Table 2.
Patient characteristics at baseline by echinocandin groups
| 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 |
*P-value < 0.05
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
aPatients did not necessarily have all the three liver function tests (AST, ALT, total bilirubin), but they had at least one
bWe expect candidiasis was the indication for echinocandin treatment for most patients; possibly undercoded in the hospitalization records
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
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
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)
fIncludes severe forms of viral hepatitis, acute and subacute necrosis of liver, chronic liver disease, cirrhosis, and liver transplant
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
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