What conditions are Zpack (azithromycin) used to treat?

Azithromycin (Z-pack) Indications

Azithromycin is FDA-approved to treat bacterial respiratory infections (pneumonia, bronchitis, sinusitis), skin/soft tissue infections, pharyngitis/tonsillitis, and sexually transmitted infections including chlamydia, gonorrhea, and chancroid. 1

FDA-Approved Respiratory Infections

Azithromycin treats the following respiratory conditions in adults:

• 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 caused by H. influenzae, M. catarrhalis, or S. pneumoniae 1
• Pharyngitis/tonsillitis from Streptococcus pyogenes as an alternative when first-line therapy cannot be used 1

Critical caveat: Azithromycin should NOT be used for pneumonia in patients with moderate-to-severe illness, cystic fibrosis, nosocomial infections, suspected bacteremia, hospitalized patients, elderly/debilitated patients, or those with immunodeficiency or functional asplenia 1. These patients require parenteral therapy.

FDA-Approved Skin and Soft Tissue Infections

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

FDA-Approved Sexually Transmitted Infections

Azithromycin treats multiple STIs with specific dosing:

• Urethritis and cervicitis due to Chlamydia trachomatis or Neisseria gonorrhoeae 1
• Genital ulcer disease (chancroid) in men caused by Haemophilus ducreyi 1
• For chlamydia, a single 1-gram dose is recommended 2
• For gonorrhea, a single 2-gram dose must be combined with ceftriaxone 1g IM/IV—never use azithromycin monotherapy due to resistance 2

Important warning: Azithromycin at recommended doses does NOT treat syphilis and may mask incubating syphilis 1. All patients with STI symptoms require serologic testing for syphilis and gonorrhea cultures at diagnosis 3, 1.

Pediatric Indications

In children, azithromycin effectively treats:

• Otitis media, pharyngitis/tonsillitis, community-acquired pneumonia, bronchitis, and skin/soft tissue infections with comparable efficacy to amoxicillin/clavulanic acid, cefaclor, and erythromycin 4
• Standard pediatric dosing is either 10 mg/kg/day for 3 days or 10 mg/kg on day 1 followed by 5 mg/kg/day for 4 days 4
• For streptococcal pharyngitis specifically, higher dosing of 12 mg/kg/day for 5 days is needed due to higher recurrence rates compared to penicillin 4
• Pertussis in infants <1 month: 10 mg/kg daily for 5 days, with monitoring for infantile hypertrophic pyloric stenosis 2

Off-Label Uses in Chronic Respiratory Disease

Long-term azithromycin prophylaxis is used for:

• Bronchiectasis with ≥3 exacerbations/year: 500 mg three times weekly or 250 mg daily for 6-12 months minimum 2
• Cystic fibrosis with chronic Pseudomonas aeruginosa: 250 mg daily or 250-500 mg three times weekly long-term if beneficial 2
• Severe uncontrolled asthma: trial of 500 mg three times weekly or 250 mg daily for 6-12 months 2

Critical screening required before chronic therapy: ECG to exclude QTc >450 ms (men) or >470 ms (women), sputum examination for non-tuberculous mycobacteria (NTM), and baseline liver function tests 3, 2. Macrolide monotherapy is contraindicated if NTM is identified, as resistance develops rapidly and treatment success becomes very poor 3.

Antimicrobial Resistance Concerns

Azithromycin use carries significant resistance risks:

• In chronic respiratory disease, macrolide-resistant pathogen colonization increases 2.7-fold compared to placebo 3
• The 68-hour half-life creates prolonged subinhibitory concentrations lasting 14-20 days, providing a "selection window" for resistant organisms 3
• Rising macrolide resistance affects treatment of STIs (gonorrhea, chlamydia), Campylobacter diarrhea, and respiratory pathogens 3
• Patients must understand that resistance may eliminate effective antibiotic options for themselves or others in the future 3

Drug Interactions and Contraindications

• Avoid aluminum/magnesium antacids taken simultaneously, as they reduce azithromycin absorption 2
• Contraindicated with QTc prolongation or drugs that prolong QT interval 3
• The FDA issued a 2013 warning about cardiovascular deaths and cardiac arrhythmias, particularly in patients with high baseline cardiovascular risk 3
• Not recommended in pregnancy for chlamydia treatment—erythromycin base or amoxicillin are preferred 3