What is the appropriate treatment approach for older children and adults with cystic fibrosis (CF) who have bacteria present in their lungs?

Treatment of Bacterial Infections in Older Children and Adults with Cystic Fibrosis

For older children (≥6 years) and adults with CF who have persistent Pseudomonas aeruginosa in their airways, chronic azithromycin therapy should be initiated to improve lung function and reduce pulmonary exacerbations. 1

Primary Treatment Strategy for Pseudomonas aeruginosa

Chronic Maintenance Therapy

• Azithromycin is the cornerstone of chronic therapy for CF patients aged 6 years and older with persistent P. aeruginosa colonization, demonstrating 3.6-6.2% improvement in FEV1 compared to placebo 1

• Dosing regimens include either 250-500 mg three times weekly or 250 mg daily, with treatment durations of 3-6 months showing sustained benefit 1

• Key benefits beyond lung function include significant reduction in pulmonary exacerbations and decreased need for additional antibiotic courses 1

• Important exclusions before starting azithromycin: patients with Burkholderia cepacia complex, atypical mycobacteria in sputum cultures, or liver disease/elevated liver function tests should not receive this therapy 1

Nebulized Antibiotic Therapy

• Inhaled tobramycin (TOBI Podhaler) is highly effective for CF patients aged 6-21 years with P. aeruginosa, achieving 12.44% relative improvement in FEV1 % predicted compared to placebo 2

• Dosing consists of 28-day on/off cycles: 4 capsules of 28 mg twice daily for 28 days, followed by 28 days off treatment 2

• Nebulized antibiotics achieve high lung concentrations with low systemic levels, though only 15-20% of medication deposits in the lungs 1

• Alternative nebulized options include colistin, gentamicin, and ceftazidime, though tobramycin has the most robust evidence 1

Acute Exacerbation Management

Oral Antibiotic Options

• Ciprofloxacin is the preferred oral fluoroquinolone for acute P. aeruginosa exacerbations, producing clinical improvement equivalent to intravenous azlocillin plus gentamicin 1

• Ciprofloxacin can extend benefits of IV therapy when given for 4 weeks following intravenous treatment 1

• Cartilage toxicity concerns are unfounded: ultrasound and MRI studies show no evidence of cartilage damage in CF patients treated with ciprofloxacin, despite animal study concerns 1

• Resistance emergence is the primary concern, not side effects, though clinical improvement often occurs despite resistant organisms 1

• Common side effects include gastrointestinal symptoms, arthralgia in older patients, sleep disorders, psychotic episodes, and photosensitivity 1

Intravenous Therapy

• IV antibiotics remain necessary for severe exacerbations, with combination therapy (beta-lactam plus aminoglycoside) preferred to reduce resistance development 1

• Standard combinations include ceftazidime, piperacillin-tazobactam, or azlocillin paired with tobramycin or gentamicin 1, 2

Management of Staphylococcus aureus

Critical Recommendation Against Prophylaxis

• Prophylactic antistaphylococcal antibiotics should NOT be used in CF patients, as the risk of earlier P. aeruginosa colonization outweighs any potential benefit 1

• The evidence shows harm: the largest study with longest follow-up (209 patients over 7 years) demonstrated greater occurrence of Pseudomonas in patients receiving staphylococcal prophylaxis with cephalexin 1

• Treatment should be reserved for active infections only, not prophylaxis, despite S. aureus being commonly identified in young CF patients 1

Emerging Pathogens and Monitoring

Bacterial Surveillance

• P. aeruginosa remains the dominant pathogen, affecting 29.8% of CF patients aged 2-5 years and 81.3% of those aged 26-30 years 1

• Other important pathogens include Stenotrophomonas maltophilia, MRSA, Achromobacter xylosoxidans, and nontuberculous mycobacteria 3, 4, 5

• Regular microbiological monitoring is essential, with sputum cultures (or throat swabs in non-expectorating patients) obtained at routine intervals 1

• Chronic colonization is defined as presence of P. aeruginosa for at least 6 months based on at least three positive cultures with at least one month intervals 1

Important Clinical Distinctions

• Colonization versus infection: colonization lacks direct inflammation/fever or indirect antibody response signs, while infection demonstrates tissue damage and inflammatory markers 1

• Early inflammation precedes infection: studies show elevated polymorphonuclear leukocytes and IL-8 in young CF patients before pathogenic bacteria are detected 6

Common Pitfalls to Avoid

• Do not use antistaphylococcal prophylaxis as it accelerates Pseudomonas acquisition 1

• Do not delay azithromycin in patients ≥6 years with persistent P. aeruginosa 1

• Do not avoid fluoroquinolones in adolescents due to cartilage concerns—this fear is not evidence-based 1

• Do not use ciprofloxacin in children <5 years as experience is very limited in this age group 1

• Do not ignore Burkholderia cepacia or atypical mycobacteria when considering azithromycin, as these are absolute contraindications 1