Michael S. Niederman

Infectious Diseases Society of America/American Thoracic Society Consensus Guidelines on the Management of Community-Acquired Pneumonia in Adults

Lionel A. Mandell, Richard G. Wunderink, Antonio Anzueto, John G. Bartlett, G. Douglas Campbell, Nathan C. Dean, Scott F. Dowell, Thomas M. File, Jr. Daniel M. Musher, Michael S. Niederman, Antonio Torres, and Cynthia G. Whitney McMaster University Medical School, Hamilton, Ontario, Canada; Northwestern University Feinberg School of Medicine, Chicago, Illinois; University of Texas Health Science Center and South Texas Veterans Health Care System, San Antonio, and Michael E. DeBakey Veterans Affairs Medical Center and Baylor College of Medicine, Houston, Texas; Johns Hopkins University School of Medicine, Baltimore, Maryland; Division of Pulmonary, Critical Care, and Sleep Medicine, University of Mississippi School of Medicine, Jackson; Division of Pulmonary and Critical Care Medicine, LDS Hospital, and University of Utah, Salt Lake City, Utah; Centers for Disease Control and Prevention, Atlanta, Georgia; Northeastern Ohio Universities College of Medicine, Rootstown, and Summa Health System, Akron, Ohio; State University of New York at Stony Brook, Stony Brook, and Department of Medicine, Winthrop University Hospital, Mineola, New York; and Cap de Servei de Pneumologia i Allergia Respiratoria, Institut Clinic del Torax, Hospital Clinic de Barcelona, Facultat de Medicina, Universitat de Barcelona, Institut d’Investigacions Biomediques August Pi i Sunyer, CIBER CB06/06/0028, Barcelona, Spain.

Resolution of ventilator-associated pneumonia: prospective evaluation of the clinical pulmonary infection score as an early clinical predictor of outcome.

ObjectivesTo prospectively evaluate the performance of the Clinical Pulmonary Infection Score (CPIS) and its components to identify early in the hospital course of ventilator-associated pneumonia (VAP) which patients are responding to therapy. DesignProspective, multicenter, in a cohort of mechanically ventilated patients. SettingThe intensive care unit of six hospitals located in the metropolitan area of Buenos Aires, Argentina. PatientsSixty-three patients, from a cohort of 472 mechanically ventilated patients hospitalized for >72 hrs, had clinical evidence of VAP and bacteriologic confirmation by bronchoalveolar lavage (BAL) or blood cultures. InterventionsBronchoscopy with BAL fluid culture and blood cultures after establishing a clinical diagnosis of VAP. All patients received antibiotics, 46 before bronchoscopy and 17 immediately after bronchoscopy. Measurements and ResultsCPIS was measured at 3 days before VAP (VAP-3); at the onset of VAP (VAP); and at 3 (VAP+3), 5 (VAP+5), and 7 (VAP+7) days after onset. CPIS rose from VAP-3 to VAP and then fell progressively in the population as a whole (p < .001), and the fall in CPIS was significant in 31 survivors, but not in 32 nonsurvivors. From the individual components of the CPIS, only the Pao2/Fio2 ratio distinguished survivors from nonsurvivors, beginning at VAP+3. When CPIS was <6 at 3 or 5 days after VAP onset, mortality was lower than in the remaining patients (p = .018). These differences also related to the finding that those receiving adequate therapy had a slight fall in CPIS and a significant increase of Pao2/Fio2 at VAP+3, whereas those getting inadequate therapy did not. ConclusionsSerial measurements of CPIS can define the clinical course of VAP resolution, identifying those with good outcome as early as day 3, and could possibly be of help to define strategies to shorten the duration of therapy.

Survival in patients with nosocomial pneumonia: impact of the severity of illness and the etiologic agent.

OBJECTIVE To assess the impact of severity of illness at different times, using the Mortality Probability Models (MPM II), and the impact of etiologic agent on survival in patients with nosocomial pneumonia. DESIGN Retrospective, observational study. SETTING Fourteen-bed medical-surgical intensive care unit (ICU) in a teaching hospital. PATIENTS Sixty-two patients with nosocomial pneumonia who were receiving early appropriate antibiotic treatment. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Severity of illness at the time of admission to the ICU (M0), 24 hrs after admission (M24), and at the time of pneumonia diagnosis (M1) was determined using MPM II. Bacteriology was established by quantitative cultures from bronchoscopic samples. The outcome measure was the crude mortality rate. The crude mortality rate in the ICU was 59.7%, compared with average predicted mortality rates of 43.5% (M0), 36.4% (M24), and 52.2% (M1). We observed significant differences in mean MPM II determinations between survivors and nonsurvivors at M1 (39.3% vs. 60.9%, p = .001) but not at M0 and M24. In the univariate analysis, the variables most predictive of mortality were the presence of coma (p = .02), inotropic medication use (p = .001), and an MPM II determination of > 50% (p = .001) when pneumonia was diagnosed (M1). Multivariate analysis showed that, in the absence of Pseudomonas aeruginosa, an MPM II determination of > 50% at M1 was associated with a relative risk of death of 4.8. The presence of P. aeruginosa was associated with an increase in the risk of death of 2.6 and 6.36 in both populations with MPM II determinations at M1 of < or = 50% and > 50%, respectively. CONCLUSIONS Severity of illness when pneumonia is diagnosed is the most important predictor of survival, and this determination should be used for therapeutic and prognostic stratification. In addition, the presence of P. aeruginosa contributed to an excess of mortality that could not be measured by MPM II alone, suggesting the importance of the pathogen in prognosis.

Telavancin versus Vancomycin for Hospital-Acquired Pneumonia due to Gram-positive Pathogens

The results from two methodologically identical double-blind studies indicate that telavancin is noninferior to vancomycin based on clinical response in the treatment of hospital-acquired pneumonia due to Gram-positive pathogens.

Impact of antibiotic resistance on clinical outcomes and the cost of care

Antibiotic-resistant organisms are common in intensive care unit infection and can be either Gram-positive or Gram-negative. A number of studies have evaluated whether these organisms can lead to excess morbidity, mortality, or cost. In general, the studies are confounded by a number of methodologic issues, including the selection of an appropriate control population. Cases and controls must be appropriately matched for the presence of infection, the presence of infection with similar organisms (but ones that are either antibiotic-sensitive or -resistant), and severity of illness. In addition, studies must account for the therapies given to patients who are infected with resistant organisms because resistance is an important risk factor for inadequate empirical therapy, and such therapy is itself a potent determinant of a number of adverse outcomes, including mortality. To date, the data with methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococcus are inconsistent with regard to the effect on mortality rates, although infection with both organisms can lead to excess length of stay and increased cost of care. When studies have been adequately controlled and powered, infection with vancomycin-resistant enterococcus has had more of an effect on the mortality rate than infection with antibiotic-sensitive enterococci. Infection with resistant Gram-negatives also has adverse impact on outcome, with excess mortality being seen in patient groups infected with Acinetobacter and Pseudomonas aeruginosa. If we are to minimize the effect of resistance on medical outcomes and cost, it will be necessary to have a current knowledge of each intensive care unit’s pathogens and susceptibility patterns, so that empirical therapy will have a good likelihood of being effective. In addition, new therapeutic agents may improve on the efficacy of older agents and could reduce cost if they allow for some patients to leave the hospital and to finish therapy with an oral formulation of a highly bioavailable agent.

Healthcare-associated pneumonia is a heterogeneous disease, and all patients do not need the same broad-spectrum antibiotic therapy as complex nosocomial pneumonia.

Purpose of review Healthcare-associated pneumonia (HCAP) develops in patients who have recently had contact with nosocomial and drug-resistant pathogens, because of a history of hospitalization in the past 90 days, need for hemodialysis or home wound care, or residence in a nursing home. HCAP was included in the 2005 American Thoracic Society/Infectious Diseases Society of America guidelines for nosocomial pneumonia, with the recommendation that all such patients receive empiric therapy with a multidrug regimen directed against drug-resistant organisms. The purpose of this review was to examine articles published since the guidelines were developed to see whether this therapy recommendation is correct. Methods All articles published since July 2004 were identified using PubMed and the key words HCAP, nursing home-acquired pneumonia, and antibiotic therapy. The search was limited to adults, with a focus on clinical trials, reviews, meta-analyses, or practice guidelines. Recent findings We identified eight unique studies of HCAP, which were either prospective or retrospective series, with bacteriologic data on both Gram-negative and Gram-positive organisms. We also examined three prospective, randomized therapy trials of nursing home-acquired pneumonia that included limited bacteriologic data. We found that patients with HCAP were a heterogeneous group, with some at risk for multidrug-resistant organisms, and others not, and this accounted for the observation that many patients were successfully treated with monotherapy regimens or with regimens used for patients with community-acquired pneumonia. Patients at risk for multidrug-resistant pathogens were those with severe illness or those with other risk factors including: hospitalization in the past 90 days, antibiotic therapy in the past 6 months, poor functional status as defined by activities of daily living score, and immune suppression. Conclusion On the basis of the risk factors identified in recent studies, we developed an algorithm for empiric therapy of HCAP, which suggests that not all such patients require a broad-spectrum multidrug regimen in order to achieve appropriate and effective therapy. This algorithm needs validation in future studies.

Markers of treatment failure in hospitalised community acquired pneumonia

Background: Lack of response to treatment in community acquired pneumonia (CAP) worsens outcome. We evaluated the systemic cytokine profile (tumour necrosis factor α, interleukin (IL)1, IL6, IL8 and IL10), C reactive protein (CRP) and procalcitonin (PCT) in patients with CAP who had treatment failure. Methods: A prospective study was performed in hospitalised patients with CAP. Cytokines, PCT and CRP measurements were obtained on day 1 and after 72 h of treatment. Treatment failure was the endpoint evaluated, with separation of those with early (⩽72 h) or late failure. Results: 453 patients were included: 84 (18%) had treatment failure, of whom 38 (8%) were early failures. Median levels of IL6, PCT and CRP on days 1 and 3 and median levels of IL8 on day 1 were significantly higher in patients with any treatment failure. Logistic regression analysis demonstrated that values above the cut-off points for IL6 (⩾169 pg/ml), IL8 (⩾14 pg/ml) and CRP (⩾21.9 mg/dl) on day 1 had independent predictive value for any treatment failure after adjustment for initial severity; relative risks (OR) found were 1.9, 2.2 and 2.6, respectively. Increased levels for CRP and PCT on day 1 were also independent predictors for early failure. Increased levels for IL6 and CRP were the best predictors of late failure. Conclusions: Serum levels of CRP, IL6 and PCT on days 1 and 3 were independently associated with a higher risk of any treatment failure. Low levels of PCT and CRP on day 1 had a high negative predictive value for early failure.

Nutritional Status and Bacterial Binding in the Lower Respiratory Tract in Patients with Chronic Tracheostomy

Patients with chronic tracheostomy often develop tracheobronchial colonization with enteric gram-negative bacilli, especially Pseudomonas aeruginosa, but pathogenic mechanisms are largely unknown. To examine this problem, we measured in-vitro bacterial adherence to airway epithelial cells from the tracheal surfaces of 15 patients with chronic tracheostomy and 18 healthy, noncolonized controls without tracheostomy. Patients with tracheostomy had more tracheal cell adherence (7.3 +/- 0.4 [SE] bacteria/cell) than controls (4.8 +/- 0.7 bacteria/cell; p = 0.008), but patients colonized by Pseudomonas species had even more binding (9.0 +/- 0.06 bacteria/cell) than those without this finding (5.8 +/- 0.8 bacteria/cell; p = 0.008). Differences between patients in lower airway cell binding of bacteria were largely related to a multifactorial assessment of patient nutritional status, the prognostic nutritional index (r = 0.67, p = 0.005). Thus, nutritional status may account in part for the common problem of tracheobronchial colonization with gram-negative bacteria in patients with chronic tracheostomy.

Health Care—Associated Pneumonia (HCAP): A Critical Appraisal to Improve Identification, Management, and Outcomes—Proceedings of the HCAP Summit

Increasingly, patients are receiving treatment at facilities other than hospitals, including long-term-health care facilities, assisted-living environments, rehabilitation facilities, and dialysis centers. As with hospital environments, nonhospital settings present their own unique risks of pneumonia. Traditionally, pneumonia in these facilities has been categorized as community-acquired pneumonia (CAP). However, the new designation for pneumonias acquired in these settings is health care-associated pneumonia (HCAP), which covers pneumonias acquired in health care environments outside of the traditional hospital setting and excludes hospital-acquired pneumonia (HAP), ventilator-associated pneumonia (VAP), and CAP. Although HCAP is currently treated with the same protocols as CAP, recent evidence indicates that HCAP differs from CAP with respect to pathogens and prognosis and, in fact, more closely resembles HAP and VAP. The HCAP Summit convened national infectious disease opinion leaders for the purpose of analyzing current literature, clinical trial data, diagnostic considerations, therapeutic options, and treatment guidelines related to HCAP. After an in-depth analysis of these areas, the infectious disease investigators participating in the summit were surveyed with regard to 10 clinical practice statements. The results were then compared with results of the same survey as completed by 744 Infectious Diseases Society of America members. The similarities and differences between those survey results are the basis of this publication.

Appropriate use of antimicrobial agents: Challenges and strategies for improvement

The use of inadequate empirical antimicrobial therapy is common in intensive care unit patients and contributes to a number of poor outcomes. Selecting appropriate antimicrobial therapy is complicated by many factors, including the large number of agents available, the presence of resistant organisms, and the general desire among practitioners to use the most focused therapy available. An important aspect of appropriate antimicrobial use is prompt initiation of adequate empirical therapy, which has been shown to improve mortality rates in hospitalized patients with pneumonia and other serious infections. Other key strategies include streamlining antimicrobial therapy when a pathogen is identified and switching from intravenous to oral therapy when clinically indicated. In addition, antibiotic rotation (or cycling) has been evaluated in several trials as a means to minimize resistance. Promoting appropriate antimicrobial therapy ultimately will require a multidisciplinary, system-oriented, institution-specific approach because each intensive care unit has its own unique flora and antimicrobial resistance patterns.