Table 2.
Univariable and multivariable analyses of factors associated with crude 30-day mortality in patients with ICU-acquired IC
| Variable | Total of patients (%) n = 330 (100) |
Non-survivors (%) n = 137 (42) |
Survivors (%) N = 193 (58) |
Univariable analysis | Multivariable analysis* | ||
|---|---|---|---|---|---|---|---|
| OR (95% CI) | p | OR (95% CI) | p | ||||
| Demographics | |||||||
| Age in years, median (IQR) | 66 (55–75) | 68 (59–77) | 64 (51–73) | 1.03 (1.01–1.05) | 0.001 | 1.04 (1.02–1.06) | < 0.001 |
| Male gender | 198 (60) | 84 (61) | 114 (59) | 1.10 (0.70–1.72) | 0.681 | ||
| Medical history | |||||||
| Diabetes mellitus | 73 (22) | 34 (25) | 39 (20) | 1.30 (0.77–2.20) | 0.321 | ||
| COPD | 44 (13) | 22 (16) | 22 (11) | 1.49 (0.79–2.81) | 0.222 | ||
| End-stage chronic renal disease | 59 (18) | 35 (26) | 24 (12) | 2.42 (1.36–4.29) | 0.003 | 1.82 (0.96–3.45) | 0.068 |
| Severe hepatic failurea | 29 (9) | 18 (13) | 11 (6) | 2.50 (1.14–5.49) | 0.022 | 3.25 (1.31–8.08) | 0.011 |
| Solid tumor | 94 (28) | 40 (29) | 54 (28) | 1.06 (0.65–1.72) | 0.809 | ||
| Hematological malignancy | 16 (5) | 5 (4) | 11 (6) | 0.63 (0.21–1.85) | 0.397 | ||
| Solid organ transplant | 18 (5) | 5 (4) | 13 (7) | 0.52 (0.18–1.51) | 0.231 | ||
| Steroid treatment | 43 (13) | 20 (15) | 23 (12) | 1.26 (0.66–2.41) | 0.477 | ||
| Immunosuppressants other than steroids | 30 (9) | 13 (9) | 17 (9) | 1.09 (0.51–2.32) | 0.832 | ||
| Age-adjusted Charlson score | 6 (3–7) | 6 (5–8) | 5 (3–7) | 1.16 (1.07–1.25) | < 0.001 | ||
| Recent exposures (within 30 days) | |||||||
| Previous abdominal surgery | 174 (53) | 65 (47) | 109 (56) | 0.70 (0.45–1.08) | 0.106 | ||
| Previous antibacterial therapy | 226 (68) | 102 (74) | 124 (64) | 1.62 (1.00–2.63) | 0.050 | 1.53 (0.89–2.64) | 0.124 |
| Previous echinocandins | 35 (11) | 12 (9) | 23 (12) | 0.71 (0.34–1.48) | 0.360 | ||
| Previous azoles | 53 (16) | 22 (16) | 31 (16) | 1.00 (0.55–1.82) | 0.999 | ||
| Previous amphotericin B | 5 (2) | 4 (3) | 1 (1) | 5.77 (0.64–52.24) | 0.119 | ||
| Baseline variables** | |||||||
| SOFA score, median (IQR) | 9 (5–12) | 10 (7–13) | 7 (4–10) | 1.16 (1.10–1.22) | < 0.001 | 1.11 (1.04–1.17) | 0.001 |
| SAPS II score, median (IQR) | 48 (35–64) | 55 (40–72) | 43 (31–56) | 1.03 (1.02–1.04) | < 0.001 | ||
| Length of ICU stay in days (IQR) | 8 (3–19) | 9 (3–20) | 8 (3–18) | 1.00 (0.99–1.01) | 0.469 | ||
| WBC (cells × 109/L), median (IQR) | 13.6 (8.2–20.2) | 13.2 (7.5–20.0) | 13.9 (8.8–20.7) | 0.99 (0.98–1.01) | 0.497 | ||
| AKI§ | 157 (48) | 81 (59) | 76 (39) | 2.23 (1.43–3.48) | < 0.001 | ||
| Infection variables | |||||||
| Type of IC | 0.193 | ||||||
| IAC | 97 (29) | 34 (25) | 63 (33) | (ref) | |||
| Candidemia | 215 (65) | 97 (71) | 118 (61) | 1.52 (0.93–2.50) | |||
| IAC plus candidemia | 18 (5) | 6 (4) | 12 (6) | 0.93 (0.32–2.69) | |||
| Candida species | 0.866 | ||||||
| Candida albicans | 162 (49) | 65 (47) | 97 (50) | (ref) | |||
| Non-Candida albicans§§ | 141 (43) | 60 (40) | 81 (42) | 1.11 (0.70–1.75) | |||
| Candida albicans plus non-Candida albicans§§§ | 27 (8) | 12 (9) | 15 (8) | 1.19 (0.53–2.72) | |||
| Presence of septic shockb | 165 (50) | 91 (66) | 74 (38) | 3.18 (2.01–5.03) | < 0.001 | 2.12 (1.24–3.63) | 0.006 |
| Presence of endocarditis | 8 (2) | 3 (2) | 5 (3) | 0.84 (0.20–3.58) | 0.816 | ||
| Fluconazole resistancec | 66 (24) | 28 (25) | 38 (23) | 1.01 (0.65–1.99) | 0.665 | ||
| Early treatment variables*** | |||||||
| Adequate source control within 24 hd | 205 (62) | 73 (53) | 132 (68) | 0.53 (0.34–0.83) | 0.006 | 0.65 (0.39–1.07) | 0.093 |
| Adequate empiric antifungals within 24 he | 93 (36) | 35 (36) | 58 (36) | 0.97 (0.57–1.63) | 0.902 | ||
Results are presented as n (%) unless otherwise indicated. AKI acute kidney injury, COPD chronic obstructive pulmonary disease, CVC central venous catheter, IC invasive candidiasis, IAC intra-abdominal candidiasis, ICU intensive care unit, IQR interquartile range, SAPS simplified acute physiology score, SOFA sequential organ failure assessment, WBC white blood cells
*Only results for variables retained in the final multivariable model (model A) are presented. Variables included in model A were also included in an additional generalized linear multivariable mixed logistic regression model with center as a random intercept (model B; standard deviation of the random effect = 0.311; model β0 = −4.329), the results of which were in line with those of model A: age (OR 1.04, 95% CI 1.02–1.06, p < 0.001); end-stage chronic renal disease (OR 1.83, 95% IC 0.95–3.52, p 0.070), severe liver failure (OR 3.41, 95% CI 1.33–8.73, p 0.010); previous antibacterial therapy (OR 1.51, 95% CI 0.86–2.63, p 0.148); SOFA score (OR 1.11, 95% CI 1.04–1.18, p 0.001); septic shock (OR 2.09, 95% CI 1.21–3.62, p 0.008), adequate source control within 24 h (OR 0.64, 95% CI 0.38–1.08, p 0.095). The Akaike information criterion (AIC) values for model A and model B were 391.1 and 392.5, respectively
**At the onset of signs and symptoms of IC
***The present exploratory model was not developed to comprehensively assess the overall impact of antifungal therapy and/or adequate source control (including those performed beyond 24 h after the onset of symptoms), which needs further dedicated investigation to be reliably evaluated
§ClCr < 60 mL/min
§§C. glabrata (n = 52), C. parapsilosis (n = 38), C. tropicalis (n = 18), C. krusei (n = 14), C. dubliniensis (n = 4), other species with lower frequency (n = 5), more than one non-Candida albicans spp. concomitantly (n = 10)
§§§C. albicans plus C. glabrata (n = 16), C. albicans plus C. parapsilosis (n = 4), other combinations with lower frequency (n = 7)
aSevere hepatic failure was defined as liver cirrhosis according to histology or in the presence of a clinical diagnosis supported by laboratory, endoscopy, and radiologic findings
bSeptic shock was defined as hypotension not responding to fluid therapy and requiring vasoactive agents
cInformation available (i.e., fluconazole tested) for 274/330 patients (83%)
dSource control was considered adequate in the following cases: (i) not necessary, (ii) devices or foreign body removal, (iii) drainage of infected fluid collections, (iv) debridement of infected solid tissue, and (v) definitive measures to correct anatomic derangements resulting in ongoing microbial contamination
eFrom the onset of signs and symptoms of IC. Empiric treatment was considered adequate when the infecting organism was ultimately shown to be susceptible to the empirically administered antifungal. This analysis was conducted in the subgroup of patients not receiving empirical antifungal or receiving empirical antifungals for treating Candida spp. for which susceptibility test results were subsequently available (257/330, 78%)