CF is an autosomal recessive disorder resulting from mutations in a single gene, located on the long arm of chromosome 7. These mutations result in the absence of a functioning cystic fibrosis transmembrane conductance regulator (CFTR), which conducts chloride across cell membranes. CFTR is expressed in exocrine glands throughout the body. In the airways, it is predominantly expressed in the submucosal glands. Abnormal or absent CFTR function clogs the glands with mucous and changes the composition and mechanical properties of the airway secretions, initiating a pathophysiologic cascade that ultimately leads to progressive and chronic lung disease. Chronic endobronchial infection and the associated intense neutrophilic inflammatory response are pathognomonic for the disease.
Individuals with CF develop pulmonary infections with a unique set of bacterial pathogens, which are acquired in an age-dependent fashion. Initial infectionsoccur shortly afterbirth andaretypicallycausedbynon–type-able Haemophilus influenzae and Staphylococcus aureus. Subsequent infections are caused by Pseudomonas aeruginosa, the most common virulent pathogen in patients with CF. Recent investigations have confirmed that infection with P. aeruginosa occurs earlier than previously believed. Up to 80% of children with CF will eventually be infected, with the initial infection occurring on average by age 2. Early strains of P. aeruginosa remain sensitive to antibiotics and can be eradicated with aggressive antimicrobial therapy. Persistent strains become mucoid, adapting to the local environment through the formation of macrocolonies and the production of an exopolysaccharide that confers resistance to phagocytosis and penetration by antibiotics. The acquisition of P. aeruginosa is associated with progression of lung disease and is a limiting factor in overall survival. The mucoid strains are associated with a more significant clinical deterioration. Late in the disease process, infections are caused by other opportunistic organisms, including Burkholderia cepacia complex, Stenotrophomonas maltophilia, Achromobacter xylosoxidans, fungi, and nontuberculous mycobacterium. B. cepacia complex is a group of closely related species that can cause a syndrome of high fever, bacteremia, severe necrotizing pneumonia, and possibly death.
Appropriate antibiotic therapy is a critical component of both periodic exacerbations and chronic maintenance therapy in CF. Antibiotic management can be divided into three phases, reflecting the progression of infection with organism as detailed above. Early in the disease process, the goal of therapy is to delay colonization with P. aeruginosa and prevent the decline in pulmonary function that accompanies it. Once colonization with P. aeruginosa has occurred, use of continuous P. aeruginosa coverage is recommended to stabilize lung function and reduce the likelihood of pulmonary exacerbations. This is often accomplished with inhaled antibiotics, or chronic therapy with fluoroquinolones. When periodic exacerbations do occur, intravenous antibiotics should be administered in addition to bronchodilators and anti-inflammatory agents. Typically, combination therapy with an aminoglycoside and β-lactam antibiotic is used to counteract P. aeruginosa and other gram-negative organisms. Table 183.1 lists antibiotic choices for the treatment of bacteria associated with pulmonary exacerbations in CF.
Regardless of the phase of therapy, antibiotic choice should be based on the periodic isolation and identification of pathogens from respiratory secretions and a review of the susceptibility profile. If multidrug resistance is suspected, the specimen should be sent to a reference lab for synergy testing or combination bactericidal testing. Expectorated sputum has been shown to be an accurate indicator of lower airway microbiology and is the preferred source of airway secretions. Cultures collected by bronchoalveolar lavagearealsoverysensitive,buttheprocedurecarriesmoreriskandcostthan simplesputumcollectionorhypertonicsaline-inducedsputumcollection.In addition, specimens from bronchoalveolar lavage may miss focal or regional disease.
Gibson RL, Burns JL, Ramsey BW. Pathophysiology and management of pulmonary infections
in cystic fibrosis. Am J Resp Crit Care Med. 2003;168:918–951.
Li Z, Kosork MR, Farrell PM, et al. Longitudinal development of mucoid Pseudomonas
aeruginosa infection and lung disease progression in children with cystic fibrosis. JAMA.
2005;293:581–588.
Rowe SM, Miller S, Sorscher EJ. Cystic fibrosis. N Engl J Med. 2005;352:1992–2001.
Review other book chapters online related to Pulmonary fibrosis:
Copyright notice for book excerpts: Copyright © 2008 Lippincott Williams & Wilkins. All rights reserved.
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More About This Book:
Title: Avoiding Common Pediatric Errors Authors: Anthony D Slonim MD, DrPH; Lisa Marcucci MD Publisher: Lippincott Williams & Wilkins Copyright: 2008 ISBN: 0-7817-7489-6 
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