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Risk Factors for Candidal Bloodstream Infections in Surgical Intensive Care Unit Patients: The NEMIS Prospective Multicenter Study

  1. Henry M. Blumberg1,2,
  2. William R. Jarvis3,
  3. J. Michael Soucie4,
  4. Jack E. Edwards5,
  5. Jan E. Patterson6,
  6. Michael A. Pfaller7,
  7. M. Sigfrido Rangel-Frausto8,9,
  8. Michael G. Rinaldi10,
  9. Lisa Saiman11,
  10. R. Todd Wiblin8,
  11. Richard P. Wenzel12, and
  12. the NEMIS Study Groupa
  1. 1 Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta
  2. 2 Epidemiology Department, Grady Memorial Hospital, Atlanta
  3. 3 Hospital Infections Program, Centers for Disease Control and Prevention, Atlanta
  4. 4 Department of Epidemiology, Rollins School of Public Health of Emory University, Atlanta
  5. 5 Division of Infectious Diseases, Department of Internal Medicine, Harbor-UCLA Medical Center, University of California Los Angeles, Los Angeles
  6. 6 Division of Infectious Diseases, Department of Internal Medicine, University of Texas Health Sciences Center at San Antonio, San Antonio, Texas
  7. 7 Division of Medical Microbiology, Department of Pathology, University of Iowa, Iowa City
  8. 8 Division of General Internal Medicine, Department of Internal Medicine, University of Iowa, Iowa City
  9. 9 Division of Hospital Epidemiology, Instituto Nacional Nutricion, Mexico City
  10. 10 Fungus Testing Laboratory, Department of Pathology, University of Texas Health Science Center at San Antonio, San Antonio, Texas
  11. 11 Division of Infectious Diseases, Department of Pediatrics, Columbia University, New York
  12. 12 Department of Internal Medicine, Medical College of Virginia, Virginia Commonwealth University, Richmond, Virginia
  1. Reprints or correspondence: Dr. Henry M. Blumberg, Division of Infectious Diseases, Emory University School of Medicine, 69 Butler St., Atlanta, GA 30303 (hblumbe{at}emory.edu).
 
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Abstract

To assess risk factors for development of candidal blood stream infections (CBSIs), a prospective cohort study was performed at 6 sites that involved all patients admitted to the surgical intensive care unit (SICU) for >48 h over a 2-year period. Among 4276 such patients, 42 CBSIs occurred (9.82 CBSIs per 1000 admissions). The overall incidence was 0.98 CBSIs per 1000 patient days and 1.42 per 1000 SICU days with a central venous catheter in place. In multivariate analysis, factors independently associated with increased risk of CBSI included prior surgery (relative risk [RR], 7.3), acute renal failure (RR, 4.2), receipt of parenteral nutrition (RR, 3.6), and, for patients who had undergone surgery, presence of a triple lumen catheter (RR, 5.4). Receipt of an antifungal agent was associated with decreased risk (RR, 0.3). Prospective clinical studies are needed to identify which antifungal agents are most protective and which high-risk patients will benefit from antifungal prophylaxis.

Over the past 2 decades, Candida species have become the fourth most common cause of bloodstream infections (BSIs) among patients in intensive care units (ICUs) [1–5]. Previous studies have suggested that possible risk factors for candidal BSI (CBSI) may include receipt of antibiotic agents, chemotherapy, or steroids; the presence of intravascular catheters; receipt of parenteral nutrition; surgery; hospitalization in an ICU; malignancy; neutropenia; and prior fungal colonization [2, 3, 6–14]. These data are limited by the fact that the large majority of studies have been retrospective, with data gathered from a single institution over a long period of time (e.g., a decade or more) [14].

Among patients cared for in ICUs, those in surgical ICUs (SICUs) are thought to be at the greatest risk for developing a CBSI [15, 16]. Given reports of the 40%–60% mortality rate associated with CBSIs, the use of antifungal prophylaxis for surgical patients has emerged as a common practice. However, there are no data to indicate whether such use is beneficial in the ICU setting [17, 18].

The National Epidemiology of Mycosis Survey (or NEMIS) was a prospective, multicenter study conducted at 6 geographically dispersed academic medical centers to examine rates of and risk factors for the development of CBSIs among patients in surgical and neonatal ICUs. A recent report from the NEMIS study group has described the methods employed in the surveillance and the great variation in the rate of CBSIs among patients in surgical and neonatal ICUs at various institutions [19]. Herein we describe the risk factors for the development of CBSIs among patients being cared for in SICUs, and we report results of molecular typing and susceptibility tests performed on Candida species isolates recovered from blood cultures.

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Patients and Methods

Study design. The NEMIS was a prospective multicenter cohort study conducted in SICUs at 6 sites in the United States [19]: Atlanta (Grady Memorial Hospital/Emory University School of Medicine); Iowa City, Iowa (University of Iowa); Los Angeles (Harbor—UCLA Medical Center); New York City (Columbia-Presbyterian Medical Center); Portland (Oregon Health Sciences University); and San Antonio (University of Texas—San Antonio Health Sciences Center and the Veterans Affairs Medical Center). The study period was from October 1993 to November 1995, but the study was initiated and data were collected slightly later at some centers than at others. All centers enrolled patients for a minimum of 18 months.

Study population and case definition. All patients admitted to an SICU at these centers for >48 h were enrolled in the study. Case patients were defined as those individuals who had a Candida species recovered from culture of a blood specimen collected >48 h after admission to the SICU. For case patients, risk factor analysis included data collected up to the time of the development of the CBSI, whereas for non—case patients in the cohort, risk factor analyses included data collected for the entire duration of the stay in the SICU.

Data abstraction. Clinical and epidemiological data on all patients enrolled in the study were collected daily by dedicated study nurses, as previously described [19]. In the first year of the study, all azole drug use was recorded as a single variable, whereas in the second year information was recorded about the specific azole drugs administered (e.g., fluconazole, itraconazole, ketoconazole, miconazole, or clotrimazole). Severity-of-illness measures, including American Society of Anesthesia (ASA) scores [20], Acute Physiology and Chronic Health Evaluation (APACHE) II scores [21], and McCabe-Jackson scores [22], were calculated for all patients at the time of admission to the SICU.

Microbiological testing. Rectal swabs and urine specimens for fungal surveillance culture were collected from each patient at the time of admission to the SICU and each week thereafter if the patient remained hospitalized in the SICU. Fungal surveillance cultures were incubated according to standard laboratory methods and isolates were identified with use of the commercial identification system API20C and VITEK Yeast Identification (bioMérieux VITEK) [23]. Antifungal susceptibility of Candida species isolates was determined by testing them against amphotericin B, flucytosine, fluconazole, and itraconazole with use of a standard broth-microdilution method, as described elsewhere [24]. Molecular typing of Candida species isolates was performed by means of pulsed-field gel electrophoresis with use of the restriction enzyme BssHII or SfiI [23]; Candida albicans isolates were typed with use of the species-specific probe Ca3 [25]. Thirty-five of 42 Candida species isolates recovered from blood were available for typing. Banding patterns were analyzed for relatedness with use of a computer-assisted system (Dendron software, version 2.0; Solltech).

Statistical analysis. Infection rates (the number of CBSIs per 1000 patient-days) were compared between groups of persons in different categories of the variable examined; the rate ratio was used as a measure of relative risk [26]. Univariate and multivariate analyses were performed with SAS software (SAS). A P value of ⩽.05 was considered significant.

A stepwise approach was used to determine which of the studied factors or variables were most strongly associated with CBSI. Variables with significant colinearity were dropped from the analysis. The remaining variables were evaluated for associations with the development of CBSI with use of proportional hazards and logistic regression [27, 28]. Because both methods yielded similar results, only the results from the analysis performed with proportional hazards regression are presented. In order to evaluate whether risk factors for the development of CBSI were different for SICU patients who did and did not have surgery, 2 regression models were used (one that included all patients in the study and another that included only those who had undergone surgery). During regression modeling, all variables that did not significantly contribute to the model were removed from consideration with use of a backward stepwise method. Regardless of statistical significance, the hospital variable was left in both models to account for potential unmeasured differences between different institutions in the risk of developing CBSI.

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Results

During the study period, 42 CBSIs developed among the 4276 admitted patients enrolled at the 6 different academic medical centers (9.82 CBSIs per 1000 admissions). Candida species accounted for 9.2% of the total number of BSIs (n = 458). The overall rate of CBSIs was 0.98 per 1000 SICU patient-days, or 1.42 per 1000 SICU central line days (i.e., days in the SICU with a central venous catheter in place). Over half of the Candida isolates recovered from blood were non-albicans species: 20 (48%) were C. albicans, 10 (24%) were Candida glabrata, 8 (19%) were Candida tropicalis, 3 (7%) were Candida parapsilosis, and 1 (2%) was Candida lusitaniae.

Most CBSI cases (76%) occurred within the first 3 weeks of admission to an SICU (figure 1). The mortality rate was significantly higher among patients who developed CBSI than among other patients; 17 (41%) of 42 patients with CBSI died, versus 351 (8%) of 4234 patients who did not develop CBSI (OR, 7.52; 95% CI, 3.9–14.6; P < .001).

Figure 1
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Figure 1

Time (in days) of onset of candidal bloodstream infection (BSI) after admission to a surgical intensive care unit (SICU). Forty-two candidal BSIs occurred during the study period.

Risk factors. The mean age (±SD) of all patients enrolled in the study was 53.5 ± 18.2 years, which did not differ significantly from the mean age of those who developed CBSI (52.1 ± 17.5 years). Rates of CBSI varied between institutions, from a low of 0.28 per 1000 patient-days at the Oregon Health Sciences Center to a high of 1.75 per 1000 patient-days at Columbia-Presbyterian Hospital [19]. In univariate analysis, the CBSI rates at Grady Memorial Hospital and Columbia-Presbyterian Hospital were significantly higher than that at Oregon (table 1), but in multivariate analyses, residence at a particular institution was not associated with an increased risk of CBSI infection (see the section on Multivariate Analysis, below). A higher severity-of-illness value, as indicated by the McCabe-Jackson, APACHE II, or ASA score at the time of admission to the SICU, was not associated with increased risk of developing a CBSI in univariate analysis (table 1).

Table 1
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Table 1

Characteristics of 4276 surgical intensive care unit patients and their risk for candidal bloodstream infection.

Of 42 patients who developed CBSIs, 41 had a central venous catheter (CVC) in place during their SICU stay prior to the development of infection (table 2). Among these 41 patients, the rate of CBSIs was 1.23 per 1000 patient-days, versus 0.11 per 1000 patient-days among patients who did not have a CVC in place (RR, 8.1; 95% CI, 1.1–59.6; P = .04). Seventy-five percent of SICU patients underwent surgery; this group had a significantly higher rate of CBSI than did the group who did not require surgery (table 2). There was a trend toward increased risk of infection among those who had an abdominal procedure performed (RR, 1.8; 95% CI, 0.9–3.4; P = .06); those who had a neurosurgical procedure performed were at significantly lower risk (RR, 0.2; 95% CI, 0.1–0.7; P = .02), and no increased or decreased risk was seen among patients who underwent orthopedic, cardiovascular, ear/nose/throat, gynecologic, or transplantation surgery (table 2).

Table 2
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Table 2

Infection rates and risk of candidal bloodstream infection for 4276 surgical intensive care unit patients, by type of procedure.

Medications associated with an increased risk of developing a CBSI in univariate analysis included receipt of parenteral nutrition, intralipid agents, vancomycin, or an antibiotic agent with activity against anaerobic organisms (including combinations of imipenem, metronidazole, clindamycin, and the extended-spectrum penicillins/β-lactamase-inhibitor drugs, such as ticarcillin/clavulanate, piperacillin/tazobactam, and ampicillin/sulbactam; table 3). Treatment with antifungal agents (amphotericin B, azoles, nystatin, or any antifungal drug) were not significantly associated with risk for developing CBSI in univariate analysis (table 4); however, in univariate analysis there was a trend toward an association between receipt of antifungal agents and a decreased risk of developing CBSI (RR, 0.6; 95% CI, 0.3–1.1; P = .09; table 4).

Table 3
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Table 3

Treatments and medications associated with increased risk of candidal bloodstream infection in 4276 surgical intensive care unit patients.

Table 4
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Table 4

Antifungal medications administered to 4276 surgical intensive care unit patients and their risk for candidal bloodstream infection.

No increased risk of developing infection was associated with the individual use of the following antibiotic agents: aminoglycosides, penicillins (including extended-spectrum penicillins and β-lactam/β-lactamase inhibitor drugs), first-, second-, or third-generation cephalosporins, imipenem, fluoroquinolones, clindamycin, metronidazole, and erythromycin (data not shown). There were no CBSIs among the 784 SICU patients who did not receive an antibiotic agent. For the 3512 patients who did receive ⩾1 antibiotic agents, there was no significant difference in rates of CBSIs with stratification by the number of days antibiotic agents were received (data not shown). Receipt of antacids, H2 blockers, corticosteroids, or sucralfate also was not associated with risk of developing CBSI (data not shown).

Among patients who developed acute renal failure, shock, or disseminated intravascular coagulation, the rate of CBSI was significantly higher than it was among patients who did not develop these conditions (table 5). Among patients who had acute respiratory distress syndrome or developed a bacterial BSI, the rate of subsequent CBSI was higher than among patients who did not develop these conditions, but the differences were not statistically significant (table 5).

Table 5
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Table 5

Clinical diagnoses assigned to 4276 surgical intensive care unit patients and their risk for candidal bloodstream infection (BSI).

Risk after colonization. As part of the study protocol, rectal swabs and urine specimens for Candida surveillance cultures were collected on admission to the SICU and then weekly for patients who remained hospitalized in the SICU. Thirty percent of patients (n = 1280) had Candida species recovered in rectal surveillance cultures, and 15% of patients (n = 627) had a positive urine culture for Candida species (table 6). The positive predictive value for developing CBSI after a rectal culture was positive for Candida was only 2.0% (26/1280), and for a positive urine culture it was 2.7% (17/627). Among patients who had Candida species recovered from urine, the rate of subsequent CBSI was higher than for those who did not, but the difference did not reach statistical significance (1.62 vs. 0.79 CBSI per 1000 patient days; RR, 1.6; 95% CI, 0.9–3.1; P = .13). Recovery of Candida species from a rectal swab or from both a urine sample and a rectal swab was not associated with an increased risk of subsequently developing CBSI (table 6).

Table 6
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Table 6

Fungal colonization among the 4276 surgical intensive care unit patients and their risk of candidal bloodstream infection.

Multivariate analyses. In multivariate analyses of the entire cohort, factors independently associated with increased risk of CBSI included prior surgery (RR, 7.3; 95% CI, 1.0–53.8; P = .05), acute renal failure (RR, 4.2; 95% CI, 2.1–8.3; P < .001), and receipt of parenteral nutrition (RR, 3.6; 95% CI, 1.8–7.5; P < .001). Receipt of an antifungal agent was associated with a decreased risk of subsequent CBSI (RR, 0.3; 95% CI, 0.1–0.6; P < .001; table 7). A second multivariate model that included only patients who underwent surgery (n = 3201) identified an association between increased risk of CBSI and having had a triple-lumen catheter placed (RR, 5.4; 95% CI, 1.2–23.6; P = .03), in addition to the factors noted above. Having undergone neurosurgical or ear/nose/throat surgery was associated with decreased risk of subsequent CBSI (table 7). Receipt of an antifungal medication was significantly associated with decreased risk, as it was in the previous model.

Table 7
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Table 7

Multivariate analyses of risk factors for candidal bloodstream infections in surgical intensive care unit (SICU) patients with and without prior surgery.

Susceptibility testing and molecular typing. Antifungal susceptibility testing was performed on Candida isolates recovered from 35 of the 42 patients who developed a BSI (table 8). All isolates were susceptible to amphotericin B, 34 (97%) to flucytosine, and 31 (89%) were susceptible to fluconazole and itraconazole. Two of 8 C. glabrata isolates were resistant to fluconazole (MIC, ⩾64 µg/mL), and 1 additional isolate demonstrated dose-dependent susceptibility (MICs, >8 µg/mL and <64 µg/mL). Two of 26 other Candida isolates (1 C. albicans and 1 C. tropicalis) were resistant to fluconazole (table 8). Molecular typing studies with use of pulsed-field gel electrophoresis, electrophoretic karyotyping, and (for C. albicans) a Ca3 probe were carried out on paired isolates from cultures of urine and blood samples from 18 patients whose urine cultures were positive for a Candida species before the onset of CBSI. Seventeen of 18 paired isolates had identical banding patterns.

Table 8
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Table 8

In vitro antifungal susceptibility of Candida species isolates recovered from blood.

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Discussion

The NEMIS SICU study is the largest prospective multicenter study to evaluate risk factors for the development of CBSI among SICU patients. There was a 6-fold variation in infection rates between institutions, from a low of 0.28 per 1000 patient-days to a high of 1.75 per 1000 patient-days. The 2 institutions with the highest rates of CBSIs are urban hospitals that care for large numbers of trauma patients. Previously reported data from the National Nosocomial Infections Surveillance (NNIS) system suggest that such patients have the greatest risk of developing nosocomial fungal infections [2, 3]. The fact that being a patient in the SICU at either of these institutions (in New York and Atlanta) was not independently associated with increased risk for development of CBSI in the multivariate analysis suggests that other risk factors accounted for the higher rate of CBSIs at those institutions.

It is interesting that ∼25% of all patients admitted to an SICU did not undergo a surgical procedure. The risk of this subset of SICU patients developing a CBSI was clearly different than that of patients who underwent a surgical procedure. Patients who underwent a surgical procedure or had a CVC were ∼11 times more likely to develop candidemia. Forty-one of the 42 CBSIs occurred in patients who had surgery and among those who had a CVC, with a rate of 1.2 per 1000 patient-days, versus 0.11 per 1000 patient-days for those who did not have a surgical procedure or a CVC.

In multivariate analyses, risk factors that were independently associated with increased risk of CBSI in our study included prior surgery (RR, 7.3), acute renal failure (RR, 4.2), and receipt of parenteral nutrition (RR, 3.6). Receipt of an antifungal drug significantly reduced the risk of developing a CBSI (RR, 0.3). When the model included only patients who underwent surgery, results were similar, but having had a triple-lumen catheter also proved to be a risk factor for developing CBSI (RR, 5.4). Our study helps further define the independent risk factors for CBSI in SICU patients and should help better identify high-risk patients in the SICU setting.

Potential risk factors for developing candidemia identified in previous studies have included receipt of antimicrobial agents, corticosteroids, chemotherapy, or parenteral therapy; hematological or solid organ malignancy; neutropenia; extensive surgery or burns; mechanical ventilation; a stay in an ICU (especially a surgical or neonatal ICU); an indwelling CVC or hemodialysis; and prior fungal colonization [2, 3, 6–11, 29, 30]. These studies have most frequently involved either patients with hematologic or solid organ malignancies exclusively or mixed patient populations [3]. Many of these previous studies have been limited by the fact that they often obtained data from a single institution or over a long period of time in order to ensure an adequate number of cases for review. In addition, few studies were prospective in design, and the few prospective studies have not focused on SICU populations. The large quantity of data and extent of data collection may account for the differences between our study and previous studies.

In our study, a high mortality rate (41%) was noted among patients who developed CBSIs, comparable to data from previous reports [3, 31–35]. Because of the high mortality rate among patients who develop CBSIs, it has been suggested that prophylactic, presumptive, or empirical therapy be given to high-risk patients in the SICU [16, 17, 36, 37]. These strategies are frequently employed, and a number of institutions have developed algorithms for deciding whether to use antifungal therapy for at-risk patients who do not have a proven invasive candidal infection [16, 38–40]. Previous investigators reported the use of oral nystatin or ketoconazole [37], but recent recommendations have focused on the use of fluconazole [16]. However, how to identify high-risk patients has been incompletely defined and has varied in different reports; there are few data on the efficacy of antifungal prophylaxis or preemptive interventions for SICU patients.

The British Society for Antimicrobial Chemotherapy Working Party has recommended empirical therapy for high-risk patients who have a urine culture that is positive for Candida and who have a “deteriorating clinical status” [38], whereas other investigators have recommended presumptive therapy for any ICU patient who has fungal colonization [36]. Our finding that fungal colonization (of the urinary tract alone and/or rectum) does not have a high positive predictive value raises doubts about this approach.

Prophylactic use of fluconazole has been shown to reduce the incidence of invasive and superficial fungal infections among bone marrow transplantation patients in randomized controlled trials [39], but the emergence of infections due to natively resistant Candida species, such as Candida krusei, has been noted with fluconazole prophylaxis in this patient population [40]. Results of fluconazole prophylaxis among patients who have neutropenia and acute leukemia have been conflicting; one study showed no statistically significant reduction in invasive fungal infections [41], whereas a more recent study did show a significant reduction in invasive fungal infections [42]. Eggimann et al. [43] conducted a randomized, placebo-controlled trial to study the efficacy of fluconazole prophylaxis among 49 high-risk surgical patients with recurrent gastrointestinal perforations or anastomotic leakages. They reported that patients who received fluconazole were less likely to have abdominal colonization or infection (peritonitis) with Candida species, but they were unable to assess whether the prophylaxis affected the risk of acquiring a CBSI because of the small number of patients enrolled.

The finding in our study that receipt of an antifungal agent was associated with a reduced risk of developing CBSI for SICU patients is important and has not been reported from previous epidemiological investigations. In our study, the use of antifungal agents was determined by the physicians caring for the patients, and guidelines for antifungal use were neither provided nor part of the study protocol. A limitation of our study was that data on the specific type of azole drug used (e.g., fluconazole, ketoconazole, itraconazole, clotrimazole, or miconazole) were not recorded in the first year of the study. This limited our ability to further determine which antifungal drug (e.g., amphotericin B or a specific azole agent) was protective. Prospective clinical trials are needed to determine which high-risk patients would benefit from prophylaxis and which antifungal agents would be most useful.

Several authors have recommended performance of serial fungal surveillance cultures and initiation of presumptive antifungal therapy if any degree of fungal colonization is noted [17, 36], if patients are colonized at ⩾2 sites, or if the colonization index is high [44] or candiduria is present in high-risk patients who are clinically unstable [38]. In our study, specimens of urine and rectal swabs for fungal surveillance culture were obtained on admission to the SICU and weekly thereafter. In 17 of 18 cases, molecular typing indicated that the colonizing strain was identical to the Candida isolate subsequently recovered from blood. Fungal colonization (defined as a urine or rectal swab culture positive for Candida species) was not associated with a statistically significant increase in risk of CBSI in univariate or multivariate analyses. Overall, 30% of the 4276 patients in the study had rectal colonization with a Candida species, 15% had urinary colonization, and 11% had both rectal and urinary colonization; however, only ∼1% of the patients in the study developed a CBSI. The finding of urinary or rectal fungal colonization alone, as assessed in our study, does not appear to be clinically useful for deciding when to start presumptive antifungal therapy.

Other investigators [17] have suggested that an elevated APACHE II score can help identify high-risk ICU patients who should start receiving prophylactic or presumptive antifungal therapy, given the findings of a retrospective study reported by Fraser et al. [33] that an elevated APACHE II score was associated with increased risk of developing CBSI. In our prospective study, however, a higher APACHE II or McCabe and Jackson score on admission was not associated with a significantly higher risk of developing CBSI.

In summary, this report demonstrates that the wide variation in the rate of CBSI between institutions is likely due to the underlying risk factors of the different patient populations served by the geographically dispersed institutions, and it defines a number of risk factors that are independently associated with increased risk of CBSI. The finding that receipt of an antifungal drug is associated with a reduced risk of developing CBSI indicates the need for additional investigations to further define which high-risk patients should be given prophylactic or presumptive therapy and which antifungal agents are most beneficial.

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Footnotes

  • Grant support: This study was supported by an educational grant from Pfizer, Inc.

  • This study was approved by the investigational review boards of each of the study sites.

  • ↵a The NEMIS Study Group comprises Michele Costigan and Jeffrey Dawson (University of Iowa), Harold Neu (deceased; Columbia University), Michael Martin (Oregon Health Sciences University), and Douglas Webb (Pfizer, Inc).

  • See the editorial commentary by Sobel and Rex on pages 187–90.

  • Received June 13, 2000.
  • Revision received December 20, 2000.
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References

  1. ↵
    1. Edwards JR Jr
    . Invasive candida infections. Evolution of a fungal pathogen. N Engl J Med 1991;324:1060-2.
    MedlineWeb of Science
  2. ↵
    1. Beck-Sague CM,
    2. Jarvis WR
    ; the National Nosocomial Infections Surveillance System. Secular trends in the epidemiology of nosocomial fungal infections in the United States. J Infect Dis 1993;167:1247-51.
    Abstract/FREE Full Text
  3. ↵
    1. Fridkin SK,
    2. Jarvis WR
    . Epidemiology of nosocomial fungal infections. Clin Microbiol Rev 1996;9:499-511.
    Abstract/FREE Full Text
    1. Jarvis WR
    . Epidemiology of nosocomial fungal infections, with emphasis on Candida species. Clin Infect Dis 1995;20:1526-30.
    Abstract/FREE Full Text
  5. ↵
    1. Jarvis WR,
    2. Martone WJ
    . Predominant pathogens in hospital infections. J Antimicrob Chemother 1992;29(Suppl A):19-24.
    Abstract/FREE Full Text
  6. ↵
    1. Bross J,
    2. Talbot GH,
    3. Maislin G,
    4. Hurwitz S,
    5. Strom BL
    . Risk factors for nosocomial candidemia: a case-control study. Am J Med 1989;87:614-20.
    MedlineWeb of Science
    1. Richet HM,
    2. Andremont A,
    3. Tancrede C,
    4. Pico JL,
    5. Jarvis WR
    . Risk factors for candidemia in patients with acute lymphocytic leukemia. Rev Infect Dis 1991;13:211-5.
    MedlineWeb of Science
    1. Wey SB,
    2. Mori M,
    3. Pfaller MA,
    4. Woolson RF,
    5. Wenzel RP
    . Risk factors for hospital-acquired candidemia. Arch Intern Med 1989;149:2349-53.
    Abstract/FREE Full Text
    1. Karabinis A,
    2. Hill C,
    3. Leclerg B,
    4. Tancrede C,
    5. Baume D,
    6. Andremont A
    . Risk factors for candidemia in cancer patients: a case-control study. J Clin Microbiol 1988;26:429-32.
    Abstract/FREE Full Text
    1. Kohmshian SV,
    2. Uwaydah A,
    3. Sobel JD,
    4. Crane LR
    . Fungemia caused by Candida species and Torulopsis glabrata in the hospitalized patient: frequency, characteristics, and evaluation of factors influencing outcome. Rev Infect Dis 1989;11:379-90.
    MedlineWeb of Science
  11. ↵
    1. Vazquez JA,
    2. Sanchez V,
    3. Dmochowski C,
    4. Dembry LM,
    5. Sobel JD,
    6. Zervos MJ
    . Nosocomial acquisition of Candida albicans: an epidemiologic study. J Infect Dis 1993;168:195-201.
    Abstract/FREE Full Text
    1. Schwartz RS,
    2. Mackintosh FR,
    3. Schrier SL,
    4. Greenberg PL
    . Multivariate analysis of factors associated with invasive fungal disease during remission-induction therapy for acute myelogenous leukemia. Cancer 1984;53:411-9.
    CrossRefMedlineWeb of Science
    1. Pittet D,
    2. Monod M,
    3. Suter PM,
    4. Frenk E,
    5. Auckenthaler R
    . Candida colonization and subsequent infections in critically ill surgical patients. Ann Surg 1994;220:751-8.
    MedlineWeb of Science
  14. ↵
    1. Nguyen HM,
    2. Peacock JE,
    3. Morris AJ,
    4. et al
    . The changing face of candidemia: emergence of non-Candida albicans species and antifungal resistance. Am J Med 1996;100:617-23.
    CrossRefMedlineWeb of Science
  15. ↵
    1. Voss A,
    2. Pfaller MA,
    3. Hollis RJ,
    4. Rhine-Chalberg J,
    5. Doebbeling BN
    . Investigation of Candida albicans transmission in a surgical intensive care unit cluster by using genomic DNA typing methods. J Clin Microbiol 1995;33:576-80.
    Abstract/FREE Full Text
  16. ↵
    1. Vincent JL,
    2. Anaissie E,
    3. Bruining H,
    4. et al
    . Epidemiology, diagnosis and treatment of systemic candidal infection in surgical patients under intensive care. Intensive Care Med 1998;24:206-16.
    CrossRefMedlineWeb of Science
  17. ↵
    1. Dean DA,
    2. Burchard KW
    . Surgical perspective on invasive candida infections. World J Surg 1998;22:127-34.
    CrossRefMedlineWeb of Science
  18. ↵
    1. Berrouane YF,
    2. Herwaldt LA,
    3. Pfaller MA
    . Trends in antifungal use and epidemiology of nosocomial yeast infections in a university hospital. J Clin Microbiol 1999;37:531-7.
    Abstract/FREE Full Text
  19. ↵
    1. Rangel-Frausto MS,
    2. Wiblin T,
    3. Blumberg HM,
    4. et al
    . National Epidemiology of Mycosis Survey (NEMIS): variations in rates of candidal bloodstream infections in seven surgical ICUs and six neonatal ICUs. Clin Infect Dis 1999;29:253-8.
    MedlineWeb of Science
  20. ↵
    1. Owens WD,
    2. Felts JA,
    3. Spitznage EL
    . ASA physical status classifications. Anesthesiology 1978;49:239-43.
    MedlineWeb of Science
  21. ↵
    1. Knaus WA,
    2. Draper EA,
    3. Waner DP,
    4. Zimmerman JE
    . APACHE II: a severity of disease classification system. Crit Care Med 1985;13:818-29.
    MedlineWeb of Science
  22. ↵
    1. McCabe WR,
    2. Jackson GG
    . Gram negative bacteremia. Arch Intern Med 1962;110:847-64.
    Abstract/FREE Full Text
  23. ↵
    1. Pfaller MA,
    2. Messer SA,
    3. Houston A,
    4. et al
    . National epidemiology of mycoses survey: a multicenter study of strain variation and antifungal susceptibility among isolates of Candida species. Diagn Microbiol Infect Dis 1998;31:289-96.
    CrossRefMedlineWeb of Science
  24. ↵
    National Committee for Clinical and Laboratory Standards (NCCLS). Reference method for broth dilution antifungal susceptibility testing of yeasts. Approved standard M27-A. Wayne, Pennsylvania: NCCLS; 1997.
  25. ↵
    1. Marco F,
    2. Lockhart SR,
    3. Pfaller MA,
    4. et al
    . Elucidating the origins of C. albicans in intensive care units of a hospital by DNA fingerprinting with the complex probe Ca3. J Clin Microbiol 1999;37:2817-28.
    Abstract/FREE Full Text
  26. ↵
    1. Miettinen OS
    . Estimability and estimation in case-referent studies. Am J Epidemiol 1976;103:226-35.
    Abstract/FREE Full Text
  27. ↵
    1. Cox DR
    . Regression models and life tables [with discussion]. J R Statist Soc B 1972;34:187-220.
  28. ↵
    1. Hosmer DW,
    2. Lemeshow S
    . Applied logistic regression. New York: John Wiley & Sons; 1989.
  29. ↵
    1. Karlowsky JA,
    2. Zhanel GG,
    3. Klym KA,
    4. Hoban DJ,
    5. Kabani AM
    . Candidemia in a Canadian tertiary care hospital from 1976 to 1996. Diagn Microbiol Infect Dis 1997;28:5-9.
    CrossRefMedlineWeb of Science
  30. ↵
    1. Wiley JM,
    2. Smith N,
    3. Leventhal BG,
    4. et al
    . Invasive fungal disease in pediatric acute leukemia with fever and neutropenia during induction chemotherapy: a multivariate analysis of risk factors. J Clin Oncol 1990;8:280-6.
    Abstract
  31. ↵
    1. Edmond MB,
    2. Wallace SE,
    3. McClish DK,
    4. Pfaller MA,
    5. Jones RN,
    6. Wenzel RP
    . Nosocomial bloodstream infections in United States hospitals: a three-year analysis. Clin Infect Dis 1999;29:239-44.
    MedlineWeb of Science
    1. Voss A,
    2. le Noble JL,
    3. Verduyn Lunel FM,
    4. Foudraine NA,
    5. Meis JFGM
    . Candidemia in intensive care unit patients: risk factors for mortality. Infection 1997;1:8-11.
  33. ↵
    1. Wey SB,
    2. Mori M,
    3. Pfaller MA,
    4. Woolson RF,
    5. Wenzel RP
    . Hospitalacquired candidemia: the attributable mortality and excess length of stay. Arch Intern Med 1988;148:2642-5.
    Abstract/FREE Full Text
    1. Fraser VJ,
    2. Jomes M,
    3. Dunkel J,
    4. Storfer S,
    5. Medof G,
    6. Dunagan WC
    . Candidemia in a tertiary care hospital: epidemiology, risk factors, and predictors of mortality. Clin Infect Dis 1992;15:414-21.
    Abstract/FREE Full Text
  35. ↵
    1. Giamarellou H,
    2. Antoniadou A
    . Epidemiology, diagnosis, and therapy of fungal infections n surgery. Infect Control Hosp Epidemiol 1996;17:558-64.
    MedlineWeb of Science
  36. ↵
    1. Eubanks PJ,
    2. de Virgilio C,
    3. Klein S,
    4. Bongard F
    . Candida sepsis in surgical patients. Am J Surg 1993;166:617-20.
    CrossRefMedlineWeb of Science
  37. ↵
    1. Savino JA,
    2. Agarwai N,
    3. Wry P,
    4. Policastro A,
    5. Cerabona T,
    6. Austria L
    . Routine prophylactic antifungal agents (clotrimazole, ketoconazole, and nystatin) in nontransplant/nonburned critically ill surgical and trauma patients. J Trauma 1994;36:20-6.
    MedlineWeb of Science
  38. ↵
    British Society for Antimicrobial Chemotherapy. Management of deep candida infection in surgical and intensive care unit patients. Intensive Care Med 1994;20:522-8.
    CrossRefMedlineWeb of Science
  39. ↵
    1. Goodman JL,
    2. Winston DJ,
    3. Greenfield RA,
    4. et al
    . A controlled trial of fluconazole to prevent fungal infections in patients undergoing bone marrow transplantation. N Engl J Med 1992;326:845-51.
    MedlineWeb of Science
  40. ↵
    1. Wingard JR,
    2. Merz WG,
    3. Rinaldi MG,
    4. Johnson TR,
    5. Karp JE,
    6. Saral R
    . Increase in Candida krusei infection among patients with bone marrow transplantation and neutropenia treated prophylactically with fluconazole. N Engl J Med 1991;325:1274-7.
    MedlineWeb of Science
  41. ↵
    1. Winston DJ,
    2. Chandrasekar PH,
    3. Lazarus HM,
    4. et al
    . Fluconazole prophylaxis of fungal infections in patients with acute leukemia. Results of a randomized placebo-controlled, double-blind, multicenter trial. Ann Intern Med 1993;118:495-503.
    Abstract/FREE Full Text
  42. ↵
    1. Rotstein C,
    2. Bow EJ,
    3. Laverdiere M,
    4. Ioannou S,
    5. Carr D,
    6. Moghaddam N
    . Randomized placebo-controlled trial of fluconazole prophylaxis for neutropenic cancer patients: benefit based on purpose and intensity of cytotoxic therapy. The Canadian Fluconazole Prophylaxis Study Group. Clin Infect Dis 1999;28:331-40.
    Abstract/FREE Full Text
  43. ↵
    1. Eggimann P,
    2. Francioli P,
    3. Bille J,
    4. et al
    . Fluconazole prophylaxis prevents intra-abdominal candidiasis in high-risk surgical patients. Crit Care Med 1999;27:1066-72.
    CrossRefMedlineWeb of Science
  44. ↵
    1. Pelz R,
    2. Lipsett PA,
    3. Swoboda S,
    4. et al
    . Proceedings and abstracts of the Annual Meeting of the Infectious Diseases Society of America (Denver). Alexandria, VA: Infectious Diseases Society of America; 1998. Do surveillance cultures predict fungal infection in critically ill patients?
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  1. Clin Infect Dis. (2001) 33 (2): 177-186. doi: 10.1086/321811
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