Appropriate use of azithromycin

Azithromycin is a macrolide antibiotic with broad-spectrum bacteriostatic activity against many Gram-positive and Gram-negative bacteria. It also has activity against Mycoplasma pneumoniae, Treponema pallidum, Chlamydia sp. and Mycobacterium avium complex. In addition azithromycin has immunomodulating effects and is used in chronic respiratory inflammatory diseases, including cystic fibrosis, as an anti-inflammatory.

Azithromycin has excellent oral bioavailability. Intravenous formulations should be reserved for patients who are unable to tolerate oral intake. A suspension is also available. Azithromycin is generally well tolerated. Serious side effects associated with azithromycin include hearing loss or impairment and QT prolongation. There have been several studies which suggest that azithromycin is associated with an increased risk of death from cardiovascular causes. Azithromycin is also considered safe in pregnancy.

Azithromycin is often used in preference to other macrolide antibiotics. It is not associated with drug interactions via cytochrome P450 3A4 (like clarithromycin) and is more acid stable (than erythromycin) which simplifies administration around food. However azithromycin is associated with clinically relevant drug interactions including warfarin, everolimus, colchicine and digoxin. Combining statins and azithromycin may increase the risk of rhabdomyolysis. Azithromycin should not be combined with other drugs which prolong the QT interval due to the risk of torsades de pointes. Due to its long half-life, interactions may occur for several days after azithromycin is ceased.

Unfortunately, since the late 1990s, macrolide-resistant infections have been increasing in Australia. Haemophilus influenzae is commonly susceptible to macrolides but resistance rates of up to 15% have been reported in Aboriginal and Torres Strait Islander children. Patients with chronic lung disease treated with azithromycin long-term have been shown in a meta-analysis to have a 2.7 fold increased risk of macrolide resistant bacteria.

There is no clear microbiological advantage for azithromycin over other atypical agents for acute respiratory infections such as doxycycline.  In regions where pneumonia due to Q fever (Coxiella burnetti) occur (e.g. northern NSW and Queensland), doxycycline represents a better choice as it provides a spectrum that includes Q fever and Legionella.

Azithromycin is particularly effective for sexually transmitted infections, intracellular enteric pathogens (like Salmonella sp.) and prophylaxis of mycobacterial disease. Unrestricted use of azithromycin, particularly for immunomodulation, is concerning in light of increasing macrolide resistance.

An excellent recent review from Australian Prescriber is available here.

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