MACROLIDES (Veterinary—Systemic) This monograph includes information on the following: Category: Antibacterial (systemic). Azithromycin; Clarithromycin; Erythromycin; Tilmicosin; Tulathromycin; Tylosin. Indications ELUS EL Some commonly used brand names are: For veterinary-labeled Note: The text between and describes uses that are not included ELCAN EL products— in U.S. product labeling. Text between and describes uses Draxxin [Tulathromycin] Pulmotil Premix that are not included in Canadian product labeling. [Tilmicosin Phosphate] The ELUS or ELCAN designation can signify a lack of product Erythro-200 [Erythromycin Tylan 10 [Tylosin availability in the country indicated. See the Dosage Forms Base] Phosphate] section of this monograph to confirm availability. Erythro-Med Tylan 40 [Tylosin [Erythromycin Phosphate] General considerations Phosphate] Macrolides are considered bacteriostatic at therapeutic concentrations Gallimycin [Erythromycin Tylan 50 [Tylosin Base] but they can be slowly bactericidal, especially against Phosphate] streptococcal bacteria; their bactericidal action is described as Gallimycin-50 Tylan 100 [Tylosin time-dependent. The antimicrobial action of some macrolides is [Erythromycin Phosphate] enhanced by a high pH and suppressed by low pH, making them Thiocyanate] less effective in abscesses, necrotic tissue, or acidic urine.{R-119} Gallimycin-100 Tylan 200 [Tylosin Base] Erythromycin is an antibiotic with activity primarily against gram- [Erythromycin Base] positive bacteria, such as Staphylococcus and Streptococcus Gallimycin-100P Tylan Soluble [Tylosin species, including many that are resistant to penicillins by means [Erythromycin Tartrate] of beta-lactamase production. Erythromycin is also active against Thiocyanate] mycoplasma and some gram-negative bacteria, including Gallimycin-200 Tylosin 10 Premix [Tylosin Campylobacter and Pasteurella species.{R-1; 10-12} It has activity [Erythromycin Base] Phosphate] against some anaerobes, but Bacteroides fragilis is usually Gallimycin PFC Tylosin 40 Premix [Tylosin resistant. Some strains of Actinomyces and Chlamydia are [Erythromycin Phosphate] inhibited by erythromycin.{R-1; 2} Most Pseudomonas, Escherichia Phosphate] coli, and Klebsiella strains are resistant to erythromycin.{R-2} Micotil [Tilmicosin Tyloved [Tylosin Base] Cross-resistance to the other macrolides can also occur.{R-1} Phosphate] Tilmicosin has in vitro activity against gram-positive organisms and Pulmotil 90 [Tilmicosin mycoplasma and is active against certain gram-negative Phosphate] organisms,{R-53} such as Histophilus somni (Haemophilus somnus),{R-89} Mannheimia (Pasteurella) haemolytica, and For human-labeled products— Pasteurella multocida.{R-53} However, M. haemolytica is more Apo-Erythro [Erythromycin Ery-Tab [Erythromycin sensitive than P. multocida to tilmicosin. Other gram-negative Base] Base] organisms tested,{R-91} including Enterobacter aerogenes, Apo-Erythro E-C Erythro-500 [Erythromycin Escherichia coli, Klebsiella pneumoniae, Pseudomonas [Erythromycin Base] Stearate] aeruginosa, Salmonella,{R-99} and Serratia species, are very Apo-Erythro-S Erythrocin [Erythromycin resistant to tilmicosin.{R-91} Some strains of Actinomyces also are [Erythromycin Stearate] Lactobionate; extremely resistant to tilmicosin.{R-99} Erythromycin Stearate] Tulathromycin has been demonstrated to be active against respiratory Biaxin [Clarithromycin] Erythromid [Erythromycin pathogens of cattle and pigs, including Actinobacillus Base] pleuropneumonia, Bordetella bronchiseptica, Haemophilus Biaxin XL [Clarithromycin] Erythromycine parasuis, Histophilus somni, Mannheimia haemolytica, [Erythromycin Stearate] Mycoplasma bovis, Mycoplasma hyopneumoniae, and E-Base [Erythromycin Novo-rythro [Erythromycin Pasteurella multocida.{R-130} Base] Estolate] Tylosin has a spectrum of activity similar to that of erythromycin but E-Mycin [Erythromycin Nu-Erythromycin-S is more active than erythromycin against certain mycoplasmas.{R- Base] [Erythromycin Stearate] 51; 105} Erybid [Erythromycin PCE [Erythromycin Base] Azithromycin, a macrolide labeled for human use, has some Base] advantages over erythromycin in the treatment of infections in ERYC [Erythromycin Base] Zithromax [Azithromycin] animals, including better oral absorption, a longer half-life, and a broader spectrum of activity than erythromycin.{R-120; 122} Note: For a listing of dosage forms and brand names by country However, the activity of azithromycin against staphylococci is not availability, see the Dosage Forms section(s). as good as that of erythromycin. Azithromycin concentrates in tissues, particularly in leukocytes, macrophages and fibroblasts and is slowly released from leukocytes.{R-119; 121} The intracellular Evidence Quality Evidence Type A Good evidence to support a recommendation for use 1 Species-specific evidence from at least one large randomized and B Moderate evidence to support a recommendation for use controlled trial (RCT) or multiple small RCTs C Insufficient evidence to support a recommendation for use 2 Species-specific evidence from a small RCT, disease models, large D Moderate evidence to support a recommendation against use case studies, pharmacokinetic studies using surrogate endpoints, or E Good evidence to support a recommendation against use evidence from well-designed trials in a different species that is considered appropriate for comparison 3 Dramatic results from either well-designed, species-specific trials without controls or small case studies 4 Pharmacokinetic studies without surrogate endpoints 5 In vitro studies 6 Opinions of respected authorities on the basis of clinical experience or reports of expert committees © 2007 The United States Pharmacopeial Convention All rights reserved reservoir of azithromycin apparently produces effective drug Pigs: Tylosin granulated is indicated for improving feed concentrations in interstitial fluids even after the plasma efficiency and growth promotion.{R-48; 49} concentrations have declined below detectable levels; plasma ELCANFoulbrood, American (treatment)EL—Bees, honey: Tylosin pharmacokinetic parameters have little correlation to the in vivo tartrate powder for oral solution is indicated in the treatment of efficacy of azithromycin. Azithromycin can be delivered to American foulbrood (Paenibacillus larvae).{R-127} infected tissues and early abscesses via leukocytes.{R-119} Leptospirosis—Sows, farrowing: Erythromycin injection is indicated Clarithromycin, another macrolide labeled for human use, is tolerated in the management of leptospirosis in sows at farrowing time.{R-7; better than erythromycin by human patients, has a broader 111} spectrum of activity than erythromycin, and, like azithromycin, it Metritis (treatment)— also concentrates in leukocytes. An in vitro study and a Cattle, beef and nonlactating dairy: Erythromycin injection and retrospective clinical study have shown clarithromycin to be at tylosin injection are indicated in the treatment of metritis least as effective as erythromycin in the treatment of Rhodococcus caused by susceptible organisms;{R-7; 51; 52; 111} however, equi infection in foals.{R-137; 138} In dogs, clarithromycin has been therapeutic regimens often emphasize evacuation of uterine shown to have a shorter half-life than azithromycin,{R-119; 124} but contents as the primary treatment. information for its clinical use in animals is otherwise limited. Sows, at farrowing time: Erythromycin injection is indicated in the treatment of metritis caused by susceptible organisms;{R-7; 111} Accepted however, therapeutic regimens often emphasize evacuation of Abscesses, hepatic (prophylaxis)—Cattle, beef: Tylosin granulated is uterine contents as the primary treatment. indicated for reduction in incidence of hepatic abscesses caused Pneumonia, bacterial (treatment)— by susceptible Fusobacterium necrophorum and Actinomyces Cattle: Erythromycin injection is indicated in the treatment of pyogenes.{R-48; 49} pneumonia and bovine respiratory disease caused by ELCANAtrophic rhinitis (treatment)EL—Pigs: Tylosin granulated is susceptible bacteria, including Pasteurella multocida.{R-7; 111} indicated for maintaining weight gain and feed efficiency in the Tilmicosin injection is indicated in the control of bovine presence of atrophic rhinitis infections.{R-49} respiratory disease in cattle at high risk for infection and in ELCANArthritis, infectious (treatment)EL—Pigs: Tylosin injection is the treatment of bovine respiratory disease caused by indicated in the treatment of swine arthritis caused by susceptible susceptible bacteria, including Mannheimia haemolytica.{R-53} Mycoplasma hyosynoviae.{R-51; 52} Tilmicosin injection is indicated in Canadian product labeling ELCANCoryza, infectious (prophylaxis)—Chickens: Erythromycin for the treatment of bovine respiratory disease associated with thiocyanate for medicated feed is indicated as an aid in the susceptible M. haemolytica or P. multocida during the first 30 CAN prevention of infectious coryza caused by susceptible days calves are in the feedlot.{R-65; 112} EL Tulathromycin organisms.EL{R-9; 54} injection is indicated in the control of bovine respiratory Coryza, infectious (treatment)—Chickens: Erythromycin phosphate disease in cattle at high risk for infection and in the treatment powder for oral solution is indicated as an aid in the control and of bovine respiratory disease associated with susceptible treatment of infectious coryza caused by susceptible organisms, bacteria, including Histophilus somni,