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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