Bronchiectasis exacerbations: The role of atypical bacteria, respiratory syncytial virus and pulmonary function tests.

BACKGROUND: Aside from the known role of common bacteria, there is a paucity of data regarding the possible role of atypical bacteria and viruses in exacerbations of non-cystic fibrosis bronchiectasis. OBJECTIVE: To explore the possible role of atypical bacteria (namely, Mycoplasma pneumoniae and Chlamydophila pneumoniae) and respiratory syncytial virus (RSV) as causative agents of bronchiectasis exacerbations. METHODS: A cohort of 33 patients was studied over a two-year period (one year follow-up for each patient). Polymerase chain reaction for the detection of M pneumoniae, C pneumoniae and RSV in bronchoalveolar lavage samples were performed during all visits. Antibody titres (immunoglobulin [Ig]M and IgG) against the aforementioned pathogens were also measured. In addition, cultures for common bacteria and mycobacteria were performed from the bronchoalveolar lavage samples. RESULTS: Fifteen patients experienced a total of 19 exacerbations during the study period. Although RSV was detected by polymerase chain reaction during stable visits in four patients, it was never detected during an exacerbation. M pneumoniae and C pneumoniae were never detected at stable visits or during exacerbations. IgM antibody titres for these three pathogens were negative in all patient visits. CONCLUSIONS: Atypical pathogens and RSV did not appear to be causative agents of bronchiectasis exacerbations.

Metabolic acidosis may be as protective as hypercapnic acidosis in an ex-vivo model of severe ventilator-induced lung injury: a pilot study.

BACKGROUND: There is mounting experimental evidence that hypercapnic acidosis protects against lung injury. However, it is unclear if acidosis per se rather than hypercapnia is responsible for this beneficial effect. Therefore, we sought to evaluate the effects of hypercapnic (respiratory) versus normocapnic (metabolic) acidosis in an ex vivo model of ventilator-induced lung injury (VILI). METHODS: Sixty New Zealand white rabbit ventilated and perfused heart-lung preparations were used. Six study groups were evaluated. Respiratory acidosis (RA), metabolic acidosis (MA) and normocapnic-normoxic (Control - C) groups were randomized into high and low peak inspiratory pressures, respectively. Each preparation was ventilated for 1 hour according to a standardized ventilation protocol. Lung injury was evaluated by means of pulmonary edema formation (weight gain), changes in ultrafiltration coefficient, mean pulmonary artery pressure changes as well as histological alterations. RESULTS: HPC group gained significantly greater weight than HPMA, HPRA and all three LP groups (P = 0.024), while no difference was observed between HPMA and HPRA groups regarding weight gain. Neither group differ on ultrafiltration coefficient. HPMA group experienced greater increase in the mean pulmonary artery pressure at 20 min (P = 0.0276) and 40 min (P = 0.0012) compared with all other groups. Histology scores were significantly greater in HP vs. LP groups (p < 0.001). CONCLUSIONS: In our experimental VILI model both metabolic acidosis and hypercapnic acidosis attenuated VILI-induced pulmonary edema implying a mechanism other than possible synergistic effects of acidosis with CO2 for VILI attenuation.

Aerosol delivery of antimicrobial agents during mechanical ventilation: current practice and perspectives.

Critically ill patients, who develop ventilator-associated pneumonia during prolonged mechanical ventilation, often require antimicrobial agents administered through the endotracheal or the tracheotomy tube. The delivery of antibiotics via the respiratory tract has been established over the past years as an alternative route in order to deliver high concentrations of antimicrobial agents directly to the lungs and avoid systemic toxicity. Since the only formal indications for inhaled/aerosolized antimicrobial agents is for patients suffering from cystic fibrosis, consequently the majority of research and published studies concerns this group of patients. Newer devices and new antibiotic formulations are currently off-label used in ambulatory cystic fibrosis patients whereas similar data for the mechanically ventilated patients do not yet exist.

Pulmonary drug delivery systems for antimicrobial agents: facts and myths.

Inhaled antimicrobial agents are used for the treatment of respiratory tract infections due to Gram-negative bacteria, mainly Pseudomonas aeruginosa. The effectiveness of the inhaled antimicrobial therapy is believed to correlate with the delivery system used. The objective of this review was to search for data supporting differentiation in clinical effectiveness between systems used for pulmonary delivery of antibiotics, including delivery using disposable nebulisers and oxygen flow. Published studies in peer-reviewed journals comparing the effectiveness of pulmonary drug delivery systems for antimicrobial agents were retrieved. The studies found were either in vitro or Phase I and Phase II clinical studies. Differences in in vitro parameters may affect the in vivo efficacy of the devices, and in vivo differences may imply differences in clinical effectiveness. The main difference between newer and older devices is the time needed for antibiotic delivery. Interpretation and association with clinical effectiveness is difficult. In conclusion, Phase III clinical trials comparing the clinical effectiveness of delivery systems, including delivery using a hospital's oxygen flow and disposable nebulisers, do not exist. Cost is an important parameter, which may be counterbalanced in cystic fibrosis patients by a better quality of life and a greater adherence to treatment.

Tigecycline for the treatment of patients with community-acquired pneumonia requiring hospitalization.

Pneumonia, along with influenza, is the leading cause of mortality associated with infectious diseases in the USA. Tigecycline is a novel antimicrobial agent that is active against a broad spectrum of pathogens. Our objective is to review the literature about the efficacy of tigecycline in community-acquired pneumonia (CAP). Data from various sources, including Pubmed, the European Medicines Agency (EMEA) and the US FDA were appraised. Tigecycline was found to be noninferior compared with levofloxacin for the treatment of patients with bacterial CAP requiring hospitalization. Recently, the drug was approved for the treatment of these patients by the FDA, but owing to some concerns, its application in the EMEA has been withdrawn. In addition, in a recent study concerns were expressed about the efficacy of tigecycline in the lungs using the current dosage. More data are needed about the pharmacokinetics of tigecycline in the lungs and its efficacy in severe CAP.

Update on the safety of linezolid.

BACKGROUND: Linezolid is still the only representative of the oxazolidinones antibiotic class. Because of its novel mechanism of action and excellent tissue penetration, it is used in a variety of approved and off-label clinical conditions. OBJECTIVES: To review the literature (including latest publications) about the adverse events of linezolid and its overall safety. RESULTS/CONCLUSION: The range of adverse events of linezolid is growing; new ones, such as nephro-toxicity and Bell's palsy, have been reported. Toxicity of linezolid is mostly related with the prolonged duration of treatment and the presence of predisposing factors. Physicians must be alerted when using linezolid for indications and duration different from the approved ones, and must be aware of the possible adverse events. In case of toxicity, the main option is the discontinuation of the drug; although, not all adverse events are fully reversible. Linezolid represents an important advance in therapeutics and is still considered safe enough, but anticipated benefits must always be counterbalanced by the possible toxicity.