Cephalosporin and Carbapenem Inhibition Zone Breakpoints ...

Vol. 31 No. 3 143Beta-lactam inhibition zone breakpoints for ESBL and non-ESBL Enterobacteriaceae:- Panarat P, et al.

143

Cephalosporin and Carbapenem Inhibition ZoneBreakpoints for Distinguishing between Extended-spectrum Beta-lactamase (ESBL)- and Non-ESBL-producing Enterobacteriaceae

Keywords: Inhibition zone, breakpoints, extended-spectrum beta-lactamase, Enterobacteriaceae, CLSI, EUCASTCorresponding author: Chusana Suankratay, M.D., Ph.D., Division of Infectious Diseases, Department of Internal Medicine, King Chulalongkorn Memorial

Hospital, Bangkok 10330, Thailand.

ORIGINAL ARTICLE

Palakorn Panarat, M.D.1, Malee Techapornroong, M.D.2, Chusana Suankratay, M.D., Ph.D.3

1Department of Internal Medicine, King Chulalongkorn Memorial Hospital, Bangkok, Thailand.2Division of Infectious Diseases, Department of Internal Medicine, Prapokklao Hospital, Chantaburi, Thailand.3Division of Infectious Diseases, Department of Internal Medicine, King Chulalongkorn Memorial Hospital, Bangkok, Thailand.

ABSTRACT

Background: In 2010, the United States Clinical Laboratory Standards Institute (CLSI) released the new

inhibition zone and minimal inhibitory concentration (MIC) breakpoints of beta-lactam antibiotics for

Enterobacteriaceae and recommended that there is no need to perform ESBL production tests. The reasons

for lowering breakpoints are based on pharmacokinetic and pharmacodynamic data as well as the MIC

distribution of clinical isolates of Enterobacteriaceae in several studies carried out in the United States. To

our knowledge, there have been no studies to determine inhibition zone distribution in comparison with

ESBL production among Enterobacteriaceae in Thailand.

Patients and methods: A descriptive study was carried out to determine the inhibition zone distribution

and breakpoints of beta-lactam antibiotics to distinguish between ESBL- and non-ESBL-producing clinical

isolates of Enterobacteriaceae from sterile specimens collected from adult patients who were hospitalized at

Prapokklao Hospital, Chantaburi, Thailand, from October 2011 to September 2013. We tested ESBL production

by using the double disc and disc combination methods for cefotaxime. Moreover, we performed Receiver

Operating Characteristic (ROC) curve to determine the most appropriate sensitivity and specificity of

inhibition zone breakpoints of all antibiotics tested to distinguish between ESBL- and non-ESBL-producing

Enterobacteriaceae.

Results: Among all 930 specimens (879 (94.5%) blood and 51 (5.5%) other sterile specimens), there were

312 ESBL-producing isolates of Enterobacteriaceae including 239 (37.2%) E. coli, 65 (27.5%) K. pneumoniae,

and 8 (16%) P. mirabilis. Five hundred and thirty-four (57.4%) specimens were from patients hospitalized

at Internal Medicine ward. Based on ROC curve, the inhibition zone breakpoint of cefotaxime to distinguish

between ESBL- and non-ESBL-producing Enterobacteriaceae was 26 mm, consistent with that recommended

by CLSI 2010. However, the inhibition zone breakpoint of cefazolin to distinguish between ESBL- and non-

ESBL-producing Enterobacteriaceae was 12 mm which was much different from that (23 mm) recommended

144 J INFECT DIS ANTIMICROB AGENTS Sep.-Dec. 2014

by CLSI 2010. In addition, based on ROC curves we could not determine the inhibition breakpoints of

ceftazidime, piperacillin/tazobactam, and all carbapenems.

Conclusions: To our knowledge, the present study is the first to determine the inhibition zone distribution

and breakpoints of beta-lactam antibiotics to distinguish between ESBL- and non-ESBL-producing

Enterobacteriaceae in Thailand. Only cefotaxime inhibition zone breakpoint is consistent with that

recommended by CLSI 2010. However, we cannot calculate the inhibition zone breakpoints due to no

correlations between the inhibition zone distributions of ceftazidime, piperacillin/tazobactam, and all

carbapenems with ESBL production in Enterobacteriaceae. (J Infect Dis Antimicrob Agents

2014;31:143-66.)

ROC curve for the inhibition zone breakpoint of cefotaxime ROC curve for the inhibition zone breakpoint of cefazolin

INTRODUCTION

Widespread use of broad-spectrum antibiotics

leads to development of drug-resistant bacteria.

One of the important mechanisms that mediate

development of antibiotic resistance is antibiotic

destruction by the enzymes. The beta-lactamases are

the most common enzymes that cause worldwide

medical problems. ESBL (Extended spectrum beta-

lactamase), one of the most common beta-lactamase,

has a property for hydrolyzing many betalactams

such as penicillins, cephalosporins, and monobactams.

However, it has no effect on cephamycins and

carbapenems. Beta-lactamase inhibitors can inhibit

this enzyme. This problem results in increasing use

of carbapenem group and other classes of antibiotic,

leading to increased hospitalization, hospital cost,

and adverse reactions from the antibiotics.1-3

ESBL was originally found in 1983.4 Bacteria


145

that produce ESBL mostly are a member of the

Enterobacteriaceae family. The most common

species are Escherichia coli, Klebsiella pneumoniae,

Klebsiella oxytoca, and Proteus mirabilis, but ESBLs

are also found in other groups of bacteria. ESBL-

producing organisms usually cause nosocomial

infection, but in the past recent years, many

institutes have reported those organisms causing

community-acquired infection.5,6

The screening methods that are used for

identification of ESBL-producing organism are

disc diffusion method or dilution antimicrobial

susceptibility and cephalosporin/clavulanate

combination discs. Broth microdilution and E-

test are used as confirmatory tests.7 Those

phenotypic tests have a sensitivity of 98% and

specificity of 96.3% compared with detection of

ESBL gene by PCR amplifications.8

Before 2010, carbapenems are the treatment

of choice for those patients with infection

caused by ESBL-producing organisms regardless

of drug-susceptibility test by disc diffusion

method. Later in 2010, the United States Clinical

Laboratory Standards Institute (CLSI) released

the new inhibition zone and minimal inhibitory

concentration (MIC) breakpoints of beta-lactam

antibiotics for Enterobacteriaceae and recommended

that testing for ESBL production is not necessary.9

The reasons for lowering breakpoints are based on

pharmacokinetic and pharmacodynamic data as

well as the MIC distribution of clinical isolates of

Enterobacteriaceae in several studies carried out

in the United States. To our knowledge, there

has been no study to determine inhibition zone

distribution in comparison with ESBL production

among Enterobacteriaceae in Thailand. Thus,

our study aim was to determine the optimal

susceptibility breakpoint criteria of cefotaxime

and other beta-lactams to distinguish between ESBL-

and non-ESBL-producing Enterobacteriaceae,

and compare it with the susceptibility breakpoint

criteria that was launched by CLSI both before 2010

and in 2010, as well as the European Committee

on Antimicrobial Susceptibility Testing 2013

(EUCAST), and the British Society for Antimicrobial

Chemotherapy 2012 (BSAC).

METHODS

Study population

This study was conducted in blood or other

sterile specimens with Escherichia coli, Klebsiella

pneumoniae, Klebsiella oxytoca , and Proteus

mirabilis grown at Prapokklao Hospital, Chantaburi,

both out-patient and in-patient department, from

October 2011 to September 2013. The study included

patients 18 years of age or older. We excluded

patients who had blood cultures or other sterile

specimens that grew other organisms, and also the

above organism but in non-sterile specimens. The

institutional review board approved the protocol.

Design

A descriptive study was carried out. The data was

obtained from Microbiology laboratory, Prapokklao

Hospital, Chantaburi, which still perform phenotypic

test for ESBL production. The collected data included

organisms, specimens, ESBL-producing property,

inhibition zone size (mm) for the interesting

antibiotics (cefazolin, cefotaxime, ceftazidime,

piperacillin/tazobactam, ertapenem, imipenem,

meropenem). We determined the ESBL-producing

property by double disc and disc combination test.

In our study we used only cefotaxime for both

methods. The cefotaxime inhibition zone breakpoint

is much more reliable than ceftazidime inhibition

zone breakpoint in prediction of ESBL production.


Statistical analysis

Our study was design to determine the suscep-

tibility breakpoint of inhibition zone to distinguish

between ESBL- and non-ESBL-producing Entero-

bacteriaceae for each antibiotic by using ROC

curve (Receiver Operating Characteristic). We

calculated the sample size with the assumption

that the ratio of ESBL-producing organisms would

be 0.3.10 Thus, 461 specimens would be required

to detect a statistical difference (type 1 error 5%,

sensitivity 90%, and range of confident interval

for sensitivity 5%). All data were analyzed by using

microsoft excel 2010 and the SPSS 13.0 software

program. The categorical variables were compared

using the chisquare test, and the continuous

variables were compared using the student two-

tailed t-test. P < 0.05 was considered statistical

significant.

RESULTS

A total of 930 blood and sterile specimens were

obtained from many subspecialty wards. Those

specimens had grown 643 E. coli, 236 K. pneumoniae,

1 K. oxytoca, and 50 P. mirabilis. The proportion of

organisms that produce ESBL was 0.33. The

proportions of ESBL-producing strain for each

organism are shown in Table 1. The baseline

characteristics between ESBL and non-ESBL group

are shown in Table 2.

Comparison of inhibition zone among Entero-

bacteriaceae (E. coli, K. pneumonia, K. oxytoca

and P. mirabilis) with criteria from CLSI 2009,

CLSI 2010, EUCAST 2013, and BSAC 2012 are

shown in Table 3. Inhibition zone distribution of

Enterobacteriaceae to cefotaxime, ceftazidime, and

cefazolin were shown in Figure 1-3. The inhibition

zones distribution for other antibiotics are shown

in supplementary index.

To distinguish ESBL- and non-ESBL producing

Enterobacteriaceae using inhibition zone, we

performed ROC curve and found that only in

cefotaxime and cefazolin, the inhibition zones can

be used with inhibition zone of 26 mm and 12 mm

respectively. With this susceptibility breakpoint,

both sensitivity and specificity are greater than 95%.

ROC curve and table of sensitivity and specificity of

cefotaxime, cefazolin, and ceftazidime are shown

in Figure 4-6 and Table 4-5, respectively. ROC curve

and table of sensitivity and specificity for other

antibiotics are shown in supplementary index.

DISCUSSION

From all 930 sterile specimens, 312 specimens

(33.55%) had ESBL-producing organisms, this

proportion is similar to the previous study from

Siriraj Hospital. The study was the cross-sectional

study that collected 346 specimens with Gram-

negative bacilli grown from 249 admitted patients

from August to September 2003. One hundred and

four specimens (30.1%) had ESBL-producing

organisms.10

Several studies demonstrated that the outcome

of treatment for infection caused by Entero-

bacteriaceae with cephalosporin was associated

with minimal inhibitory concentration (MIC) and

pharmacokinetic/pharmacodynamics more than

ESBL producing property.15 This rationale motivated

reference institutes; CLSI and EUCAST, to adjust the

recommended susceptibility breakpoint criteria in

2010. Physicians can use MIC as a guidance to select

cephalosporin for treatment.15,16

From our study, the susceptibility breakpoint

that has high sensitivity (95%) and specificity (99%)

is inhibition zone of 26 mm for cefotaxime, which is

equal to that of CLSI 2010. Also, the susceptibility

breakpoint for cefazolin can also distinguish ESBL-


147

Table 2. Comparison of baseline characteristics between organisms that produce and not produce ESBL.

MICU - Medicine intensive care unit, CCU - Coronary care unit, SICU - Surgery care unit

IPDs - In-patient departments, OPD - Out-patient department

scitsiretcarahC puorgLBSE puorgLBSE-noN eulavP

DSegaegarevA:egA

)sraey(

49.519.26 19.6176.26 2048.0

)%(elaM:redneG )%31.55(271 )51.54(972 4400.0

draW

enicidemlanretnI )%81.26(491 )%20.55(043 8100.0

UCCdnaUCIM )%65.2(8 )%38.5(63

scidepohtrOdnayregruS )%38.02(56 )%8.71(011

UCIS )%12.3(01 )%26.1(01

sDPIrehtO )%69.0(3 )%31.1(7

slatipsohytinummoCdnaDPO )%62.01(23 )%16.81(511

snemicepS

worramenobdnadoolB )%13.29(882 )%36.59(195 8641.0

diulflanipsorbereC )%29.1(6 )%92.1(8

diulflaivonyS )%29.1(6 )%56.0(4

diulflaruelP )%35.3(11 )%34.2(51

diulflaidracireP )%23.0(1 )%0(0

± ± ±

Table 1. Proportion of Enterobacteriaceae that produce and non- ESBL isolates.

)n(smsinagrO segatnecrepdnasetalosifo.oN

iloc.E )346( LBSE 932 %71.73

LBSE-noN 404 %38.26

eainomuenp.K )632( LBSE 56 %45.72

LBSE-noN 171 %64.27

acotyxo.K )1( LBSE 0 %0

LBSE-noN 1 %001

silibarim.P )05( LBSE 8 %61

LBSE-noN 24 %48

)039(latoT LBSE 213 %55.33

LBSE-noN 816 %54.66


Table 3. Inhibition zone distribution of ESBL-producing Enterobacteriaceae for various types of antibiotics

separated by criteria of 3 institutes.

Pip/tazo – piperacillin/tazobactam, R – Resistant, I – Intermediate resistant, S – Susceptible

setutitsnI 21)0102erofeb(ISLC 11)0102(ISLC 31)3102(TSACUE 41)2102(CASB

rofairetirC

emixatofeC

setalosi%

R I S R I S R S R S

41 22-51 32 22 52-32 62 71 02 32 03

50.28 30.61 29.1 70.89 46.0 82.1 59.29 31.5 70.89 82.1

rofairetirC

emidizatfeC

setalosi%

R I S R I S R S R S

41 71-51 81 71 02-81 12 91 22 22 72

24.73 54.22 31.04 78.95 39.21 12.72 30.86 11.22 56.28 60.3

rofairetirC

nilozafeC

setalosi%

R I S R I S R S R S

41 71-51 81 91 22-02 32 elbaliavatoN elbaliavatoN

93.89 0 16.1 93.89 46.0 79.0 elbaliavatoN elbaliavatoN

rofairetirC

ozat/piP

setalosi%

R I S R I S R S R S

71 02-81 12 71 02-81 12 71 02 02 32

16.4 74.31 19.18 16.4 74.31 19.18 69.2 48.68 90.81 55.85

rofairetirC

menepimI

setalosi%

R I S R I S R S R S

31 51-41 61 91 22-02 32 61 22 61 12

86.0 0 23.99 63.1 0 46.89 86.0 46.89 86.0 46.89

rofairetirC

meneporeM

setalosi%

R I S R I S R S R S

31 51-41 61 91 22-02 32 61 22 91 72

0 0 001 76.0 0 33.99 0 33.99 76.0 89.49

rofairetirC

menepatrE

setalosi%

R I S R I S R S R S

51 81-61 91 81 12-91 22 22 52 51 82

0 33.0 76.99 33.0 66.0 99 99.0 63.59 0 51.87

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149

Figure 1. Inhibition zone distribution of Enterobacteriaceae to cefotaxime.

Figure 2. Inhibition zone distribution of Enterobacteriaceae to ceftazidime.


Figure 3. Inhibition zone distribution of Enterobacteriaceae to cefazolin.

Figure 4. ROC curve using inhibition zone of cefotaxime

for distinguish ESBL-and non-ESBL producing

Enterobacteriaceae (AUC = 0.973).


151

Figure 5. ROC curve using inhibition zone of cefazolin


Enterobacteriaceae (AUC = 0.965)

Figure 6 ROC curve using inhibition zone of ceftazidime

for distinguish ESBL- and non-ESBL producing



)mm(enoznoitibihnI )%(ytivitisneS )%(yticificepS

01 59 49

11 59 59

21 59 69

31 49 69

51 49 89

)9002ISLC(81 29 89

)0102ISLC(32 26 99

Table 5. Sensitivity and specificity for each value of inhibition zone of

cefazolin.

and non-ESBL producing Enterobacteriaceae with

inhibition zone of 12 mm (sensitivity 95%,

specificity 96%), which is much different from

CLSI 2010 criteria (23 mm). This difference of

inhibition zone may be due to the different strains

of Enterobacteriaceae between Thailand and

USA. There was a study by Silke Polsfuss et al in

2012, that compared non-susceptible breakpoints

of inhibition zone between CLSI 2010 and EUCAST

2010. They found that 118 of 236 specimens (50%)

were ESBL-producing strains (tested by phenotypic

and molecular method), and non-susceptible

breakpoint criteria of both CLSI 2010 (≤ 27 mm)

and EUCAST 2010 (< 21 mm) for cefotaxime

had similar sensitivity of 99.2%. However, for

ceftazidime with criteria of EUCAST 2011 (< 22 mm,

10 mcg/disc) had a sensitivity of 77.1%, which

more than 65.3% from CLSI 2010 (< 22 mm, 30

mcg/disc) criteria.17 This study had a result

similar to our study using ROC curve, in the point

that we can use susceptible breakpoints of inhibition

zone of cefotaxime to distinguish ESBL- and non-

ESBL producing Enterobacteriaceae with high

sensitivity and specificity. Moreover, susceptibility


)3102TSACUE(02 69 59

12 69 79

)9002ISLC(32 59 89

52 59 89

)0102ISLC(62 59 99

92 09 99

)2102CASB(03 48 99


cefotaxime.


153

breakpoint value of those studies and our study

are close (27 VS 26 mm).

For the non-susceptibility breakpoint criteria

for cefotaxime from EUCAST 2013 (< 20 mm),

our study demonstrated that the sensitivity was

of 96% and specificity was of 95%. While those

criteria from BSAC 2012 (< 30 mm), the sensitivity

and specificity was 84% and 99% respectively.

From this study, non-susceptibility breakpoint

criteria for cefotaxime by CLSI 2010 have the best

sensitivity and specificity.

From Table 3, the ESBL-producing strains have a

proportion of susceptible category for ceftazidime

more than those for cefotaxime in all criteria from

CLSI, EUCAST, and BSAC. This finding may be

derived from ESBL in our study which are a

member in Family CTX-M (cefotaximase), which

have property to hydrolyze cefotaxime in higher

degree than ceftazidime, resulting in high level

resistance to cefotaxime but low level resistance

or susceptible to ceftazidime. This explanation is

supported by the study carried out in Siriraj Hospital

and Thammasat Hospital in 200818, which found

that CTX-M was the most common (> 99%) family

among ESBL produced by 362 strains of E. coli and

K. pneumoniae. The most common type of CTX-M

is CTX-M-14 and CTX-M-15, which are similar to

epidemiology of CTX-M worldwide and currently

are the most spreading strains.19 This also explains

why we cannot use inhibition zone of ceftazidime

to differentiate ESBL-producing from non-ESBL

producing organisms in our and in many studies.

However, our study did not investigate the strains

of ESBL, so we cannot conclude that ESBL in our

study is a member in CTX-M.

For betalactam/betalactamase inhibitors, eg.

piperacillin/tazobactam, is unable to use inhibition

zone as a screening test because of different degree

of ESBL to hydrolyze beta-lactamase inhibitors,

which are mostly hydrolyze ESBL.

However, the clinical outcome of treatment for

infection caused by ESBL- and non-ESBL producing

organism may not be different as shown in

SENTRY study (83% and 80% respectively).20

Among ESBL-producing organisms, clinical success

rates from treatment with cephalosporin was

81.8%, fluoroquinolone was 81.8%, BL/BLI was

87.5%, and cephalosporin plus aminoglycoside/

fluoroquinolone was 83.3%. These success rates

were not different from treatment with carbapenem

alone, which was 81.8%. This study concluded that

ESBL production alone is not the independent

factor determining treatment failure.19,20

There are many limitations in our study. First, we

used phenotypic test to determine ESBL production,

which are not reliable as genotypic test or molecular

test. Secondly, for drug susceptibility in our study

we used inhibition zone, while standard method

should use MIC value. For clinical use, we should

consider parameter calculated from MIC, such as

percent time above MIC or pharmacokinetics/

pharmacodynamics by using Monte Carlo’s simulation.

Lastly, our study was not compared to our inhibition

zone breakpoint and clinical outcome, so clinical use

should be aware.

CONCLUSION

To our knowledge, the present study is the first

to determine the inhibition zone distributions and

breakpoints of beta-lactam antibiotics to dis-

tinguish between ESBL- and non-ESBL-producing

Enterobacteriaceae in Thailand. Only cefotaxime

inhibition zone breakpoint is consistent with that

recommended by CLSI 2010. However, we cannot

calculate the inhibition zone breakpoints due to no

correlations between the inhibition zone distributions


of ceftazidime, piperacillin/tazobactam, and all

carbapenems with ESBL production in Entero-

bacteriaceae.

ACKNOWLEDGEMENTS

We thank the Department of Microbiology of

Prapokklao Hospital, Chantaburi for providing the

data in this study.

References

1. Schwaber MJ, Carmeli Y. Carbapenem-resistant

Enterobacteriaceae: a potential threat. JAMA

2008;300:2911-3.

2. Rupp ME, Fey PD. Extended spectrum beta-lactamase

(ESBL)-producing Enterobacteriaceae: considerations

for diagnosis, prevention and drug treatment. Drugs

2003;63:353-65.

3. 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.

4. 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.

5. Tenover FC, McGowan JE Jr. Reasons for the

emergence of antibiotic resistance. Am J Med Sci

1996;311:9-16.

6. Pitout JD, Nordmann P, Laupland KB, Poirel L.

Emergence of Enterobacteriaceae producing extended-

spectrum beta-lactamases (ESBLs) in the community.

J Antimicrob Chemother 2005;56:52-9.

7. Paterson DL, Bonomo RA. Extended-spectrum beta-

lactamases: a clinical update. Clin Microbiol Rev

2005;18:657-86.

8. Kohner PC, Robberts FJ, Cockerill FR, III, Patel R.

Cephalosporin MIC distribution of extended-

spectrum-{beta}-lactamase- and pAmpC-producing

Escherichia coli and Klebsiella species. J Clin

Microbiol 2009;47:2419-25.

9. Dudley MN, Ambrose PG, Bhavnani SM, Craig WA,

Ferraro MJ, Jones RN. Background and rationale

for revised clinical and laboratory standards

institute interpretive criteria (Breakpoints) for

Enterobacteriaceae and Pseudomonas aeruginosa:

I. Cephalosporins and Aztreonam. Clin Infect Dis

2013;56:1301-9.

10. Chayakulkeeree M, Junsriwong P, Keerasuntonpong

A, Tribuddharat C, Thamlikitkul V. Epidemiology of

extended-spectrum beta-lactamase producing gram-

negative bacilli at Siriraj Hospital, Thailand, 2003.

Southeast Asian J Trop Med Public Health 2005;36:

1503-9.

11. Clinical and Laboratory Standards Institute (CLSI).

Performance standards for antimicrobial susceptibility

testing. Twenty-third informational supplement;

M100-S23. Wayne, PA: CLSI; 2013.

12. Clinical and Laboratory Standards Institute (CLSI).

Performance standards for antimicrobial susceptibility

testing. Nineteenth informational supplement;

M100-S19. Wayne, PA: CLSI; 2009.

13. The European Committee on Antimicrobial Susceptibility

Testing (EUCAST). Breakpoint tables for interpretation

of MICs and zone diameters; version 3.1. Basel,

Switzerland: EUCAST; 2013.

14. The British Society for Antimicrobial Chemotherapy

(BSAC). Methods for antimicrobial susceptibility

testing; version 11.1. Birmingham, UK: BSAC; 2012.

15. Kahlmeter G. Breakpoints for intravenously used

cephalosporins in Enterobacteriaceae--EUCAST and

CLSI breakpoints. Clin Microbiol Infect 2008;14

(Suppl 1):169-74.

16. Kiratisin P. Effect of MIC interpretative breakpoint

revision on cephalosporin and carbapenem suscep-

tibility among ESBL-producing Enterobacteriaceae.


155

Asian Biomedicine 2012;6:713-21.

17. Polsfuss S, Bloemberg GV, Giger J, Meyer V, Hombach

M. Comparison of European Committee on Anti-

microbial Susceptibility Testing (EUCAST) and CLSI

screening parameters for the detection of extended-

spectrum beta-lactamase production in clinical

Enterobacteriaceae isolates. J Antimicrob Chemother

2012;67:159-66.

18. Kiratisin P, Apisarnthanarak A, Laesripa C, Saifon P.

Molecular characterization and epidemiology of

extended-spectrum-beta-lactamase-producing

Escherichia coli and Klebsiella pneumoniae isolates

causing health care-associated infection in Thailand,

where the CTX-M family is endemic. Antimicrob


19. Bonnet R. Growing group of extended-spectrum

beta-lactamases: the CTX-M enzymes. Antimicrob


20. Hawser SP, Badal RE, Bouchillon SK, Hoban DJ, Hsueh

PR. Comparison of CLSI 2009, CLSI 2010 and EUCAST

cephalosporin clinical breakpoints in recent clinical

isolates of Escherichia coli, Klebsiella pneumoniae

and Klebsiella oxytoca from the SMART Global

Surveillance Study. Int J Antimicrob Agents 2010;36:

293-4.

21. Bhavnani SM, Ambrose PG, Craig WA, Dudley MN,

Jones RN; SENTRY Antimicrobial Surveillance

Program. Outcomes evaluation of patients with ESBL-

and non-ESBL-producing Escherichia coli and

Klebsiella species as defined by CLSI reference

methods: report from the SENTRY Antimicrobial

Surveillance Program. Diagn Microbiol Infect Dis

2006;54:231-6.

Supplementary index

Figure 1. Inhibition zone distribution of Enterobacteriaceae to cefotaxime.


Figure 2. Inhibition zone distribution of cefotaxime to ESBL-producing E. coli, K. pneumonia, P. mirabilis.

Figure 3. Inhibition zone distribution of Enterobacteriaceae to ceftazidime.


157

Figure 4. Inhibition zone distribution of ceftazidime to ESBL-producing E. coli, K. pneumonia, P. mirabilis.

Figure 5. Inhibition zone distribution of Enterobacteriaceae to cefazolin.


Figure 6. Inhibition zone distribution of cefazolin to ESBL-producing E. coli, K. pneumonia, P. mirabilis.

Figure 7. Inhibition zone distribution of Enterobacteriaceae to piperacillin/tazobactam.


159

Figure 8. Inhibition zone distribution of piperacillin/tazobactam to ESBL-producing E. coli, K. pneumonia,

P. mirabilis.

Figure 9. Inhibition zone distribution of Enterobacteriaceae to imipenem.


Figure 10. Inhibition zone distribution of imipenem to ESBL-producing E. coli, K. pneumonia, P. mirabilis.

Figure 11. Inhibition zone distribution of Enterobacteriaceae to meropenem.


161

Figure 12. Inhibition zone distribution of meropenem to ESBL-producing E. coli, K. pneumonia, P. mirabilis.

Figure 13. Inhibition zone distribution of Enterobacteriaceae to ertapenem.


Figure 14. Inhibition zone distribution of ertapenem to ESBL-producing E. coli, K. pneumonia, P. mirabilis.

Figure 15. ROC curve using inhibition zone of cefotaxime




163

Figure 16. ROC curve using inhibition zone of cefazolin




)3102TSACUE(02 69 59

12 69 79

)9002ISLC(32 59 89

52 59 89

)0102ISLC(62 59 99

92 09 99

)2102CASB(03 48 99


cefotaxime.


Figure 17. ROC curve using inhibition zone of ceftazidime

for distinguish ESBL and non-ESBL producing



01 59 49

11 59 59

21 59 69

31 49 69

51 49 89

)9002ISLC(81 29 89

)0102ISLC(32 26 99


cefazolin.


165

Figure 18. ROC curve using inhibition zone of Piperacillin/

tazobactam for distinguish ESBL and non-ESBL

producing Enterobacteriaceae (AUC = 0.430).

Figure 19. ROC curve using inhibition zone of imipenem

for distinguish ESBL and non-ESBL producing



Figure 20. ROC curve using inhibition zone of

meropenem for distinguish ESBL and non-

ESBL producing Enterobacteriaceae (AUC =

0.482).

Figure 21. ROC curve using inhibition zone of

ertapenem for distinguish ESBL and non-

ESBL producing Enterobacteriaceae (AUC =

0.472).

Cephalosporin and Carbapenem Inhibition Zone Breakpoints ...

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