What is a Z-Pak (azithromycin) used to treat in patients?

What is a Z-Pak (Azithromycin) Used For?

A Z-Pak (azithromycin) is FDA-approved to treat bacterial respiratory tract infections (community-acquired pneumonia, acute bacterial sinusitis, acute exacerbations of chronic bronchitis), pharyngitis/tonsillitis, uncomplicated skin infections, and sexually transmitted infections (urethritis, cervicitis, chancroid), but should never be used as monotherapy for hospitalized patients or in areas where pneumococcal macrolide resistance exceeds 25%. 1

FDA-Approved Indications in Adults

• Respiratory tract infections: Community-acquired pneumonia caused by Chlamydophila pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae, or Streptococcus pneumoniae in patients appropriate for oral therapy 1
• Acute bacterial sinusitis caused by H. influenzae, Moraxella catarrhalis, or S. pneumoniae 1
• Acute bacterial exacerbations of COPD caused by H. influenzae, M. catarrhalis, or S. pneumoniae 1
• Pharyngitis/tonsillitis caused by Streptococcus pyogenes as an alternative when first-line therapy cannot be used 1
• Uncomplicated skin and skin structure infections caused by Staphylococcus aureus, Streptococcus pyogenes, or Streptococcus agalactiae 1
• Sexually transmitted infections: Urethritis and cervicitis caused by Chlamydia trachomatis or Neisseria gonorrhoeae, and genital ulcer disease (chancroid) caused by Haemophilus ducreyi 1

FDA-Approved Indications in Pediatric Patients

• Acute otitis media caused by H. influenzae, M. catarrhalis, or S. pneumoniae 1
• Community-acquired pneumonia caused by C. pneumoniae, H. influenzae, M. pneumoniae, or S. pneumoniae in patients appropriate for oral therapy 1
• Pharyngitis/tonsillitis caused by S. pyogenes as an alternative when first-line therapy cannot be used 1

Off-Label Uses Supported by Guidelines

• Cystic fibrosis maintenance therapy: Chronic azithromycin (typically 250-500 mg three times weekly) reduces pulmonary exacerbations and improves lung function in CF patients ≥6 years with persistent Pseudomonas aeruginosa colonization 2
• Bronchiectasis with chronic infection: Long-term azithromycin reduces exacerbation frequency, though eradication of respiratory pathogens is inconsistent 2
• Nontuberculous mycobacterial (NTM) infections: Azithromycin is a key component of multidrug regimens for MAC lung disease, but must never be used as monotherapy to prevent macrolide resistance 2
• Severe bacterial gastroenteritis: IV azithromycin 500 mg daily for 2-5 days is first-line for dysentery or severe watery diarrhea, particularly when fluoroquinolone-resistant Campylobacter is suspected 3
• Acne vulgaris: Off-label use as a systemic antibiotic, though monotherapy should be avoided 2

Critical Contraindications and Warnings

• Never use azithromycin alone for hospitalized pneumonia patients—it provides inadequate coverage for typical bacterial pathogens like S. pneumoniae and requires combination with a β-lactam (ceftriaxone) 4
• Avoid in areas with high macrolide resistance: Azithromycin monotherapy should only be used when local pneumococcal macrolide resistance is documented <25% 4, 5
• Cardiac risk: Azithromycin can cause fatal cardiac arrhythmias including torsades de pointes; avoid in patients with known QT prolongation 5
• Not appropriate for severe pneumonia: Do not use in patients with cystic fibrosis, nosocomial infections, known/suspected bacteremia, hospitalization requirements, elderly/debilitated patients, or those with immunodeficiency 1
• Tuberculosis masking: Empiric azithromycin for pneumonia may delay TB diagnosis; consider TB screening in high-risk populations before initiating therapy 5
• Syphilis: Azithromycin should not be relied upon to treat syphilis; all patients with sexually-transmitted urethritis/cervicitis require serologic testing for syphilis 1

Typical Dosing Regimens

• Community-acquired pneumonia (outpatient): 500 mg on day 1, then 250 mg daily for days 2-5 (total 5 days) 4
• Acute bacterial sinusitis/COPD exacerbation: 500 mg daily for 3 days 1
• Streptococcal pharyngitis: 12 mg/kg/day for 5 days in children (higher dose needed due to recurrence risk with standard dosing) 6
• Sexually transmitted infections: Single 1-gram dose for uncomplicated chlamydial urethritis/cervicitis 1
• Cystic fibrosis maintenance: 250 mg (weight <40 kg) or 500 mg (weight ≥40 kg) three times weekly 2
• Severe gastroenteritis: 1000 mg single dose or 500 mg daily for 3 days 3

Antimicrobial Spectrum

• Enhanced activity compared to erythromycin: H. influenzae (including ampicillin-resistant strains), M. catarrhalis, N. gonorrhoeae, Ureaplasma urealyticum, Borrelia burgdorferi 7, 8
• Good activity against atypical pathogens: Mycoplasma pneumoniae, Chlamydophila pneumoniae, Legionella species 6, 7, 9
• Activity against susceptible strains: Erythromycin- and penicillin-susceptible S. pneumoniae, methicillin-susceptible S. aureus, S. pyogenes, S. agalactiae 6, 8
• Cross-resistance: Erythromycin-resistant organisms are also resistant to azithromycin 7, 9

Pharmacokinetic Advantages

• Tissue-selective distribution: Achieves high tissue concentrations (exceeding those of erythromycin) despite low serum levels, with concentrations remaining above MIC for several days after dosing 8, 9
• Intracellular accumulation: Rapidly penetrates phagocytic cells with release at local infection sites 8
• Long half-life: Terminal elimination half-life up to 5 days allows once-daily dosing and short treatment courses 7, 9
• Acid stability: Superior oral bioavailability compared to erythromycin 8

Common Pitfalls to Avoid

• Do not use for hospitalized pneumonia without a β-lactam: Combination with ceftriaxone is mandatory for adequate pneumococcal coverage 4
• Do not use in high macrolide-resistance areas: Treatment failure occurs when pneumococcal resistance exceeds 25% 4, 5
• Do not use for dysentery without considering alternatives: While azithromycin is first-line, rifaximin has 50% failure rates for invasive pathogens 3
• Do not use as monotherapy for NTM infections: Macrolide resistance develops rapidly without companion drugs 2
• Do not administer with aluminum/magnesium antacids: Reduces absorption significantly 3
• Do not use in patients requiring hospitalization for pneumonia: Risk factors include moderate-to-severe illness, cystic fibrosis, nosocomial acquisition, bacteremia, elderly/debilitated status, or immunodeficiency 1