Burnens, André

Maranta, Christian A.

Perreten, Vincent

Stegmann, Ramona

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J Antimicrob Chemother 2010doi:10.1093/jac/dkq241Advance publication 1 July 2010Human infection associatedwith methicillin-resistantStaphylococcus pseudintermedius ST71Ramona Stegmann1, Andre´ Burnens2,Christian A. Maranta3 and Vincent Perreten1*1Institute of Veterinary Bacteriology, Vetsuisse Faculty, Universityof Berne, Berne, Switzerland; 2Medica, Medical LaboratoriesDr F. Kaeppeli, POB, 8024 Zu¨rich, Switzerland; 3Orlpraxen Ku¨snacht,Seestr. 29, 8700 Ku¨snacht, Switzerland*Corresponding author. Tel: +41-31-631-2430; Fax: +41-31-631-2634;E-mail: vincent.perreten@vbi.unibe.chKeywords: MRSP, zoonosis, antibiotic resistanceSir,Staphylococcus pseudintermedius is one of the most commonpathogens isolated from skin and post-operative infections indogs and cats1,2 and can also occasionally cause infections inhumans.3,4 People working or living with animals are morelikely to be colonized with S. pseudintermedius in their nasal cav-ities5 and human infection acquired from dogs has been recentlyreported.4 In recent years, there have been increasing numbersof infections in dogs and cats caused by methicillin-resistantS. pseudintermedius (MRSP) and a predominant MRSP clone isdisseminating in dogs and cats throughout Europe.1,2 ThisMRSP clone belongs to the multilocus sequence type (MLST)ST71, spa type t02 and SmaI PFGE group J (ST71-t02-J) and con-tains the staphylococcal cassette chromosome element SCCmecII–III.1 It displays resistance to many classes of antibiotics andrepresents a challenge for therapy. Here, we report, to our knowl-edge, the first case of a human infection caused by MRSP ST71emphasizing its zoonotic potential and therapeutic challenge.An adult patient presented to the doctor in 2009 withheadache, watery eyes and a small oedema over the right eye.The patient had a history of recurrent rhinosinusitis and threesurgical interventions had been performed over the previous 6years, the last one in 2005. CT illustrated an obliteration of theright sinus frontalis with an expansive mucocele. Yet another sur-gical intervention was absolutely essential and post-operativetreatment for 3 weeks with 500 mg of ciprofloxacin twice perday and 300 mg of clindamycin three times per day was given.Five weeks post-operatively, a purulent infection appeared.After 10 days of treatment with 875 mg of amoxicillin/125 mgof clavulanic acid twice daily and 300 mg of clindamycin threetimes daily and no improvement, a sample was sent for bacterio-logical analysis. The laboratory identified a multidrug-resistantTable 1. MICs of 22 antibiotics and antibiotic resistance genes in S. pseudintermedius ST71, strain 27366Antibiotics Resistance breakpointsa (mg/L) MICs (mg/L) Resistance genesAmikacin ≥64 ≤16 —Amoxicillin/clavulanic acid ≥8/4 8/4 mecACefalotin ≥32 32 mecAChloramphenicol ≥32 8 —Clindamycin ≥4 .8 erm(B)Enrofloxacin ≥4 .16 grlA (Ser80Ile); gyrA (Ser84Leu)Erythromycin ≥8 .16 erm(B)Fusidic acid NA ≤0.12 —Gentamicin ≥16 16 aac(6′)-Ie-aph(2)-IaKanamycin ≥64 .128 aph(3′)-IIILinezolid ≥8 ≤1 —Mupirocin NA ≤4 —Nitrofurantoin ≥128 ≤16 —Oxacillin ≥0.5b .8 mecAPenicillin ≥0.25 8 blaZ; mecAQuinupristin/dalfopristin ≥4 1 —Rifampicin ≥4 ≤0.12 —Streptomycin ≥32 .32 ant(6)-IaTetracycline ≥16 .32 tet(K)Trimethoprim/sulfamethoxazole ≥4/76 .8/152 dfr(G)/NDTrimethoprim ≥16 .128 dfr(G)Vancomycin ≥32b ≤1 —NA, not available; ND, not determined; —, no gene was detected.aResistance breakpoints were those recommended for Staphylococcus spp. in the CLSI Informational Supplement M100-S20 (www.clsi.org), exceptfor streptomycin, for which the breakpoint from the French Society for Microbiology (www.sfm.asso.fr) was used.bThis breakpoint is applicable to CoNS.Research letters2047JACStaphylococcus belonging to the Staphylococcus intermediusgroup (SIG) using the ID 32 STAPH system (bioMe´rieux, Marcyl’E´toile, France) and disc diffusion susceptibility testing (OxoidLtd, Basingstoke, UK). Based on these results, a local treatmentwith fusidic acid gauze and application of 2% mupirocin oint-ment four times a day for 8 days followed by a topical glucocor-ticoid/antibiotic combination therapy (0.5 mg/g fluocinonide,2.5 mg/g neomycin, 0.25 mg/g gramicidin and 100000 IU/g nys-tatin) packing for 4 days improved the local condition. Six weeksafter the purulent infection, the wound had healed with scarringand no bacterium was detectable in a repeat smear. Localfollow-up treatment with steroids and routine check-ups con-firmed the absence of residual infection.The multidrug-resistant Staphylococcus isolate was furtheridentified as MRSP ST71-t02-J containing SCCmec II–III usingMLST typing, spa typing, PFGE and SCCmec typing methodsdescribed previously.1 MICs of antibiotics were determined inMueller–Hinton broth using custom Sensititre susceptibilityNLV73 plates (Trek Diagnostics System, East Grinstead, UK)except for rifampicin, trimethoprim, kanamycin and fusidic acid,which were tested using home-made microbroth dilution plates.Antibiotic resistance genes were detected using a microarray.6Mutations in topoisomerase genes gyrA and grlA were identifiedby sequencing of PCR products7 (Table 1). The isolate was suscep-tible to the antibiotics amikacin, chloramphenicol, fusidic acid,linezolid, nitrofurantoin, the combination quinupristin/dalfopristin,rifampicin and vancomycin (Table 1).The patient owned a male dog that needed home carebecause of various clinical problems such as diabetes, recurrentwarts and abdominal tumour. The dog had consultations invarious clinics and underwent several antibiotic treatments(details of substances could not be ascertained). The dog waseuthanized before samples could be taken to determinewhether it was a carrier of the strain. The patient also ownedhorses and cats; all of them were in good health without clinicalsigns. Even if the ultimate source of the MRSP infection could notbe identified, the patient was infected with the same MRSP clone(ST71-t02-J with SCCmec II–III) that has been disseminating indogs over Europe in recent years.1A case similar to the one reported here has been described in theUSA, where a woman developed sinusitis caused by a methicillin-resistant SIG whose origin could be attributed to her pet dog.8 Inthat case, vancomycin and linezolid were used for treatment.The increasing number of dogs carrying MRSP constitutes arisk for pet owners to become colonized with MRSP, and MRSPinfections in humans may also increase in the near future. It istherefore important to recognize MRSP as a zoonotic pathogenand have antibiotics available for the treatment of MRSP infec-tions in humans. Therefore, antibiotics such as mupirocin, linezo-lid, quinupristin/dalfopristin, rifampicin and vancomycin that areused for decolonization or as ‘last resort antibiotics’ againstmethicillin-resistant staphylococci in humans should not beused for treatment in animals.AcknowledgementsWe are grateful to Anne-Sylvie Passen-Borel, Veterinary Practice Ru¨ti, forproviding clinical information on the dog and to Russell Kempker, EmoryUniversity School of Medicine, Atlanta, who kindly gave us informationrelated to the SIG case in the USA.FundingThis study was partially supported by the installation grant of theVetsuisse Faculty of the University of Berne to V. P.; some of the datahave been generated as part of our routine work.Transparency declarationsNone to declare.References1 Perreten V, Kadlec K, Schwarz S et al. Clonal spread ofmethicillin-resistant Staphylococcus pseudintermedius in Europe andNorth America: an international multicentre study. J AntimicrobChemother 2010; 65: 1145–54.2 Kadlec K, Schwarz S, Perreten V et al. Molecular analysis of methicillin-resistant Staphylococcus pseudintermedius of feline origin from differentEuropean countries and North America. J Antimicrob Chemother 2010;65: 1826–8.3 Van Hoovels L, Vankeerberghen A, Boel A et al. First case ofStaphylococcus pseudintermedius infection in a human. J Clin Microbiol2006; 44: 4609–12.4 Chuang CY, Yang YL, Hsueh PR et al. Catheter-related bacteremiacaused by Staphylococcus pseudintermedius refractory to antibiotic-locktherapy in a hemophilic child with dog exposure. J Clin Microbiol 2010;48: 1497–8.5 Weese JS, van Duijkeren E. Methicillin-resistant Staphylococcus aureusand Staphylococcus pseudintermedius in veterinary medicine. VetMicrobiol 2010; 140: 418–29.6 Perreten V, Vorlet-Fawer L, Slickers P et al. Microarray-based detectionof 90 antibiotic resistance genes of Gram-positive bacteria. J ClinMicrobiol 2005; 43: 2291–302.7 Descloux S, Rossano A, Perreten V. Characterization of new staphylococcalcassette chromosome mec (SCCmec) and topoisomerase genes influoroquinolone- and methicillin-resistant Staphylococcus pseudinter-medius. J Clin Microbiol 2008; 46: 1818–23.8 Kempker R, Mangalat D, Kongphet-Tran Tet al. Beware of the pet dog: acase of Staphylococcus intermedius infection. Am J Med Sci 2009; 338:425–7.J Antimicrob Chemother 2010doi:10.1093/jac/dkq224Advance publication 16 June 2010Successful treatment with tigecyclineof two patients with complicatedurinary tract infections caused byextended-spectrum b-lactamase-producing Escherichia coliSuzanne E. Geerlings1*, Karlijn A. M. I. van Donselaar-van der Pant2 and Ingrid Keur2Research letters2048

Human infection associated with methicillin-resistant Staphylococcus pseudintermedius ST71

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