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Javier Garau

Publications and source records attributed to Javier Garau.

31 records · Page 2Linked to original sources
PubMed2003

Why do we need to eradicate pathogens in respiratory tract infections?

Evidence from studies in otitis media, acute bacterial sinusitis and acute exacerbations of chronic bronchitis indicate that clinical efficacy is dependent on bacterial eradication. Failure to eradicate bacterial pathogens increases the potential for clinical failure, incurring further costs, and may also select and maintain bacteria that are resistant to a wide range of antimicrobials. Bacteriologically confirmed clinical failures have been reported in pneumococcal pneumonia with both macrolides and older fluoroquinolones (ciprofloxacin, ofloxacin, and levofloxacin). These failures were due to the involvement of resistant pathogens (macrolides) or suboptimal pharmacokinetics/pharmacodynamics (PK/PD) (quinolones). However, persistent positive blood cultures have not been reported during therapy with adequate doses of benzylpenicillins or aminopenicillins. Treatment failure, driven by the failure to eradicate pathogens, leads to both economic and environmental costs, hospitalization being the major cost driver. Failure to achieve bacterial eradication may also lead to the development and spread of resistance. Different types of antimicrobials appear to be driving resistance to different extents, and this may be due to suboptimal PK/PD. In conclusion, factors to consider when prescribing include an accurate diagnosis, knowledge of local epidemiology, the role of PK/PD principles in antimicrobial choice, clinical outcomes in relation to bacteriologic efficacy, and resistance and its bacteriologic and clinical impact. The vicious cycle of infection, inappropriate therapy, bacteriologic failure, selection/spread of resistance and further infection needs to be broken by the use of appropriate treatments to achieve bacterial eradication.

Anti-Bacterial Agents↗
PubMed2003

Pseudomonas aeruginosa pneumonia.

PURPOSE OF REVIEW: Recent articles of clinical interest on Pseudomonas aeruginosa respiratory tract infections including CAP, nosocomially-acquired pneumonia, particularly in the ventilated patient, and chronic infections in cystic fibrosis patients are reviewed. RECENT FINDINGS: The growing importance of P. aeruginosa as an etiologic agent of CAP, the occurrence of CAP in previously healthy adults and its high prevalence as an etiologic agent of late VAP are stressed in recent studies. The effect of antibiotics on the recovery of bacteria in respiratory samples of patients with VAP can be marked and as early as 12 h after administration of antimicrobials certain organisms are no longer cultivable; in contrast, P. aeruginosa can still be recovered even after 48 h of adequate therapy. Type III secretory proteins are recognized as important virulent factors in P. aeruginosa. This phenotype predicts a worse outcome in patients with VAP. Fluoroquinolones have a major role in the emergence of multiply resistant P. aeruginosa in patients with VAP. Pharmacokinetic/pharmacodynamic parameters of antimicrobials with antipseudomonal activity are gaining importance as a means of optimization of antibiotic therapy. In CF, the knowledge of the pharmacokinetics and bioavailability of inhaled tobramycin and its long term beneficial effect in lung function are important developments in this area. SUMMARY: P. aeruginosa continues to be a serious problem worldwide as a cause of respiratory tract infections in selected populations. Microbiologic diagnosis remains difficult and plagued with pitfalls. The application of modern PK/PD concepts should help to optimize antibiotic therapy of this increasingly difficult to treat infection, particularly at the respiratory tract level and with an increasing prevalence of resistance to all antipseudomonal agents. Inhaled antibiotics, particularly tobramycin, are increasingly used for the prevention and treatment of P. aeruginosa infection in CF patients.

Animals↗
PubMed2002

Hospital-acquired pneumococcal bacteremia.

To assess the most relevant features of hospital-acquired pneumococcal bacteremia, all cases of pneumococcal bacteremia at a single teaching hospital that occurred during 1988-2000 were prospectively studied. During this period, 374 cases of pneumococcal bacteremia were documented; 39 (10%) of these episodes were hospital acquired. Twenty-nine (74%) cases occurred during the period of December through May. Eleven (28%) of 39 patients had received antimicrobial agents in the month before the onset of bacteremia. All patients had underlying diseases that predisposed them to pneumococcal infection. The most common origin of infection was the respiratory tract, followed by the intra-abdominal region. Fifteen strains were fully susceptible to penicillin, and 20 were intermediately resistant. Only 25 strains were susceptible to erythromycin; all strains that were resistant to erythromycin were penicillin nonsusceptible. Eighteen (46%) of 39 patients died; the mortality rate related to infection was 39%.

Adult↗
PubMed2002

Failure of macrolide antibiotic treatment in patients with bacteremia due to erythromycin-resistant Streptococcus pneumoniae.

The rate of macrolide resistance among Streptococcus pneumoniae is increasing, but some investigators have questioned its clinical relevance. We conducted a matched case-control study of patients with bacteremic pneumococcal infection at 4 hospitals to determine whether development of breakthrough bacteremia during macrolide treatment was related to macrolide susceptibility of the pneumococcal isolate. Case patients (n=86) were patients who had pneumococcal bacteremia and an isolate that was either resistant or intermediately resistant to erythromycin. Controls (n=141) were patients matched for age, sex, location, and year that bacteremia developed who had an erythromycin-susceptible pneumococcus isolated. Excluding patients with meningitis, 18 (24%) of 76 case patients and none of 136 matched controls were taking a macrolide when blood was obtained for culture (P=.00000012). Moreover, 5 (24%) of 21 case patients with the low-level-resistant M phenotype and none of 40 controls were taking a macrolide (P=.00157). These data show that development of breakthrough bacteremia during macrolide or azalide therapy is more likely to occur among patients infected with an erythromycin-resistant pneumococcus, and they also indicate that in vitro macrolide resistance resulting from both the efflux and methylase mechanisms is clinically relevant.

Adolescent↗
PubMed2002

The efficacy and safety of oral pharmacokinetically enhanced amoxycillin-clavulanate 2000/125 mg, twice daily, versus oral amoxycillin-clavulanate 1000/125 mg, three times daily, for the treatment of bacterial community-acquired pneumonia in adults.

This double-blind, double-dummy, parallel-group study was designed to show that a pharmacokinetically enhanced formulation of oral amoxycillin-clavulanate (16:1, 2000/125 mg), twice daily, is at least as effective clinically and microbiologically as oral amoxycillin-clavulanate 1000/125 mg, three times daily, in the 10 day treatment of community-acquired pneumonia (CAP) in adults. The pharmacokinetically enhanced formulation is designed to provide higher serum concentrations of amoxycillin for a longer period than standard dosing to achieve coverage of Streptococcus pneumoniae isolates with amoxycillin-clavulanic acid minimum inhibitory concentrations (MICs) up to and including 4 mg/l. A total of 344 patients with CAP from 77 centres received amoxycillin-clavulanate 2000/125 mg twice daily for 10 days (169 patients) or amoxycillin-clavulanate 1000/125 mg three times daily for 10 days (175 patients). The most common pathogen isolated was S. pneumoniae (52.3% of patients, amoxycillin-clavulanate 2000/125 mg group; 46.8% of patients, amoxycillin-clavulanate 1000/125 mg group). In the clinical per-protocol (PP) population at test of cure (days 18-39), the clinical success rate in the amoxycillin-clavulanate 2000/125 mg group was at least as good as in the amoxycillin-clavulanate 1000/125 mg group (91.5 and 93.0%, respectively; 95% CI, -8.3, 5.4). The radiological and bacteriological success rates at test of cure for the PP populations were 92.4 and 90.6% in the amoxycillin-clavulanate 2000/125 mg group and 93.9 and 84.4% in the amoxycillin-clavulanate 1000/125 mg group, respectively. The clinical, bacteriological and radiological success rates at the end of therapy (days 11-17) for the PP populations were all over 85%. Both regimens were well tolerated, with no differences in adverse events between the groups. Amoxycillin-clavulanate 2000/125 mg, twice daily, is well tolerated and at least as effective clinically as amoxycillin-clavulanate 1000/125 mg, three times daily, in patients with CAP and may also be appropriate for the treatment of infections due to S. pneumoniae strains with high-level penicillin resistance.

Adult↗
PubMed2002

Treatment of drug-resistant pneumococcal pneumonia.

The increasing prevalence of resistance to penicillin and other drugs among pneumococci has considerably complicated the empirical treatment of community-acquired pneumonia. Penicillin resistance has become widespread and is a worldwide occurrence. Resistance to other classes of antibiotics traditionally used as alternatives in the treatment of pneumococcal infections has also increased markedly during recent years. In some areas of the USA, Europe, and east Asia a prevalence of macrolide resistance as high as 35% or more has been reported recently. From the clinical standpoint, a growing number of failures following the use of these agents has been described. Resistance to fluoroquinolones remains low but several failures have been reported in different parts of the world. Pharmacokinetic/pharmacodynamic parameters have become essential at the time of making a rational choice and calculation of dosage. Penicillin G remains the mainstay of therapy for the treatment of penicillin-susceptible pneumococcal pneumonia. Penicillin-resistant pneumococcal pneumonia (minimum inhibitory concentration <4 microg/mL) can be safely treated with adequate betalactams at the right dosage. The new fluoroquinolones are very active and effective in pneumococcal pneumonia. Caution should be exercised in the widespread prescription of these drugs if we are to limit the rate of resistance to these agents.

Adult↗
PubMed2002

Pulmonary capillary hemangiomatosis associated with primary pulmonary hypertension: report of 2 new cases and review of 35 cases from the literature.

Pulmonary capillary hemangiomatosis (PCH) is a rare cause of primary pulmonary hypertension characterized by thin-walled microvessels infiltrating the peribronchial and perivascular interstitium, the lung parenchyma, and the pleura. These proliferating microvessels are prone to bleeding, resulting in accumulation of hemosiderin-laden macrophages in alveolar spaces. Here we report 2 cases of PCH with pulmonary hypertension, 1 of them associated with mechanical intravascular hemolysis, a feature previously reported in other hemangiomatous diseases, but not in PCH. Case 2 was diagnosed by pulmonary biopsy; to our knowledge the patient is the second adult to be treated with interferon alpha-2a. Review of the literature identified 35 patients with PCH and pulmonary hypertension. The prognosis is poor and median survival was 3 years from the first clinical manifestation. Dyspnea and right heart failure are the most common findings of the disease. Hemoptysis, pleural effusion, acropachy, and signs of pulmonary capillary hypertension are less common. Chest X-ray or computed tomography scan usually shows evidence of interstitial infiltrates, pulmonary nodules, or pleural effusion. Hemodynamic features include normal wedge pressures. Radiologic and hemodynamic findings are undifferentiated from those of pulmonary veno-occlusive disease but differ from other causes of primary pulmonary hypertension. Epoprostenol therapy, considered the treatment of choice in patients with primary pulmonary hypertension, may produce pulmonary edema and is contraindicated in patients with PCH. Regression of lesions was reported in 1 patient treated with interferon therapy and 2 other patients stabilized, including our second patient. PCH was treated successfully by lung transplantation in 5 cases. Early recognition of PCH in patients with suspected primary pulmonary hypertension is possible based on clinical and radiologic characteristics. Diagnosis by pulmonary biopsy is essential for allowing appropriate treatment.

Angiogenesis Inhibitors↗
PubMed2002

Mortality after hospitalization for COPD.

OBJECTIVES: To identify variables associated with mortality in patients admitted to the hospital for acute exacerbation of COPD. DESIGN: Prospective cohort study. SETTING: Acute-care hospital in Barcelona (Spain). PATIENTS: One hundred thirty-five consecutive patients hospitalized for acute exacerbation of COPD, between October 1996 and May 1997. MEASUREMENTS AND RESULTS: Clinical, spirometric, and gasometric variables were evaluated at the time of inclusion in the study. Socioeconomic characteristics, comorbidity, dyspnea, functional status, depression, and quality of life were analyzed. Mortality at 180 days, 1 year, and 2 years was 13.4%, 22%, and 35.6%, respectively. Sixty-four patients (47.4%) were dead at the end of the study (median follow-up duration, 838 days). Greater mortality was observed in the bivariate analysis among the oldest patients (p < 0.0001), women (p < 0.01), and unmarried patients (p < 0.002). Hospital admission during the previous year (p < 0.001), functional dependence (Katz index) [p < 0.0004], greater comorbidity (Charlson index) [p < 0.0006], depression (Yesavage Scale) [p < 0.00001]), quality of life (St. George's Respiratory Questionnaire [SGRQ]) [p < 0.01], and PCO(2) at discharge (p < 0.03) were also among the significant predictors of mortality. In the multivariate analysis, the activity SGRQ subscale (p < 0.001; odds ratio [OR], 2.62; confidence interval [CI], 1.43 to 4.78), comorbidity (p < 0.005; OR, 2.2; CI, 1.26 to 3.84), depression (p < 0.004; OR, 3.6; CI, 1.5 to 8.65), hospital readmission (p < 0.03; OR, 1.85; CI, 1.26 to 3.84), and marital status (p < 0.0002; OR, 3.12; CI, 1.73 to 5.63) were independent predictors of mortality. CONCLUSIONS: Quality of life, marital status, depressive symptoms, comorbidity, and prior hospital admission provide relevant information of prognosis in this group of COPD patients.

Acute Disease↗
PubMedDate not supplied

Application of pharmacokinetics and pharmacodynamics to antimicrobial therapy of community-acquired respiratory tract infections.

To achieve bacteriologic and clinical success, sufficient concentrations of antimicrobial at the site of infection must be maintained for an adequate period of time. These dynamics are determined by combining drug pharmacokinetic and pharmacodynamic (PK/PD) data with minimum inhibitory concentrations. Bacteriologically confirmed failures have been reported in otitis media and, with a lesser degree of evidence, in pneumococcal pneumonia with a variety of agents that include beta-lactams, macrolides and fluoroquinolones. These failures have been shown to be due to infection by resistant pathogens or suboptimal therapy. However, no clinical failure has been reported during therapy for bacteremic pneumococcal pneumonia with adequate doses of beta-lactams. The failures reported with macrolides or fluoroquinolones have been due to either preexisting resistance to these agents that cannot be overcome by increasing the dose of the antimicrobial or, more rarely, the emergence of resistance during therapy. In this review, we offer an overview of the most important attributes of the main antimicrobials that are currently used in the treatment of community-acquired respiratory tract infections from a PK/PD perspective.

Anti-Bacterial Agents↗