Appropriateness and delay to initiate therapy in ventilator-associated pneumonia.

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.

Blood cultures have limited value in predicting severity of illness and as a diagnostic tool in ventilator-associated pneumonia.

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 < 205, and use of H(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.

[Clinical contribution of the newer fluoroquinolones in acute bacterial exacerbation of chronic bronchitis]. / Contribucion clínica de las nuevas fluoroquinolonas en las exacerbaciones agudas de la bronquitis crónica.

Acute exacerbations occur frequently in patients with chronic bronchitis and the majority of these patients benefit from antimicrobial therapy. The ideal antimicrobial agent for the management of acute exacerbations of chronic bronchitis (AECB) should have good activity against the common bacterial pathogens associated with these exacerbations (non-typable Haemophilus influenzae, Moraxella catarrhalis and pneumococci); it should be resistant to bacterial betalactamases; penetrate well into pulmonary tissues and secretions; kill bacteria without inducing excessive airway inflammation; be easy to take (given once or twice a day) in order to ensure high patient compliance, and be cost-effective. Fluoroquinolone antibiotics have demonstrated efficacy in the treatment of AECB, but because of the limited activity of certain older agents in this class when administered in standard doses against Streptococcus pneumoniae, they have not be extensively used for this indication. Newer agents including levofloxacin, grepafloxacin, sparfloxacin and trovafloxacin have excellent activity against both Gram positive and Gram negative pathogens likely to be involved in AECB. These agents can be administered once daily, making patient compliance and a successful therapeutic outcome more likely. The new quinolones offer promising alternatives for antimicrobial therapy in outpatients with AECB, particularly those with underlying co-morbidity and severe obstruction.

Contribucion clínica de las nuevas fluoroquinolonas en las exacerbaciones agudas de la bronquitis crónica. / [Clinical contribution of the newer fluoroquinolones in acute bacterial exacerbation of chronic bronchitis]

Acute exacerbations occur frequently in patients with chronic bronchitis and the majority of these patients benefit from antimicrobial therapy. The ideal antimicrobial agent for the management of acute exacerbations of chronic bronchitis (AECB) should have good activity against the common bacterial pathogens associated with these exacerbations (non-typable Haemophilus influenzae, Moraxella catarrhalis and pneumococci); it should be resistant to bacterial betalactamases; penetrate well into pulmonary tissues and secretions; kill bacteria without inducing excessive airway inflammation; be easy to take (given once or twice a day) in order to ensure high patient compliance, and be cost-effective. Fluoroquinolone antibiotics have demonstrated efficacy in the treatment of AECB, but because of the limited activity of certain older agents in this class when administered in standard doses against Streptococcus pneumoniae, they have not be extensively used for this indication. Newer agents including levofloxacin, grepafloxacin, sparfloxacin and trovafloxacin have excellent activity against both Gram positive and Gram negative pathogens likely to be involved in AECB. These agents can be administered once daily, making patient compliance and a successful therapeutic outcome more likely. The new quinolones offer promising alternatives for antimicrobial therapy in outpatients with AECB, particularly those with underlying co-morbidity and severe obstruction.

Contribucion clínica de las nuevas fluoroquinolonas en las exacerbaciones agudas de la bronquitis crónica / [Clinical contribution of the newer fluoroquinolones in acute bacterial exacerbation of chronic bronchitis]

Acute exacerbations occur frequently in patients with chronic bronchitis and the majority of these patients benefit from antimicrobial therapy. The ideal antimicrobial agent for the management of acute exacerbations of chronic bronchitis (AECB) should have good activity against the common bacterial pathogens associated with these exacerbations (non-typable Haemophilus influenzae, Moraxella catarrhalis and pneumococci); it should be resistant to bacterial betalactamases; penetrate well into pulmonary tissues and secretions; kill bacteria without inducing excessive airway inflammation; be easy to take (given once or twice a day) in order to ensure high patient compliance, and be cost-effective. Fluoroquinolone antibiotics have demonstrated efficacy in the treatment of AECB, but because of the limited activity of certain older agents in this class when administered in standard doses against Streptococcus pneumoniae, they have not be extensively used for this indication. Newer agents including levofloxacin, grepafloxacin, sparfloxacin and trovafloxacin have excellent activity against both Gram positive and Gram negative pathogens likely to be involved in AECB. These agents can be administered once daily, making patient compliance and a successful therapeutic outcome more likely. The new quinolones offer promising alternatives for antimicrobial therapy in outpatients with AECB, particularly those with underlying co-morbidity and severe obstruction.

Impact of BAL data on the therapy and outcome of ventilator-associated pneumonia.

STUDY OBJECTIVE: To define the impact of BAL data on the selection of antibiotics and the outcomes of patients with ventilator-associated pneumonia (VAP). DESIGN: Prospective observation and bronchoscopy with BAL, performed within 24 h of establishing a clinical diagnosis of a new episode of hospital-acquired VAP or progression of a prior episode of nosocomial pneumonia (NP). SETTING: A 15-bed medical and surgical ICU. PATIENTS: One hundred thirty-two patients hospitalized for more than 72 h, who were mechanically ventilated and had a new or progressive lung infiltrate plus at least two of the following three clinical criteria for VAP: abnormal temperature (> 38 degrees C or < 35 degrees C), abnormal leukocyte count (> 10,000/mm3 or < 3,000/mm3), purulent bronchial secretions. INTERVENTIONS: Bronchoscopy with BAL within 24 h of establishing a clinical diagnosis of VAP or progression of an infiltrate due to prior VAP or NP. All patients received antibiotics, 107 prior to bronchoscopy and 25 immediately after bronchoscopy. RESULTS: Sixty-five of the 132 patients were BAL positive (BAL[+]), satisfying a microbiologic definition of VAP (> 10(4) cfu/mL), while 67 were BAL negative (BAL[-]). The BAL(+) patients had no differences in mortality, prior antibiotic use, and demographic features when compared with the BAL(-) patients. More of the BAL(+) patients (38/65) satisfied all three clinical criteria of VAP than did BAL(-) patients (24/67) (p < 0.05). A total of 50 BAL(+) patients received antibiotic therapy prior to bronchoscopy, and when this prior therapy was adequate (n = 16), as defined by the results of BAL, then mortality was 38%, while if prior therapy was inadequate (n = 34), mortality was 91% (p < 0.001), and if no therapy was given (n = 15), mortality was 60%. When therapy changes were made after bronchoscopy, more patients (n = 42) received adequate therapy, but mortality in this group was comparable to mortality among those who continued to receive inadequate therapy (n = 23). A total of 46 of the 65 BAL(+) patients died, with 23 of these deaths occurring during the 48 h after the bronchoscopy, before BAL results were known. When BAL data became available, 37 of the 42 surviving patients received adequate therapy, but their mortality was comparable to the patients who continued to receive inadequate therapy. CONCLUSIONS: Patients with a strong clinical suspicion of VAP have a high mortality rate, regardless of whether BAL cultures confirm the clinical diagnosis of VAP. When adequate antibiotic therapy is initiated very early (ie, before performing bronchoscopy), mortality rate is reduced if this empiric therapy is adequate, compared to when this therapy is inadequate or no therapy is given. If adequate therapy is delayed until bronchoscopy is performed or until BAL results are known, mortality is higher than if it had been given at the time of first establishing a clinical diagnosis of VAP. When patients were changed from inadequate antibiotic therapy to adequate therapy, based on the results of BAL, mortality was comparable to those who continued to receive inadequate therapy. Thus, even if bronchoscopy can accurately define the microbial etiology of VAP, this information becomes available too late to influence survival.

[Community-acquired pneumonia in adults. Clinical practice guideline for Argentina. Study Group on Community Acquired Pneumonia]. / Neumonía adquirida en la comunidad (NAC) en adultos. Guía de práctica clínica para la Argentina. Grupo de Estudio de las NAC.

Community-acquired pneumonia (CAP) affects approximately 1% of the population annually. Initial antimicrobial therapy is most often empirical. Guidelines designed in other countries for the empirical management of CAP are not recommended for use in Argentina. Studies from other countries were considered together with unpublished local data to define the potential etiologic microorganisms and their antimicrobial susceptibility. Recommended diagnostic tests, groups of patients for different therapies and hospitalization criteria were defined. Severe CAP requiring intensive care was distinguished from the rest because of its distinct spectrum of etiologic agents and its high mortality, requiring a more focused therapy. Age, coexisting conditions and severity of illness were taken into account in the election of therapy.