Nosocomial pneumonia: Current etiology and impact on antimicrobial therapy.

Nosocomial pneumonia is an infection with high clinical impact and high morbimortality in which Pseudomonas aeruginosa plays a priority role, especially in the critically ill patient. Conventional antipseudomonal treatments, historically considered as standard, are currently facing important challenges due to the increase of antimicrobial resistance. In recent years, new antimicrobials have been developed with attractive sensitivity profiles and remarkable efficacy in clinical scenarios of nosocomial pneumonia including bacteremia, mechanical ventilation, infections with multidrug-resistant organisms or situations of therapeutic failure. This new evidence underscores the need to update current clinical guidelines for the antimicrobial treatment of nosocomial pneumonia, especially in the most critically ill patients.

Utility of two biomarkers for directing care among patients with non-severe community-acquired pneumonia.

The aim of the present study is to evaluate the usefulness of two biomarkers-procalcitonin (PCT) and C-reactive protein (CRP)-in addition to the CURB-65 score for assessing the site of care and the etiology of non-severe community-acquired pneumonia (CAP). We conducted a prospective observational study from April 1, 2006, to June 30, 2007, in a single teaching hospital in northern Spain among patients with non-severe CAP. In addition to collecting data needed to determine the CURB-65 score, microbial cultures were taken and levels of PCT and CRP were measured. We compared the prognostic accuracy of these biomarkers with the CURB-65 score to predict hospitalization and microbial etiology using receiver operating characteristic (ROC) curves. A total of 344 patients with non-severe CAP were enrolled; 73 were admitted to the hospital and 271 were treated on an outpatient basis. An etiologic diagnostic was made for 44 %, with atypical pathogens predominating. Levels of PCT and CRP increased with increasing CURB-65 scores. Patients admitted to the hospital had higher PCT and CRP levels than outpatients (p < 0.001). For predicting hospitalization, PCT had a better area under the ROC curve (AUC) (0.81) than the CURB-65 score alone (0.77). For PCT plus the CURB-65 score, the AUC increased significantly from 0.77 to 0.83. In patients with bacterial CAP, the biomarker levels were significantly higher than among patients with atypical or viral etiology (p < 0.001). PCT with a cut-off point of 0.15 ng/mL was the best predictor for bacterial etiology and for select patients eligible for outpatient care. In conclusion, levels of PCT and CRP positively correlate with increasing severity of CAP and may have a role in predicting both patients who can safely receive outpatient care and the microbial etiology in patients with low CURB-65 scores.

Weekly docetaxel as second-line therapy for patients with advanced breast cancer resistant to previous anthracycline treatment.

This phase II trial evaluated the efficacy and toxicity of weekly docetaxel as treatment of advanced metastatic breast cancer patients resistant to prior anthracycline chemotherapy. After the first 18 patients, the initial dose (40 mg/m2, 30-min i.v. infusion for 6 consecutive weeks, followed by 2-week rest) was reduced to 36 mg/m2 in the remaining 17 patients due to the incidence of toxicity (28% grade 3-4 asthenia). Overall response rate was 34% (95% CI, 19-50): two complete (6%) and ten partial responses (28%) were found. The median duration of response was 6.8 months, the median time to disease progression was 8.4 months, and the median overall survival was 13.6 months (median follow-up of 11.4 months). Neutropenia was the only severe hematologic toxicity (17% of patients), whereas asthenia, nail, ocular and skin disorders were the most common nonhematologic toxicities. Only one death during further follow-up was related to toxicity (caused by pulmonary fibrosis). In conclusion, we found weekly docetaxel to be an active and safe chemotherapy regimen for patients with metastatic breast resistant to previous anthracyclines. This weekly regimen caused minimal myelosupression, while retaining significant activity against advanced breast cancer. Both factors provide attractive possibilities for the development of combination therapies incorporating weekly docetaxel. Nevertheless, the number of patients receiving either dose (40 and 36 mg/m2) which we studied is low and our results require confirmation on larger groups of patients.