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Background Community-acquired pneumonia (CAP) guidelines have improved the treatment and outcomes of patients with CAP, primarily by standardization of initial empirical therapy. But current society-published guidelines exclude immunocompromised patients. Research Question There is no consensus regarding the initial treatment of immunocompromised patients with suspected CAP. Study Design and Methods This consensus document was created by a multidisciplinary panel of 45 physicians with experience in the treatment of CAP in immunocompromised patients. The Delphi survey methodology was used to reach consensus. Results The panel focused on 21 questions addressing initial management strategies. The panel achieved consensus in defining the population, site of care, likely pathogens, microbiologic workup, general principles of empirical therapy, and empirical therapy for specific pathogens. Interpretation This document offers general suggestions for the initial treatment of the immunocompromised patient who arrives at the hospital with pneumonia.

Background In Japan, the routine use of early antiviral therapy for patients with influenza is standard. Methods This multicenter prospective cohort evaluation of hospitalized patients with laboratory-confirmed influenza identified prognostic factors among the patients receiving antiviral therapy. Results Of 1,345 patients with influenza (766 pediatric, 579 adult), excluding those aged Streptococcus pneumoniae (12.3%); Staphylococcus aureus (10.9%), including methicillin-resistant S aureus (MRSA) 3.3%; Enterobacteriaceae (8.1%); and Pseudomonas aeruginosa (3.3%). Of the adult patients, 151 were classified as having community-acquired pneumonia (CAP) and 60 as having health-care-associated pneumonia (HCAP). Inappropriate therapy was more common in HCAP than in CAP (15.2% vs 2%, P = .001). Potential multidrug-resistant (MDR) pathogens were more common (21.7% vs 2.6%, P P = .002) and P aeruginosa (8.3% vs 1.3%, P = .021). Using Cox proportional hazards modeling with prescribed independent variables, male sex, severity score, serum albumin levels (malnutrition), and pneumonia were associated with survival 30 days from the onset of influenza. Conclusions Among the prognostic factors, malnutrition and pneumonia are amenable to medical intervention. An opportunity exists to improve empirical therapy for patients with HCAP and influenza. Trial Registry Japan Medical Association Center for Clinical Trials; No.: JMA-IIA00123; URL: http://www.jmacct.med.or.jp/en/

Pneumonia is a major cause of morbidity and mortality among nursing home residents. The approach to managing these patients has lacked uniformity because of the paucity of clinical trials, complexity of underlying comorbid diseases, and heterogeneity of administrative structures. The decision to hospitalize nursing home patients with pneumonia varies among institutions depending on staffing level, availability of diagnostic testing, and laboratory support. In the absence of comparative studies, choice of empirical antibiotic therapy continues to be based on expert opinion. Validated prognostic scoring models are needed for risk stratification. Pneumococcal and influenza vaccination are the primary prevention measures. As of January 2010, Medicare no longer pays for consultation codes; thus, practitioners must instead use existing evaluation and management service codes when providing these services.

Background Community-acquired pneumonia (CAP) with a pneumonia severity index (PSI) score in risk class V (PSI-V) is a potentially life-threatening condition, yet the majority of patients are not admitted to the ICU. The aim of this study was to characterize CAP patients in PSI-V to determine the risk factors for ICU admission and mortality, and to assess the performance of CAP severity scores in this population. Methods Prospective observational study including hospitalized adults with CAP in PSI-V from 1996 to 2003. Clinical and laboratory data, microbiological findings, and outcomes were recorded. The PSI score; modified American Thoracic Society (ATS) score; the confusion, urea, respiratory rate, low BP (CURB) score, and CURB plus age of ≥ 65 years score were calculated. A reduced score based on the acute illness variables contained in the PSI was also obtained. Results A total of 457 patients were included in the study (mean [± SD] age, 79 ± 11 years), of whom 92 (20%) were admitted to the ICU. Patients in the ward were older (mean age, 82 ± 10 vs 70 ± 10 years, respectively) and had more comorbidities. ICU patients experienced significantly more acute organ failures. The mortality rate was higher in ICU patients, but also was high for non-ICU patients (37% vs 20%, respectively; p=0,003). A low level of consciousness (odds ratio [OR], 3.95; 95% confidence interval [CI], 2 to 5) and shock (OR, 24.7; 95% CI, 14 to 44) were associated with a higher risk of death. The modified ATS severity rule had the best accuracy in predicting ICU admission and mortality. Conclusions Most CAP patients PSI-V were treated on a hospital ward. Those admitted to the ICU were younger and had findings of more acute illness. The PSI performed well as a mortality prediction tool but was less appropriate for guiding site-of-care decisions.

Background and study objectives: The range and relative impact of microbial pathogens, particularly viral pathogens, as a cause of community-acquired pneumonia (CAP) in hospitalized adults has not received much attention. The aim of this study was to determine the microbial etiology of CAP in adults and to identify the risk factors for various specific pathogens. Methods: We prospectively studied 176 patients (mean [± SD] age, 65.8 ± 18.5 years) who had hospitalized for CAP to identify the microbial etiology. For each patient, sputum and blood cultures were obtained as well as serology testing for Mycoplasma pneumoniae and Chlamydophila pneumoniae , urinary antigen testing for Legionella pneumophila and Streptococcus pneumoniae , and a nasopharyngeal swab for seven respiratory viruses. Results: Microbial etiology was determined in 98 patients (55%). S pneumoniae (49 of 98 patients; 50%) and respiratory viruses (32%) were the most frequently isolated pathogen groups. Pneumococcal pneumonia was associated with tobacco smoking of > 10 pack-years (odds ratio [OR], 2.6; 95% confidence interval [CI], 1.2 to 5.4; p = 0.01). Respiratory viruses were isolated more often in fall or winter (28%; p = 0.011), and as an exclusive etiology tended to be isolated in patients ≥ 65 years of age (20%; p = 0.07). Viral CAP was associated with antimicrobial therapy prior to hospital admission (OR, 4.5; 95% CI, 1.4 to 14.6). Conclusions: S pneumoniae remains the most frequent pathogen in adults with CAP and should be covered with empirical antimicrobial treatment. Viruses were the second most common etiologic agent and should be tested for, especially in fall or winter, both in young and elderly patients who are hospitalized with CAP.

Acute upper viral respiratory infection (VRI) is the number one cause of illness for which patients seek medical care in the United States. Rhinoviruses, members of the family Picornaviridae, are the causative pathogens in more than half of VRIs, and they are associated with acute exacerbations of respiratory disease, including asthma, sinusitis, otitis media, and COPD. Owing to the lack of commercial availability of rapid and cost-effective laboratory tests to confirm the presence of VRI, the diagnosis is most commonly made empirically, based on patient history and physical examination. Currently, no antiviral agents that are active against picornaviruses are available for clinical use. Antimicrobial agents, frequently prescribed for VRIs, are not active against viruses, and their inappropriate and widespread use has contributed to an increase in antimicrobial resistance among bacteria commonly involved in respiratory tract infections. Several newer antiviral agents are being evaluated for treatment of VRIs. Although a variety of mechanisms and agents have been tested, few have shown significant clinical benefit in human trials. The most advanced antiviral agent in clinical trials is pleconaril, a novel viral capsid–binding inhibitor with potent and highly specific in vitro activity against the majority of serotypes of rhinoviruses and enteroviruses. Clinical trials of pleconaril for the treatment of VRIs have been conducted, and the role of pleconaril in patients with chronic lung disease is being evaluated.

Nosocomial pneumonia is the second most frequent nosocomial infection and represents the leading cause of death from infections that are acquired in the hospital. In the last decade, a large body of data has accumulated that points to the substantial impact of inadequate antibiotic treatment as a major risk factor for infection-attributed mortality in ventilator-associated pneumonia (VAP) patients. In most instances, high-risk pathogens (eg, highly resistant Gram-negative bacilli, such as Pseudomonas aeruginosa and Acinetobacter spp, as well as methicillin-resistant staphylococci) are the predominant microorganisms causing excess mortality. Among various risk factors for mortality from VAP, which include the severity of the underlying disease and the degree of functional physiologic impairment caused by the pulmonary infectious process, only inappropriate antibiotic therapy is directly amenable to modification by clinicians. Secondary modifications of an initially failing antibiotic regimen do not substantially improve the outcome for these critically ill patients. Therefore, the best approach for reducing infection-related mortality seems to be the initial institution of an adequate and broad-spectrum antibiotic regimen in severely ill patients, which should be modified in a de-escalating strategy when the results from microbiologic testing become available. To circumvent the inherent danger of the emergence of resistance in ICU patients, additional measures have to be implemented and tested in clinical trials to reduce antibiotic consumption, shorten the duration of antibiotic treatment, and reduce the selection pressure on the ICU flora. This latter goal could be met by new antibiotic strategies including scheduled changes of recommended empiric antibiotic regimens at fixed intervals on a rotating basis.

Study objective: To conduct a cost-effectiveness analysis of IV-to-oral regimens of azithromycin vs cefuroxime with or without erythromycin in the treatment of patients hospitalized with community-acquired pneumonia (CAP). Patients: Of the 268 evaluable patients enrolled into a randomized, multicenter clinical trial of adults, 266 patients had sufficient data to be included in this cost-effectiveness analysis. One hundred thirty-six patients received azithromycin, and 130 patients received cefuroxime with or without erythromycin. Methods: A pharmacoeconomic analysis from the hospital provider perspective was conducted. Health-care resource utilization was extracted from the clinical database and converted to national reference costs. Decision analysis was used to structure and characterize outcomes. Sensitivity analyses were performed, and statistics were applied to the cost-effectiveness ratios. Results: The clinical success and adverse event rates and antibiotic-related length of stay were 78%, 11.8%, and 5.8 days for the azithromycin group and 75%, 20.7%, and 6.4 days for the group receiving cefuroxime with or without erythromycin, respectively. Geometric mean treatment costs were $4,104 (95% confidence interval [CI], $3,874 to $4,334) for the azithromycin group, and $4,578 (95% CI, $4,319 to $4,837) for the group receiving cefuroxime with or without erythromycin (p 0.06). The cost-effectiveness ratios were $5,265 per expected cure for the azithromycin group, and $6,145 per expected cure for group receiving cefuroxime with or without erythromycin (p 0.05). Conclusions: Despite a higher per-dose purchase price, overall costs with azithromycin tended to be lower due to decreased duration of therapy, lower preparation and administration costs, and reduced hospital length of stay. As empiric therapy, azithromycin monotherapy was cost-effective compared to cefuroxime with or without erythromycin for patients hospitalized with CAP who have no underlying cardiopulmonary disease, and no risk factors for either drug-resistant pneumococci or enteric Gram-negative pathogens. (CHEST 2002; 122:1271–1279)

Study objectives We evaluated the role of sputum examination in the management of patients with community-acquired pneumonia (CAP) in a primary-care hospital without microbiologic laboratory facilities. Design and interventions A diagnostic strategy using regular collection of sputum samples, Gram staining in a local laboratory, and mailing of samples to a commercial laboratory for culture analysis. Setting A 200-bed primary-care hospital without subspeciality physicians. Patients One hundred sixteen consecutive patients with a diagnosis of CAP were prospectively evaluated during a 12-month period. Results Of 116 patients, 42 patients (36%) were capable of producing a sputum sample. Age ≥ 75 years (odds ratio [OR], 0.4; 95% confidence interval [CI], 0.18 to 0.93) and prior ambulatory antimicrobial treatment (OR, 3.2; 95% CI, 1.2 to 8.4) were independent predictors of sputum production. A delay in collection and processing of sputum samples of > 24 h was present in 31% and 39%, respectively. A delay in collection yielded an increased number of Gram-negative enteric bacilli and nonfermenters (44% vs 7%, p = 0.056). A delay in processing was associated with an increased number of Candida spp isolates (33% vs 9%, p = 0.16). The overall diagnostic yield was low (10 of 116 patients, 9%) due to a limited number of valid samples (n = 23 of 42 patients, 55%) and a limited number of definitely or probably positive samples on Gram's stain and culture (n = 10 of 42 patients, 24%). Prior ambulatory antimicrobial treatment was associated with a reduction in diagnostic yield (14% vs 56%, p = 0.09). The impact of diagnostic results on antimicrobial treatment decisions was minimal, with antimicrobial treatment directed to diagnostic results in only one patient. Conclusions We conclude that in this setting representative of primary-care hospitals in Germany, sputum had a low diagnostic yield and did not contribute significantly to patient management.

In Japan, the routine use of early antiviral therapy for patients with influenza is standard.This multicenter prospective cohort evaluation of hospitalized patients with laboratory-confirmed influenza identified prognostic factors among the patients receiving antiviral therapy.Of 1,345 patients with influenza (766 pediatric, 579 adult), excluding those aged1 year (who are not approved for antiviral therapy), 97.7% (1,224 of 1,253) received antiviral therapy. Among the adult patients, 24 (4.1%) died within 30 days, whereas none of the pediatric patients died. Five hundred twenty-eight (91.2%) adult patients had influenza A, 509 (87.9%) had a chronic underlying illness, and 211 (36.4%) had radiographically confirmed pneumonia. Twenty of the 24 patients who died had pneumonia of the following etiologies: Streptococcus pneumoniae (12.3%); Staphylococcus aureus (10.9%), including methicillin-resistant S aureus (MRSA) 3.3%; Enterobacteriaceae (8.1%); and Pseudomonas aeruginosa (3.3%). Of the adult patients, 151 were classified as having community-acquired pneumonia (CAP) and 60 as having health-care-associated pneumonia (HCAP). Inappropriate therapy was more common in HCAP than in CAP (15.2% vs 2%, P = .001). Potential multidrug-resistant (MDR) pathogens were more common (21.7% vs 2.6%, P.001) in patients with HCAP, particularly MRSA (10% vs 0.7%, P = .002) and P aeruginosa (8.3% vs 1.3%, P = .021). Using Cox proportional hazards modeling with prescribed independent variables, male sex, severity score, serum albumin levels (malnutrition), and pneumonia were associated with survival 30 days from the onset of influenza.Among the prognostic factors, malnutrition and pneumonia are amenable to medical intervention. An opportunity exists to improve empirical therapy for patients with HCAP and influenza.Japan Medical Association Center for Clinical Trials; No.: JMA-IIA00123; URL: http://www.jmacct.med.or.jp/en/.

Study objective: To determine the cost-effectiveness of sequential IV to oral gatifloxacin therapy vs IV ceftriaxone with or without IV erythromycin to oral clarithromycin therapy to treat community-acquired pneumonia (CAP) patients requiring hospitalization. Patients: Two hundred eighty-three patients enrolled in a randomized, double-blind, clinical trial were eligible for inclusion in the cost-effectiveness analysis. Methods: Data collected included patient demographics, clinical and microbiological outcomes, length of stay (LOS), and antibiotic-related LOS (LOSAR). Costs evaluated include drug acquisition (level 1); plus costs of preparation, dispensing, and administration, treating adverse events, and clinical failures (level 2); plus hospital per diem costs (level 3). Robustness of economic findings was tested using sensitivity analyses. Results: Two hundred three patients were clinically and economically evaluable (98 receiving gatifloxacin and 105 receiving ceftriaxone). IV erythromycin was administered to 35 patients in the ceftriaxone-treated group. Oral conversion was achieved in 98% of patients in each group. Clinical cure and microbiological eradication rates did not differ statistically (98% and 97% with gatifloxacin vs 92% and 92% with ceftriaxone, respectively). Overall, neither geometric mean LOS nor LOSAR differed significantly (4.2 days and 4.1 days with gatifloxacin vs 4.9 days and 4.9 days with ceftriaxone, respectively). Treatment failures in the ceftriaxone group contributed to a mean incremental increase in LOSAR of 1.09 days and increased mean cost per patient. The geometric mean costs per patient (level 3) were $5,109 for gatifloxacin and $6,164 for ceftriaxone (p = 0.011). The cost-effectiveness ratios (mean cost per expected success) were $5,236:1 and $7,047:1 for gatifloxacin and ceftriaxone, respectively. Conclusions: Gatifloxacin monotherapy for CAP patients requiring hospitalization is clinically effective and provides an economic advantage compared to the regimen of ceftriaxone with or without erythromycin IV with a switch to oral clarithromycin.

Use of nucleic acid amplification techniques has increased the identification of respiratory viruses (RVs) in adult patients with community-acquired pneumonia (CAP). The objectives of the present study were to identify RV in patients with CAP using three different sampling methods and to compare CAP virus proportions and types with two comparison groups.The study population included 183 adult patients with CAP, 450 control subjects, and 201 patients with nonpneumonic lower respiratory tract infection (NPLRTI). Each participant was sampled by oropharyngeal swab, nasopharyngeal swab, and nasopharyngeal washing, and the samples were tested for detection of 12 RVs by multiplex TaqMan Hydrolysis probe-based real-time polymerase chain reaction (Integrated DNA Technology; Coralville, IA).At least one RV was identified in 58 patients with CAP (31.7%) compared with 32 (7.1%) in control subjects and 104 (51.7%) in patients with NPLRTI (P.01 and P.01, respectively). Coronaviruses were identified in 24 (13.1%) patients with CAP, compared with 17 (3.8%) in control subjects, and 21 (10.4%) patients with NPLRTI. Respiratory syncytial virus was identified in 13 (7.1%), four (0.9%), and seven (3.5%); rhinovirus in nine (4.9%), nine (2.0%), and 15 (7.5%); and influenza virus in eight (4.4%), two (0.4%), and 63 (31.3%) patients with CAP, control subjects, and patients with NPLRTI, respectively.The proportion of RV involvement in CAP is higher than previously reported. The proportion of RV identified in healthy subjects is significantly lower than in CAP, but it is not zero and should be weighed when interpreting corresponding proportions among patients.

The role of infection in exacerbations of COPD remains controversial and incompletely understood. Although some investigators believe that bacteria are not important for patients with exacerbation, we disagree and believe that patients with at least two of the three cardinal symptoms of exacerbation should receive antibiotic therapy. With an open-minded view of the area, we review the data, showing that bacteriologic studies, pathologic investigations, and clinical trials all support roles for bacteria and antibiotic therapy in this disease. Still, many questions remain, and future studies will be needed to better define the mechanisms of bacterial invasion in the bronchitic patient and to develop effective vaccines to prevent exacerbations. In the meantime, we must rely on antibiotic therapy, and we will need prospective studies to corroborate preliminary findings showing that different patients may require different therapies; thus, patient subsetting may be vital in the selection of antibiotic therapy for exacerbations of COPD.

F ew investigators have studied the role of bronchoscopy in evaluating and managing patients with nosocomial pneumonia who are not responding to initial antibiotic therapy. This discussion examines whether the information provided by bronchoscopy has value in this setting, as well as whether the concept of using bronchoscopy for the nonresponding patient is a logical one. Importantly, serial bronchoscopy is generally performed while the patient is receiving antibiotic therapy. Such therapy can reduce the yield and accuracy of quantitative cultures of respiratory secretions. The presumption for using serial cultures in the nonresponding patient is that bacteria are present that have not been eliminated by currently administered antibiotics. Moreover, these organisms can be identified early enough so that changes in therapy will improve the outcome in these patients.

Objectives To determine the effect of age, severity of lung disease, severity and frequency of exacerbation, steroid use, choice of an antibiotic, and the presence of comorbidity on the outcome of treatment for an acute exacerbation of COPD. Design A retrospective chart analysis over 24 months. Setting A university Veterans Affairs medical center. Patients Outpatients with COPD who were treated with an antibiotic over a period of 24 months for an acute exacerbation of COPD. Methods Severity of an acute exacerbation of COPD was defined using the criteria of Anthonisen et al: increased dyspnea, increased sputum volume, and increased sputum purulence. Severity of lung disease was stratified based on FEV 1 percent predicted using American Thoracic Society guidelines (stage I, FEV 1 ≥ 50%; stage II, FEV 1 35 to 49%; stage III, FEV 1 Results One-hundred seven patients with COPD (mean age ± SD, 66.9 ± 9.5 years) experienced 232 exacerbations over 24 months. First-line antibiotics (trimethoprim-sulfamethoxazole, ampicillin/amoxicillin, and erythromycin) were used to treat 78% of all exacerbations. Treatment failure was noted in 12.1% of first exacerbations and 14.7% of all exacerbations, with more than half the failures requiring hospitalization. Host factors that were independently associated with treatment failure included the following: FEV 1 Conclusion The results of our study suggest that patient host factors and not antibiotic choice may determine treatment outcome. Prospective studies in appropriately stratified patients are needed to validate these findings.

Study objective In patients with severe COPD, acute infective exacerbations are frequent. Streptococcus pneumoniae and Haemophilus influenzae are the most commonly isolated bacteria in sputum cultures from these patients. We hypothesized that in patients with advanced disease, Gram-negative bacteria other than H influenzae play at least an equally important role. Methods We evaluated clinical data and sputum culture results from 211 unselected COPD patients admitted to our hospital with an acute infective exacerbation of COPD. One hundred twelve patients fulfilled our protocol criteria of reliable microbiologic results and reproducible lung function tests; the patients were categorized according to the recently published three stages of severity. Results Lung function tests revealed an FEV 1 of ≥50% of the predicted value in 30 patients (stage I), an FEV 1 of 35% to 1 of ≤35% of the predicted value in 34 patients (stage III). Bacteria were classified into three groups: group 1 contained S pneumoniae and other Gram-positive cocci; group 2, H influenzae and Moraxella catarrhalis ; and group 3, Enterobacteriaceae and Pseudomonas spp. For all patients together, the most frequently isolated bacteria were group 3 organisms (Enterobacteriaceae and Pseudomonas spp, 48.2%), followed by group 1 organisms (S pneumoniae and other Gram-positive cocci, 30.4%), and group 2 organisms ( H influenzae and M catarrhalis , 21.4%). In stage I patients, 14 of 30 had bacteria from group 1, seven of 30 had group 2, and nine of 30 had group 3. In stage II patients, eight of 30 had group 1 bacteria, 10 of 30 had group 2, and 12 of 30 had group 3. In stage III patients, 12 of 52 had group 1 bacteria, seven of 52 had group 2, and 22 of 52 had group 3. The three groups of bacteria causing infective exacerbations were unevenly distributed among the three severity stages of lung function (p=0.016). Conclusion There is a correlation between deterioration of lung function and the bacteria isolated from patients with infective exacerbations of COPD. In acute infective exacerbations, Enterobacteriaceae and Pseudomonas spp are the predominant bacteria in patients with an FEV 1

We evaluated the conditions of 33 patients who completed an outpatient pulmonary rehabilitation program to determine what types of improvements occurred, and whether these changes were related to the baseline degree of ventilatory impairment, to determine whether rehabilitation was beneficial to patients, regardless of the degree of underlying lung dysfunction. Endurance measurements, including sustained submaximal performance on a cycle ergometer and the 12-minute walk distance (1,349 +/- 625 feet to 1,700 +/- 670 feet) increased significantly (p less than 0.01), as did multiple educational and subjective parameters. Maximal exercise performance on a graded cycle test improved very little, with a decline in the ventilatory equivalent for oxygen consumption (VE/VO2) being the only significant change (48.2 +/- 28.3 L/ml to 36.6 +/- 8.7 L/ml). Of the observed changes, only one endurance measurement, the sustained submaximal exercise performance, correlated with FEV1 (r = 0.5, p less than 0.01), but only if it was expressed as an absolute number (liters) and not as percent predicted. Lung function did not correlate with changes in the 12-minute walk distance, in maximal exercise performance on the cycle ergometer or with changes in educational and subjective parameters. We conclude that because the magnitude of change in both physiologic and psychologic parameters was not directly related to lung function, the benefits of rehabilitation can extend to all patients with chronic lung disease, regardless of the severity of preexisting pulmonary dysfunction.

1990;97;170-181 Chest M S Niederman, D E Craven, A M Fein and D E Schultz Pneumonia in the critically ill hospitalized patient. http://chestjournal.chestpubs.org/content/97/1/170.citation can be found online on the World Wide Web at: The online version of this article, along with updated information and services ) ISSN:0012-3692 http://chestjournal.chestpubs.org/site/misc/reprints.xhtml ( without the prior written permission of the copyright holder. reserved. No part of this article or PDF may be reproduced or distributed Chest Physicians, 3300 Dundee Road, Northbrook, IL 60062. All rights of been published monthly since 1935. Copyright1990by the American College is the official journal of the American College of Chest Physicians. It has Chest

Community-acquired pneumonia (CAP) with a pneumonia severity index (PSI) score in risk class V (PSI-V) is a potentially life-threatening condition, yet the majority of patients are not admitted to the ICU. The aim of this study was to characterize CAP patients in PSI-V to determine the risk factors for ICU admission and mortality, and to assess the performance of CAP severity scores in this population.Prospective observational study including hospitalized adults with CAP in PSI-V from 1996 to 2003. Clinical and laboratory data, microbiological findings, and outcomes were recorded. The PSI score; modified American Thoracic Society (ATS) score; the confusion, urea, respiratory rate, low BP (CURB) score, and CURB plus age of/= 65 years score were calculated. A reduced score based on the acute illness variables contained in the PSI was also obtained.A total of 457 patients were included in the study (mean [+/- SD] age, 79 +/- 11 years), of whom 92 (20%) were admitted to the ICU. Patients in the ward were older (mean age, 82 +/- 10 vs 70 +/- 10 years, respectively) and had more comorbidities. ICU patients experienced significantly more acute organ failures. The mortality rate was higher in ICU patients, but also was high for non-ICU patients (37% vs 20%, respectively; p = 0,003). A low level of consciousness (odds ratio [OR], 3.95; 95% confidence interval [CI], 2 to 5) and shock (OR, 24.7; 95% CI, 14 to 44) were associated with a higher risk of death. The modified ATS severity rule had the best accuracy in predicting ICU admission and mortality.Most CAP patients PSI-V were treated on a hospital ward. Those admitted to the ICU were younger and had findings of more acute illness. The PSI performed well as a mortality prediction tool but was less appropriate for guiding site-of-care decisions.

Study objectives To evaluate clinical characteristics and treatment patterns among patients with ventilator-associated pneumonia (VAP), including the implementation of and outcomes associated with deescalation therapy. Design Prospective, observational, cohort study. Setting Twenty ICUs throughout the United States. Patients A total of 398 ICU patients meeting predefined criteria for suspected VAP. Interventions Prospective, handheld, computer-based data collection regarding routine VAP management according to local institutional practices, including clinical and microbiological characteristics, treatment patterns, and outcomes. Measurements and results The most frequent ICU admission diagnoses in patients with VAP were postoperative care (15.6%), neurologic conditions (13.3%), sepsis (13.1%), and cardiac complications (10.8%). The mean (± SD) duration of mechanical ventilation prior to VAP diagnosis was 7.3 ± 6.9 days. Major pathogens were identified in 197 patients (49.5%) through either tracheal aspirate or BAL fluid and included primarily methicillin-resistant Staphylococcus aureus (14.8%), Pseudomonas aeruginosa (14.3%), and other Staphylococcus species (8.8%). More than 100 different antibiotic regimens were prescribed as initial VAP treatment, the majority of which included cefepime (30.4%) or a ureidopenicillin/monobactam combination (27.9%). The mean duration of therapy was 11.8 ± 5.9 days. In the majority of cases (61.6%), therapy was neither escalated nor deescalated. Escalation of therapy occurred in 15.3% of cases, and deescalation occurred in 22.1%. The overall mortality rate was 25.1%, with a mean time to death of 16.2 days (range, 0 to 49 days). The mortality rate was significantly lower among patients in whom therapy was deescalated (17.0%), compared with those experiencing therapy escalation (42.6%) and those in whom therapy was neither escalated nor deescalated (23.7%; χ 2 = 13.25; p = 0.001). Conclusions Treatment patterns for VAP vary widely from institution to institution, and the overall mortality rate remains unacceptably high. The deescalation of therapy in VAP patients appears to be associated with a reduction in mortality, which is an association that warrants further clinical study.

Nosocomial pneumonia is the second most frequent nosocomial infection and represents the leading cause of death from infections that are acquired in the hospital. In the last decade, a large body of data has accumulated that points to the substantial impact of inadequate antibiotic treatment as a major risk factor for infection-attributed mortality in ventilator-associated pneumonia (VAP) patients. In most instances, high-risk pathogens (eg, highly resistant Gram-negative bacilli, such as Pseudomonas aeruginosa and Acinetobacter spp, as well as methicillin-resistant staphylococci) are the predominant microorganisms causing excess mortality. Among various risk factors for mortality from VAP, which include the severity of the underlying disease and the degree of functional physiologic impairment caused by the pulmonary infectious process, only inappropriate antibiotic therapy is directly amenable to modification by clinicians. Secondary modifications of an initially failing antibiotic regimen do not substantially improve the outcome for these critically ill patients. Therefore, the best approach for reducing infection-related mortality seems to be the initial institution of an adequate and broad-spectrum antibiotic regimen in severely ill patients, which should be modified in a de-escalating strategy when the results from microbiologic testing become available. To circumvent the inherent danger of the emergence of resistance in ICU patients, additional measures have to be implemented and tested in clinical trials to reduce antibiotic consumption, shorten the duration of antibiotic treatment, and reduce the selection pressure on the ICU flora. This latter goal could be met by new antibiotic strategies including scheduled changes of recommended empiric antibiotic regimens at fixed intervals on a rotating basis.

To conduct a cost-effectiveness analysis of IV-to-oral regimens of azithromycin vs cefuroxime with or without erythromycin in the treatment of patients hospitalized with community-acquired pneumonia (CAP).Of the 268 evaluable patients enrolled into a randomized, multicenter clinical trial of adults, 266 patients had sufficient data to be included in this cost-effectiveness analysis. One hundred thirty-six patients received azithromycin, and 130 patients received cefuroxime with or without erythromycin.A pharmacoeconomic analysis from the hospital provider perspective was conducted. Health-care resource utilization was extracted from the clinical database and converted to national reference costs. Decision analysis was used to structure and characterize outcomes. Sensitivity analyses were performed, and statistics were applied to the cost-effectiveness ratios.The clinical success and adverse event rates and antibiotic-related length of stay were 78%, 11.8%, and 5.8 days for the azithromycin group and 75%, 20.7%, and 6.4 days for the group receiving cefuroxime with or without erythromycin, respectively. Geometric mean treatment costs were 4,104 US dollars (95% confidence interval [CI], 3,874 to 4,334 US dollars) for the azithromycin group, and 4,578 US dollars (95% CI, 4,319 to 4,837 US dollars) for the group receiving cefuroxime with or without erythromycin (p = 0.06). The cost-effectiveness ratios were 5,265 US dollars per expected cure for the azithromycin group, and 6,145 US dollars per expected cure for group receiving cefuroxime with or without erythromycin (p = 0.05).Despite a higher per-dose purchase price, overall costs with azithromycin tended to be lower due to decreased duration of therapy, lower preparation and administration costs, and reduced hospital length of stay. As empiric therapy, azithromycin monotherapy was cost-effective compared to cefuroxime with or without erythromycin for patients hospitalized with CAP who have no underlying cardiopulmonary disease, and no risk factors for either drug-resistant pneumococci or enteric Gram-negative pathogens.

We evaluated the role of sputum examination in the management of patients with community-acquired pneumonia (CAP) in a primary-care hospital without microbiologic laboratory facilities.A diagnostic strategy using regular collection of sputum samples, Gram staining in a local laboratory, and mailing of samples to a commercial laboratory for culture analysis.A 200-bed primary-care hospital without subspeciality physicians.One hundred sixteen consecutive patients with a diagnosis of CAP were prospectively evaluated during a 12-month period.Of 116 patients, 42 patients (36%) were capable of producing a sputum sample. Ageor = 75 years (odds ratio [OR], 0.4; 95% confidence interval [CI], 0.18 to 0.93) and prior ambulatory antimicrobial treatment (OR, 3.2; 95% CI, 1.2 to 8.4) were independent predictors of sputum production. A delay in collection and processing of sputum samples of24 h was present in 31% and 39%, respectively. A delay in collection yielded an increased number of Gram-negative enteric bacilli and nonfermenters (44% vs. 7%, p = 0.056). A delay in processing was associated with an increased number of Candida spp isolates (33% vs. 9%, p = 0.16). The overall diagnostic yield was low (10 of 116 patients, 9%) due to a limited number of valid samples (n = 23 of 42 patients, 55%) and a limited number of definitely or probably positive samples on Gram's stain and culture (n = 10 of 42 patients, 24%). Prior ambulatory antimicrobial treatment was associated with a reduction in diagnostic yield (14% vs. 56%, p = 0.09). The impact of diagnostic results on antimicrobial treatment decisions was minimal, with antimicrobial treatment directed to diagnostic results in only one patient.We conclude that in this setting representative of primary-care hospitals in Germany, sputum had a low diagnostic yield and did not contribute significantly to patient management.

Study objectives To define the usefulness of blood cultures for confirming the pathogenic microorganism and severity of illness in patients with ventilator-associated pneumonia (VAP). Design Prospective observational study using BAL and blood cultures collected within 24 h of establishing a clinical diagnosis of VAP. Setting A 15-bed medical and surgical ICU. Patients One hundred and sixty-two patients receiving mechanical ventilation hospitalized for > 72 h who had new or progressive lung infiltrate plus at least two of three clinical criteria for VAP. Interventions BAL and blood culture performed within 24 h of establishing a clinical diagnosis of VAP. Measurements and results Ninety patients were BAL positive (BAL+), satisfying a microbiological definition of VAP (≥ 10 4 cfu/mL), 72 patients were BAL negative (BAL−). Bacteremia was diagnosed when at least two sets of blood cultures yielded a microorganism or when only one set was positive, but the same bacteria was present at a concentration≥ 10 4 cfu/mL in the BAL fluid. Bacteremia was significantly more frequent in the BAL+ than in the BAL− group (22/90 patients vs 5/72 patients; p=0.006). In 6 of 22 BAL+ patients with bacteremia, an extrapulmonary site of infection was the source of bacteremia. Sensitivity of blood culture for disclosing the pathogenic microorganism in BAL+ patients was 26%, and the positive predictive value to detect the pathogen was 73%. Factors associated with mortality were age > 50 years, simplified acute physiology score> 14, prior inadequate antibiotic therapy, Pao 2 /fraction of inspired oxygen 2 blockers. By multivariate analysis, only the use of prior inadequate antimicrobial therapy (odds ratio [OR], 6.47) and age > 50 years (OR, 5.12) were independently associated with higher mortality. The rate of complications was not different in patients with bacteremia. Conclusions Blood cultures have a low sensitivity for detecting the same pathogenic microorganism as BAL culture in patients with VAP. The presence of bacteremia does not predict complications, it is not related to the length of stay, and it does not identify patients with more severe illness. Inadequacy of prior antimicrobial therapy and age > 50 years were the only factors associated with mortality in a multivariate analysis. Blood cultures in patients with VAP are clearly useful if there is suspicion of another probable infectious condition, but the isolation of a microorganism in the blood does not confirm that microorganism as the pathogen causing VAP.

Sepsis syndrome frequently results in endothelial injury in many organ systems. To evaluate neutrophil-pulmonary endothelial cell interaction in the sepsis syndrome, we studied 39 critically ill patients prospectively and 20 normal volunteers. Thirteen patients with sepsis (mean age, 71.4 years), 14 patients in an intensive care unit control group (mean age 65.4 years), and 12 patients admitted with acute myocardial infarction (mean age, 66.8 years) were evaluated. Blood samples were drawn from septic patients within 24 hours and from ICU and MI patients within 72 hours of admission. All sepsis patients were culture positive, 6 of 13 from the blood. Both renal failure and ARDS developed in 54 percent of septic patients. 51Cr-labelled neutrophils were prepared and added to bovine pulmonary endothelial cell monolayers with and without added phorbol myristate acetate. Endothelial cells with adherent PMA and nonadherent PMN's, were harvested and radioactivity in each fraction measured with a gamma scintillation counter. Baseline and maximally stimulated (PMA, 3.0 ng/ml) neutrophil adherence to endothelial cells were similar in all patients groups. However, in septic patients, PMA-stimulated PMN adherence was reduced at lower doses, most significantly in those who developed ARDS within 24 to 48 hours of admission (p less than 0.05). Seventy-one percent of patients who developed ARDS had reduced stimulated adherence (PMA 1.0 ng/ml) compared to 22 percent of critically ill patients who did not. We conclude that diminished adherence of neutrophils to endothelium in response to low-level PMA stimulation is significantly more common in patients with sepsis who develop ARDS. Our findings suggest that PMN-endothelial cell interaction is altered by the time sepsis is clinically recognized but before the development of ARDS. We speculate that the observed reduction in adherence of the PMN to endothelial cells may be a consequence of down-regulation by mediators generated in the inflammatory response to sepsis and/or the need for active participation of septic endothelium in this interaction.

Although fiberoptic bronchoscopy (FOB) has been traditionally used to evaluate nonresolving pneumonia, its efficacy is unknown. We, therefore, reviewed FOB in 35 consecutive patients who had (1) a roentgenographic infiltrate, (2) cough, (3) either temperature greater than 38.1 degrees C, leukocytosis, sputum production, (4) symptoms present for at least ten days, and antibiotic therapy for at least one week. Known lung cancer and AIDS were excluded. Fiberoptic bronchoscopy was diagnostic in 86 percent (12/14) in whom a specific cause was found. No patient had endobronchial cancer. Two patients with nondiagnostic FOB and persistent systemic symptoms had open lung biopsy specimens showing Wegener's granulomatosis and bronchiolitis obliterans with organizing pneumonia (BOOP). Twenty-one patients with nondiagnostic FOB had no final diagnoses other than community-acquired pneumonia. We conclude that FOB is extremely useful in finding a specific diagnosis for a nonresolving pneumonia when a specific diagnosis can be made. Fiberoptic bronchoscopy was most likely to yield a specific diagnosis in nonsmoking patients with multilobar infiltrates of long duration and could have been avoided in older, smoking, or otherwise compromised patients with lobar or segmental infiltrates with no decrease in diagnostic yield in our series.

Tracheobronchial colonization by Gram-negative bacteria is common in mechanically ventilated patients. Pseudomonas sp are commonly isolated from the lower airways. We hypothesized that Pseudomonas sp would preferentially colonize the lower airway and would be more common in patients with poor nutritional status. We serially collected 75 pairs of upper and lower respiratory tract cultures from 14 patients treated with mechanical ventilation for at least one week, examined patterns of airway colonization and routes of bacterial entry for Pseudomonas sp and other enteric Gram-negative bacteria (EGNB), and related these findings to host-associated factors, including nutritional status. Pseudomonas sp were the most common species isolates taken from the lower airway, found in nine of 14 patients and in 41.3 percent of all cultures. In contrast to other EGNB, Pseudomonas sp were found significantly (p≤0.05) more often in the tracheobronchial tree (31 of 75 cultures) than in the oropharynx (18 of 75 cultures). Primary colonization of the lower airway by Pseudomonas sp was found in four patients, while other EGNB never followed this pattern when subjects were studied with cultures taken every third day. A host-related factor related to lower airway colonization by Pseudomonas species was poor nutritional status, assessed by a multifactorial index (p≤0.01). We conclude that in mechanically ventilated patients, Pseudomonas sp colonize the lower airway in a different pattern and by a different route from those of other EGNB. The findings that Pseudomonas sp preferentially colonize the tracheobronchial tree may be important for the design of strategies to prevent airway colonization. The recognition that poor nutritional status, a potentially modifiable host-related factor, favors lower airway growth of Pseudomonas sp suggests one direction for future infection-control efforts. (Chest 1989; 95:155-61)

Colonization of the lower respiratory tract by enteric Gram-negative bacilli (EGNB) has been a frequent finding in patients with long-term tracheostomies; however, the association of hospitalization and certain features of serious illness with this phenomenon has not been clearly established. Because such factors can render the oropharynx more susceptible to EGNB colonization, we sought to discover whether they can also have this effect on the tracheobronchial tree and its microflora. Thus, we collected serial paired culture samples from these two mucosal sites in 15 subjects with long-term tracheostomies and examined patterns and rates of colonization and related these findings to clinical parameters. In 49 sets of cultures, we found that EGNB (especially Pseudomonas species) were present in significantly fewer upper-airway cultures (36.7 percent) than lower-airway cultures (75.5 percent) (p = 0.009). At the tracheobronchial site, seven subjects had persistent EGNB colonization, all with Pseudomonas species, while only one subject had this finding at the oropharyngeal site (p = 0.015). Patients with persistent tracheobronchial colonization were more ill than those without this finding. They were treated with higher doses of prednisone (p=0.06), received antibiotics more offen, and developed purulent tracheobronchitis more often (100 percent vs 25 percent) than patients without persistent colonization. In addition, in the month following the culture survey, four subjects developed pneumonia, and three of these had previous persistent tracheobronchial colonization. The findings suggest that in this population of patients, there was an enhanced susceptibility for more frequent and more persistent EGNB colonization of the lower respiratory tract than the upper respiratory tract and that these two mucosal sites became colonized independently of one another. Furthermore, persistent colonization was associated with greater clinical illness and may have predisposed patients to symptomatic infection.