Cystic Fibrosis

• Most common in Caucasian population
• Most common mutation is deltaF508
• Autosomal recessive trait (if both parents are carriers, 25% chance of child not having the gene, 25% chance of child having the disease, 50% chance of child being carrier)

Defect in CFTR chloride channel results in decreased chloride secretion and increased sodium absorption (decr H20 secretion) - leads to altered viscosity of fluid excreted by exocrine glands and mucosal obstruction

• Resp system: airway obstruction, chronic airway colonization/infx, chronic cough/sputum production, acute exacerbations, decreased exercise tolerance, digital clubbing, barrel chest, sinusitis
• GI system: pancreatic insufficiency leading to malabsorption and maldigestion, failure to thrive, vitamin deficiencies, recurrent pancreatitis, meconium ileus, distal intestinal obstruction syndrome, hepatobiliary disease, hypoproteinemia, CF related diabetes
• Salt loss thru salty sweat
• Sterility
• Late maturation - delayed puberty
• menstrual irregularities
• anemia
• arthritis
• osteopenia/osteoporosis

• Airway clearance - chest physiotherapy, high-frequency chest compression vest QD to BID
• Albuterol
• Mucolytics (Dornase alfa, hypertonic saline for inhalation pretreated with bronchodilator, N-acetylcysteine)
• LABA in pts with wheezing/dyspnea who benefit from albuterol
• Montelukast, antihistamines, intranasal steroids in pts with reactive airways or rhinitis
• PO corticosteroids NOT recommended for maintenance
• Antiinflammatory treatment - Azithromycin (3d/wk), high-dose ibuprofen, inhaled corticosteroid

• Pancreatic enzyme replacement -
• decr stool freq, incr stool quality, weight gain
• contains lipase, amylase, protease
• Enteric coated - capsules can be opened and mixed with acidic foods (but not in bottles)
• Infants - can mix with applesauce or rice cereal and give milk after - make sure no particles are left in mouth after - can cause ulcers
• Generics have dissolution probs - don't use
• Different brands are not bioequiv
• 1500-2000 units lipase/120 ml milk or 500-1000 units lipase/kg/meal

• Fat soluble vitamin supplementation
• Appetite stimulants
• Ursodiol to slow progression of liver disease
• PEG (miralax) for distal intestinal obstruction syndrome

• Oral or IV Fluoroquinolones (cipro or levofloxacin) - good for outpt treatment of mild resp exacerbation - not good for long-term d/t resistance which happens quickly with FQ monotx
• IV antipseudomonal beta-lactams (piperacillin, pip/tazo, ceftazidime, cefepime, imipenem, meropenem, aztreonam)
• IV aminoglycosides (tobramycin, gentamicin, amikacin)
• Combos for more severe exacerbations - IV antipseudomonal beta lactam plus IV AG (e.g. ceftazidime + tobramycin) - combos promote less resistance and may provide synergy

Azithromycin - taken 3x/wk

• tobramycin - it can suppress bacterial overgrowth of P. aeruginosa
• Used on a 28d on/28d off schedule
• leads to improved lung fxn, reduced microbes in sputum and fewer hospitalizations for IV abx

Inhaled aztreonam was recently approved for pts > or = 7 yoa (given tid)

• Methicillin-sensitive:
• amox-clav
• dicloxacillin
• 1st or 2nd gen cephs
• TMP/SMX
• clindamycin

• Methicillin-resistant:
• TMP/SMX
• clindamycin
• minocycline
• linezolid

• amox-clav
• ceph
• TMP/SMX

• TMP/SMX
• minocycline

CF pts have higher volumes of distribution and enhanced total body clearance of many abx to use higher doses more frequently