Open Access

Susceptibility of important Gram-negative pathogens to tigecycline and other antibiotics in Latin America between 2004 and 2010

Annals of Clinical Microbiology and Antimicrobials201211:29

https://doi.org/10.1186/1476-0711-11-29

Received: 27 April 2012

Accepted: 29 September 2012

Published: 22 October 2012

Abstract

Background

The Tigecycline Evaluation and Surveillance Trial (T.E.S.T.) is a global surveillance study of antimicrobial susceptibility. This study reports data from Gram-negative isolates collected from centers in Latin America between 2004 and 2010.

Methods

Consecutive bacterial isolates were tested at each center using broth microdilution methodology as described by the Clinical Laboratory Standards Institute (CLSI). Susceptibility was determined using the CLSI interpretive criteria. For tigecycline the US Federal Drug Administration (FDA) criteria were used.

Results

A total of 16 232 isolates were analyzed. Susceptibility to imipenem, meropenem, and tigecycline was >95% against both non-extended-spectrum β-lactamase (ESBL) and ESBL producing Escherichia coli. Susceptibility to amikacin was also >95% for non-ESBL E. coli. 24.3% of E. coli were ESBL producers, ranging from 11.2% (58/519) in Colombia to 40.3% (31/77) in Honduras. Greater than 90% of non-ESBL Klebsiella pneumoniae were susceptible to tigecycline, carbapenems and amikacin. 35.3% of K. pneumoniae were ESBL producers, ranging from 17.2% (36/209) in Venezuela to 73.3% (55/75) in Honduras, with only imipenem and tigecycline maintaining >90% susceptibility. Greater than 90% of Klebsiella oxytoca, Enterobacter spp., and Serratia marcescens were susceptible to amikacin, carbapenems and tigecycline. The highest rates of susceptibility against Acinetobacter baumannii were seen for minocycline (89.4%) and imipenem (62.5%), while 95.8% of the A. baumannii isolates displayed an MIC ≤2 μg/mL for tigecycline.

Conclusions

In this study carbapenems and tigecycline remain active against Enterobacteriaceae and A. baumannii; however, there is cause for concern with carbapenem non-susceptible isolates reported in all countries included in this study.

Keywords

TigecyclineLatin AmericaResistanceSusceptibilityCarbapenems

Background

Tigecycline is a glycylcycline licensed by the US Food and Drug Administration (FDA) for the treatment of complicated skin and skin structure infections (cSSSI), complicated intra-abdominal infections (cIAIs) and community acquired bacterial pneumonia (CAP). The Tigecycline Evaluation and Surveillance Trial (T.E.S.T.) is a global surveillance study with the aim of assessing and reporting the antimicrobial susceptibility of tigecycline and comparator agents globally, regionally, and for individual countries. T.E.S.T. was initiated in 2004 and to date 60 countries have contributed with Gram-positive and Gram-negative isolates and susceptibility data. Antimicrobial surveillance studies, such as T.E.S.T., play a key role in charting antimicrobial resistance.

The Latin American region is recognized as facing a significant challenge with high levels of antimicrobial resistance among important Gram-negative organisms including Escherichia coli and Klebsiella spp. and the non-fermenters Acinetobacter spp. and Pseudomonas aeruginosa[13]. In recent years, extended-spectrum β-lactamases (ESBLs) have increased in type and frequency among Enterobacteriaceae and carbapenemases have emerged[4, 5]. In the case of the non-fermentative Gram-negative bacilli multidrug-resistance is an increasing problem with limited, or no treatment option[6].

In this report we present data from the Latin American region of Gram-negative isolates collected between 2004 and 2010. The isolates collected between 2004 and 2007 were previously reported by Rossi et al.[7].

Methods

Organism collection

Gram-negative isolates were collected from 12 countries in Latin America between 2004 and 2010. Centers were distributed as follows: 12 in Argentina, 3 in Brazil, 5 in Chile, 14 in Colombia, 1 in El Salvador, 4 in Guatemala, 2 in Honduras, 1 in Jamaica, 15 in Mexico, 1 in Nicaragua, 2 in Panama, and 6 in Venezuela. The Gram-negative isolates submitted were consecutive and determined to be clinically significant using local criteria. Permissible clinical sources included blood, respiratory tract, urine (limited to no more than 25% of all isolates), skin, wound, and fluids. For each year, each participant center was required to identify and conduct susceptibility tests on Acinetobacter spp. (15), E. coli (25), Enterobacter spp. (25), Serratia spp. (10), Klebsiella spp. (25) and Haemophylus influenzae (15). A single isolate per patient was accepted. Inclusion in the study was independent of the patient’s medical history, previous antimicrobial use, sex and age. No banked or stored isolates were accepted.

Antimicrobial susceptibility testing

Each study center carried out antimicrobial susceptibility testing using broth microdilution methodology (Sensititre® plates [TREK Diagnostic Systems, West Sussex, England] or MicroScan® panels [Siemens, Sacramento, CA, USA]) as described by the Clinical and Laboratory Standards Institute (CLSI)[8]. Gram-negative isolates were tested against amikacin, amoxicillin-clavulanate, ampicillin, cefepime, ceftazidime, ceftriaxone, imipenem, levofloxacin, meropenem, minocycline, piperacillin-tazobactam, and tigecycline. In 2006, unreliability of the imipenem testing led to a switch from MicroScan® panels with imipenem to Sensititre® plates with meropenem. The presence or abscence of β-lactamase among H. influenzae was determined using the preferred method of each center.

Quality control strains used in the testing were E. coli ATCC 25922 and P. aeruginosa ATCC 27853. Confirmation of isolate identification and management of a centralized database were performed by a central laboratory (Laboratories International for Microbiology Studies, a division of International Health Management Associates, Inc. [IHMA, Schaumburg, IL, USA]).

Antimicrobial susceptibility was determined using CLSI interpretive criteria[9, 10]. For tigecycline, the FDA approved breakpoints, as provided in the package insert, were used[11].

Extended spectrum β-lactamase (ESBL) determination

Testing for ESBL production was carried out on isolates of E. coli and Klebsiella spp. according to the CLSI guidelines[9]. The methodology used Mueller-Hinton agar (Remel, Inc., Lenexa, KS, USA) and cefotaxime (30 μg), cefotaxime-clavulanic acid (30/10 μg), ceftazidime (30 μg), and ceftazidime-clavulanic acid (30/10 μg) discs (Oxoid, Inc., Ogdensburg, NY, USA). Quality control was carried out using K. pneumoniae ATCC 700603 (ESBL-positive) and E. coli ATCC 25922 (ESBL-negative).

Multidrug-resistant Acinetobacter baumannii

Multidrug resistance among isolates of A. baumannii was defined as resistance to levofloxacin, amikacin, carbapenems (imipenem and/or meropenem), ceftazidime and piperacillin-tazobactam.

Results

Antimicrobial susceptibility data on 16 232 Gram-negative isolates collected in Latin America between 2004 and 2010 are presented in Table1. Susceptibility among the E. coli isolates (both ESBL and non-ESBL producers) was >95% for carbapenems and tigecycline. Susceptibility to amikacin was also >95% against non-ESBL producing E. coli (MIC90 8 μg/mL) but decreased to 89.7% against ESBL producers (MIC90 32 μg/mL). A total of 24.3% of the E. coli collected from Latin America were identified as ESBL producers with percentages of ESBL production varying from 11.2% (58/519) in Colombia to 40.3% (31/77) in Honduras (Figure1). Data on susceptibility to imipenem and meropenem by country are presented in Table2. Among E. coli isolates, ESBL producers displayed slightly lower susceptibility to meropenem than non-ESBL producing isolates.
Table 1

Antimicrobial activity against Gram-negative organisms collected from Latin America (2004 – 2010)

Organisms/antimicrobial

 

MIC (mg/L)

Percentage

N

50

90

Range

S

I

R

non-ESBL E. coli

       

Amikacin

2711

2

8

≤0.5 to ≥128

97.2

1.2

1.7

Amoxi/clav

2711

8

32

≤0.12 to ≥64

60.5

21.2

18.4

Ampicillin

2711

≥64

≥64

≤0.5 to ≥64

28.6

1.5

69.9

Cefepime

2711

≤0.5

4

≤0.5 to ≥64

94.3

2.1

3.6

Ceftazidimea

2711

≤8

16

≤1 to ≥64

-

-

11.7

Ceftriaxone

2711

≤0.06

32

≤0.06 to ≥128

82.0

2.3

15.6

Imipenem

485

0.25

0.5

≤0.06 to ≥32

98.6

0.6

0.8

Levofloxacin

2711

0.25

≥16

≤0.008 to ≥16

60.9

3.0

36.2

Meropenem

2226

≤0.06

0.12

≤0.06 to ≥32

98.6

0.4

1.0

Minocycline

2711

4

16

≤0.5 to ≥32

62.4

14.3

23.2

Pip/taz

2711

2

32

≤0.06 to ≥256

88.8

5.2

6.0

Tigecycline

2711

0.25

0.5

≤0.008 to ≥32

99.7

0.2

<0.1c

ESBL E. coli

       

Amikacin

870

4

32

≤0.5 to ≥128

89.7

5.1

5.3

Amoxi/clav

870

16

32

0.25 to ≥64

21.1

42.5

36.3

Cefepime

870

32

≥64

≤0.5 to ≥64

28.2

14.3

57.6

Ceftazidimea

870

16

≥64

≤1 to ≥64

-

-

65.5

Ceftriaxone

870

≥128

≥128

≤0.06 to ≥128

1.1

2.0

96.9

Imipenem

143

0.25

0.5

≤0.06 to 8

97.9

0.7

1.4

Levofloxacin

870

≥16

≥16

0.015 to ≥16

11.5

3.4

85.1

Meropenem

727

≤0.06

0.12

≤0.06 to ≥32

96.4

1.2

2.3

Minocycline

870

4

≥32

≤0.5 to ≥32

52.3

14.6

33.1

Pip/taz

870

8

64

≤0.06 to ≥256

73.9

16.1

10.0

Tigecycline

870

0.25

0.5

≤0.008 to 4

99.8

0.2

0.0

Non-ESBL K. pneumoniae

       

Amikacin

1917

2

8

≤0.5 to ≥128

93.4

1.8

4.8

Amoxi/clav

1917

4

≥64

0.25 to ≥64

67.5

10.0

22.5

Cefepime

1917

≤0.5

16

≤0.5 to ≥64

87.7

2.8

9.4

Ceftazidimea

1917

≤8

32

≤1 to ≥64

-

-

17.2

Ceftriaxone

1917

≤0.06

≥128

≤0.06 to ≥128

77.1

1.4

21.5

Imipenem

275

0.5

0.5

≤0.06 to ≥32

98.9

0.0

1.1

Levofloxacin

1917

0.06

≥16

≤0.008 to ≥16

80.1

2.1

17.7

Meropenem

1642

≤0.06

0.25

≤0.06 to ≥32

94.6

1.0

4.4

Minocycline

1917

4

≥32

≤0.5 to ≥32

65.8

11.1

23.1

Pip/taz

1917

4

≥256

≤0.06 to ≥256

79.6

6.2

14.2

Tigecycline

1917

0.5

1

≤0.008 to ≥32

96.9

2.3

0.8

ESBL K. pneumoniae

       

Amikacin

1045

8

≥128

≤0.5 to ≥128

71.2

8.3

20.5

Amoxi/clav

1045

32

≥64

≤0.12 to ≥64

13.1

30.6

56.3

Cefepime

1045

32

≥64

≤0.5 to ≥64

29.2

12.1

58.8

Ceftazidimea

1045

32

≥64

≤2 to ≥64

-

-

81.1

Ceftriaxone

1045

≥128

≥128

≤0.06 to ≥128

1.0

1.2

97.8

Imipenem

199

0.5

1

≤0.06 to 16

96.0

2.5

1.5

Levofloxacin

1045

8

≥16

≤0.008 to ≥16

38.2

5.5

56.4

Meropenem

846

≤0.06

2

≤0.06 to ≥32

89.0

2.4

8.6

Minocycline

1045

8

≥32

≤0.5 to ≥32

49.0

17.1

33.9

Pip/taz

1045

64

≥256

0.12 to ≥256

34.5

20.8

44.7

Tigecycline

1045

0.5

2

0.03 to 16

93.7

4.9

1.4

K. oxytoca

       

Amikacin

311

2

8

≤0.5 to ≥128

94.9

1.6

3.5

Amoxi/clav

311

4

32

0.25 to ≥64

69.1

11.9

19.0

Cefepime

311

≤0.5

16

≤0.5 to ≥64

85.5

5.8

8.7

Ceftazidimea

311

≤8

32

≤1 to ≥64

-

-

20.9

Ceftriaxone

311

0.12

≥128

≤0.06 to ≥128

68.5

2.9

28.6

Imipenem

76

0.5

0.5

≤0.06 to 1

100

0.0

0.0

Levofloxacin

311

0.06

≥16

≤0.008 to ≥16

81.0

1.3

17.7

Meropenem

235

≤0.06

0.12

≤0.06 to 16

97.4

1.3

1.3

Minocycline

311

2

16

≤0.5 to ≥32

77.5

10.3

12.2

Pip/taz

311

2

128

≤0.06 to ≥256

83.6

6.1

10.3

Tigecycline

311

0.25

1

0.06 to 4

97.7

2.3

0.0

Enterobacter spp.

       

Amikacin

2804

2

32

≤0.5 to ≥128

89.2

4.4

6.5

Amoxi/clav

2804

≥64

≥64

≤0.12 to ≥64

4.7

3.0

92.3

Cefepime

2804

≤0.5

≥64

≤0.5 to ≥64

81.4

4.6

14.1

Ceftazidimea

2804

≤8

≥64

≤1 to ≥64

-

-

40.5

Ceftriaxone

2804

1

≥128

≤0.06 to ≥128

51.9

2.6

45.5

Imipenem

493

0.5

1

≤0.06 to ≥32

95.9

2.6

1.4

Levofloxacin

2804

0.12

≥16

≤0.008 to ≥16

78.2

3.1

18.8

Meropenem

2311

≤0.06

0.5

≤0.06 to ≥32

94.3

1.9

3.8

Minocycline

2804

4

≥32

≤0.5 to ≥32

61.9

17.7

20.3

Pip/taz

2804

4

≥256

≤0.06 to ≥256

70.1

11.7

18.1

Tigecycline

2804

0.5

2

≤0.008 to ≥32

96.0

3.5

0.5

S. marcescens

       

Amikacin

1126

2

64

≤0.5 to ≥128

82.6

7.2

10.2

Amoxi/clav

1126

≥64

≥64

≤0.12 to ≥64

4.4

2.9

92.6

Cefepime

1126

≤0.5

32

≤0.5 to ≥64

83.6

3.7

12.7

Ceftazidimea

1126

≤8

32

≤1 to ≥64

-

-

17.5

Ceftriaxone

1126

0.5

≥128

≤0.06 to ≥128

67.8

3.4

28.9

Imipenem

229

0.5

1

≤0.06 to 8

91.7

6.1

2.2

Levofloxacin

1126

0.25

4

≤0.008 to ≥16

86.2

4.4

9.3

Meropenem

897

≤0.06

0.25

≤0.06 to 8

96.2

1.8

2.0

Minocycline

1126

4

16

≤0.5 to ≥32

61.3

23.6

15.1

Pip/taz

1126

2

64

≤0.06 to ≥256

84.0

6.9

9.1

Tigecycline

1126

1

2

≤0.008 to 16

95.5

3.7

0.8

H. influenzae

       

Amoxi/clav

908

0.5

1

≤0.12 to 16

99.3

0.0

0.7

Ampicillin

908

≤0.5

16

≤0.5 to ≥64

78.7

2.5

18.7

Cefepime

908

≤0.5

≤0.5

≤0.5 to 8

99.6

--

--

Ceftazidimeb

902

≤8

≤8

≤8 to 16

--

--

--

Ceftriaxone

908

≤0.06

≤0.06

≤0.06 to 2

100

--

--

Imipenem

217

0.5

1

≤0.06 to 4

100

--

--

Levofloxacin

908

0.015

0.03

≤0.008 to 2

100

--

--

Meropenem

691

≤0.06

0.12

≤0.06 to 0.5

100

--

--

Minocycline

908

≤0.5

1

≤0.5 to 16

98.7

0.8

0.6

Pip/taz

908

≤0.06

≤0.06

≤0.06 to 4

99.7

0.0

0.3

Tigecycline

908

0.12

0.25

≤0.008 to 0.5

98.8

--

--

A. baumannii

       

Amikacin

1806

64

≥128

≤0.5 to ≥128

30.4

12.0

57.6

Cefepime

1806

32

≥64

≤0.5 to ≥64

25.3

14.4

60.3

Ceftazidime

1806

≥64

≥64

≤1 to ≥64

18.5

7.8

73.8

Ceftriaxone

1806

≥128

≥128

≤0.06 to ≥128

10.5

11.1

78.4

Imipenem

307

2

≥32

≤0.06 to ≥32

62.5

3.9

33.6

Levofloxacin

1806

8

≥16

≤0.008 to ≥16

20.9

11.4

67.8

Meropenem

1499

≥32

≥32

≤0.06 to ≥32

33.9

5.5

60.6

Minocycline

1806

≤0.5

8

≤0.5 to ≥32

89.4

4.6

6.0

Pip/taz

1806

≥256

≥256

≤0.06 to ≥256

18.7

9.1

72.2

Tigecycline

1806

0.5

2

≤0.008 to ≥32

--

--

--

P. aeruginosa

       

Amikacin

2734

4

≥128

≤0.5 to ≥128

71.8

8.1

20.0

Cefepime

2734

8

≥64

≤0.5 to ≥64

59.8

15.2

25.1

Ceftazidime

2734

≤8

≥64

≤1 to ≥64

54.9

10.6

34.5

Imipenem

461

1

16

0.12 to ≥32

66.8

15.0

18.2

Levofloxacin

2734

2

≥16

0.015 to ≥16

52.6

6.1

41.4

Meropenem

2273

2

≥32

≤0.06 to ≥32

64.2

9.6

26.2

Minocycline

2734

16

≥32

≤0.5 to ≥32

--

--

--

Pip/taz

2734

16

≥256

≤0.06 to ≥256

75.3

0.0

24.7

Tigecycline

2734

8

≥32

≤0.008 to ≥32

--

--

--

S, susceptible; I, intermediate; R, resistant; amoxi/clav, amoxicillin-clavulanate; pip/taz, piperacillin-tazobactam.

-- No CLSI breakpoints available.

a The ceftazidime testing range against the Enterobacteriaceae started at 8 μg/mL, therefore susceptible and intermediate classifications can not be calculated.

b The ceftazidime testing range against H. influenzae started at 8 μg/mL, therefore a susceptible classification can not be calculated.

c 0.04%, 1 isolate, collected in 2009. The isolate was collected in Mexico in 2009 from a male inpatient. The isolate was also resistant to amoxicillin-clavulanate, ampicillin, ceftriaxone, and minocycline.

Figure 1

Percentage of Escherichia coli and Klebsiella pneumoniae isolates identified as ESBL producers in each Latin American country a involved in T.E.S.T. (2004–2010). E. coli N values: Argentina, 101/769; Brazil, 43/247; Chile, 94/271; Colombia, 58/519; Guatemala, 81/263; Honduras, 31/77; Mexico, 398/1044; Panama, 16/100; Venezuela, 32/218; Latin America, 870/3581. K. pneumoniae N values: Argentina, 270/694; Brazil, 105/214; Chile, 147/243; Colombia, 81/432; Guatemala, 96/189; Honduras, 55/75; Mexico, 191/754; Panama, 35/89; Venezuela, 36/209; Latin America, 1045/2962. a Data from El Salvador, Jamaica and Nicaragua are not included in the analysis by country because fewer than 50 isolates were collected; however, their data are included in the total for Latin America.

Table 2

Antimicrobial susceptibility (%S) to the carbapenems among Gram-negative organisms collected from individual countries (2004 – 2010)

  

Country

Antimicrobial

 

Argentina

Brazil

Chile

Colombia

Guatemala

Honduras

Mexico

Panama

Venezuela

non-ESBL E. coli

          

Imipenem

N

216/219

40/40

47/47

67/71

-

-

64/64

-

21/21

 

%S

98.6

100

100

94.4

-

-

100

-

100

Meropenem

N

448/449

164/164

130/130

386/390

174/182

45/46

569/582

84/84

165/165

 

%S

99.8

100

100

99.0

95.6

97.8

97.8

100

100

ESBL E. coli

          

Imipenem

N

28/29

10/10

29/29

17/18

-

-

51/52

-

-

 

%S

96.6

100

100

94.4

-

-

98.1

-

 

Meropenem

N

71/72

32/33

65/65

38/40

76/81

30/31

337/346

16/16

27/29

 

%S

98.6

97.0

100

95.0

93.8

96.8

97.4

100

93.1

non-ESBL K. pneumoniae

          

Imipenem

N

120/121

17/17

29/29

34/35

-

-

47/47

-

10/10

 

%S

99.2

100

100

97.1

-

-

100

-

100

Meropenem

N

297/303

88/92

63/67

290/316

83/93

16/20

495/516

53/54

156/163

 

%S

98.0

95.7

94.0

91.8

89.2

80.0

95.9

98.1

95.7

ESBL K. pneumoniae

          

Imipenem

N

91/93

20/23

35/35

16/18

-

-

19/19

-

-

 

%S

97.8

87.0

100

88.9

-

-

100

-

-

Meropenem

N

170/177

78/82

102/112

47/63

76/96

50/55

160/172

32/35

28/31

 

%S

96.0

95.1

91.1

74.6

79.2

90.9

93.0

91.4

90.3

K. oxytoca

          

Imipenem

N

32/32

-

-

13/13

-

-

11/11

-

-

 

%S

100

-

-

100

-

-

100

-

-

Meropenem

N

38/38

17/17

15/15

37/38

-

-

106/110

-

-

 

%S

100

100

100

97.4

-

-

96.4

-

-

Enterobacter spp.

          

Imipenem

N

210/222

44/47

58/58

56/59

-

-

58/58

-

25/25

 

%S

94.6

93.6

100

94.9

-

-

100

-

100

Meropenem

N

494/502

187/195

161/171

347/384

83/105

29/34

622/651

66/70

176/183

 

%S

98.4

95.9

94.2

90.4

79.0

85.3

95.5

94.3

96.2

S. marcescens

          

Imipenem

N

83/91

18/20

30/31

37/41

-

-

23/26

-

10/11

 

%S

91.2

90.0

96.8

90.2

-

-

88.5

-

90.9

Meropenem

N

203/210

77/78

70/71

138/144

42/45

14/15

220/234

25/25

69/70

 

%S

96.7

98.7

98.6

95.8

93.3

93.3

94.0

100

98.6

A. baumannii

          

Imipenem

N

72/148

13/30

35/39

21/35

-

-

30/30

-

7/11

 

%S

48.6

43.3

89.7

60.0

-

-

100

-

63.6

Meropenem

N

48/321

29/118

37/139

95/220

43/141

14/51

202/333

8/48

21/96

 

%S

15.0

24.6

27.0

43.2

30.4

27.5

60.7

16.7

21.9

a Data on El Salvador, Jamaica and Nicaragua not included in the analysis by country because fewer than 50 isolates collected.

The most active antimicrobial agents against non-ESBL producing K. pneumoniae were tigecycline (MIC90 1 μg/mL), carbapenems (imipenem MIC90 0.5 μg/mL and meropenem MIC90 0.25 μg/mL) and amikacin (MIC90 8 μg/mL) (Table1). All tested antimicrobial agents displayed reduced activity against ESBL-producing K. pneumoniae, with only imipenem and tigecycline recording percentage susceptibilities of >90% (96.0% and 93.7%, respectively). In particular, susceptibilities to levofloxacin against ESBL-producing isolates of E. coli and K. pneumoniae were lower when compared with non-ESBL-producing strains (11.5% vs. 60.9% and 38.2% vs 80.1%, respectively) (Table1). Among K. pneumoniae 35.3% were ESBL producers and percentages ranged from 17.2% (36/209) in Venezuela to 73.3% (55/75) in Honduras (Figure1). Both ESBL and non-ESBL-producing K. pneumoniae displayed higher resistance levels to carbapenemes than E. coli in all countries (Table2).

Amikacin, carbapenems and tigecycline were the most active agents against K. oxytoca (>94% susceptibility) and Enterobacter spp. (>89% susceptibility). Against isolates of S. marcescens the carbapenems and tigecycline were the most active agents (>91% susceptibility) (Table1). Among these three species rates of susceptibility to the carbapenems were ≥90% in all countries where data were available, with the exception of susceptibility to meropenem among isolates of Enterobacter spp. collected in Guatemala and Honduras (79.0% and 85.3%, respectively) and susceptibility to imipenem among isolates of S. marcescens from Mexico (88.5%) (Table2).

Almost all of antimicrobials in the panel were active against H. influenzae with susceptibility varying from 78.7% for ampicillin to 100% for ceftriaxone, imipenem, levofloxacin, and meropenem (Table1). Almost 20% of isolates (181/908) were β-lactamase producers.

For A. baumannii susceptibility was less than 50% for seven of the nine antimicrobial agents (Table1). The most active agents were minocycline (89.4%, MIC90 8 μg/mL) and imipenem (62.5%, MIC90 ≥32 μg/mL). Tigecycline showed good activity against A. baumannii: although no breakpoints are available for this agent, 95.8% of the isolates displayed an MIC ≤2 μg/mL. Low rates of carbapenem susceptibility were observed in most countries (Table2); the lowest rates were reported for meropenem among isolates from Argentina (15.0%) and Panama (16.7%). A total of 600 isolates (33.2%) were multidrug-resistant, among them the MIC90 for minocycline and tigecycline were 8 and 2 μg/mL, respectively.

Among P. aeruginosa collected the most active agents were piperacillin-tazobactam, with 75.3% of isolates susceptible (MIC90 ≥256 μg/mL), and amikacin with 71.8% (MIC90 ≥128 μg/mL) (Table1).

Discussion

This study reports on rates of antimicrobial susceptibility among important Gram-negative organisms collected from centers in Latin America between 2004 and 2010. It provides an update to the work of Rossi et al.[7] who reported on Gram-negative and Gram-positive organisms collected as part of T.E.S.T. between 2004 and 2007. The isolates reported on by Rossi et al.[7] are also included in the dataset studied in this report. Rates of ESBL-producing E. coli and K. pneumoniae are similar to the mentioned study and are also similar to those reported by Villegas et al.[3] for Latin American isolates collected in 2008 as part of the SMART study.

This study shows important variations in the rate of ESBL production by country, reaching values around 40% in E. coli and >50% for K. pneumoniae, which are similar to those observed in the Asia/Pacific region by Farrell et al.[12] for both organisms and by Hawser et al. 2009[13] for E. coli. However, it should be noted that these rates may be affected by the type of infection and population analyzed in each particular center or even by ward[2]. Considering that these are common nosocomial pathogens causing severe morbidity and mortality in critically ill patients and that the available choices of antibiotic treatments for these microorganisms are seriously reduced, there is increasing clinical concern for successful patient management where ESBL isolates are prevalent. Antimicrobial susceptibility rates were lower among ESBL-producing isolates when compared with non-ESBL producers with the exception of tigecycline, imipenem and meropenem where little or no changes in susceptibility (<6.0%) were observed between both groups. ESBL-producing K. pneumoniae are frequently associated with multidrug resistance[14]. In particular, susceptibility to commonly-used antimicrobials including piperacillin-tazobactam and fluoroquinolones was reduced among ESBL-producing isolates. The worrying increase in resistance to these antibiotics among ESBL-producing organisms has been associated with the simultaneous presence of other resistance determinants[1517]. The most common risk factor for resistance to fluoroquinolones in ESBL-producing strains is a previous history of high-level consumption of both extended-spectrum cephalosporin and quinolone antibiotics. These antibiotics are widely used in the region: Wirth et al. reported an increased use of fluoroquinolones in Latin America over a period of 10 years (1997–2007), where in some countries consumption doubled or even tripled[18].

It has been previously reported that tigecycline and carbapenems, along with amikacin, are highly active against the Enterobacteriaceae collected from countries in Latin American[19, 20]. In the current study, susceptibility to tigecycline ranged between 99.8% against ESBL-producing E. coli to 93.7% against ESBL-producing K. pneumoniae. Imipenem susceptibility ranged between 100% against K. oxytoca to 91.7% against S. marcescens and meropenem susceptibility ranged between 98.6% against non-ESBL-producing E. coli to 89.0% against ESBL-producing K. pneumoniae. The range of tigecycline MICs was greater than reported by Rossi et al.[7] against E. coli, K. pneumoniae, and Enterobacter spp.; however, this was due to single isolates at the top of the testing range (MIC ≥32 mg/L).

It is worth noting that resistance to meropenem has been observed across Latin America among members of the Enterobacteriaceae. The situation may not appear as poor for imipenem, with higher rates of susceptibility reported. However, it should be noted that imipenem susceptibility testing stopped in 2006 and switched to meropenem, meaning that the results for meropenem give a more current picture of carbapenem susceptibility in Latin America. In the late 1990s and early part of the 21st century, carbapenem resistance in Enterobacteriaceae was infrequent and resistance mechanisms were related to the presence of ESBL or overproduction of AMP-C β-lactamases associated with reduced outer membrane permeability[21, 22]. Enterobacteriaceae producing carbapenemases were first reported in the USA[23] and have now been reported in various parts of the world, including several countries in Latin America where class A carbapenemase KPC-2 enzymes are prevalent[5, 2426]. The results of this study, along with reports of decreasing susceptibility to imipenem among Klebsiella spp. in Latin America[27] demonstrate the importance of antimicrobial resistance surveillance and further analysis of the carbapenem-resistant Enterobacteriaceae identified in this dataset is warranted.

H. influenzae are frequently susceptible to available antimicrobials. In this study susceptibility was >98% to the agents tested, with the exception of ampicillin (78.7% susceptible) largely due to the production of β-lactamase. This is in agreement with the global T.E.S.T. findings published by Garrison et al.[28].

A. baumannii is a problematic organism frequently associated with multidrug resistance and 33.2% of the isolates in this study were defined as such. The antimicrobial with the highest rate of susceptibility against the whole A. baumannii population was minocycline. Tigecycline was also active, with 95.8% of isolates displaying an MIC ≤2mg/L. These results are similar to those reported by Rossi et al.[7] for Latin America isolates collected between 2004 and 2007 and Garrison et al.[24] who reported on a global collection from the T.E.S.T. study collected between 2004 and 2007. Susceptibility to the carbapenems was 62.5% for imipenem and 33.9% for meropenem which are lower than the global rates reported by Garrison et al. (82.3% and 59.0%, respectively) and lower than the Latin American rates reported by Gales et al.[29] for Acinetobacter spp. collected between 2001 and 2004 (86.4% and 83.6%, respectively). Susceptibility also varied by country, Tognim et al.[30] reported as part of the SENTRY study that carbapenem resistance among Acinetobacter spp. varied between countries within Latin America with Argentina a particular ‘hot spot’ of resistance. Our results suggest this is a continuing situation with the lowest rates of susceptibility to meropenem reported among isolates from Argentina.

Conclusions

Surveillance of antimicrobial susceptibility plays a key role in guiding appropriate antimicrobial therapy. In this study the carbapenems and tigecycline continue to be active against the Enterobacteriaceae and A. baumannii; however, there is cause for concern with carbapenem non-susceptible isolates reported in all countries included in this study. The in vitro activity (MIC90) of tigecycline was similar to that reported for isolates collected during Phase 3 clinical trials[31].

Declarations

Acknowledgements

The authors wish to acknowledge and thank the Latin American T.E.S.T. investigators and laboratories for their participation in this study, as well as the staff at IHMA for their coordination of T.E.S.T and Dr. Marcela Radice for revision of and critical discussion regarding this manuscript. This study was sponsored by Pfizer Inc.

No authors were paid for their contributions to this manuscript.

Medical writing support was provided by Wendy Hartley PhD at Micron Research Ltd, Chatteris, UK and was funded by Pfizer Inc. Micron Research Ltd also provided data management services which were funded by Pfizer Inc.

Authors’ Affiliations

(1)
Laboratorio de Microbiología, Hospital Aleman
(2)
Pfizer Inc

References

  1. Moet GJ, Jones RN, Biedenbach DJ, Stilwell MG, Fritsche TR: Contemporary causes of skin and soft tissue infections in North America, Latin America, and Europe: report from the SENTRY Antimicrobial Surveillance Program (1998–2004). Diagn Microbiol Infect Dis. 2007, 57: 7-13. 10.1016/j.diagmicrobio.2006.05.009View ArticlePubMedGoogle Scholar
  2. Villegas MV, Kattan JN, Quinteros MG, Casellas JM: Prevalence of extended-spectrum β-lactamases in South America. Clin Microbiol Infect. 2008, 14 (Suppl 1): 154-158.View ArticlePubMedGoogle Scholar
  3. Villegas MV, Blanco MG, Sifuentes-Osornio J, Rossi F: Increasing prevalence of extended-spectrum-β-lactamase among Gram-negative bacilli in Latin America - 2008 update from the Study for Monitoring Antimicrobial Resistance Trends (SMART). Braz J Infect Dis. 2011, 15: 34-39.PubMedGoogle Scholar
  4. Dhillon RHP, Clark J: ESBLs: a clear and present danger?. Crit Care Res Pract. 2012, 2012: 625170-Epub 2011 Jun 6,PubMedPubMed CentralGoogle Scholar
  5. Gomez SA, Pasteran FG, Faccone D, Tijet N, Rapoport M, Lucero C, Lastovetska O, Albornoz E, Galas M, Melano RG, Corso A, Petroni A,: Clonal dissemination of Klebsiella pneumoniae ST258 harbouring KPC-2 in Argentina. Clin Microbiol Infect. 2011, 17: 1520-1524. 10.1111/j.1469-0691.2011.03600.xView ArticlePubMedGoogle Scholar
  6. Neonakis IK, Spandidos DA, Petinaki E: Confronting multidrug-resistant Acinetobacter baumannii: a review. Int J Antimicrob Agents. 2011, 37: 102-109. 10.1016/j.ijantimicag.2010.10.014View ArticlePubMedGoogle Scholar
  7. Rossi F, García P, Ronzon B, Curcio D, Dowzicky MJ: Rates of antimicrobial resistance in Latin America (2004–2007) and in vitro activity of the glycylcycline tigecycline and of other antibiotics. Braz J Infect Dis. 2008, 12: 405-415.View ArticlePubMedGoogle Scholar
  8. Clinical and Laboratory Standards Institute: Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically, Approved standard. 2009, ISBN ISBN 1-56238-689-1, PA: Document M7-A8. Clinical and Laboratory Standards Institute Wayne, 8,Google Scholar
  9. Clinical and Laboratory Standards Institute: Performance standard for antimicrobial susceptibility testing: 20th information supplement. Document M100-S20. 2010, Wayne, PA: Clinical and Laboratory Standards Institute,Google Scholar
  10. Clinical and Laboratory Standards Institute: Performance standard for antimicrobial susceptibility testing: 20th informational supplement (June 2010 update). 2010, Wayne, PA: Document M100-S20U, Clinical and Laboratory Standards Institute,Google Scholar
  11. Tygacil® Product Insert.http://www.pfizerpro.com/hcp/tygacil,
  12. Farrell DJ, Turnidge JD, Bell J, Sader HS, Jones RN: The in vitro evaluation of tigecycline tested against pathogens isolates in eight countries in the Asia-Western Pacific region (2008). J Infect. 2010, 60: 440-451. 10.1016/j.jinf.2010.03.024View ArticlePubMedGoogle Scholar
  13. Hawser SP, Bouchillon SK, Hoban DJ, Badal RE, Hsueh PR, Paterson DL: Emergence of high levels of extended-spectrum-β-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: 3280-3284. 10.1128/AAC.00426-09View ArticlePubMedPubMed CentralGoogle Scholar
  14. Mosqueda-Gómez JL, Montaño-Loza A, Rolón AL, Cervantes C, Bobadilla-del-Valle JM, Silva-Sánchez J, Garza-Ramos U, Villasís-Keever A, Galindo-Fraga A, Palacios GM, Ponce-de-León A, Sifuentes-Osornio J: Molecular epidemiology and risk factors of bloodstream infections caused by extended-spectrum β-lactamase-producing Klebsiella pneumoniae A case–control study. Int J Infect Dis. 2008, 12: 653-659. 10.1016/j.ijid.2008.03.008View ArticlePubMedGoogle Scholar
  15. Paterson DL, Bonomo RA: Extended-spectrum beta-lactamases: a clinical update. Clin Microbiol Rev. 2005, 18: 657-686. 10.1128/CMR.18.4.657-686.2005View ArticlePubMedPubMed CentralGoogle Scholar
  16. Martinez-Martinez L, Pascual A, Conejo Mdel C, Garcia I, Joyanes P, Domenech-Sanchez A, Benedi VJ: Energy-dependent accumulation of norfloxacin and porin expression in clinical isolates of Klebsiella pneumoniae and relationship to extended-spectrum beta-lactamase production. Antimicrob Agents Chemother. 2002, 46: 3926-3932. 10.1128/AAC.46.12.3926-3932.2002View ArticlePubMedPubMed CentralGoogle Scholar
  17. Patterson JE, Hardin TC, Kelly CA, Gracia RC, Jorgensen JH: Association of antibiotic utilization measures and control of multiple-drug resistance in Klebsiella pneumoniae. Infect Control Hosp Epidemiol. 2000, 21: 455-458. 10.1086/501787View ArticlePubMedGoogle Scholar
  18. Wirtz VJ, Dreser A, Gonzales R: Trends in antibiotic utilization in eight Latin American countries, 1997–2007. Rev Panam Salud Publica. 2010, 27: 219-225.View ArticlePubMedGoogle Scholar
  19. Fernández Canigia L, Kaufman S, Lanata L, Vay C, Giovanakis M, Bantar C: Multicenter study to assess the in vitro activity of tigecycline by disk diffusion test against clinical isolates from Argentina. Chemotherapy. 2009, 55: 20-27. 10.1159/000167788View ArticlePubMedGoogle Scholar
  20. Bantar C, Curcio D, Fernández Canigia L, García P, Guzmán Blanco M, Leal AL,: Comparative in vitro activity of tigecycline against bacteria recovered from clinical specimens in Latin America. J Chemother. 2009, 21: 144-152.View ArticlePubMedGoogle Scholar
  21. Melano R, Corso A, Petroni A, Centron D, Orman B, Pereyra A, Moreno N, Galas M: Multiple antibiotic-resistance mechanisms including a novel combination of extended-spectrum β-lactamases in a Klebsiella pneumoniae clinical strain isolated in Argentina. J Antimicrob Chemother. 2003, 52: 36-42. 10.1093/jac/dkg281View ArticlePubMedGoogle Scholar
  22. Martínez-Martínez L, Pascual A, Hernández-Allés S, Alvarez-Diaz D, Suárez AI, Tran J, Benedí VJ, Jacoby GA: Roles of β-lactamases and porins in activities of carbapenems and cephalosporins against Klebsiella pneumoniae. Antimicrob Agents Chemother. 1999, 43: 1669-1673.PubMedPubMed CentralGoogle Scholar
  23. Bratu S, Landman D, Haag R, Recco R, Eramo A, Alam M, Quale J: Rapid spread of carbapenem-resistant Klebsiella pneumoniae in New York City: a new threat to our antibiotic armamentarium. Arch Intern Med. 2005, 165: 1430-1435. 10.1001/archinte.165.12.1430View ArticlePubMedGoogle Scholar
  24. Radice M, Power P, Gutkind G, Fernández K, Vay C, Famiglietti A, Ricover N, Ayala JA: First class A carbapenemase isolates from Enterobacteriaceae in Argentina. Antimicrob Agents Chemother. 2004, 48: 1068-1069. 10.1128/AAC.48.3.1068-1069.2004View ArticlePubMedPubMed CentralGoogle Scholar
  25. Pasteran FG, Otaegui L, Guerriero L, Radice G, Maggiora R, Rapoport M, Faccone D, Di Martino A, Galas M: Klebsiella pneumoniae carbapenemase-2, Buenos Aires, Argentina. Emerg Infect Dis. 2008, 14: 1178-1180. 10.3201/eid1407.070826View ArticlePubMedPubMed CentralGoogle Scholar
  26. Villegas MV, Lolans K, Correa A, Suarez CJ, Lopez JA, Vallejo M, Quinn JP,: First detection of the plasmid-mediated class A carbapenemase KPC-2 in clinical isolates of Klebsiella pneumoniae from South America. Antimicrob Agents Chemother. 2006, 50: 2880-2882. 10.1128/AAC.00186-06View ArticlePubMedGoogle Scholar
  27. Gales AC, Jones RN, Sader HS: Contemporary activity of colistin and polymyxin B against a worldwide collection of Gram-negative pathogens: results from the SENTRY antimicrobial surveillance program (2006–2009). J Antimicrob Chemother. 2011, 66: 2070-2074. 10.1093/jac/dkr239View ArticlePubMedGoogle Scholar
  28. Garrison MW, Mutters R, Dowzicky MJ: In vitro activity of tigecycline and comparator agents against a global collection of Gram-negative and Gram-positive organisms: tigecycline Evaluation and Surveillance Trial 2004 to 2007. Diagn Microbiol Infect Dis. 2009, 65: 288-299. 10.1016/j.diagmicrobio.2009.07.010View ArticlePubMedGoogle Scholar
  29. Gales AC, Jones RN, Sader HS: Global assessment of the antimicrobial activity of polymyxin B against 54 731 clinical isolates of Gram-negative bacilli: report from the SENTRY antimicrobial surveillance programme (2001–2004). Clin Microbiol Infect. 2006, 12: 315-321. 10.1111/j.1469-0691.2005.01351.xView ArticlePubMedGoogle Scholar
  30. Tognim MC, Andrade SS, Silbert S, Gales AC, Jones RN, Sader HS: Resistance trends of Acinetobacter spp. in Latin America and characterization of international dissemination of multi-drug resistant strains: five-year report of the SENTRY Antimicrobial Surveillance Program. Int J Infect Dis. 2004, 8: 284-291. 10.1016/j.ijid.2003.11.009View ArticlePubMedGoogle Scholar
  31. Bradford PA, Weaver-Sands DT, Petersen PJ: In vitro activity of tigecycline against isolates from patients enrolled in Phase 3 clinical trials of treatment for complicated skin and skin-structure infections and complicated intra-abdominal infections. Clin Infect Dis. 2005, 41: S315-S332. 10.1086/431673View ArticlePubMedGoogle Scholar

Copyright

© Fernández-Canigia and Dowzicky; licensee BioMed Central Ltd. 2012

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Advertisement