Background
Methods
Design and study population
Screening, microbiological cultures, and Candida score
Serological biomarkers
Multiplex quantitative real-time PCR (MRT-PCR)
Study protocol and collection of data
Definitions
Statistical analysis
Results
Study population and salient findings
Operation | Surgical procedures | Total | ||
---|---|---|---|---|
1st | 2nd | 3rd | ||
Surgery of the esophagus | ||||
Esophagectomy with/without gastrectomy | 13 | 4 | 2 | 19 |
Surgery of the stomach | ||||
Gastric bypass (gastroduodenostomy, gastrojejunal, Roux-en-Y) | 7 | 7 | 1 | 15 |
Radical subtotal gastrectomy | 4 | 2 | 6 | |
Total gastrectomy | 4 | 1 | 1 | 6 |
Partial gastrectomy plus vagus nerve transection | 2 | 2 | ||
Gastrorraphy | 1 | 1 | ||
Gastrostomy | 1 | 1 | ||
Surgery of the gallbladder, biliary tract, and liver | ||||
Cholecystectomy | 26 | 1 | 27 | |
Biliary tract surgery (cholecystostomy, bypasses, sphincteroplasty, etc.) | 11 | 4 | 5 | 20 |
Segmental hepatectomy | 6 | 6 | ||
Resection hydatid cyst | 3 | 3 | ||
Open drainage of liver abscess | 1 | 1 | 2 | |
Resection hepatic tumor | 1 | 1 | ||
Multiple or simple hepatorrhaphy | 1 | 1 | ||
Surgery of the pancreas | ||||
Duodenocephalic pancreatectomy | 11 | 2 | 13 | |
Drainage pancreatic abscess | 9 | 1 | 10 | |
Distal, subtotal pancreatectomy or resection of pancreatic lesions | 5 | 1 | 1 | 7 |
Surgery of the small intestine and colon | ||||
Intestinal resection: duodenectomy, enterocolectomy, enterectomy, jejunectomy | 34 | 10 | 2 | 46 |
Subtotal colectomty (includes hemicolectomy and sigmoidectomy) | 37 | 5 | 1 | 43 |
Colostomy or ileostomy (includes sigmoidostomy) duodenostomy | 16 | 19 | 4 | 39 |
Intestinal anastomoses without resection (small intestine, small-large intestine, large intestine) | 15 | 4 | 2 | 21 |
Total colectomy | 7 | 7 | ||
Appendectomy | 3 | 3 | ||
Closure of stoma | 1 | 1 | 1 | 3 |
Drainage of diverticular abscess | 2 | 2 | ||
Reduction of intestinal volvolus. Intestinal intussusception | 2 | 2 | ||
Meckel’s diverticulum resection | 1 | 1 | ||
Retroperitoneum | ||||
Drainage of intraperitoneal abscess (including epiploic, iliac fossa, perisplenic and perigastric) | 5 | 12 | 17 | |
Enterotomy: foreign body | 2 | 2 | ||
Drainage retroperitoneal abscess | 1 | 1 | 2 | |
Other | ||||
Exploratory laparotomy | 29 | 32 | 18 | 79 |
Drainage of abdominal wall abscess | 2 | 2 | 2 | 6 |
Hernia repair with/without mesh | 2 | 2 | 4 | |
Splenectomy. Splenorrhaphy | 1 | 1 | 2 | |
Drainage subphrenic or subdiaphragmatic abscess | 1 | 1 | 2 | |
Resection lesion in the mesenterium or omentum | 1 | 1 | ||
Aortobifemoral bypass | 1 | 1 | ||
Endovascular repair of abdominal aortic aneurysm | 1 | 1 | ||
Placement Bogota bag | 1 | 1 | ||
Ileofemoral thromboendarterectomy | 1 | 1 | ||
Total | 426 |
Diagnosis |
P value | ||||||
---|---|---|---|---|---|---|---|
Total | NCI | LGCC | HGCC | IAC | Candidemia | ||
(n = 233) | (n = 48) | (n = 130) | (n = 24) | (n = 20) | (n = 11) | ||
Age, years, mean (± SD) | 66.7 ± 13.2 | 66.9 ± 11.9 | 65.8 ± 13.9 | 70.7 ± 9.2 | 67.1 ± 15.7 | 67.5 ± 12.2 | .597 |
Male/female, % | 67.0/33.0 | 72.9/27.1 | 70.0/30.0 | 50.0/50.0 | 60.0/40.0 | 54.5/45.5 | .228 |
ICU admission | |||||||
APACHE II | 18.4 ± 6.3 | 18.1 ± 6.2 | 18.5 ± 6.1 | 18.2 ± 7.1 | 19.6 ± 7.0 | 18.3 ± 6.5 | .925 |
SOFAa
| 7 (5 ; 9) | 6.5 (5 ; 8) | 7 (5 ; 10) | 7.5 (4.5; 9.5) | 6.5 (4 ; 10) | 7.5 (5 ; 9) | .583 |
Maximum score during ICU stay | |||||||
APACHE II | 18.7 ± 6.3 | 17.7 ± 6.6 | 18.3 ± 6.1 | 21.4 ± 7.7 | 19.4 ± 5.0 | 19.5 ± 4.7 | .162 |
SOFAa
| 7 (5–10) | 7 (4–9) | 7 (5–10) | 7 (5–10) | 7 (5–12) | 9 (5.5–10) | .702 |
Candida score
a
| 4 (3–4) | 3 (2–4) | 4 (3–4) | 4 (3–5) | 4.5 (4–5) | 3 (3–4) | < .001 |
ICU length of stay, daysa
| 15 (10–25) | 12 (8–19) | 14 (9–25) | 21 (17–28) | 14 (11–19) | 16 (8–38) | .017 |
Hospital length of stay, daysa
| 37 (21–57) | 34 (22–45) | 33 (19–59) | 48 (33–68) | 37 (26–58) | 40 (32–59) | .097 |
Patient type, no. (%) | .180 | ||||||
Medical | 22 (9.4) | 5 (10.4) | 12 (9.2) | 2 (8.3) | 0 | 3 (27.3) | |
Surgical*
| 211 (90.6) | 43 (89.6) | 118 (90.8) | 22 (91.7) | 20 (100) | 8 (72.7) | |
Pancreatitis not intervened | 22 (9.4) | 5 (10.4) | 12 (9.2) | 2 (8.3) | 0 | 3 (27.3) | .232 |
Site of abdominal surgery, no. (%) | .701 | ||||||
Esophagus | 13 (6.2) | 4 (9.3) | 5 (4.2) | 2 (9.1) | 2 (10.0) | 0 | |
Stomach/duodenum | 21 (10.0) | 1 (2.3) | 14 (11.9) | 3 (13.6) | 3 (15.0) | 0 | |
Biliary tract/pancreas | 58 (27.5) | 9 (20.9) | 38 (32.2) | 5 (22.7) | 3 (15.0) | 3 (37.5) | |
Small intestine | 45 (21.3) | 13 (30.2) | 21 (17.8) | 4 (18.2) | 5 (25.0) | 2 (25.0) | |
Colon | 59 (28.0) | 12 (27.9) | 32 (27.1) | 6 (27.3) | 6 (30.0) | 3 (37.5) | |
Others | 15 (7.1) | 4 (9.3) | 8 (6.8) | 2 (9.1) | 1 (5.0) | 0 | |
Surgery type**, no. (%)†
| .556 | ||||||
Emergency | 135 (64.0) | 24 (55.8) | 78 (66.1) | 13 (59.1) | 15 (75.0) | 5 (62.2) | |
Elective | 76 (36.0) | 19 (44.2) | 40 (33.9) | 9 (40.9) | 5 (25.0) | 3 (37.5) | |
Surgical procedure**, no. (%) | .023 | ||||||
One | 113 (53.6) | 23 (53.5) | 70 (59.3) | 11 (50.0) | 4 (20.0) | 5 (62.5) | |
≥ Two | 98 (46.4) | 20 (46.5) | 48 (40.7) | 11 (50.0) | 16 (80.0) | 3 (37.5) | |
Underlying illnesses, no. (%) | |||||||
Solid tumor | 84 (36.1) | 19 (39.6) | 43 (33.1) | 10 (41.7) | 8 (40.0) | 4 (36.4) | .853 |
Diabetes mellitus | 67 (28.8) | 13 (27.1) | 35 (26.9) | 8 (33.3) | 7 (35.0) | 4 (36.4) | .830 |
COPD | 37 (15.9) | 13 (27.1) | 17 (13.1) | 3 (12.5) | 4 (20.0) | 0 | .112 |
Chronic renal failure | 26 (11.2) | 3 (6.2) | 14 (10.8) | 5 (20.8) | 2 (10.0) | 2 (18.2) | .337 |
Heart failure | 16 (6.9) | 3 (6.2) | 6 (4.6) | 5 (20.8) | 0 | 2 (18.2) | .023 |
Chronic liver failure | 9 (3.9) | 4 (8.3) | 3 (2.3) | 2 (8.3) | 0 | 0 | .201 |
Oncohematologic process | 3 (1.3) | 0 | 2 (1.5) | 1 (4.2) | 0 | 0 | .635 |
Antifungal treatment, no. (%) | 119 (51.1) | 21 (43.8) | 58 (44.6) | 11 (45.8) | 18 (90.0) | 11 (100) | < .001 |
ICU mortality, no. (%) | 50 (21.5) | 8 (16.7) | 30 (23.1) | 7 (29.7) | 4 (20.0) | 1 (9.1) | .605 |
Overall mortality, no. (%) | 68 (29.2) | 10 (20.8) | 41 (31.5) | 8 (33.3) | 8 (40.0) | 1 (9.1) | .277 |
Included patients |
n = 185*
|
---|---|
Risk factors, no. (%) | |
Broad-spectrum antibiotics | 184 (99.5) |
Urinary catheter | 183 (98.9) |
Central venous catheter | 183 (98.9) |
Arterial catheter | 165 (89.2) |
Mechanical ventilation | 156 (84.3) |
Parenteral nutrition | 155 (83.8) |
Corticosteroids | 73 (39.5) |
Renal replacement therapy | 54 (29.2) |
Candida colonization (n = 154) | |
Low-grade Candida spp. colonization, no. (%) | 130 (84.4) |
High-grade Candida spp. colonization, no. (%) | 24 (15.6) |
Candida score ≥ 3; first week/during study | 96/142 (51.9) |
Candida infection (n = 31) | |
Severity of Candida infection at diagnosis | |
No sepsis/sepsis | 3/5 |
Severe sepsis/septic shock | 9/14 |
Causative Candida spp
| |
C. albicans
| 16 (51.6) |
C. glabrata
| 7 (22.6) |
C. parapsilosis
| 3 (9.7) |
C. tropicalis
| 1 3.2) |
C. krusei
| 1 (3.2) |
C. dubliniensis
| 1 (3.2) |
C. famata
| 1 (3.2) |
C. albicans + C. glabrata
| 1 (3.2) |
Time between hospital admission to infection, daysa
| 16 (6.5–19.5) |
Time between ICU admission to infection, daysa
| 7 (2–13) |
Hospital/ICU mortality, no. (%) | 9 (29.0/5 (16.1) |
Systemic antifungal therapy (SAT) (n = 119)**
| |
Empirical therapy for suspected IC (n = 90)***
| |
Multifocal colonization, no. (%) | 50 (55.6) |
Clinical situation, no. (%) | |
No sepsis/sepsis | 8 (8.9)/17 (18.9) |
Severe sepsis/septic shock | 29 (32.2)/36 (40.0) |
APACHE II | 17.8 ± 6.2 |
SOFAa
| 6 (5–9) |
Candida score | 4 (3–4) |
Time between of hospital/and beginning of SAT, daysa
| 11 (7–19) |
Time between ICU admission and beginning of SAT, daysa
| 7 (1–11) |
Hospital/ICU mortality, no. (%) | 29 (32.2)/23 (25.6) |
Therapy for documented infection (n = 29)***
| |
Clinical situation | |
No sepsis/sepsis | 3 (10.3)/4 (13.8) |
Severe sepsis/septic shock | 8 (27.6)/14 (48.3) |
APACHE II | 18.8 ± 6.8 |
SOFAa
| 6.5 (4–10) |
Candida score | 4 (3–5) |
Time between of hospital/ICU admission and beginning of SAT, daysa
| |
Candidemia (11) | 15 (4.5 ; 22)/6.5 (1 ; 16) |
Intra-abdominal candidiasis (18) | 12.5 (8 ; 17)/7 (3 ; 12) |
Antifungal agents (>1 agent/patient) | |
Days of therapy (first SAT)a
| 15 (8–21) |
Diagnostic value of BDG (cutoffs 80, 100 and 200 pg/mL), CAGTA, mannan-Ag, mannan-Ab, and C-PCR alone
Candida spp colonization | ||||||
---|---|---|---|---|---|---|
NCI | LGCC | HGCC | IAC | Candidemia |
P
| |
N = 48 |
N = 130 |
N = 24 |
N = 20 |
N = 11 | ||
BDG ≥ 80 pg/mL, no. (%) | 16/46 (34.8)a
| 50/124 (40.3)a
| 17/24 (70.8)b
| 15/20 (75.0)b
| 8/10 (80.0)b
| < .001 |
BDG ≥ 100 pg/mL, no. (%) | 16/46 (34.8)a
| 45/125 (36.0)a
| 14/24 (58.3)a,b
| 13/20 (65.0)b
| 8/10 (80.0) b
| .004 |
BDG ≥ 200 pg/mL, no. (%) | 10/47 (21.3)a
| 20/128 (15.6)a
| 11/24 (45.8)b
| 10/20 (50.0)b
| 8/10 (80.0)b
| < .001 |
CAGTA positive, no. (%) | 10/47 (21.3)a
| 44/128 (34.4)a
| 17/24 (70.8)b
| 8/20 (40.0)a,b
| 8/10 (80.0)b
| < .001 |
Mannan-Ag positive, no. (%) | 10/48 (20.8)a
| 40/127 (31.5)a
| 15/24 (62.5)b
| 8/20 (40.0)a,b
| 5/10 (50.0)a,b
| .007 |
Mannan-Ab positive, no. (%) | 6/48 (12.5) | 12/128 (9.4) | 4/24 (16.7) | 5/20 (25.0) | 3/11 (27.3) | .126 |
C-PCR positive, no. (%) | 14/23 (60.9) | 37/54 (68.5) | 6/8 (75.0) | 12/14 (85.7) | 9/11(81.8) | .525 |
Invasive candidiasis | Sensitivity % | Specificity % | NPV % | PPV % |
---|---|---|---|---|
(95 % CI) | (95 % CI) | (95 % CI) | (95 % CI) | |
BDG ≥ 80 pg/mL | 76.7 (57.7–90.1) | 57.2 (49.9–64.3) | 94.1 (89.1–96.8) | 21.7 (17.7–26.4) |
BDG ≥ 100 pg/mL | 70.0 (50.6–85.3) | 61.5 (54.3–68.4) | 93.0 (88.4–95.9) | 21.9 (17.3–27.3) |
BDG ≥ 200 pg/mL | 60.0 (40.6–77.3) | 79.4 (73.1–84.8) | 92.9 (89.4–95.4) | 30.5 (22.7–39.6) |
CAGTA positive | 53.3 (34.3–71.7) | 64.3 (57.2–71.0) | 90.1 (86.0–93.2) | 18.4 (13.3–24.8) |
Mannan-Ag positive | 43.3 (25.5–62.6) | 67.3 (60.3–73.8) | 88.7 (85.0–91.6) | 16.7 (11.3–24.0) |
Mannan-Ab positive | 25.8 (11.9–44.6) | 89.0 (83.8–93.0) | 88.6 (86.2–90.6) | 26.7 (15.1– 42.6) |
C-PCR positive | 84.0 (63.9–95.5) | 32.9 (23.1–44.0) | 87.5 (73.1–94.8) | 26.9 (22.7–31.6) |
Diagnostic value of combined use of BDG (cutoffs 80, 100 and 200 pg/mL), CAGTA, mannan-Ag, mannan-Ab, and C-PCR
Candida spp. colonization
| |||||||
---|---|---|---|---|---|---|---|
NCI | LGCC | HGCC | IAC | Candidemia |
P
| ||
N = 48 |
N = 130 |
N = 24 |
N = 20 |
N = 11 | |||
BDG ≥80 pg/mL | CAGTA | 21 (43.8)a
| 75 (57.7)a
| 21 (87.5)b
| 18 (90.0)b
| 10 (90.9)b
| < .001 |
Mannan-Ag | 21 (43.8)a
| 71 (54.6)a,c
| 21 (87.5)b
| 16 (80.0)b
| 9 (81.8)b,c
| <.001 | |
Mannan-Ab | 21 (43.8)a
| 61 (46.9)a
| 19 (79.2)b,c
| 15 (75.0)c
| 8 (72.7)a,c
| .002 | |
C-PCR | 14/23 (60.9) | 32/54 (59.3) | 5/8 (62.5) | 11/14 (78.6) | 8/11 (72.7) | .724 | |
BDG ≥100 pg/mL | CAGTA | 21 (43.8)a
| 72 (55.4)a
| 20 (83.3)b
| 16 (80.0)b
| 10 (90.9)b
| < .001 |
Mannan-Ag | 21 (43.8)a
| 68 (52.3)a, c
| 19 (79.2)b
| 14 (70.0)a, b, c
| 9 (81.8)c
| .009 | |
Mannan-Ab | 21 (43.8) | 57 (43.8) | 16 (66.7) | 13 (65.0) | 8 (72.7) | .053 | |
C-PCR | 14/23 (60.9) | 28/54 (51.9) | 5/8 (62.5) | 10/14 (71.4) | 8/11 (72.7) | .606 | |
BDG ≥200 pg/mL | CAGTA | 16 (33.3)a
| 54 (41.5)a
| 19 (79.2)b
| 14 (70.0)b
| 10 (90.9)b
| < .001 |
Mannan-Ag | 15 (31.2)a
| 52 (40.0)a
| 18 (75.0)b
| 13 (65.0)b
| 9 (81.8)b
| < .001 | |
Mannan-Ab | 13 (27.1)a
| 33 (25.4)a
| 13 (54.2)b
| 12 (60.0)b
| 8 (72.7)b
| < .001 | |
C-PCR | 10/23 (43.5) | 21/54 (38.9) | 3/8 (37.5) | 10/14 (71.4) | 8/11 (72.7) | .089 | |
CAGTA positive | Mannan-Ag | 15 (31.2)a
| 63 (48.5)b
| 21 (87.5)c
| 11 (55.0)a,b
| 10 (90.9)c
| < .001 |
Mannan-Ab | 14 (29.2)a
| 53 (40.8)a,c
| 18 (75.0)b
| 12 (60.0)b,c
| 8 (72.7)b
| < .001 | |
C-PCR | 8/23 (34.8) | 25/54 (46.3) | 5/8 (62.5) | 6/14 (42.9) | 8/11 (72.7) | .278 | |
C-PCR positive | Mannan-Ag | 5/23 (21.7)a
| 21/54 (38.9)a
| 5/8 (62.5)a,b
| 7/14 (50.0)a
| 8/11 (72.7)b
| .037 |
Mannan-Ab | 8/23 (34.8) | 19/54 (35.2) | 1/8 (12.5) | 7/14 (50.0) | 8/11 (72.7) | .073 | |
Mannan-Ag positive | Mannan-Ab | 13 (27.1)a
| 51 (39.2)a,b
| 17 (70.8)c
| 12 (60.0)b,c
| 5 (45.5)a,c
| .003 |
Invasive candidiasis | Sensitivity % | Specificity % | NPV % | PPV % | |
---|---|---|---|---|---|
(95 % CI) | (95 % CI) | (95 % CI) | (95 % CI) | ||
BDG ≥80 pg/mL | CAGTA | 90.3 (74.2–98.0) | 42.1 (35.2–49.2) | 96.6 (90.5–98.8) | 19.3 (16.9–22.0) |
Mannan-Ag | 80.6 (62.5–92.5) | 44.1 (37.1–51.2) | 93.7 (87.7–96.9) | 18.1 (15.2–21.5) | |
Mannan-Ab | 74.2 (42.9–57.1) | 50.0 (42.9–57.1) | 92.7 (87.2–95.9) | 18.5 (15.1–22.6) | |
C-PCR | 76.0 (54.9–90.6) | 40.0 (29.5–51.2) | 85.0 (72.9–92.3) | 27.1 (22.0–33.0) | |
BDG ≥100 pg/mL | CAGTA | 83.9 (66.3–94.5) | 44.1 (37.1–51.2) | 94.7 (88.7–97.6) | 18.7 (15.9–21.9) |
Mannan-Ag | 74.2 (55.4–88.1) | 46.5 (39.5–53.7) | 92.2 (86.4–95.6) | 17.6 (14.3–21.4) | |
Mannan-Ab | 67.7 (48.6–83.3) | 53.5 (46.3–60.5) | 91.5 (86.5–94.8) | 18.3 (14.4–22.9) | |
C-PCR | 72.0 (50.6–87.9) | 44.7 (33.9–55.9) | 84.4 (73.5–91.4) | 27.7 (21.9–34.3) | |
BDG ≥200 pg/mL | CAGTA | 77.4 (58.9–96.9) | 55.9 (48.8–62.9) | 94.2 (89.3–96.9) | 21.2 (17.4–25.6) |
Mannan-Ag | 71.0 (52.0–85.8) | 57.9 (50.8–64.8) | 92.9 (88.1–95.8) | 20.6 (16.4–25.5) | |
Mannan-Ab | 64.5 (45.4–80.8) | 70.8 (64.0–77.0) | 92.9 (88.9–95.5) | 25.3 (19.5–32.2) | |
C-PCR | 72.0 (50.6–87.9) | 60.0 (48.8–70.5) | 87.9 (79.1–93.3) | 34.6 (27.0–43.1) | |
CAGTA positive | Mannan-Ag | 67.7 (48.6–83.3) | 51.0 (43.9–58.1) | 91.2 (85.9–94.6) | 17.5 (13.8–21.9) |
Mannan-Ab | 64.5 (45.4–80.8) | 57.9 (50.8–64.8) | 91.4 (86.7–94.5) | 19.0 (14.8–24.2) | |
C-PCR | 56.0 (34.9–75.6) | 55.3 (44.1–66.1) | 81.0 (72.5–87.4) | 26.9 (19.5–35.9) | |
C-PCR positive | Mannan-Ag | 60.0 (38.7–78.9) | 63.5 (52.4–73.7) | 84.4 (76.5–90.0) | 32.6 (24.0–42.5) |
Mannan-Ab | 54.8 (36.0–72.7) | 78.7 (72.4–84.1) | 91.9 (88.4–94.4) | 28.3 (20.7–37.5) | |
Mannan-Ag positive | Mannan-Ab | 54.8 (36.0–72.7) | 59.9 (52.8–66.7) | 89.6 (85.2–92.8) | 17.3 (12.8–23.1) |