Skip to main content

Table 5 Adjusted incidence rate ratios of severe hepatotoxicity – final model for main analysis

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

 

Patients treated with anidulafungin versus caspofungin (N = 6131)

Patients treated with anidulafungin versus micafungin (N = 8247)

IRR (95% CI)

P-value

IRR (95% CI)

P-value

Echinocandin exposure

 Anidulafungin versus caspofungin

1.43 (1.14, 1.79)*

0.0022*

 Anidulafungin versus micafungin

1.19 (0.92, 1.54)

0.1825

Demographics

 Age categories (ref: 18–49 years)

  50–64 years

1.06 (0.87, 1.30)

0.5517

1.06 (0.89, 1.25)

0.5101

  65+ years

1.10 (0.90, 1.35)

0.3317

1.14 (0.96, 1.36)

0.1245

 Female (ref: male)

0.91 (0.79, 1.07)

0.2511

0.97 (0.86, 1.11)

0.6880

 Cerner dataset (ref: Humedica)

0.76 (0.58, 1.00)*

0.0466*

0.82 (0.69, 0.99)*

0.0379*

 Admission through ER

0.80 (0.67, 0.96)*

0.0151*

0.77 (0.64, 0.92)*

0.0053*

Baseline liver function

 ALT grade (ref: 0)a

  1

1.13 (0.91, 1.41)

0.2746

1.13 (0.93, 1.37)

0.2236

  2

1.17 (0.85, 1.62)

0.3291

1.31 (1.00, 1.72)*

0.0484*

  3

1.91 (1.29, 2.82)*

0.0013*

1.71 (1.24, 2.37)*

0.0012*

  4

2.38 (1.40, 4.05)*

0.0014*

2.34 (1.53, 3.58)*

< 0.0001*

 AST grade (ref: 0)a

  1

1.75 (1.40, 2.20)*

< 0.0001*

1.96 (1.61, 2.39)*

< 0.0001*

  2

2.24 (1.66, 3.02)*

< 0.0001*

2.63 (2.02, 3.41)*

< 0.0001*

  3

3.90 (2.73, 5.57)*

< 0.0001*

4.67 (3.45, 6.33)*

< 0.0001*

  4

4.62 (2.79, 7.63)*

< 0.0001*

6.89 (4.56, 10.4)*

< 0.0001*

 Bilirubin grade (ref: 0)a

  1

1.71 (1.33, 2.19)*

< 0.0001*

1.63 (1.32, 2.01)*

< 0.0001*

  2

2.84 (2.24, 3.60)*

< 0.0001*

2.77 (2.28, 3.36)*

< 0.0001*

  3

13.8 (10.9, 17.3)*

< 0.0001*

12.1 (9.96, 14.7)*

< 0.0001*

  4

25.9 (19.3, 34.7)*

< 0.0001*

17.2 (13.3, 22.1)*

< 0.0001*

Fungal infection

 Prior use of in-hospital echinocandin

1.31 (0.99, 1.74)

0.0567

 Number of fungal infection sites (ref: 1)

   ≥ 2

0.81 (0.54, 1.20)

0.2935

0.85 (0.61, 1.19)

0.3479

  No candidiasis ICD-9-CM codes

1.59 (1.29, 1.95)*

< 0.0001*

1.36 (1.14, 1.61)*

0.0005*

Comorbidities

 Charlson Comorbidity Index (ref: 0)

  1

0.79 (0.59, 1.06)

0.1111

0.77 (0.60, 1.00)

0.0545

  2

0.80 (0.61, 1.04)

0.0990

0.99 (0.78, 1.25)

0.9042

  3

0.75 (0.56, 1.01)

0.0599

1.28 (1.00, 1.65)*

0.0496*

   ≥ 4

1.17 (0.90, 1.52)

0.2497

1.41 (1.12, 1.78)*

0.0036*

 Liver diseases

  Esophageal varices

1.83 (1.10, 3.05)*

0.0194*

1.65 (1.11, 2.46)*

0.0130*

  Liver disease secondary to biliary pathologies

1.15 (0.91, 1.45)

0.2427

1.18 (0.98, 1.42)

0.0768

  Other liver disease

1.96 (1.53, 2.51)*

< 0.0001*

1.52 (1.26, 1.83)*

< 0.0001*

 Other comorbidities

  Diabetes

0.67 (0.55, 0.83)*

0.0002*

0.90 (0.76, 1.06)

0.2073

  Endocarditis

0.59 (0.40, 0.87)*

0.0073*

  Gastroesophageal reflux disease

0.83 (0.62, 1.11)

0.2089

0.90 (0.72, 1.13)

0.3778

  Hypertension

0.72 (0.59, 0.89)*

0.0022*

0.78 (0.67, 0.92)*

0.0022*

  Neutropenia

1.26 (1.00, 1.59)*

0.0470*

  Organ failures

1.21 (0.99, 1.47)

0.0602

1.18 (0.98, 1.42)

0.0756

  Sepsis

1.46 (1.22, 1.75)*

< 0.0001*

1.34 (1.15, 1.56)*

0.0001*

 Renal dysfunction (CKD stage) (ref: Stage 1 [GFR ≥ 90 mL/min/1.73 m])

  Stage 2 (GFR 60–89)

1.21 (0.91, 1.63)

0.1915

  Stage 3 (GFR 30–59)

1.24 (0.93, 1.64)

0.1378

  Stage 4 (GFR 15–29)

1.53 (1.14, 2.06)*

0.0047*

  Stage 5 (GFR < 15)

1.07 (0.79, 1.45)

0.6534

Risk factors for fungal infection

 Admission to ICU or CCU

1.32 (1.15, 1.53)*

0.0001*

 Use of central venous catheter

0.73 (0.62, 0.87)*

0.0003*

 Surgery

0.63 (0.53, 0.74)*

< 0.0001*

0.66 (0.57, 0.76)*

< 0.0001*

Hospital formulary proxy (ref: anidulafungin only covered)

 All three echinocandins covered

0.97 (0.71, 1.33)

0.8532

1.17 (0.85, 1.60)

0.3382

 Anidulafungin and caspofungin covered

0.95 (0.69, 1.29)

0.7249

0.93 (0.68, 1.27)

0.6426

 Anidulafungin and micafungin covered

1.22 (0.79, 1.87)

0.3701

1.12 (0.80, 1.58)

0.5090

 Caspofungin and micafungin covered

0.95 (0.59, 1.52)

0.8169

1.01 (0.71, 1.44)

0.9584

 Caspofungin only covered

1.11 (0.76, 1.62)

0.5756

 Micafungin only covered

1.00 (0.69, 1.44)

0.9910

Hepatotoxic drugs initiated in the baseline period

 Number of distinct hepatotoxic drugs (ref: 0–5)

  6–10

0.73 (0.57, 0.93)*

0.0095*

  11–25

0.58 (0.46, 0.73)*

< 0.0001*

  26–48

0.42 (0.25, 0.69)*

0.0006*

 Acetaminophen

0.82 (0.70, 0.96)*

0.0135*

 Antibiotics

0.94 (0.83, 1.07)

0.3741

  1. *P-value < 0.05
  2. Abbreviations: ALT alanine aminotransferase, AST aspartate transaminase, CI confidence interval, 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, IRR incidence rate ratio
  3. aUnknown categories not shown