NCCLS (1997) Approved standard M27-A.Rex JH et al. Clin Infect Dis (1997) 24:235-247.Pfaller M. A., et al. Diagn Microbiol Infect Dis (1999); 35:19-25.

All fungal blood culture isolates were identified at the participating institutions by the routine method in use at each laboratory. The isolates were sent to the University of Iowa College of Medicine (Iowa City) for storage and further characterization by reference identification and susceptibility testing methods.

Surveillance programs of blood stream infections (BSI) are essential sources of information to identify antimicrobial resistance trends and to detect emerging pathogens. Candida BSI are important as they currently rank as the fourth most common cause of nosocomial BSI with a mortality remaining high despite appropriate antifungal treatment.

The SENTRY Antimicrobial Surveillance Program is a longitudinal surveillance program designed to track antimicrobial resistance trends on a global scale.

In the present study, we focused on BSI caused by Candida spp. and described the variations in species and antifungal susceptibility for 3 azoles compounds among isolates from the 13 medical centers in 10 European countries (including Israel and Turkey).

G. Prod’hom1, J. Bille1, R. Jones2, and Sentry Participants Group 3[Europe]1Univ. Hosp., Lausanne, Switzerland; 2The JONES Group/JMI Laboratories, North Liberty, IA

Poster # 266 Guy Prod’homInstitue de Microbiologie

Rue du Bugnon 44, Lausanne, Switzerland CH-1011Phone: 41-21-314-4077 Fax: 41-21-314-4060

Email:guy.prodhom@chuv.hospvd.ch

CONCLUSIONS

1. C. albicans represented 57% of 138 Candida BSI isolates from 13 hospitals in 10 European countries in 1999-2000.

2. The results document the excellent in vitro activities of fluconazole, itraconazole, ravuconazole in particular with no resistance in C. albicans, C. parapsilosis and C. tropicalis.

3. Ravuconazole was more potent in vitro than itraconazole for all species tested.

4. Continued surveillance at an international level is important to monitor any change in species distribution and antifungal susceptibilty among invasive strains of Candida species and other fungal pathogens.

Species Distribution and Antifungal Susceptibility (AFS) Patterns for Candida Bloodstream Isolates from the SENTRY Participants Group [Europe] 1999 – 2000

REFERENCES

A156-21

RESULTS

During the 24-month study period a total of 138 Candida BSIs were reported by 13 European SENTRY Program participants (Figure, table 1). The difference in the proportion of BSIs due to C. albicans varied considerably among the various participating sites. Although the numbers were quite small at some locations, the percentage ranged from 40% to 80% for institutions with 10 isolates. Overall, non-C. albicans species were more frequent in the south countries of Europe (Italy, Spain, Turkey, Israel) compared to the other countries – 46% compared to 36% (data not shown).

The frequency of BSIs due to the various species of Candida is presented in Table 2. The distribution of some non- C. albicans species (in particular C. parapsilosis and C. tropicalis) show differences compared to that reported earlier by Pfaller et al. (1999).

Table 3 summarizes the in vitro antifungal activities of fluconazole, itraconazole and ravuconazole. A broad range of MICs was observed with each antifungal agent. The majority of strains were susceptible to the 3 azoles.

Ravuconazole show lower MICs than itraconazole against C. albicans, C. glabrata, C. parapsilosis and C. tropicalis BSI isolates.

INTRODUCTION

MATERIALS AND METHODS

Antifungal susceptibilitly testing of Candida isolates, was performed by the reference broth microdilution method described by the National Committee for Clinical Laboratory Standards (NCCLS). Interpretive criteria for fluconazole and itraconazole were those published by Rex et al. and the NCCLS: isolates were classified as resistant if the MIC was > 64 mg/l for fluconazole. This breakpoint was apply to all Candida species (including C. glabrata) with the exception of C. krusei, which is considered inherently resistant to fluconazole. For itraconazole, isolates were classified as resistant if the MIC was > 1 mg/l. No breakpoints were applied for ravuconazole.

SUSCEPTIBILITY TESTING

TABLE 2: Species Distribution of Candida BSI, European SENTRY Program 1999-2000 compared to 1997

Species1997*

(170 isolates)1999-2000

(138 isolates)

C. albicans 57 53

C. glabrata 12 12

C. kefyr 1 0

C. krusei 4 1

C. lusitaniae 1 0

C. parapsilosis 14 21

C. tropicalis 10 6

C. spp 0 7

% of Isolates

*Pfaller et al., 1999

TABLE 1: Geographic location and number of isolates of yeast blood stream infections due to Candida spp.

Country % Candida albicans*No. of Isolates

Belgium 1 -

England 3 -

France 15 60

Germany 10 40

Israel 18 39

Italy – 1 2 -

Italy – 2 17 71

Spain – 1 16 50

Spain – 2 7 -

Sweden 4 -

Switzerland 14 79

Turkey – 1 15 67

Turkey – 2 16 44

Overall 138 57

*only for institutions with >10 isolates

TABLE 3. Antifungal activities of fluconazole, itraconazole and ravuconazole against BSI isolates of Candida spp.

a: % resistant, percent resistant by using NCCLS interpretive criteria : fluconazole resistance at > 64 mg/l and itraconazole resistance at > 1 mg/l, ravuconazole: no interpretive criteria.

b: Includes C. kefyr (two isolates) and C. lusitaniae (two isolates).

79 Fluconazole

Itraconazole

Ravuconazole

0.12-0.5

0.015-0.25

0.006-0.06

0.25

0.03

0.006

0.25

0.06

0.015

0

0

17 Fluconazole

Itraconazole

Ravuconazole

0.12-128

0.06-4

0.006-2

4

0.5

0.12

32

2

1

5.9

41.2

5 Fluconazole

Itraconazole

Ravuconazole

4-64

0.25-2

0.12-1

16

0.5

0.25

64

2

1

40.0

19 Fluconazole

Itraconazole

Ravuconazole

0.25-2

0.06-0.5

0.006-0.06

1

0.12

0.03

2

0.25

0.06

0

0

14 Fluconazole

Itraconazole

Ravuconazole

0.12-16

0.03-1

0.006-1

1

0.12

0.06

2

0.5

0.25

0

7.1

4 Fluconazole

Itraconazole

Ravuconazole

0.25-16

0.06-2

0.006-0.5

0.25

0.12

0.012

16

2

0.5

0

25.0

138 Fluconazole

Itraconazole

Ravuconazole

0.12-128

0.015-4

0.006-2

0.25

0.06

0.006

4

0.5

0.25

2.2

8.0

Prof. J. Bille Prof. R. Canton Prof. G. FrenchProf. M. Struelens Prof. P. Shah

European SENTRY Scientific Adisory Committee (ESSAC)

European SENTRY Participants3

Country CityInvestigator

NameSite Name

Belgium Univ. Libre de Bruxelles- Hôpital Erasme Brussels M. Struelens

England St. Thomas's Hospital Medical School London G. French

France CHU de Lille, Hôpital Calmette Lille M. Roussel

DelvallezGermany Klinikum der J. W.

Goethe Universität Frankfurt P. ShahIsrael Chaim Sheba

Medical Center Tel-Hashomer N. KellerItaly – 1 Policlinico A. Gemelli Roma G. FaddaItaly – 2 Universita degli Studi

di Genova Genova G. SchitoSpain – 1 University Hospital

V. de Macarena Sevilla A. PascualSpain – 2 Hospital Ramon y Cajal Madrid R. Canton

MorenoSweden University Hospital Linkoping H. HanbergerSwitzerland University Hospital -

CHUV Lausanne J. BilleTurkey – 1 Hacettepe Universitesi

Tip Fakultesi Ankara D. GurTurkey – 2 Marmara Universitesi

Tip Fakultesi Istanbul V. Korten

Geographic Location, European SENTRY Program 1999 - 2000

Belgium

Switzerland

ItalySpain

England

Sweden

France

TurkeyIsrael

Germany

C. albicans

C. glabrata

C. krusei

C. parapsilosis

C. tropicalis

Candida spp.b

All organisms

SpeciesAntifungal

AgentsRangeNo. of

Isolates50% 90%

MIC (mg/l)%

Resistanta