What is Zpak (azithromycin) used for?

What is Z-Pak (Azithromycin) Used For?

Z-Pak (azithromycin) is FDA-approved for treating community-acquired respiratory tract infections, skin and soft tissue infections, and sexually transmitted infections caused by susceptible bacteria, though it should NOT be first-line for most conditions due to increasing resistance and safety concerns. 1

FDA-Approved Indications

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 exacerbations of COPD due to H. influenzae, Moraxella catarrhalis, or S. pneumoniae 1
• Acute bacterial sinusitis due to 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

Critical caveat: Azithromycin should NOT be used in pneumonia patients with moderate-to-severe illness, cystic fibrosis, nosocomial infections, bacteremia, hospitalization requirements, elderly/debilitated status, or immunodeficiency 1

Skin and Soft Tissue Infections

• Uncomplicated skin infections due to Staphylococcus aureus, Streptococcus pyogenes, or Streptococcus agalactiae 1
• Abscesses typically require surgical drainage in addition to antibiotics 1

Sexually Transmitted Infections

• Urethritis and cervicitis due to Chlamydia trachomatis or Neisseria gonorrhoeae 1
• Genital ulcer disease in men due to Haemophilus ducreyi (chancroid) 1

Important warning: Azithromycin at recommended doses does NOT treat syphilis adequately and may mask incubating syphilis 1. All patients with STIs should receive serologic testing for syphilis and appropriate gonorrhea cultures 1

Current Guideline Recommendations (When NOT to Use Z-Pak First-Line)

Sexually Transmitted Infections - Use Doxycycline Instead

Doxycycline is now preferred over azithromycin for chlamydial and non-gonococcal urethritis 2. Azithromycin should only be used if:

• Doxycycline has failed 2
• Doxycycline is contraindicated 2
• Major adherence concerns exist with the longer doxycycline regimen 2

This recommendation reflects declining efficacy: azithromycin cure rates for Mycoplasma genitalium dropped from 85.3% before 2009 to only 67.0% since 2009 3. Additionally, azithromycin efficacy is 97% versus doxycycline's 100% for chlamydia, with non-inferiority not established 2

Community-Acquired Pneumonia - Consider Resistance Patterns

• Azithromycin monotherapy is acceptable for previously healthy outpatients WITHOUT comorbidities 3
• For patients WITH comorbidities, combine azithromycin with a β-lactam (high-dose amoxicillin, amoxicillin-clavulanate, ceftriaxone, cefpodoxime, or cefuroxime) 3
• Do NOT use azithromycin monotherapy in regions with >25% macrolide-resistant S. pneumoniae 3
• For hospitalized patients, combine azithromycin with β-lactam for coverage of S. pneumoniae and Legionella species 3

Pregnancy Considerations

• Azithromycin is the preferred macrolide during pregnancy as it is safer than clarithromycin 3
• However, for chlamydia in pregnancy, erythromycin base or amoxicillin remain recommended regimens, with azithromycin as an alternative 2

Critical Safety Warnings

Cardiac Toxicity

Azithromycin can cause fatal cardiac arrhythmias including QT prolongation, ventricular tachycardia, and torsades de pointes 3. Avoid or use with extreme caution in patients with:

• Known QT prolongation 3
• History of torsades de pointes 3
• Concurrent use with terfenadine, astemizole, pimozide, or cisapride 3

Tuberculosis Risk

Empiric azithromycin for pneumonia may delay tuberculosis diagnosis 4. Consider TB screening in high-risk populations before initiating therapy 3, 4

Non-Tuberculous Mycobacteria (NTM)

Current NTM infection is an absolute contraindication for azithromycin monotherapy 3. Screen patients with clinical suspicion via sputum samples before starting therapy 2. Long-term azithromycin monotherapy risks developing macrolide-resistant NTM, which has very poor treatment success rates 2

Resistance Development

Azithromycin's long half-life creates a 14-20 day "window" of subinhibitory drug concentrations that promotes resistance development 4. Meta-analyses show a 2.7-fold increased risk of macrolide resistance among respiratory pathogens in patients receiving azithromycin 2

Dosing Considerations

• Standard adult dosing varies by indication (see FDA label for specifics) 1
• Typical duration is 3-5 days for respiratory infections 5, 6
• Single 1-gram dose for chlamydial urethritis/cervicitis 1, 7
• Once-daily dosing enhances compliance compared to multiple-daily-dose regimens 5, 8, 7

When Azithromycin IS Appropriate

• Cystic fibrosis with persistent Pseudomonas aeruginosa: Long-term azithromycin (500mg three times weekly or 250mg daily) improves lung function and reduces exacerbations 3
• Pregnancy when macrolide needed: Azithromycin is safer than clarithromycin 3
• Single-dose STI treatment when adherence is critical concern: Though not first-line 1
• Legionella pneumonia: As part of combination therapy 3