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Table 2 Patient characteristics at baseline by echinocandin groups

From: Retrospective cohort study comparing the risk of severe hepatotoxicity in hospitalized patients treated with echinocandins for invasive candidiasis in the presence of confounding by indication

Patient characteristics at baseline

Anidulafungin

Caspofungin

Micafungin

P-value

(N = 1700)

(N = 4431)

(N = 6547)

Anidulafungin versus caspofungin

Anidulafungin versus micafungin

Demographics

 Age at admission, n (%)

<  0.001*

<  0.001*

  18–49 years

420 (24.7)

988 (22.3)

1528 (23.3)

  

  50–64 years

651 (38.3)

1463 (33.0)

2234 (34.1)

  

  65+ years

629 (37.0)

1980 (44.7)

2785 (42.5)

  

 Male, n (%)

947 (55.7)

2221 (50.1)

3371 (51.5)

< 0.001*

0.002*

 Race, n (%)

<  0.001*

<  0.001*

  Caucasian

988 (58.1)

3205 (72.3)

4912 (75.0)

  

  Black or African American

469 (27.6)

844 (19.0)

1120 (17.1)

  

  Asian

28 (1.6)

95 (2.1)

64 (1.0)

  

  Other/unknown

215 (12.6)

287 (6.5)

451 (6.9)

  

 Source dataset, n (%)

< 0.001*

<  0.001*

  Cerner

509 (29.9)

3114 (70.3)

3307 (50.5)

  

  Humedica

1191 (70.1)

1317 (29.7)

3240 (49.5)

  

 Admission through ER, n (%)

221 (13.0)

1947 (43.9)

1359 (20.8)

< 0.001*

<  0.001*

Liver functiona

 AST grade, n (%)

< 0.001*

<  0.001*

  0

491 (28.9)

1717 (38.7)

2785 (42.5)

  

  1

490 (28.8)

1392 (31.4)

1884 (28.8)

  

  2

263 (15.5)

569 (12.8)

772 (11.8)

  

  3

248 (14.6)

468 (10.6)

673 (10.3)

  

  4

204 (12.0)

273 (6.2)

430 (6.6)

  

  Unknown

4 (0.2)

12 (0.3)

3 (0.0)

  

 ALT grade, n (%)

< 0.001*

<  0.001*

  0

773 (45.5)

2582 (58.3)

3725 (56.9)

  

  1

395 (23.2)

969 (21.9)

1424 (21.8)

  

  2

182 (10.7)

401 (9.0)

534 (8.2)

  

  3

177 (10.4)

294 (6.6)

442 (6.8)

  

  4

127 (7.5)

144 (3.2)

269 (4.1)

  

  Unknown

46 (2.7)

41 (0.9)

153 (2.3)

  

 Total bilirubin grade, n (%)

< 0.001*

<  0.001*

  0

663 (39.0)

2056 (46.4)

3653 (55.8)

  

  1

272 (16.0)

664 (15.0)

853 (13.0)

  

  2

265 (15.6)

708 (16.0)

909 (13.9)

  

  3

314 (18.5)

516 (11.6)

692 (10.6)

  

  4

156 (9.2)

174 (3.9)

279 (4.3)

  

  Unknown

30 (1.8)

313 (7.1)

161 (2.5)

  

 Overall grade of hepatotoxicity, n (%)

<  0.001*

<  0.001*

  Grade 0

320 (18.8)

1207 (27.2)

2035 (31.1)

  

  Grade 1

390 (22.9)

1182 (26.7)

1693 (25.9)

  

  Grade 2

302 (17.8)

892 (20.1)

1140 (17.4)

  

  Grade 3

524 (30.8)

971 (21.9)

1395 (21.3)

  

  Grade 4

164 (9.6)

179 (4.0)

284 (4.3)

  

Fungal infection

 Prior use of in-hospital echinocandin, n (%)

106 (6.2)

232 (5.2)

390 (6.0)

0.125

0.667

 Candidiasis diagnosisb,c, n (%)

574 (33.8)

877 (19.8)

1307 (20.0)

<  0.001*

<  0.001*

 Number of distinct candidiasis ICD-9-CM diagnosis codes, n (% patients with a candidiasis diagnosis)

< 0.001*

<  0.001*

  1

382 (66.6)

760 (86.7)

1130 (86.5)

  

  2

158 (27.5)

107 (12.2)

159 (12.2)

  

   ≥ 3

34 (5.9)

10 (1.1)

18 (1.4)

  

Comorbiditiesc

 CCId, n (%)

< 0.001*

<  0.001*

  0

268 (15.8)

1473 (33.2)

1759 (26.9)

  

  1

182 (10.7)

551 (12.4)

832 (12.7)

  

  2

223 (13.1)

798 (18.0)

1221 (18.6)

  

  3

219 (12.9)

530 (12.0)

875 (13.4)

  

   ≥ 4

808 (47.5)

1079 (24.4)

1860 (28.4)

  

 Specific comorbidities, n (%)

  Liver diseases

   Esophageal varices

41 (2.4)

42 (0.9)

83 (1.3)

< 0.001*

<  0.001*

   Liver disease secondary to biliary pathologiese

275 (16.2)

330 (7.4)

648 (9.9)

< 0.001*

<  0.001*

   Other liver diseasef

217 (12.8)

322 (7.3)

629 (9.6)

< 0.001*

<  0.001*

  Other comorbidities

   Diabetes

477 (28.1)

848 (19.1)

1489 (22.7)

< 0.001*

<  0.001*

   Endocarditis

168 (9.9)

89 (2.0)

185 (2.8)

< 0.001*

<  0.001*

   Gastroesophageal reflux disease

147 (8.6)

386 (8.7)

704 (10.8)

0.936

0.011*

   Hypertension

913 (53.7)

1292 (29.2)

2325 (35.5)

< 0.001*

<  0.001*

   Neutropenia

145 (8.5)

354 (8.0)

542 (8.3)

0.489

0.739

   Organ failures

1179 (69.4)

2071 (46.7)

3372 (51.5)

< 0.001*

<  0.001*

   Sepsis or septic shock

1165 (68.5)

2080 (46.9)

3137 (47.9)

< 0.001*

<  0.001*

  Renal dysfunction (CKD stage)g

<  0.001*

<  0.001*

   Stage 1 (GFR ≥ 90 mL/min/1.73 m)

154 (9.1)

411 (9.3)

729 (11.1)

  

   Stage 2 (GFR 60–89)

240 (14.1)

898 (20.3)

1363 (20.8)

  

   Stage 3 (GFR 30–59)

482 (28.4)

1282 (29.0)

1786 (27.3)

  

   Stage 4 (GFR 15–29)

401 (23.6)

953 (21.5)

1395 (21.3)

  

   Stage 5 (GFR < 15)

423 (24.9)

883 (19.9)

1271 (19.4)

  

Risk factors for fungal infection, n (%)

 Admission to ICU or CCU

1280 (75.3)

2330 (52.6)

3184 (48.6)

< 0.001*

<  0.001*

 Use of central venous catheter

744 (43.8)

590 (13.3)

1262 (19.3)

< 0.001*

<  0.001*

 Surgery

698 (41.1)

1492 (33.7)

1773 (27.1)

< 0.001*

<  0.001*

Hospital formulary proxy, n (%)

<  0.001*

<  0.001*

 All three echinocandins covered

358 (21.1)

1243 (28.1)

1797 (27.4)

  

 Anidulafungin and caspofungin covered

527 (31.0)

1322 (29.8)

0 (0.0)

  

 Anidulafungin and micafungin covered

216 (12.7)

0 (0.0)

350 (5.3)

  

 Caspofungin and micafungin covered

0 (0.0)

330 (7.4)

2742 (41.9)

  

 Single agent covered

599 (35.2)

1536 (34.7)

1658 (25.3)

  

Hepatotoxic drugs initiated in the baseline periodh

 Number of distinct hepatotoxic drugs, median [IQR]

12.0 (8.0, 16.0)

12.0 (8.0, 15.0)

12.0 (9.0, 17.0)

< 0.001*

0.123

  Acetaminophen, n (%)

1255 (73.8)

3629 (81.9)

5373 (82.1)

< 0.001*

<  0.001*

  Antibiotics, n (%)

785 (46.2)

2384 (53.8)

3357 (51.3)

< 0.001*

<  0.001*

  Antidiabetics, n (%)

22 (1.3)

96 (2.2)

98 (1.5)

0.026*

0.534

  Antimycobacterials, n (%)

58 (3.4)

116 (2.6)

125 (1.9)

0.094

< 0.001*

  Antiretrovirals, n (%)

40 (2.4)

38 (0.9)

56 (0.9)

< 0.001*

< 0.001*

  Chemotherapies, n (%)

87 (5.1)

271 (6.1)

401 (6.1)

0.136

0.117

  Non-steroidal anti-inflammatory drug, n (%)

622 (36.6)

1567 (35.4)

2456 (37.5)

0.371

0.482

  Psychotropics, n (%)

484 (28.5)

1379 (31.1)

1917 (29.3)

0.043*

0.512

  1. *P-value < 0.05
  2. Abbreviations: ALT alanine aminotransferase, AST aspartate transaminase, CCI Charlson comorbidity index, CCU critical care unit, CKD chronic kidney disease, ER emergency room, GFR glomerular filtration rate, ICD-9-CM 9th International Classification of Disease, Clinical Modification, ICU intensive care unit, IQR inter-quartile range
  3. aPatients did not necessarily have all the three liver function tests (AST, ALT, total bilirubin), but they had at least one
  4. bWe expect candidiasis was the indication for echinocandin treatment for most patients; possibly undercoded in the hospitalization records
  5. cDefined based on ICD-9-CM diagnosis codes. Since diagnosis dates werenot available in the Cerner database, diagnoses were measured over the entire duration of the hospitalization
  6. dCCI, an index that was developed to predict one-year mortality in hospitalized patients; CCI is calculated based on the presence of ICD-9-CM diagnosis codes for 17 comorbidities associated with high risk of death, such as cancer, myocardial infarction, congestive heart failure, diabetes, and others; values range from 0 to 33, with higher values indicating higher risk of death
  7. eIncludes cholelithiasis and other disorders of gallbladder (e.g., acute cholecystitis, obstruction of gallbladder, fistula of gallbladder) or biliary tract (e.g., postcholecystectomy syndrome cholangitis, obstruction of bile duct)
  8. fIncludes severe forms of viral hepatitis, acute and subacute necrosis of liver, chronic liver disease, cirrhosis, and liver transplant
  9. g Levey AS, Coresh J, Balk E, Kausz AT, Levin A, Steffes MW, Hogg RJ, Perrone RD, Lau J, Eknoyan G et al. National Kidney Foundation practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Ann Intern Med 2003;139(2):137–147
  10. hHepatotoxic medications, based on the literature, were identified using National Drug Codes (NDC) and classified using Generic Product Identifier (GPI) and American Hospital Formulary Service (AHFS) categories; these medications include acetaminophen and selected drugs in the following classes: antibiotics, antidiabetics, antimycobacterials, antiretrovirals, chemotherapies, non-steroidal anti-inflammatory drugs, and psychotropics
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BMC Infectious Diseases

ISSN: 1471-2334

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