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(Chest. 2003;124:1021-1029.)
© 2003 American College of Chest Physicians

The Influence of Infection on Hospital Mortality for Patients Requiring > 48 h of Intensive Care*

Steven Osmon, MD; David Warren, MD; Sondra M. Seiler, BS; William Shannon, PhD; Victoria J. Fraser, MD and Marin H. Kollef, MD, FCCP

* From the Pulmonary and Critical Care Division (Drs. Osmon and Kollef), the Division of Infectious Diseases (Drs. Warren and Fraser, and Ms. Seiler), and the Division of General Medical Sciences and Biostatistics (Dr. Shannon), Washington University School of Medicine, 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: kollefm{at}msnotes.wustl.edu


   Abstract
TOP
 Abstract
Introduction
 Materials and Methods
 Results
 Discussion
 References
 
Objective: To determine the influence of microbiologically confirmed infection on hospital mortality among patients requiring intensive care for > 48 h.

Design: Prospective cohort study.

Setting: Medical ICU of the Barnes-Jewish Hospital, an urban teaching hospital.

Patients: A total of 893 patients requiring intensive care for > 48 h.

Interventions: Prospective patient surveillance and data collection.

Measurements and main results: Three hundred seventy-two patients (41.7%) requiring intensive care for > 48 h had a microbiologically confirmed infection. Only six patients (0.7% [1.6% of patients with microbiologically confirmed infections]) received inadequate antimicrobial therapy during the first 24 h of treatment, and 248 patients (27.8%) died during hospitalization. Compared to hospital survivors, hospital nonsurvivors were significantly more likely to have a microbiologically confirmed infection (53.2% vs 37.2%, respectively; p < 0.001) and to develop severe sepsis (45.6% vs 28.7%, respectively; p < 0.001). Cirrhosis and the requirement for vasopressors were the only variables identified by multiple logistic regression analysis as independent risk factors for hospital mortality in all patient groupings of severity of illness. Multiple logistic regression analysis also demonstrated that underlying malignancy (adjusted odds ratio [AOR], 1.98; 95% CI, 1.55 to 2.53), chronic renal insufficiency (AOR, 1.57; 95% CI, 1.31 to 1.87), cirrhosis (AOR, 1.94; 95% CI, 1.48 to 2.53), temperature > 38.3°C (AOR, 1.72; 95% CI, 1.47 to 2.02), severe sepsis (AOR, 2.78; 95% CI, 1.94 to 3.98), positive culture for vancomycin-resistant enterococci (AOR, 1.78; 95% CI, 1.51 to 2.09), and the presence of multiple infections (AOR, 1.65; 95% CI, 1.28 to 2.14) were independently associated with the requirement for therapy with vasopressors.

Conclusions: Microbiologically confirmed infections are common among patients requiring medical intensive care for > 48 h. Despite the administration of adequate antimicrobial therapy, microbiologically confirmed infections appear to be an important cause of hemodynamic instability and increased hospital mortality. These data suggest that clinical efforts aimed at the prevention of infections and improvements in the medical management of patients with severe infections, especially those associated with hemodynamic instability and the need for vasopressors, are required to achieve further improvements in patient outcomes.

Key Words: antibiotics • hospital • infection • mortality • outcome • shock • vasopressors


   Introduction
TOP
 Abstract
 Introduction
Materials and Methods
 Results
 Discussion
 References
 
Bacterial infections are common among patients requiring intensive care. In a 1-day point-prevalence study conducted in European ICUs,1 a total of 10,038 patients were reviewed, of whom 4,501 (44.8%) had a microbiologically confirmed infection. Pneumonia (46.9%), lower respiratory tract infection (17.8%), urinary tract infection (17.6%), and bloodstream infection (12.0%) were the most frequent types of infections described in these ICUs. The Enterobacteriaceae (34.4%), Staphylococcus aureus (30.1%), and Pseudomonas aeruginosa (28.7%) were the most common pathogens associated with infection. Similarly, among 181,993 patients admitted to medical ICUs in the United States, urinary tract infections were the most frequent nosocomial infection (31%), followed by pneumonia (27%) and primary bloodstream infection (19%).2 Bacterial infections were the most common cause of hospital-acquired infection with coagulase-negative staphylococci (36%), enterococci (16%), and S aureus (13%) being the most common blood isolates. P aeruginosa (21%) and S aureus (20%) were the most common isolates from pneumonia, and Candida albicans was the most common single pathogen isolated from the urine.

Despite the common occurrence of infections among patients requiring intensive care, there are few clinical data describing the overall impact of infections on patient outcomes, especially hospital mortality. Most recently, the influence of inadequate or delayed antimicrobial treatment of serious infections on hospital mortality has been well-described.3 4 5 6 7 8 9 10 11 12 13 14 Therefore, we performed a prospective cohort study with two main goals. The first goal was to establish the frequency of microbiologically confirmed infections among patients requiring > 48 h of medical intensive care. Our second goal was to describe the relationship between microbiologically confirmed infections and hospital mortality in this patient cohort.


   Materials and Methods
TOP
 Abstract
 Introduction
 Materials and Methods
Results
 Discussion
 References
 
Study Location and Patients
This study was conducted at a university-affiliated, urban teaching hospital, Barnes-Jewish Hospital (1,400 beds). During a 20-month period (ie, February 2000 to October 2001), all patients requiring admission to the medical ICU (19 beds) for > 48 h were eligible for this investigation. This inclusion criterion was prospectively selected to minimize the enrollment of patients with rapidly fatal illnesses and self-limited conditions not requiring more prolonged intensive care. Patients were excluded from this investigation if they had transferred from another hospital, if they had undergone a bone marrow transplant, or if they had been temporally transferred to the medical unit from another ICU due to staffing issues. The medical ICU is a closed unit with a multidisciplinary team providing patient care under the direction of attending physicians who are board-certified in critical care medicine. This study was approved by the Washington University School of Medicine Human Studies Committee.

Study Design and Data Collection
A prospective cohort study design was employed with the main outcome measure being in-hospital mortality. We also assessed secondary outcomes, including the lengths of hospitalization and intensive care, the number of acquired organ system derangements, and the occurrence of microbiologically confirmed infection.

For all study patients, the following characteristics were prospectively recorded by one of the investigators: age; gender; race; severity of illness based on APACHE (acute physiology and chronic health evaluation) II scores15 ; and the presence of congestive heart failure, COPD, underlying malignancy, recent chemotherapy, seropositivity for HIV, diabetes mellitus, chronic renal insufficiency, cirrhosis, and solid organ transplantation. Specific processes of medical care examined during patients’ intensive care stay included the following: administration of antacids, sucralfate, histamine type-2 receptor antagonists, or corticosteroids; the number of central venous catheters placed; enteral nutrition; mechanical ventilation; the need for reintubation; the placement of a tracheostomy; surgery prior to ICU admission; the use of vasopressors; and the adequacy of the initially prescribed antibiotics for microbiologically confirmed infections. Infection variables also were examined, including leukocytosis, the development of new radiographic lung infiltrates, the presence of purulent sputum, temperature > 38.3°C, the presence of severe sepsis,16 the presence of Clostridium difficile infection, bloodstream infection, ventilator-associated pneumonia, hospital- acquired pneumonia in patients not requiring mechanical ventilation, tracheobronchitis, urinary tract infection, skin and soft-tissue infection, and community-acquired pneumonia; colonization with vancomycin-resistant enterococci; and the presence of multiple microbiologically confirmed infections.

One of the investigators (SS) made daily rounds in the medical ICU to identify eligible patients. Patients who were entered into the study were prospectively followed up until they were discharged from the hospital or had died. Discharge from the hospital was defined as patient transfer from the hospital to home, to a skilled nursing facility, or to a private rehabilitative hospital. All patients suspected of having a microbiologically confirmed infection were prospectively and independently reviewed by a board-certified infectious disease physician (VJF) to confirm the diagnosis and the adequacy of the prescribed antimicrobial therapy using the criteria described below. Patients could not be entered into the study more than once during the same hospitalization.

Definitions
All definitions were selected prospectively as part of the original study design. We calculated APACHE II scores on the basis of the clinical data available from the first 24-h period of intensive care.15 The definition used for severe sepsis was the one proposed by the American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference.16 The Organ System Failure Index was modified from that used by Rubin and coworkers.17 One point was given for acquired dysfunction of each organ system. Renal dysfunction was defined as a twofold increase in baseline creatinine level or an absolute increase in baseline creatinine level of 176.8 µmol/L (ie, 2.0 mg/dL). Hepatic dysfunction was defined as an increase in total bilirubin level to > 34.2 µmol/L (ie, 2.0 mg/dL). Pulmonary dysfunction was defined as one of the following: (1) a requirement for mechanical ventilation for a diagnosis of pneumonia, COPD, asthma, or pulmonary edema (cardiogenic or noncardiogenic); (2) a PaO2 of < 60 mm Hg while receiving a fraction of inspired oxygen of >= 0.50; or (3) the use of at least 10 cm H2O of positive end-expiratory pressure, hematologic dysfunction, the presence of disseminated intravascular coagulation, a leukocyte count of < 1,000 cells/µL (ie, 1.0 x 109 cells/L) or a platelet count of < 75 x 103 cells/µL (ie, 75 x 109 cells/L), neurologic dysfunction, a new focal deficit (eg, hemiparesis after cerebral infarction) or a new generalized process (eg, seizures or coma), GI dysfunction, GI hemorrhage requiring transfusion, or new ileus or diarrhea lasting for > 24 h and unrelated to previous bowel surgery. Cardiac dysfunction was defined as acute myocardial infarction, cardiac arrest, or the new onset of congestive heart failure.

Community-acquired infections (ie, urinary tract, bloodstream, pneumonia, and soft-tissue infections) were defined according to the patient’s hospital admission diagnosis and the treating physicians’ orders in the medical record documenting the need for antibiotic treatment of a specific community-acquired infection. Additionally, all community-acquired infections were required to be established within 48 h of hospital admission. Similar temporal cutoffs for separating community-acquired infections from hospital-acquired infections have been proposed by other investigators.18 Patients residing at a nursing home, a skilled care facility, or a rehabilitation center who developed an infection requiring hospital admission were classified as having community-acquired infection. Nosocomial infections (ie, urinary tract, bloodstream, pneumonia, and skin or soft-tissue infections) were defined according to the criteria established by the Centers for Disease Control and Prevention.19 The identified source of infection was required to be documented in the patient’s medical record. Clinically suspected infections without microbiological confirmation by either special stains (eg, Gram stain or potassium hydroxide stain) or a positive culture were not classified as microbiologically confirmed infection.

The diagnostic criteria for ventilator-associated pneumonia were modified from the criteria established by the American College of Chest Physicians.18 Ventilator-associated pneumonia was considered to be present when a new or progressive roentgenographic infiltrate developed in conjunction with one of the following: radiographic evidence of pulmonary abscess formation (ie, cavitation within preexisting pulmonary infiltrates); histologic evidence of pneumonia in lung tissue; a positive blood or pleural fluid culture; or two conditions from among fever, leukocytosis, and purulent tracheal aspirate. Blood and pleural fluid cultures could not be related to another source, and both had to have been obtained within 48 h before or after the clinical suspicion of ventilator-associated pneumonia. Microorganisms recovered from blood or pleural fluid cultures also had to be identical to the organisms recovered from cultures of respiratory secretions (ie, tracheal aspirates or BAL fluid).

A new radiographic infiltrate (ie, not attributed to community-acquired pneumonia present on hospital admission) was prospectively defined as one occurring > 48 h after the start of therapy with mechanical ventilation. Persistence was defined as the infiltrate presenting roentgenographically for at least 72 h. Fever was defined as an increase in the core temperature of >= 1°C and a core temperature of > 38.3°C. Leukocytosis was defined as a 25% increase in circulating leukocytes from baseline and a leukocyte count of > 10 x 103 cells/mm3 (ie, 10 x 109 cells/L). Tracheal aspirates were considered purulent if a Gram stain showed > 25 neutrophils per high-power field.

The criteria employed to assess the adequacy of antimicrobial treatment for microbiologically confirmed infections are similar to those described in previous investigations of infection in the intensive care setting.3 13 20 Antimicrobial therapy for microbiologically confirmed infections was considered to be adequate when at least one antibiotic with in vitro activity against the microorganisms associated with infection was included in the treatment regimen within the first 24 h. The hospital’s microbiology laboratory determined the antimicrobial susceptibility of clinical isolates following break points established by the National Committee for Clinical Laboratory Standards. The empiric antimicrobial therapy policy for the medical ICU required the treatment of community-acquired pneumonia with either a new generation fluoroquinolone (eg, moxifloxacin) or a combination of a nonpseudomonal third-generation cephalosporin (eg, ceftriaxone) in combination with a macrolide antibiotic (eg, clarithromycin). The empiric treatment of serious hospital-acquired infections required a combination of an antistaphylococcal drug (eg, vancomycin or linezolid for methicillin-resistant staphylococci) and at least one antibiotic with Gram-negative activity (eg, ciprofloxacin, cefepime, imipenem, or piperacillin-tazobactam). For patients at increased risk for infection with antibiotic-resistant, Gram-negative bacteria (eg, P aeruginosa and Acinetobacter species), two antibiotics directed against Gram-negative bacteria were initially administered, one of which could be an aminoglycoside.21 The initial empiric treatment of fungal infection with fluconazole was recommended in patients at increased risk for fungal infection (eg, those who had received previous antibiotic treatment, had neutropenia, or had experienced multiple invasive devices). The initial empiric antimicrobial regimen was modified or narrowed within 48 h based on the results of special stains and cultures. This de-escalation of the initial empiric antimicrobial regimen was monitored by the pharmacist making rounds with the critical care team.21 22

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 Wilcoxon rank-sum test for non-normally distributed variables. The {chi}2 or Fisher exact test was used to compare categoric variables. The primary data analysis compared hospital nonsurvivors with survivors. The probability of survival during hospitalization for patients with and without a microbiologically confirmed infection was calculated according to the Kaplan-Meier method and was compared by the log-rank test. We performed multiple logistic regression analysis using a commercial statistical software package (SAS; SAS Institute; Cary, NC).23

A stepwise approach was used to enter new terms into the logistic regression model, in which hospital mortality was the dependent outcome variable, and 0.05 was set as the limit for the acceptance or removal of new terms. Variables with a p value < 0.15 were entered into the multivariate analysis based on models that were judged a priori to be clinically sound.24 This was prospectively determined to be necessary to avoid producing spuriously significant results with multiple comparisons. The results of the logistic regression analysis are reported as adjusted odds ratios (AORs) with 95% confidence intervals (CIs). Relative risks and their 95% CIs were calculated using standard methods. Values are expressed as the mean ± SD (for continuous variables) or as a percentage of the group from which they were derived (for categoric variables). All p values were two-tailed, and p values of <= 0.05 were considered to indicate statistical significance.


   Results
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
Discussion
 References
 
Patients
A total of 893 consecutive patients requiring admission to the medical ICU for > 48 h were evaluated. The mean age of the patients was 58.7 ± 17.0 years (range, 15 to 102 years), and the mean APACHE II score was 23.0 ± 7.4 (range, 5 to 47). There were 441 men (49.4%) and 452 women (50.6%).

Microiologically Confirmed Infection
Three hundred seventy-two patients (41.7%) had a microbiologically confirmed infection. Among the patients with a microbiologically confirmed infection, 194 (52.1%) had a urinary tract infection, 118 (31.7%) had a bloodstream infection, 73 (19.6%) had community-acquired pneumonia, 37 (9.9%) had a hospital-acquired lower respiratory tract infection (eg, tracheobronchitis, ventilator-associated pneumonia, or hospital-associated pneumonia), 7 (1.9%) had a skin or soft-tissue infection, and 301 (80.9%) had multiple infections. The most common pathogens associated with bloodstream infection were S aureus (29 patients), Candida species (26 patients), Enterococcus species (19 patients), coagulase-negative staphylococci (17 patients), P aeruginosa (9 patients), and other Gram-negative bacteria (31 patients). Among patients with hospital-acquired lower respiratory tract infections, the most common pathogens included S aureus (12 patients), P aeruginosa (10 patients), and other Gram-negative bacteria (23 patients). Among patients with community-acquired pneumonia, Streptococcus pneumoniae (32 patients), S aureus (25 patients), Haemophilus influenzae (14 patients), P aeruginosa (6 patients), and other Gram-negative bacteria (6 patients) were most common. The APACHE II scores of patients with a microbiologically confirmed infection were statistically greater than the scores of patients without infection (Fig 1 ).



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  		Figure 1. Box plots of APACHE II scores for patients with and without microbiologically confirmed infections. Boxes represent the 25th to 75th percentiles with 50th percentile value within the boxes (solid line). The 10th and 90th percentiles are shown as capped bars, and symbols (•) mark the 5th and 95th percentiles.

 
Risk Factors for Mortality
A total of 248 patients (27.8%) died during their hospitalization. Patients with a microbiologically confirmed infection had a statistically greater hospital mortality rate compared to patients without infection (35.5% vs 22.3%, respectively; p < 0.001). Kaplan-Meier plots of the probability of remaining alive during hospitalization are shown in Figure 2 for patients with and without microbiologically confirmed infection. Patients with microbiologically confirmed infection had a statistically higher probability of in-hospital mortality compared to patients without evidence of infection (p < 0.001 [log rank test]). Among the baseline characteristics (Table 1 ) examined, hospital nonsurvivors were statistically older, had greater APACHE II scores, and had a higher prevalence of underlying malignancy, chronic renal insufficiency, the need for dialysis, and cirrhosis. Hospital nonsurvivors required significantly more central lines, were more likely to receive enteral nutrition, mechanical ventilation, vasopressors, and sucralfate, and to require reintubation (Table 2 ). The development of new infiltrates seen on chest radiographs, purulent sputum, temperature > 38.3°C, severe sepsis, primary bloodstream infection with a central vein catheter in place, secondary bloodstream infection, ventilator-associated pneumonia, urinary tract infection, skin or soft-tissue infection, multiple infections, culture positivity for vancomycin-resistant enterococci, and the presence of a microbiologically confirmed infection were statistically more common among hospital nonsurvivors (Table 3 ).



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  		Figure 2. Kaplan-Meier curves depicting the probability of survival in patients with microbiologically confirmed infections ({circ}) and patients without microbiologically confirmed infections (•) according to the duration of hospitalization (p < 0.001 [by the log rank test].

 

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  		Table 1. Baseline Characteristics of Study Patients According to Hospital Mortality*

 

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  		Table 2. Process-of-Care Variables According to Hospital Mortality*

 

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  		Table 3. Infection Variables According to Hospital Mortality*

 
Multiple logistic regression analysis demonstrated that underlying malignancy (AOR, 1.90; 95% CI, 1.46 to 2.50; p = 0.015), chronic renal insufficiency (AOR, 2.30; 95% CI, 1.89 to 2.80; p < 0.001), cirrhosis (AOR, 2.89; 95% CI, 2.16 to 3.86; p < 0.001), APACHE II score (in 1-U increments) [AOR, 1.05; 95% CI, 1.04 to 1.07; p < 0.001], mechanical ventilation (AOR, 1.78; 95% CI, 1.39 to 2.27; p = 0.018); temperature > 38.3°C (AOR, 1.50;95% CI, 1.24 to 1.81; p = 0.035), skin and soft-tissue infection (AOR, 10.71; 95% CI, 3.52 to 32.59; p = 0.033), and therapy with vasopressors (AOR, 3.08; 95% CI, 2.53 to 3.76; p < 0.001) were independently associated with hospital mortality. Variables independently associated with hospital mortality for patients with APACHE II scores of < 20, between 20 and 25, and > 25 are shown in Table 4 . Cirrhosis and the requirement for vasopressors were the only variables associated with mortality for all groups of severity of illness examined.


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  		Table 4. Variables Independently Associated With Hospital Mortality*

 
Risk Factors for Vasopressors
Multiple logistic regression analysis demonstrated that underlying malignancy (AOR, 1.98; CI, 1.55 to 2.53; p = 0.005), chronic renal insufficiency (AOR, 1.57; CI, 1.31 to 1.87; p = 0.012), cirrhosis (AOR, 1.94; CI, 1.48 to 2.53; p = 0.014), temperature > 38.3°C (AOR, 1.72; CI, 1.47 to 2.02; p = 0.001), severe sepsis (AOR, 2.78; CI, 1.94 to 3.98; p = - 0.004), positive culture for vancomycin-resistant enterococci (AOR, 1.78; CI, 1.51 to 2.09; <0.001), and the presence of multiple infections (AOR, 1.65; CI, 1.28 to 2.14; p = 0.05) were independently associated with the use of vasopressors.

Secondary Outcomes
Hospital nonsurvivors were statistically more likely to develop acquired organ derangements (Table 5 ). The length of intensive care was statistically greater for hospital nonsurvivors compared to hospital survivors. No difference in hospital length of stay was demonstrated.


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  		Table 5. Patient Secondary Outcomes According to Hospital Mortality*

 

   Discussion
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
References
 
We demonstrated that microbiologically confirmed infections are common among medical patients requiring intensive care for > 48 h. Despite the majority of infected patients receiving adequate antimicrobial treatment, the hospital mortality rate for patients with microbiologically confirmed infection was 35.5% and was statistically greater than the rate of hospital mortality for patients without infection. The requirement for vasopressors was identified as the only process-of-care variable associated with hospital mortality for all groupings of patient severity of illness (Table 4) . This suggests that modification of this variable, as a potential risk factor for hospital mortality, could improve patient outcomes. Alternatively, the need for vasopressors may be a marker for severe sepsis. Variables independently associated with the use of vasopressors included the presence of underlying malignancy, chronic renal insufficiency, cirrhosis, severe sepsis, being culture positive for vancomycin-resistant enterococci, and the presence of multiple microbiologically confirmed infections.

Despite the widespread presence of infected patients within ICUs, few clinical studies have examined the influence of microbiologically confirmed infection on hospital mortality.1 3 7 Our study is unique in examining this association in a patient cohort having a low prevalence of inadequate initial antimicrobial treatment for microbiologically confirmed infections. Previous investigations have shown that delays in the administration of an antimicrobial regimen with demonstrated in vitro activity against the infecting microorganism is associated with greater hospital mortality.3 4 5 6 7 8 9 10 11 12 13 14 More recently, the same finding has been demonstrated for patients with severe sepsis.20 25 These data suggest that the prescribed antimicrobial treatment for patients with serious infections and severe sepsis is one of the most important determinants of clinical outcome that the physician can influence directly. The low prevalence of inadequate antimicrobial treatment in our study population allowed us to assess more directly the impact of microbiologically confirmed infections on hospital mortality.

It is important to note that our study does not prove a causal relationship between microbiologically confirmed infections and hospital mortality. However, our analysis suggests that the prevention of microbiologically confirmed infections and advances in the management of infected patients requiring vasopressors (ie, patients with infection-related shock) may result in improvements in the clinical outcomes of infected patients. Although it seems logical that such interventions should be developed and implemented on a wide-scale basis, available clinical studies suggest that these specific types of interventions have not been routinely applied. Our study also suggests that antimicrobial treatment of microbiologically confirmed infections represents only one process-of-care variable influencing the outcomes of infected patients requiring intensive care.

The prevention of microbiologically confirmed infections is increasingly being recognized as an important issue because of the escalating emergence of antimicrobial resistance among community- acquired and hospital-acquired pathogens.26 Community efforts successfully targeting the prevention of infections include the use of vaccines (eg, polyvalent pneumococcal and influenza vaccine),27 more judicious use of antibiotics to prevent the emergence of resistant pathogens,28 programs providing education, nutritional support, and routine medical care to economically disadvantaged communities, and interventions that foster a better awareness among physicians of patient populations that are at increased risk for serious infections (eg, urinary tract infections in pregnancy or fever in neutropenic hosts) and of the dangers of unnecessary antibiotic use.29 30 Unfortunately, the prevention of serious community-acquired infections, many of which will require intensive care, has been limited by overall noncompliance with these interventions on the part of physicians and the communities they serve.31 32

Similarly, there have been numerous studies performed suggesting that many hospital-acquired infections can be prevented by employing readily available processes and interventions. These studies have focused on the use of protocols or educational programs to improve infection control practices,33 vaccines directed against high-risk pathogens such as S aureus and P aeruginosa,34 and the application of novel antimicrobial drugs and devices to prevent infections.35 However, many of the interventions aimed at the prevention of hospital-acquired infections are not routinely applied due to a lack of clinician understanding of the importance of these interventions36 and increasing shortages of nurses and other health-care providers, especially within ICUs.37 The unavailability of adequate physician and nursing staffing of ICUs makes it increasingly likely that optimal application of infection control practices will not occur despite their demonstrated cost-effectiveness.38 Therefore, efforts directed at improving the availability of skilled health-care providers within the hospital setting may be the most important future intervention influencing the development of hospital-acquired infections.

Our study suggests that efforts aimed at reducing the need for therapy with vasopressors among patients with severe sepsis also may reduce hospital mortality. However, the observational design of our study does not allow us to ascertain with certainty that improved hemodynamic management improves outcomes in this patient population. A recent interventional study found improved hospital mortality among patients with septic shock receiving aggressive, goal-targeted interventions in the emergency department as opposed to routine management.39 The early application of goal-targeted fluid resuscitation, RBC transfusion, and the application of vasopressors to achieve predefined end points in vital signs and physiologic indicators of tissue perfusion seems logical.40 Similarly, the application of agents directed at attenuating the host’s inflammatory response and organ failure in patients with severe sepsis also have been demonstrated to be beneficial.25 To achieve optimal clinical outcomes will likely require the use of multiple interventions such as the early treatment of infection with appropriate antimicrobial therapy, adequate resuscitation of tissue hypoperfusion, and the use of specific antisepsis therapies in appropriate patients. This is supported by the recent Protein C Worldwide Evaluation in Severe Sepsis investigation that found both adequate initial antimicrobial treatment and the use of activated protein C to be associated with a survival advantage among patients with severe sepsis (H. Levy, MD; personnel communication; July 2002).25

Our study has several limitations. First, it was performed within a single ICU with a low prevalence of inadequate antimicrobial treatment of microbiologically confirmed infections. Therefore, the results may not be generalizable to other hospitals. Second, it is possible that we misclassified some infected patients as a result of false-negative culture results, especially if cultures had been obtained after the patient began antimicrobial treatment. Third, we did not examine specific infections as determinants of hospital mortality (eg, community-acquired pneumonia or hospital-acquired bloodstream infection). This was purposefully done to determine the broad relationship between microbiologically confirmed infections and mortality, and because our sample size limited such subgroup analyses. Fourth, we did not examine the timing of antibiotic administration in relationship to when patients arrived at the hospital14 or when their infections were first diagnosed.13 Fifth, we did not examine whether increased severity of illness predisposed the patient to infection, as has been demonstrated by other investigators.41 Finally, our hospital nonsurvivors were statistically older than the survivors (Table 1) . This age disparity is a confounding factor as it implies a less robust patient population among the nonsurvivors with potentially greater mortality from less severe insult. Despite these limitations, our study provides prospective data to determine the relationship between microbiologically confirmed infection and hospital mortality.

In summary, we showed that microbiologically confirmed infections are common among medical patients requiring prolonged intensive care and are associated with a high rate of hospital mortality. Efforts directed at the prevention of community-acquired and hospital-acquired infections seem most likely to influence the occurrence of such infections and the outcomes of individuals who are at risk for infection. Decreased staffing within hospitals, increasing health-care costs, and socioeconomic barriers appear to prohibit the application of widespread infection-prevention measures. Similarly, readily available efforts aimed at improving the management of hemodynamically unstable infected patients also may improve clinical outcomes.39 This is supported by our finding that the use of vasopressors was the only potentially modifiable factor associated with nonsurvival throughout APACHE II severity-of-illness stratification.


   Acknowledgements
 
The authors thank Ms. Cheri Hill for her assistance in preparing this manuscript, and Robyn Schaiff, PharmD, and Scott Micek, PharmD, for their clinical efforts in the medical ICU during this study.


   Footnotes
 
Abbreviations: AOR = adjusted odds ratio; APACHE = acute physiology and chronic health evaluation; CI = confidence interval

This work was supported by funding from the Centers for Disease Control and Prevention Cooperative Agreement (grant No. U50/CCU717925), by the Barnes-Jewish Hospital Foundation, and by restricted grants from Bayer Corporation and Wyeth-Ayerst Laboratories.

Received for publication December 11, 2002. Accepted for publication February 27, 2003.


   References
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 References
 

  1. Vincent, JL, Bihari, DJ, Suter, PM, et al (1995) The prevalence of nosocomial infection in intensive care units in Europe: results of the European Prevalence of Infection in Intensive Care (EPIC) Study. JAMA 274,639-644[Abstract]
  2. Richards, MJ, Edwards, JR, Culver, DH, et al Nosocomial infections in medical intensive care units in the United States: National Nosocomial Infections Surveillance System. Crit Care Med 1999;27,887-892[CrossRef][ISI][Medline]
  3. Kollef, MH, Sherman, G, Ward, S, et al Inadequate antimicrobial treatment of infections: a risk factor for hospital mortality among critically ill patients. Chest 1999;115,462-474[CrossRef][ISI][Medline]
  4. Luna, CM, Vujachich, P, Neiderman, MS, et al Impact of BAL data on the therapy and outcome of ventilator-associated pneumonia. Chest 1997;111,676-685[ISI][Medline]
  5. Alvarez-Lerma, F Modifications of empiric antibiotic treatment in patients with pneumonia acquired in the intensive care unit: ICU-Acquired Pneumonia Study Group. Intensive Care Med 1996;22,387-394[CrossRef][ISI][Medline]
  6. Rello, J, Gallego, M, Mariscal, D, et al The value of routine microbial investigation in ventilator-associated pneumonia. Am J Respir Crit Care Med 1997;156,196-200[Abstract/Free Full Text]
  7. Heyland, DK, Cook, DJ, Griffith, L, et al The attributable morbidity and mortality of ventilator-associated pneumonia in the critically ill patient. Am J Respir Crit Care Med 1999;159,1249-1256[Abstract/Free Full Text]
  8. Kollef, MH, Ward, S The influence of mini-BAL cultures on patient outcomes: implications for the antibiotic management of ventilator-associated pneumonia. Chest 1998;113,412-420[ISI][Medline]
  9. Kollef, MH Inadequate antimicrobial treatment: an important determinant of outcome for hospitalized patients. Clin Infect Dis 2000;31,S131-S138[CrossRef][ISI][Medline]
  10. Dupont, H, Mentec, H, Sollet, JP, et al Impact of appropriateness of initial antibiotic therapy on the outcome of ventilator-associated pneumonia. Intensive Care Med 2001;27,355-362[CrossRef][ISI][Medline]
  11. Lautenbach, E, Patel, JB, Bilker, WB, et al Extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae: risk factors for infection and impact of resistance on outcomes. Clin Infect Dis 2001;32,1162-1171[CrossRef][ISI][Medline]
  12. Cosgrove, SE, Kaye, KS, Eliopoulous, GM, et al Health and economic outcomes of the emergence of third-generation cephalosporin resistance in Enterobacter species. Arch Intern Med 2002;162,185-190[Abstract/Free Full Text]
  13. Iregui, M, Ward, S, Sherman, G, et al Clinical importance of delays in the initiation of appropriate antibiotic treatment for ventilator-associated pneumonia. Chest 2002;122,262-268[CrossRef][ISI][Medline]
  14. Meehan, TP, Fine, MJ, Krumholz, HM, et al Quality of care, process, and outcomes in elderly patients with pneumonia. JAMA 1997;278,2080-2084[Abstract]
  15. Knaus, WA, Draper, EA, Wagner, DP, et al APACHE II: a severity of disease classification system. Crit Care Med 1985;13,818-829[ISI][Medline]
  16. American College of Chest Physicians/Society of Critical Care Medicine.. American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference: definitions for sepsis and multiple organ failure and guidelines for the use of innovative therapies in sepsis. Chest 1992;101,1644-1655[CrossRef][ISI][Medline]
  17. Rubin, DB, Wiener-Kronish, JP, Murray, JF, et al Elevated von Willebrand factor antigen is an early phase predictor of acute lung injury in nonpulmonary sepsis syndrome. J Clin Invest 1990;86,474-480[ISI][Medline]
  18. Pingleton, SK, Fagon, JY, Leeper, KV, Jr Patient selection for clinical investigation of ventilator-associated pneumonia: criteria for evaluating diagnostic techniques. Chest 1992;102,553S-556S[ISI]
  19. Garner, JS, Jarvis, WR, Emori, TB, et al CDC definitions for nosocomial infections. Am J Infect Control 1988;16,128-140[CrossRef][ISI][Medline]
  20. Garnacho-Montero J, Garcia-Garmendia JL, Barrero-Almodovar AE, et al. Impact of the outcome of adequate empirical antibiotherapy in patients admitted to the ICU by sepsis. Crit Care Med (in press)
  21. Ibrahim, EH, Ward, S, Sherman, G, et al Experience with a clinical guideline for the treatment of ventilator-associated pneumonia. Crit Care Med 2001;29,1109-1115[CrossRef][ISI][Medline]
  22. Gruson, D, Hilbert, G, Vargas, F, et al Rotation and restricted use of antibiotics in a medical intensive care unit: impact on the incidence of ventilator-associated pneumonia caused by antibiotic-resistant Gram-negative bacteria. Am J Respir Crit Care Med 2000;162,837-843[Abstract/Free Full Text]
  23. SAS Institute.. SAS/STAT user’s guide 1990;vol 2,1071-1126 SAS Institute. Cary, NC:
  24. Concato, J, Feinstein, AR, Holford, TR The risk of determining risk with multivariable models. Ann Intern Med 1993;118,201-210[Abstract/Free Full Text]
  25. Bernard, GR, Vincent, JL, Laterre, PF, et al Efficacy and safety of recombinant human activated protein C for severe sepsis. N Engl J Med 2001;344,699-709[Abstract/Free Full Text]
  26. Niederman, MS Impact of antibiotic resistance on clinical outcomes and the cost of care. Crit Care Med 2001;29,N114-N120[CrossRef][ISI][Medline]
  27. Reid, KC, Grizzard, TA, Poland, GA Adult immunizations: recommendations for practice. Mayo Clin Proc 1999;74,377-384[ISI][Medline]
  28. Kollef, MH, Fraser, VJ Antibiotic resistance in the intensive care unit. Ann Intern Med 2001;134,298-314[Abstract/Free Full Text]
  29. Freudenberg, N, Silver, D, Carmona, JM, et al Health promotion in the city: a structured review of the literature on interventions to prevent heart disease, substance abuse, violence and HIV infection in US metropolitan areas, 1980–1995. J Urban Health 2000;77,443-457[CrossRef][ISI][Medline]
  30. Gonzales, R, Steiner, JF, Lum, A, et al Decreasing antibiotic use in ambulatory practice: impact of a multidimensional intervention on the treatment of uncomplicated acute bronchitis in adults. JAMA 1999;281,1512-1519[Abstract/Free Full Text]
  31. Nyquist, AC, Gonzales, R, Steiner, JF, et al Antibiotic prescribing for children with colds, upper respiratory tract infections, and bronchitis. JAMA 1998;279,875-877[Abstract/Free Full Text]
  32. Opstelten, W, Hak, E, Verheij, TJ, et al Introducing a pneumococcal vaccine to an existing influenza immunization program: vaccination rates and predictors of noncompliance. Am J Med 2001;111,474-479[CrossRef][ISI][Medline]
  33. Ostrowsky, BE, Trick, WE, Sohn, AH, et al Control of vancomycin-resistant enterococcus in health care facilities in a region. N Engl J Med 2001;344,1427-1433[Abstract/Free Full Text]
  34. Shinefield, H, Black, S, Fattom, A, et al Use of a Staphylococcus aureus conjugate vaccine in patients receiving hemodialysis. N Engl J Med 2002;346,491-496[Abstract/Free Full Text]
  35. Newton, T, Still, JM, Law, E A comparison of the effect of early insertion of standard latex and silver-impregnated latex Foley catheters on urinary tract infections in burn patients. Infect Control Hosp Epidemiol 2002;23,217-218[CrossRef][ISI][Medline]
  36. Rello, J, Lorente, C, Bodi, M, et al Why do physicians not follow evidence-based guidelines for preventing ventilator-associated pneumonia? A survey based on the opinions of an international panel of intensivists. Chest 2002;122,656-661[CrossRef][ISI][Medline]
  37. Fridkin, SK, Pear, SM, Williamson, TH, et al The role of understaffing in central venous catheter-associated bloodstream infections. Infect Control Hosp Epidemiol 1996;17,150-158[ISI][Medline]
  38. Needleman, J, Buerhaus, P, Mattke, S, et al Nurse-staffing levels and the quality of care in hospitals. N Engl J Med 2002;346,1715-1722[Abstract/Free Full Text]
  39. Rivers, E, Nguyen, B, Havstad, S, et al Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med 2001;345,1368-1377[Abstract/Free Full Text]
  40. Evans, TW Hemodynamic and metabolic therapy in critically ill patients. N Engl J Med 2001;345,1417-1418[Free Full Text]
  41. Girou, E, Stephan, F, Novara, A, et al Risk factors and outcome of nosocomial infections: results of a matched case-control study of ICU patients. Am J Respir Crit Care Med 1998;157,1151-1158[Abstract/Free Full Text]



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Chronic obstructive pulmonary disease and nosocomial infections
Prashant S Borade, et al.
Chest Online, 17 Feb 2005 [Full text]
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