Quantitation of Candida albicans Ergosterol Content Improves the Correlation between In Vitro Antifungal Susceptibility Test Results and In Vivo Outcome after Fluconazole Treatment in a Murine Model of Invasive Candidiasis

DOI: 10.1128/AAC.44.8.2081-2085.2000

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Fig. 1.
Survival curves for mice infected with C. albicans isolates which were, by the M27-A method, susceptible (A), resistant (B), or resistant with trailing (C and D) to fluconazole. The results represent the means of at least two separate experiments. There were 10 mice per group in each experiment. FLZ, fluconazole; MKD, milligrams per kilogram per day.

Table 2.

Effect of fluconazole on recovery of CFU from kidney tissue of C. albicans-infected mice

Isolate no.^b	Fluconazole dose (mg/kg/day)	CFU per g of kidney tissue (10⁴) at day 6 sacrifice		P^a for indicated pairs of doses (mg/kg/day)
Isolate no.^b	Fluconazole dose (mg/kg/day)	Median	Range	0 vs 1	0 vs 5	1 vs 5
1 (S)	0	57	41–73
	1	1	0.9–1.4	<0.005
	5	0.53	0.32–0.74		<0.005	n.s.
2 (R)	0	337	40–630
	1	177	120–235	n.s.
	5	583	300–1,100		n.s.	n.s.
3 (Rtr)	0	45	3.5–78
	1	5	3.5–7.1	<0.05
	5	1.5	0.7–2.4		<0.05	<0.01
4 (Rtr)	0	127	63–192
	1	0.44	0.3–0.6	<0.025
	5	0.08	0.05–0.11		<0.025	<0.005

↵a P values were obtained using Student's t test; n.s., not significant (P> 0.05).
↵b Interpretation of fluconazole susceptibilities as determined by the M27-A broth microdilution method are in parentheses. S, susceptible; Rtr, resistant with trailing growth; R, resistant.

Table 3.

Correlation between the SQM MICs and treatment response compared with the M27-A MICs and treatment response

Isolate	MIC		Day 3				Day 6
	SQM	M27-A method	% Survival^a		Fungal burden^b		% Survival		Fungal burden
	SQM	M27-A method	1 mg/kg/day [0.9, 0.5]^c	5 mg/kg/day [1.0, 0.3]	1 mg/kg/day [0.6, 0.8]	5 mg/kg/day [1.0, 0.2]	1 mg/kg/day [0.9, 0.5]	5 mg/kg/day [1.0, 0.3]	1 mg/kg/day [1.0, 0.3]	5 mg/kg/day [1.0, 0.2]
1	1.0	0.125	90	90	13	19	90	90	1.9	9.3
2	54	>64	33	55	106	123	33	55	85	86
3	1.0	>64 (tr^d)	90	95	51	0.02	90	95	0.15	0.06
4	1.0	>64 (tr)	65	90	93	11	65	90	0.67	0.13

↵a Number of animals alive at the indicated day/total number of animals infected × 100.
↵b 10⁴ CFU/g of kidney tissue.
↵c Pearson's coefficients of correlation between the SQM and M27-A MICs (in that order) and therapeutic outcome are given in brackets.
↵d tr, trailing growth.