I, Dolejska M, Radimersky T, Klimes J, Friedman M, Aarestrup FM, et al. Antimicrobial-resistant faecal Escherichia coli in wild mammals in central Europe: multiresistant Escherichia coli producing extended-spectrum beta-lactamases in wild boars. J Appl Microbiol 2010;108:1702-11.

80. Rooney PJ, O'Leary MC, Loughrey AC, McCalmont M, Smyth B, Donaghy P, et al. Nursing homes as a reservoir of extended- spectrum beta-lactamase (ESBL)-producing ciprofloxacin- resistant Escherichia coli. J Antimicrob Chemother 2009; 64:635-41.

81. March A, Aschbacher R, Dhanji H, Livermore DM, Böttcher A, Sleghel F, et al. Colonization of residents and staff of a long-term-care facility and adjacent acute-care hospital geriatric unit by multiresistant bacteria. Clin Microbiol Infect 2010;16:934-44.

82. Sasaki T, Hirai I, Niki M, Nakamura T, Komalamisra C, Maipanich W, et al. High prevalence of CTX-M beta-lac-tamase-producing Enterobacteriaceae in stool specimens obtained from healthy individuals in Thailand. J Antimicrob Chemother 2010;65:666-8.

83. Rodríguez-Baño J, López-Cerero L, Navarro MD, Díaz de Alba P, Pascual A. Faecal carriage of extended-spectrum beta-lacta-mase-producing Escherichia coli: prevalence, risk factors and molecular epidemiology. J Antimicrob Chemother 2008;62: 1142-9.

84. Gudiol C, Calatayud L, Garcia-Vidal C, Lora-Tamayo J, Cisnal M, Duarte R, et al. 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 2010;65:333-41.

85. Nicoletti J, Kuster SP, Sulser T, Zbinden R, Ruef C, Ledergerber B, et al. Risk factors for urinary tract infections due to ciprofloxacin-resistant Escherichia coli in a tertiary care urology department in Switzerland. Swiss Med Wkly 2010;140: w13059.

86. Rodríguez-Baño J, Picón E, Gijón P, Hernández JR, Ruíz M, Peña C, et al; Spanish Network for Research in Infectious Diseases (REIPI). Community-onset bacteremia due to extended-spec-trum beta-lactamase-producing Escherichia coli: risk factors



and prognosis. Clin Infect Dis 2010;50:40-8.87. Ben-Ami R, Rodríguez-Baño J, Arslan H, Pitout JD, Quentin C,

Calbo ES, et al. A multinational survey of risk factors for infection with extended-spectrum beta-lactamase-producing enterobacteriaceae in nonhospitalized patients. Clin Infect Dis 2009;49:682-90.

88. Azap OK, Arslan H, Serefhanoğlu K, Colakoğlu S, Erdoğan H, Timurkaynak F, et al. Risk factors for extended-spectrum beta-lactamase positivity in uropathogenic Escherichia coli isolated from community-acquired urinary tract infections.

Clin Microbiol Infect 2010;16:147-51.89. Laupland KB, Church DL, Vidakovich J, Mucenski M, Pitout JD.

Community-onset extended-spectrum beta-lactamase (ESBL) producing Escherichia coli: importance of international travel. J Infect 2008;57:441-8.

90. Freeman JT, McBride SJ, Heffernan H, Bathgate T, Pope C, Ellis-Pegler RB. Community-onset genitourinary tract infection due to CTX-M-15-Producing Escherichia coli among travelers to the Indian subcontinent in New Zealand. Clin Infect Dis 2008;47:689-92.

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