The clinical significance of Candida colonization of respiratory tract secretions in critically ill patients B
←
→
Page content transcription
If your browser does not render page correctly, please read the page content below
Journal of Critical Care (2008) 23, 11–17
The clinical significance of Candida colonization of
respiratory tract secretions in critically ill patientsB
Marie-Soleil Delisle a , David R. Williamson b,c , Marc M. Perreault c,d ,
Martin Albert b,c , Xuran Jiang e , Daren K. Heyland e,⁎
a
Hôpital de l'Enfant-Jésus, Québec, Québec, Canada
b
Hôpital du Sacré-Cœur de Montréal, Montréal, Québec, Canada
c
Université de Montréal, Montréal, Québec, Canada
d
Centre Universitaire de Santé McGill, Montréal, Québec, Canada
e
Queens University, Kingston, Ontario, Canada
Keywords:
Abstract
Candida;
Purpose: Clinical uncertainty exists regarding the significance of colonization confined to respiratory
colonization;
tract secretions with Candida sp in critically ill patients. Our objectives were to describe such
Candida airway
colonization, its associated risk factors, and to examine the clinical outcomes in patients with a
colonization;
clinical suspicion of ventilator-associated pneumonia with isolated Candida colonization compared to
Pneumonia;
those without.
Ventilator-associated
Materials and Methods: In a retrospective analysis of the Canadian ventilator-associated pneumonia
pneumonia;
study, patients were divided into 2 groups according to the isolated presence or absence of Candida
Critical care
in the respiratory tract enrollment culture. We compared length of mechanical ventilation, intensive
care unit and hospital stay, and mortality outcomes between groups. We used multiple logistic
regression analysis to determine factors independently associated with Candida colonization and
hospital mortality.
Results: Of the 639 eligible patients, 114 (17.8%) were colonized with Candida in the enrollment
culture. A multivariate analysis identified female sex (odds ratio [OR], 1.65; 95% confidence interval
[CI], 1.02-2.65), number of comorbidities (OR, 1.35; 95% CI, 1.08-1.71), worsening or persistent
infiltrate at randomization (OR, 1.92; 95% CI, 1.09-1.38), antibiotics started within 3 days of
randomization (OR, 3.16; 95% CI, 1.71-5.83), and on antibiotics at randomization but all started
more than 3 days before randomization (OR, 3.04; 95% CI, 1.68-5.50) as variables associated with
Candida respiratory tract colonization. A significant increase in median hospital stay (59.9 vs 38.6 days,
P = .006) and hospital mortality (34.2% vs 21.0%, P = .003) was observed in patients with Candida
colonization. In a multivariate model, Candida colonization of the respiratory tract was independently
associated with hospital mortality (OR, 2.47; 95% CI, 1.39-4.37).
Conclusion: Respiratory tract Candida colonization is associated with worse clinical outcomes and is
independently associated with increased hospital mortality. However, it is unclear whether Candida
☆
This study was supported by grants from the Canadian Institutes of Health Research and Physicians' Services Incorporated of Ontario, and by unrestricted
grants from AstraZeneca, Bayer, and Merck Frosst.
⁎ Corresponding author. Tel.: +613 549 6666x3339, fax: +1 613 548 1351.
E-mail address: dkh2@queensu.ca (D.K. Heyland).
0883-9441/$ – see front matter © 2008 Elsevier Inc. All rights reserved.
doi:10.1016/j.jcrc.2008.01.00512 M.-S. Delisle et al.
colonization is causally related to poor outcomes or whether it is a marker for increased morbidity
and mortality.
© 2008 Elsevier Inc. All rights reserved.
1. Introduction using a 2 × 2 factorial design to either bronchoscopy or
endotracheal aspirate (ETA) groups and to receive treatment
Fungal infection and colonization are becoming major with either 2 broad-spectrum antibiotics or a single broad-
clinical challenges in patients in the intensive care unit (ICU) spectrum antibiotic. Subjects were followed prospectively
[1-12]. Candida colonization from various sites has been for 28 days or until death or hospital discharge.
associated with prolonged ICU and hospital stays as well as
increased health care costs in mixed medical, surgical, and 2.2. Population
trauma populations [10]. Although some studies address
Candida colonization mainly in surgical ICU patients, few Adult patients were included in the VAP trial if they were
examine other ICU populations. Wey et al [13] identified admitted to an ICU for more than 96 hours, if they were
Candida colonization at one or multiple sites as an mechanically ventilated for more than 48 hours, and if they
independent risk factor for candidemia. Although numerous fulfilled criteria for a clinical suspicion of VAP. The criteria
risk factors for candidemia have been reported, none of these for clinical suspicion of pneumonia had to be met within
risk factors have been studied for association with an 48 hours of enrollment [22]. Immunocompromised patients,
increased risk of Candida colonization at any site [13-16]. defined as post–organ transplantation, HIV or neutropenic
Isolation of Candida sp from respiratory tract secretions is (b1000 absolute neutrophils) patients, or those receiving
frequent in mechanically ventilated, non-immunocompro- corticosteroids more than 20 mg/d of prednisone or
mised patients [9,11,17-20]. Studies assessing the signifi- equivalent for more than 6 months, were excluded, as well
cance of colonization of respiratory tract secretions as patients infected or colonized with Pseudomonas species
specifically are scarce and leave the matter unclear or methicillin-resistant Staphylococcus aureus, and those
[9,11,17-20]. The clinical relevance of isolated respiratory unlikely to be discharged from ICU within 3 weeks. The
tract secretion Candida colonization in contrast to coloniza- complete VAP study design and results have been published
tion of multiple sites has also not been established. Recently, elsewhere [22].
in a mixed medical and surgical population, Azoulay et al [21] Within 12 hours of randomization, respiratory tract cultures
found an association between Candida colonization of the (either bronchoalveolar lavage [BAL] or ETA) were obtained.
respiratory tract secretions and a prolonged period of For this analysis, we divided patients in 2 groups according to
mechanical ventilation (MV), longer ICU and hospital stay, whether Candida was present or not in the enrollment
and an increased risk for Pseudomonas VAP but no difference specimen. Because we focused on Candida colonization
in mortality. Of note, 39.7% of patients in that study had confined to respiratory tract secretions, patients with a positive
extrapulmonary Candida colonization. No studies have Candida culture at any site in the 7-day period preceding
described the risk factors and outcomes of patients with randomization and from any site other than the respiratory tract
isolated Candida colonization of respiratory tract secretions on day of randomization were excluded from this analysis.
in a North American setting. Cultures other than respiratory samples obtained at randomi-
The primary objective of this study of patients with a zation were performed according to clinicians' judgment.
clinical suspicion of a VAP was to describe the characteristics Sample procurement and laboratory processing were
of patients with isolated Candida colonization (confined to standardized. The BAL and ETA were performed in a
the respiratory tract secretions only) and to determine the risk standardized manner according to conventional techniques.
factors associated with Candida colonization. Our secondary Both ETA and BAL specimens were transported immedi-
objectives were to compare patients with and without Can- ately to the laboratory.
dida colonization in terms of duration of MV, ICU and
hospital stay; and ICU, hospital, and 28-day mortality. 2.3. Data collection
2. Materials and methods Upon enrollment in the VAP trial, demographics such as
age, sex, height, weight, primary admission diagnosis
2.1. Design category, number of comorbid diseases, APACHE (Acute
physiology and chronic health evaluation) II score, type of
We conducted a retrospective cohort study on a subset of ICU, date and time of randomization, admission to the
patients from the Canadian randomized, multicenter VAP hospital, admission to the ICU, and start of MV were
trial [22]. In this trial, ICU patients with a clinical suspicion recorded for all patients [23]. Daily monitoring was then
of a VAP from 28 participating centers were randomized performed on all patients for signs and symptoms ofSignificance of Candida colonization of respiratory tract secretions 13
infection, organ dysfunction, and other ICU-acquired MV, length of stay, and mortality are described using Kaplan-
complications [24]. During hospitalization, newly acquired Meier estimates of the median and quartiles and were
diagnoses, duration of MV, need for vasopressors, and compared between groups using the log-rank test. To identify
hemodialysis were recorded. Culture results from all sites factors independently associated with Candida colonization
and antibiotic use for the 7 days before enrollment and and increased mortality in colonized patients vs noncolonized
throughout the study period were recorded. We recorded patients, we used logistic regression including patient
secondary outcome measures of days of MV, in the ICU and characteristics with a univariate model significance level of
in the hospital, as well as occurrence of fungemia and ICU, 0.20: age, sex, APACHE II score, number of comorbidities,
in-hospital, and 28-day mortality. presence vs absence of Candida in respiratory tract secre-
tions, admission diagnosis category (sepsis, trauma, and
neurologic condition assessed independently), BAL vs ETA
2.4. Statistical analysis diagnostic method, antibiotic monotherapy vs combination
therapy, use of vasopressors during hospitalization, anti-
Baseline patient characteristics were compared between biotics started within 3 days before randomization vs no
patients with and without the presence of Candida in the antibiotic, antibiotics started prior to 3 days before randomi-
respiratory tract enrollment culture. Categorical variables are zation vs no antibiotics, multiple organ dysfuncfion score on
described as counts and percentages and were tested using the day 1, and PaO2/FiO2 ratio also on day 1. Variables identified
χ2 test. Continuous variables are described as means with from the univariate model with a significance level of 0.20 or
SDs and compared using independent t test. Mortality less were included in a multivariate analysis, in addition to
outcomes between the colonized patients vs noncolonized age, sex, APACHE II score, bronchoscopy vs ETA groups,
patients were compared using Fisher exact test. Length of and combination antibiotic therapy vs monotherapy to
Fig. 1 Patient flowchart.14 M.-S. Delisle et al.
determine relevant risk factors. All tests are two-sided, and a sample within 7 days before randomization, or had Candida-
P value of less than .05 was considered statistically positive culture from other sites within that same period or on
significant. Analyses were completed with SAS Version 9.1 day of randomization; 21 were excluded because of Candida
(SAS Institute, Cary, NC). found in their respiratory tract secretions on the day of
randomization and a positive Candida culture from other
sites within 7 days before or on the day of randomization.
3. Results We found Candida colonization confined to respiratory
tract secretions on the day of randomization in 114 (17.8%)
Of the 740 patients enrolled in the VAP study between of 639 patients (Fig. 1). The proportion of patients whose
May 2000 and February 2005, we included 639 for analysis. positive Candida cultures were isolated via the ETA or BAL
One patient withdrew consent and was not considered arms of the VAP trial were 15.6% (n = 49) and 20.0%
further. We excluded an additional 100 patients: 79 had (n = 65), respectively (P = .15).
Candida-negative respiratory tract secretions sample on Various types of Candida sp were isolated from res-
randomization day, but positive respiratory tract secretion piratory tract secretion specimens collected at randomization.
Table 1 Baseline patient characteristics
Colonized Noncolonized Total P
n = 114 n = 525 N = 639
Age 59.6 ± 16.8 58.9 ± 18.4 59.0 ± 18.1 .71
Male sex (n [%]) 71 (62.3) 377 (71.8) 448 (70.1) .04
Admission category (n [%]) .69
Medical 72 (63.2) 321 (61.1) 393 (61.5)
Surgical 42 (36.8) 204 (38.9) 246 (38.5)
Primary diagnosis system (n [%]) .007
Cardiovascular 33 (28.9) 128 (24.2) 161 (25.2) .31
Gastrointestinal 9 (7.9) 44 (8.4) 53 (8.3) .87
Neurologic 7 (6.1) 80 (15.2) 87 (13.6) .01
Renal 1 (0.9) 3 (0.6) 4 (0.6) .68
Respiratory 25 (21.9) 75 (14.3) 100 (15.6) .71
Sepsis 8 (7.0) 11 (2.1) 19 (3.0) .04
Trauma 24 (21.1) 146 (27.8) 170 (26.6) .005
Other condition 7 (6.1) 38 (7.2) 45 (7.0) .14
No. of comorbidities .04
0 24 (21.1) 174 (33.1) 198 (31.0)
1 28 (24.6) 136 (25.9) 164 (25.7)
2 28 (24.6) 95 (18.1) 123 (19.2)
3 34 (29.8) 120 (22.9) 154 (24.1)
APACHE II 20.4 ± 6.4 19.8 ± 6.2 19.9 ± 6.3 .37
PaO2/Fio2 201.1 ± 77.0 221.4 ± 84.5 217.6 ± 83.5 .02
Day 1 MODS 6.0 ± 2.7 5.5 ± 3.0 5.6 ± 2.9 .11
Days on MV 7.7 ± 4.5 7.5 ± 5.6 7.5 ± 5.4 .82
Days in ICU 8.0 ± 4.3 7.6 ± 5.6 7.6 ± 5.3 .37
CXR at enrollment (n [%]) .001
New infiltrate 20 (17.5) 172 (32.8) 192 (30.0)
Worsening or 94 (82.5) 353 (67.2) 447 (70.0)
persistent
infiltrate
On antibiotics at randomization (n [%]) b.001
Not on an any within 3 d 21 (18.4) 227 (43.2) 248 (38.8)
Yes but none started 53 (46.5) 155 (29.5) 208 (32.6)
within 3 d
New antibiotics started 40 (35.1) 143 (27.2) 183 (28.6)
within 3 d
On antifungal agents 8 (7.0) 14 (2.7) 22 (3.4) .02
On vasopressors 32 (28.1) 112 (21.3) 144 (22.5) .12
MODS indicates multiple organ dysfunction score.Significance of Candida colonization of respiratory tract secretions 15
secretion Candida colonization: female sex (odds ratio
Table 2 Mortality outcomes of patients with and without
[OR], 1.65; 95% confidence interval [CI], 1.02-2.65; P =
Candida colonization of respiratory tract secretions
.04), number of comorbidities (OR, 1.35; 95% CI, 1.08-
Colonized Noncolonized RR (95% CI) P 1.71; P = .01), worsening or persistent infiltrate at
n = 114 n = 525 (Colonized/ randomization (OR, 1.92; 95% CI, 1.09-1.38; P = .02),
noncolonized) antibiotics started within 3 days of randomization (OR,
28-d 27 (23.7) 86 (16.4) 1.45 (0.99-2.12) .08 3.16; 95% CI, 1.71-5.83; P = .02), and on antibiotics at
mortality randomization but all started more than 3 days before
ICU 24 (21.1) 73 (13.9) 1.51 (1.00-2.29) .06 randomization (OR, 3.04; 95% CI, 1.68-5.50; P = .02).
mortality Candida colonization of respiratory tract secretions was
Hospital 39 (34.2) 110 (21.0) 1.63 (1.20-2.21) .003 less common in patients admitted for neurologic reasons
mortality (OR, 0.35; 95% CI, 0.14-0.87; P = .02).
RR indicates relative risk. We present mortality data in Table 2, whereas results for
other clinical outcomes are outlined in Table 3. A
significant increase in hospital mortality (34.2% vs 21.0%
Candida albicans was accounted for in 65.3% of P = .003) was observed in the colonized group. Hospital
samples. Torulopsis glabrata was isolated in 1.3% of stay was also significantly longer (59.9 vs 38.6 days, P =
samples, whereas other non-albicans sp were found in .006) in this group. All other outcomes tended to be worse
6.7% of airway specimen. One specimen (0.7%) was iden- in the colonized group but were not significantly different
tified to have non–Candida albicans yeast species, and between groups. Candidemia subsequently developed in 1
finally, 26% of samples grew yeast not further speciated and 4 patients from the colonized and noncolonized groups,
by the local laboratory. All non–albicans sp were isolated respectively. Of note, 34 patients (29.8%) in the colonized
in colonized patients who were on antifungals at time group and 72 (13.7%) in the noncolonized group received
of randomization. antifungals at some point during the course of the VAP trial
Patients with and without isolated Candida colonization (P b .001). Fluconazole was the most commonly used
of respiratory tract secretions at randomization are agent. Mortality in colonized patients who received
compared in Table 1. Male patients were more frequently antifungals was not significantly different from patients
found in the noncolonized group (71.8% vs 62.3%, P = who did not receive such treatment (38.2% vs 32.5%, P =
.04). Patients in the colonized group were more frequently .67). In addition, no significant difference in mortality was
admitted for sepsis (7.0% vs 2.1%, P = .005) and found in patients excluded from the study because of
respiratory conditions (21.9% vs 14.3%, P = .04) but multiple sites Candida colonization compared with patients
less often for neurologic conditions (6.1% vs 15.2%, P = with respiratory tract Candida colonization only (41.9% vs
.01). A significantly lower PaO2/FiO2 ratio was observed in 34.2%, P = .33).
the colonized group (201.1 vs 221.4, P = .02). More Logistic regression showed a significant association
patients in the colonized group had worsening or persistent between Candida colonization of respiratory tract secretions
infiltrate as opposed to a new infiltrate at the time that and hospital mortality (OR, 2.38; 95% CI, 1.38-4.11). Other
VAP was suspected. They were also more frequently on factors significantly independently associated with increased
antibiotics (81.6% vs 56.7%, P b .001) and antifungal hospital mortality were older age (OR, 1.06; 95% CI, 1.04-
agents (7.0% vs 2.7%, P = .02) at randomization. Those 1.08), increased number of comorbidities (OR, 1.38; 95% CI,
with colonization had greater number of comorbid 1.11 -1.70), and admission for neurologic disorders (OR,
conditions (P = .04). Bacterial VAP was documented 2.48; 95% CI, 1.28-4.78).
through BAL or ETA culture results in 72 (63.2%) Although patients with pseudomonal colonization or
colonized patients compared to 417 (79.4%) patients in infection at randomization were excluded from the VAP
the noncolonized group (P b .001). trial, 1.8% (n = 2) of patients in the colonized group and
A multivariate analysis identified the following variables 1.3% (n = 7) of patients in the noncolonized group developed
as carrying a significantly higher risk of respiratory tract subsequent pseudomonal superinfection (P = .67).
Table 3 Clinical outcomes of patients with and without Candida colonization of respiratory tract secretions
Colonized Noncolonized P
n (%) Median (IQR) n (%) Median (IQR)
Time on ventilator (d) 91 (79.8) 10.9 (3.9, 32.7) 447 (85.1) 8.1 (3.8, 18.1) .06
ICU length of stay (d) 88 (77.2) 14.1 (6.2, 43.2] 439 (83.6) 11.6 (6.1, 25.2) .07
Hospital length of stay (d) 73 (64.0) 59.9 (24.2, –) 407 (77.5) 38.6 (21.0, 111.0) .006
IQR indicates interquartile range.16 M.-S. Delisle et al.
4. Discussion possibly numerous contributing factors. However, when
multivariate logistic regression was performed, only Can-
We conducted a retrospective analysis of data from a large dida colonization of respiratory tract secretions, number of
randomized trial of diagnostic strategies and empiric comorbidities, and admission for neurologic reasons were
antibiotics in patients with a clinical suspicion of VAP to found to be associated with increased hospital mortality.
assess whether isolated Candida colonization of respiratory A multivariate analysis suggests that patients who develop
tract secretions impacts on patient outcomes. Our main Candida colonization of respiratory tract secretions are
finding is that isolated Candida colonization of respiratory generally sicker and have recently received antibiotics than
tract secretions is associated with a longer hospital length of those who do not. Further prospective trials are required to
stay and increased hospital mortality. confirm which patient characteristics are risk factors for
Previous studies have suggested that Candida coloniza- respiratory tract secretions Candida colonization and whether
tion without Candida infection or candidemia is associated such colonization is independently associated with worse
with worse clinical outcomes in nonsurgical populations. clinical outcomes. The question also remains as to whether
Olaechea et al demonstrated that critically ill patients with isolated Candida colonization of respiratory tract secretions
Candida colonization, defined as the presence of Candida carries a different burden of illness than multiple-site Can-
sp in nonsignificant samples obtained from the urine, dida colonization. In our study, mortality between these 2
stomach, oropharynx, or tracheal aspirates, experienced a groups of patients did not differ significantly, but this would
prolonged ICU stay by 6.2 days (OR, 1.69; 95% CI, 1.53- need to be further explored in future trials, along with
1.87, P b.001) and an extended hospital stay by 8.6 days (OR, comparison of other outcomes such as length of ICU or
1.27; 95% CI, 1.16-1.40, P b .001), resulting in increased hospital stay, length of MV, or incidence of subsequent
health care costs [10]. This interesting finding left unan- pseudomonal VAP.
swered the question of whether Candida colonization at a The issue as to whether respiratory tract secretions Can-
specific site was significantly associated with worse clinical dida colonization is associated with or responsible for an
outcomes. Recently, Azoulay et al [21] have observed that increased burden of illness remains unclear. The retro-
patients with Candida airway colonization, defined as spective design of our analysis does not provide an answer.
recovery of Candida from the respiratory tract, had a However, the fact that few patients in either study group
significantly longer period of MV (13 vs 6 days, P b .0001), developed candidemia possibly indicates that it may not be a
ICU stay (17 vs 9 days, P b.0001), and hospital stay (36 vs 22 major cause of death in this population. The published
days, P b .0001) as compared to patients not colonized with literature suggests that isolation of Candida from the
Candida from the respiratory tract. However, they found no respiratory tract correlates poorly with candidiasis [18,19].
difference in ICU or hospital mortality. Our results show a This further raises the question as to whether initiating
trend for longer duration of MV and length of ICU stay, as antifungal treatment would be beneficial, which can only be
well as for increased ICU and 28-day mortality. Though not addressed with rigorous randomized trials.
significant, these results are in keeping with those obtained by An association between Pseudomonas and the presence
Azoulay et al. Furthermore, 39.7% of patients with Candida of Candida sp has been suggested previous trials [21,25]. In
airway colonization in that study had extrapulmonary our study, a comparable proportion of patients in each group
colonization, raising the issue of different findings depending developed subsequent pseudomonal pneumonia superinfec-
on patient populations. To our knowledge, no previous study tion. The fact that patients with pseudomonal colonization
has demonstrated a relationship between respiratory tract and infection were excluded from the VAP trial by design
Candida colonization and increased mortality. and the small number of patients prevents firm conclusions
Admission characteristics other than respiratory tract to be drawn on the matter.
secretion colonization by Candida also identify patients with The strengths of our study include the large number of
a worse outcome. Colonized patients were more often admitted patients enrolled, the prospective data collection in a
with pulmonary conditions, were more often on antibiotics, multicenter, randomized controlled setting, and airway
tended to have more comorbid diseases, have a lower PaO2/ specimen collection done by protocol. We collected data on
FiO2 ratio, and were more often identified as having a persistent both invasive and noninvasive techniques to obtain micro-
or worsening infiltrate. These conditions suggest that biological specimens on mechanically ventilated patients.
colonized patients were sicker upon admission to ICU, yet There are several limitations to this analysis including the
APACHE II score calculated at that time was similar between assumption that isolation of Candida from respiratory tract
groups. This is similar to findings by Azoulay et al, which culture specimens indicates colonization and not infection.
observed that patients colonized in the respiratory tract have However, this is in concordance with similar studies [10,21].
been more often admitted for acute respiratory failure, were As a normal colonizer of the gastrointestinal tract and oral
more infected at admission, yet were less often admitted for cavity, Candida spreads along the respiratory tract after
coma and less often directly admitted to ICU. These common intubation or aspiration of gastric content [12,21]. It is then
findings suggest that patients with Candida colonization of usually observed in small number in respiratory tract
respiratory tract secretions are at risk of worse outcome with quantitative cultures without clinical evidence of pneumoniaSignificance of Candida colonization of respiratory tract secretions 17
[12,21]. It was not possible in this study to examine the risk of [4] Rangel-Frausto MS, Wiblin T, Blumberg HM, Saiman L, Patterson J,
aspiration pneumonia or other respiratory conditions asso- Rinaldi M, et al. National epidemiology of mycoses survey (NEMIS):
variations in rate of bloodstream infections due to Candida sp. in
ciated with Candida colonization of the respiratory tract seven surgical intensive care units and six neonatal intensive care units.
because these were not documented in the VAP trial. Candidal Clin Infect Dis 1999;29:253-8.
invasion of the lung parenchyma after hematogenous [5] Wey SB, Mori M, Pfaller MA, Woolson RF, Wenzel RP. Hospital-
dissemination would be frequently associated with real acquired candidemia: the attributable mortality and excess length of
stay. Arch Intern Med 1988;148:2642-5.
clinical pneumonia but unlikely to have happened in the
[6] Wenzel RP. Nosocomial candidemia: risk factors and attributable
course of our trial as only 5 patients developed documented mortality. Clin Infect Dis 1995;20:1531-4.
candidemia [12,18,19,21]. Clinical suspicion of VAP was [7] Rentz AM, Halpern MT, Bowden R. The impact of candidemia on
generally attributed to bacterial causative agents. We did not length of hospital stay, outcome and overall cost of illness. Clin Infect
routinely perform surveillance cultures of all other sites to be Dis 1998;27:781-8.
sure that patients were truly only colonized in the respiratory [8] Charles PE, Doise JM, Quenot JP, Aube H, Dalle F, Chavanet P, et al.
Candidemia in critically ill patients : difference of outcome between
tract. This study was done in the context of a clinical medical and surgical patients. Intern Care Med 2003;29:2162-9.
suspicion of VAP and does not generalize to patients without [9] Pittet D, Monod MM, Suter PM, Frenk E, Auckenthaler R. Candida
such a suspicion. Moreover, a proportion of patients in each colonization and subsequent infections in critically ill surgical patients.
group received antifungal treatment. The decision to initiate Ann Surg 1994;220(6):751-8.
or stop treatment was at clinicians' discretion and could be [10] Olaechea PM, Palomar M, Léon-Gil C, Álvarez-Lerma F, Jordá R,
Nolla-Salas J, et al. Economic impact of Candida colonization and
done at any time during the 28-day study period. Therefore, Candida infection in the critically ill patient. Eur J Clin Microbiol
the impact of antifungal treatment on patient outcomes and on Infect Dis 2004;23:323-30.
our results could not be adequately measured within this [11] Charles PE, Dalle F, Aube H, Doise JM, Quenot JP, Aho LS. Candida
study, or controlled for as a confounding variable. spp. colonization significance in critically ill medical patients: a
prospective study. Intensive Care Med 2005;31:393-400.
[12] Azoulay E, Cohen Y, Zahar JR, Garrouste-Orgeas M, Adrie C, Moine
5. Conclusion P, et al. Practices in non neutropenic ICU patients with Candida-
positive airway specimens. Intensive Care Med 2004;30:1384-9.
Our study demonstrates an association between isolated [13] Wey SB, Mori M, Pfaller MA, Woolson RF, Wenzel RP. Risk factors
for hospital-acquired candidemia. A matched case-control study. Arch
Candida colonization of respiratory tract secretions and
Intern Med 1989;149:2349-53.
increased hospital mortality and hospital length of stay. [14] Fraser VJ, Jones M, Dunkel J, Storfer S, Medoff G, Dunagan WC.
Whether Candida colonization of respiratory tract secretions Candidemia in a tertiary care hospital: epidemiology, risk factors and
is a marker of disease severity or contributes directly to predictors of mortality. Clin Infect Dis 1992;15:414-21.
mortality and prolonged hospital stay requires further [15] Jarvis WR. Epidemiology of nosocomial fungal infections, with
emphasis on Candida species. Clin Infect Dis 1995;20:1526-30.
evaluation. One way to address this question is to conduct
[16] Bross J, Talbot GH, Maislin G, Hurwitz S, Strom BL. Risk factors
a prospective randomized trial of pharmacologic strategies to for nosocomial candidemia: a case-control study in adults without
eliminate or reduce the colonization of Candida and evaluate leukemia. Am J Med 1989;87:614-20.
the effect of such an intervention on clinically important [17] Eggiman P, Pittet D. Candidoses du sujet non neutropénique: de la
outcomes in critically ill mechanically ventilated patients colonisation à l'infection. Ann Fr Anesth Réanim 2001;20:382-8.
[18] El-Ebiary M, Torres A, Fàbregas N, Puig de la Bellacasa J, González J,
with or without a clinical suspicion of pneumonia.
Ramirez J, et al. Significance of the isolation of Candida species from
respiratory samples in critically ill, non neutropenic patients. Am J
Acknowledgments Respir Crit Care Med 1997;156:583-90.
[19] Rello J, Esandi ME, Díaz E, Mariscal D, Gallego M, Vallès J. The role
of Candida sp isolates from bronchoscopic samples in nonneutropenic
We thank the ICU nurses and physicians in participating
patients. Chest 1998;114:146-9.
centers, and research coordinators of the Canadian Critical [20] Wood C, Mueller EW, Croce MA, et al. Candida sp. isolated from
Care Trials Group listed in the appendix of the original bronchoalveolar lavage: clinical significance in critically ill trauma
article [22]. patients. Intensive Care Med 2006;32(4):599-603.
[21] Azoulay E, Timsit JF, Tafflet M, de Lassence A, Darmon M, Zahar JR, et
al. Candida colonization of the respiratory tract and subsequent Pseu-
References domonas ventilator-associated pneumonia. Chest 2006;129:110-7.
[22] Heyland D, Dodek P, Muscedere J, Day A. A randomized trial of
[1] Banerjee SN, Emori TG, Culver DH, Gaynes RP, Jarvis WR, Horan T, diagnostic techniques for ventilator-associated pneumonia. N Engl J
et al. Secular trends in nosocomial primary bloodstream infections in Med 2006;355:2619-30.
the United States, 1980-1989. Am J Med 1991;91:86S-9S. [23] Knaus WA, Draper EA, Wagner DP, Zimmerman JE. APACHE II: a
[2] Beck-Sagué CM, Jarvis W. Secular trends in the epidemiology of severity of disease classification system. Crit Care Med 1985;13:
nosocomial fungal infections in the United States, 1980-1990. National 818-29.
Nosocomial Infections Surveillance System. J Infect Dis 1993;167: [24] Marshall JC, Cook DJ, Christou NV, Bernard GR, Sprung CL,
1247-51. Sibbald WJ. Multiple organ dysfunction score: a reliable descriptor
[3] Vincent JL, Bihari DJ, Suter PM, et al. The prevalence of nosocomial of a complex clinical outcome. Crit Care Med 1995;23:1638-52.
infection in intensive care units in Europe: results of the European [25] Nseir S, Jozefowicz E, Cavestri B, et al. Impact of antifungal treatment
Prevalence of Infection in Intensive Care (EPIC) Study; EPIC on Candida-Pseudomonas interaction: a preliminary retrospective
International Advisory Committee. JAMA 1995;274:639-44. case-control study. Intensive Care Med 2007;33(1):137-42.You can also read
