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Original Research: Critical Care |

The Occurrence and Impact of Bacterial Organisms Complicating Critical Care Illness Associated With 2009 Influenza A(H1N1) InfectionSuperinfection in the Critically Ill with H1N1 FREE TO VIEW

John Muscedere, MD; Marianna Ofner, PhD; Anand Kumar, MD; Jennifer Long, MSc; Francois Lamontagne, MD; Deborah Cook, MD; Allison McGeer, MD; Clarence Chant, PharmD; John Marshall, MD; Philippe Jouvet, MD, PhD; Robert Fowler; for the ICU-FLU Group* and the Canadian Critical Care Trials Group
Author and Funding Information

From the Department of Medicine (Dr Muscedere), Queen’s University, Kingston, ON; the Public Health Agency of Canada (Dr Ofner), Ottawa, ON and Winnipeg, MB; the Winnipeg Health Sciences Centre and St. Boniface Hospital (Dr Kumar), University of Manitoba, Winnipeg, MB; the Sunnybrook Health Sciences Center (Ms Long and Dr Fowler), University of Toronto, Toronto, ON; the Clinical Research Centre Étienne Le Bel and Department of Medicine (Dr Lamontagne), Université de Sherbrooke, Sherbrooke, QC; the Faculty of Health Sciences (Dr Cook), McMaster University, Hamilton, ON; Mt. Sinai Hospital (Dr McGeer), University of Toronto, Toronto, ON; St. Michael’s Hospital (Drs Chant and Marshall), Toronto, ON; and the Sainte-Justine Research Center (Dr Jouvet), Université de Montréal, QC, Canada.

Correspondence to: John Muscedere, MD, Room 5-411, Angada 4, Kingston General Hospital, 76 Stuart St, Kingston, ON, K7M 9H3, Canada; e-mail: muscedej@kgh.kari.net

*

A complete list of study participants is located in e-Appendix 1.


Funding/Support: The authors have reported to CHEST that no funding was received for this study.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2013;144(1):39-47. doi:10.1378/chest.12-1861
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Background:  Although secondary infections are recognized as a cause of morbidity and mortality in seasonal influenza, their frequency, characteristics, and associated clinical outcomes in 2009 influenza A(H1N1) (A[H1N1])-related critical illness are unknown.

Methods:  In a prospective cohort of adult patients admitted to Canadian ICUs with influenza A(H1N1) infection, the frequency and associated clinical outcomes of prevalent (culture taken within 72 h of ICU admission) and ICU-acquired (culture taken after 72 h from ICU admission) positive bacterial cultures were determined.

Results:  Among 681 patients, the mean age was 47.9 years (SD, 15.1), APACHE (Acute Physiology and Chronic Health Examination) II score was 21.0 (9.9), and 573 patients (84.0%) were invasively mechanically ventilated. Positive cultures were obtained in 259 patients (38.0%): 77 (29.7%) had prevalent, 115 (44.4%) had ICU-acquired, and 40 (15.4%) had both; culture date was unavailable in 27 (10.4%). The most common bacterial organisms isolated were coagulase-negative staphylococci, Staphylococcus aureus, Pseudomonas species, and Streptococcus pneumoniae. Antibiotics were prescribed in 661 (97.1%), with 3.8 (1.9) prescriptions per patient. Patients with any positive culture had longer days of mechanical ventilation (mean [SD], 15.2 [10.7] vs 10.7 [9.0]; P < .0001), ICU stay (median [interquartile range (IQR)], 18.2 [12.5] days vs 10.8 [9.0] days, P < .0001), and hospitalization (median [IQR], 30.7 [20.7] days vs 19.2 [17.4] days, P < .0001) and a trend toward increased hospital mortality (25.1% vs 19.9%, P = .15). Patients with ICU-acquired positive cultures had worse outcomes compared with those with positive prevalent cultures or who were culture-negative.

Conclusion:  Culture-based evidence of secondary infections commonly complicates A(H1N1)-related critical illness and is associated with worse clinical outcomes despite nearly ubiquitous antibiotic administration.

Figures in this Article

The strain of influenza A virus, 2009 A(H1N1) (A[H1N1]), has been documented to cause respiratory failure in a substantial percentage of those infected and believed to be at lower risk of severe influenza-related illness.1 Patients who develop respiratory failure from A(H1N1) may require prolonged mechanical ventilation (MV) and have a propensity to develop multisystem organ failure; death occurs in approximately 20%.24

In non-A(H1N1) influenza outbreaks, much of the associated morbidity and mortality has been ascribed to secondary bacterial infections.5,6 Postulated reasons for increased susceptibility to coinfections are viral damage to respiratory epithelium allowing bacterial binding to bronchial surfaces; apoptosis of macrophages and neutrophils, both of which are vital for bacterial clearance; and Toll-like receptor desensitization.7,8 Influenza strains are not uniform in their ability to promote susceptibility to or increase morbidity or mortality from secondary infections, and A(H1N1), in an animal model of secondary infection with Streptococcus pneumonia, was associated with increased mortality as compared with seasonal influenza.9 However, unlike seasonal influenza, there is limited clinical information on coinfections for A(H1N1). In an autopsy study of patients dying after infection with A(H1N1), secondary bacterial respiratory infections were found in 29%, the most common pathogens being Streptococcus pneumoniae, Staphylococcus aureus, and Streptococcus pyogenes.10 Two studies have reported on the acquisition of community-acquired bacterial coinfection in critically ill patients with A(H1N1). Rice et al11 found that 30% of patients had bacterial coinfections within 72 h of admission, with S aureus being the most common pathogen, and the majority of these were methicillin resistant. In contrast, Martin-Loeches et al12 reported the presence of coinfection in 17.5% of patients, with S pneumoniae being the most prevalent bacterial pathogen. In both of these studies, nosocomial bacterial infections were not described. Secondary infections may be particularly important in critically ill patients with A(H1N1), and important gaps in our knowledge remain. First, the incidence of coinfection and spectrum of pathogens in those who are critically ill needs to be further described. Second, the incidence of infections acquired in the ICU and their impact on outcomes in patients with A(H1N1) remains unknown. This may be particularly important, since critically ill patients are vulnerable to nosocomial infections, and influenza may increase susceptibility to coinfection.13,14

Because of the lack of reference standards, the separation of infection from colonization in critically ill patients is difficult and may not be indicative of pathology present15,16; further pathogens believed to be colonizers may be associated with adverse outcomes.1719 For these reasons, it is appropriate to base descriptions of the impact and incidence of coinfections in the critically ill on all positive cultures. Accordingly, we sought to determine the prevalence, incidence, treatment, and outcome of patients with coexistent or secondarily acquired bacterial respiratory tract or bloodstream-positive cultures among a large cohort of critically ill patients with confirmed or probable A(H1N1).

This was a multicenter observational study (ICU-FLU study) of adult (age > 18 years) critically ill patients with confirmed or probable infection with A(H1N1) admitted to Canadian ICUs between April 2009 and April 2010 (e-Appendix 1). Case definitions for confirmed or probable A(H1N1) infection were those of the World Health Organization and the Canadian National Microbiology Laboratory.20 Data were collected retrospectively or prospectively, initially using a paper-based case report form (CRF) from April 2009 to August 2009 (wave 1).21 In October 2009, an updated electronic CRF was implemented nationally (wave 2), and the paper-based CRF was phased out.21 Data collection details have been previously described.2 Critically ill patients were defined as those admitted to an adult or pediatric ICU requiring: MV (invasive or noninvasive), an Fio2 ≥ 60%, or IV infusion of inotropic or vasopressor medications.2 The ICU-FLU database includes demographics such as age, sex, ethnicity, comorbidities, copresenting illnesses, pregnancy status, presentation symptoms, symptom onset dates, hospital and ICU admission and discharge, ventilation initiation and liberation, death or discharge from hospital, severity of illness at presentation (APACHE [Acute Physiology and Chronic Health Examination] II22), daily Sequential Organ Failure Assessment (SOFA) score,23 therapies administered, and microbiologic cultures.

For this report, the primary outcome measure was the frequency of bacterial organisms cultured from blood or the respiratory tract in patients with A(H1N1)-related critical illness, described as prevalent (culture taken within 72 h of ICU admission) and ICU acquired (culture taken ≥ 72 h after ICU admission). For respiratory cultures, if the patient was intubated, both endotracheal aspirates and bronchoscopically obtained specimens were included; for nonintubated patients, sputum cultures were included. Fungal organisms were excluded from the analysis. Secondary outcomes included frequency of organisms, antibiotics administered, duration of MV, days free of MV at 28 days, and mortality (ICU and hospital). If appropriate, organisms were then further classified into those with high risk for resistance (high-risk organisms [HROs]24)—Pseudomonas species, methicillin-resistant S aureus, Stenotrophomonas maltophilia, Acinetobacter species; and SPICE organisms25Serratia species, Pseudomonas species, indole-positive Proteeae (Proteus vulgaris, Morganella morganii, Providencia species), Citrobacter species, Enterobacter species.

Data on antibiotic usage were abstracted. In wave 1, antibiotic data were limited to antibiotic use (ie, “yes” or “no”) and start and stop dates; therefore, detailed antibiotic use data are reflective only of wave 2 patients. Antibiotic usage was described using the following parameters: number of antibiotics per day, antibiotic-free days (alive and off antibiotics) in the first 28 days after ICU admission, total number of prescriptions of individual drugs, and duration and number of antibiotic classes per patient.

Data were checked for errors by manual inspection and electronic range limits. Research ethics board (REB) approval was granted by Sunnybrook Health Sciences REB (#130-2009) at the central coordinating center on April 30, 2009, and by each local REB.

Statistical Analyses

Descriptive statistics included frequency analysis (percentages) for categorical variables and means (SD) for normally distributed continuous variables, or medians (interquartile range [IQR]) for skewed data. To test for differences, we used two-sample t tests for continuous variables and χ2 test for discrete variables. The Kaplan-Meier method was used to depict the probability of survival and to generate survival curves. A logistic regression model was used to investigate the relationship between explanatory variables and hospital mortality. Linear regression was used to study the explanatory measures of interest in relation to length of stay in the ICU, length of stay in the hospital, and 28-day MV-free days.26 Associations between each explanatory variable were studied by way of a multicollinearity matrix (Pearson r and Spearman r for nonparametric data) to ensure none were correlated > 0.8. Each explanatory factor was singly entered into the logistic model, and factors found to be significant were set aside and ranked by comparing the change in deviance associated with the inclusion of the factor with critical values for a χ2 distribution based on the appropriate degrees of freedom (P ≤ .05). The variables identified as significant were entered into a multivariate model, using a method analogous to forward selection in multiple linear regression. A method similar to backward selection was then used to confirm the results. Age and sex were forced into the multivariable models. Regression analyses were based on all patients with complete information on the variables in the model. Interaction effects were not tested. Total sample size is provided where data are missing. Extreme outliers were censored. Reported P values reflect a two-tailed α level of .05. Statistical analyses were conducted using SAS, version 9.2 (SAS Institute Inc).

From 50 ICUs across Canada from April 2009 to April 2010, 754 patients with confirmed or probable A(H1N1) were enrolled: 254 patients from wave 1 and 500 from wave 2. Of these, 62 patients were ≤ 18 years of age; age was not available for one patient. For those > 18 years, outcome data were not available in 10 patients, and analysis was restricted to the remaining 681 adults (Fig 1). Baseline patient characteristics are listed in Table 1. Overall, patients were young, of moderate illness severity, and primarily presented with respiratory symptoms; 84.7% received invasive MV on ICU admission.

Figure Jump LinkFigure 1. Patient flowchart. A(H1N1) = 2009 influenza A(H1N1).Grahic Jump Location
Table Graphic Jump Location
Table 1 —Baseline Patient Characteristics

Data are presented as No. (%) unless otherwise noted. A(H1N1) = 2009 influenza A(H1N1); APACHE = Acute Physiology and Chronic Health Evaluation; IQR = interquartile range.

a 

Total sample size is 681. Where data are unavailable, sample size for data is provided.

b 

Major comorbidities as defined by the National Advisory Committee on Immunization.

Of the study cohort, 259 patients (38.0%) had positive blood or respiratory cultures during their ICU stay; 77 (29.7%) were prevalent, 115 (44.4%) were ICU acquired, 40 (15.4%) had both, and culture date was unavailable in 27 (10.4%) (Table 2). In the 40 patients with both prevalent and ICU-acquired positive cultures, the same organism(s) was identified in both in 23 (57.5%). Nearly all received treatment with antibiotics (97.1%); median was 4.0 (IQR, 3.0-7.0) antibiotic prescriptions per patient and 3.8 (SD, 1.9) distinct antibiotics during their ICU stay (Table 2). Patients received antibiotics for the majority of their of ICU stay, with only 4.2 (SD, 5.4) antibiotic-free days by day 28.

Table Graphic Jump Location
Table 2 —Characteristics of Positive Bacterial Cultures and Antibiotic Use

Data are presented as No. (%) unless otherwise noted. Antibiotic use for wave 1 was collected only as a yes/no variable. In wave 2, detailed antibiotic use was collected. See Table 1 legend for expansion of abbreviations.

a 

Total sample size is 681. Where data are unavailable, sample size for data is provided.

b 

Inclusive of all days up to 28 d, not solely days with antibiotic use.

In the 538 positive cultures, the most common bacterial organisms overall were coagulase-negative staphylococci (17.7%), S aureus (15.2%), Pseudomonas species (13.9%), and S pneumoniae (8.6%) (Table 3). Coagulase-negative Staphylococcus followed by Pseudomonas were the most common bacteria isolated in ICU-acquired positive cultures, whereas S aureus and S pneumoniae were the most commonly isolated bacteria from prevalent cultures, accounting for > 50% of the bacterial species isolated. Identification of HRO and SPICE organisms only occurred in 24.0% and 18.2% of all cultures, respectively. In 136 patients (20.0%), blood cultures were positive, with a total of 192 organisms; 158 cultures (81.8%) were gram-positive, and the majority were ICU acquired (e-Table 1). The most common blood isolates were coagulase-negative staphylococci (41.4%), undifferentiated staphylococci (10.5%), S pneumoniae (9.1%), enterococci (6.8%), and S aureus (5.2%). In 169 patients (24.8%) with 346 positive respiratory tract cultures, the majority were ICU acquired, with S aureus, S pneumoniae, and methicillin-resistant S aureus accounting for 20.4% (e-Table 2). S aureus was the most common bacterial organism in prevalent cultures (22.8%) and Pseudomonas among ICU-acquired cultures (16.8%).

Table Graphic Jump Location
Table 3 —Frequency of Organisms Isolated According to Date of Acquisition

Data are presented as No. (%). MRSA = methicillin-resistant Staphylococcus aureus; SPICE = Serratia species, Pseudomonas species, indole-positive Proteeae (Proteus vulgaris, Morganella morganii, Providencia species), Citrobacter species, Enterobacter species. See Table 1 legend for expansion of other abbreviations.

a 

Source of positive culture is missing for 27 patients and 41 cultures.

b 

Species of Staphylococcus not further differentiated.

On comparison, patients with and without positive cultures had similar baseline characteristics, including underlying comorbidities and duration of symptoms before ICU admission (Table 4). However, APACHE II score was higher in patients who had positive cultures (mean [SD], 23.0 [9.6] vs 19.7 [9.9]; P < .0001) as was maximum SOFA score (mean [SD], 10.3 [6.3] vs 8.2 [6.4]; P < .0001). Patients with positive cultures had increased morbidity as demonstrated by increased duration of MV, ICU stay, hospital stay, and a trend toward increased hospital mortality (24.7% vs 19.9%, P = .15) but similar ICU mortality. Kaplan-Meier survival curves for 90 days postenrollment (Fig 2) were not statistically different (P = .20).

Table Graphic Jump Location
Table 4 —Characteristics, Treatments, and Outcomes of Critically Ill Patients With Positive Cultures Compared With Those Without

Total sample may vary depending on data available. If data unavailable, sample size for each variable is included in each cell. LOS = length of stay; SOFA = Sequential Organ Failure Assessment. See Table 1 legend for expansion of other abbreviations.

a 

P value is for comparison between the No Positive Culture and Positive Culture Groups.

b 

Major comorbidities as defined by National Advisory Committee on Immunization.

Figure Jump LinkFigure 2. Ninety-day Kaplan-Meier survival curve comparing patients without positive cultures to those with positive cultures.Grahic Jump Location

When characterized as culture-negative, prevalent, or ICU-acquired positive cultures, patients had similar baseline characteristics, with the exception of BMI and baseline severity of illness (Table 5, e-Table 3). BMI was higher in those with ICU-acquired cultures. Patients who had ICU-acquired positive cultures, compared with those who were culture-negative or had prevalent positive cultures, had greater morbidity as demonstrated by increased duration of MV, ICU stay, and hospital stay. Hospital mortality was similar between those with positive prevalent, ICU-acquired cultures and those without any positive cultures (26.0% vs 26.1% vs 19.9%, P = .25). In logistic regression analysis (e-Table 4), after adjustment, only APACHE II was independently associated with hospital mortality.

Table Graphic Jump Location
Table 5 —Characteristics, Treatments, and Outcomes of Critically Ill Patients With Only Prevalent or ICU-Acquired Positive Cultures Compared With No Positive Cultures

Patients with both prevalent and incident positive cultures were excluded from this analysis (n = 40), and date of culture was unavailable for 27 patients. Total sample may vary depending on data available. Where data were unavailable, sample size is included in each cell. See Table 1 and 4 legends for expansion of abbreviations.

a 

P value is for comparison between the three groups.

b 

Major comorbidities as defined by National Advisory Committee on Immunization.

Coincident positive respiratory and bloodstream cultures were common in patients with A(H1N1)-related critical illness, occurring in approximately 40% during the course of their critical illness. The majority of positive cultures were ICU acquired and were associated with increased morbidity, including prolonged MV, ICU stay, and hospital stay. Although less than one-half of patients had positive bacterial cultures, almost all were treated with antibiotics, commonly many and for prolonged periods. However, the isolation of HROs and SPICE organisms was relatively uncommon in this fairly young group of patients with relatively few comorbid conditions.

Our findings are important for several reasons. First, we studied a severely ill cohort of patients infected with A(H1N1), all of whom required ICU admission, and > 80% required MV. Less than one-quarter had prevalent positive bacterial cultures, suggesting that in the majority the severity of illness and respiratory dysfunction was likely due to influenza rather than secondary infections. This is similar to the report by the National Heart, Lung and Blood Institute ARDSnet group.11 Second, our study highlights the uncertainty about bacterial coinfections in patients with A(H1N1)-related critical illness. Perhaps related to the fear of undertreatment in this seriously ill group of patients, they were treated with multiple and prolonged courses of antibiotics. Third, our study demonstrates an association between positive cultures overall and increased morbidity. The majority of these were acquired in the ICU, and as a group they were also associated with increased morbidity. Although it is unclear if the bacterial infections observed were an intrinsic feature of A(H1N1) or were secondary to ICU admission, as occurs in other critically ill patients,27 these patients should receive aggressive measures to prevent ICU-acquired infections.28,29

In addition, our study highlights that critically ill patients with A(H1N1) experience substantial morbidity and mortality irrespective of coinfection; patients without any positive cultures experience substantial morbidity and mortality, suggesting that secondary infections are not the dominant cause of morbidity/mortality as postulated for previous pandemics. This is in contrast to the view of influenza as a mild disease that is associated with death in patients without substantial comorbidities only when bacterial coinfections occur.

Our study has a number of strengths. First, the ICU-FLU study represents a large national database of A(H1N1)-related critical illness that contains detailed patient-level information, including data on non-influenza infections. Data were collected by trained research coordinators and extensively validated at sites and the coordinating center. Our dataset contains the majority of all episodes of A(H1N1)-related critical illness in Canada, and it is unlikely that our findings are subject to selection bias. This series captured approximately two-thirds of all patients known by the Public Health Agency of Canada to have A(H1N1)-related critical illness during waves 1 and 2; the baseline characteristics and outcomes of our patient population are similar to the whole population of A(H1N1) critically ill.30 We obtained information from every region in Canada, including academic and community centers, enhancing the generalizability of our findings within Canada and to other similar jurisdictions.

Our study also has potential limitations. Data on specific individual antibiotics used in wave 1 were not collected, and antibiotic results are predominantly reflective of wave 2. Second, conducting research in a pandemic, with increased clinical workload and potentially fewer resources, is challenging and may lead to incomplete data. Third, distinguishing infection from colonization in the ICU is very challenging. This is particularly problematic for coagulase-negative staphylococci, which represented the majority of isolates from blood cultures. For this reason, we have chosen to rely on culture results and did not use case-based infection adjudication. Although we were able to document the apparent impact of positive cultures on outcomes, it is possible that our results overestimate the occurrence of infections. However, because of imperfect sensitivity of respiratory and bloodstream sampling, and concomitant use of broad-spectrum antibiotics, it is more likely that our findings represent a conservative estimation of infection rates. Finally, as with any observational study, the associations found cannot imply causation and may be influenced by unmeasured or unrecognized confounding variables.

In this multicenter national study, we found that among patients with A(H1N1)-related critical illness, secondary respiratory and bloodstream organisms were common, and the majority were ICU acquired. Antibiotics were extensively prescribed in spite of the lack of positive cultures in the majority of patients. Further research is required to be able to identify which patients have ongoing bacterial infections and when antibiotics can be safely discontinued. Positive blood and respiratory cultures were associated with increased morbidity, and the prevention of secondary infection in patients with influenza-related critical illness should be an important focus.

Author contributions: Drs Muscedere and Fowler led the development and completion of this manuscript and take responsibility for the integrity of the work.

Dr Muscedere: contributed to developing the analytic plan for study data, provided input on the study, provided input and editing on the manuscript, and approved the final version of the manuscript.

Dr Ofner: contributed to developing the analytic plan for study data, provided input on the study, provided input and editing on the manuscript, and approved the final version of the manuscript.

Dr Kumar: contributed to developing the analytic plan for study data, provided input on the study, provided input and editing on the manuscript, and approved the final version of the manuscript.

Ms Long: contributed to developing the analytic plan for study data, provided input on the study, conducted statistical analyses, provided input and editing on the manuscript, and approved the final version of the manuscript.

Dr Lamontagne: contributed to developing the analytic plan for study data, provided input on the study, provided input and editing on the manuscript, and approved the final version of the manuscript.

Dr Cook: contributed to developing the analytic plan for study data, provided input on the study, provided input and editing on the manuscript, and approved the final version of the manuscript.

Dr McGeer: contributed to developing the analytic plan for study data, provided input on the study, provided input and editing on the manuscript, and approved the final version of the manuscript.

Dr Chant: contributed to developing the analytic plan for study data, provided input on the study, provided input and editing on the manuscript, and approved the final version of the manuscript.

Dr Marshall: contributed to developing the analytic plan for study data, provided input on the study, provided input and editing on the manuscript, and approved the final version of the manuscript.

Dr Jouvet: contributed to developing the analytic plan for study data, provided input on the study, provided input and editing on the manuscript, and approved the final version of the manuscript.

Dr Fowler: contributed to developing the analytic plan for study data, provided input on the study, provided input and editing on the manuscript, and approved the final version of the manuscript.

Financial/nonfinancial disclosures: The authors have reported to CHEST the following conflicts of interest: Dr Ofner is employed by the Public Health Agency of Canada. Dr Kumar has received unrestricted research grants from Roche, Pfizer Inc, and Astellas Pharma US Inc. Dr Chant has participated in selected paid advisory groups. None of the groups have been with products that are mentioned in this manuscript or directly related. Drs Muscedere, Lamontagne, Cook, McGeer, Marshall, Jouvet, and Fowler, and Ms Long have reported that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Other contributions: We thank The Public Health Agency of Canada, the Ontario Ministry of Health and Long Term Care, the Heart and Stroke Foundation of Canada, and the Canadian Institutes of Health Research for providing support for the original study.

Additional information: The e-Appendix and e-Tables can be found in the “Supplemental Materials” area of the online article.

A(H1N1)

2009 influenza A(H1N1)

APACHE

Acute Physiology and Chronic Health Examination

CRF

Case Report Form

HRO

high-risk organism

IQR

interquartile range

MV

mechanical ventilation

REB

research ethics board

SOFA

Sequential Organ Failure Assessment

SPICE

Serratia species, Pseudomonas species, indole-positive Proteeae (Proteus vulgaris, Morganella morganii, Providencia species), Citrobacter species, Enterobacter species

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Schoenfeld DA, Bernard GR; ARDS Network. Statistical evaluation of ventilator-free days as an efficacy measure in clinical trials of treatments for acute respiratory distress syndrome. Crit Care Med. 2002;30(8):1772-1777. [CrossRef] [PubMed]
 
Vincent JL, Rello J, Marshall J, et al; EPIC II Group of Investigators. International study of the prevalence and outcomes of infection in intensive care units. JAMA. 2009;302(21):2323-2329. [CrossRef] [PubMed]
 
Muscedere J, Dodek P, Keenan S, Fowler R, Cook D, Heyland D; VAP Guidelines Committee and the Canadian Critical Care Trials Group. Comprehensive evidence-based clinical practice guidelines for ventilator-associated pneumonia: prevention. J Crit Care. 2008;23(1):126-137. [CrossRef] [PubMed]
 
Frasca D, Dahyot-Fizelier C, Mimoz O. Prevention of central venous catheter-related infection in the intensive care unit. Crit Care. 2010;14(2):212. [CrossRef] [PubMed]
 
Helferty M, Vachon J, Tarasuk J, Rodin R, Spika J, Pelletier L. Incidence of hospital admissions and severe outcomes during the first and second waves of pandemic (H1N1) 2009. CMAJ. 2010;182(18):1981-1987. [PubMed]
 

Figures

Figure Jump LinkFigure 1. Patient flowchart. A(H1N1) = 2009 influenza A(H1N1).Grahic Jump Location
Figure Jump LinkFigure 2. Ninety-day Kaplan-Meier survival curve comparing patients without positive cultures to those with positive cultures.Grahic Jump Location

Tables

Table Graphic Jump Location
Table 1 —Baseline Patient Characteristics

Data are presented as No. (%) unless otherwise noted. A(H1N1) = 2009 influenza A(H1N1); APACHE = Acute Physiology and Chronic Health Evaluation; IQR = interquartile range.

a 

Total sample size is 681. Where data are unavailable, sample size for data is provided.

b 

Major comorbidities as defined by the National Advisory Committee on Immunization.

Table Graphic Jump Location
Table 2 —Characteristics of Positive Bacterial Cultures and Antibiotic Use

Data are presented as No. (%) unless otherwise noted. Antibiotic use for wave 1 was collected only as a yes/no variable. In wave 2, detailed antibiotic use was collected. See Table 1 legend for expansion of abbreviations.

a 

Total sample size is 681. Where data are unavailable, sample size for data is provided.

b 

Inclusive of all days up to 28 d, not solely days with antibiotic use.

Table Graphic Jump Location
Table 3 —Frequency of Organisms Isolated According to Date of Acquisition

Data are presented as No. (%). MRSA = methicillin-resistant Staphylococcus aureus; SPICE = Serratia species, Pseudomonas species, indole-positive Proteeae (Proteus vulgaris, Morganella morganii, Providencia species), Citrobacter species, Enterobacter species. See Table 1 legend for expansion of other abbreviations.

a 

Source of positive culture is missing for 27 patients and 41 cultures.

b 

Species of Staphylococcus not further differentiated.

Table Graphic Jump Location
Table 4 —Characteristics, Treatments, and Outcomes of Critically Ill Patients With Positive Cultures Compared With Those Without

Total sample may vary depending on data available. If data unavailable, sample size for each variable is included in each cell. LOS = length of stay; SOFA = Sequential Organ Failure Assessment. See Table 1 legend for expansion of other abbreviations.

a 

P value is for comparison between the No Positive Culture and Positive Culture Groups.

b 

Major comorbidities as defined by National Advisory Committee on Immunization.

Table Graphic Jump Location
Table 5 —Characteristics, Treatments, and Outcomes of Critically Ill Patients With Only Prevalent or ICU-Acquired Positive Cultures Compared With No Positive Cultures

Patients with both prevalent and incident positive cultures were excluded from this analysis (n = 40), and date of culture was unavailable for 27 patients. Total sample may vary depending on data available. Where data were unavailable, sample size is included in each cell. See Table 1 and 4 legends for expansion of abbreviations.

a 

P value is for comparison between the three groups.

b 

Major comorbidities as defined by National Advisory Committee on Immunization.

References

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Vincent JL, Rello J, Marshall J, et al; EPIC II Group of Investigators. International study of the prevalence and outcomes of infection in intensive care units. JAMA. 2009;302(21):2323-2329. [CrossRef] [PubMed]
 
Muscedere J, Dodek P, Keenan S, Fowler R, Cook D, Heyland D; VAP Guidelines Committee and the Canadian Critical Care Trials Group. Comprehensive evidence-based clinical practice guidelines for ventilator-associated pneumonia: prevention. J Crit Care. 2008;23(1):126-137. [CrossRef] [PubMed]
 
Frasca D, Dahyot-Fizelier C, Mimoz O. Prevention of central venous catheter-related infection in the intensive care unit. Crit Care. 2010;14(2):212. [CrossRef] [PubMed]
 
Helferty M, Vachon J, Tarasuk J, Rodin R, Spika J, Pelletier L. Incidence of hospital admissions and severe outcomes during the first and second waves of pandemic (H1N1) 2009. CMAJ. 2010;182(18):1981-1987. [PubMed]
 
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