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SummaryThere are no prospective comparison of the etiology and clinical outcome between hospital-acquired pneumonia (HAP) and nursing home-acquired pneumonia (NHAP) in non-intubated elderly. This study prospectively evaluated the etiology of HAP and NHAP in non-intubated elderly. A prospective cohort study was carried out in a rural region of Japan where the population over 65 years of age represents 30% of the population. A total of 108 patients were enrolled. There were 33 patients with HAP and 75 with NHAP. Etiologic diagnosis was established in 78.8% of HAP and in 72% of NHAP patients. The most frequent pathogens were Chlamydophila pneumoniae followed by Streptococcus pneumoniae, Staphylococcus aureus and Influenza virus. The frequency of Streptococcus pneumoniae and Influenza virus was significantly higher, whereas the frequency of Staphylococcus aureus and Enterobacteriaceae was significantly lower in NHAP compared to HAP. Performance and nutritional status were significantly worse in patients with HAP than in those with NHAP. Hospital mortality was significantly lower in patients with NHAP compared to those with HAP. This study demonstrated that C. pneumoniae, Streptococcus pneumoniae, Staphylococcus aureus and Influenza virus are frequent causative agents of pneumonia in non-intubated elderly and that the responsible pathogens and clinical outcome differ between NHAP and HAP.

We investigated the role of the clinical pulmonary infection score (CPIS), serum levels of procalcitonin (PCT), C-reactive protein (CRP), and serum amyloid A (SAA) in the detection of patients with early ventilator-associated pneumonia (VAP).Observational study in a university hospital. In 58 patients with severe brain injury receiving mechanical ventilation, CPIS, PCT, CRP and SAA were evaluated at ICU entry and at days 3 to 4 of hospital stay for VAP diagnosis (confirmed by endotracheal aspirate or BAL cultures).We found the following: (1) PCT at entry was increased in patients who later had early VAP develop (25 patients) compared to no VAP (median, 1.4 ng/mL; 25-75 percentiles, 0.14-0.78; vs median, 0.2 ng/mL; 25-75 percentiles, 0.76-2.4, p0.001; sensitivity, 76%; and specificity, 75%); (2) CPIS increased at the day of VAP diagnosis, compared to entry (median, 6.6+/-1.1 vs 1.5+/-1.1, p0.001; sensitivity, 97%; specificity, 100%), while other serum inflammatory markers did not change; and (3) deterioration in oxygenation and changes in tracheal secretions were the main determinants of CPIS changes.PCT may be a useful marker to predict which patients subsequently have early VAP. The CPIS could help as an early way to detect the patients with early VAP and who need further diagnostic testing.

Systemic sepsis and pneumonia are common predisposing factors for ARDS, which can serve as the initial manifestation of the multisystem organ failure syndrome. Primary pneumonia that necessitates ICU admission leads to ARDS in approximately 10% of patients. Systemic infection can also lead to ARDS, but when bacteremia alone is present, the risk is low (probably less than 5%). If the septic syndrome with a hemodynamic and end-organ response develops, the ARDS may follow in as many as 40% of patients. When multiple risk factors for acute lung injury are present, the risk of developing ARDS rises dramatically. The septic syndrome, acute lung injury, and multiorgan failure are closely tied to one another because bacterial cell walls can activate inflammatory mediators, such as interleukin-1 and tumor necrosis factor, which can in turn lead to the septic syndrome and inflammatory injury to the lung. Clinical features, more than serum markers, have been the best predictors of whether lung injury will follow sepsis, indicating that the mere presence of mediators alone cannot cause ARDS and that there are individual susceptibility factors in the effects of these mediators. With the advent of monoclonal antibodies and new anti-inflammatory drugs, prevention of progression from sepsis to multiorgan failure may become possible. Pneumonia is the most common infection that complicates ARDS once it is established, and the mortality rate may approach 90%. The existence of acute lung injury, its predisposing conditions, coexisting illnesses, and the therapeutic interventions used for patients with lung injury all can interfere with lung host defenses and set the stage for bacterial infection of the already-injured lung. This infection appears to add to the propagation of the multiple system organ failure that has already begun. In the future, it may become possible to prevent this infection, which would be a welcome development, because currently, we are stymied in our efforts to diagnose and treat pneumonia in the setting of acute lung injury. Preventive efforts will follow from an understanding of the pathogenesis of pneumonia and in the future may include topical antibiotics, selective digestive decontamination, and prophylactic passive immunotherapy.

Pneumonia is a major cause of morbidity and mortality in hospitalized patients. Topical antibiotics offer many potential advantages in the prevention and treatment of pneumonia in these patients. These include a high delivery of drug to the site of infection, and the potential for little systemic absorption with less toxicity than parenteral therapy. Previous clinical studies have produced mixed results, however. Emergence of resistant organisms and failure of the aerosol to penetrate into areas of diseased lung have been blamed for the failure of many previous studies to achieve positive results. In all of these studies, however, little attention has been paid to the delivery system, the dosage administered, the regional distribution in the lung, and the pharmacokinetics of the aerosol. Aerosolized pentamidine, however, has been studied with respect to the above factors, and has been shown to be clearly efficacious in the prevention of Pneumocystis carinii pneumonia. It should serve as a model for the testing of topical antibiotic therapy in other conditions.

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.

Ventilator associated pneumonia (VAP) is the most frequent infectious complication in critically ill patients, associated with a prolonged length of stay in the intensive care unit (ICU) and a significantly increased risk of death [1, 2]. The attributable mortality of VAP varies with the infecting organism and with the patient population [3]; for example, mortality is higher in patients with acute respiratory distress syndrome (ARDS) [4], as well as in medical compared to surgical patients with VAP. The natural history of resolution of VAP is not well defined, but mortality of VAP has been well studied, and the clinical predictors of mortality have also been characterized [5, 6, 7]. It is reasonable to assume that patients at a high risk of death from VAP are more likely to have delayed resolution, or prolonged recovery, if they survive an episode of VAP [7].

Objective.Nosocomial pneumonia is the leading cause of mortality attributed to nosocomial infection. Appropriate empirical therapy has been associated with improved survival, but data are limited regarding the etiologic agents of hospital-acquired pneumonia in non-ventilated patients (HAP). This evaluation assessed whether the currently recommended empirical therapy is appropriate for both ventilator-associated pneumonia (VAP) and HAP by evaluating the infecting flora.Design.Prospectively collected hospitalwide surveillance data was obtained by infection control professionals using standard Centers for Disease Control and Prevention definitions.Setting.A tertiary care academic hospital.Patients.All patients admitted from 2000 through 2003.Results.A total of 588 episodes of pneumonia were reported in 556 patients: 327 episodes of VAP in 309 patients, and 261 episodes of HAP in 247 Patients. The infecting flora in ventilated patients included gram-positive cocci (32.0% [oxacillin-susceptible Staphylococcus aureus {OSSA}, 9.25%; oxacillin-resistant Staphylococcus aureus {ORSA}, 17.75%]), gram-negative bacilli (59.0% {Pseudomonas aeruginosa, 17.50%; Stenotrophomonas maltophilia, 6.75%; Acinetobacter species, 7.75%), and miscellaneous pathogens (9.0%). The infecting flora in nonventilated patients included gram-positive cocci (42.59% [OSSA, 13.33%; ORSA, 20.37%]), gram-negative bacilli (39.63% [P. aeruginosa, 9.26%; S. maltophilia, 1.11%; Acinetobacter species, 3.33%), and miscellaneous pathogens (17.78%).Conclusions.Our data demonstrated that patients with HAP, compared with those with VAP, had a similar frequency of infection with ORSA but less commonly had infections due to P. aeruginosa, Acinetobacter species, and S. maltophilia. However, the overall frequency of infection with these pathogens was sufficiently high to warrant the use of empirical therapy likely to be active against them. Our data supports using the currently recommended empirical therapy for both HAP and VAP.

To describe the use of a 'de-escalation' strategy to deliver appropriate empiric therapy for ventilator-associated pneumonia, without the overuse of antibiotics.Initial empiric therapy can be appropriate in 80-90% of ventilator-associated pneumonia patients, if it is selected on the basis of local microbiologic data or individual patient surveillance cultures. Following initial empiric therapy, de-escalation means using microbiologic and clinical data to change from an initial broad-spectrum, multidrug empiric therapy regimen to a therapy with fewer antibiotics and agents of narrower spectrum. In spite of early success with this approach there is an opportunity to de-escalate more often, particularly in patients with negative pretherapy cultures, and in those whose cultures show multidrug-resistant organisms, including Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus. In addition, it is possible to reduce the total duration of therapy, particularly when the initial therapy is accurate. When de-escalation has been employed, it has led to less antibiotic usage, shorter durations of therapy, fewer episodes of secondary pneumonia and reduced mortality, without increasing the frequency of antibiotic resistance.De-escalation is a promising strategy for optimizing the responsible use of antibiotics while allowing the delivery of prompt and appropriate empiric therapy of ventilator-associated pneumonia.

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.

Bacteria play a leading role in acute exacerbations of chronic obstructive pulmonary disease (COPD), but we lack predictors of bacterial etiology. We developed a prediction model for infection with gram-negative enteric bacteria (GNEB) and Pseudomonas aeruginosa. Clinical presentation, sputum characteristics, microbial sputum patterns, lung function and previous and concomitant medication were prospectively recorded in patients with moderate to severe exacerbation of COPD. Risk factors for a specific bacterial etiology were c alculated and a prediction model developed. A total of 193 patients with acute exacerbation were included. In 121 (62.6%) of them a microbial etiology could be identified, most frequently Haemophilus influenzae (32 strains), Streptococcus pneumoniae (22 strains) and P. aeruginosa (12 strains). Multivariate analysis identified severe airflow obstruction and use of systemic steroids as predictors for exacerbation due to gram-negative enteric bacilli and P. aeruginosa. A prediction model including FEV1 < 35% of predicted value, systemic steroid use and prior antibiotic therapy within preceeding 3 months had a negative predictive of 89%, being a helpful tool in excluding patients at risk of exacerbation due to gram-negative enteric bacilli and P. aeruginosa when all criteria are absent. A simple prediction model based on three factors may identify COPD patients at low risk for exacerbations with gram-negative enteric bacilli and P. aeruginosa. Bacterial Etiology in COPD Exacerbations.

The management of ventilator-associated pneumonia (VAP) requires a strategy for antibiotic use that achieves prompt and accurate empirical therapy without overusing antibiotics. Although, efforts at better diagnosis and antibiotic restriction have been attempted, "de-escalation" may be a more useful and effective strategy, and one that can achieve these goals while improving patient outcomes. The centerpiece of this approach is to initiate empirical therapy with a broad-spectrum treatment regimen, based on knowledge of local patterns of microbiology and antimicrobial resistance. Prior to therapy, patients require collection of a lower respiratory tract sample for culture. After 2 to 3 days, the clinical course can be assessed and the culture data reviewed, and in responding patients, efforts can be made to change the initial broad-spectrum therapy. This de-escalation can involve focusing to a more narrow spectrum agent, reducing the number of antibiotics, stopping therapy altogether in patients not likely to have infection, and making efforts to reduce duration of therapy. When this strategy has been used, outcomes such as the frequency of secondary infection, antimicrobial resistance, and mortality have improved. Additional information is needed to apply this approach more widely, especially in patients infected with multidrug-resistant organisms and in those with negative lower respiratory tract cultures.

Inappropriate therapy (IT) and delayed initiation of appropriate therapy (DIAT) result in inadequate therapy in patients with ventilator-associated pneumonia (VAP). The aim of the current study was to assess the impact of DIAT in VAP. A total of 76 mechanically ventilated patients with bacteriologically confirmed VAP were prospectively evaluated in the intensive care unit of six hospitals in Buenos Aires, Argentina. Appropriate therapy was defined as coverage of all the identified pathogens by the antimicrobial therapy administered at the time of VAP clinical diagnosis. The clinical pulmonary infection score was measured during the 3 days before, at the onset and during the days which followed the onset of VAP. A total of 24 patients received adequate therapy; mortality was 29.2%. The remaining 52 patients received either IT (n = 16) or DIAT (n = 36); the mortality was 63.5% combined, and 75.0 and 58.3% for IT and DIAT, respectively (statistically significant compared with adequate therapy). Inappropriate therapy and delayed initiation of appropriate therapy increased the mortality of ventilator-associated pneumonia. Patients with inappropriate therapy and/or delayed initiation of appropriate therapy had a more gradual increase in clinical pulmonary infection score than those receiving adequate therapy, and this increase was found to occur prior to the time of the clinical diagnosis. In conclusion, these findings might provide the rationale for a trial of earlier initiation of therapy, based on clinical grounds in an effort to improve the outcome of patients with ventilator-associated pneumonia.

Haemophilus influenzae is the most common bacterial pathogen associated with acute exacerbations of chronic bronchitis (AECB). This study determined the rate of bacterial eradication of H. influenzae during AECB treated with either macrolides or moxifloxacin. Adult AECB patients with H. influenzae were included in a pooled analysis of four double-blind, multicentre, randomised trials. Patients received either moxifloxacin (400 mg qd for 5-10 days) or macrolides (azithromycin 500 mg/250 mg qd for 5 days or clarithromycin 500 mg bid for 5-10 days). Bacterial eradication and clinical success were recorded at the test-of-cure visit (7-37 days post-therapy). Of 2555 patients in the intent-to-treat population, 910 were microbiologically valid and 292 (32%) had H. influenzae cultured at baseline. Bacterial eradication of H. influenzae was significantly higher with moxifloxacin vs. macrolide-treated patients (93.0% [133/143] vs. 73.2% [109/149], respectively, P = 0.001). Moxifloxacin also demonstrated higher eradication rates compared with azithromycin (96.8% vs. 84.6%, P = 0.019) and clarithromycin (90.1% vs. 64.2%, P = 0.001) analysed separately. Clinical success was 89.5% (128/143) for moxifloxacin vs. 85.2% (127/149) for the macrolide group (P = 0.278); similar results were found when moxifloxacin was compared individually with each macrolide. For patients with AECB due to H. influenzae, moxifloxacin provided superior bacterial eradication rates than macrolide therapy.

Current strategies and guidelines for the treatment of community-acquired pneumonia are directed toward making care cost effective, by treating patients on an outpatient basis whenever possible. The use of the new fluoroquinolones could help to achieve these goals. These agents are highly bioavailable and can facilitate the oral treatment of certain patients who otherwise might be admitted to the hospital, as outpatients. The good absorption and bioavailability of these agents can allow moderately ill patients to rapidly achieve effective serum levels of the drug after oral administration and can also facilitate early discontinuation of intravenous therapy and early discharge for responding inpatients. For inpatients or outpatients with clinical risk factors for acquiring drug-resistant pneumococci, quinolones represent a reliable monotherapy option and an effective alternative to a beta-lactam/macrolide combination. Although the in vitro differences among the various quinolones remain of unclear clinical relevance, preliminary data suggest that agents with enhanced in vitro activity against pneumococci, such as moxifloxacin, may have greater clinical efficacy and may lead to more-rapid resolution of fever and, potentially, less selection of future pneumococcal resistance to quinolones than that associated with agents with less intrinsic activity.

There has long been a controversy about whether to use a clinical or microbiologic approach to diagnose ventilator-associated pneumonia (VAP) and about which approach to use in managing patients. Although the clinical approach has often been criticized, a number of recent studies have shown that it is possible to use such an approach to effectively manage patients. This approach involves using all available clinical data to define the presence of pneumonia and then to initiate empiric therapy in a timely fashion, based on therapy guidelines, modified by local microbiologic data. Often the clinical diagnosis is made using the clinical pulmonary infection score, and this tool can be very accurate, especially if it incorporates a Gram stain of a lower-respiratory-tract sample. Once the clinical diagnosis of VAP is made, all patients should have a tracheal aspirate collected for culture, followed by prompt initiation of therapy. Using a clinical approach to management, the key decision point is not whether to start antibiotics, but whether to continue them at day 2-3. This requires serial clinical evaluation to define whether a response to empiric therapy has occurred. Based on this assessment, in conjunction with the results of tracheal aspirate cultures, therapy can be either modified or continued. A number of studies have shown that the clinical approach leads to a large number of patients receiving adequate empiric therapy, while still permitting de-escalation of antibiotic regimens, along with short durations of therapy. Thus a clinical approach to management can be successful in allowing for effective management of VAP, without promoting the unnecessary use of broad-spectrum antimicrobial therapy.

To compare the efficacy and tolerability of ceftriaxone plus azithromycin with those of levofloxacin in the treatment of hospitalized patients with moderate to severe community-acquired pneumonia (CAP).Randomized, open-label multicenter trial with 1 : 1 treatment allocation in an inpatient setting.212 male or female inpatients with a clinical diagnosis of CAP were included in the study. In each treatment group50% of patients had a pneumonia severity index of IV or V.Open-label treatment with either intravenous (IV) ceftriaxone 1g and IV azithromycin 500 mg daily or IV levofloxacin 500 mg daily. Patients who improved clinically were switched to oral follow-on therapy with either azithromycin 500 mg/day or levofloxacin 500 mg/day. At the clinician's discretion, oral cefuroxime axetil was added to the treatment regimen of patients who received oral azithromycin if a macrolide resistant pneumococcal isolate was documented.Overall, both study treatments were well tolerated. Favorable clinical outcomes in clinically evaluable patients were demonstrated in 91.5% of patients treated with ceftriaxone plus azithromycin and 89.3% (95% CI -7.1%, 11.4%) of patients treated with levofloxacin at the end of therapy visit and in 89.2% and 85.1% (95% CI -6.7%, 14.8%) patients, respectively, at the end of study visit. Bacteriological eradication rates for both treatments were equivalent with the exception of Streptococcus pneumoniae; 44% of isolates were eradicated with levofloxacin compared with 100% of isolates with ceftriaxone plus azithromycin.As acknowledged by international CAP treatment guidelines, the combination of a third-generation cephalosporin and a macrolide is at least as efficacious as monotherapy with a fluoroquinolone with enhanced anti-pneumococcal activity, for hospitalized patients with moderate to severe CAP. Combined medication with a macrolide and third-generation cephalosporin may be preferred over fluoroquinolones as first-line therapy of hospitalized patients with CAP to minimize the development of multiresistant nosocomial Gram-negative bacilli.

The National Heart, Lung, and Blood Institute, along with the Centers for Disease Control and Prevention and the National Institute of Allergy and Infectious Diseases, convened a panel to develop recommendations for treatment, prevention, and research for respiratory failure from severe acute respiratory syndrome (SARS) and other newly emerging infections. The clinical and pathological features of acute lung injury (ALI) from SARS appear indistinguishable from ALI from other causes. The mainstay of treatments for ALI remains supportive. Patients with ALI from SARS who require mechanical ventilation should receive a lung protective, low tidal volume strategy. Adjuvant treatments recommended include prevention of venous thromboembolism, stress ulcer prophylaxis, and semirecumbent positioning during ventilation. Based on previous experience in Canada, infection control resources and protocols were recommended. Leadership structure, communication, training, and morale are an essential aspect of SARS management. A multicenter, placebo-controlled trial of corticosteroids for late SARS is justified because of widespread clinical use and uncertainties about relative risks and benefits. Studies of combined pathophysiologic endpoints were recommended, with mortality as a secondary endpoint. The group recommended preparation for studies, including protocols, ethical considerations, Web-based registries, and data entry systems.

Objectives: This study was conducted to investigate the potential equivalence in clinical efficacy and assess safety of a 5 or 7 day regimen of oral telithromycin (800mg once daily) and a 10 day regimen of oral clarithromycin (500mg twice daily) in treating community-acquired pneumonia (CAP). Bacteriological efficacy was also compared. Methods: This was a multicentre, randomized, double-blind, active-controlled study. Patients with mild to moderate CAP received telithromycin 800mg once a day for 5 (n 5 193) or 7 (n 5 195) days or clarithromycin 500mg twice a day for 10 days (n 5 187). In these groups, 159, 161 and 146 patients, respectively, completed the study. Results: At the post-therapy/test-of-cure evaluation, clinical cure rates (per-protocol clinical population) were 89.3% (5 days) and 88.8% (7 days) for telithromycin, and 91.8% for clarithromycin 10 days. Satisfactory bacteriological outcome rates (per-protocol bacteriological population) were 87.7% and 80.0% for 5 and 7 days of telithromycin, respectively, and 83.3% for 10 days of clarithromycin. Bacteriological eradication rates in the respective treatment groups were, for Streptococcus pneumoniae, 95.8% (23/24), 96.7% (29/30) and 88.5% (23/26); for Haemophilus influenzae, 88.0% (22/25), 84.0% (21/25) and 88.2% (15/17) and for Moraxella catarrhalis, 1/1, 4/5 and 3/4. Both telithromycin regimens demonstrated clinical efficacy against pneumococcal bacteraemia (19/19), atypical pathogens (9/9) and erythromycin-resistant S. pneumoniae isolates (5/5). Most treatment-emergent adverse events were mild to moderate in intensity with most commonly reported adverse events involving the gastrointestinal system. Conclusions: Telithromycin 800mg administered once a day for 5 or 7 days was as effective and safe as clarithromycin 500mg administered twice a day for 10 days in treating patients with CAP caused by common respiratory pathogens, including macrolide-resistant isolates, and pneumococcal bacteraemia.

To 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.Prospective, multicenter, in a cohort of mechanically ventilated patients.The intensive care unit of six hospitals located in the metropolitan area of Buenos Aires, Argentina.Sixty-three patients, from a cohort of 472 mechanically ventilated patients hospitalized for72 hrs, had clinical evidence of VAP and bacteriologic confirmation by bronchoalveolar lavage (BAL) or blood cultures.Bronchoscopy 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.CPIS 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 Pao /Fio ratio distinguished survivors from nonsurvivors, beginning at VAP+3. When CPIS was6 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 Pao /Fio at VAP+3, whereas those getting inadequate therapy did not.Serial 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.

To assess the relationship between concentrations of bronchoalveolar cytokines and bacterial burden (quantitative bacterial count) in intubated patients with a presumptive diagnosis of community-acquired pneumonia.A cross-sectional and clinical investigation. SETTING Medical/surgical and respiratory intensive care unit of a tertiary 1,200-bed medical center.According to the time course of community-acquired pneumonia at the time of study with bronchoalveolar lavage, 69 mechanically ventilated patients were divided into three subgroups: primary (n = 11), referral (n = 23), and treated (n = 35) community-acquired pneumonia.Bronchoalveolar lavage was performed in the most abnormal area on chest radiograph by fiberoptic bronchoscope. Bronchoalveolar lavage fluid was processed for quantitative bacterial culture. The concentrations of bronchoalveolar lavage cytokines (tumor necrosis factor-alpha, interleukin-1 beta, interleukin-6, interleukin-8, and interleukin-10) also were measured.Thirty-two patients had a positive bacterial culture (bronchoalveolar lavageor = 10 colony-forming units/mL)., and made up 76% of pathogens recovered at high concentrations. The concentrations of bronchoalveolar lavage interleukin-1 beta were 199.1 +/- 32.1 and 54.9 +/- 13.0 pg/mL (mean +/- se) in the patients with positive and negative bacterial culture, respectively (p.001). Bronchoalveolar lavage interleukin- 1 beta was significantly higher in the patients with a high bacterial burden (p.001), with mixed bacterial infection (p.001), and with pneumonia (p.001), compared with values in patients without these features. The relationship between bacterial load and concentrations of bronchoalveolar lavage interleukin-1 beta was very strong in the patients with primary and referral community-acquired pneumonia but was borderline in treated community-acquired pneumonia.The common pathogens were similar to the core pathogens of hospital-acquired pneumonia, probably due to antibiotic effects, delayed sampling, and superimposed nosocomial infection. Since the concentration of bronchoalveolar lavage interleukin-1 beta was correlated with bacterial burden in the alveoli, it may be a marker for progressive and ongoing inflammation in patients who have not responded to pneumonia therapy and who have persistence of bacteria in the lung.

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.

Results from studies comparing health care resource use (HCRU), costs of treatment, and cost-effectiveness of linezolid compared with vancomycin therapy in the treatment of hospitalized patients with methicillin-resistant Staphylococcus aureus (MRSA) nosocomial pneumonia are limited in the published literature. We therefore conducted an analysis to compare the HCRU, costs of treatment, and cost-effectiveness of linezolid compared with vancomycin in the treatment of hospitalized patients with MRSA nosocomial pneumonia using data from a Phase IV clinical trial. The economic effect of moderate to severe adverse events (MSAEs) and the development of renal failure were also evaluated.We performed a post hoc analysis of data from a Phase IV, double-blind, randomized, comparator-controlled, multicenter trial that compared linezolid and vancomycin treatment in patients with MRSA nosocomial pneumonia. HCRU and costs were compared based on treatment, development of MSAEs, and development of renal failure using data from the modified intent-to-treat population. Predictors of costs were evaluated using generalized linear models. A piggyback cost-effectiveness analysis was conducted to assess the incremental cost-effectiveness ratio of linezolid versus vancomycin, given the significantly higher clinical success of linezolid compared with vancomycin found in the trial.Overall, HCRU and costs were similar between the linezolid and vancomycin treatment groups; drug costs were significantly higher and dialysis costs significantly lower for linezolid- compared with vancomycin-treated patients. Total treatment costs were approximately $8000 higher (P = .046) for patients who developed renal failure compared with those who did not. Renal failure occurred more commonly in patients randomized to receive vancomycin (15%) compared with linezolid (4%; P.001). Region, ventilator-associated pneumonia, clinical failure, and development of renal failure were associated with significantly higher total costs. The point estimate incremental cost-effectiveness ratio for linezolid compared with vancomycin was $16,516 per treatment success, with linezolid dominant in 24% and dominated in2% of bootstrapped samples.This phase 4 clinical trial conducted in patients with MRSA-confirmed nosocomial pneumonia reveals that linezolid- compared with vancomycin-treated patients had similar HCRU and total overall costs. Fewer patients developed renal failure during the study while taking linezolid compared with vancomycin, and patients with a documented MSAE or renal failure had increased HCRU and costs. In summary, linezolid may be a cost-effective treatment strategy in MRSA-confirmed nosocomial pneumonia.

The diagnosis of ventilator associated pneumonia remains confusing and controversial, with no clear consensus about whether the decision to start antibiotic therapy, in the setting of suspected infection, should be guided by clinical criteria or by microbiologic data collected by quantitative sampling of lower airway secretions (1). This controversy exists because the clinical definition of pneumonia is quite sensitive, but not very specific, and many patients with the clinical diagnosis of VAP may have a non-infectious etiology for their findings of fever, purulent sputum and leukocytosis, in the setting of a new or progressive pulmonary infiltrate.

Community-acquired pneumonia (CAP) is a common illness associated with increasing mortality rates that parallel the site of care. While outpatients have a risk of dying of 65 years), derived from the British Thoracic Society rule,5 and the Pneumonia Severity Index (PSI)1—predict mortality by giving a point …

Publisher Summary The quinolone antibiotic class is extremely useful for the therapy of common respiratory infections, including the community-acquired pneumonia (CAP), hospital-acquired pneumonia (HAP), and the acute exacerbation of chronic bronchitis. These agents have become popular due to their antimicrobial spectrum of activity combined with the pharmacokinetic advantages that include excellent penetration into respiratory tissue and high bioavailability with oral therapy. The latest members of the quinolone class, moxifloxacin and gatifloxacin, have the added advantages of effective activity against multidrug-resistant S. pneumoniae , two bacterial targets that impede resistance development, improved activity against anaerobes, metabolism that does not rely on the cytochrome P450 system, and dosage that does not require alteration in the setting of renal or hepatic impairment (moxifloxacin) or hepatic impairment alone (gatifloxacin). Current clinical practice has several important utilities for quinolone use that include the therapy of difficult-to-treat infections such as acute exacerbations of chronic bronchitis (AECB) in complicated patients and patients with severe nosocomial pneumonia, the early switch from intravenous to oral therapy in patients with either CAP or HAP, and the possibility of using oral therapy for patients who would otherwise require admission for parenteral therapy with other antimicrobials. Trovafloxacin has activity against both P. aeruginosa and respiratory tract anaerobes, but the use of this agent has been greatly restricted because of its hepatic toxicity. The place of these new quinolones in the future management of respiratory infection is still being defined, but they are likely to become the drugs of choice for various patient groups.

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.

The purpose of the study was to validate the criteria used in the guidelines of the American Thoracic Society (ATS) for severe community-acquired pneumonia (CAP). Severe pneumonia was defined as admission to the intensive care unit (ICU). Overall 331 nonsevere (84%) and 64 severe cases (16%) of CAP were prospectively studied. Mortality was 19 of 395 (5%) and 19 of 64 (30%), respectively. Single severity criteria as well as the ATS definition of severe pneumonia were assessed calculating the operative indices. A modified prediction rule including minor (baseline) and major (baseline or evolutionary) criteria was derived. Single minor criteria at admission had a low sensitivity and positive predictive value. Defining severe pneumonia according to the ATS guidelines had a high sensitivity (98%). However, specificity and positive predictive value were low (32% and 24%, respectively). A modified prediction rule (presence of two or three minor criteria [systolic blood pressure < 90 mm Hg, multilobar involvement, PaO2/FIO2 < 250] or one of two major criteria [requirement of mechanical ventilation, presence of septic shock]) had a sensitivity of 78%, a specificity of 94%, a positive predictive value of 75%, and a negative predictive value of 95%. The ATS definition of severe pneumonia was highly sensitive but insufficiently specific and had a low positive predictive value. Our suggested modified rule had a more balanced performance and, if validated in an independent population, may represent a more accurate definition of severe CAP.

Community-acquired pneumonia (CAP) is responsible for an average of 4.5 million visits annually to physicians' offices, emergency departments, and outpatient clinics. However, there have been few studies using national data on the costs of treating CAP. Without such data, it is difficult to assess whether new therapies and treatment strategies are needed to improve patient outcomes. We conducted a retrospective analysis based on national incidence data and paid claims data for patients treated for CAP to assess the frequency of services rendered and costs to the health-care system. Records were selected for the study based on a primary diagnosis of CAP according to the International Classification of Diseases, 9th Revision. Incidence data were derived from the National Health and Nutrition Examination Survey III. Medicare was the primary source of data for patients agedor =65 years. Data from the National Healthcare Cost and Utilization Project, the National Ambulatory Medical Care Survey, and the National Hospital Ambulatory Medical Care Survey were used to determine the cost of treating patients aged65 years. We arrived at a total cost of $4.8 billion for treating patients agedor =65 years and $3.6 billion for treating patients aged65 years. These calculations were based on the following: 1.1 million hospital discharges resulting in inpatient costs of $4.4 billion (52.4% of the $8.4 billion) for the 0.6 million patients agedor =65 years and $3.1 billion (36.9% of the $8.4 billion) for the 0.5 million patients aged65 years. The average hospital length of stay was 7.8 days with an average cost of $7166 for patients agedor =65 years and 5.8 days with an average cost of $6042 for younger patients. Room and board represented the largest percentage of the average hospital bill for patients with CAP. Inpatient physician service costs were $305 million and $192 million for theor =65 and65 groups, respectively. Based on 1.1 million outpatient office visits for those agedor =65 years and 3.3 million visits for those aged65, total outpatient costs were $119 million and $266 million, respectively. Given the overwhelming cost burden for CAP in the hospital setting, any new therapy that allows patients to be treated in the outpatient setting could result in significant savings, especially for patients agedor =65 years.

Although colitis is often seen in critically all patients who have received multiple broad-spectrum antibiotics, there are no reports describing severe sepsis as a result of Clostridium difficile infection. We describe three cases of severe sepsis with local intestinal Clostridium difficile infection as the only identifiable etiology. The mechanism of severe sepsis may be a derangement of the gastrointestinal barrier function. This could result in absorption of microbes or endotoxin or activation of inflammatory cascades in the submucosa of the intestine or liver.