Healthcare resource utilization and economic burden of antifungal management in patients with hematologic malignancy in Japan: a retrospective database study

Figures & data

Figure 1. Study attrition: allo-HSCT cohort.

Figure 2. Study attrition: AML/MDS cohort.

Table 1. Demographic and baseline characteristics of the allo-HSCT cohort.

	Total (N = 863)		Group A (N = 26)		Group B (N = 51)		Group C (N = 249)		Group D (N = 537)		p-value (Group A vs. Group C)	p-value (Group B vs. Group D)
	N	%	N	%	N	%	N	%	N	%
Age at index date, year
Mean	50.0		52.7		48.5		50.2		49.9		.3525	.5097
SD	14.1		13.6		13.1		13.4		14.5
Median	53		58		47		54		52		.2991	.3906
Age category
18–30	113	13.1	2	7.7	6	11.8	29	11.7	76	14.2	.8859	.2578
31–40	112	13.0	2	7.7	6	11.8	35	14.1	69	12.9
41–50	167	19.4	5	19.2	17	33.3	39	15.7	106	19.7
51–60	218	25.3	9	34.6	10	19.6	76	30.5	123	22.9
≧61	253	29.3	8	30.8	12	23.5	70	28.1	163	30.4
Gender
Female	367	42.5	14	53.9	20	39.2	112	45.0	221	41.2	.3879	.7879
Male	496	57.5	12	46.1	31	60.8	137	55.0	316	58.8
Antifungal use during look back period
Yes	517	59.9	15	57.7	19	37.3	154	61.9	329	61.3	.6787	.0009
Stem source
Bone marrow	187	21.7	4	15.4	5	9.8	15	6.0	163	30.4	.2172	.0012
Peripheral blood	199	23.1	4	15.4	22	43.1	44	17.7	129	24.0
Cord blood	477	55.3	18	69.2	24	47.1	190	76.3	245	45.6
Indication for allo-HSCT
Acute myeloid leukemia (AML)	415	48.1	13	50.0	27	52.9	115	46.2	260	48.4	.7105	.5368
Acute lymphoblastic leukemia (ALL)	144	16.7	5	19.2	6	11.8	48	19.3	85	15.8	.9955	.4432
Myelodysplastic syndrome (MDS)	238	27.6	4	15.4	11	21.6	46	18.5	177	33.0	1.0000	.0955
Lymphoma	135	15.6	0	0.0	11	21.6	37	14.9	87	16.2	.0320	.3256
Others	843	97.7	26	100.0	49	96.1	244	98.0	524	97.6	1.0000	.3793
Form of medication intake (at index)
Oral	259	30.0	5	19.2	12	23.5	79	31.7	163	30.4	.1881	.3084
Injection	33	3.8	0	0.0	1	2.0	6	2.4	26	4.8	1.0000	.4998
Bed size
200–499	197	22.8	9	34.6	9	17.6	90	36.1	89	16.6	.8772	.8442
≧500	666	77.2	17	65.4	42	82.4	159	63.9	448	83.4
Year of admission
2010	1	0.1	0	0.0	0	0.0	0	0.0	1	0.2	.3982	.0326
2011	48	5.6	0	0.0	0	0.0	8	3.2	40	7.5
2012	61	7.1	0	0.0	2	3.9	8	3.2	51	9.5
2013	59	6.8	0	0.0	3	5.9	19	7.6	37	6.9
2014	90	10.4	3	11.5	5	9.8	35	14.1	47	8.8
2015	156	18.1	6	23.1	12	23.5	41	16.5	97	18.1
2016	159	18.4	2	7.7	8	15.7	39	15.7	110	20.5
2017	264	30.6	13	50.0	16	31.4	92	37.0	143	26.6
2018	25	2.9	2	7.7	5	9.8	7	2.8	11	2.1
Charlson comorbidity index (CCI)
Mean	4.3		3.2		3.9		3.8		4.6		.2056	.0554
SD	2.4		1.7		2.8		2.5		2.3		.2372	.0041
0	21	2.4	2	7.7	2	3.9	5	2.0	12	2.2
1	20	2.3	2	7.7	2	3.9	10	4.0	6	1.1
2	154	17.8	4	15.4	14	27.5	60	24.1	76	14.2
3	178	20.6	7	26.9	11	21.6	78	31.3	82	15.3
≧4	490	56.8	11	42.3	22	43.1	96	38.6	361	67.2

Abbreviations. SD, standard deviation; allo-HSCT, allogeneic hematopoietic stem cell transplantation.

Population grouping based on antifungal use:

• Group A: Single antifungal therapy (fluconazole only) [n = 26].

• Group B: Single antifungal therapy (non-fluconazole single antifungal only) [n = 51].

• Group C: Multiple antifungal therapy (fluconazole-containing antifungal regimen) [n = 249].

• Group D: Multiple antifungal therapy (non-fluconazole-containing antifungal regimen) [n = 537].

• Group E: No antifungal drug use [n = 0].

Figure 3. Antifungal treatments received by the allo-HSCT and AML/MDS cohorts.

Table 2. Demographic and baseline characteristics of the AML/MDS.

	Total (N = 4498)		Group A (N = 889)		Group B (N = 823)		Group C (N = 1344)		Group D (N = 904)		Group E (N = 538)		p-value (Group A vs. Group C)	p-value (Group B vs. Group D)
	N	%	N	%	N	%	N	%	N	%	N	%
Age at index date, year
Mean	65.0		63.7		64.2		64.2		65.0		70.7		.3655	.2172
SD	14.7		15.0		15.1		14.9		13.9		13.2
Median	68		67		67		67		68		73		.4107	.5816
Age category
18–30	151	3.4	36	4.1	27	3.3	50	3.7	26	2.9	12	2.2	.2809	.2661
31–40	204	4.5	39	4.4	49	6.0	72	5.4	37	4.1	7	1.3
41–50	378	8.4	92	10.4	74	9.0	110	8.2	77	8.5	25	4.7
51–60	564	12.5	129	14.5	92	11.2	179	13.3	122	13.5	42	7.8
≧61	3201	71.2	593	66.7	581	70.6	933	69.4	642	71.0	452	84.0
Gender
Female	1698	37.8	333	37.5	296	36.0	531	39.5	322	35.6	216	40.2	.3300	.8807
Male	2800	62.3	556	62.5	527	64.0	813	60.5	582	64.4	322	59.8
Antifungal use during look-back period
Yes	507	11.3	111	12.5	92	11.2	138	10.3	109	12.1	57	10.6	.1031	.5695
AML/MDS during index hospitalization
Cytarabine	3906	86.8	809	91.0	766	93.1	1083	80.6	745	82.4	503	93.5	<.0001	<.0001
Daunorubicin	1255	27.9	257	28.9	208	25.3	482	35.9	249	27.5	59	11.0	.0006	.2853
Idarubicin	1669	37.1	282	31.7	274	33.3	601	44.7	449	49.7	63	11.7	<.0001	<.0001
Enocitabine	573	12.7	65	7.3	43	5.2	288	21.4	159	17.6	18	3.4	<.0001	<.0001
Form of medication intake (at index)
Oral	633	14.1	146	16.4	84	10.2	275	20.5	128	14.2	0	0.00	.0169	.0124
Injection	166	3.7	3	0.3	24	2.9	83	6.2	56	6.2	0	0.00	<.0001	.0012
Bed size
200–499	2123	47.2	396	44.5	431	52.4	601	44.7	440	48.7	255	47.4
≥500	2227	49.5	444	49.9	369	44.8	704	52.4	445	49.2	265	49.3
Year of admission
2010	3	0.1	1	0.1	0	0.0	1	0.1	1	0.1	0	0.00	<.0001	.3626
2011	337	7.5	40	4.5	65	7.9	125	9.3	70	7.7	37	6.9
2012	318	7.1	39	4.4	65	7.9	106	7.9	76	8.4	32	6.0
2013	410	9.1	70	7.9	68	8.3	121	9.0	108	12.0	43	8.0
2014	609	13.5	105	11.8	116	14.1	186	13.8	127	14.1	75	13.9
2015	828	18.4	190	21.4	149	18.1	237	17.6	153	16.9	99	18.4
2016	965	21.5	202	22.7	165	20.1	290	21.6	179	19.8	129	24.0
2017	968	21.5	228	25.7	180	21.9	266	19.8	177	19.6	117	21.8
2018	60	1.3	14	1.6	15	1.8	12	0.9	13	1.4	6	1.1
Charlson Comorbidity Index (CCI)
Mean	3.4		3.2		3.4		3.3		3.5		3.8		.2614	.4270
SD	2.2		2.0		2.2		2.1		2.4		2.4
0	163	3.6	30	3.4	27	3.3	46	3.4	44	4.9	16	3.0	.0590	.2575
1	57	1.3	9	1.0	13	1.6	15	1.1	9	1.0	11	2.0
2	1801	40.0	372	41.8	312	37.9	598	44.5	349	38.6	170	31.6
3	1018	22.6	225	25.3	208	25.3	268	19.9	204	22.6	113	21.0
≥4	1459	32.4	253	28.5	263	32.0	417	31.0	298	33.0	228	42.4

Abbreviation. SD, standard deviation.

Population grouping based on antifungal use:

• Group A: Single antifungal therapy (fluconazole only) [n = 889]

• Group B: Single antifungal therapy (non-fluconazole single antifungal only) [n = 823]

• Group C: Multiple antifungal therapy (fluconazole-containing antifungal regimen) [n = 1344]

• Group D: Multiple antifungal therapy (non-fluconazole-containing antifungal regimen) [n = 904]

• Group E: No antifungal drug use [n = 538]

Table 3. Hospitalization and HCRU during follow up period for the allo-HSCT cohort.

	Total (N = 863)		Group A (N = 26)		Group B (N = 51)		Group C (N = 249)		Group D (N = 537)		p-value (Group A vs. Group C)	p-value (Group B vs. Group D)
	N	％	N	％	N	％	N	％	N	％
Index hospitalization
Length of index hospitalization
Mean	112.5		94.4		93.2		122.9		110.3		.0451	.1248
SD	74.1		35.1		40.0		71.2		78.6
Median	93		92		88		106		90		.0862	.5306
ICU stay days ICU hospitalization days
N, %	58	6.7	0	0.0	4	7.8	18	7.2	36	6.7	.2342	.7690
Mean	8.8				6.0		8.4		9.3			.2266
SD	5.1				5.4		5.0		5.1
Median	9.5				4.0		8.0		11.5			.3011
Total hospitalization
Total hospitalization days
Mean	111.0		94.4		93.2		121.8		108.5		.0379	.1170
SD	66.0		35.1		40.0		65.8		68.5
Median	93		92		88		106		90		.0862	.5244
Number of readmissions
N, %	2	0.2	0	0.0	0	0.0	0	0.0	2	0.4		1.0000
Mean	1.0								1.0
SD	0.0								0.0
Median	1								1
Total readmission days
N, %	2	0.2	0	0.0	0	0.0	0	0.0	2	0.4		1.0000
Mean	42.5								42.5
SD	34.7								34.7
Median	43								43
Number of outpatient visit
N, %	608	70.5	24	92.3	40	78.4	186	74.7	358	66.7	.0443	.0860
Mean	28.6		18.2		25.7		20.1		34.1		.4765	.0207
SD	20.0		7.6		19.0		12.7		21.9
Median	23		17		22		18		30		.7627	.0213
Imaging
X ray
N	712	82.5	18	69.2	30	58.8	206	82.7	458	85.3	.1104	<.0001
Mean	12.5		6.7		8.7		11.5		13.4		.0696	.0969
SD	13.7		3.0		7.8		11.1		15.1
Median	7		7		6		7		8		.2951	.2642
CT (excluding cisterna)
N	726	84.1	22	84.6	43	84.3	212	85.1	449	83.6	1.0000	.8970
Mean	4.8		2.2		3.7		4.5		5.1		.0340	.0972
SD	5.1		1.2		3.5		4.9		5.4
Median	3		2		3		3		3		.0221	.1888
Microbiologic examination
(1→3)-beta-D-glucan
N	863	100.0	26	100.0	51	100.0	249	100.0	537	100.0
Mean	15.3		10.4		11.3		13.8		16.5		.0899	.0035
SD	11.7		7.1		6.7		10.1		12.7
Median	13		7		11		12		13		.0761	.0016
Aspergillus antigen
N	590	68.4	3	11.5	29	56.9	135	54.2	423	78.8	<.0001	.0004
Mean	10.9		2.7		10.3		7.4		12.1		.3409	.3339
SD	9.8		2.9		5.5		8.6		10.1
Median	9		1		10		3		10		.2637	.9384
Culture procedure
N	852	98.7	26	100.0	51	100.0	248	99.6	527	98.1	1.0000	1.0000
Mean	61.2		15.2		38.0		34.9		78.2		.0449	.0008
SD	75.3		11.5		31.8		49.6		84.5
Median	32		12		27		19		58		.0031	.0002

Abbreviations. SD, standard deviation; ICU, intensive care unit; IFI, invasive fungal infections.

Population grouping based on antifungal use:

• Group A: Single antifungal therapy (fluconazole only) [n = 26].

• Group B: Single antifungal therapy (non-fluconazole single antifungal only) [n = 51].

• Group C: Multiple antifungal therapy (fluconazole-containing antifungal regimen) [n = 249].

• Group D: Multiple antifungal therapy (non-fluconazole-containing antifungal regimen) [n = 537].

• Group E: No antifungal drug use [n = 0].

Table 4. Hospitalization and HCRU during follow up period for the AML/MDS cohort.

	Total (N = 4498)		Group A (N = 889)		Group B (N = 823)		Group C (N = 1344)		Group D (N = 904)		Group E (N = 538)		p-value (Group A vs. Group C)	p-value (Group B vs. Group D)
	N	％	N	％	N	％	N	％	N	％	N	％
Hospitalization
Index hospitalization
Length of index hospitalization
Mean	64.9		52.5		60.6		73.5		81.8		42.1		<.0001	<.0001
SD	55.4		38.7		48.4		62.8		62.5		41.7
Median	44		38		42		49		61		32		<.0001	<.0001
ICU stay days ICU
N, %	80	1.8	5	0.6	13	1.6	29	2.2	26	2.9	7	1.3	.0026	.0701
Mean	6.9		4.2		5.7		7.9		7.4		4.9		.1412	.3204
SD	4.9		5.5		4.6		5.0		5.0		2.5
Median	7.0		2.0		6.0		9.0		7.0		6.0		.1392	.3213
Total hospitalization
Total hospitalization days
Mean	108.0		107.7		101.9		117.7		118.8		75.9		.0007	<.0001
SD	69.3		64.3		66.7		70.0		73.0		61.8
Median	98		106		95		106		107		64		.0044	<.0001
Number of readmissions
N, %	2278	50.6	547	61.5	395	48.0	716	53.3	379	41.9	241	44.8	.0001	.0113
Mean	2.3		2.5		2.3		2.3		2.2		2.3		.0208	.4446
SD	1.3		1.3		1.3		1.3		1.3		1.4
Median	2		2		2		2		2		2		.0053	.3574
Total readmission days
N, %	2278	50.6	547	61.5	395	48.00	716	53.27	379	41.9	241	44.80	.0001	.0113
Mean	85.8		89.6		85.95		84.2		89.1		76.3		.0496	.3904
SD	49.5		46.8		48.8		49.3		53.7		49.7
Median	80		86		83		79		81		66		.0195	.7177
Number of outpatient visits
N, %	3177	70.6	691	77.7	575	69.9	979	72.8	592	65.5	340	63.2	.0093	.0521
Mean	21.7		18.1		13.6		27.7		26.3		17.7		<.0001	<.0001
SD	30.7		23.3		17.0		37.4		37.2		22.3
Median	11		11		10		13		10		11		.0019	.0001
Imaging
X ray
N	4158	92.4	799	89.9	763	92.7	1252	93.2	868	96.0	476	88.5	.0056	.0027
Mean	6.1		3.4		4.9		7.4		9.2		3.2		<.0001	<.0001
SD	7.5		3.1		5.1		8.0		10.7		3.3
Median	4		3		3		5		6		2		<.0001	<.0001
CT (excluding cisterna)
N	3131	69.6	488	54.9	539	65.5	1087	80.9	751	83.1	266	49.4	<.0001	<.0001
Mean	2.9		1.8		2.1		3.6		3.8		1.8		<.0001	<.0001
SD	2.8		1.3		1.7		3.0		3.5		1.5
Median	2		1		1		3		3		1		<.0001	<.0001
Microbiologic examination
(1→3)-beta-D-glucan
N	4421	98.3	869	97.8	813	98.8	1338	99.6	904	100.0	497	92.4	.0001	.0006
Mean	6.2		3.8		4.5		8.3		8.9		2.9		<.0001	<.0001
SD	8.0		2.8		3.3		10.9		9.4		3.4
Median	4		3		4		6		7		2		<.0001	<.0001
Aspergillus antigen
N	998	22.2	97	10.9	102	12.4	425	31.6	338	37.4	36	6.7	<.0001	<.0001
Mean	4.9		2.1		2.0		5.2		6.3		2.6		.0074	.0002
SD	9.9		2.3		2.0		11.0		11.3		2.9
Median	2		1		1		2		2		1		.0002	<.0001
Culture procedure
N	4155	92.4	779	87.6	759	92.2	1312	97.6	892	98.7	413	76.8	<.0001	<.0001
Mean	18.5		7.9		10.2		26.3		28.3		7.6		<.0001	<.0001
SD	40.4		9.5		10.2		56.5		47.2		15.9
Median	9		5		7		12		15		5		<.0001	<.0001

Abbreviations. SD, standard deviation; ICU, intensive care unit; IFI, invasive fungal infections.

Population grouping based on antifungal use:

• Group A: Single antifungal therapy (fluconazole only) [n = 889].

• Group B: Single antifungal therapy (non-fluconazole single antifungal only) [n = 823].

• Group C: Multiple antifungal therapy (fluconazole-containing antifungal regimen) [n = 1344].

• Group D: Multiple antifungal therapy (non-fluconazole-containing antifungal regimen) [n = 904].

• Group E: No antifungal drug use [n = 538].

Table 5. Costs (in USD) for the allo-HSCT cohort during follow up period.

	Total	Group A	Group B	Group C	Group D	p-value (Group A vs. Group C)	p-value (Group B vs. Group D)
	N = 863	N = 26	N = 51	N = 249	N = 537
Total (inpatient + outpatient)
Mean	180,541	110,403	153,561	170,109	191,336	.0017	.0123
SD	100,584	36,204	86,571	95,370	104,052
Median	153,788	104,085	135,832	144,200	160,816	.0007	.0054
Hospitalization (inpatient)
Total
Mean	165,551	98,529	138,542	159,920	173,973	.0014	.0222
SD	102,312	34,522	86,930	95,903	106,982
Median	133,798	91,617	114,820	131,265	139,973	.0003	.0136
Index hospitalization
Mean	148,213	89,533	111,337	144,989	156,052	.0018	.0019
SD	95,066	32,170	47,023	89,084	101,217
Median	117,334	82,063	107,389	118,252	121,972	.0002	.0025
Readmission
Mean	53,838	–	–	–	53,838
SD	49,669	–	–	–	49,669
Median	53,838	–	–	–	53,838
Outpatient
Total
Mean	21,275	12,862	19,148	13,639	26,045	.7625	.0359
SD	18,283	9,725	16,220	12,065	19,991
Median	14,828	10,105	14,674	10,885	20,899	.9006	.0296
Costs of interest
Drug cost
Antifungal drugs
Mean	18,175	3476	12,628	12,970	21,827	<.0001	<.0001
SD	14,906	3829	8433	10,778	16,028
Median	14,757	1,979	11,040	9675	19,159	<.0001	<.0001
Antibacterial drugs
Mean	3046	1433	2544	3252	3074	.0005	.2139
SD	2725	748	1979	2528	2912
Median	2248	1431	2322	2678	2107	<.0001	.4524
Platelets
Mean	29,890	11,026	18,531	29,101	32,243	.0015	.0046
SD	31,373	8,024	15,840	27,944	34,070
Median	19,318	8786	14,378	20,255	19,969	<.0001	.0008
Red blood cells
Mean	3020	1297	2069	2999	3214	.0028	.0207
SD	2908	1132	1403	2608	3163
Median	2072	1218	1690	2127	2304	.0004	.0607
Examination cost
X ray
Mean	119	79	76	105	131	.1964	.0018
SD	107	53	89	94	114
Median	88	78	47	76	98	.4209	<.0001
CT (Excluding cisterna)
Mean	581	327	540	524	622	.0657	.3143
SD	520	292	476	490	540
Median	400	200	409	360	478	.0204	.3969
(1→3)-beta-D-glucan
Mean	579	382	417	430	673	.3909	<.0001
SD	371	255	229	273	394
Median	471	279	404	362	627	.2552	<.0001
Aspergillus antigen
Mean	207	62	227	147	228	.2886	.9819
SD	172	85	162	176	167
Median	165	32	214	66	181	.2118	.8301
Culture procedure
Mean	865	258	637	566	1055	.0323	.0032
SD	920	144	523	727	995
Median	540	224	537	353	781	.0005	.0029

Abbreviations. SD, standard deviation; IFI, invasive fungal infections; anti-CMV, anti-cytomegalovirus; G-CSF, granulocyte-colony stimulating factor; CT, computerized tomography; EGD, esophagogastroduodenoscopy; MRI, magnetic resonance imaging; USD, US dollar equivalents.

Population grouping based on antifungal use:

• Group A: Single antifungal therapy (fluconazole only) [n = 26].

• Group B: Single antifungal therapy (non-fluconazole single antifungal only) [n = 51].

• Group C: Multiple antifungal therapy (fluconazole-containing antifungal regimen) [n = 249].

• Group D: Multiple antifungal therapy (non-fluconazole-containing antifungal regimen) [n = 537].

• Group E: No antifungal drug use [n = 0].

Table 6. Costs (in USD) for the AML/MDS cohort during follow up period.

	Total	Group A	Group B	Group C	Group D	Group E	p-value (Group A vs. Group C)	p-value (Group B vs. Group D)
	N = 4498	N = 889	N = 823	N = 1344	N = 904	N = 538
Total (inpatient + outpatient)
Mean	105,929	93,288	86,402	129,884	124,610	65,451	<.0001	<.0001
SD	71,367	55,827	53,466	79,238	76,206	56,042
Median	93,676	88,360	80,543	112,995	111,724	54,983	<.0001	<.0001
Hospitalization (inpatient)
Total
Mean	95,369	84,682	80,575	115,156	112,186	57,969	<.0001	<.0001
SD	60,725	49,048	49,989	64,004	64,650	49,218
Median	87,019	81,772	73,822	104,808	103,024	46,365	<.0001	<.0001
Index hospitalization
Mean	51,657	36,182	43,457	64,842	70,164	25,735	<.0001	<.0001
SD	41,375	24,690	29,122	48,047	45,716	23,615
Median	39,991	29,288	35,495	51,055	58,492	19,127	<.0001	<.0001
Readmission
Mean	57,946	54,621	55,875	61,361	64,964	47,708	.0013	.0019
SD	38,217	33,062	37,452	39,310	43,707	34,713
Median	51,255	49,299	47,829	53,872	56,441	40,791	.0055	.0021
Outpatient
Total
Mean	14,950	11,071	8340	20,219	18,970	11,839	<.0001	<.0001
SD	27,885	21,022	14,558	35,172	32,172	20,748
Median	4446	4036	3755	5038	5061	4337	<.0001	<.0001
Costs of interest
Drug cost
Antifungal drugs
Mean	6620	2613	4232	8463	10,488	3998	<.0001	<.0001
SD	9284	4514	5490	9802	12,432	6054
Median	3542	1215	2588	5178	6828	2127	<.0001	<.0001
Antibacterial drugs
Mean	2502	1992	2231	2962	3163	1242	<.0001	<.0001
SD	2491	1870	2229	2745	2829	1492
Median	1768	1488	1639	2232	2393	663	<.0001	<.0001
Platelets
Mean	20,909	17,193	16,281	25,628	25,149	13,959	<.0001	<.0001
SD	21,806	17,102	15,227	24,921	25,088	17,651
Median	14,378	12,138	11,981	17,485	17,443	8499	<.0001	<.0001
Red blood cells
Mean	2786	2472	2340	3161	3284	2218	<.0001	<.0001
SD	2387	2091	1965	2520	2584	2455
Median	2127	1950	1849	2482	2482	1418	<.0001	<.0001
Examination cost
X ray
Mean	80	66	67	92	105	51	<.0001	<.0001
SD	76	61	55	75	105	50
Median	57	47	51	74	74	37	<.0001	<.0001
CT (Excluding cisterna)
Mean	402	283	297	511	495	258	<.0001	<.0001
SD	389	292	243	449	443	237
Median	270	200	200	360	360	185	<.0001	<.0001
(1→3)-beta-D-glucan
Mean	275	224	204	353	344	153	<.0001	<.0001
SD	286	209	180	338	337	190
Median	201	187	172	249	238	125	<.0001	<.0001
Aspergillus antigen
Mean	138	83	58	152	183	106	.0004	<.0001
SD	241	168	125	244	284	254
Median	33	33	17	33	49	17	<.0001	<.0001
Culture procedure
Mean	459	291	286	623	654	230	<.0001	<.0001
SD	677	417	331	799	872	431
Median	262	207	215	345	357	131	<.0001	<.0001

Abbreviations. SD, standard deviation; IFI, invasive fungal infections; anti-CMV, anti-cytomegalovirus; G-CSF, granulocyte-colony stimulating factor; CT, computerized tomography; EGD, esophagogastroduodenoscopy; MRI, magnetic resonance imaging; USD, US dollar equivalents.

Population grouping based on antifungal use:

• Group A: Single antifungal therapy (fluconazole only) [n = 889].

• Group B: Single antifungal therapy (non-fluconazole single antifungal only) [n = 823].

• Group C: Multiple antifungal therapy (fluconazole-containing antifungal regimen) [n = 1344].

• Group D: Multiple antifungal therapy (non-fluconazole-containing antifungal regimen) [n = 904].

• Group E: No antifungal drug use [n = 538].

Data availability statement

The data that support this study’s findings are available from MSD K.K., Tokyo, Japan upon request. Some restrictions apply to the availability of these data, which were used under license for this research study.