Cryptococcus neoformans/gattii Species Complexes from Pre-HIV Pandemic Era Contain Unusually High Rate of Non-Wild-Type Isolates for Amphotericin B

Figures & data

Figure 1 Geometric mean (GM) MIC of four antifungal agents between C. neoformans species complex (black bar) and C. gattii species complex (white bar). Only the p-value of the statistically significant difference is shown.

Abbreviations: AMB, amphotericin B; 5FC, 5-fluorocytosine; ITC, itraconazole; FLC, fluconazole.

Figure 2 Geometric mean (GM) MIC of four antifungal agents among different genotypes in C. neoformans species complex. Only the p-value of the statistically significant difference is shown.

Abbreviations: AMB, amphotericin B; 5FC, 5-fluorocytosine; ITC, itraconazole; FLC, fluconazole.

Table 1 Number of Wild Type Strains Among C. neoformans/gattii Species Complexes Based on Epidemiological Cutoff Values (ECVs)

Species	Number of Wild Type Strains (Percentage)
	Amphotericin B	5 - Fluorocytosine	Itraconazole	Fluconazole
C. neoformans/VNI (clinical)^a	39/118 (33.1%)	112/118 (94.9%)	118/118 (100.0%)	118/118 (100.0%)
C. neoformans/VNI (environmental)	1/25 (4.0%)	24/25 (96.0%)	25/25 (100.0%)	25/25 (100.0%)
C. neoformans/VNI (veterinary)	2/3 (66.7%)	3/3 (100.0%)	3/3 (100.0%)	3/3 (100.0%)
Total of C. neoformans/VNI strains	42/146 (28.8%)	140/146 (95.9%)	146/146 (100.0%)	146/146 (100.0%)
C. gattii/VGI (clinical)	3/5 (60.0%)	5/5 (100.0%)	5/5 (100.0%)	5/5 (100.0%)
C. gattii/VGI (veterinary)	0/1 (0%)	1/1 (100.0%)	1/1 (100.0%)	1/1 (100.0%)
C. deuterogattii/VGII (clinical)	1/1 (100.0%)	1/1 (100.0%)	1/1 (100.0%)	1/1 (100.0%)
Total of C. gattii/VGI and VGII strains	4/7 (57.1%)	7/7 (100.0%)	7/7 (100.0%)	7/7 (100.0%)

Note: ^aIsolated from 98 different patients.

Table 2 Association Analysis of Amphotericin B Susceptibility Patterns Based on ECVs Among C. neoformans/VNI Between Clinical and Environmental Isolates

Sources	No. of Isolates (Percentage)		P value^a
	Wild Type	Non-Wild Type
Clinical (n = 118)^b	39 (33.1%)	79 (66.9%)	0.003
Environmental(n = 25)	1 (4.5%)	24 (96.0%)

Notes: ^aAnalyzed by two-tailed Fisher’s exact test. ^bIsolated from 98 different patients.

Table 3 Comparative Amphotericin B Susceptibility Patterns of Clinical VNI Strains with and Without Prior Amphotericin Therapy

Prior AMB Treatment	Non-Wild Type	Wild Type	P value^a
No (n = 66)	45 (68.2%)	21 (31.8%)	0.498
Yes (n = 20)	12 (60.0%)	8 (40.0%)

Notes: Only VNI strains were included in this analysis as ECV was not available for other C. neoformans genotypes. ^aAnalyzed by two-tailed Fisher’s exact test.

Table 4 Comparative Amphotericin B Susceptibility Patterns of Clinical Strains Between with or Without Prior AMB-Treatment with Environmental Strains Among C. neoformans Species Complex

GM MIC of Clinical Isolates(n = 113, µg/mL)		GM MIC of Environmental Isolates (n = 37, µg/mL)	P value^a
With prior AMB-treatment (n = 35)	0.76 ± 0.53		0.159
Without prior AMB-treatment(n = 78)	0.98 ± 0.70	0.85 ± 0.66	0.488

Note: ^aAnalyzed by two-tailed Mann–Whitney U-Test.