Results from the ARTEMIS DISK Global Antifungal Surveillance Study, 1997 to 2007: a 10.5-Year Analysis of Susceptibilities of Candida Species to Fluconazole and Voriconazole as Determined by CLSI Standardized Disk Diffusion

M. A. Pfaller; D. J. Diekema; D. L. Gibbs; V. A. Newell; D. Ellis; V. Tullio; A. Rodloff; W. Fu; T. A. Ling; and the Global Antifungal Surveillance Group

doi:10.1128/JCM.02117-09

DOI: 10.1128/JCM.02117-09

Article Figures & Data

Tables

TABLE 1.

Species distribution of Candida isolates over 10.5 years^a

Organism	Isolates tested by period:
	1997-2000		2001-2004		2005-2007		1997-2007
	No.	% of total	No.	% of total	No.	% of total	No.	% of total
Candida albicans	39,152	70.9	71,027	62.9	57,598	65.0	167,777	65.3
C. glabrata	5,634	10.2	12,963	11.5	10,342	11.7	28,939	11.3
C. tropicalis	2,996	5.4	8,496	7.5	7,050	8.0	18,542	7.2
C. parapsilosis	2,633	4.8	7,783	6.9	5,005	5.6	15,421	6.0
C. krusei	1,207	2.2	2,840	2.5	2,239	2.5	6,286	2.4
C. guilliermondii	367	0.7	902	0.8	508	0.6	1,777	0.7
C. lusitaniae	276	0.5	674	0.6	559	0.6	1,509	0.6
C. kefyr	182	0.3	527	0.5	517	0.6	1,226	0.5
C. inconspicua	9	0.02	276	0.2	290	0.3	575	0.2
C. famata	123	0.2	375	0.3	247	0.3	745	0.3
C. rugosa	35	0.06	469	0.4	134	0.2	638	0.2
C. dubliniensis	1	<0.01	113	0.1	197	0.2	311	0.1
C. norvegensis	11	0.02	135	0.1	113	0.1	259	0.1
C. lipolytica	7	0.01	80	0.07	50	0.06	137	0.05
C. sake			20	0.02	67	0.08	87	0.03
C. pelliculosa	1	<0.01	47	0.04	40	0.05	88	0.03
C. apicola					57	0.06	57	0.02
C. zeylanoides	4	<0.01	50	0.04	20	0.02	74	0.03
C. valida			9	<0.01	12	0.01	21	<0.01
C. intermedia			10	<0.01	14	0.01	24	<0.01
C. pulcherrima			6	<0.01	8	<0.01	14	<0.01
C. haemulonii			6	<0.01	3	<0.01	9	<0.01
C. stellatoidea					7	<0.01	7	<0.01
C. utilis					6	<0.01	6	<0.01
C. humicola			2	<0.01	4	<0.01	6	<0.01
C. lambica					5	<0.01	5	<0.01
C. ciferrii					2	<0.01	2	<0.01
C. colliculosa					2	<0.01	2	<0.01
C. holmii					1	<0.01	1	<0.01
C. marina					1	<0.01	1	<0.01
C. sphaerica					1	<0.01	1	<0.01
Candida spp. NOS^b	2,591	4.7	6,186	5.5	3,558	4.0	12,335	4.8
Total	55,229	100.0	112,996	100.0	88,647	100.0	256,882	100.0

↵ a Includes all specimen types and all locations in hospitals from 142 institutions in 41 countries.
↵ b Candida spp. NOS, Candida species not otherwise identified.

TABLE 2.

Geographic variation in frequency of common and uncommon species of Candida: ARTEMIS, 2001 to 2007^a

Species	Species distribution (%) by region (total no. of isolates)^b:
Species	APAC (44,674)	EU (109,643)	AF/ME (8,259)	LAM (27,395)	NAM (11,682)	Total (201,653)
C. albicans	64.4	67.9	67.1	51.8	48.9	63.8
C. glabrata	12.6	11.3	8.8	7.4	21.1	11.6
C. tropicalis	11.7	4.9	6.6	13.2	7.3	7.7
C. parapsilosis	7.4	4.2	6.0	10.3	13.6	6.3
C. krusei	1.2	3.4	1.6	1.4	3.1	2.5
C. guilliermondii	0.4	0.5	0.1	2.2	0.5	0.7
C. inconspicua	<0.1	0.5		<0.1	<0.1	0.3
C. rugosa	0.4	<0.1	<0.1	1.2	<0.1	0.3
C. norvegensis	<0.1	0.2	<0.1	<0.1	0.2	0.1

↵ a Includes all specimen types and all locations in hospitals from 133 institutions.
↵ b Abbreviations: APAC, Asia-Pacific; EU, Europe; AF/ME, Africa-Middle East; LAM, Latin America; NAM, North America.

TABLE 3.

In vitro susceptibilities of Candida spp. to fluconazole and voriconazole as determined by CLSI disk diffusion testing^a

Species	Fluconazole^b			Voriconazole^b
Species	No. of isolates tested	% S	% R	No. of isolates tested	% S	% R
C. albicans	128,625	98.0	1.4	125,965	98.5	1.2
C. glabrata	23,305	68.7	15.7	22,968	82.9	10.0
C. tropicalis	15,546	91.0	4.1	15,198	89.5	5.4
C. parapsilosis	12,788	93.2	3.6	12,453	97.0	1.8
C. krusei	5,079	8.6	78.3	5,005	83.2	7.6
C. guilliermondii	1,410	73.5	11.4	1,375	90.5	5.7
C. lusitaniae	1,233	92.1	5.4	1,215	96.7	2.0
C. kefyr	1,044	96.5	2.7	1,032	98.7	0.9
C. inconspicua	566	22.6	53.2	563	90.6	3.9
C. famata	622	79.1	10.3	606	90.3	5.0
C. rugosa	603	49.9	41.8	580	69.3	21.2
C. dubliniensis	310	96.1	2.6	308	98.4	1.0
C. norvegensis	248	41.9	40.7	247	91.5	4.0
C. lipolytica	130	66.2	28.5	128	77.3	14.1
C. sake	87	85.1	11.5	87	92.0	6.9
C. pelliculosa	87	89.7	6.9	86	94.2	4.7
C. apicola	57	98.2	1.8	57	98.2	1.8
C. zeylanoides	70	67.1	24.3	67	85.1	6.0
C. valida	21	23.8	61.9	22	81.8	13.6
C. intermedia	24	95.8	4.2	25	100.0	0.0
C. pulcherrima	14	100.0	0.0	14	100.0	0.0
C. haemulonii	9	88.9	11.1	9	88.9	11.1
C. stellatoidea	7	85.7	0.0	7	85.7	14.3
C. utilis	6	83.3	0.0	7	100.0	0.0
C. humicola	6	50.0	50.0	6	50.0	33.3
C. lambica	5	0.0	80.0	5	40.0	20
C. ciferrii	2	50.0	50.0	2	50.0	0.0
C. colliculosa	2	100.0	0.0	2	100.0	0.0
C. holmii	1	100.0	0.0	1	100.0	0.0
C. marina	1	0.0	0.0	1	100.0	0.0
C. sphaerica	1	100.0	0.0	1	100.0	0.0
Candida spp.^c	9,744	86.2	8.9	9,577	93.6	4.1

↵ a Isolates were obtained from 133 institutions, 2001 to 2007.
↵ b Fluconazole and voriconazole disk diffusion testing was performed in accordance with CLSI document M44-A (7). The interpretive breakpoints (zone diameters) were as follows: S, ≥19 mm (fluconazole) and ≥17 mm (voriconazole); R, ≤14 mm (fluconazole) and ≤13 mm (voriconazole).
↵ c Candida species, not otherwise specified.

TABLE 4.

In vitro susceptibilities of fluconazole-resistant isolates of Candida spp. to voriconazole as determined by CLSI disk diffusion testing^a

Species	No. of isolates tested	% S	% SDD	% R
C. albicans	1,782	28.1	8.4	63.6
C. glabrata	3,550	19.1	21.7	59.2
C. tropicalis	629	17.0	15.3	67.7
C. parapsilosis	431	39.2	20.4	40.4
C. krusei	3,889	79.6	11.3	9.2
C. guilliermondii	157	43.9	16.6	39.5
C. lusitaniae	63	55.6	17.5	27.0
C. kefyr	27	66.7	7.4	25.9
C. inconspicua	297	83.8	10.1	6.1
C. famata	62	37.1	24.2	38.7
C. rugosa	242	28.1	21.5	50.4
C. dubliniensis	8	62.5	0.0	37.5
C. norvegensis	100	81.0	10.0	9.0
C. lipolytica	37	29.7	27.0	43.2
C. sake	9	44.4	11.1	44.4
C. pelliculosa	6	16.7	16.7	66.7
C. apicola	1	0.0	0.0	100.0
C. zeylanoides	15	46.7	26.7	26.7
C. valida	14	71.4	7.1	21.4
C. intermedia	1	100.0	0.0	0.0
C. haemulonii	1	0.0	0.0	100.0
C. humicola	3	0.0	33.3	66.7
C. lambica	4	25.0	50.0	25.0
C. ciferrii	1	0.0	100.0	0.0
Candida spp.^b	850	47.6	14.6	37.8

↵ a Isolates obtained from 133 institutions, 2001 to 2007. The zone diameters for voriconazole disk diffusion susceptibility categories were as follows: S, ≥17 mm; SDD, 14 to 16 mm; R, ≤13 mm.
↵ b Candida species not otherwise identified.

TABLE 5.

Trends in in vitro resistance to fluconazole among Candida spp. as determined by CLSI disk diffusion testing over a 10.5-year period^a ^, ^b

Species	1997-2000		2001-2004		2005-2007
Species	No. of isolates tested	% R	No. of isolates tested	% R	No. of isolates tested	% R
C. albicans	39,152	0.9	71,027	1.4	57,598	1.4
C. glabrata	5,634	19.2	12,963	15.9	10,342	15.4
C. tropicalis	2,996	3.6	8,496	4.5	7,050	3.6
C. parapsilosis	2,633	2.5	7,783	3.5	5,005	3.6
C. krusei	1,207	65.8	2,840	77.5	2,239	79.3
C. guilliermondii	367	12.5	902	9.9	508	14.2
C. lusitaniae	276	2.9	674	4.3	559	6.6
C. kefyr	182	3.3	527	3.6	517	1.7
C. inconspicua	9	55.6	276	52.2	290	54.1
C. famata	123	17.1	375	12.5	247	6.9
C. rugosa	35	34.3	238	50.7	134	10.4
C. dubliniensis	1	0.0	113	2.7	197	2.0
C. norvegensis	11	54.5	135	36.3	113	46.0
C. lipolytica	7	0.0	80	37.5	50	14.0
C. sake			20	10.0	67	11.9
C. pelliculosa	1	0.0	47	0.0	40	15.0
C. apicola					57	1.8
C. zeylanoides	4	0.0	50	28.0	20	15.0
C. valida			9	66.7	12	58.3
C. intermedia			10	0.0	14	7.1
C. pulcherrima			6	0.0	8	0.0
C. haemulonii			6	0.0	3	33.3
C. stellatoidea					7	0.0
C. utilis					6	0.0
C. humicola			2	50.0	4	50.0
C. lambica					5	80.0
C. ciferrii					2	50.0
C. colliculosa					2	0.0
C. holmii					1	0.0
C. marina					1	0.0
C. sphaerica					1	0.0
Candida spp.^c	2,591	10.5	6,186	8.2	3,558	10.1

↵ a Includes all specimen types and all hospital locations in 141 institutions.
↵ b % R, percent resistant (zone diameter, ≤14 mm).
↵ c Candida species not otherwise identified.

TABLE 6.

Trends in in vitro resistance to voriconazole among Candida spp. as determined by CLSI disk diffusion testing over a 7-year period^a ^, ^b

Species	2001-2004		2005		2006		2007
Species	No. of isolates tested	% R	No. of isolates tested	% R	No. of isolates tested	% R	No. of isolates tested	% R
C. albicans	68,575	1.2	18,630	1.5	18,965	1.0	19,795	1.0
C. glabrata	12,643	10.3	3,185	9.5	3,413	10.2	3,727	9.4
C. tropicalis	8,171	6.1	2,136	4.5	2,317	3.8	2,574	5.1
C. parapsilosis	7,464	1.8	1,581	1.9	1,724	1.3	1,687	1.8
C. krusei	2,765	7.7	684	7.9	742	6.5	814	8.0
C. guilliermondii	872	4.9	184	6.5	155	9.7	164	5.5
C. lusitaniae	655	1.8	163	3.1	195	0.5	202	3.0
C. kefyr	514	0.8	173	2.9	153	0.0	192	0.0
C. inconspicua	274	5.5	77	2.6	89	2.2	123	2.4
C. famata	359	6.4	87	1.1	72	1.4	88	5.7
C. rugosa	446	26.7	33	3.0	38	0.0	63	4.8
C. dubliniensis	111	0.9	57	0.0	70	1.4	70	1.4
C. norvegensis	134	2.2	36	0.0	47	10.4	29	6.9
C. lipolytica	79	17.7	17	0.0	14	14.3	18	11.1
C. sake	20	0.0	13	7.7	27	11.1	27	7.4
C. pelliculosa	47	0.0	14	14.3	19	5.3	6	16.7
C. apicola					44	2.3	13	0.0
C. zeylanoides	48	8.3	7	0.0	2	0.0	10	0.0
C. valida	9	11.1	7	28.6	1	0.0	5	0.0
C. intermedia	10	0.0	8	0.0	3	0.0	4	0.0
C. pulcherrima	6	0.0	2	0.0	4	0.0	2	0.0
C. haemulonii	6	0.0	2	50.0	1	0.0
C. stellatoidea							7	14.3
C. utilis			1	0.0	2	0.0	4	0.0
C. humicola	2	50.0			2	50.0	2	0.0
C. lambica					2	0.0	3	33.3
C. ciferrii					1	0.0	1	0.0
C. colliculosa					1	0.0	1	0.0
C. holmii							1	0.0
C. marina							1	0.0
C. sphaerica							1	0.0
Candida spp.^c	6,022	4.7	1,183	4.9	1,031	2.4	1,341	2.0

↵ a Isolates were obtained from 133 institutions.
↵ b % R, percent resistant (zone diameter, ≤13 mm).
↵ c Candida species not otherwise identified.

TABLE 7.

Geographic variation in the in vitro susceptibilities of common and uncommon species of Candida to fluconazole and voriconazole, 2001 to 2007^a

Species	Antifungal agent	APAC		EU		AF/ME		LAM		NAM
Species	Antifungal agent	No. of isolates	% R	No. of isolates	% R	No. of isolates	% R	No. of isolates	% R	No. of isolates	% R
C. albicans	Fluconazole	28,781	0.9	74,408	1.3	5,539	0.6	14,178	2.1	5,718	5.1
	Voriconazole	27,827	0.8	72,873	1.1	5,502	0.3	13,711	1.7	5,681	3.6
C. glabrata	Fluconazole	5,629	13.0	12,439	16.3	728	16.2	2,039	15.1	2,470	19.5
	Voriconazole	5,515	8.2	12,288	9.8	705	8.1	2,000	11.3	2,460	14.6
C. tropicalis	Fluconazole	5,178	6.5	5,349	2.9	544	2.6	3,625	2.6	850	4.4
	Voriconazole	5,062	8.4	5,128	3.9	542	2.4	3,522	3.7	836	5.3
C. parapsilosis	Fluconazole	3,294	4.3	4,578	2.6	499	15.0	2,830	2.1	1,587	3.5
	Voriconazole	3,120	1.7	4,487	1.1	496	11.1	2,779	0.9	1,517	2.4
C. krusei	Fluconazole	532	73.5	3,678	80.8	134	72.4	370	66.8	361	74.0
	Voriconazole	516	5.0	3,637	7.7	134	4.5	351	14.0	363	5.5
C. guilliermondii	Fluconazole	178	13.5	567	13.8	12	8.3	590	9.0	63	7.9
	Voriconazole	175	10.9	558	6.1	12	0.0	567	3.7	63	4.8
C. inconspicua	Fluconazole	4	25.0	558	53.0			2	100.0	2	100.0
	Voriconazole	4	0.0	555	3.8			2	50.0	2	0.0
C. rugosa	Fluconazole	165	32.1	89	10.1	1	0.0	339	55.5	9	22.2
	Voriconazole	145	6.9	87	1.1	1	0.0	338	32.8	9	11.1
C. norvegensis	Fluconazole	7	14.3	204	49.0	1	0.0	13	0.0	21	0.0
	Voriconazole	7	0.0	203	4.9	1	0.0	13	0.0	21	0.0

↵ a For definitions of abbreviations, see Table 2, footnote b.

TABLE 8.

Susceptibilities of C. krusei, C. inconspicua, and C. norvegensis to fluconazole and voriconazole by clinical service^a

Clinical service (total no. of isolates)	Antifungal agent	C. krusei		C. inconspicua		C. norvegensis
Clinical service (total no. of isolates)	Antifungal agent	No. of isolates tested	% R^b	No. of isolates tested	% R	No. of isolates tested	% R
Hematology-oncology (11,930)	Fluconazole	757	83.1	113	51.3	24	50.0
	Voriconazole	741	9.6	113	5.3	24	4.2
Medical (47,024)	Fluconazole	1,128	79.9	101	42.6	68	33.8
	Voriconazole	1,106	7.8	101	4.0	68	2.9
Surgical (12,659)	Fluconazole	316	78.5	62	61.3	25	28.0
	Voriconazole	320	5.6	62	1.6	25	0.0
ICU (27,758)	Fluconazole	706	79.0	78	50.0	26	42.3
	Voriconazole	692	6.6	76	2.6	26	0.0
Dermatology (3,001)	Fluconazole	32	71.9	4	75.0	2	0.0
	Voriconazole	31	6.5	4	50.0	2	0.0
Urology (1,954)	Fluconazole	40	60.0	4	25.0	6	83.3
	Voriconazole	40	7.5	4	0.0	6	16.7
Outpatient (15,810)	Fluconazole	212	74.5	17	23.5	23	34.8
	Voriconazole	213	10.3	17	5.9	22	0.0
Other NOS (81,517)	Fluconazole	1,888	75.9	187	61.5	74	47.3
	Voriconazole	1,862	7.0	186	3.2	74	8.1

↵ a Isolates were obtained from 133 institutions.
↵ b % R, percent resistant (zone diameter, ≤14 mm [fluconazole] and ≤13 mm [voriconazole]).

TABLE 9.

Susceptibilities of C. krusei, C. inconspicua, and C. norvegensis to fluconazole and voriconazole by specimen type^a

Specimen type/site (total no. of isolates)	Antifungal agent	C. krusei		C. inconspicua		C. norvegensis
Specimen type/site (total no. of isolates)	Antifungal agent	No. of isolates tested	% R^b	No. of isolates tested	% R	No. of isolates tested	% R
Blood (20,704)	Fluconazole	459	74.5	24	37.5	13	7.7
	Voriconazole	459	8.5	24	4.2	13	0.0
NSBF (8,650)	Fluconazole	246	80.5	45	51.1	18	55.6
	Voriconazole	243	4.5	45	4.4	18	0.0
Urine (25,881)	Fluconazole	518	80.1	26	53.8	23	56.5
	Voriconazole	516	11.4	26	7.7	23	8.7
Respiratory tract (56,961)	Fluconazole	1,787	79.2	231	51.5	64	42.2
	Voriconazole	1,760	7.8	229	2.2	63	1.6
Skin/soft tissue (11,221)	Fluconazole	252	81.7	23	26.1	23	8.7
	Voriconazole	251	8.0	23	4.3	23	0.0
Genital tract (44,839)	Fluconazole	566	71.9	62	62.9	19	52.6
	Voriconazole	553	6.9	62	4.8	19	0.0
Miscellaneous NOS (33,397)	Fluconazole	1,251	79.2	155	58.7	88	43.2
	Voriconazole	1,223	5.8	154	5.2	88	8.0