What are the indications for Azithromycin (macrolide antibiotic)?

Indications for Azithromycin

Azithromycin is FDA-approved for treating acute bacterial respiratory infections (sinusitis, COPD exacerbations, community-acquired pneumonia), pharyngitis/tonsillitis, uncomplicated skin/soft tissue infections, and sexually transmitted infections (chlamydial urethritis/cervicitis, gonococcal infections when combined with ceftriaxone, and chancroid). 1

FDA-Approved Acute Infections in Adults

Respiratory Tract Infections

• Acute bacterial exacerbations of COPD caused by Haemophilus influenzae, Moraxella catarrhalis, or Streptococcus pneumoniae 1
• Acute bacterial sinusitis due to the same pathogens 1
• Community-acquired pneumonia caused by Chlamydophila pneumoniae, H. influenzae, Mycoplasma pneumoniae, or S. pneumoniae in patients appropriate for oral therapy 1
  • Critical caveat: Do NOT use azithromycin for pneumonia in patients with cystic fibrosis, nosocomial infections, suspected bacteremia, hospitalized patients, elderly/debilitated patients, or those with immunodeficiency/functional asplenia 1

Pharyngitis/Tonsillitis

• Streptococcal pharyngitis/tonsillitis as an alternative when first-line therapy (penicillin) cannot be used 1
• Important limitation: Penicillin remains the drug of choice; azithromycin lacks data for preventing rheumatic fever 1

Skin and Soft Tissue Infections

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

Sexually Transmitted Infections

• Chlamydial urethritis/cervicitis: Single 1-gram dose 2, 1
• Gonococcal urethritis/cervicitis: Single 2-gram dose, MUST be combined with ceftriaxone 1g IM/IV due to resistance 2
• Chancroid (genital ulcer disease in men due to Haemophilus ducreyi) 1
  • Efficacy in women not established due to limited trial data 1

Critical warning for STIs: Azithromycin does not treat syphilis; all patients with urethritis/cervicitis require serologic testing for syphilis and gonorrhea cultures at diagnosis 1

Pediatric Indications

Respiratory Infections in Children

• Community-acquired pneumonia, bronchitis, and other respiratory infections with efficacy equivalent to amoxicillin/clavulanic acid, cefaclor, or erythromycin 3
• Mycoplasma or Chlamydia pneumonia: Macrolides are first-line empirical treatment in children ≥5 years old 4
• Otitis media: Standard 3-day (10 mg/kg/day) or 5-day regimens (10 mg/kg day 1, then 5 mg/kg/day for 4 days) are as effective as amoxicillin/clavulanic acid 3
• Streptococcal pharyngitis/tonsillitis: Requires higher dosing (12 mg/kg/day for 5 days) due to higher recurrence rates compared to penicillin 3

Other Pediatric Uses

• Skin and soft tissue infections with efficacy similar to cefaclor or dicloxacillin 3
• Trachoma: Oral azithromycin as effective as ocular tetracycline 3
• Pertussis in infants <1 month: 10 mg/kg daily for 5 days, with monitoring for infantile hypertrophic pyloric stenosis 2

Long-Term Prophylactic Therapy

Bronchiectasis

• Patients with ≥3 exacerbations per year: Azithromycin 500 mg three times weekly OR 250 mg daily for minimum 6-12 months 4, 2, 5
• Reduces exacerbation rates from 1.57-2.05 per year to 0.59-0.84 per year 4
• Effective in patients both with and without Pseudomonas aeruginosa 4

COPD

• Exacerbation prevention: 250 mg three times weekly 5

Severe Uncontrolled Asthma

• Trial therapy: 500 mg three times weekly or 250 mg daily for 6-12 months; discontinue if no benefit 2

Cystic Fibrosis with Chronic Pseudomonas

• Chronic suppressive therapy: 250 mg daily or 250-500 mg three times weekly, continue long-term if beneficial 2

HIV/AIDS with Disseminated MAC

• Secondary prophylaxis: 500 mg daily lifelong in combination with ethambutol 2

Critical Safety Considerations Before Prescribing

Cardiac Screening

• Obtain ECG before initiating therapy to assess QTc interval 2, 5, 6
• Contraindicated if QTc >450 ms (men) or >470 ms (women) due to risk of torsades de pointes 2, 6

Non-Tuberculous Mycobacteria (NTM) Screening

• Screen for NTM before starting long-term therapy: Examine sputum samples if any clinical suspicion 4
• Active NTM infection is an absolute contraindication to low-dose macrolide monotherapy 4
• Macrolide-resistant NTM has very poor treatment outcomes; azithromycin must never be used as monotherapy for NTM 4

Drug Interactions

• Avoid aluminum/magnesium antacids: Reduce azithromycin absorption by 24% when taken simultaneously 2, 5, 6

Resistance Considerations

• Long-term use increases macrolide resistance 2.7-fold, with resistance rates reaching 48.7% 4, 6
• Erythromycin-resistant organisms are also resistant to azithromycin 7
• Discuss antimicrobial resistance risks with patients before starting chronic therapy 4

Common Pitfalls to Avoid

• Never use azithromycin monotherapy for gonococcal infections—always combine with ceftriaxone due to widespread resistance 2
• Do not rely on azithromycin for pneumonia in severely ill patients with risk factors (see respiratory section above) 1
• Amoxicillin remains first-line for suspected S. pneumoniae pneumonia at any age; azithromycin is reserved for atypical pathogens 4
• For Staph aureus infections, use macrolide or flucloxacillin plus amoxicillin combination 4
• Susceptibility testing is mandatory for streptococcal pharyngitis due to emerging resistance 1