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LETTErS To ThE EDITor A Review of Azithromycin Dosing Dear Editor, I am confused about the dose of azithromycin (15 mg/ kg Q 12 H) given in the article Feline Rhinitis & Upper Respiratory Disease (July/August 2012 issue, page 14). I have gone to many lectures given by Dr. Richard Ford and his preferred dose is 5 mg/kg Q 24 H. Kirk's Current Veterinary Therapy provides a dose of 5 to 10 mg/kg every other day. Obviously, the article's dose is much higher than the others. Please enlighten me on the discrepancy. —Randy Brunswick, DVM Brunswick Animal Hospital, Normal, Illinois Author Responds Thank you so much for your question regarding azithromycin dosing. This is a great question, especially due to the huge range of doses that have been reported for use in cats, with often little explanation in the literature about why specific dosing regimens were chosen. Description. Azithromycin is a macrolide antibiotic that has been increasingly recommended for a variety of infections in cats over the last 10 to 15 years. It is an azalide semisynthetic derivative of erythromycin, and the additional methyl group on azithromycin (compared to erythromycin) increases acid stability of the drug, improves its tissue distribution, and enhances interaction with bacterial ribosomes, thereby improving the antibacterial spectrum.1 Antimicrobial activity. Like all macrolides, azithromycin accumulates in phagocytic cells, facilitating distribution to sites of infection. In comparison to erythromycin, azithromycin has greater activity against selected gram-negative organisms, Mycoplasma species, and protozoa (eg, Toxoplasma gondii, Cryptosporidium species); however, it has less activity against gram-positive organisms.1 Azithromycin is generally thought to be bacteriostatic against these pathogens in vitro; however, it is bactericidal against very susceptible organisms. There is some evidence to suggest that it can be bactericidal at higher concentrations,2 and given good tissue distribution of the drug, azithromycin accumulates in selected tissues at bactericidal concentrations.1 Indications. Azithromycin has been suggested for use in cats (and dogs) with respiratory tract infections given its good spectrum of activity against bacterial pathogens classically involved in respiratory tract infections. That being said, it is important to remember that azithrocmyin is not approved for use in dogs or cats (nor are other macrolide derivative antimicrobials); thus, where a suitable veterinary alternative exists, owner consent must be obtained for off-label use. Administration. Part of the challenge in determining dosing regimens in cats relates to the controversy surrounding the classification of macrolides as concentration- or timedependent antimicrobials. Realistically, azithromycin is time 8 Today's Veterinary Practice January/February 2013 dependent for some organisms and concentration dependent for others;1 thus, a single dosing scheme for all organisms is not appropriate. Before choosing a dosing scheme for a particular patient, it is important to consider both the pharmacokinetics and pharmacodynamics of azithromycin. Pharmacokinetics. Bioavailability, pharmacokinetics, and tissue distribution of azithromycin have been described in cats. Its pharmacokinetic profile in general is characterized by low plasma drug concentrations, but high and persistent tissue concentrations.2 • Oral bioavailability is fair (58%), although less than that for dogs (> 90%).3 • Maximum drug concentration (Cmax) is 0.97 ± 0.65 mcg/ mL, and occurs at a Tmax of 0.85 ± 0.72 H. • Plasma drug concentration following IV administration (5 mg/kg) in cats is approximately 8 mcg/mL at 1 H, decreasing to 0.1 mcg/mL at 12 H. • Plasma drug concentration following PO administration (5 mg/kg) in cats is 1 mcg/mL at 1 H, decreasing to 0.1 mcg/mL at 12 H. • Elimination half-life is 35 H (mean, with a range of 29–51 H and exceeding 72 H in some tissues, such as the kidney).3 Pharmacodynamics. Dosing should ideally also be based on pharmacodynamics, but this information is lacking in companion animals. It has been suggested that daily dosing of azithromycin should be considered in cats (and dogs) because (1) the Clinical Laboratory and Standards Institute susceptible breakpoint for azithromycin is 4 mcg/mL and (2) serum concentrations decline to less than 0.1 mcg/mL at 12 H.1 It has also been suggested that since time to steady state is approximately 3 to 5 days, a loading dose of 15 mg/kg should be given, followed by once daily dosing at a minimum of 5 mg/ kg. Without a loading dose, the drug may not reach steady state for 10 days.1 Fortunately, azithromycin appears safe and well tolerated in cats; therefore, higher loading doses and increased frequency are recommended in certain situations. Respiratory Infections. When I use azithromycin for upper respiratory tract infections in cats, I am usually administering it to cats with severe clinical signs (ie, it is not my first line drug) and when infection with Chlamydophila and/or Mycoplasma is a concern. In these cases, I usually start with 15 mg/kg Q 24 H (NOT 15 mg/kg Q 12 H as the article had suggested) for at least the first 5 days, followed by Q 48 H dosing. Until pharmacodynamic studies and more clinical trials evaluating azithromycin for certain disease states are performed, a variation in recommended doses will continue to be likely. —Claire R. Sharp, BSc, BVMS (Hon), MS, CMAVA, Diplomate ACVECC; Tufts University References 1. Boothe DM. Antimicrobial drugs. In Boothe DM (ed): Small Animal Clinical Pharmacology and Therapeutics. Philadelphia: Elsevier Saunders, 2011. 2. Jordan DG. Pharm profile: Azithromycin. Compend Cont Ed Pract Vet 2001; 23:242-269. 3. Hunter RP, Lynch MJ, Ericson JF, et al. Pharmacokinetics, oral bioavailability and tissue distribution of azithromycin in cats. J Vet Pharmacol Ther 1995; 18(1):38-46.