Table 2.
Reported experience with the use of the colonization index (CI)
| Reference | Type of patient; study design | Number of patients | Number of invasive candidiasis cases | CI monitoring | Number of surveillance cultures | Main CI findings | Authors’ conclusion |
|---|---|---|---|---|---|---|---|
| General studies (n = 7) | |||||||
| Tran et al. [51] | Cardiac surgery; prospective | 81 | 7 | Preoperatively, day 6 or at discharge | 773 (mean, 8.8/patient); 116 (16.3 %) positive |
CI ↑ in 57 % developing IC, 23 % uninfected; CI associated with female sex (45 vs. 21 %), catheter duration (13 vs. 11 days), length of ICU stay (5.7 vs. 4.9 days) CI did not change in 43 % developing IC, 72 % uninfected |
“This study showed that three epidemiological factors—duration of the intravascular catheterization and medical devices, length of stay in the SICU and the sex of the patient—were associated in elective cardiovascular surgical patients with an increase of the Candida spp. colonization index, which helps to identify high-risk patients for Candida infections” |
| Yazdanparast et al. [52] | Cardiac surgery; prospective | 131: coronary artery bypass grafting with (n = 72) and without (n = 59) extracorporeal circulation | 0 | Preoperatively, postoperatively (day not specified) | 147 | In patients requiring extracorporeal circulation, ↑ CI associated with more antibiotic use (1.50 ± 0.83 vs. 1.08 ± 0.40; different agents; p = 0.0055) | “Epidemiological data obtained from this study show that coronary artery bypass grafting with extracorporeal circulation procedure is associated with an increase in the use of antibiotics and subsequently a higher risk of Candida colonization-infection” |
| Charles et al. [37] | Mixed ICU, patients with candidemia; retrospective | 51: 20 MICU, 32 SICU (p < 0.05) | 51 | Daily for 7 days before candidemia | Not specified (mean, 3.2/patient before candidemia) |
Mean CI in 46 assessed: 0.56 ± 0.39 CI ≥ 0.50 in 21 (45.6 %) MICU 0.74 ± 0.31 vs. SICU 0.45 ± 0.40 (p = 0.01) Mean CI in survival 0.46 vs. death 0.63 (p = 0.04) Better ICU outcome associated with prior surgery [HR, 0.25 (0.09–0.67)], antifungal treatment [HR, 0.11 (0.04–0.30)], absence of neutropenia [HR, 0.10 (0.02–0.45)] |
“Candidemia occurrence is associated with a high mortality rate among critically ill patients. Differences in underlying conditions could account for the poorer outcome of the medical patients. Screening for fungal colonization could allow identification of such high-risk patients and, in turn, improve outcome” |
| Charles et al. [38] | Medical ICU, stay >7 days; prospective | 92 | 1 (septic shock with typical maculopapular rash, positive skin biopsy) | Weekly (mean, 3.2/patient) | 1,696 (mean, 18.4/patient) |
CI ≥ 0.50 in 36 (39.1 %), almost all with detectable fungal colonization on ICU admission Predictors of CI ≥ 0.5: Candida colonization at admission [OR 18.80 (5.21–67.79)], >2 days bladder catheterization [OR, 10.44 (1.61–67.85)] CI ↑ associated with days on broad-spectrum antibiotics [β = 0.01 (0.01–0.02)], hematological malignancy [β = 0.41 (0.09–0.73)], candiduria [β = 0.2 (0.09–0.31)] Empirical antifungal treatment prescribed in 14/36 (39 %) with CI ≥ 0.5, 7/56 (13 %) with CI < 0.5 (p = 0.007) |
“Candida spp. multiple-site colonization is frequently reached among the critically ill medical patients. Broad spectrum antibiotic therapy was found to promote fungal growth in patients with prior colonization. Since most of the invasive candidiasis in the ICU setting are thought to be subsequent to colonization in high-risk patients, reducing antibiotic use could be useful in preventing fungal infections” |
| Eloy et al. [53] | Mixed ICU, risk factors (antibiotics or hospital stay >8 days, neutropenia); prospective |
75: 46 MICU, 29 SICU |
4 MICU (2 respiratory tract, 2 urinary); 5 SICU (4 peritonitis, 1 urinary) | At admission, weekly | 901; 469 (52 %) positive |
Accuracy of CI > 0.5 in predicting IC in MICU: sens, 75 %; spec, 35 %; PPV, 10 %; NPV, 94 % In SICU: sens, 100 %; spec, 50 %; PPV, 29 %; NPV, 100 % |
“Serological tests failed to differentiate infected from non-infected patients. The Pittet’s CI identified infected surgical patients (Fisher exact test, 0.052), which are in the population with CI > 0.5” |
| Agvald-Ohman et al. [54] | Mixed ICU, stay >7 days; prospective | 59 | 10 | At admission, then weekly | 401; 149 (37 %) positive |
32 (54 %) received antifungals: 10 with IC [mean CI, 0.7; 8 had digestive surgery, 7 had CIs > 0.5 (<0.8 in 6)]; 22 without IC (mean CI, 0.26; 7 had digestive surgery, 9 had CIs > 0.5) 17/25 (68 %) with CIs ≥ 0.5 on day 7 received antifungals Predictors of IC: CI > 0.5 (OR, 19.1 [2.4–435]), digestive surgery [OR, 60 (2.4–infinity)] |
“High colonization index and recent extensive gastro-abdominal surgery were significantly correlated with IC. The results indicate that ICU patients exposed to extensive gastro-abdominal surgery would benefit from early antifungal prophylaxis” |
| Massou et al. [55] | Medical ICU, stay >2 days and at least one risk factor; prospective | 100 | 15 | At admission, then weekly | 816 (including 143 blood cultures) |
CI ≥ 0.5 in 53 (53 %), predicted only by corticosteroids [OR, 5.1 (1.02–25.2)] Accuracy of CI > 0.5 in predicting IC: sens, 93 %; spec, 48 %; PPV, 26 %; NPV, 98 % Only neutropenia predicted invasive candidiasis [OR, 18.3 (2.9–114)] |
“CI has the advantage to provide quantified data of the patient’s situation in relation to the colonization. But, it isn’t helpful with patients having an invasive candidiasis in medical intensive care unit” |
| Candiduria studies (n = 5) | |||||||
| Chabasse [56] | 15 mixed ICUs, one major or two minor risk factors and candiduria; prospective | 135 | 0 | At time of candiduria and/or candidemia | Not available |
Candiduria: <103, 56 (42 %); 103–104, 21 (16 %); >104, 56 (42 %) CI > 0.5 in 36/76 tested (65 % with candiduria >104, 31 % with candiduria <104; p = 0.003) |
“Quantification of candiduria could be useful to select patients at high risk for disseminated candidiasis” |
| Dubau et al. [57] | Surgical ICU, stay or antibiotics >7 days or postoperative fistula and CRP > 100 mg/ml; prospective | 89 | 1/35 empirically treated with CIs ≥ 0.5; 0 with CIs < 0.5; 22 candiduria | On inclusion, then weekly | 2,238 |
Absence of candiduria: CI = 0.3–0.47 (p = 0.008) Presence of candiduria: CI = 0.57–0.87 (p = 0.0001) |
“The presence of a candiduria was significantly associated with an increased invasive candidiasis” |
| Sellami et al. [58] | Mixed ICU, stay >3 days; prospective | 162 | 6; 56 candiduria | On inclusion, then weekly | Not available |
Candiduria: <103, 12 (21 %); 103–104, 16 (29 %); >104, 28 (50 %) Mean CI = 0.47 candiduria, 0.8 IC (n = 6) CI > 0.5 in 67 % candiduria >104 |
“Candiduria superior or equal to 104 UFC/ml associated with risk factors may predict invasive candidiasis in critically ill patients” |
| Charles et al. [38] | Medical ICU, stay > 7 days; prospective | 92 | 9 | Weekly | 1,696 (mean, 18.4/patient) | ↑ CI associated with: days on broad-spectrum antibiotics [β = 0.01 (0.01–0.02)], hematological malignancy [β = 0.41 (0.09–0.73)], candiduria [β = 0.2 (0.09–0.31)] | “Since most of the invasive candidiasis in the ICU setting are thought to be subsequent to colonization in high-risk patients, reducing antibiotic use could be useful in preventing fungal infections” |
| Ergin et al. [59] | Mixed ICU, stay >7 days; prospective | 100 | 9 (5 candidemia, 4 urinary); 42 candiduria | On inclusion, then weekly | 1,691 (mean, 17/patient) |
CI > 0.2, 42 (42 %); CI > 0.2 and <0.5, 34 (34 %); CI ≥ 0.5, 8 (8 %) Accuracy of CI ≥ 0.5 in predicting invasive candidiasis: sens, 100 %; spec, 64 %; PPV, 21 %; NPV, 100 % |
“Candida colonization and Candida colonization index may be used as useful parameters to predict invasive Candida infections” |
| Prophylaxis studies (n = 6) | |||||||
| Laverdière et al. [60] | Neutropenia (leukemia or BMT); prospective, double-blinded, randomized: prophylaxis (fluconazole, 400 mg/day orally) vs. placebo | 266 | 41: 9/135 (6.7 %) fluconazole, 32/131 (24.4 %) placebo (p < 0.001) | On randomization, at end of prophylaxis | 1,904; 458 (21 %) positive |
Colonization ↓ (39–36 %) fluconazole, ↑ (37–73 %) placebo (p < 0.0001) CI ↓ (0.18–0.16) fluconazole, ↑ (0.18–0.39) placebo (p < 0.001) Accuracy of CI ≤ 0.25 in predicting IC at baseline: sens, 39 %; spec, 82 %; PPV, 28 %; NPV, 88 % At end of prophylaxis: sens, 76 %; spec, 69 %; PPV, 69 %; NPV, 94 % |
“Fluconazole prevented and reduced fungal colonization of the alimentary tract and subsequent invasive fungal infections… In cancer patients, a colonization index ≤0.25 at the initiation of chemotherapy clearly predicts a low risk of invasive fungal infection” |
| Garbino et al. [40] | Mixed ICU, >2 days mechanical ventilation and expected continuation for ≥72 h; prospective, double-blinded randomized: prophylaxis (fluconazole, 100 mg/day iv) vs. placebo plus selective digestive decontamination (polymyxin B, neomycin, vancomycin) | 204 | 6/103 (5.8 %) fluconazole, 16/101 (16 %) placebo (p < 0.001) | Daily | Not available |
Colonization: 29/55 (53 %) fluconazole, 40/51 (78 %) placebo (p = 0.01) CI ↓ (0.26–0.13) fluconazole, ↑ (0.26–0.50) placebo (p < 0.001) Mean pre-infection CI in patients with candidemia (n = 10): 0.89 |
“…fluconazole prophylaxis in selected, high-risk critically ill patients decreases the incidence of Candida infection, in particular, candidemia” |
| Normand et al. [61] | Mixed ICU, >2 days mechanical ventilation; prospective, open-label, nystatin vs. placebo | 98 | 0 | On randomization, then every 3 days | Not available |
Colonization: 0/51 nystatin, 12/47 (25 %) placebo (p < 0.01) CI ↓ (0.1–0.05) nystatin, ↑ (0.1–0.25) placebo (p < 0.05) |
“Oral nystatin prophylaxis efficiently prevented Candida spp. colonization in ICU patients at low risk of developing invasive candidiasis” |
| Senn et al. [46] | Surgical ICU, recurrent gastrointestinal perforation/anastomotic leakage or acute necrotizing pancreatitis; prospective, non-comparative, caspofungin prophylaxis | 19 | 1 (6–8 expected in this high-risk group without prophylaxis) | On inclusion, then twice in week 1, then weekly until end of follow-up | Not available (median, 4 sites/patient screened) | CI ↓ (0.5–0.3) during prophylaxis (p = 0.03) | “Despite limitations such as the open single-center non-comparative design and the small sample size, the observations of this proof-of-concept study suggest that caspofungin may be efficacious and safe for prevention of intra-abdominal candidiasis in surgical patients with a high-risk profile” |
| Giglio et al. [62] | Surgical/trauma ICU, >2 days mechanical ventilation; prospective, randomized, open-label: prophylaxis (oral nystatin, 3 × 1 million U/day) vs. placebo | 99 | 0 | On inclusion, then every 3 days until end of follow-up (day 15) | 2,569; 746 (29 %) positive |
Overall: CI ↓ (0.12–0.0) nystatin, ↑ (0.2–0.44) placebo (p < 0.05) Colonization at entry: CI ↓ (0.1–0.0) nystatin, ↑ (0.2–0.42) placebo (p < 0.05) |
“The present trial shows that nystatin pre-emptive therapy in surgical/trauma ICU patients significantly reduces fungal colonization, even in those colonized at admission” |
| Chen et al. [63] | Mixed ICU, mechanical ventilation; prospective, randomized, open-label: prophylaxis (oral nystatin, 3 × 1 million U/day) vs. placebo | 124 | 8: 3/60 (0.5 %) nystatin, 5/64 (7.8 %) placebo (p > 0.05) | On inclusion, every 3 days until end of follow-up (day 9) | Not available; 874 positive |
CCI at day 6: 0.19 nystatin, 0.39 placebo (p < 0.05) At day 9: 0.0 nystatin, 0.45 placebo (p < 0.05) Length of ICU stay: 9.6 ± 3.5 days nystatin, 11.9 ± 6.3 days placebo (p < 0.05) |
“Nystatin might reduce the colonization by Candida albicans and was associated with shorter ICU stay” |
CRP C-reactive protein, BMT bone marrow transplant, MICU medical ICU, SICU surgical ICU, sens sensitivity, spec specificity, PPV positive predictive value, NPV negative predictive value