MRSA, mupirocin, potentiated sulphonamides, pyotraumatic dermatitis.

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1 TREATMENT OF PYOTRAUMATIC DERMATITIS INFECTED WITH METHICILLIN- RESISTANT STAPHYLOCOCCUS AUREUS IN THREE PET PSITTACINES STEPHEN SMITH BVETMED(HONS) CERTZOOMED MRCVS NEIL A FORBES BVETMED RFP DIPECAMS FRCVS Great Western Exotic Vets Unit 10 Berkshire House, County Park, Shrivenham Road, Swindon, SN1 2NR KEYWORDS MRSA, mupirocin, potentiated sulphonamides, pyotraumatic dermatitis. ABSTRACT Methicillin-resistant Staphylococcus aureus (MRSA) is becoming increasingly recognized as a pathogenic organism in veterinary practice. Although MRSA has been reported in dogs, cats, horses, chicken and cows, this is the first reported case series of infections in psittacine birds in a UK avian referral hospital. The three psittacines presented as referral cases with chronic pyoderma. All birds were self-mutilating the infected area, and they had all previously received various treatments, including antibiotics. Swabs of the skin wounds isolated MRSA and treatment of all cases comprised oral sulfamethoxazole and trimethoprim, cleaning with diluted chlorhexadine and topical application of mupirocin ointment. Clinical signs improved or resolved completely, and all three cases were culture negative for MRSA two to seven weeks after starting treatment. This clinical report demonstrates that oral potentiated sulfonamides, chlorhexidine cleaning and topical mupirocin ointment may be an effective treatment for MRSA in psittacines. 1 INTRODUCTION Methicillin-resistant Staphylococcus aureus (MRSA) has become a worldwide health problem and has recently been subjected to increased public awareness. The prevalence of MRSA carriage in the human community in the UK is largely unknown but appears to be on the increase (BOAG why the caps 2004), with the prevalence of MRSA infections in the human blood stream rising to an alarming 44.5% in 2002 (TIEMERSMA 2004). Due to the increased public concern over the consequences of MRSA infection, this has lead to more detailed consideration and concern of MRSA as a pathogenic organism in veterinary practice. The first report of MRSA in domestic animals involved mastitis in dairy cows in Belgium in 1972 (DEVRIESE 1972). Since that time case reports have also documented MRSA infections in dogs, horses, chickens, pigeons and wild birds (TOMLIN J et al. 1999, GORTEL K et al. 1999, HARTMANN FA et al. 1997, KAWANO et al. 1996, SCHWARZ and WERCKENTHIN 2004, NASCIMENTO 2003).

2 There is increasing evidence that inter-species transmission of MRSA occurs (MANIAN 2003, WALLER 2005), making colonisations and infections in domestic animals of particular interest with regard to mutual dissemination between humans and animals. This interest should therefore extend to pet psittacine birds, since there is often significant close contact with the owner, making owner-bird transfer possible. In avian medicine, staphylococcal infections have been linked with pyoderma, ulcerative dermatitis, bumblefoot and chronic feather destructive disorders in pet psittacines (BAUK, 1997). Whilst MRSA has been isolated from other non-pet birds, this is the first reported case series of infections in pet psittacine birds presented to a UK avian referral hospital. The purpose of this clinical report was to highlight the importance of testing for MRSA in pet psittacines, and to suggest an appropriate treatment protocol for the MRSA infections diagnosed in these cases. Both of these aims are important to enable prompt effective treatment of the pet bird, as well as making avian vets and owners aware of the zoonotic risks of MRSA from their pet birds. 2 CLINICAL REPORT Case 1: An 11 year old, male, African Grey parrot (Psittacus erithacus) was presented as a referral case with a 3 week history of painful dermatitis, unresponsive to treatment with enrofloxacin (Baytril; Bayer) 5mg/kg PO BID. Clinical examination demonstrated markedly inflamed and exudative areas of skin on the ventral aspects of both wings, and the corresponding areas of body wall. These lesions were consistent with Superficial Chronic Ulcerative Dematitis (SCUD). Other aspects of the clinical examination were unremarkable, and the bird was otherwise bright and alert. Under general anaesthesia, blood was taken for haematology and biochemistry, and full body radiography was performed. No significant abnormalities were detected. Swabs were taken from the affected areas and were stained with Gram s stain and submitted for culture and sensitivity. Cytology showed large numbers of extra-cellular and intra-cellular gram positive cocci. Since the lesions were very severe and painful, the bird was hospitalised for treatment comprising potentiated amoxicillin (Synulox; Pfizer) 150mg/kg PO BID, butorphenol (Torbugesic; Fort Dodge) 2mg/kg IM SID 30 minutes prior to treatment, topical bathing with 1:250 diluted quaternary ammonium and biguanidine compound disinfectant (F10; Health and Hygiene) SID and topical application of aloe vera cream SID. After four days of treatment there was no improvement and the culture and sensitivity results were received. This showed a heavy growth of mixed coliforms and a scanty growth of coagulase positive staphylococcus, identified as MRSA. Trimethoprim (Tribrissen) and oxytetracycline were the only antibiotics that both groups of bacteria were sensitive to. The MRSA cultured was resistant to amoxicillin, potentiated amoxicillin, cephalexin, enrofloxacin, polymixin B, marbofloxacin, clindamycin and oxacillin. At this point the treatment protocol was modified to trimethoprim and sulfamethoxazole (Septrin; GlaxoSmithKline) 100mg/kg PO BID, butorphenol 2mg/kg IM SID 30 minutes prior to treatment, topical silver sulfadiazine cream (Flamazine; Smith & Nephew) SID and topical bathing with 1:30 dilution of chlorhexidine (Hibitane; Bioglan). Over the following 12 days there was some improvement in the lesions, but this only reached a certain point so a further swab was taken for repeat culture and sensitivity. After four days the results showed no coliforms but a heavy growth of MRSA with the same sensitivity pattern as before. At this point the flamazine cream was stopped, and replaced with daily application

3 of mupirocin ointment (Bactroban 2%; Beecham); the other medications remained unchanged. Treatment was continued for a further week, and the lesions continued to resolve slowly. Another swab was submitted for culture and sensitivity, which showed no growth of MRSA. Treatment was continued for a further week, and another swab submitted also showed no growth of MRSA. The time taken to achieve a second negative MRSA culture was 42 days after starting treatment with trimethoprim and sulfamethoxazole, silver sulfadiazine and chlorhexidine, and 26 days after starting treatment with mupirocin ointment. The patient was discharged with the above meds for treatment at home for a further 4 weeks, and 2 weeks after cessation of treatment, there had been no recurrence. On further questioning of the owner, it became known that the owner s daughter worked in a nursing home. Case 2: A 14 year old, male, African Grey parrot (Psittacus erithacus), presented with a several month history of plucking around the tail base. Minimal investigation and treatment had been attempted at the previous veterinary surgery, but the owner had a very limited budget for further investigation. Since the lesions were centred around the tail base, separate swabs were taken of the skin in that area, and of the preen gland oil. Both samples showed a moderate growth of MRSA with a similar sensitivity pattern to case 1; the only difference being that this MRSA was not resistant to clindamycin. Treatment was initiated with trimethoprim and sulfamethoxazole 100mg/kg PO BID, topical mupirocin ointment SID and topical bathing with 1:30 dilution of chlorhexidine SID. Due to financial constraints and poor owner compliance, 4 weeks later at re-examination, the bird was significantly improved, although had not been receiving the trimethoprim and sulfamethoxazole for the previous week. Treatment was continued with mupirocin and chlorhexadine for a further 2 weeks and then on the third week, another swab was taken from the preen gland oil for culture. There was no growth of MRSA at this point, and clinical signs had resolved. The time taken to achieve negative culture in this case was 7 weeks, although this may have been shorter if tested sooner. The owner of this bird had a chronic illness and was frequently in hospital. Case 3: A 3 year old, male, Nanday conure (Nandayus nenday) with an intermittent 21 month history of feather plucking and self-trauma to the cervical and tibio-tarsal regions. In this time, bacterial infections had been suspected based on cytology, but no cultures had been performed. Treatment had previously included potentiated amoxicillin, cephalexin, trimethoprim and sulfamethoxazole and ketoconazole. Interestingly the best response to treatment in that time had been seen with the trimethoprim and sulfamethoxazole. Examination of the bird revealed the lesion distribution to be confined to the tibio-tarsal area where there was erythematous and exudative dermatitis. Haematology, biochemistry, PBFD PCR and radiology revealed no significant abnormalities. A swab from the skin showed a heavy growth of MRSA with the same sensitivity results as the isolate in case 2. Treatment was started with trimethoprim and sulfamethoxazole 100mg/kg PO BID, topical mupirocin ointment SID and topical bathing with 1:30 dilution of chlorhexidine SID, and 2 weeks later the skin lesions had completely healed. Repeat culture of the skin, and culture from the choana were negative for MRSA at that time. The time taken to achieve negative culture in this case was 2 weeks from initiating specific treatment. There was no history of contact with human health care facilities or staff in this case.

4 3 DISCUSSION This case series shows that MRSA infection should be considered in pet parrots where there is a chronic history of feather plucking, self-mutilation or infection. As reported cases of MRSA are on the increase, there should be thorough consideration of previous treatments, including dose and duration of therapy (MAY 2006). Choana, uropygial gland and cloaca have been found to be the main sites for staphylococcal colonization in pigeons and chickens (KAWANO et al. 1996, SCHWARZ and WERCKENTHIN 2004). In this clinical series MRSA was isolated from the uropygial gland in one case, but the other cases were isolated from skin lesions. There are no studies documenting the prevalence of MRSA on the skin of parrots. The treatment protocols chosen were initially based in the sensitivity results. Most MRSA isolates typically remain sensitive to potentiated sulphonamides (MAY 2006) and this was confirmed by the sensitivity testing in each case. In case 1, silver sulfadiazine cream and chlorhexadine were chosen since they have been shown to be effective against MRSA in burn wounds (ACIKEL et al. 2003, SNELLING and ROBERTS 1988). However, after initial improvement, the progress slowed and repeat cultures showed MRSA was still present. Mupirocin is an antibacterial agent with a novel chemical structure unrelated to other antibiotics. It blocks protein synthesis in bacteria by inhibiting bacterial isoleucyl-trna synthetase. This unique action means mupirocin lacks cross-resistance with other antibacterial agents and has activity against multi-resistant strains of bacteria (TENNANT 2005). Mupirocin has been evaluated widely in the treatment of MRSA and has shown to be effective (STROCK 1990). Topical use has resulted in a 99.6% reduction in MRSA numbers in wound infections (RODE et al. 1988) and in another study eliminated MRSA in all (59) wounds treated (RODE et al. 1989). Therefore, mupirocin 2% ointment was used in the described cases, all of which eventually became culture negative. This case series has shown that treatment in parrots of MRSA infected wounds with to trimethoprim and sulfamethoxazole 100mg/kg PO BID, topical mupirocin 2% ointment SID and topical bathing with 1:30 dilution of chlorhexidine SID is effective in achieving resolution of the clinical signs and negative culture results in two to seven weeks from the onset of treatment. The time taken to produce negative cultures may have been shorter if more frequent swabs were cultured. Evidence of zoonotic transmission of MRSA from an asymptomatic dog to its owner has been described (MANIAN 2003). Isolation of MRSA from skin lesions of pet parrots shows that they are also at risk from MRSA infections, as with humans and other domestic mammals. It also raises suspicion that they may act as a reservoir for zoonotic infection of susceptible humans since the bird and owner typically live in close proximity and contact. In a study of cloacal microflora in great tit and blue tit nestlings, it was found that the make up of the flora was influenced more by environmental proximity then genetics (LUCAS and HEEB 2005). This case series warns that use of antibiotics for extended periods without culture and sensitivity testing will inevitably lead to more widely resistant staphylococcal strains, for which there may be no effective antibiotic. Treatment options may be limited to euthanasia in severe cases.

5 In conclusion, MRSA infections can occur in pet parrots, and this clinical series suggests a potentially effective treatment protocol. More investigation is required to determine the prevalence of MRSA in healthy UK parrot populations and the risk of transfer of infection from bird to owner. 4 CITATION INDEX 1. ACIKEL C, ONCUL O, ULKUR E, et al. Comparison of silver sulfadiazine 1%, mupirocin 2% and fusidic acid 2% for the topical antibacterial effect in methicillinresistant staphylococcal-infected, full skin thickness rat burn wounds. J Burn Care Rehabil 2003; 24(1): BAUK L. Avian dermatology. In: ALTMAN RB, CLUBB SL, DORRESTEIN GM, QUESENBERRY K (eds): Avian Medicine and Surgery. Philadelphia, PA: WB Saunders 1997; BOAG A, LOEFFLER A, LLOYD DH. Methicillin-resistant Staphylococcus aureus isolates from companion animals. Vet Rec 2004; 154(13): DEVRIESE LA, VNADAMME LR, FAMEREE L. Methicillin (cloxacillin)-resistant Staphylococcus aureus strains isolated from bovine mastitis cases. Zbl. Veterinarmedizin Reihe 1972; B19: GORTEL K, CAMPBELL KL, KAKOMA I, et al. Methicillin resistance among staphylococci isolated from dogs. Am J Vet Res 1999; 60(12): HARTMANN FA, TROSTLE SS, KLOHNEN AAO. Isolation of methicillin-resistant Staphylococcus aureus from a postoperative wound infection in a horse. J Am Vet Med Assoc 1997; 211(5): KAWANO J, SHIMIZU A, SAITOH Y, et al. Isolation of methicillin-resistant coagulase-negative staphylococci from chickens. J Clin Microb 1996; 34(9): LUCAS FS and HEEB P. Environmental factors shape cloacal bacterial assemblages in great tit parus major and blue tit P. caeruleus nestlings. J Avian Biol 2005; 36: MANIAN FA. Asymptomatic nasal carriage of mupirocin-resistant, methicillin resistant Staphylococcus aureus (MRSA) in a pet dog associated with MRSA infection in household contacts. Clin Infect Dis 2003; 36: MAY ER. Bacterial skin disease: Current thoughts on pathogenesis and management. Vet Clin NA, Sm Anim Pract 2006, 36(1): NASCIMENTO AM, CURSINO L, GONCALVES-DORNELAS H, et al. Antibioticresistant gram-negative bacteria in birds from the Brazilian Atlantic forest. The Condor 2003; 105: RODE H, de WET PM, MILLAR AJ, et al. Bacterial efficacy of mupirocin in multiantibiotic resistant Staphylococcal aureus burn wound infection. J Antimicrob Chemother 1988; 21(5): RODE H, HANSLO D, de WET PM, et al. Efficacy of mupirocin in methicillinresistant Staphylococcal aureus burn wound infection. Antimicrob Agents Chemother 1989; 33(8): SCHWARZ S and WERCKENTHIN C. Antibiotic resistance in staphylococci isolated from pigeons. Vet Derm 2004; 5(9): SNELLING CF and ROBERTS FJ. Comparison of silver sulfadiazine 1% with and without 1% chlorhexadine digluconate for topical antibacterial effect in the burnt infected rat. J Burn Care Rehabil 1988; 9(1): STROCK LL, LEE MM, RUTAN RL, et al. Topical bactroban (mupirocin): efficacy in treating burn wounds infected with methicillin-resistant staphylococci. J Burn Care Rehabil 1990; 11(5):

6 17. TENNANT B. BSAVA Small animal formulary, 2006.BSAVA, Gloucester. 18. TIEMERSMA EW, BRONZWAER S, LYYTIKAINEN O, et al. Methicillin resistant Staphylococcus aureus in Europe, Emerg Inf Dis 2004; 10(9). ( 19. TOMLIN J, PEAD MJ, LLOYD DH et al. Methicillin-resistant Staphylococcus aureus infections in 11 dogs. Vet Rec 1999; 144: WALLER A. The creation of a new monster: MRSA and MRSI Important emerging veterinary and zoonotic diseases. Vet Journ 2005; 169:

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