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

1
Species Distribution and Antifungal
Susceptibility (AFS) Patterns for Candida
Bloodstream Isolates from the SENTRY
Participants Group Europe 1999 2000
G. Prodhom1, J. Bille1, R. Jones2, and Sentry
Participants Group 3Europe 1Univ. Hosp.,
Lausanne, Switzerland 2The JONES Group/JMI
Laboratories, North Liberty, IA
Poster 266
Guy Prodhom Institue de Microbiologie Rue du
Bugnon 44, Lausanne, Switzerland CH-1011 Phone
41-21-314-4077 Fax [phone] Emailguy.p
rodhom_at_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.
RESULTS
TABLE 3. Antifungal activities of fluconazole,
itraconazole and ravuconazole against BSI
isolates of Candida spp.
INTRODUCTION
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 ³ 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.
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).
AntifungalAgents
Range
No. of Isolates
MIC (mg/l)
Resistanta
50
90
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
European SENTRY Participants3
5
Fluconazole Itraconazole Ravuconazole
4-64 0.25-2 0.12-1
16 0.5 0.25
64 2 1
40.0
Country
City
InvestigatorName
Site 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 Delvallez Germany K
linikum der J. W. Goethe Universität Frankfurt P
. Shah Israel Chaim Sheba Medical
Center Tel-Hashomer N. Keller Italy 1
Policlinico A. Gemelli Roma G. Fadda Italy 2
Universita degli Studi di Genova Genova G.
Schito Spain 1 University Hospital V. de
Macarena Sevilla A. Pascual Spain 2 Hospital
Ramon y Cajal Madrid R. Canton Moreno Sweden Un
iversity Hospital Linkoping H. Hanberger Switzerla
nd University Hospital - CHUV Lausanne J.
Bille Turkey 1 Hacettepe Universitesi Tip
Fakultesi Ankara D. Gur Turkey 2 Marmara
Universitesi Tip Fakultesi Istanbul V. Korten
MATERIALS AND METHODS
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.
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
Geographic Location, European SENTRY Program 1999
- 2000
SUSCEPTIBILITY TESTING
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
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 gt 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 gt 1 mg/l. No breakpoints
were applied for ravuconazole.
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
European SENTRY Scientific Adisory Committee
(ESSAC)
Prof. J. Bille Prof. R. Canton Prof. G.
French Prof. M. Struelens Prof. P. Shah
a resistant, percent resistant by using NCCLS
interpretive criteria  fluconazole resistance at
gt 64 mg/l and itraconazole resistance at gt 1
mg/l, ravuconazole no interpretive criteria. b
Includes C. kefyr (two isolates) and C.
lusitaniae (two isolates).
REFERENCES
NCCLS (1997) Approved standard M27-A. Rex JH et
al. Clin Infect Dis (1997) 24235-247. Pfaller M.
A., et al. Diagn Microbiol Infect Dis (1999)
3519-25.
A156-21