Optimal airway antimicrobial therapy for cystic fibrosis: the role of inhaled aztreonam lysine

Importance of the field: Chronic endobronchial infection in cystic fibrosis (CF) leads to progressive lung function loss and respiratory failure. Most adult CF patients are infected with Pseudomonas aeruginosa, an important predictor of mortality. Suppressing chronic P. aeruginosa infection with inhaled antibiotics is standard of care for CF patients.

Areas covered in this review: This review describes the development (2003 – 2010) of aztreonam lysine 75 mg powder and solvent for nebulizer solution (AZLI; Cayston^®), an aerosolized formulation of the monobactam antibiotic aztreonam.

What the reader will gain: AZLI was studied in patients with CF and chronic P. aeruginosa airway infection. In placebo-controlled trials, AZLI improved respiratory symptoms, increased forced expiratory volume in 1 sec (FEV₁), decreased sputum P. aeruginosa density, and was well tolerated. An open-label follow-on trial of nine ‘on/off’ courses showed that AZLI was safe and the effect durable with repeated administration. AZLI was recently approved for use in CF patients in Australia and the USA, and conditionally approved in Canada and the European Union. AZLI is given three times daily for 28 days (2 – 3 min/dose), followed by 28 days off-drug. AZLI is used only with the Altera Nebulizer System?, which provides appropriate particle size and small airway deposition, and has excellent portability.

Take home message: AZLI is a new therapy that is safe and effectively improves respiratory symptoms and FEV₁ in patients with CF.     

Renal disease

AMA Category 1 credit (2 hr), AAFP Prescribed credit (2 hr), and AOA Category 28 credit (1 hr) may be obtained by reading the article beginning on page 72 and submitting the related quiz. The other articles in this group are followed by self-assessment questions.     

Operative Techniques in the Fetal Rabbit

The development of fetal surgical techniques has made the antenatal correction of congenital defects possible. These techniques have evolved from trials with animal models, permitting increasingly sophisticated operations with low morbidity and mortality. Experimental models range from large animals offering longer gestations but with single pregnancies and high cost, to smaller animals offering multiple pregnancies at reduced cost but with shorter gestations. This paper describes operative techniques in the fetal rabbit and its advantages as a fetal surgical model. Experience with the pregnant rabbit has shown it to be a suitable surgical model for several reasons. Pregnancies are multiple, increasing cost effectiveness and permitting operation on up to eight fetuses per litter without fetal loss. Techniques that promote fetal survival include local housing of does several days prior to operation and preoperative sedation. Spontaneous mask ventilation provides ease of anesthetic administration and titration. Overall surgery is well tolerated with a low incidence of intraoperative complications. Rabbit models have been used in the study of transamniotic fetal feeding, abdominal wall defects, and wound healing. These techniques have resulted in postoperative fetal viability approaching 90%, with negligible maternal mortality in over 4000 fetal operations, thereby making the rabbit a manageable cost-effective model of fetal surgery.     

Triple Therapy in COPD: What We Know and What We Don't

Triple inhaled therapy for chronic obstructive pulmonary disease (COPD) consists of an inhaled corticosteroid (ICS), a long-acting β₂-agonist (LABA) and a long-acting muscarinic antagonist (LAMA) taken in combination. Triple therapy is recommended by the Global initiative for Chronic Obstructive Lung Disease (GOLD) for patients who experience recurrent exacerbations despite treatment with either a dual bronchodilator (preferred initial therapy) or LABA/ICS combination (alternative initial therapy). Although there is evidence for the greater efficacy of triple therapy compared with LABA/ICS and LAMA monotherapy with regards to improved lung function, health status, and exacerbation rate, the efficacy of triple therapy when compared with dual bronchodilation (LABA/LAMA) is as yet unknown. As ICS use is associated with an increased risk of developing pneumonia, it is important to assess the risk/benefit ratio of triple therapy on an individual basis, and identify patients most likely to benefit. The role of elevated blood eosinophils as a biomarker for the identification of candidates for ICS treatment is currently debated, and further prospective evidence is required. This review assesses evidence for the efficacy and safety of triple therapy and postulates on the prospective evidence from ongoing studies. The potential for treating patients who experience further exacerbations on dual bronchodilation according to phenotype is also considered, as well as withdrawal of ICS from triple therapy in patients who are unlikely to benefit.