Open Access

Emerging resistance among bacterial pathogens in the intensive care unit – a European and North American Surveillance study (2000–2002)

  • Mark E Jones1Email author,
  • Deborah C Draghi1,
  • Clyde Thornsberry1,
  • James A Karlowsky1,
  • Daniel F Sahm1 and
  • Richard P Wenzel2
Annals of Clinical Microbiology and Antimicrobials20043:14

https://doi.org/10.1186/1476-0711-3-14

Received: 04 June 2004

Accepted: 29 July 2004

Published: 29 July 2004

Abstract

Background

Globally ICUs are encountering emergence and spread of antibiotic-resistant pathogens and for some pathogens there are few therapeutic options available.

Methods

Antibiotic in vitro susceptibility data of predominant ICU pathogens during 2000–2 were analyzed using data from The Surveillance Network (TSN) Databases in Europe (France, Germany and Italy), Canada, and the United States (US).

Results

Oxacillin resistance rates among Staphylococcus aureus isolates ranged from 19.7% to 59.4%. Penicillin resistance rates among Streptococcus pneumoniae varied from 2.0% in Germany to as high as 20.2% in the US; however, ceftriaxone resistance rates were comparably lower, ranging from 0% in Germany to 3.4% in Italy. Vancomycin resistance rates among Enterococcus faecalis were ≤ 4.5%; however, among Enterococcus faecium vancomycin resistance rates were more frequent ranging from 0.8% in France to 76.3% in the United States. Putative rates of extended-spectrum β-lactamase (ESBL) production among Enterobacteriaceae were low, <6% among Escherichia coli in the five countries studied. Ceftriaxone resistance rates were generally lower than or similar to piperacillin-tazobactam for most of the Enterobacteriaceae species examined. Fluoroquinolone resistance rates were generally higher for E. coli (6.5% – 13.9%), Proteus mirabilis (0–34.7%), and Morganella morganii (1.6–20.7%) than other Enterobacteriaceae spp (1.5–21.3%). P. aeruginosa demonstrated marked variation in β-lactam resistance rates among countries. Imipenem was the most active compound tested against Acinetobacter spp., based on resistance rates.

Conclusion

There was a wide distribution in resistance patterns among the five countries. Compared with other countries, Italy showed the highest resistance rates to all the organisms with the exception of Enterococcus spp., which were highest in the US. This data highlights the differences in resistance encountered in intensive care units in Europe and North America and the need to determine current local resistance patterns by which to guide empiric antimicrobial therapy for intensive care infections.

Keywords

Intensive-care unit antibiotic susceptibility

Background

Antimicrobial resistance has emerged as an important factor in predicting outcomes and overall resource use after infections in intensive care units (ICU) [1]. Globally ICUs are encountering emergence and spread of antibiotic-resistant pathogens. For some pathogens there are few therapeutic options available, e.g., vancomycin-resistant Enterococcus faecium. Awareness of these problems has been underscored with data from a number of surveillance studies aimed at improving the use of empiric therapy. In the United States there have been several national programs, which have focused on both the etiology of infections and resistance patterns of nosocomial or ICU infections including the National Nosocomial Infections Surveillance (NNIS) [2] and more recently an ICU-specific study examining the epidemiology of antimicrobial resistance, Project ICARE [3, 4]. Stephen et al. collected strains from 28 ICUs from across the United States as part of the SENTRY Antimicrobial Surveillance Program in 2001 [5].

European data on the antimicrobial resistance of ICU pathogens has also been collected in several recent surveillance studies. A large prevalence survey of nosocomial infections in ICUs in 17 countries was published in 1995 [6], and more recently a number of nation-specific surveys were reported [79]. Several key points emerge: first, antimicrobial resistance among ICU pathogens is generally increasing, but variations do exist among different countries, probably due to individual antimicrobial use patterns; second, when new medical practices and alternative antimicrobials are introduced changes in the dominant microbial etiologies may emerge prompting novel empiric selections; and third, the standards of hygiene and infection control also vary across countries. Finally, appropriate therapy of ICU infections directed by local resistance data can have significant consequences for both patient and the healthcare system. It is against this background that local resistance surveillance programs are of most value in developing appropriate therapeutic guidelines for specific infections and patient types. For example, the recent modification to the American Thoracic Society guidelines for the treatment of hospital-acquired pneumonia [10] considered contemporary resistance data. Local surveillance data can be applied to other infections to assist in local formulary policy such as those governing treatment of nosocomial urinary tract infections [11].

This study using TSN program reports the antimicrobial resistance profiles of bacterial isolates from ICU patients in five countries during the period 2000–2002. The relevance of these recent nation-specific data will be discussed on a country-by-country basis, as part of improving and updating empiric therapeutic approaches to specific pathogens causing infections in the ICU setting according to each country. These surveillance programs help to maintain current knowledge of susceptibilities and relevant treatment options.

Methods

TSN Database – United States and Europe

TSN is a queriable, real-time database that electronically assimilates daily antimicrobial susceptibility testing and patient demographic data from a network of geographically dispersed laboratories in the United States (283 hospital sites), France (63 hospital sites), Germany (169 hospital sites), Italy (48 hospital sites) and Canada (87 hospital sites) [12].

Laboratories included in TSN include those servicing university, community, and private hospitals with bed sizes ranging from 100 to >1000 beds. Routine diagnostic susceptibility testing results are collected daily from each participating laboratory. The methods used by these laboratories include VITEK (bioMérieux, St. Louis, MO), MicroScan (Dade-Microscan, Sacramento, CA), Sceptor and Pasco MIC/ID (Becton Dickinson, Sparks, MD) and Etest (AB Biodisk, Solna, Sweden), as well as manual broth microdilution MIC, disk diffusion and agar dilution. TSN reflects current testing in participant laboratories and represents the data reported to physicians from the respective laboratories [13].

Although some European countries have alternate breakpoints, all data forwarded to TSN Databases are derived from hospitals that utilized NCCLS standards and definitions (United States, Canada, Italy, and Germany) [14] or the Comité de L'Antibiogramme de La Societé Français de Microbiologie (France) [15] thus standardizing datasets. Results were interpreted as susceptible, intermediate (if available), or resistant in TSN, based upon the NCCLS interpretative guidelines in place during 2001 [16]. In addition, a series of quality-control filters (i.e., critical rule sets) were used in TSN to screen susceptibility test results for patterns indicative of testing error and suspect results were removed from analysis for laboratory confirmation. In TSN, any result from the same patient with the same organism identification and the same susceptibility pattern received within five days was considered a repeat culture and was counted only once in the database.

Bacterial species and antimicrobials tested

For this study, data from TSN results for each individual database from January 1, 2000 through to December 31, 2002 were included in the analysis to determine the proportion of species and their susceptibility to antimicrobial agents commonly tested in clinical laboratories throughout the participating regions. Only isolates derived from patients located in hospital ICUs were considered in the analysis. Gram-positive species included in the analysis were comprised of S. aureus, coagulase negative staphylococci, Enterococcus faecalis,Enterococcus faecium, Streptococcus pyogenes, Streptococcus pneumoniae and viridans group streptococci. Gram-negative species studied comprised the predominantly encountered enteric species (Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae, Proteus mirabilis, Morganella morganii and Serratia marcescens), and Pseudomonas aeruginosa and Acinetobacter spp.

The antibiotics studied are listed in Tables 2,3,4,5. Among E. coli, putative ESBL production was defined as those isolates that were intermediate or resistant (non-susceptible) to ceftazidime [17]. Given the large number of isolate results included in the majority of analyses in this study, statistical analysis was not performed, as even subtle differences in percent resistance (<1%) to an antimicrobial agent for any time period or demographic parameters would be reported as highly significant (P <0.001).
Table 2

S. aureus, Coagulase-negative staphylococci, E. faecalis, and E. faecium isolated from ICU patients during 2000–2002

  

United States

Canada

Italy

Germany

Francea

Organism

Agent

Total n

%S

%R

Total n

%S

%R

Total n

%S

%R

Total n

%S

%R

Total n

%S

%R

Staphylococcus aureus

Ampicillin

19,703

6.7

93.3

3,792

12.6

87.4

1,665

5.6

94.4

2,867

16.2

83.8

15

6.7

93.3

 

Cefepime

1,260

52.9

46.9

NTb

NT

NT

304

15.8

84.2

483

80.5

17.0

<10

NAc>

NA

 

Cefotaxime

6,898

50.2

49.7

220

55.5

44.5

671

36.4

63.6

729

92.0

8.0

490

63.9

36.1

 

Ceftriaxone

5,914

45.6

54.3

153

69.3

30.7

1,048

28.1

71.8

220

88.6

11.4

23

73.9

26.1

 

Ciprofloxacin

24,350

47.4

51.0

5,958

74.5

24.1

4,600

39.7

58.6

5,243

73.4

26.1

316

57.0

40.5

 

Gentamicin

35,034

85.6

13.7

6,641

89.4

10.3

5,531

40.9

58.0

5,735

90.0

9.7

10,100

90.4

9.4

 

Oxacillin

44,939

47.7

52.3

10,105

80.3

19.7

6,147

40.6

59.4

6,475

79.0

21.0

10,512

59.4

40.6

 

Teicoplanin

NT

NT

NT

NT

NT

NT

5,868

100

0

4,632

99.8

0.2

8,232

100

0

 

Vancomycin

43,245

100

0

7,882

100

0

5,937

100

0

5,276

100

0

9,453

100

0

Staphylococcus aureus

                

OSSA

Ampicillin

9,047

14.5

85.5

3,055

15.7

84.3

741

12.6

87.4

2,414

19.3

80.7

10

0

100

 

Cefepime

672

99.1

0.4

NT

NT

NT

49

98.0

2.0

387

99.5

0.3

NT

NT

NT

 

Cefotaxime

3,451

99.7

0.2

122

100

0

244

100

0

653

100

0

312

100

0

 

Ceftriaxone

2,707

99.5

0.2

106

100

0

295

99.0

0.3

194

100

0

16

100

0

 

Ciprofloxacin

11,827

91.2

6.5

4,692

93.5

4.8

1,902

91.4

4.9

4,171

91.4

8.0

188

90.4

6.4

 

Gentamicin

16,951

98.3

1.4

5,384

98.1

1.8

2,223

95.1

4.5

4,527

98.4

1.5

5,958

99.4

0.5

 

Oxacillin

21,416

100

0

8,110

100

0

2,495

100

0

5,115

100

0

6,244

100

0

 

Teicoplanin

NT

NT

NT

NT

NT

NT

2,402

100

0

3,593

99.9

0.1

5,018

100

0

 

Vancomycin

20,110

100

0

6,046

100

0

2,430

100

0

4,002

100

0

5,580

100

0

Staphylococcus aureus

                

ORSA

Ampicillin

10,656

0

100

737

0

100

924

0

100

453

0

100

<10

NA

NA

 

Cefepime

588

0

100

NT

NT

NT

255

0

100

96

4.2

84.4

<10

NA

NA

 

Cefotaxime

3,447

0.6

99.3

98

0

100

427

0

100

76

23.7

76.3

178

0.6

99.4

 

Ceftriaxone

3,207

0

100

47

0

100

753

0.3

99.7

26

3.8

96.2

<10

NA

NA

 

Ciprofloxacin

12,523

6.1

93.1

1,266

3.9

95.5

2,698

3.3

96.4

1,072

3.3

96.6

128

7.8

90.6

 

Gentamicin

18,083

73.7

25.2

1,257

52.0

46.8

3,308

4.5

94.0

1,208

58.7

40.5

4,142

77.5

22.2

 

Oxacillin

23,523

0

100

1,995

0.2

99.8

3,652

0

100

1,360

0

100

4,268

0

100

 

Teicoplanin

NT

NT

NT

NT

NT

NT

3,466

100

0

1,039

99.7

0.3

3,214

100

0

 

Vancomycin

23,135

100

0

1,836

100

0

3,507

100

0

1,274

100

0

3,873

100

0

Staphylcoccus species, coagulase-negative

                
 

Ampicillin

16,288

5.7

94.3

3,533

6.3

93.7

2,142

10.6

89.4

4,075

8.1

91.9

<10

NA

NA

 

Cefepime

991

11.8

88.1

<10

NA

NA

116

0

100

625

11.0

73.1

<10

NA

NA

 

Cefotaxime

5,538

17.7

82.3

240

17.9

82.1

335

16.7

83.3

625

37.4

62.4

174

28.7

69.0

 

Ceftriaxone

3,471

14.8

84.8

116

22.4

77.6

512

11.7

88.3

412

25.0

74.8

<10

NA

NA

 

Ciprofloxacin

18,829

40.2

58.3

5,366

44.4

54.7

5,102

42.7

54.0

6,197

29.5

67.6

198

44.4

53.0

 

Gentamicin

27,248

51.5

38.1

5,571

40.6

47.3

5,241

33.8

60.7

6,848

41.5

51.7

9,422

46.8

51.5

 

Oxacillin

35,135

15.8

84.2

9,172

20.6

79.4

5,961

15.2

84.8

7,442

18.6

81.4

9,884

30.1

69.9

 

Teicoplanin

NT

NT

NT

NT

NT

NT

5,797

93.7

2.4

5,096

95.6

0.7

7,670

84.6

3.1

 

Vancomycin

34,424

100

0

8,239

100

0

5,937

100

0

6,953

100

0

8,300

100

0

Staphylcoccus species, coagulase-negative

                

Oxacillin susceptible

Ampicillin

2,582

35.7

64.3

638

34.6

65.4

437

51.7

48.3

824

39.6

60.4

<10

NA

NA

 

Cefepime

117

100

0

NT

NT

NT

NT

NT

NT

<10

NA

NA

NT

NT

NT

 

Cefotaxime

978

99.5

0.2

42

100

0

56

100

0

128

100

0

54

92.6

0

 

Ceftriaxone

523

98.3

0.4

26

100

0

59

100

0

103

100

0

<10

NA

NA

 

Ciprofloxacin

2,844

82.4

16.6

988

91.8

7.6

779

87.7

10.1

1,103

89.5

9.2

78

83.3

14.1

 

Gentamicin

4,424

93.5

4.2

1,068

91.9

5.3

698

94.3

5.3

1,263

96.5

2.7

2,822

93.9

5.4

 

Oxacillin

5,565

100

0

1,886

99.9

0.1

904

100

0

1,383

100

0

2,980

100

0

 

Teicoplanin

NT

NT

NT

NT

NT

NT

890

99.1

0.3

691

98.4

0.3

2,454

95.8

0.2

 

Vancomycin

5,240

100

0

1,587

100

0

897

100

0

981

100

0

2,467

100

0

Staphylcoccus species, coagulase-negative

                

Oxacillin resistant

Ampicillin

13,706

0.1

99.9

2,895

0

100

1,705

0

100

3,251

0.2

99.8

<10

NA

NA

 

Cefepime

874

0

99.9

<10

NA

NA

116

0

100

624

10.9

73.2

<10

NA

NA

 

Cefotaxime

4,560

0.1

99.9

198

0.5

99.5

279

0

100

497

21.3

78.5

120

0

100

 

Ceftriaxone

2,948

0

99.8

90

0

100

453

0.2

99.8

309

0.0

99.7

<10

NA

NA

 

Ciprofloxacin

15,985

32.7

65.8

4,378

33.7

65.3

4,323

34.7

61.9

5,094

16.5

80.2

120

19.2

78.3

 

Gentamicin

22,824

43.3

44.7

4,503

28.5

57.3

4,543

24.5

69.2

5,585

29.1

62.8

6,600

26.6

71.3

 

Oxacillin

29,570

0

100

7,286

0

100

5,057

0

100

6,059

0

100

6,904

0

100

 

Teicoplanin

NT

NT

NT

NT

NT

NT

4,907

92.7

2.8

4,405

95.1

0.8

5,216

79.3

4.5

 

Vancomycin

29,184

100

0

6,652

100

0

5,040

100

0

5,972

100

0

5,833

100

0

Enterococcus faecalis

                
 

Ampicillin

7,865

98.8

1.2

1,000

99.4

0.6

1,289

95.3

4.7

1,902

99.6

0.4

1,183

99.5

0.2

 

Ciprofloxacin

3,311

56.9

38.7

625

45.3

50.4

1,159

64.0

31.1

2,012

39.7

39.5

559

78.5

17.0

 

Gentamicin (HL Testing)

5,503

65.1

34.8

706

63.0

36.8

1,156

62.9

37.1

965

64.8

35.2

1,563

63.6

13.4

 

Teicoplanin

NT

NT

NT

<10

NA

NA

1,248

97.1

2.4

1,294

99.7

0.2

1,747

99.9

0.1

 

Vancomycin

7,656

95.1

4.5

1,005

98.3

0.9

1,303

96.7

2.8

1,636

99.4

0.3

1,811

99.7

0.2

Enterococcus faecium

                
 

Ampicillin

3,896

9.7

90.3

383

17.2

82.8

260

21.5

78.5

481

12.3

87.7

151

41.7

49.7

 

Ciprofloxacin

1,846

5.3

92.5

221

10.9

85.5

234

10.3

77.4

591

6.9

73.9

66

21.2

39.4

 

Gentamicin (HL Testing)

2,512

57.5

42.5

291

59.5

40.5

223

67.7

32.3

349

60.2

39.8

263

65.4

12.2

 

Teicoplanin

23

8.7

87.0

<10

NA

NA

234

86.3

13.7

517

97.9

2.1

266

99.6

0.4

Vancomycin

4,066

23.2

76.3

415

85.1

14.5

264

75.4

24.2

628

93.9

4.8

247

98.4

0.8

 

aNCCLS breakpoints were used for all countries, except (CA-SFM) bNot tested cNot applicable if <10 isolates were tested

Table 3

S. pneumoniae, S. pyogenes, S. agalactiae, and Viridans group streptococci isolated from ICU patients during 2000–2002

  

United States

Canada

Italy

Germany

Francea

Organism

Agent

Total n

%S

%R

Total n

%S

%R

Total n

%S

%R

Total n

%S

%R

Total n

%S

%R

Streptococcus pneumoniae

Amoxicillin

120

91.7

2.5

31

100

0

60

93.3

6.7

17

100

0

1,328

71.2

2.3

 

Cefepime

22

90.9

4.5

25

60.0

12.0

66

90.9

7.6

NTb

NT

NT

<10

NAc

NA

 

Cefotaxime

1,571

82.2

6.3

145

93.8

0.7

108

93.5

4.6

63

100

0

1,181

77.1

0.8

 

Ceftriaxone

2,373

88.3

3.2

145

91.7

0.7

145

91.7

3.4

29

100

0

544

80.1

0.6

 

Clarithromycin

184

71.7

25.5

56

69.6

30.4

90

64.4

31.1

<10

NA

NA

NT

NT

NT

 

Erythromycin

3,029

67.9

30.5

539

78.5

20.8

313

69.6

28.1

405

88.6

9.4

1,567

59.0

38.8

 

Levofloxacin

2,133

99.1

0.4

356

98.6

1.1

174

98.3

0.6

340

99.4

0.3

62

98.4

1.6

 

Penicillin

3,096

51.5

20.2

325

59.1

7.1

198

77.3

7.6

102

96.1

2.0

1,387

45.5

17.9

 

Vancomycin

2,865

100

-c

271

100

-

231

100

-

190

100

-

1,479

100

-

Streptococcus pyogenes

                
 

Amoxicillin

NT

NT

NT

NT

NT

NT

NT

NT

NT

NT

NT

NT

58

100

0

 

Cefepime

<10

NA

NA

NT

NT

NT

NT

NT

NT

NT

NT

NT

NT

NT

NT

 

Cefotaxime

32

100

-

29

100

-

<10

NA

NA

11

100

-

30

100

-

 

Ceftriaxone

75

100

-

<10

NA

NA

<10

NA

NA

<10

NA

NA

<10

NA

NA

 

Clarithromycin

19

84.2

5.3

<10

NA

NA

17

88.2

11.8

NT

NT

NT

NT

NT

NT

 

Erythromycin

118

92.4

6.8

102

81.4

11.8

59

74.6

23.7

63

84.1

11.1

170

82.9

14.7

 

Levofloxacin

71

97.2

1.4

<10

NA

NA

<10

NA

NA

61

77.0

4.9

NT

NT

NT

 

Penicillin

140

100

-

97

100

-

58

100

-

64

100

-

139

100

-

 

Vancomycin

121

100

-

42

100

-

12

100

-

34

100

-

162

100

-

Streptococcus agalactiae

                
 

Amoxicillin

NT

NT

NT

NT

NT

NT

NT

NT

NT

NT

NT

NT

165

100

0

 

Cefepime

28

100

-

NT

NT

NT

<10

NA

NA

NT

NT

NT

NT

NT

NT

 

Cefotaxime

71

100

-

17

100

-

24

100

-

50

100

-

50

100

-

 

Ceftriaxone

184

100

-

<10

NA

NA

38

100

-

37

100

-

<10

NA

NA

 

Clarithromycin

21

81.0

9.5

<10

NA

NA

21

71.4

28.6

NT

NT

NT

<10

NA

NA

 

Erythromycin

489

76.3

21.7

222

82.9

14.9

121

77.7

18.2

192

83.9

10.9

588

79.9

16.2

 

Levofloxacin

333

97.9

1.2

<10

NA

NA

51

98.0

0

180

91.1

1.7

173

99.4

0

 

Penicillin

518

100

-

226

100

-

145

100

-

184

100

-

369

100

-

 

Vancomycin

463

100

-

179

100

-

143

100

-

65

100

-

526

100

-

Streptococcus viridans group

                
 

Amoxicillin

NT

NT

NT

NT

NT

NT

NT

NT

NT

NT

NT

NT

268

92.9

0.7

 

Cefepime

23

95.7

4.3

NT

NT

NT

12

66.7

33.3

NT

NT

NT

NT

NT

NT

 

Cefotaxime

434

83.6

11.1

101

92.1

4.0

31

90.3

9.7

75

97.3

2.7

56

94.6

0

 

Ceftriaxone

678

87.3

7.7

130

89.2

3.8

99

81.8

18.2

40

97.5

2.5

<10

NA

NA

 

Clarithromycin

34

52.9

38.2

21

76.2

19.0

21

71.4

23.8

<10

NA

NA

NT

NT

NT

 

Erythromycin

959

57.2

37.7

289

71.6

23.2

192

64.6

32.8

796

88.1

9.2

626

59.9

31.6

 

Levofloxacin

331

96.1

2.7

<10

NA

NA

16

87.5

0

93

89.2

4.3

<10

NA

NA

 

Penicillin

1,047

63.7

6.2

303

79.2

0

61

78.7

8.2

<10

NA

NA

452

69.0

3.1

Vancomycin

1,095

100

-

276

100

-

180

100

-

277

100

-

580

100

-

 

aNCCLS breakpoints were used for all countries, except France (CA-SFM) bNot tested cBreakpoints do not currently exist to interpret as S (susceptible) or R (resistant)

Table 4

Enterobacteriaceae isolated from ICU patients during 2000–2002

  

United States

Canada

Italy

Germany

Francea

Organism

Agent

Total n

%S

%R

Total n

%S

%R

Total n

%S

%R

Total n

%S

%R

Total n

%S

%R

Escherichia coli

Cefepime

10,356

98.1

1.5

207

98.1

1.9

1,426

98.1

1.4

2,830

98.6

1.2

4,358

98.9

0.6

 

Cefotaxime

9,086

96.5

2.2

3,231

96.3

2.5

1,748

94.5

3.8

5,828

97.8

1.8

9,362

98.8

0.6

 

Ceftazidime

14,574

95.3

3.0

4,438

97.7

1.6

2,548

94.7

3.7

3,924

97.9

1.6

9,164

97.8

1.2

 

Ceftriaxone

15,897

97.4

1.7

3,829

96.8

2.2

1,423

94.4

4.2

534

99.8

0.2

834

98.6

1.0

 

Ciprofloxacin

17,294

89.0

10.7

5,028

90.3

9.5

2,616

87.0

12.7

4,615

86.7

12.4

8,577

93.1

6.5

 

Gentamicin

20,581

92.4

6.5

6,654

92.8

5.3

2,650

92.2

6.6

4,825

94.3

5.2

9,442

95.4

4.2

 

Imipenem

15,353

100

0

3,386

100

0

2,254

100

0

5,172

100

0

8,994

100

0

 

Levofloxacin

14,920

88.2

11.6

776

85.1

13.9

496

86.5

13.3

3,137

88.2

11.0

NTb

NT

NT

 

Piperacillin-tazobactam

13,573

93.1

3.6

4,305

95.1

2.4

1,879

95.8

2.4

5,637

93.6

3.4

7,255

95.4

1.1

 

Trimethoprim-sulfamethoxazole

20,296

79.2

20.7

6,737

84.6

15.3

2,440

75.0

24.9

5,598

73.1

26.6

9,028

78.2

21.1

Klebsiella oxytoca

                
 

Cefepime

1,476

96.2

3.3

19

100

0

255

99.6

0

566

96.8

2.7

478

97.1

0.4

 

Cefotaxime

1,324

92.7

4.7

486

94.2

4.5

230

96.5

1.7

1,117

93.8

4.4

865

96.3

0.8

 

Ceftazidime

1,909

91.7

7.0

661

94.9

4.1

361

83.4

15.2

749

95.3

4.5

870

98.3

0.5

 

Ceftriaxone

2,035

89.9

6.6

536

93.8

2.8

197

81.7

2.0

83

97.6

0

79

87.3

2.5

 

Ciprofloxacin

2,226

92.5

5.9

745

96.0

3.0

368

96.7

3.0

905

90.1

7.8

815

94.5

4.8

 

Gentamicin

2,569

89.9

8.3

857

95.0

4.9

366

89.6

3.0

1,016

98.2

1.2

865

97.1

2.4

 

Imipenem

2,061

100

0

516

100

0

337

100

0

1,062

100

0

845

100

0

 

Levofloxacin

1,754

93.3

3.4

159

96.9

1.3

133

97.0

3.0

560

94.6

3.2

NT

NT

NT

 

Piperacillin-tazobactam

1,801

82.7

13.9

624

91.2

7.1

313

81.8

11.2

1,113

78.9

18.1

742

88.3

10.4

 

Trimethoprim-sulfamethoxazole

2,467

92.5

7.5

863

96.3

3.6

308

95.1

4.9

1,084

93.7

6.3

802

94.1

5.7

Klebsiella pneumoniae

                
 

Cefepime

7,276

95.8

3.4

98

100

0

552

93.5

5.6

1,068

95.7

3.5

840

95.6

3.0

 

Cefotaxime

6,243

91.0

6.1

1,411

97.9

1.5

850

76.7

16.4

2,414

93.1

6.0

1,553

94.4

1.9

 

Ceftazidime

9,597

88.5

10.1

2,238

97.5

2.2

1,142

69.8

28.5

1,665

90.0

8.2

1,591

92.5

5.2

 

Ceftriaxone

10,337

92.7

4.7

1,736

97.9

1.1

816

75.2

15.0

166

98.8

0.6

112

86.6

5.4

 

Ciprofloxacin

11,089

89.9

8.4

2,484

91.8

7.2

1,190

88.2

9.9

2,128

85.4

9.4

1,473

89.5

8.7

 

Gentamicin

13,012

91.6

7.0

2,906

96.7

2.9

1,211

81.4

14.5

2,065

91.6

6.1

1,553

97.1

2.7

 

Imipenem

10,263

100

0

1,766

100

0

1,066

100

0

2,351

100

0

1,567

100

0

 

Levofloxacin

9,626

91.0

6.4

485

93.4

3.7

287

78.4

21.3

1,228

92.6

4.4

NT

NT

NT

 

Piperacillin-tazobactam

9,359

85.9

7.4

2,160

91.5

2.7

746

82.2

14.6

2,408

84.9

8.3

1,286

89.4

5.1

 

Trimethoprim-sulfamethoxazole

12,641

88.6

11.1

2,924

92.8

7.1

1,103

82.0

18.0

2,324

82.2

17.2

1,443

88.2

10.9

Morganella morganii

                
 

Cefepime

566

95.9

2.3

<10

NA

NA

121

97.5

2.5

262

94.7

5.0

412

96.1

0.2

 

Cefotaxime

499

78.8

8.4

156

91.0

3.8

144

74.3

6.3

437

86.7

3.9

678

81.1

5.9

 

Ceftazidime

715

73.6

17.3

256

79.7

10.9

213

75.6

15.0

313

84.0

7.7

673

78.6

8.0

 

Ceftriaxone

806

91.1

2.2

219

96.3

1.4

125

91.2

3.2

22

86.4

0

57

84.2

5.3

 

Ciprofloxacin

841

78.1

20.7

292

94.2

4.5

220

87.3

9.5

344

97.7

2.0

634

88.6

8.5

 

Gentamicin

967

84.0

14.1

329

94.5

4.6

222

90.1

8.6

378

96.8

2.1

679

95.6

3.4

 

Imipenem

784

100

0

196

100

0

206

100

0

402

100

0

649

99.8

0

 

Levofloxacin

725

78.1

19.3

42

95.2

4.8

55

90.9

9.1

251

98.0

1.6

NT

NT

NT

 

Piperacillin-tazobactam

725

91.2

5.1

254

97.2

1.6

150

94.0

3.3

430

94.2

3.5

564

91.0

4.6

 

Trimethoprim-sulfamethoxazole

936

75.1

24.7

329

91.8

8.2

193

79.8

20.2

435

93.1

6.9

627

83.9

14.2

Proteus mirabilis

                
 

Cefepime

1,964

98.2

1.0

20

100

0

395

87.6

11.4

599

99.2

0.8

736

99.0

0.1

 

Cefotaxime

1,794

99.1

0.5

295

99.7

0

441

69.4

23.4

1,209

98.8

0.7

1,503

99.5

0.1

 

Ceftazidime

2,684

98.0

1.1

463

99.4

0.2

630

86.0

9.4

821

98.5

1.0

1,505

99.3

0.2

 

Ceftriaxone

3,034

99.4

0.3

392

99.5

0

385

80.5

13.8

77

98.7

0

72

100

0

 

Ciprofloxacin

3,169

85.2

12.7

504

95.2

4.6

657

70.6

22.7

980

92.9

5.1

1,424

90.9

6.8

 

Gentamicin

3,796

91.5

7.7

698

92.6

7.2

670

61.6

37.2

992

92.9

5.9

1,509

91.3

7.9

 

Imipenem

2,850

100

0

367

100

0

580

100

0

1,020

100

0

1,319

100

0

 

Levofloxacin

2,825

87.8

10.5

94

100

0

202

61.9

34.7

688

96.5

2.3

<10

NAc

NA

 

Piperacillin-tazobactam

2,715

97.7

0.8

449

98.2

0.2

465

95.7

2.8

1,201

98.6

0.8

1,231

99.3

0.2

 

Trimethoprim-sulfamethoxazole

3,706

85.2

14.7

708

89.4

10.6

615

61.6

38.0

1,159

80.8

19.1

1,411

79.7

18.6

Serratia marcescens

                
 

Cefepime

3,653

96.7

2.3

52

96.2

1.9

497

96.8

2.2

546

94.1

3.5

509

98.6

0.2

 

Cefotaxime

3,134

87.0

5.7

670

92.8

2.7

470

79.6

9.8

951

84.0

7.5

809

81.5

3.3

 

Ceftazidime

4,718

89.7

7.9

1,113

95.2

3.0

738

81.4

13.3

851

89.7

7.5

812

94.7

3.0

 

Ceftriaxone

4,710

90.5

4.6

846

95.4

1.7

444

86.7

6.3

160

45.6

0

115

77.4

4.3

 

Ciprofloxacin

5,006

91.0

6.7

1,292

85.0

11.7

757

83.5

4.5

978

72.6

12.4

787

78.9

10.5

 

Gentamicin

5,905

92.9

5.9

1,313

94.6

5.2

758

97.4

2.1

665

92.9

6.3

808

91.6

6.6

 

Imipenem

4,960

100

0

880

100

0

727

100

0

1,018

100

0

805

100

0

 

Levofloxacin

4,356

94.3

4.2

264

92.4

4.2

266

95.5

1.5

595

87.6

6.6

<10

NA

NA

 

Piperacillin-tazobactam

4,337

88.1

5.1

1,155

91.6

3.3

547

92.7

3.8

1,053

77.6

3.1

749

82.6

2.4

Trimethoprim-sulfamethoxazole

5,697

95.9

3.9

1,325

94.9

5.1

646

81.4

18.6

908

88.1

10.9

699

84.1

13.6

 

aNCCLS breakpoints were used for all countries, except France (CA-SFM) bNot tested cNot applicable if <10 isolates were tested

Table 5

P. aeruginosa and Acinetobacter spp isolated from ICU patients during 2000–2002

  

United States

Canada

Italy

Germany

France

Organism

Agent

Total n

%S

%R

Total n

%S

%R

Total n

%S

%R

Total n

%S

%R

Total n

%S

%R

Acinetobacter species

Cefepime

5,162

43.8

40.2

97

67.0

23.7

475

17.9

73.7

623

74.2

10.8

857

28.0

40.3

 

Cefotaxime

3,830

23.3

49.9

705

36.7

34.9

555

11.0

78.7

1,254

34.9

24.6

671

15.4

38.7

 

Ceftazidime

5,954

42.2

40.8

1,162

70.8

22.9

692

25.6

68.5

988

66.7

14.5

1,106

34.9

35.5

 

Ceftriaxone

4,709

16.3

55.9

874

32.4

28.7

452

8.8

72.6

104

42.3

11.5

81

9.9

51.9

 

Ciprofloxacin

5,808

39.7

58.0

1,156

72.1

25.9

686

21.1

76.7

1,126

74.8

22.9

1,038

37.7

61.2

 

Gentamicin

6,618

47.2

47.2

1,185

72.8

22.8

768

23.3

72.4

979

82.0

14.1

936

49.3

43.5

 

Imipenem

6,006

87.0

7.5

918

95.8

1.9

569

77.9

19.0

1,253

96.2

3.4

1,088

93.8

3.8

 

Levofloxacin

5,099

43.8

52.2

489

61.1

25.6

295

13.9

75.3

840

82.0

10.5

NTb

NT

NT

 

Meropenem

2,154

66.3

26.5

348

93.7

4.9

455

74.5

13.6

1,024

96.0

3.4

147

68.0

28.6

 

Piperacillin

4,658

35.4

45.9

959

66.5

19.5

635

19.5

69.9

1,171

59.7

12.9

805

35.0

50.3

 

Piperacillin-tazobactam

3,429

53.6

28.5

903

70.7

23.1

425

35.1

46.4

1,225

81.8

7.5

878

74.5

10.5

 

Trimethoprim-sulfamethoxazole

5,697

51.4

48.4

1,155

74.8

25.2

750

44.1

55.7

1,234

83.6

15.6

93

45.2

52.7

Pseudomonas aeruginosa

                
 

Cefepime

20,220

72.5

12.4

371

73.3

12.4

5,056

58.9

28.9

3,483

80.3

7.8

7,967

52.6

16.2

 

Cefotaxime

11,283

9.2

50.4

1,836

13.3

47.5

4,181

6.0

70.7

2,689

7.7

52.2

NT

NT

NT

 

Ceftazidime

26,353

71.2

17.4

6,036

73.7

13.4

7,640

56.7

31.3

5,141

76.2

14.9

8,547

70.2

14.9

 

Ceftriaxone

14,066

12.1

56.4

2,847

11.3

59.7

3,383

8.4

70.4

154

26.6

7.8

NT

NT

NT

 

Ciprofloxacin

26,700

62.8

33.1

5,924

67.2

30.2

7,388

58.4

38.8

4,746

68.6

24.4

8,560

55.3

40.6

 

Gentamicin

29,268

69.4

21.5

5,951

72.2

15.9

7,522

52.2

41.7

3,913

74.0

14.3

7,327

44.0

46.1

 

Imipenem

26,076

73.5

22.1

3,775

77.9

18.2

7,057

59.7

27.8

4,412

70.5

19.0

8,575

69.5

21.4

 

Levofloxacin

21,059

62.7

31.7

713

56.8

33.5

2,427

44.9

51.0

2,953

68.0

23.9

NT

NT

NT

 

Meropenem

7,540

76.0

18.2

1,266

80.3

14.5

4,082

57.3

32.7

4,351

77.8

13.8

1,818

81.1

6.4

 

Piperacillin

22,855

77.7

22.2

5,520

80.9

18.8

7,004

63.1

36.7

4,554

81.7

14.1

8,454

64.1

24.1

 

Piperacillin-tazobactam

21,848

85.5

14.4

4,190

91.0

9.0

5,252

77.7

22.0

4,746

85.8

10.7

8,256

69.6

15.9

Trimethoprim-sulfamethoxazole

15,618

3.6

96.4

4,283

4.0

96.0

7,054

4.1

95.8

3,375

4.2

95.8

NT

NT

NT

 

aNCCLS breakpoints were used for all countries, except France (CA-SFM) bNT = not tested

Results

In vitro susceptibility data from over 220,000 isolates from ICUs in five countries over the period 2000–2002 were assimilated. The most frequent species isolated from infections in the ICU was S. aureus, being most common in three of the five countries (Table 1). The oxacillin resistance rates among S. aureus varied markedly across countries from 19.7% in Canada to 59.5% in Italy. E. coli (7.7%–15.5%) and P. aeruginosa (10.8%–22.3%) were the most frequent Gram-negative organisms encountered. The Gram-positive genus Enterococcus, either as E. faecalis, E. faecium or non-speciated isolates accounted for <10% of isolates in most countries with E. faecalis being the most common species <4.3%. Community-acquired respiratory pathogens such as Streptococcus pneumoniae and Haemophilus influenzae were relatively uncommon in all five countries.
Table 1

Incidence of pathogens isolated from ICU patients by country (%)

United States

Canada

Italy

Germany

France

Organism

Incidence (%)

Organism

Incidence (%)

Organism

Incidence (%)

Organism

Incidence (%)

Organism

Incidence (%)

S. aureus a

20.2

S. aureus a

17.4

P. aeruginosa

22.3

CNS

16.4

S. aureus 1

17.2

CNSb

15.9

CNS

16.1

CNS

18.7

S. aureus a

13.6

CNS

16.7

P. aeruginosa

13.1

E. coli

12.6

S. aureus a

18.1

E. coli

12.3

E. coli

15.5

E. coli

9.2

P. aeruginosa

11.3

E. coli

7.7

P. aeruginosa

10.8

P. aeruginosa

13.8

K. pneumoniae

5.8

Enterococcus spp

7.6

E. faecalis

3.9

Enterococcus spp

7.4

S. pneumoniae

3.3

Enterococcus spp

5.4

K. pneumoniae

5.5

K. pneumoniae

3.5

K. pneumoniae

5.4

E. cloacae

3.3

E. cloacae

4.3

E. cloacae

4.2

Enterococcus spp

3.3

E. cloacae

4.7

E. faecalis

3.0

E. faecalis

3.7

S. marcenscens

2.5

E. cloacae

2.6

E. faecalis

4.3

K. pneumoniae

2.7

S. marcescens

2.7

H. influenzae

2.1

S. marcescens

2.2

P. mirabilis

2.6

P. mirabilis

2.5

A. baumanii

2.6

E. faecalis

2.1

P. mirabilis

1.9

K. oxytoca

2.4

Enterococcus spp

2.3

Enterobacteriaceaec (all species combined)

29.5

Enterobacteriaceae (all species combined)

33.0

Enterobacteriaceae (all species combined)

30.2

Enterobacteriaceae (all species combined)

36.0

Enterobacteriaceae (all species combined)

32.1

Total (n)

26,624

Total (n)

54,445

Total (n)

34,609

Total (n)

48,385

Total (n)

62,459

aProportion of S. aureus testing as MRSA was USA (52.3%), Canada (19.7%), Italy (59.4%), Germany (21.0%), and France (40.6%) bCNS = Coagulase-negative staphylococci cEnterobacteriaceae includes all species of genera occurring at >0.1%

Tables 2,3,4,5 show the antimicrobial susceptibility profiles of various Gram-positive and Gram-negative pathogens isolated from ICU patients against a range of relevant antimicrobials.

Specifically notable susceptibility patterns include the vancomycin susceptibility of all strains of staphylococci. Generally, there was a low proportion of vancomycin resistant E. faecalis <5%, whereas vancomycin-resistant E. faecium was more prevalent ranging from 0.8% in France to 76.3% in the United States, with a wide inter-country variation (Table 2). Penicillin resistance rates varied among S. pneumoniae, from 2.0% in Germany to 20.2% in the US with concurrent ceftriaxone resistance rates of 0% in Germany to 3.4% in Italy (Table 3).

β-lactam activity was assessed by comparing four different cephalosporins and a β-lactam/β-lactamase inhibitor combination, piperacillin-tazobactam. Overall, the putative production of ESBLs among E. coli was low, <6%, but ceftazidime resistance was reported at higher rates in K. pneumoniae and S. marcescens, with the highest rates seen in M. morganii, from 16.0% in Germany to 26.4% in the United States (Table 4). Among the gram-negative organisms tested, ceftriaxone resistance rates were usually lower than ceftazidime, with the exception among P. aeruginosa and Acinetobacter spp. Cefepime, a fourth generation cephalosporin with anti-pseudomonal activity was also more active than ceftazidime (Table 5). Against the Enterobacteriaceae, the β-lactam combination agent piperacillin-tazobactam was generally less active than ceftriaxone. These species showed a wide variation in fluoroquinolone susceptibility among both species and countries. Gentamicin resistance rates among the Enterobacteriaceae varied from 1.2% among K. oxytoca from Germany to 37.2% in P. mirabilis from Italy. Ciprofloxacin resistance rates among E. coli ranged from 6.5% in France to 12.7% in Italy. Variable fluoroquinolone resistance rates among S. marcescens were also demonstrated, with a range of resistance from 4.5% in Italy to 12.4% in Germany.

Discussion

Data derived from international surveillance studies, such as those presented here, can provide a unique contemporary perspective on the susceptibility of commonly encountered organisms to commonly used antibiotics. Such surveillance systems play a crucial role in detecting emerging trends in resistance. Comparisons of these with data of other recent surveillance programs show the wide variations in susceptibility profiles and the need for ongoing unit-specific surveys.

In Germany the prevalence of resistance among gram-positive organisms remained comparatively low with an incidence of 21% MRSA. In 2000, Frank et al. reported that 96% of German isolates of S. marcescens and M. morganii were susceptible to ceftazidime, yet in this study we found 89.7% and 84.0%, respectively [9]. A similar decrease in activity was noted with E. coli and ciprofloxacin between the two studies, 91% in 1996–1997 compared with 86.7% in this study. Marked decreases in susceptibility of P. aeruginosa in Germany were also evident, with no agent showing >85.8% susceptibility (piperacillin-tazobactam) compared with most agents having 85%–94% susceptibility in 1996–1997. Changes of 15–20% have been reported with ceftazidime, imipenem, ciprofloxacin and meropenem, while piperacillin-tazobactam has shown the smallest decrease in susceptibility with <6% over the 4-year period. Piperacillin plus or minus tazobactam and cefepime were the most active agents, based on susceptibility, against P. aeruginosa in Germany. Conversely, ceftriaxone and imipenem were the most active agents, based on susceptibility, against Klebsiella spp., which account for almost 8% of ICU isolates.

Staphylococcal species from French ICU isolates showed a high proportion of oxacillin resistance, 40.6% and 69. 9% of S. aureus and coagulase-negative staphylococci spp., respectively. S. pneumoniae showed penicillin resistance of 17.9%, higher than the other four countries, although the activity of third-generation cephalosporins, ceftriaxone and cefotaxime, showed only 0.6% and 0.8% resistance, respectively. Despite a lower ceftazidime susceptibility breakpoint compared to NCCLS standards (MIC 4 μg/ml instead of 8 μg/ml) putative ESBL expression were slightly lower in France than in Germany in 2000–2002. Ceftazidime non-susceptibility rates among E. coli, K. oxytoca, and P. mirabilis were ≤ 2.2%; however, ceftazidime non-susceptibility rates among K. pneumoniae, M. morganii and S. marcescens were 7.5%, 21.4%, and 5.3%, respectively. Imipenem was active against all Enterobacteriaceae. Against P. aeruginosa and Acinetobacter spp., imipenem resistance rates were 21.4% and 3.8%, respectively. Previously, a lower imipenem resistance of 24% among French isolates of P. aeruginosa was reported [7].

Among the Italian isolates of staphylococci, oxacillin resistance occurred in 59.4% of S. aureus and 84.8% of coagulase-negative isolates. This MRSA rate was similar to that reported by Frank et al. from bacteremic isolates in Italy; however, they reported an increase in MRSA from 25% to 55% over the period 1997 to 2001 [18]. Vancomycin resistance rates of 2.8% for E. faecalis and 24.2% for E. faecium are some of the highest rates recorded in Europe, although still modest compared to rates experienced in the United States; however, teicoplanin was more active with 2.4% and 13.7% of strains being resistant, respectively. Pneumococcal resistance to penicillin and erythromycin was 7.6% and 28.1%, respectively. The impact of alterations in penicillin-binding protein that reduce penicillin susceptibility have less effect on the activity of third-generation cephalosporins such as ceftriaxone with 3.4% and cefotaxime with 4.6% resistance, respectively. S. pyogenes was fully susceptible to penicillin; however, 11.8% of isolates were resistant to clarithromycin and 23.7% were resistant to erythromycin.

The proportion of ESBLs was slightly higher in Italy with E. coli showing ceftazidime non-susceptibility of 5.3%, whereas K. pneumoniae and K. oxytoca demonstrated 30.2% and 16.6% ceftazidime non-susceptibility, respectively. Fluoroquinolone resistance rates among the Enterobacteriaceae, using ciprofloxacin as a marker, varied from 3.0% for K. oxytoca to 22.7% for P. mirabilis, and 12.7% for E. coli. Thus, among Enterobacteriaceae, ciprofloxacin was generally less active than the third-generation cephalosporin, ceftriaxone. P. aeruginosa and Acinetobacter spp. strains from Italian ICUs demonstrated significant resistance rates. Isolates of P. aeruginosa showed resistance rates of >28% for all agents tested except piperacillin-tazobactam. Thus empiric therapy for possible pseudomonal infections will require combination therapy. Acinetobacter spp. showed a similar lack of susceptibility except to imipenem and meropenem (19.0% and 13.6% resistant). An increase in fluoroquinolone resistance in E. coli and K. pneumoniae in bacteremic isolates from Italy was observed during 1997–2001, with rates of 26.7% and 24%, respectively [9]. An increase in ureidopenicillin resistance was noted in P. aeruginosa isolates in Italy from 30% to 37% in a 4-year period [9]. This study showed 22.0% piperacillin-tazobactam and 36.7% piperacillin resistance among ICU P. aeruginosa isolates.

In Canada oxacillin-resistance among S. aureus was noted in 19.7% and coagulase-negative staphylococci in 79.4%. Vancomycin resistance was reported among 0.9% and 14.5% of E. faecalis and E. faecium, respectively. The lowest rate of penicillin resistance in S. pneumoniae in this study was noted from Canada at 7.1%; however, clarithromycin resistance was 30.4%. Ceftriaxone showed 0.7% resistance whereas cefepime exhibited 12.0% resistance among pneumococci from the ICU.

Overall the susceptibility rates for Gram-negative isolates from Canadian ICUs were higher than those in the other four countries examined. A low rate of ESBLs was reported, but there was variable activity of piperacillin-tazobactam which showed >9% resistance among Klebsiella spp. and S. marcescens tested. The rate of fluoroquinolone resistance was similar to those of other countries with E. coli showing 13.9% levofloxacin resistance. Among Enterobacteriaceae, <10% of most species were resistant to third-generation cephalosporins tested with the exception of ceftazidime and M. morganii. Resistance among P. aeruginosa and Acinetobacter spp. was generally lower than in other countries apart from Germany. Only piperacillin-tazobactam showed reliable activity against P. aeruginosa (9% resistant), while resistance to all other agents was >19%. Acinetobacter spp. remained susceptible to only the carbapenems, imipenem and meropenem.

Comparison of the data from Canadian isolates with those from the United States shows some significant differences. This demonstrates the limitations of pooling Canadian and United States data since the differences between the two regions, such as the rate of MRSA, may have some impact on empiric therapy. Data from the NNIS system has previously reported an increasing trend towards resistance within ICUs in the United States [19]. Oxacillin resistance among staphylococci from ICUs in the United States was 52.3% and 84.2% for S. aureus and coagulase-negative species, respectively.

This value is identical to that of S. aureus and very similar to the CNS data reported by the 1999 NNIS system. The NNIS highlighted a 37% increase in MRSA over the period 1994–98 to 1999, but only a 2% increase among CNS strains [4]. Vancomycin resistance in the United States was observed in 4.5% of E. faecalis; however, over 76% E. faecium were vancomycin non-susceptible.

Although streptococci are uncommon ICU pathogens they can be rapidly invasive and possibly fatal unless adequate therapeutic approaches are adopted. S. pneumoniae in the United States has acquired a range of resistance mechanisms with resistance to penicillin and the macrolides, clarithromycin and erythromycin, being common, 20.2% and 25.5%–30.5% respectively. The newer generation cephalosporins, ceftriaxone, cefotaxime and cefepime showed good activity against pneumococci, 3.2%, 6.3% and 4.5% resistant, respectively. Less than 1.0% of isolates were resistant to levofloxacin. These data are similar to other recent reports [20].

For Enterobacteriaceae which account for approximately 30% of all isolates from ICU infections, the incidence of putative ESBLs was low in E. coli, 4.7% but ceftazidime non-susceptibility was higher in K. oxytoca 8.3%,K. pneumoniae 11.5%,S. marcescens 10.3% and M. morganii 26.4%. These data are consistent with other recent reports [21]. Fluoroquinolone resistance was observed in all Enterobacteriaceae tested, in the US for example, resistance rates were as follows, using ciprofloxacin as a marker: E. coli

Specifically, enteric bacteria showed changes over this time. Fluoroquinolone resistance doubled among E. coli isolates from 3.3–5.5% to 10.8–11.4% [22]. This study showed a generally higher level of activity among third-generation cephalosporins than other reports [23], with ceftriaxone showing <10% resistance rates against most species tested. Piperacillin-tazobactam showed less consistent activity with some species being >14% resistant, e.g. Klebsiella spp.,P. aeruginosa, and Acinetobacter spp. present significant therapeutic challenges in ICUs in the United States. With the exception of cefepime, all other tested antimicrobials demonstrated >12% resistance to P. aeruginosa, many considerably higher. Piperacillin-tazobactam showed the next lowest resistance rate, 14.4%, with all other agents having rates of 17% or higher. Non-susceptibility to ciprofloxacin among P. aeruginosa was 37.2%, higher than in the Neuberger report. Sahm et al. reported a 10% increase in fluoroquinolone resistance among P. aeruginosa in the United States, whereas resistance emerged more slowly with the other classes of antimicrobials tested [12]. Acinetobacter infections continue to present significant therapeutic challenges due to the extensive resistance mechanisms demonstrated by the >25% resistance shown in Table 5. Only imipenem has any reliable activity against Acinetobacter spp. with an 87% susceptibility rate.

There are several implications of these data. It is essential that local surveillance programs be maintained in each country's ICU setting. The local data are vital to the formulary committees as they select appropriate agents to treat infections. There are clear differences among the five countries studied in this report. Although the predominant pathogens are similar, ongoing surveillance is essential to detect the emergence of resistant species. It is clear that certain classes of compounds are losing activity against the ICU pathogens tested. For example, the fluoroquinolones have reduced susceptibility among many Gram-negative species as well as staphylococci; however, the newer class members have enhanced activity against pneumococci. Advanced-generation cephalosporins have variable activity, with ceftriaxone showing consistently good activity against the Enterobacteriaceae and some staphylococci. Ceftazidime has lost potency due to the emergence of ESBL enzymes and also has diminished activity against P. aeruginosa. Piperacillin-tazobactam is generally active against P. aeruginosa in ICUs. The aminoglycoside, gentamicin has shown continued activity against most Enterobacteriaceae in all five countries, and modest activity against S. aureus but not against CNS strains. The gentamicin susceptibility of P. aeruginosa ranged from 44.0% in France to 74.0% in Germany, whereas Acinetobacter spp . showed more variable gentamicin susceptibility varying from 23.3% in Italy to 82.0% in Germany. These local data should be considered when treating infections in the ICU.

Use of agents with anti-pseudomonal activity such as cefepime, piperacillin-tazobactam or the carbapenems should preferably be reserved for patient types or infections where this pathogen is present or risk factors exist, as per the ATS Community acquired-pneumonia guidelines [24]. A combination of a third-generation cephalosporin such as ceftriaxone with vancomycin may be appropriate for bloodstream infections based upon the NNIS etiology data from 1992–1999.

Conclusions

The current study confirmed the emergence of fluoroquinolone resistance among various Gram-negative species and staphylococci, which may be increasing due to the heightened use of these drugs; however the reported ESBL rates among Enterobacteriaceae was lower than noted in other studies and appeared to be stable. The prevalence of MRSA, perhaps the most significant resistant hospital pathogen, varied among the five countries and appeared to be increasing. Parenteral cephalosporins such as ceftriaxone and cefotaxime remained quite active against Enterobacteriaceae. Up-to-date susceptibility data should be made available as rapidly as possible to physicians so that appropriate targeted empirical therapy can be instituted, this approach can assist in maintaining the activity of the current antimicrobials. While local surveillance studies remain crucial, national surveillance studies such as this can provide an invaluable data source to provide guidance in formulary decision-making.

Declarations

Acknowledgments

We thank F. Hoffmann-La Roche Ltd., Basel, Switzerland for financial support of this study. Additionally, we thank the many clinical microbiology laboratories around the world that contribute data to TSN Databases, without whom such studies would not be possible.

Authors’ Affiliations

(1)
Focus Technologies
(2)
Virginia Commonwealth University

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Copyright

© Jones et al; licensee BioMed Central Ltd. 2004

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.

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