When is it appropriate to prescribe a Z pack (azithromycin)?

When to Prescribe Azithromycin (Z-Pack)

Azithromycin should NOT be routinely prescribed for acute bronchitis or uncomplicated upper respiratory infections, as these are predominantly viral and antibiotics provide no benefit while increasing adverse events. 1

Appropriate Indications for Azithromycin

Confirmed Bacterial Infections

Community-Acquired Pneumonia (CAP)

• For hospitalized patients (non-ICU): Azithromycin combined with a beta-lactam (cefotaxime, ceftriaxone, or ampicillin-sulbactam) is recommended 1
• For ICU patients: Beta-lactam plus azithromycin or a fluoroquinolone is the minimal recommended treatment 1
• Azithromycin monotherapy may be considered only for carefully selected outpatients with nonsevere disease and no risk factors for drug-resistant S. pneumoniae or gram-negative pathogens 1

Pertussis (Whooping Cough)

• Adults: 500 mg on day 1, followed by 250 mg daily on days 2-5 1, 2
• Children ≥6 months: 10 mg/kg (max 500 mg) on day 1, then 5 mg/kg daily (max 250 mg) on days 2-5 1, 2
• Infants <6 months: Azithromycin is preferred over erythromycin due to significantly lower risk of infantile hypertrophic pyloric stenosis; dose is 10 mg/kg daily for 5 days 1, 2
• Treatment is most effective when started early (within first 2 weeks of cough onset) 2

Sexually Transmitted Infections

• Chlamydia: Single 1g oral dose for adults and children >8 years or weighing >45 kg 3, 4
• Urethritis/cervicitis due to Chlamydia trachomatis or Neisseria gonorrhoeae 4
• Chancroid (genital ulcer disease in men due to Haemophilus ducreyi) 4

Streptococcal Pharyngitis

• Only as an alternative to first-line therapy (penicillin) in patients who cannot use penicillin 1, 4
• Must confirm group A Streptococcus with rapid antigen test or culture before prescribing 1
• Important caveat: Azithromycin does NOT prevent rheumatic fever as effectively as penicillin 1, 4

Acute Bacterial Sinusitis

• Only when bacterial infection is confirmed or highly suspected based on clinical criteria 5
• 500 mg once daily for 3 days has shown efficacy 5

Skin and Soft Tissue Infections

• Uncomplicated infections due to Staphylococcus aureus, Streptococcus pyogenes, or Streptococcus agalactiae 4
• Abscesses require surgical drainage in addition to antibiotics 4

When NOT to Prescribe Azithromycin

Acute Bronchitis

• Do not prescribe antibiotics unless pneumonia is suspected 1
• Over 90% of acute bronchitis cases are viral 1
• Purulent or colored sputum does NOT indicate bacterial infection 1
• Studies show azithromycin causes significantly more adverse events than placebo without clinical benefit 1

Viral Pharyngitis

• Patients with cough, nasal congestion, conjunctivitis, hoarseness, diarrhea, or oral ulcers/vesicles have viral illness and should not receive antibiotics 1

Common Cold or Viral Upper Respiratory Infections

• These do not respond to antibacterial therapy 4

Critical Safety Considerations Before Prescribing

Cardiac Risk Assessment (MANDATORY)

• Obtain baseline ECG to assess QTc interval 1, 4
• Do not prescribe if QTc >450 ms (men) or >470 ms (women) 1, 4
• Avoid in patients with: known QT prolongation, history of torsades de pointes, congenital long QT syndrome, bradyarrhythmias, uncompensated heart failure, uncorrected hypokalemia/hypomagnesemia 4
• Avoid concurrent use with Class IA (quinidine, procainamide) or Class III (dofetilide, amiodarone, sotalol) antiarrhythmics 4

Hepatic Function

• Check baseline liver function tests 1
• Use with caution in patients with impaired hepatic function 4
• Discontinue immediately if signs of hepatitis occur 4

Drug Interactions

• Azithromycin does NOT inhibit cytochrome P450 (unlike erythromycin and clarithromycin), making it safer with fewer drug interactions 1
• Monitor prothrombin time if patient is on warfarin 4
• Do not take simultaneously with aluminum- or magnesium-containing antacids 1, 4

Contraindications

• History of hypersensitivity to any macrolide 2
• Myasthenia gravis (may cause exacerbation) 4

Microbiological Testing Requirements

Before Prescribing:

• Perform appropriate culture and susceptibility testing when possible 4
• For pharyngitis: rapid antigen test or throat culture for group A Streptococcus 1
• For pneumonia: sputum culture to identify causative organism 4
• For sexually transmitted infections: serologic test for syphilis and cultures for gonorrhea 4
• Check for nontuberculous mycobacteria (NTM) in patients with chronic respiratory conditions; avoid macrolide monotherapy if NTM identified 1

Resistance Monitoring:

• Some strains of S. pyogenes are resistant to azithromycin; susceptibility testing should be performed 4
• Macrolide resistance rates vary by region and should inform prescribing decisions 1

Common Pitfalls to Avoid

1. Do not prescribe for acute bronchitis "just in case" - this is the leading cause of inappropriate antibiotic use in adults 1
2. Do not assume colored sputum means bacterial infection - purulence is due to inflammatory cells, not bacteria 1
3. Do not use azithromycin alone for severe pneumonia - combination therapy with a beta-lactam is required 1
4. Do not rely on azithromycin to treat or prevent syphilis - it is inadequate for this purpose 4
5. Do not skip the ECG - cardiac complications including torsades de pointes can be fatal 4