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(Chest. 2003;124:2244-2255.)
© 2003 American College of Chest Physicians

Determinants of Candidemia and Candidemia-Related Death in Cardiothoracic ICU Patients*

Argyris S. Michalopoulos, MD, FCCP; Stefanos Geroulanos, MD and Spyros D. Mentzelopoulos, MD

* From the Department of Intensive Care Medicine (Dr. Geroulanos), Onassis Cardiac Surgery Center; and Henry Dunant General Hospital (Drs. Michalopoulos and Mentzelopoulos), Athens, Greece.

Correspondence to: Spyros D. Mentzelopoulos, MD, 12 Ioustinianou St, 11473, Athens, Greece; e-mail: sdm{at}hol.gr.


   Abstract
TOP
 Abstract
Introduction
 Materials and Methods
 Results
 Discussion
 Conclusion
 References
 
Study objectives: To develop and prospectively validate models of independent predictors of candidemia and candidemia-related death in cardiothoracic ICU (CICU) patients.

Design: (1) An initial, prospective, one-center, case-control, independent predictor-model determining study; and (2) a prospective, two-center, model-validation study.

Setting: The initial study was performed at the 14-bed CICU of the Onassis Cardiac Surgery Center, Athens, Greece; the model-validation study was performed at the Onassis Cardiac Surgery Center CICU and the 12-bed CICU of Henry Dunant General Hospital, Athens, Greece.

Patients: In the initial study, 4,312 patients admitted to the Onassis Center CICU between March 1997 and October 1999 were considered for enrollment; 30 candidemic and 120 control patients (case/control ratio, 1/4) matched according to potential confounders were ultimately enrolled. In the model-validation study, 2,087 patients admitted to the Onassis and Henry Dunant CICUs between November 1999 and May 2002 were prospectively enrolled.

Measurements and results: Models of predictors of candidemia and associated death were constructed with stepwise logistic regression and subsequently validated. Independent candidemia predictors were ongoing invasive mechanical ventilation (IMV) >= 10 days, hospital-acquired bacterial infection and/or bacteremia, cardiopulmonary bypass duration > 120 min, and diabetes mellitus. Model performance was as follows: sensitivity, 53.3%/57.9%; specificity, 100%/100%; positive predictive value (PPV), 100%/100%; negative predictive value (NPV), 88.9%/99.6%; and accuracy, 90.1%/99.6% (initial/model-validation study values, respectively). IMV >= 10 days and hospital-acquired bacterial infection/bacteremia were the two strongest candidemia predictors. APACHE (acute physiology and chronic health evaluation) II score >= 30 at candidemia onset independently predicted candidemia-related death with 80.0%/85.7% sensitivity, 80%/75% specificity, 66.7%/66.7% PPV, 88.9%/88.9% NPV, and 80.0%/78.9% accuracy (initial/model-validation study values, respectively).

Conclusions: We provided a set of easily determinable independent predictors of the occurrence of candidemia in CICU patients. Our results provide a rationale for implementing preventive measures in the form of independent predictor control, and initiating antifungal prophylaxis in high-risk CICU patients.

Key Words: acute physiology and chronic health evaluation • antifungal agents • bacterial infection • candida • candidemia • cardiopulmonary bypass • diabetes mellitus • ICU • respiration, artificial • risk factors


   Introduction
TOP
 Abstract
 Introduction
Materials and Methods
 Results
 Discussion
 Conclusion
 References
 
Candida species are the fourth most frequent isolate in ICU patients with nosocomial bloodstream infections.1 2 Predictors of invasive fungal infections in medical/surgical and surgical ICU patients have been provided1 3 4 5 6 7 ; however, the cardiothoracic ICU (CICU) subpopulation exhibits characteristics, such as increased comorbidity,8 preceding extensive surgery with cardiopulmonary bypass (CPB), and increased postoperative morbidity,9 10 11 12 13 14 15 which could render these patients particularly susceptible to candidemia. In the present investigation, we sought to construct and prospectively validate logistic regression models of determinants of candidemia and associated mortality in CICU patients.


   Materials and Methods
TOP
 Abstract
 Introduction
 Materials and Methods
Results
 Discussion
 Conclusion
 References
 
Patients
The initial, case-control, prospective study was approved by the Review Board of the Onassis Cardiac Surgery Center, Athens, Greece; 4,312 adults, subjected to CPB-employing cardiac operations between March 1997 and October 1999 were candidates for enrollment. Exclusion criteria were immunodeficiency,16 bacterial infection requiring hospitalization within the month preceding the operation, and preoperative exposure to an invasive device apart from that required for emergency coronary angiography or mechanical circulatory support. Antibiotic prophylaxis included a second-generation cephalosporin in coronary artery bypass grafting (CABG) procedures and a third-generation cephalosporin in conjunction with teicoplanin in-valve replacement and mixed (CABG and valve replacement) procedures.

Following CICU admission, patients received mechanical ventilation with a Siemens 300C ventilator (Siemens AG; Berlin, Germany). Ventilatory parameters were adjusted to maintain PaO2 >= 70 mm Hg, PaCO2 between 35 mm Hg and 45 mm Hg, and inspiratory plateau airway pressure < 30 cm H2O. External positive end-expiratory pressure (PEEPe) was applied to maintain alveolar recruitment.17 Preventive measures against aspiration of gastric contents (semirecumbent positioning of patients, confirmation of adequate endotracheal tube cuff function by auscultation and manometry every 12 to 24 h, aspiration of subglottic secretions every 4 to 8 h, and use of small-bore nasogastric tubes for any prescribed enteral feeding in conjunction with metoclopramide to prevent duodenal reflux)18 were taken. Stress ulcer prophylaxis was with ranitidine.19 In diabetic patients, blood sugar was determined every 2 h. Hyperglycemia (blood glucose > 200 mg/dL) was treated with IV infusion of short-acting insulin targeted to maintain glucose levels between 120 mg/dL and 180 mg/dL.20 21

Patients with at least one blood culture result positive for Candida species were assigned to the candidemia group (CAG).3 For each CAG member, four patients admitted within the same month and matched to the former according to gender, body mass index, agents administered for general anesthesia and postoperative sedation, CPB technique (nonpulsatile, hypothermic), and type of employed cardioplegia were assigned to the control group (CG).

Cultures
In all patients with clinical evidence of infection or sepsis,22 reference (initial) and follow-up culture samples (venous blood, tips of removed intravascular catheters,3 endotracheal aspirates, urine, and BAL/protected specimen brush23 in case of suspected ventilator-associated pneumonia [VAP]) were obtained. Follow-up blood, urine, and endotracheal aspirate cultures were to be repeated at least twice until ICU discharge. Immediately after the obtainment of the reference culture samples, empirical antibiotic therapy with two or more broad-spectrum agents was started.

Blood culture samples were processed with the BACTEC 9240 (Becton Dickinson; Franklin Lakes, NJ). Subcultures were done in blood, blood anaerobic, McConkey, Sabouraud, and chocolate agar. Other specimens were inoculated in blood, blood anaerobic, McConkey, Sabouraud, chocolate, cooked meat, and thioglycolate agar. Cultures were incubated at 35°C. For aerobic cultures, a 5% CO2-containing atmosphere was used. Microorganisms were identified with the API system (Biomérieux SA; Marcy l’Etoile, France).

Risk Factors
The tested risk factors for candidemia and associated death (Table 1 ) were chosen a priori by investigator consensus and based on published or in-press articles until February 1997.3 4 24 25 26 27 As also shown in Table 1 , the rationale for the selection of several risk factors was supported by the appropriate bibliographic references.11 28 29 30 31 32 33 34 35 36 37 38 39 40 The APACHE (acute physiology and chronic health evaluation) II score at candidemia onset3 was also evaluated as risk factor for candidemia-related death.3


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  		Table 1.. Tested Risk Factors for Candidemia and Associated Death, and Corresponding Literature References and/or Rationale for Selection*

 
Definitions
Infections were defined according to standard criteria.41 VAP was defined as fever >= 38.5°C, purulent tracheal aspirates, leukocytosis (cell count > 12,000/µL), new or persistent radiographic lung infiltrates, and positive protected specimen brush culture result.42 Bacteremia was defined as isolation of a high-grade pathogen (eg, Staphylococcus aureus) from a blood culture specimen or identification of a skin contaminant or skin flora in two or more separate blood culture specimens from the same patient drawn from different venipuncture sites. Catheter-related infection was defined by clinical systemic inflammatory response syndrome (SIRS)/sepsis,22 and isolation of the same strain(s) of pathogen(s) from cultures of peripheral blood and catheter tip, in the absence of another likely source of infection.

Standard definitions were used for comorbid conditions.43 44 45 Low cardiac output syndrome was defined as cardiac index < 2.0 L/min/m2 body surface area for > 12 h despite maintenance of pulmonary artery wedge pressure within 10 mm Hg and 20 mm Hg. Acute renal failure was defined as rise of >= 2 mg/dL in serum creatinine relative to its preoperative level not responsive to treatment with IV fluids, inotropes, and diuretics for >= 24 h. Lastly, death attributable to candidemia was defined as by Nolla-Salas and coworkers.3

Statistical Analysis
Data analysis was performed with SPSS 10.0 (SPSS; Chicago, IL). Dichotomous or categorical variables were compared with the {chi}2 or the Fisher exact test, and continuous variables with a two-tailed, independent samples t test or the Mann-Whitney U test. For risk factors significantly associated with candidemia by univariate analyses, odds ratios (ORs) were determined. Models predicting the occurrence of candidemia and associated death were constructed with forward, stepwise, logistic regression; p < 0.2 and p < 0.05 were used for covariate inclusion and retention, respectively. Model sensitivity, specificity, positive predictive value (PPV)/negative predictive value (NPV), and accuracy were also determined. Values are reported as number (percentage), or percentage, or mean ± SD, or median (interquartile range) as appropriate. Significance was set at p < 0.05; reported p values are two-tailed.

Model Validation Study
The logistic regression models were prospectively validated at the Onassis Cardiac Surgery Center and Henry Dunant General Hospital, Athens, Greece. Following review board approval, 2,087 CICU patients (Onassis Center, n = 1,286; Henry Dunant, n = 801) fulfilling the inclusion criteria of the initial study were enrolled between November 1999 and May 2002. Antibiotic prophylaxis, mechanical ventilatory support, and glycemic control were as above. In all patients with clinical evidence of infection or sepsis,22 reference (initial) blood culture samples were obtained; in these patients, follow-up blood culture samples were then obtained every 48 to 72 h thereafter until ICU discharge or death occurred. Culture samples from other body sites were also obtained according to the judgment of the attending physicians. In patients with all independent candidemia predictors, additional alimentary tract culture specimens (oropharyngeal and rectal swabs, and gastric aspirates) were obtained on day 10 of ongoing invasive mechanical ventilation (IMV). Model validation included sensitivity, specificity, PPV/NPV, and accuracy analyses.


   Results
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
Discussion
 Conclusion
 References
 
The pooled (initial and validation study) candidemia incidence was 7.7 per 1,000 CICU admissions, as opposed to previously reported incidence of 2.0 per 1,000 medical/surgical ICU admissions.3 During the initial study, 30 patients acquired candidemia (CAG) and 120 patients were assigned to the CG. Table 2 displays patient characteristics. In the CAG, the maximal PEEPe employed for >= 12 h prior to candidemia onset was 9.9 ± 2.1 cm H2O, as opposed to 4.6 ± 3.3 cm H2O in the CG (p < 0.001). The peak daily frequency of hyperglycemic episodes was five episodes (range, four to seven episodes) and one-and-one-half episodes (range, one to two episodes) in CAG and CG patients, respectively (p < 0.001). Each CAG patient had two or more episodes per 24 h during the course of an infection.


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  		Table 2.. Patient Characteristics in the Initial, Model-Determining Study*

 
Hospital-acquired bacterial infection and/or bacteremia requiring administration of two or more broad-spectrum antibiotics preceded candidemia in all CAG members. Gram-negative bacteremia was confirmed in 26 CAG patients (86.7%) and 4 CG patients (3.3%). VAP was diagnosed in 24 CAG patients (80%) and in 4 CG patients (3.3%); it was caused by Gram-negative bacteria in 21 CAG patients (70%) and 2 CG patients (1.7%). Central venous catheter-related infection occurred in three CAG patients (10%) and three CG patients (2.5%).

Factors significantly associated with candidemia by univariate analyses are presented in Table 3 . In the CAG, the median number of predisposing factors was 8 (range, 6 to 13). Candidemia was caused by Candida albicans, Candida parapsilosis, Candida glabrata, Candida tropicalis, and Candida krusei in 21 patients (70%), 3 patients (10%), 2 patients (6.7%), 2 patients (6.7%), and 2 patients (6.7%) in the CAG, respectively. C albicans was simultaneously isolated from blood and central venous catheter tip in four cases.


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  		Table 3.. Factors Significantly Associated With Candidemia by Univariate Regression Analysis*

 
Logistic regression identified four independent candidemia determinants, namely, ongoing IMV >= 10 days, hospital-acquired bacterial infection and/or bacteremia prior to candidemia, CPB duration > 120 min, and diabetes mellitus (Table 4 ). The median interval between candidemia onset and start of antifungal therapy was 2 days (range, 2 to 3 days). Death attributable to candidemia occurred solely within the CICU in 10 CAG patients (33.3%) who exhibited higher APACHE II scores at candidemia onset relative to the 20 others in the CAG group: 31.5 (range, 29.75 to 34.25) vs 23.5 (range, 18.00 to 26.75) [p < 0.001]. All candidemia survivors were ultimately discharged from the CICU and hospital after a protracted total hospital stay that always exceeded 35 days. APACHE II score >= 30 at candidemia onset independently predicted candidemia-related death (Table 4) .


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  		Table 4.. Independent Predictors of Candidemia and Candidemia-Related Death According to Stepwise Logistic Regression Analysis

 
During the validation study, 19 patients acquired candidemia (Onassis Center, n = 12; Henry Dunant Hospital, n = 7) at 15 days (range, 11 to 23 days) after CICU admission. Patient characteristics as well as maximal applied PEEPe for >= 12 h, hyperglycemia frequency, and incidence of postoperative complications were comparable with the respective of the initial study (data not shown). C albicans and C parapsilosis were isolated from the blood of 17 patients (89.5%) and 2 patients (10.5%) with candidemia, respectively. Candidemia-related death occurred in 7 patients (36.8%), whereas all 12 candidemia survivors were ultimately discharged from the hospital after a stay that always exceeded 33 days. The delay in starting antifungal therapy relative to candidemia onset was 2 days (range, 1 to 2.25 days). Both models exhibited similar sensitivities, specificities, PPV/NPV, and accuracies relative to the initial study (Table 5 ). In the 11 validation study members who had all four independent candidemia predictors, C albicans was isolated in "high counts" (defined as > 300 cfu/mL)46 from all three alimentary tract sites, and subsequently from blood.


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  		Table 5.. Results of the Validation of the Logistic Regression Models of the Initial Study*

 

   Discussion
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
Conclusion
 References
 
We identified independent risk factors for candidemia and associated death in CICU patients.

Determinants of Candidemia
Ongoing IMV for >= 10 days was the strongest predictor. IMV predisposes to VAP,47 a frequently observed complication in the CAG. The required antibiotic therapy could have facilitated alimentary tract colonization by Candida species,47 48 whereas the VAP and antibiotic therapy associated endotoxemia should have damaged the intestinal mucosal barrier.49 50 Also, PEEPe exacerbates the post-CPB intestinal hypoperfusion,51 52 thus contributing to further mucosal barrier breakdown. All the aforementioned factors might predispose to the spread of Candida species into the systemic circulation53 and development of candidemia.

The second strongest predictor was hospital-acquired bacterial infection and/or bacteremia. Such conditions could predispose to candidemia via mechanisms described just above for VAP. Hospital infection aggravates illness severity (increased APACHE II score), and is associated with SIRS, clinical sepsis, multiple-organ dysfunction,54 and prolonged IMV and inotropic support. Postoperative bloodstream infection or bacteremia has been causally linked to prolonged CPB,51 IMV (VAP),54 55 and intravascular catheters.54 56 In subsequently candidemic patients, we determined a high VAP incidence (80 to 89.5%) relative to the literature reported (1 to 52%).57 Factors such as CPB-related pulmonary dysfunction9 and CPB endotoxemia-related pulmonary leukostasis58 59 might have been contributory. In contrast, the frequency of central venous catheter-related infection was low relative to the frequency of catheter indwelling time > 72 h (15.4% vs 100%), whereas the rate of possible catheter-related candidemia was also low (<= 3.3%). Thus, the association between catheter indwelling time > 72 h and candidemia was probably mediated by increased illness severity, mandating prolonged use of invasive devices.

The third predictor was prolonged conventional CPB duration. CPB duration > 100 min is associated with postoperative splanchnic hypoperfusion leading to intestinal intramucosal acidosis and increased intestinal mucosal permeability.51 60 The latter is also enhanced by the CPB associated endotoxemia,58 whereas any ischemic intestinal mucosal damage is exacerbated by potent {alpha}-adrenergic receptor agonists.51 60 Thus, the entry of microorganisms into the systemic circulation is facilitated.51 A subsequent, CPB-related bloodstream infection51 may then further promote bacterial/fungal translocation51 53 via mechanisms described above.

The fourth predictor was diabetes mellitus. This relationship should be partly mediated by the effects of hyperglycemia on the concomitant microvascular disease progression and host defense mechanisms.61 Diabetic vasculopathy may exacerbate the CPB-related splanchnic (and consequently intestinal) hypoperfusion,51 61 whereas hyperglycemia also results in neutrophil and lymphocyte dysfunction, and impaired opsonization.61 62 63 64 The importance of each host defense component in killing fungal pathogens has been described.65 In our practice, we apply standard guidelines for glycemic control,20 21 which has proved difficult to achieve in diabetics under inotropic support and infectious stress, however.

With regard to the rest of the candidemia-associated factors (Table 3) , both diabetes and prolonged conventional CPB are risk factors for increased postoperative transfusion requirements and frequency of re-exploration,11 66 postoperative renal dysfunction,66 67 and increased CICU length of stay.66 68 Prolonged conventional CPB is also associated with increased aortic cross-clamp time,69 and increased risk for postoperative low cardiac output syndrome (with subsequent dependency on inotropic support and/or intra-aortic balloon counterpulsation),67 and ischemia-related GI dysfunction.51 The latter could well be the cause of the observed more frequent total parenteral nutrition use in subsequently candidemic patients.70

Interestingly, the independent candidemia predictors seem to be some form of surrogate for VAP and prolonged (> 72 h) antibiotic therapy. Both VAP (OR, 115.9; 95% confidence interval [CI], 13.1 to 1,031.3; p < 0.001) and antibiotic therapy (Table 3) were significantly associated with candidemia. However, since VAP is causally linked to both prolonged IMV47 and candidemia, it fits the definition of an intervening variable71 ; thus, it was appropriate to exclude it from our multiple logistic regression model.71 Prolonged antibiotic therapy should also be regarded as an intervening variable, since it is causally linked to both hospital-acquired bacterial infection/bacteremia and candidemia.

Candidemia-Related Mortality
We found that APACHE II score >= 30 at candidemia onset was independently associated with candidemia-related death (rate, 33.3 to 36.8%). In contrast, Nolla-Salas and coworkers3 found that APACHE II score > 20 at candidemia onset was associated with candidemia-related death (rate, 21.7%) in medical/surgical ICU patients. In the present study, the higher APACHE II scores at candidemia onset (median, 26.5; range, 14 to 38; vs median, 19; range, 1 to 39) [Table 2 ] probably reflected the higher incidence of serious postoperative complications (Table 3) relative to the general surgery enrollees of the Nolla-Salas et al.3

Study Limitations
In our model-validation study, we did not prospectively collect data testing a potential association of antifungal prophylaxis with improved outcomes (eg, decreased mortality rate, earlier weaning from IMV, and shorter CICU and hospital stays) in a subset of our at-risk population of 19 patients. Such data would undoubtedly have been of major clinical importance; however, to test outcomes based on administration of antifungal prophylaxis, the CAG of our validation study would have to be subdivided in two subgroups (one receiving antifungal prophylaxis and one receiving placebo), the small size of which might result in increased probability of type II errors in the between-subgroup comparisons. Furthermore, the initiation of antifungal prophylaxis on IMV day 10 might actually have had interfered with the occurrence of candidemia72 (see "Results" for timing of laboratory confirmation of candidemia) and, consequently, the validation of our model.

Clinical Implications
In the validation phase, our model exhibited high PPVs and NPVs, and accuracy (99.6 to 100%), resulting in a very low percentage (< 0.5%) of incorrect predictions with respect to the occurrence of candidemia. In view of the fact that prophylactic fluconazole use decreases the incidence of candidal infections in high-risk, critically ill, surgical patients,72 the delay in starting antifungal therapy is associated with increased candidemia-related mortality rate,3 and lack of antifungal therapy increases candidemia-related mortality rate by approximately 75%,73 we offer a set of comprehensive recommendations based on the results of the present study.

Our model of candidemia determinants exhibited a poor sensitivity (53.3 to 57.9%), implying a substantial percentage (46.7 to 42.1%) of false-negative predictions (ie, missed identification of CICU patients bound to acquire candidemia); however, the use of the strongest predictor of our model (IMV >= 10 days, exhibiting 96.7 to 100% sensitivity) alone should identify most or all patients at high risk for candidemia with high NPV/accuracy (99.2 to 100% and 99.3 to 99.4%, respectively) but low validation-study PPV (59.4%) [implying that false-positive predictions would probably exceed 40%]. Thus, in CICUs where fluconazole-susceptible Candida species are prevalent, the employment of IMV >= 10 days as a sole criterion to start high-dose prophylaxis (10 mg/kg/d) of (the well-tolerated) fluconazole74 75 76 77 78 can be recommended; the additional use of hospital-acquired bacterial infection/bacteremia (the second strongest candidemia predictor not recommended for use as "sole criterion" due to its very low PPV; Table 5 ) would result in a 3.9% rise in PPV (Table 6 ). The separate/combined use of the two weakest candidemia predictors (CPB > 120 min and diabetes mellitus) is not recommended, mainly due to their moderate-to-low sensitivities, and very low PPVs (Table 5) .


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  		Table 6.. Validation Study Data

 
In CICUs, where fluconazole-resistant Candida species are emerging with increasing frequency,76 77 78 79 liposomal amphotericin B79 could be alternatively considered. In such centers, the 100% specificity of our four-predictor model (no false-positive predictions) would be of obvious importance due to the toxicity of amphotericin80 81 82 ; however, the poor model sensitivity would still result in missed identification of at-risk patients. Thus, we would additionally recommend daily surveillance blood cultures for patients having the first (with or without the second) strongest candidemia predictor of our model. The new triazoles voriconazole, posaconazole, and ravuconazole may constitute additional, effective alternatives for antifungal prophylaxis.75 76 77 Voriconazole is almost as effective as liposomal amphotericin B in patients with febrile neutropenia83 and superior to the latter in the reduction of breakthrough fungal infections, while exhibiting less infusion-related toxicity and nephrotoxicity.83 Voriconazole has recently been recommended for the treatment of refractory fungal infections in surgical patients84 ; however, since experience with the newer triazoles is still limited, we would offer the same recommendations as for liposomal amphotericin B.

Figure 1 illustrates our recommendations in algorithm form.85 Nevertheless, future multicenter research testing outcomes in at-risk CICU patient groups (as defined by our model or its two strongest predictors) receiving (or not) antifungal prophylaxis is warranted; subdivisions of such patient groups with respect to high (>= 30) and/or rising APACHE II scores, clinical signs of SIRS/sepsis,22 and weaning candidacy86 87 would probably be useful.



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  		Figure 1.. Antifungal prophylaxis algorithm for CICU patients at high risk for candidemia. *Recommended for early isolation of potentially drug-resistant fungi (see also Pfaller et al85 ); in such cases, following susceptibility testing, the appropriate antifungal agent should be administered. **Recommended for timely diagnosis of candidemia. BI = bacterial infection.

 
Preventive Measures
It could be argued that IMV dependence is mainly a reflection of illness severity, and infectious complications are more frequent in sicker patients; therefore, it would be difficult to control the two strongest candidemia predictors. However, evidence-supported strategies expediting weaning from IMV and facilitating infection control actually exist. Thus, in patients at high risk of extubation failure,88 89 and potentially reversible, associated risk factors (eg, anemia, residual sedation, and excessive respiratory secretions)89 should be identified and appropriately treated, and extubation followed by noninvasive ventilation (NIV) should be considered.88 89 90 The prolonged presence of endotracheal tubes facilitates bacterial colonization of the tracheobronchial tree,91 92 whereas pooled secretions above endotracheal tube cuffs constitute a source of aspiration and can cause VAP.91 92 93 94 In addition, the still nonpreventable formation of biofilm on endotracheal tubes further promotes the occurrence of VAP.95 96 Consequently, and additionally based on the high VAP incidence (80 to 89.5%) in the present study in subsequently candidemic CICU patients, we would strongly recommend the use of NIV to facilitate weaning from IMV of CICU patients at high risk for candidemia (or even those receiving IMV for > 72 h),97 even in the absence of directly supportive, published outcome data. In the presence of contraindication(s) to NIV98 and high risk of extubation failure,89 recently described pharmacologic and nonpharmacologic strategies96 97 aiming to prevent VAP should be implemented.

As for the prevention of hospital-acquired infections in general, evidence-based preventive strategies have been recently described in detail.99 100 We wish to stress the importance of hand disinfection, patient isolation, control of antimicrobial use, and selective digestive decontamination in high-risk patients.99 100

Regarding the control of prolonged CPB duration, off-pump coronary artery bypass now constitutes an effective and safe alternative to traditional coronary revascularization, without the potentially deleterious CPB effects.101 Even complex procedures are now feasible, resulting in significant reductions in CPB duration and aortic cross-clamp times.102 Several studies102 103 104 105 106 107 108 109 have demonstrated that off-pump coronary artery bypass exhibits significant advantages relative to conventional CABG. Also, endoscopic CABG with the use of robotic systems may prove a new, effective, minimally invasive alternative in the future.110

Regarding patients with diabetes mellitus, the preoperative control of the associated microvascular and macrovascular disease-induced impairment of host defenses61 may not be attainable; however, hyperglycemia (the hallmark of diabetes mellitus) is associated with abnormalities in lymphocyte number and function,62 63 and impairs polymorphonuclear leukocyte function, irrespective of the duration of and physiologic etiology for the increased glucose levels.61 111 112 113 114 115 116 117 118 Rassias et al118 showed that in cardiac surgery, "aggressive" intraoperative insulin treatment attenuates the intraoperative hyperglycemia/CPB/anesthesia-related post-CPB reduction in neutrophil phagocytotic activity; a trend toward reduced incidence of postoperative infectious complications was also observed. Furthermore, Zerr et al119 demonstrated that postoperative glycemic control by an "aggressive" protocol of continuous IV insulin infusion lowers the risk of wound infection in diabetic CICU patients. Thus, to reduce the risk of infectious complications in diabetic CICU patients, perioperative glycemic control should (and could)116 117 be tightened, in order to minimize the time of blood glucose levels exceeding 200 mg/dL.61


   Conclusion
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 Conclusion
References
 
We provided a set of easily determinable independent predictors of the occurrence of candidemia in CICU patients. Our results provide a rationale for both implementing preventive measures in the form of independent predictor control, and initiating antifungal prophylaxis in high-risk CICU patients.


   Acknowledgements
 
The authors thank microbiologist Dr. George V. Georgoulias for his help during the validation study.


   Footnotes
 
Abbreviations: APACHE = acute physiology and chronic health evaluation; CABG = coronary artery bypass grafting; CAG = candidemia group; CG = control group; CI = confidence interval; CICU = cardiothoracic ICU; CPB = cardiopulmonary bypass; IMV = invasive mechanical ventilation; NIV = noninvasive ventilation; NPV = negative predictive value; OR = odds ratio; PEEPe = external positive end-expiratory pressure; PPV = positive predictive value; SIRS = systemic inflammatory response syndrome; VAP = ventilator-associated pneumonia

Received for publication December 3, 2002. Accepted for publication April 28, 2003.


   References
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 Conclusion
 References
 

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