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Veterinary Therapeutics Fall 2010 (Vol 11, No 3)

Efficacy of Tylosin Tartrate on Canine Staphylococcus intermedius Isolates In Vitro

by Brian A. Scott, DVM, Joel E. Mortensen, PhD, Tricia M. McKeever, PhD, Dawn B. Logas, DVM, DACVD

    Clinical Relevance

    In the past 5 years, the incidence of canine skin infections caused by resistant strains of Staphylococcus (pseud)intermedius has increased. Many older antibiotics are used to treat these infections because the sensitivity can be demonstrated in vitro. Additionally, many of these older drugs are efficacious and unlikely to induce multidrug resistance. More than a decade ago, the antibiotic tylosin tartrate was reported to be efficacious in vitro and in vivo against Staphylococcus intermedius. The purpose of this study was to determine whether S. (pseud)intermedius isolated from untreated pyoderma cases at veterinary referral centers across the United States are sensitive in vitro to this antibiotic. Minimum inhibitory concentrations for tylosin tartrate and other commonly used antibiotics were determined for 103 isolates. Most (82.61%) of the isolates not exposed to antibiotics in the 3 months before submission were sensitive to tylosin tartrate. These findings suggest that tylosin tartrate warrants further study as a first-line option for the treatment of dogs initially presenting with pyoderma.


    Bacterial pyoderma is one of the most common canine skin disorders,1,2 and Staphylococcus (pseud)intermedius is the primary cutaneous pathogen of dogs.3 Systemic antibiotic therapy is often required for S. (pseud)intermedius pyoderma. Commonly recommended antibiotics include β-lactamase–resistant drugs such as amoxicillin clavulanate, cephalosporins, clindamycin, enrofloxacin, lincomycin, oxacillin, and potentiated sulfonamides.1

    Tylosin is a macrolide antibiotic produced by the actinomycete Streptomyces fradiae. Other antibiotics in the macrolide group include azithromycin, carbomycin, clarithromycin, erythromycin, josamycin, kitasamycin, oleandomycin, spiramycin, telithromycin, and triacetyloleandomycin.4–7 Macrolide antibiotics are characterized by high lipid solubility. They are bacteriostatic by virtue of binding to the 50S ribosomal subunit of susceptible bacteria, thereby inhibiting polypeptide translocation of aminoacyl–transfer RNA, which inhibits polypeptide synthesis. Additionally, macrolides can be bactericidal at high concentrations against susceptible bacteria and can affect the expression of bacterial virulence mechanisms even at concentrations below their optimal minimum inhibitory concentration (MIC).8,9 Resistance may develop rapidly or slowly, and cross-resistance between macrolides is well recognized.

    Tylosin tartrate is well absorbed from the gastrointestinal (GI) tract, with side effects rarely being reported.4–7 Staphylococci can be resistant to erythromycin but sensitive to tylosin tartrate.10 Tylosin tablets were available for use in dogs in Canada until the late 1990s. Several studies during this time showed the efficacy of tylosin tartrate against Staphylococcus intermedius in vivo and in vitro, and no adverse GI effects were reported.11–13 The purpose of this study was to determine whether tylosin tartrate is still active in vitro against current S. intermedius isolates from dogs with pyoderma.

    Materials and Methods

    One hundred and three isolates of S. intermedius were collected from 180 dogs presenting during the summer of 2009 to veterinary dermatology specialty referral practices across the United States (Colorado, Florida, Louisiana, Minnesota, New York, South Carolina, Tennessee, and Texas). Each dog was diagnosed with either superficial (epidermis and hair-follicle involvement) or deep (tissues deeper than the hair follicle) pyoderma by a veterinary dermatologist. The presence of bacterial cocci was confirmed via cytology before the collection of a sample with a sterile culturette. Age, breed, sex, antibiotic history for the past 3 months, and zip code of each animal were recorded along with the site cultured.

    All culturettes were shipped to the microbiology laboratory at Cincinnati Children’s Hospital, where they were plated on mannitol salt agar and incubated at 35°C for 48 hours. At 24 and 48 hours, representative colonies were subcultured onto 5% sheep blood agar and incubated for 24 hours. Following the manufacturer’s recommendations, isolates were tested with the VITEK 2 system, version: 04 01 (bioMerieux). The VITEK 2 system detects metabolic changes by fluorescence-based methods that facilitate the identification of bacteria within 3 hours. This system monitors the kinetics of bacterial growth and calculates the MIC using a unique algorithm designed to concur with Clinical and Laboratory Standards Institute (CLSI) reference methods.14 This automation allows multiple isolates to be evaluated simultaneously. Determinations of MIC breakpoints for sensitivity and resistance were based on CLSI guidelines for animal bacterial isolates as of June 2009.

    Tylosin tartrate sensitivities were ascertained using JustOne Custom MIC Strips (TREK Diagnostic Systems, Magellan Biosciences, Cleveland, Ohio), according to the manufacturer’s instructions. These strips for serial dilution and MIC determination are custom-made for antibiotics for which standard MIC plates are not currently available. The strips were inoculated and read manually according to the manufacturer’s and CLSI guidelines.15 MIC breakpoints for tylosin tartrate are not available for S. intermedius in dogs, but all sensitive isolates had MICs of <0.25 µg/mL, and all resistant isolate MICs were >32 µg/mL.

    After this study had begun, a move was initiated to reclassify S. intermedius as S. pseudintermedius. Because the List of Bacterial Names with Standing in Nomenclature (LBSN) still classified these isolates as S. intermedius, the VITEK 2 system version: 04 01 likewise reported them as S. intermedius according to the CLSI guidelines for animal isolates at that time. As DNA phenotyping was not performed on any of the isolates, we felt it was best to refer to them as S. intermedius.

    A χ-square test was used to investigate whether there was a difference in sensitivity among cephalexin, ciprofloxacin, clindamycin, erythromycin, gentamicin, potentiated sulfonamides (trimethoprim–sulfamethoxazole), tetracycline, and tylosin tartrate and to determine whether antibiotic use in the previous 3 months affected in vitro sensitivity. Tylosin tartrate was compared with each antibiotic individually. In addition, the isolates that were resistant to oxacillin were investigated to see whether they were sensitive to tylosin tartrate, clindamycin, erythromycin, and ciprofloxacin, because alternative drugs for the treatment of methicillin-resistant strains of S. intermedius are always needed. All data were analyzed in Stata, version 10 (Stata Corporation, College Station, Texas).


    S. intermedius was isolated in pure culture from 103 dogs. A total of 98% of the isolates were from superficial infections, with 2% from deep infections. Most of the organisms (68%) were obtained from under crusts. Intact pustules accounted for 13% of the isolates, and the remaining 19% of organisms were collected from under the leading edge of epidermal collarettes. There was no statistically significant age, breed, or sex predilection.

    Individual antibiotics, including tylosin tartrate, were evaluated independently to determine the specific effect each antibiotic had on the sensitivity of collected isolates. Most of the isolates were sensitive to clindamycin, erythromycin, potentiated sulfonamides, and tylosin tartrate, with a higher percentage showing sensitivity to cephalexin, gentamycin, and ciprofloxacin (Table 1). Many of the isolates that showed resistance to oxacillin showed sensitivity to tylosin tartrate and other antibiotics (Table 2). This analysis was performed because of the increasing frequency of methicillin-resistant strains of S. intermedius. Fifty-nine percent of the dogs had received antibiotics in the past 3 months (Table 3). Antibiotic exposure in the 3 months before isolate submission significantly decreased the sensitivity of the isolates to all antibiotics (e.g., cephalexin [P = .001], ciprofloxacin [P = .001], clindamycin [P = .003], erythromycin [P = .005], tylosin tartrate [P = .005]; Table 3). This drop in sensitivity was clearly demonstrated by comparison with isolates from animals without antibiotic exposure for 3 months before submission (Table 4).


    Tylosin tartrate showed excellent efficacy in vitro (90.5%) against S. intermedius isolates in a prior study, which reported an identical sensitivity for erythromycin.11 A second study by the same authors also reported excellent efficacy (91.3%) for tylosin, but the sensitivity of half of the isolates in that study was based on erythromycin because the commercially available test for tylosin had been discontinued.13 However, it was noted that staphylococci can show resistance to erythromycin and still be sensitive to tylosin tartrate.9 As the current data show, tylosin tartrate remained effective (68.93%) in vitro against S. intermedius (pseudintermedius) in dogs with pyoderma in 2009.

    As efficacy was significantly better in animals not treated with antibiotics in the 3 months preceding isolate submission (82.61%), it would seem that tylosin tartrate may be a better empirical choice in the treatment of initial-presentation canine pyoderma cases. Culture and sensitivity studies should be performed before selecting tylosin tartrate for pyoderma cases previously treated with other antibiotics. Before proceeding with any in vivo work, pharmacokinetic studies should be done to determine whether tylosin tartrate is a dose- or a time-dependent antibiotic.

    Antimicrobial resistance has continued to be a focus for extensive research16–30 over the 25 years since Scott et al published their initial papers11,13 about the efficacy of tylosin tartrate. In two recent studies,31,32 S. intermedius isolates were shown to be resistant to macrolide antibiotics at a rate of 27.9% and 21.1%, respectively. The isolates in the current study showed higher resistance levels that increased further when the dog had received antibiotics in the 3 months before isolate submission. Isolates not exposed to macrolide antibiotics in the 3 months before isolate submission showed a lower incidence of resistance than in the most recent studies.31,32 As all of these isolates came from dermatology specialty referral practices, some selection for more resistant organisms would be expected.


    Additional antibiotics in the armamentarium for initial-presentation staphylococcal pyoderma would be beneficial for veterinary practitioners. Most of the S. intermedius isolates in this study showed sensitivity to tylosin tartrate in vitro; therefore, tylosin tartrate can still be considered effective against S. intermedius isolates in vitro. Tylosin tartrate would be a good choice for the treatment of initial-presentation superficial canine pyoderma because it shows similar efficacy to clindamycin and is currently less expensive. Studies concerning pharmacokinetics, dosing, and dose- versus time-dependent efficacy should be completed before initiating any in vivo clinical studies.

    Downloadable PDF

    This study was funded by the Microbiology Research Fund at Cincinnati Children’s Hospital.
    Correspondence should be sent to Dr. Scott at dermdvm@gmail.com.

    1. Scott DW, Miller WH, Griffin CE. Small Animal Dermatology VI. Philadelphia: WB Saunders; 2001:274-335.

    2. Scott DW, Paradis M. A survey of canine and feline skin disorders in a university practice: Small Animal Clinic, University of Montreal, Saint-Hyacinthe, Quebec (1987-1988). Can Vet J 1990;31:830-835.

    3. Ihrke PJ. Integumentary infections. In: Greene CE, ed. Infectious Diseases of the Dog and Cat III. St. Louis: Saunders Elsevier; 2006:807-815.

    4. Burrows GE. Pharmacotherapeutics of macrolides, lincomycins and spectinomycin. JAVMA 1980;176:1072-1077.

    5. Johnson DE, ed. The Bristol Veterinary Handbook of Antimicrobial Therapy II. Evansville: Bristol-Myers US Pharmaceutical and Nutritional Group; 1987:261-265.

    6. McEvoy GK, ed. AHFS drug information 93. Bethesda: American Society of Hospital Pharmacists; 1993:190-207.

    7. Tenson T, Lovmar M, Ehrenberg M. The mechanism of action of macrolides, lincosamides, and streptogramin B reveals the nascent peptide exit path in the ribosome. J Mol Biol 2003;330:1005-1014.

    8. Giguere S, Prescott JF, Baggot JD, et al. Antimicrobial Therapy in Veterinary Medicine IV. Oxford: Blackwell; 2006:191-206.

    9. Shryock TR, Mortensen JE, Baumholtz M. The effects of macrolides on the expression of virulence mechanisms. J Antimicrob Chemother 1998;41:505-512.

    10. Matsuoka M, Endou K, Nakajima Y. Localization of a determinant mediating partial macrolide resistance in Staphylococcus aureus. Microbiol Immunol 1990;34:643-652.

    11. Scott DW, Miller WH, Cayette SM, Bagladi MS. Efficacy of tylosin tablets for the treatment of pyoderma due to Staphylococcus intermedius infections in dogs. Can Vet J 1994;35:617-621.

    12. Harvey RG. Tylosin in the treatment of canine superficial pyoderma. Vet Rec 1996;138:185-187.

    13. Scott DW, Miller WH, Rothstein SE, Bagladi MS. Further studies on the efficacy of tylosin tablets for the treatment of pyoderma due to Staphylococcus intermedius in dogs. Can Vet J 1996;37(10):617-618.

    14. Joyanes P, Conejo MDC, Martinez-Martinez L, Perea E. Evaluation of the VITEK 2 System for the identification and susceptibility testing of three species of nonfermenting gram-negative rods frequently isolated from clinical samples. J Clin Microbiol 2001;39(9):3247-3253.

    15. Jorgensen JH, Crawford SA. Assessment of two commercial susceptibility test methods for determination of daptomycin MICs. J Clin Microbiol 2006;44(6):2126-2129.

    16. Boerlin P, Burnens AP, Frey PK, Nicolet J. Molecular epidemiology and genetic linkage of macrolide and aminoglycoside resistance in Staphylococcus intermedius of canine origin. Vet Microbiol 2001;79:155-169.

    17. Hoekstra KA, Paulton RJL. Clinical prevalence and antimicrobial susceptibility of Staphylococcus aureus and Staphylococcus intermedius in dogs. J Appl Microbiol 2002;93:406-413.

    18. Prescott JF, Hanna WJB, Reid-Smith R, Drost K. Antimicrobial drug use and resistance in dogs. Can Vet J 2002;43(2):107-116.

    19. Holm BR, Petersson U, Morner A, et al. Antimicrobial resistance in staphylococci from canine pyoderma: a prospective study of first-time and recurrent cases in Sweden. Vet Rec 2002;151:600-605.

    20. Guardabassi L, Loeber ME, Jacobson A. Transmission of multiple antimicrobial-resistant Staphylococcus intermedius between dogs affected by deep pyoderma and their owners. Vet Microbiol 2004;98:23-27.

    21. Guardabassi L, Schwarz S, Lloyd DH. Pet animals as reservoirs of antimicrobial-resistant bacteria. J Antimicrob Chemother 2004;54:321-332.

    22. Pottumarthy S, Schapiro JM, Prentice JL, et al. Clinical isolates of Staphylococcus intermedius masquerading as methicillin-resistant Staphylococcus aureus. J Clin Microbiol 2004;42:5881-5884.

    23. Loeffler A, Boag AK, Sung J, et al. Prevalence of methicillin-resistant Staphylococcus aureus among staff and pets in a small animal referral hospital in the UK. J Antimicrob Chemother 2005;56:692-697.

    24. Wetzstein HG. Comparative mutant prevention concentrations of pradofloxacin and other veterinary fluoroquinolones indicate differing potentials in preventing selection of resistance. Antimicrob Agents Chemother 2005;49:4166-4173.

    25. Authier S, Paquette D, Labrecque O, Messier S. Comparison of susceptibility to antimicrobials of bacterial isolates from companion animals in a veterinary diagnostic laboratory in Canada between 2 time points 10 years apart. Can Vet J 2006;47:774-778.

    26. Morris DO, Rook KA, Shofer FS, Rankin SC. Screening of Staphylococcus aureus, Staphylococcus intermedius, and Staphylococcus schleiferi isolates obtained from small animals for antimicrobial resistance: a retrospective review of 749 isolates (2003-2004). Vet Derm 2006;17:332-337.

    27. Jones RD, Kania SA, Rohrbach BW, et al. Prevalence of oxacillin- and multidrug-resistant staphylococci in clinical samples from dogs: 1,772 samples (2001-2005). JAVMA 2007;230:221-227.

    28. Sasaki T, Kikuchi K, Tanaka Y, et al. Methicillin-resistant Staphylococcus pseudintermedius in a veterinary teaching hospital. J Clin Microbiol 2007;45:1118-1125.

    29. Bagcigil FA, Moodley A, Baptiste KE, et al. Occurrence, species distribution, antimicrobial resistance and clonality of methicillin- and erythromycin-resistant staphylococci in the nasal cavity of domestic animals. Vet Microbiol 2007;121:307-315.

    30. Ahmadi M, Javadi S, Maroofi S. Prevalence of coagulase-positive staphylococci in the skin of dogs: antibacterial resistance and plasmid profile of the isolates. Comp Clin Pathol 2009;18:39-42.

    31. Pedersen K, Pedersen K, Jensen H, et al. Occurrence of antimicrobial resistance in bacteria from diagnostic samples from dogs. J Antimicrob Chemother 2007;60:775-781.

    32. Vanni M, Tognetti R, Pretti C, et al. Antimicrobial susceptibility of Staphylococcus intermedius and Staphylococcus schleiferi isolated from dogs. Res Vet Sci 2009;87:192-195.

    References »

    NEXT: In Vitro Comparison of Staphylococcus pseudintermedius Susceptibility to Common Cephalosporins Used in Dogs


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