Start empiric coverage for resistant gram-negative organisms in patients with cystic fibrosis (CF) andexacerbations of pulmonary disease
Start empiric coverage for resistant gram-negative organisms in patients with cystic fibrosis (CF) andexacerbations of pulmonary disease: Excerpt from Avoiding Common Pediatric Errors
Author:
Jennifer Maniscalco, MD
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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.
Suggested Readings
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.
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Book Source Details
- Book Title: Avoiding Common Pediatric Errors
- Author(s): Anthony D Slonim MD, DrPH; Lisa Marcucci MD
- Year of Publication: 2008
- Copyright Details: Avoiding Common Pediatric Errors, Copyright © 2008 Lippincott Williams & Wilkins.
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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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