Drug Reference

Azithromycin

Azithromycin dihydrate

Brand names:Zithromax, Z-Pak, Zmax

AntibioticTCCC Doctrine

A macrolide antibiotic with broad gram-positive and atypical pathogen coverage, used in tactical and prolonged field care for respiratory infections, soft tissue infections in penicillin-allergic patients, and select sexually transmitted infections. Azithromycin's long half-life enables once-daily or even single-dose regimens.

Mission Capable - No Impact

Administration does not impair the recipient's ability to remain operational. Standard mission performance is preserved at therapeutic doses.

Pharmacology and Actions

Azithromycin inhibits bacterial protein synthesis by binding to the 50S ribosomal subunit, preventing translocation during translation. The drug concentrates in tissues at levels much higher than serum concentrations, which contributes to its prolonged tissue effect and short dosing courses. Spectrum includes Streptococcus species, Haemophilus influenzae, Moraxella catarrhalis, Mycoplasma, Chlamydia, and Legionella. Activity against Staphylococcus is limited and increasingly compromised by macrolide resistance.

Indications

  • Community-acquired pneumonia in tactical or austere environments
  • Skin and soft tissue infection in penicillin-allergic casualties
  • Acute bacterial sinusitis or otitis media in prolonged field care
  • Sexually transmitted infections (chlamydia, gonorrhea co-treatment)
  • Traveler's diarrhea prophylaxis or treatment in deployment medicine
  • Pertussis treatment or prophylaxis

Absolute Contraindications

  • Known azithromycin or macrolide allergy
  • History of cholestatic jaundice or hepatic dysfunction with prior macrolide use
  • Concurrent use with QT-prolonging medications in patients with known long QT syndrome

Precautions and Side Effects

Gastrointestinal upset, nausea, and diarrhea are the most common adverse effects. QT interval prolongation can occur and is more significant with IV administration or in patients with electrolyte abnormalities. Hepatotoxicity is rare but possible. Macrolides interact with multiple medications metabolized through CYP3A4; review medication list for interactions. Resistance to macrolides is increasing in many respiratory pathogens, which limits empiric use in some settings.

Adult Dosing

IV / IO
Hospital/severe infection: 500 mg IV once daily. Rarely used in prehospital settings. Onset: Immediate after infusion
PO
Standard 5-day Z-Pak: 500 mg PO on day 1, then 250 mg PO once daily on days 2 through 5. Alternative single-dose regimens: 1 gram PO single dose for uncomplicated chlamydia; 2 grams PO single dose for gonorrhea co-treatment. Travelers' diarrhea: 1 gram PO single dose or 500 mg PO daily for 3 days. Onset: 30 minutes to 1 hour (rapid absorption)

Pediatric Dosing

Pediatric dosing for community-acquired pneumonia: 10 mg/kg PO on day 1 (max 500 mg), then 5 mg/kg PO daily on days 2 through 5 (max 250 mg). Pediatric tactical use is uncommon; consult medical control.

Pharmacokinetics

Peak Effect: PO: 2 to 3 hours after dose

Duration: Tissue half-life 68 hours (enables short dosing courses and once-daily regimens)

Storage and Handling

Store tablets and capsules at controlled room temperature (15 to 30 degrees Celsius). Protect from moisture. Oral suspension requires refrigeration after reconstitution and has limited shelf life.

Reconstitution:

Tablets and capsules require no reconstitution. IV powder vials require reconstitution with 4.8 mL sterile water, then further dilution in 250 to 500 mL NSS or D5W for infusion.

TCCC and TECC Role

Azithromycin is not a primary TCCC wound prophylaxis antibiotic; the algorithm specifies cefadroxil or cephalexin for oral wound prophylaxis. Azithromycin's role in TCCC and prolonged field care is treatment of established or suspected respiratory infections, atypical pneumonia, and as an alternative in penicillin-allergic casualties when cephalosporin cross-reactivity is a concern. The single-dose regimens for STI treatment also make azithromycin a useful drug for deployment medicine kits.

Field Context

Azithromycin is the macrolide carried for respiratory infections and for penicillin-allergic casualties who need broad-spectrum oral coverage. The single-dose and short-course regimens are operationally attractive in deployment settings where medication compliance over 7 to 10 days is difficult to ensure. Increasing macrolide resistance has eroded azithromycin's reliability for some indications, particularly Streptococcus pneumoniae, so it should not be the sole agent for severe bacterial pneumonia in austere environments.

Common Mistake

Reaching for azithromycin as a wound infection prophylaxis when cefadroxil or cephalexin are the indicated agents. Azithromycin does not have reliable Staphylococcus aureus coverage and should not be substituted for the cephalosporin-class agents specified in TCCC wound prophylaxis. Use it for respiratory, atypical, and STI indications, not wound coverage.

Clinical Reference Notice

This drug profile is provided as educational reference material for trained medical providers. It is not medical advice, not a substitute for formal training, and not a substitute for current published guidelines or medical direction.

Drug administration is governed by your scope of practice, agency standing orders, medical director protocols, and applicable state and federal regulations. Controlled substances are subject to additional handling, accountability, and documentation requirements per DEA and state law. Always verify dosing, indications, contraindications, and route of administration against current published guidelines and your local protocols before administration.

If this content is being viewed during a medical emergency, call 911 immediately and follow the direction of your local emergency dispatch and medical control. Do not use this reference as a substitute for emergency medical services.

Drug information evolves. Last reviewed dates and source citations are provided for each entry. Confirm currency against the cited source before clinical use.

Penn Tactical Solutions publishes this reference for educational purposes. PTS does not provide medical direction and does not assume responsibility for clinical decisions made in the field. Clinical responsibility rests with the administering provider, their medical director, and their agency.

Educational reference for trained medical providers. Not medical advice. Not a substitute for formal training, current published guidelines, or medical direction. Drug administration is governed by your scope of practice, agency standing orders, medical director protocols, and applicable state and federal regulations. Controlled substances require additional storage, accountability, and documentation per DEA and state law.

In a medical emergency, call 911. This reference is not a substitute for emergency medical services.

Verify dosing, indications, and contraindications against current published guidelines and your local protocols before administration. Confirm content currency against the source citation. Penn Tactical Solutions does not provide medical direction. Clinical responsibility rests with the administering provider, their medical director, and their agency.

Azithromycin

Azithromycin dihydrate
Antibiotic
Mission Capable - No Impact
Adult Dosing
IV/IO Hospital/severe infection: 500 mg IV once daily. Rarely used in prehospital settings. (Immediate after infusion)
PO Standard 5-day Z-Pak: 500 mg PO on day 1, then 250 mg PO once daily on days 2 through 5. Alternative single-dose regimens: 1 gram PO single dose for uncomplicated chlamydia; 2 grams PO single dose for gonorrhea co-treatment. Travelers' diarrhea: 1 gram PO single dose or 500 mg PO daily for 3 days. (30 minutes to 1 hour (rapid absorption))
Pediatric
Pediatric dosing for community-acquired pneumonia: 10 mg/kg PO on day 1 (max 500 mg), then 5 mg/kg PO daily on days 2 through 5 (max 250 mg). Pediatric tactical use is uncommon; consult medical control.
Contraindications
Known azithromycin or macrolide allergy| History of cholestatic jaundice or hepatic dysfunction with prior macrolide use| Concurrent use with QT-prolonging medications in patients with known long QT syndrome
Common Mistake
Reaching for azithromycin as a wound infection prophylaxis when cefadroxil or cephalexin are the indicated agents. Azithromycin does not have reliable Staphylococcus aureus coverage and should not be substituted for the cephalosporin-class agents specified in TCCC wound prophylaxis. Use it for respiratory, atypical, and STI indications, not wound coverage.