Daptomycin Bactericidal Activity and Correlation between Disk and Broth Microdilution Method Results in Testing of Staphylococcus aureus Strains with Decreased Susceptibility to Vancomycin

Helio S. Sader; Thomas R. Fritsche; Ronald N. Jones

doi:10.1128/AAC.01491-05

DOI: 10.1128/AAC.01491-05

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FIG. 1.
Time-kill curve results for strain 170A tested against daptomycin (top) and vancomycin (bottom).
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FIG. 2.
Scattergram showing the correlation between the daptomycin broth microdilution MIC and disk zone diameter results.
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FIG. 3.
Scattergram showing the correlation between the vancomycin broth microdilution MIC and disk zone diameter results.
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FIG. 4.
Scattergram showing the correlation between the daptomycin broth microdilution and Etest MIC results.

Tables

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TABLE 1.

MIC and MBC results for daptomycin and vancomycin

Antimicrobial agent/organism (total no. of isolates)	No. of isolates (cumulative %) at MIC/MBC (μg/ml) of:
Antimicrobial agent/organism (total no. of isolates)	≤0.12	0.25	0.5	1	2	4	8	16	>16
MIC
Daptomycin
MRSA-WT (102)^a	2 (2.0)	41 (42.2)	56 ^b (97.1)	3 (100.0)	0	0	0	0	0
hVISA (88)	0	2 (2.3)	52 (61.4)	34 (100.0)	0	0	0	0	0
VISA (17)	0	0	2 (11.8)	7 (52.9)	7 (94.1)	1 (100.0)	0	0	0
Vancomycin
MRSA-WT (102)^a	−^c	−	9 (8.8)	82 (89.2)	11 (100.0)	0	0	0	0
hVISA (88)	−	−	0 (0.0)	9 (10.2)	61 (79.5)	18 (100.0)	0	0	0
VISA (17)	−	−	0 (0.0)	0 (0.0)	0 (0.0)	11 (64.7)	6 (100.0)	0	0
MBC
Daptomycin
MRSA-WT (102)^a	0	29 (28.4)	65 (92.2)	7 (99.0)	1 (100.0)	0	0	0	0
hVISA (88)	0	2 (2.3)	35 (40.9)	49 (97.7)	2 (100.0)	0	0	0	0
VISA (17)	0	0	2 (11.8)	4 (35.3)	8 (82.4)	3 (100.0)	0	0	0
Vancomycin
MRSA-WT (102)^a	−	−	2 (2.0)	38 (39.2)	23 (61.8)	9 (70.6)	15 (85.3)	4 (89.2)	11 (100.0)
hVISA (88)	−	−	0	3 (3.4)	9 (14.9)	5 (19.3)	3 (22.7)	7 (30.7)	61 (100.0)
VISA (17)	−	−	0	0	0	0	0	0	17 (100.0)

↵ a Clinical MRSA isolate with vancomycin MIC of ≤2 μg/ml (homogeneous populations) collected from medical centers worldwide in 2003.
↵ b The underlined numbers are modal values.
↵ c —, dilution not tested.

TABLE 2.

Distribution of isolates according to MBC/MIC ratio for daptomycin and vancomycin

MBC/MIC ratio	No. of isolates (%)
	Daptomycin			Vancomycin
	MRSA-WT	hVISA	VISA	MRSA-WT	hVISA	VISA
1	80 (78.4)	69 (78.4)	12 (70.6)	42 (41.2)	11 (12.5)
2	22 (21.6)	19 (21.6)	5 (29.4)	19 (18.6)	5 (5.7)
4				12 (11.8)	4 (4.5)
8				14 (13.7)	7 (8.0)
≥16				15 (14.7)^a	61 (69.3)^a	17 (100.0)^a

↵ a All isolates had vancomycin MBCs of >16 μg/ml.

TABLE 3.

Time-kill curve results for vancomycin and daptomycin tested against bacteremic MRSA strains

Isolate	Antimicrobial agent	Reduction in log₁₀ CFU/ml at^a:				Activity category^b
Isolate	Antimicrobial agent	T₄	T₈	T₂₄^b	T₄₈	Activity category^b
170A	Vancomycin	0.9	1.7	2.0	2.8	Static
	Daptomycin	4.8	5.6	6.3^c	−^d	Cidal
100A	Vancomycin	0.5	1.1	1.9	2.1	Static
	Daptomycin	6.1^c	6.1^c	6.1^c	−	Cidal^e
13851A	Vancomycin	0.7	1.1	2.9	4.3	Static^e
	Daptomycin	4.8	6.1^c	6.1^c	−	Cidal
16546A	Vancomycin	0.3	0.8	2.6	3.6	Static^f
	Daptomycin	3.5	4.8	5.7^c	−	Cidal^g
14382A	Vancomycin	0.1	0.4	1.7	3.0	Static
	Daptomycin	2.7	4.4	5.6^c	5.6^c	Cidal
2345A	Vancomycin	0.5	1.0	2.4	3.4	Static^e
	Daptomycin	4.0	6.0^c	6.0^c	6.0^c	Cidal
2308A	Vancomycin	0.8	1.3	3.0	4.1	Cidal
	Daptomycin	4.2	6.0^c	6.0^c	−	Cidal
1416A	Vancomycin	0.1	0.8	2.8	3.9	Static^e
	Daptomycin	3.4	4.8	5.9^c	−	Cidal
2336A	Vancomycin	0.4	0.9	3.2	5.6^c	Cidal
	Daptomycin	3.2	5.8^c	5.8^c	−	Cidal
16542A	Vancomycin	0.3	1.0	3.8	5.5^c	Cidal
	Daptomycin	3.2	4.1	5.5^c	−	Cidal
16160A	Vancomycin	0.5	1.7	3.6	4.2	Cidal
	Daptomycin	2.2	2.6	3.8	6.0^c	Cidal
5642A	Vancomycin	0.5	0.7	2.4	3.7	Static^e
	Daptomycin	2.6	4.0	4.3	−	Cidal^g
561A	Vancomycin	0.3	0.8	2.0	3.6	Static^e
	Daptomycin	3.6	5.7^c	5.7^c	−	Cidal
16325A	Vancomycin	(0.1)^h	0.3	2.3	3.2	Static^e
	Daptomycin	3.8	6.0^c	6.0^c	−	Cidal
456A	Vancomycin	0.5	1.3	3.6	3.9	Cidal
	Daptomycin	4.5	5.6^c	5.6^c	−	Cidal
424A	Vancomycin	0.4	1.0	3.5	3.5	Cidal
	Daptomycin	3.1	5.7^c	4.8	−	Cidal
3811A	Vancomycin	1.0	1.6	2.8	3.9	Static^e
	Daptomycin	2.8	3.7	4.9	−	Cidal
14854A	Vancomycin	0.8	1.2	3.0	4.2	Cidal
	Daptomycin	4.4	5.2	6.0^c	−	Cidal
ATCC 29213	Vancomycin	1.2	1.4	2.7	4.6	Static^e
	Daptomycin	3.2	5.9^c	5.9^c	5.9^c	Cidal
ATCC 43300	Vancomycin	0.7	1.0	2.8	3.7	Static^f
	Daptomycin	2.3	2.9	4.0	−	Cidal^g
ATCC 33591	Vancomycin	0.5	1.3	3.8	4.5	Cidal
	Daptomycin	4.0	4.8	5.7^c	−	Cidal

↵ a Compared to the initial inoculum. The values represent averages of 2×, 4×, and 8× reductions in log₁₀ CFU/ml.
↵ b Bactericidal (Cidal) activity was defined as ≥3 log₁₀ reduction in the initial inoculum within 24 h of incubation.
↵ c No bacterial growth was detected.
↵ d −, incubated for 24 h only.
↵ e Bactericidal activity was achieved only at 48 h of incubation.
↵ f Bactericidal activity was achieved at 24 h when tested at 4× and/or 8× MIC.
↵ g Bacteriostatic activity when tested at 2× MIC.
↵ h Value in parentheses represents the increase in the log₁₀ CFU/ml.