Treatment of candidaemia in a nationwide setting; increased survival with primary echinocandin treatment

Figures & data

Figure 1 Species distribution and prior AFT by hospital department at the time of candidemia diagnosis.

Abbreviation: AFT, antifungal treatment.

Table 1 Species distribution according to prior AFT

	No prior AFT N=679 % (95% CI)	Prior AFT N= 162% (95% CI)	Prior azole^a N=132 % (95% CI)	Prior echinocandins^b N=22 % (95% CI)
Species identification
C. albicans	54.5 (50.7-58.3)	40.7 (33.1—48.7)	43.2 (34.6—52.1)	27.3 (10.7—50.2)
C. glabrata	28.0 (24.6-31.5)	31.5 (24.4—39.2)	31.8 (24.0—40.5)	36.4 (17.2—59.3)
C. krusei	2.4 (1.4—3.8)	11.7 (7.2—17.7)	12.9 (7.7—19.8)	9.1 (1.1—29.2)
Candida tropicalis	3.7 (2.4—5.4)	3.1 (I.0—7.I)	3.0 (0.8—7.6)	4.5 (0.1—22.8)
Candida parapsilosis	2.8 (1.7—4.3)	2.5 (0.7—6.2)	1.5 (0.2—5.4)	9.1 (1.1—29.2)
Others'	4.4 (3.0—6.2)	6.8 (3.4—11.8)	4.5 (I.7—9.6)	9.1 (1.1—29.2)
Polyfungal	4.1 (2.8—5.9)	3.7 (I.4—7.9)	3.0 (0.8—7.6)	4.5 (0.1—22.8)

Notes: ^aOne hundred twenty-seven cases received fluconazole, three cases received posaconazole, and two cases received voriconazole. ^bTwenty-one cases received caspofungin and one case received anidulafungin. ^cOther species, ie, Candida dubliniensis, Candida lusitaniae, and Candida kefyr (see Table S1).

Abbreviation: AFT, antifungal treatment.

Table 2 AFT according to hospital department at the time of candidemia diagnosis

	Total No (%)	ICUNo (%)	Hematology No (%)
Initial AFT after BCC	n=683	n=305	n=30
Azole^a	358 (52.4)	164 (53.8)	9 (30.0)
Echinocandins^b	302 (44.2)	135 (44.3)	17 (56.7)
Amphotericin B	23 (3.4)	6 (2.0)	4 (13.3)
Adequate 1. AFT	576 (84.3)	262 (85.9)	25 (83.3)
Second AFT	n=257	n= 115	n= 12
Azole^c	113 (44.0)	47 (40.9)	1 (8.3)
Echinocandins^d	123 (47.9)	61 (53.0)	5 (41.7)
Amphotericin B	21 (8.2)	7 (6.1)	6 (50.0)
Adequate 2. treatment	247 (96.1)	112 (97.4)	11 (91.7)

Notes: ^aThree hundred fifty-five cases received fluconazole and three cases received voriconazole.

b Two hundred seventy-eight cases received caspofungin and 24 cases received anidulafungin.

c One hundred eleven cases received fluconazole and two cases received voriconazole.

c One hundred nine cases received caspofungin and 14 cases received anidulafungin.

Abbreviations: AFT, antifungal treatment; BCC, blood culture collection; ICU, intensive care unit.

Figure 2 Proportion of patients receiving adequate treatment according to choice of initial antifungal agent.

Note: *100% of amphotericin B-treated cases were adequately treated in both initial and second AFT.
Abbreviation: AFT, antifungal treatment.

Table 3 Treatment and mortality

	TotalNo (%)	Deaths No (%)	Crude Cox HR (95% CI)	Adjusted Cox HR (95% CI)
0- to 7-Day mortality	n=837	n=l98
Prior antifungal treatment	162 (19.4)	33 (16.7)	0.80 (0.55-1.16)	l.24^a (0.84-1.84)
Prior adequate treatment	92 (11.0)	18 (9.1)	0.78 (0.48-1.26)	l.12^a (0.68-1.84)
0- to 14-Day mortality	n=837	n=28l
Treatment after BC	683 (81.6)	160 (56.9)	0.13 (0.10-0.17)	0.l2^b (0.l0-0.l6)
Received treatment	n=682	n=l60
Azole as primary treatment	357 (52.3)	89 (55.6)	Ref	Ref
Echinocandins as primary treatment	302 (44.3)	62 (38.8)	0.79 (0.57-1.09)	0.76^b (0.55-l.06)
amphotericin B as primary treatment	23 (3.4)	9 (5.6)	1.79 (0.90-3.56)	l.50^b (0.74-3.07)
adequate initial Aft	576 (84.3)	131 (81.9)	0.81 (0.54-1.21)	0.80^b (0.53-l.l9)
0- to 14-Day mortality by species
C. glabrata or C. krusei^c	n=223	n=53
Azole as primary treatment	93 (41.7)	27 (50.9)	Ref	Ref
echinocandins as primary treatment	122 (54.7)	22 (41.5)	0.57 (0.32-0.99)	0.50^b (0.28-0.89)
Amphotericin B as primary treatment	8 (3.6)	4 (7.6)	2.27 (0.79-6.49)	l.78^b (0.58-5.4l)
Adequate initial AFT	134 (60.1)	28 (52.8)	0.70 (0.41-1.20)	0.62^b (0.36-l.08)
C. albicans or C. tropicalis^c	n=374	n=88
Azole as primary treatment	223 (59.6)	51 (58.0)	Ref	Ref
echinocandins as primary treatment	144 (38.5)	34 (38.6)	1.01 (0.65-1.55)	l.00^b (0.65-l.55)
Amphotericin B as primary treatment	7 (1.9)	3 (3.4)	2.51 (0.78-8.04)	2.30^b (0.7l-7.46)
0- to 30-Day mortalityi^c	n=682	n=239
Azole as primary treatment	357 (52.4)	129 (54.0)	ref	ref
Echinocandins as primary treatment	302 (44.3)	101 (42.3)	0.89 (0.68-1.15)	0.86^b (0.66-l.l2)
Amphotericin B as primary treatment	23 (3.4)	9 (3.8)	1.24 (0.63-2.44)	l.04^b (0.52-2.07)
Adequate initial AFT	576 (84.3)	197 (82.4)	0.83 (0.60-1.16)	l^b (omitted)
0- to 30-Day mortality by species
C. glabrata or C. krusei^c	n=223	n=78
Azole as primary treatment	93 (41.7)	39 (50.0)	Ref	Ref
Echinocandins as primary treatment	122 (54.7)	35 (44.9)	0.60 (.038-0.95)	0.56^b (0.35-0.90)
Amphotericin B as primary treatment	8 (3.6)	4 (5.1)	1.55 (0.56-4.35)	l.26^b (0.44-3.65)
Adequate initial AFT	134 (60.1)	42 (53.9)	0.71 (0.45-1.1!)	0.66^b (0.42-l.04)
C. albicans or C. tropicalis^c	n=374	n= 135
Azole as primary treatment	223 (59.6)	76 (56.3)	Ref	Ref
Echinocandins as primary treatment	144 (38.5)	56 (41.5)	1.15 (0.81-1.62)	l.l4^b (0.80-l.60)
Amphotericin B as primary treatment	7 (1.9)	3 (2.2)	1.65 (0.52-5.23)	l.49^b (0.47-4.78)
0- to 365-Day mortality	n=682	n=390
Azole as primary treatment	357 (52.4)	199 (51.0)	Ref	Ref
Echinocandins as primary treatment	302 (44.3)	177 (45.4)	1.03 (0.84-1.26)	0.99^b (0.8l-l.22)
Amphotericin B as primary treatment	23 (3.4)	14 (3.6)	1.22 (0.71-2.10)	0.97^b (0.55-l.69)
Adequate initial AFT	576 (84.3)	318 (81.5)	0.75 (0.58-0.97)	l^b (omitted)
0- to 365-Day mortality by species
C. glabrata or C. krusei^c	n=223	n= 141
Azole as primary treatment	93 (41.7)	64 (45.4)	Ref	Ref
Echinocandins as primary treatment	122 (54.7)	70 (49.7)	0.71 (0.51-1.00)	0.66^b (0.46-0.93)
Amphotericin B as primary treatment	8 (3.6)	7 (5.0)	1.71 (0.79-3.74)	l.44^b (0.65-3.l8)
Adequate initial AFT	134 (60.1)	79 (56.0)	0.74 (0.53-1.04)	0.70^b (0.50-0.98)
C. albicans or C. tropicalis^c	n=374	n=203
Azole as primary treatment	223 (59.6)	108 (53.2)	Ref	Ref
Echinocandins as primary treatment	144 (38.5)	90 (44.3)	1.38 (1.04-1.82)	l.37^b (l.03-l.8l)
Amphotericin B as primary treatment	7 (1.9)	5 (2.5)	1.98 (0.81-4.85)	l.82^b (0.69-4.27)

Notes: ^aSee supplement DAG1: Adjusted for fungal treatment after blood sampling, hematologic disease, and abdominal surgery.

b See supplement DAG2: Adjusted for fungal treatment before blood sampling, hematologic disease, and abdominal surgery.

c Only patients receiving treatment were included.

Table S1 Species distribution

Species	No.	%
C. albicans	437	52.0
C. glabrata	241	28.7
C. krusei	35	4.2
C. tropicalis	30	3.6
C. parapsilosis	23	2.7
C. dubliniensis	15	1.8
C. lusitaniae	6	0.7
C. kefyr	5	0.6
C. norvegensis	3	0.4
C. guilliermondii	3	0.4
C. orthopsilosis	2	0.2
C. pelliculosa	2	0.2
C. inconspicua	1	0.1
C. palmioleophila	1	0.1
S. cerevisiae	3	0.4
Polyfungal	34	4.0
Total	841	100.0

Figure S1 Flow chart of the study population.

Figure S2 Directed Acyclic Graphs (DAG s): Prior antifungal treatment and 7-day mortality.

Figure S3 Directed Acyclic Graphs (DAGs) showing antifungal treatment after blood culture collection and 14-day mortality.