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Original Research: CRITICAL CARE MEDICINE |

Analysis of 30-Day Mortality for Clostridium difficile-Associated Disease in the ICU Setting* FREE TO VIEW

Claire Kenneally, MD; Jamie M. Rosini, PharmD; Lee P. Skrupky, PharmD; Joshua A. Doherty, BS; James M. Hollands, PharmD; Emily Martinez, PharmD; Wendi McKenzie, PharmD; Theresa Murphy, PharmD; Jennifer R. Smith, PharmD; Scott T. Micek, PharmD; Marin H. Kollef, MD, FCCP
Author and Funding Information

*From the Department of Pulmonary and Critical Care Medicine (Drs. Kenneally and Kollef), Washington University School of Medicine; Department of Pharmacy (Drs. Rosini, Skrupky, Hollands, Martinez, McKenzie, Murphy, Smith, and Micek), Barnes-Jewish Hospital; and Medical Informatics (Mr. Doherty), BJC Healthcare, St. Louis, MO.

Correspondence to: Marin H. Kollef, MD, FCCP, Washington University School of Medicine, 660 South Euclid Ave, Campus Box 8052, St. Louis, MO 63110; e-mail: mkollef@im.wustl.edu



Chest. 2007;132(2):418-424. doi:10.1378/chest.07-0202
Text Size: A A A
Published online

Objective: To examine the 30-day mortality rate among patients with Clostridium difficile-associated disease (CDAD) requiring intensive care.

Design: A retrospective, single-center, observational, cohort study.

Setting: Barnes-Jewish Hospital, a 1,200-bed, urban, teaching facility.

Patients: Adult patients admitted to the ICU identified to have CDAD by enzyme immunoassay.

Interventions: Retrospective data collection from automated hospital, microbiology, and pharmacy databases.

Measurements and main results: Two hundred seventy-eight patients with CDAD admitted to an ICU were identified over a 2-year period. Two hundred six patients (74.1%) received prior antibiotic therapy. The overall 30-day mortality rate was 36.7% (n = 102). Logistic regression analysis identified septic shock (adjusted odds ratio, 1.96; 95% confidence interval [CI], 1.47 to 2.61; p = 0.018), ward-to-ICU transfer (adjusted odds ratio, 2.12; 95% CI, 1.62 to 2.79; p = 0.006), and increasing APACHE (acute physiology and chronic health evaluation) II scores (1-point increments) [adjusted odds ratio, 1.09; 95% CI, 1.07 to 1.12; p < 0.001] as independent predictors for 30-day mortality. The attributable mortality associated with CDAD was estimated to be 6.1% (95% CI, − 1.7 to 13.9%; p = 0.127). CDAD was associated with an excess ICU length of stay (2.2 days) and hospital length of stay (4.5 days).

Conclusions: We found a high 30-day crude mortality among patients with CDAD in the ICU setting. Although the attributable mortality from CDAD was relatively low, excess length of stay in the ICU and hospital was observed with CDAD. ICUs should routinely employ infection control efforts aimed at minimizing the occurrence of CDAD because of the excess morbidity associated with this nosocomial infection.

Figures in this Article

Clostridium difficile-associated disease (CDAD) is defined as an otherwise-unexplained syndrome that occurs in association with the presence of C difficile infection in the GI tract.1CDAD is an important nosocomial infection among critically ill patients usually presenting with diarrhea, abdominal pain, hypotension, electrolyte perturbations, and fever.25 The therapeutic approach for CDAD is early diagnosis and administration of appropriate antimicrobial therapy.1Although infection with C difficile accounts for < 25% of the cases of antibiotic-associated diarrhea, it accounts for the majority of cases of colitis associated with antibiotic therapy often requiring surgical intervention including colectomy.4

CDAD has been linked to increasing rates of morbidity and mortality.57 The mechanism for this enhanced virulence is not clear, but epidemic strains of C difficile associated with greater virulence have been identified to be positive for binary toxin and to be resistant to fluoroquinolones.9 The enhanced mortality of CDAD has been predominantly recognized in older hospitalized patients.1011 However, risk factors for hospital mortality among critically ill patients with CDAD have not previously been identified despite the increasing prevalence of this disease in the ICU setting.

We performed a clinical study with two main goals. Our first goal was to determine the 30-day crude mortality rate for patients with CDAD in the ICU. Our second objective was to identify potential risk factors associated with 30-day mortality for this group of patients and to assess the attributable mortality associated with CDAD among critically ill patients.

Study Location and Patients

This study was conducted at a university-affiliated, urban, teaching hospital: Barnes-Jewish Hospital (1,200 beds). During a 2-year period (January 2004 to December 2005), all patients in an ICU (medical, surgical, neurosurgical, cardiac, and cardiothoracic surgery) with a diagnosis of CDAD were eligible for this investigation. Patients with CDAD transferred to an ICU from another hospital, patients with a do-not-resuscitate order in their medical records, and those with a previous diagnosis of CDAD during the same hospital stay were excluded from evaluation. This study was approved by the Washington University School of Medicine Human Studies Committee, and informed consent was waived.

Study Design and Data Collection

A retrospective cohort study design was employed with the main outcome measure being 30-day mortality. Additionally, we assessed secondary outcomes including hospital length of stay, status after colectomy, and the patient’s disposition at the time of hospital discharge. Clinical characteristics evaluated are given in Tables 1, 2 . A computerized list of patients with CDAD was generated by the Medical Informatics Department through retrospective query of the Microbiology Laboratory database at Barnes-Jewish Hospital (performed by J.A.D.), which allowed identification of potential study patients. Patients could not be entered into the study more than once, and only the index case was included for analysis.

Definitions

All definitions were selected prospectively as part of the original study design. APACHE (acute physiology and chronic health evaluation) II scores were calculated based on clinical data available on the day of ICU admission.12CDAD was defined by the presence of diarrhea or pseudomembranous colitis and a positive assay finding for C difficile toxin A, toxin B, or both toxins A and B. Septic shock was defined as the need to employ vasopressors to maintain a mean arterial pressure ≥ 65 mm Hg.13 Patients undergoing a surgical procedure (abdominal, vascular, neurosurgical, cardiothoracic) were classified as surgical, and all others were classified as medical.

Microbiological Data

A commercial enzyme immunoassay was employed to detect toxins A and B (ProSpecT Clostridium difficile Toxin A/B Microplate Assay; Remel; Lenexa, KS). Fresh stool specimens were collected in clean, leak-proof containers or modified Cary-Blair transport medium. All specimens were stored at 2 to 8°C and tested within 48 h of collection. Positive and negative controls were included each time the test was performed. A microplate reader (spectrophotometer) capable of reading bichromatically 450/620–650 nm was employed (Automated Microplate Reader; BIO-TEK Instruments; Winooski, VT).

Statistical Analysis

All comparisons were unpaired, and all tests of significance were two tailed. Continuous variables were compared using the Student t test for normally distributed variables and the Mann-Whitney U test for nonnormally distributed variables. χ2 or Fisher exact test were used to compare categorical variables. The primary data analysis compared 30-day nonsurvivors with survivors. We performed multiple logistic-regression analysis using statistical software (Version 11.0 for Windows; SPSS; Chicago, IL). Multivariate analysis using a forward stepwise approach was performed using models that were judged a priori to be clinically sound. This was prospectively determined to be necessary to avoid producing spuriously significant results with multiple comparisons. All potential risk factors significant at the 0.2 level in univariate analyses were entered into the model.

Attributable mortality was assessed using a case-control analysis. Control patients from the ICU were matched on gender, admission year, and APACHE II score (± 3 points) a priori to control for gender, temporal differences, and severity of illness. The attributable mortality due to CDAD was defined as the crude mortality rate of the control patients without CDAD subtracted from the cases with CDAD. The point estimate of attributable mortality due to CDAD is reported with 95% confidence intervals (CIs).

Patients

A total of 289 consecutive patients with CDAD were initially evaluated. Eleven patients were excluded because of prior hospitalization for CDAD. The remaining 278 patients constituted the study cohort; of whom 102 patients (36.7%) died within 30 days of the diagnosis of CDAD. The mean age of the study patients was 63.9 ± 15.9 years (range, 17 to 96 years), and the average APACHE II score was 20.4 ± 6.4 (range, 5 to 38). There were 148 men (53.2%) and 130 women (46.8%); 196 patients (70.5%) were white, and 74 patients (26.6%) were African American.

Patient Characteristics and Infection-Related Processes According to 30-Day Mortality

Thirty-day nonsurvivors were significantly older, had a greater APACHE II scores, were more likely to have a medical diagnosis and underlying malignancy, and had a lower serum albumin levels compared to 30-day survivors (Table 1). Thirty-day nonsurvivors also were more likely to have a positive C difficile toxin result on the hospital ward prior to ICU transfer, to have septic shock, and to have colonic thickening visualized on CT (Table 2).

Patient Characteristics According to Location of CDAD Acquisition

One hundred sixteen patients (41.7%) had a first positive C difficile toxin assay result from a stool specimen collected on a hospital ward prior to ICU transfer, and 162 patients (58.3%) had a first positive toxin assay result from a stool specimen collected while in the ICU. Patients with a first positive C difficile toxin result collected on a hospital ward prior to ICU transfer were significantly less likely to have received prior antibiotics (67.2% vs 79.0%, p = 0.027) and more likely to have evidence of colonic thickening on CT (38.8% vs 20.4%, p < 0.001). Time to receiving the first dose of antimicrobial therapy for CDAD after collection of a first positive toxin assay result was significantly longer for patients transferred to the ICU from a hospital ward (24.1 ± 23.5 h vs 18.1 ± 17.9 h, p = 0.022). All other comparisons for the variables in Tables 1 and 2 were not statistically different.

Multivariate Analysis

Multivariate logistic regression analysis identified the presence of septic shock, hospital ward-to-ICU transfer, and increasing APACHE II scores as independent determinants of 30-day mortality (Table 3 ). All possible combinations of variables entered into the logistic regression analysis yielded a final model, with hospital ward-to-ICU transfer as an independent determinant of 30-day mortality.

Attributable Mortality

Control patients (n = 278) had a 30-day mortality rate of 30.6%, yielding an attributable mortality of 6.1% (95% CI, − 1.7 to 13.9%; p = 0.127) for patients with CDAD.

Secondary Outcomes

Length of stay in the ICU (15.8 ± 18.2 days vs 9.9 ± 9.5 days, p = 0.002) and hospital (33.3 ± 32.5 days vs 16.9 ± 12.9 days, p ≤ 0.001) were significantly longer among 30-day survivors compared to nonsurvivors. No difference was observed in performance of colectomy (Table 2). Among the 30-day survivors, 84 patients (47.4%) were discharged to a skilled nursing home, 69 patients (39.2%) were sent home, 6 patients (3.4%) were sent to another hospital, and 17 patients (9.7%) died after the 30th day following the diagnosis of CDAD.

ICU length of stay was longer for patients with CDAD compared to those without CDAD (13.7 ± 15.8 days vs 11.5 ± 11.3 days, p = 0.069). Similarly, hospital length of stay was significantly longer for patients with CDAD (27.3 ± 28.1 days vs 22.8 ± 19.8 days, p = 0.030). Kaplan-Meier plots of the probability of remaining in the hospital are shown in Figure 1 for patients with and without CDAD. Patients with CDAD had a significantly higher probability of remaining in the hospital longer compared to patients without CDAD (p = 0.0491, log-rank test).

We observed a crude 30-day mortality rate of 36.7% for patients with CDAD in the ICU setting. We also identified potential risk factors for 30-day mortality among critically ill patients with CDAD, including greater severity of illness, the presence of septic shock, and having CDAD develop on the hospital ward prior to ICU transfer. CDAD was associated with a 6.1% attributable mortality rate and prolonged lengths of stay in the ICU and hospital. These findings suggest that mortality due to CDAD in the ICU is driven by factors similar to those observed in ICU patients without CDAD.

Previous investigations57 have identified high rates of morbidity and mortality among hospitalized patients with CDAD. Loo et al3 found a similar crude mortality rate (24.8%) and attributable mortality rate (6.9%) among patients with CDAD reported from a multi-institutional outbreak. However, attributable mortality and risk factors for mortality in critically ill patients with CDAD have not previously been systematically evaluated. Increasing age and severity of illness are markers or predictors of mortality that have been identified in most studies1415 conducted in the ICU setting. Similarly, the presence of septic shock is associated with a greater overall risk of death.13 Admission to the ICU after previous hospitalization on a hospital ward has also been demonstrated to be associated with a greater risk of hospital mortality. Indeed, lead-time and admission-source biases have been found to be important and often unrecognized factors linked to ICU outcome.1622

A potential explanation for the greater risk of death for patients with CDAD developing on the hospital ward requiring subsequent transfer to the ICU may be a delay in recognition and treatment of this infection on our hospital wards. This is supported by the longer observed duration of time for antimicrobial therapy to be initiated for CDAD identified on the hospital wards prior to ICU transfer. The greater incidence of colonic thickening on CT among patients with CDAD transferred to the ICU from a hospital ward also supports the presence of more severe disease possibly related to delayed treatment in this specific subgroup of patients. To our knowledge, this is the first study linking patient location at the time of initial suspicion and outcome for CDAD. However, we did not observe a significant difference in the time to start of antimicrobial treatment between survivors and nonsurvivors with CDAD. Therefore, factors other than the timing of antibiotic treatment, including greater severity of illness, likely contributed to the observed mortality of patients with CDAD.

Several important limitations of this investigation should be noted. First, we only evaluated patients in the ICU (Appendix). Therefore, we selected a group of patients recognized to have a greater risk of hospital mortality. Second, we may not have identified all patients with CDAD in the ICU setting because we did not routinely screen for this infection. Third, we probably did not identify all of the important determinants of outcome for patients with CDAD. We specifically did not evaluate organism-specific characteristics in this investigation. We also used an enzyme immunoassay to detect toxins A and B and stool samples were not always immediately processed. Thus we may have missed the diagnosis of CDAD in some patients. Additionally, our observation that patients with colonic thickening on CT were less likely to survive their hospitalization is not supported by other investigations. A recent systematic CT evaluation23 found that half of the patients with CDAD had an abnormal finding, with segmental colonic disease more common than diffuse. Positive scan results were more likely in patients with leukocytosis, abdominal pain, and fever. However, specific CT findings did not correlate with clinical parameters and could not predict surgical treatment.23

Another important limitation of our study is that it was not intended to assess specific treatments for CDAD. Nevertheless, the delay in starting antimicrobial treatment for ward-to-ICU transfer patients is consistent with findings in other infections. Delays in starting appropriate antimicrobial treatment for patients with pneumonia, bloodstream infection, and sepsis have all been associated with a greater risk of hospital mortality.13,2426 Patients transferred from a hospital ward to the ICU were found to have longer time delays in the start of antimicrobial therapy for CDAD compared to patients with CDAD diagnosed in the ICU. Further studies are needed to evaluate the importance of timing of antimicrobial therapy for CDAD as it relates to outcomes. A more appropriate treatment time interval to examine in future studies may be from the onset of diarrhea to the start of antibiotic therapy. This may allow the impact of antimicrobial timing from disease onset to be more accurately assessed. Finally, our institution has not seen any of the epidemic strains of C difficile associated with greater virulence. Therefore, our data may not be applicable to institutions having infection associated with this specific pathogen.

The potential impact of CDAD on patient outcomes necessitates the use of measures aimed at preventing this nosocomial infection. CDAD is one disease in which sound hand hygiene has been shown to be helpful in reducing the occurrence of infection.1 Appropriate use of antimicrobial agents, avoiding the prescription of unnecessary courses of therapy, and using the shortest course of treatment that is clinically acceptable are also at the center of preventing CDAD.89 Specific infection control measures targeting CDAD are also useful. McMullen et al27recently demonstrated in our hospital that implementation of an intensive environmental cleaning of ICUs using a hypochlorite solution (1:10 mixture of household bleach with water) resulted in a relative risk reduction of CDAD of 78% compared to the baseline period prior to implementation of this program. This was simultaneously achieved in two different ICUs (medical and surgical units) that validated this approach to environmental cleaning. Bleach has previously been demonstrated to inactivate the spores of C difficile within 15 min of application on surfaces, providing a mechanism for its ability to reduce transmission of CDAD.28

In summary, patients with CDAD in an ICU have a high risk of hospital mortality, although we did not observe a significant attributable mortality due to CDAD compared to ICU patients without this infection. Given the morbidity associated with CDAD in critically ill patients, systematic infection control efforts should be implemented aimed at preventing the horizontal transmission of this infection. Once signs and symptoms of CDAD occur in critically ill patients, confirmation of the diagnosis should be attempted along with administration of appropriate antimicrobial treatment.

Abbreviations: APACHE = acute physiology and chronic health evaluation; CDAD = Clostridium difficile-associated disease; CI = confidence interval

The authors have no conflicts of interest to report for this work.

Table Graphic Jump Location
Table 1. Baseline Patient Characteristics at ICU Admission*
* 

Data are presented as No. (%) or mean ± SD.

 

Measured from hospital admission to collection of positive stool specimen finding for C difficile toxin.

Table Graphic Jump Location
Table 2. Infection-Related Variables*
* 

Data are presented as No. (%) or mean ± SD.

 

Septic shock requires administration of either dopamine or norepinephrine to support mean BP > 65 mm Hg.

 

Sixty-nine nonsurvivors and 81 survivors underwent CT of the abdomen.

§ 

Measured in hours from when first positive toxin assay result was collected.

Table Graphic Jump Location
Table 3. Multivariate Analysis of Independent Risk Factors for Hospital Mortality*
* 

Other covariates not presented had a p value > 0.05, including case mix, underlying malignancy, serum albumin, and colonic thickening on CT (Hosmer-Lemeshow goodness-of-fit test, p = 0.528).

Figure Jump LinkFigure 1. Kaplan-Meier curves depicting the probability of remaining hospitalized in patients with CDAD (dotted line) and patients without CDAD (solid line) [p = 0.0491, log-rank test].Grahic Jump Location
Table Graphic Jump Location
Table 4. Appendix: ICU Admission Characteristics
* 

Immediately following a surgical procedure.

Bartlett, JG (2006) Narrative review: the new epidemic ofClostridium difficile-associated enteric disease.Ann Intern Med145,758-764. [PubMed]
 
Pepin, J, Saheb, N, Coulombe, MA, et al Emergence of fluoroquinolones as the predominant risk factor forClostridium difficile-associated diarrhea: a cohort study during an epidemic in Quebec.Clin Infect Dis2005;41,1254-1260. [PubMed] [CrossRef]
 
Loo, VG, Poirier, L, Miller, MA, et al A predominantly clonal multi-institutional outbreak ofClostridium difficile-associated diarrhea with high morbidity and mortality.N Engl J Med2005;353,2442-2449. [PubMed]
 
McDonald, LC, Killgore, GE, Thompson, A, et al An epidemic, toxin gene-variant strain ofClostridium difficile.N Engl J Med2005;353,2433-2441. [PubMed]
 
Muto, CA, Pokrywka, M, Shutt, K, et al A large outbreak ofClostridium difficile-associated disease with an unexpected proportion of deaths and colectomies at a teaching hospital following increased fluoroquinolone use.Infect Control Hosp Epidemiol2005;26,273-280. [PubMed]
 
McEllistrem, MC, Carman, RJ, Gerding, DN, et al A hospital outbreak ofClostridium difficiledisease associated with isolates carrying binary toxin genes.Clin Infect Dis2005;40,265-272. [PubMed]
 
Dallal, RM, Harbrecht, BG, Boujoukas, AJ, et al FulminantClostridium difficile: an underappreciated and increasing cause of death and complications.Ann Surg2002;235,363-372. [PubMed]
 
Bartlett, JG, Perl, TM The newClostridium difficile: what does it mean?N Engl J Med2005;353,2503-2505. [PubMed]
 
Loge, RV Oral fluoroquinolone therapy forClostridium difficileenterocolitis.JAMA1989;261,2063-2064
 
Pepin, J, Valiquette, L, Alary, ME, et al Clostridium difficile-associated diarrhea in a region of Quebec from 1991 to 2003: a changing pattern of disease severity.Can Med Assoc J2004;171,466-472
 
Karlström, O, Fryklund, B, Tullus, K, et al A prospective nationwide study ofClostridium difficile-associated diarrhea in Sweden.Clin Infect Dis1998;26,141-145. [PubMed]
 
Knaus, WA, Draper, EA, Wagner, DP, et al APACHE II: a severity of disease classification system.Crit Care Med1985;13,818-829. [PubMed]
 
Micek, ST, Roubinian, N, Heuring, T, et al A before-after study of a standardized hospital order set for the management of septic shock.Crit Care Med2006;34,2707-2713. [PubMed]
 
Le Gall, JR, Lemeshow, S, Saulnier, F A new Simplified Acute Physiology Score (SAPS II) based on a European/North American multicenter study.JAMA1993;270,2957-2963. [PubMed]
 
Niskanen, M, Kari, A, Halonen, P Five-year survival after intensive care: comparison of 12,180 patients with the general population.Crit Care Med1996;24,1962-1967. [PubMed]
 
Combes, A, Luyt, CE, Trouillet, JL, et al Adverse effect on a referral intensive care unit’s performance of accepting patients transferred from another intensive care unit.Crit Care Med2005;33,705-710. [PubMed]
 
Tunnell, RD, Millar, BW, Smith, GB The effect of lead-time bias on severity of illness scoring, mortality prediction and standardized mortality ratio in intensive care: a pilot study.Anaesthesia1998;53,1045-1053. [PubMed]
 
Dragsted, L, Jorgensen, J, Jensen, NH, et al Interhospital comparisons of patient outcome from intensive care: importance of lead-time bias.Crit Care Med1989;17,418-422. [PubMed]
 
Rosenberg, AL, Hofer, TP, Strachan, C, et al Accepting critically ill transfer patients: adverse effect on a referral center’s outcome and benchmark measures.Ann Intern Med2003;138,882-890. [PubMed]
 
Rapoport, J, Teres, D, Lemeshow, S, et al Timing of intensive care unit admission in relation to ICU outcome.Crit Care Med1990;18,1231-1235. [PubMed]
 
McGloin, H, Adam, SK, Singer, M Unexpected deaths and referrals to intensive care of patients on general wards: are some cases potentially avoidable?J R Coll Physicians Lond1999;33,255-259. [PubMed]
 
Lundberg, JS, Perl, TM, Wiblin, T, et al Septic shock: an analysis of outcomes for patients with onset on hospital wards versus intensive care units.Crit Care Med1998;26,1020-1024. [PubMed]
 
Ash, L, Baker, ME, O’Malley, CM, Jr, et al Colonic abnormalities on CT in adult hospitalized patients withClostridium difficilecolitis: prevalence and significance of findings.Am J Roentgen2006;186,1393-1400
 
Morrell, M, Fraser, VJ, Kollef, MH Delaying the empiric treatment of Candida bloodstream infection until positive blood culture results are obtained: a potential risk factor for hospital mortality.Antimicrob Agents Chemother2005;49,3640-3645. [PubMed]
 
Micek, ST, Lloyd, AE, Ritchie, DJ, et al Pseudomonas aeruginosabloodstream infection: importance of appropriate initial antimicrobial treatment.Antimicrob Agents Chemother2005;49,1306-1311. [PubMed]
 
Kollef, MH Inadequate antimicrobial treatment: an important determinant of outcome for hospitalized patients.Clin Infect Dis2000;31,S131-S138. [PubMed]
 
McMullen, KM, Zack, J, Coopersmith, C, et al The use of hypochlorite solution to lower rates ofClostridium difficile-associated diarrhea.Infect Control Hosp Epidemiol2007;28,123-130. [PubMed]
 
Perez, J, Springthorpe, VS, Sattar, SA Activity of selected oxidizing microbicides against the spores ofClostridium difficle: relevance to environmental control.Am J Infect Control2005;33,320-325. [PubMed]
 

Figures

Figure Jump LinkFigure 1. Kaplan-Meier curves depicting the probability of remaining hospitalized in patients with CDAD (dotted line) and patients without CDAD (solid line) [p = 0.0491, log-rank test].Grahic Jump Location

Tables

Table Graphic Jump Location
Table 1. Baseline Patient Characteristics at ICU Admission*
* 

Data are presented as No. (%) or mean ± SD.

 

Measured from hospital admission to collection of positive stool specimen finding for C difficile toxin.

Table Graphic Jump Location
Table 2. Infection-Related Variables*
* 

Data are presented as No. (%) or mean ± SD.

 

Septic shock requires administration of either dopamine or norepinephrine to support mean BP > 65 mm Hg.

 

Sixty-nine nonsurvivors and 81 survivors underwent CT of the abdomen.

§ 

Measured in hours from when first positive toxin assay result was collected.

Table Graphic Jump Location
Table 3. Multivariate Analysis of Independent Risk Factors for Hospital Mortality*
* 

Other covariates not presented had a p value > 0.05, including case mix, underlying malignancy, serum albumin, and colonic thickening on CT (Hosmer-Lemeshow goodness-of-fit test, p = 0.528).

Table Graphic Jump Location
Table 4. Appendix: ICU Admission Characteristics
* 

Immediately following a surgical procedure.

References

Bartlett, JG (2006) Narrative review: the new epidemic ofClostridium difficile-associated enteric disease.Ann Intern Med145,758-764. [PubMed]
 
Pepin, J, Saheb, N, Coulombe, MA, et al Emergence of fluoroquinolones as the predominant risk factor forClostridium difficile-associated diarrhea: a cohort study during an epidemic in Quebec.Clin Infect Dis2005;41,1254-1260. [PubMed] [CrossRef]
 
Loo, VG, Poirier, L, Miller, MA, et al A predominantly clonal multi-institutional outbreak ofClostridium difficile-associated diarrhea with high morbidity and mortality.N Engl J Med2005;353,2442-2449. [PubMed]
 
McDonald, LC, Killgore, GE, Thompson, A, et al An epidemic, toxin gene-variant strain ofClostridium difficile.N Engl J Med2005;353,2433-2441. [PubMed]
 
Muto, CA, Pokrywka, M, Shutt, K, et al A large outbreak ofClostridium difficile-associated disease with an unexpected proportion of deaths and colectomies at a teaching hospital following increased fluoroquinolone use.Infect Control Hosp Epidemiol2005;26,273-280. [PubMed]
 
McEllistrem, MC, Carman, RJ, Gerding, DN, et al A hospital outbreak ofClostridium difficiledisease associated with isolates carrying binary toxin genes.Clin Infect Dis2005;40,265-272. [PubMed]
 
Dallal, RM, Harbrecht, BG, Boujoukas, AJ, et al FulminantClostridium difficile: an underappreciated and increasing cause of death and complications.Ann Surg2002;235,363-372. [PubMed]
 
Bartlett, JG, Perl, TM The newClostridium difficile: what does it mean?N Engl J Med2005;353,2503-2505. [PubMed]
 
Loge, RV Oral fluoroquinolone therapy forClostridium difficileenterocolitis.JAMA1989;261,2063-2064
 
Pepin, J, Valiquette, L, Alary, ME, et al Clostridium difficile-associated diarrhea in a region of Quebec from 1991 to 2003: a changing pattern of disease severity.Can Med Assoc J2004;171,466-472
 
Karlström, O, Fryklund, B, Tullus, K, et al A prospective nationwide study ofClostridium difficile-associated diarrhea in Sweden.Clin Infect Dis1998;26,141-145. [PubMed]
 
Knaus, WA, Draper, EA, Wagner, DP, et al APACHE II: a severity of disease classification system.Crit Care Med1985;13,818-829. [PubMed]
 
Micek, ST, Roubinian, N, Heuring, T, et al A before-after study of a standardized hospital order set for the management of septic shock.Crit Care Med2006;34,2707-2713. [PubMed]
 
Le Gall, JR, Lemeshow, S, Saulnier, F A new Simplified Acute Physiology Score (SAPS II) based on a European/North American multicenter study.JAMA1993;270,2957-2963. [PubMed]
 
Niskanen, M, Kari, A, Halonen, P Five-year survival after intensive care: comparison of 12,180 patients with the general population.Crit Care Med1996;24,1962-1967. [PubMed]
 
Combes, A, Luyt, CE, Trouillet, JL, et al Adverse effect on a referral intensive care unit’s performance of accepting patients transferred from another intensive care unit.Crit Care Med2005;33,705-710. [PubMed]
 
Tunnell, RD, Millar, BW, Smith, GB The effect of lead-time bias on severity of illness scoring, mortality prediction and standardized mortality ratio in intensive care: a pilot study.Anaesthesia1998;53,1045-1053. [PubMed]
 
Dragsted, L, Jorgensen, J, Jensen, NH, et al Interhospital comparisons of patient outcome from intensive care: importance of lead-time bias.Crit Care Med1989;17,418-422. [PubMed]
 
Rosenberg, AL, Hofer, TP, Strachan, C, et al Accepting critically ill transfer patients: adverse effect on a referral center’s outcome and benchmark measures.Ann Intern Med2003;138,882-890. [PubMed]
 
Rapoport, J, Teres, D, Lemeshow, S, et al Timing of intensive care unit admission in relation to ICU outcome.Crit Care Med1990;18,1231-1235. [PubMed]
 
McGloin, H, Adam, SK, Singer, M Unexpected deaths and referrals to intensive care of patients on general wards: are some cases potentially avoidable?J R Coll Physicians Lond1999;33,255-259. [PubMed]
 
Lundberg, JS, Perl, TM, Wiblin, T, et al Septic shock: an analysis of outcomes for patients with onset on hospital wards versus intensive care units.Crit Care Med1998;26,1020-1024. [PubMed]
 
Ash, L, Baker, ME, O’Malley, CM, Jr, et al Colonic abnormalities on CT in adult hospitalized patients withClostridium difficilecolitis: prevalence and significance of findings.Am J Roentgen2006;186,1393-1400
 
Morrell, M, Fraser, VJ, Kollef, MH Delaying the empiric treatment of Candida bloodstream infection until positive blood culture results are obtained: a potential risk factor for hospital mortality.Antimicrob Agents Chemother2005;49,3640-3645. [PubMed]
 
Micek, ST, Lloyd, AE, Ritchie, DJ, et al Pseudomonas aeruginosabloodstream infection: importance of appropriate initial antimicrobial treatment.Antimicrob Agents Chemother2005;49,1306-1311. [PubMed]
 
Kollef, MH Inadequate antimicrobial treatment: an important determinant of outcome for hospitalized patients.Clin Infect Dis2000;31,S131-S138. [PubMed]
 
McMullen, KM, Zack, J, Coopersmith, C, et al The use of hypochlorite solution to lower rates ofClostridium difficile-associated diarrhea.Infect Control Hosp Epidemiol2007;28,123-130. [PubMed]
 
Perez, J, Springthorpe, VS, Sattar, SA Activity of selected oxidizing microbicides against the spores ofClostridium difficle: relevance to environmental control.Am J Infect Control2005;33,320-325. [PubMed]
 
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CHEST Journal Articles
Nosocomial Pneumonia*: The Importance of a De-escalating Strategy for Antibiotic Treatment of Pneumonia in the ICU
PubMed Articles
  • CHEST Journal
    Print ISSN: 0012-3692
    Online ISSN: 1931-3543