Surgical procedures at the maxillary sinuses and upper cheek teeth controlled by the c-arch technique

Deckblatt-Impressum persönlicher Dank Inhaltsverzeichnis Abkürzungsverzeichnis Einleitung Literaturübersicht Eigene Untersuchungen Diskussion Zusammenfassung Summary Literaturverzeichnis Anhang Danksagung Lebenslauf SelbständigkeitserklärungBackenzahnerkrankungen beim Pferd stellen eine häufig auftretende Problematik in der Veterinärmedizin dar. Die auftretenden Veränderungen an den Molaren und Prämolaren sind in der Regel irreversibel. Oft sind Backenzähne so massiv geschädigt, dass eine Extraktion unumgänglich ist. Bei Infektionen kommt es häufig zum Übertreten der bestehenden Entzündung auf den Alveolarknochen. Dieser wird zerstört und ein Übergriff auf die Oberkieferhöhle wird möglich. Muss ein Backenzahn schließlich entfernt werden, sind verschiedene Techniken bekannt: die orale Extraktion, die laterale Bukkotomie sowie die Repulsions- methode. Jede dieser Techniken besitzt ihre Vor- und Nachteile und ist nicht in jedem Fall anwendbar. Für die Wahl der Operationstechnik ist eine genaue Diagnostik notwendig. Während die laterale Bukkotomie als jüngste Methode hauptsächlich für die Prämolaren geeignet ist, findet die orale Extraktion, als älteste und einfachste Methode, sowohl bei alten Pferden mit kurzen Zahnwurzeln und/oder stark geschädigten Backenzähnen, als auch bei jungen Pferden zur Entfernung persistierender Milchzähne Anwendung. Die langen, fest in der Alveole verankerten Zahnwurzeln in Kombination mit dem geringen Öffnungswinkel des Pferdemaules machen eine orale Extraktion eines Backenzahnes oft unmöglich. Die Repulsionsmethode durch die eröffnete Oberkieferhöhle ist ebenfalls eine sehr alte Methode. Die Eröffnung der Oberkieferhöhle kann entweder mittels Trepanation oder Knochenflap-Technik geschehen. Die Schwierigkeit dieser Technik liegt in der Lagebestimmung der Zahnwurzel des zu extrahierenden Zahnes. Die Lage der Zahnwurzel muss von außen auf einer gedachten Linie nach (Günther, et al., 1967) bestimmt werden. Denn oberhalb des bestimmten Lagepunktes der Zahnwurzel wird die Kieferhöhle eröffnet und der Stempel blind aufgesetzt. Diese nur ungenaue Bestimmung kann zu fatalen Folgen für den Patienten führen, da eine Schädigung oder gar Entfernung des benachbarten Zahnes möglich ist. Ebenfalls kann es, durch massive Krafteinwirkung auf den Zahnstempel, zur Zerstörung der Alveole oder des Gaumendaches kommen. Anders ist es bei einer Zahnextraktion unter Anwendung der intraoperativen Durchleuchtung mit Hilfe der C-Bogen-Technik. Hier besteht für den Operateur während des gesamten chirurgischen Eingriffs die Möglichkeit alle seine operativen Handlungen zu kontrollieren. So ist unter anderem die exakte Identifikation des zu entfernenden Zahnes möglich, sowie eine ständige Kontrolle der Platzierung des Instrumentariums. Um die Zahnwurzeln der Backenzähne bei der intraoperativen Durchleuchtung exakt beurteilen zu können, muss eine möglichst überlagerungsfreie Darstellung der einzelnen Zahnreihen gelingen. Dazu muss der C-Bogen in einem Winkel von 115° für die rechte und 245° für die linke Backenzahnreihe an den Pferdekopf heran gefahren werden. Zusätzlich ermöglicht die intraoprative Durchleuchtungs- kontrolle eine Überprüfung der Alveole direkt im Anschluss an die Zahnextraktion auf vollständige Entfernung des Zahnes. Befinden sich noch Fragmente im Zahnfach, können diese sofort entfernt werden, ohne, dass eine erneute Vollnarkose notwendig wird. Verbleibende Zahnreste behindern den Granulationsvorgang im Zahnfach massiv. Durch den Abstoßungsprozess entstehen Fistelkanäle, welche eine erneute chirurgische Entfernung in Narkose notwendig machen. Wie die Auswertung der stationären Patientenkartei bestätigt, resultiert aus dieser verbesserten Operationstechnik ein Vermeiden der obengenannten intraoperativen Komplikationen und es wird eine bessere Genesung für den Patienten gewährleistet. Um die Zahnwurzeln der Backenzähne exakt beurteilen zu können, muss eine möglichst überlagerungsfreie Darstellung der einzelnen Zahnreihen gelingen, dazu muss der C-Bogen in einem Winkel von 115° für die rechte und 245° für die linke Backenzahnreihe an den Pferdekopf heran gefahren werden. Durch eine Serie von Röntgenaufnahmen, die während einer Zahnextraktion gemacht wurde, soll die gute Darstellbarkeit mit Hilfe der C -Bogen-Technik demonstriert werden. Ziel dieser Dissertation ist es, das operative Handling und die Genauigkeit der C-Bogen-Navigation bei chirurgischen Eingriffen an den Oberkieferhöhlen und backenzähnen beim Pferd zu demonstrieren. Die Einsatzmöglichkeiten dieser Methode im Bereich der Oberkieferhöhlen und backenzähne soll erläutert werden. Außerdem wird deutlich, dass die häufig auftretenden intraoperativen Komplikationen bei der Durchführung des retrograden Ausstempelns vermieden und diese historische Methode somit verbessert werden kann. Dies wurde durch Eigenversuche an Schlachtpferdeköpfen erprobt und anhand einer Auswertung der stationären Patientenkartei bewiesen.Dental diseases present a frequently appearing problem in equine medicine. The appearing changes at the molar and premolar teeth are normally irreversible. Often the molars are so massively damaged, that an extraction is unavoidable. Infections lead frequently to the encroachment of the existing infection to the alveolar bone, which will be destroyed and an encroachment of the inflammation on the maxillary sinus becomes possible. Must a molar finally be removed, different techniques are known: the oral extraction, the lateral buccotomy as well as the Repulsion. Each of these techniques owns their before- and disadvantages and therefore not each technology is applicable in each case. For the choice of the surgical technique an exact diagnostic is necessary. While the lateral buccotomy is suitable as latest method, mainly for the premolar teeth, oral extraction, as oldest and simplest method, applies only at old horses with short roots and/or greatly damaged teeth, as well as at the removal of persistent temporary teeth of young horses. Long roots firmly with the alveolus connected in combination with the limited oral access of the equine mouth makes an oral extraction of premolar and molar teeth often impossible. The repulsion through the opened maxillary sinus is likewise a very old method. The opening of the maxillary sinus can happen either by means of trepanation or bone- flap. The difficulty of this technology is situated in the determination the root of the tooth, which should be extracted, because the position of the root must be seted from external face of the equine head on a remembered line after Guenther, et al. (1967). Because above the certain position of the root the maxillary sinus is opened and the punch is put on it blindly. This only inaccurate determination can lead to fatal consequences for the patient, because a damage or maybe a removal of the adjacent tooth is possible. Likewise, through the excessive force which is influencing on the dental punch, the alveolus or the palatine bone might be destructed. The case is different by tooth extraction with application of the intraoperative illumination with the C-arch. This offers the surgeon during the whole surgical procedure the possibility to controll all his operative acts. So among others an exact identification of the tooth which should be removed is possible, as well as the permanent control of the placement of the instrumentarium. By the intraoperative fluoroscopy controll the alveolus can be checked immediately following the tooth extraction on complete removal. If still fragments are found in the tooth socket, these could be removed immediately, without, a renewed general anesthetic. Retained tooth fragments disturb the granulation in the dental socket massively. The remaining dental rests appear fistulation, which make a renewed surgical removal in anaesthesia necessary. The evaluation of the stationary patients confirm, that an improved surgical technique results in avoiding of the above- mentioned intraoperative complications, thus guaranteed a better recovery for the patient. To be able to judge the roots of the molars exactly, the superimpositon of the contralateral dental arcades must be prevented. To reach this the C-arch must be driven in an angle of 115 degree for the right and 245 degree for the left dental arcade at the equine head. A serie of x-rays was made during a tooth extraction, to demonstrate the very good representation which would reached with the help of the C-arch-technology. The aim of this theses is, to demonstrate the operative handling and precision of the C-arch navigation by surgery at the maxillary sinuses and premolar and molar teeth at the horse and to illustrate the possibilities of using from this method in the area of the equine upper jaw. Moreover becomes clear, that the frequently appearing of intraoprative complications, which appear by the accomplishment of retrograde repulsion could be avoided and thus this process can be improved. This was tested with heads of slaughterhorses and poved with an evaluation of the stationary patients

Methicillin-resistant Staphylococcus aureus ST398 in Humans and Animals, Central Europe

Isolates found in persons and animals in Germany and Austria show a genetic relationship

Genome-Wide Association Studies for the Detection of Genetic Variants Associated With Daptomycin and Ceftaroline Resistance in Staphylococcus aureus

Background: As next generation sequencing (NGS) technologies have experienced a rapid development over the last decade, the investigation of the bacterial genetic architecture reveals a high potential to dissect causal loci of antibiotic resistance phenotypes. Although genome-wide association studies (GWAS) have been successfully applied for investigating the basis of resistance traits, complex resistance phenotypes have been omitted so far. For S. aureus this especially refers to antibiotics of last resort like daptomycin and ceftaroline. Therefore, we aimed to perform GWAS for the identification of genetic variants associated with DAP and CPT resistance in clinical S. aureus isolates. Materials/methods: To conduct microbial GWAS, we selected cases and controls according to their clonal background, date of isolation, and geographical origin. Association testing was performed with PLINK and SEER analysis. By using in silico analysis, we also searched for rare genetic variants in candidate loci that have previously been described to be involved in the development of corresponding resistance phenotypes. Results: GWAS revealed MprF P314L and L826F to be significantly associated with DAP resistance. These mutations were found to be homogenously distributed among clonal lineages suggesting convergent evolution. Additionally, rare and yet undescribed single nucleotide polymorphisms could be identified within mprF and putative candidate genes. Finally, we could show that each DAP resistant isolate exhibited at least one amino acid substitution within the open reading frame of mprF. Due to the presence of strong population stratification, no genetic variants could be associated with CPT resistance. However, the investigation of the staphylococcal cassette chromosome mec (SCCmec) revealed various mecA SNPs to be putatively linked with CPT resistance. Additionally, some CPT resistant isolates revealed no mecA mutations, supporting the hypothesis that further and still unknown resistance determinants are crucial for the development of CPT resistance in S. aureus. Conclusion: We hereby confirmed the potential of GWAS to identify genetic variants that are associated with antibiotic resistance traits in S. aureus. However, precautions need to be taken to prevent the detection of spurious associations. In addition, the implementation of different approaches is still essential to detect multiple forms of variations and mutations that occur with a low frequency.Peer Reviewe

Antibiotic resistance and molecular epidemiology of Staphylococcus aureus in Nigeria

<p>Abstract</p> <p>Background</p> <p><it>Staphylococcus aureus </it>is an important pathogen causing a wide range of infections in the hospital and community setting. In order to have adequate information for treatment of <it>S. aureus </it>infections, it is crucial to understand the trends in the antibiotic-resistance patterns. In addition, the occurrence and changes in types of <it>S. aureus</it>, clonal identities, and their geographic spread is essential for the establishment of adequate infection control programmes. In this study, 68 <it>S. aureus </it>isolates obtained from clinical and non-clinical sources in Nigeria between January and April 2009 were characterized using phenotypic and molecular methods.</p> <p>Results</p> <p>All the <it>S. aureus </it>isolates were susceptible to teicoplanin, vancomycin, phosphomycin, fusidic acid, rifampicin, daptomycin, mupirocin, linezolid and tigecycline. Sixteen percent of the isolates were resistant to oxacillin, while 55% and 72% of isolates were resistant to tetracycline and trimethoprim/sulphamethoxazole (cotrimoxazole), respectively (Table <tblr tid="T1">1</tblr>). There was excellent correlation between the broth microdilution assay and detection of antibiotic resistance genes by the multiplex PCR, in the determination of <it>S. aureus </it>resistance to erythromycin, gentamicin, methicillin and tetracycline. A total of 28 <it>spa </it>types were identified in the study, and the predominant <it>spa </it>type among the methicillin-susceptible <it>S. aureus </it>(MSSA) isolates was t084 (13 isolates). The t037-ST241-SCC<it>mec</it>III type was the only clone identified in Maiduguri (North-East Nigeria) while in South-West Nigeria, diversity among the MRSA isolates (t451-ST8-SCC<it>mec</it>V; t008-ST94-SCC<it>mec</it>IV; t002-ST5-SCC<it>mec</it>V; t064-ST8-SCC<it>mec</it>V) was observed. The toxin genes <it>seh </it>and <it>etd </it>were detected in isolates affiliated with clonal complexes CC1, CC80 and sequence type ST25, respectively. The proportion of PVL-positive isolates among MSSA was high (40%). Most of the PVL-positive MSSA isolates were obtained from wound infections and associated with clonal complexes CC1, CC30, CC121 and with sequence type ST152.</p> <tbl id="T1"> <title> <p>Table 1</p> </title> <caption> <p>Antibiotic resistance profile of <it>S. aureu</it><it>s </it>(MSSA and MRSA) from Nigeria</p> </caption> <tblbdy cols="4"> <r> <c> <p/> </c> <c cspan="3" ca="left"> <p><b>Number (%) of resistant isolates among</b>:</p> </c> </r> <r> <c ca="left"> <p><b>Antibiotic</b></p> </c> <c ca="left"> <p><b>MSSA</b></p> <p><b>(n = 57)</b></p> </c> <c ca="left"> <p><b>MRSA</b></p> <p><b>(n = 11)</b></p> </c> <c ca="left"> <p><b>Total</b></p> <p><b>(n = 68)</b></p> </c> </r> <r> <c cspan="4"> <hr/> </c> </r> <r> <c ca="left"> <p>Penicillin</p> </c> <c ca="left"> <p>49 (86)</p> </c> <c ca="left"> <p>11 (100)</p> </c> <c ca="left"> <p>60 (88.2)</p> </c> </r> <r> <c ca="left"> <p>Oxacillin</p> </c> <c ca="left"> <p>0 (0)</p> </c> <c ca="left"> <p>11 (100)</p> </c> <c ca="left"> <p>11 (16.2)</p> </c> </r> <r> <c ca="left"> <p>Teicoplanin</p> </c> <c ca="left"> <p>0 (0)</p> </c> <c ca="left"> <p>0 (0)</p> </c> <c ca="left"> <p>0 (0)</p> </c> </r> <r> <c ca="left"> <p>Vancomycin</p> </c> <c ca="left"> <p>0 (0)</p> </c> <c ca="left"> <p>0 (0)</p> </c> <c ca="left"> <p>0 (0)</p> </c> </r> <r> <c ca="left"> <p>Gentamicin</p> </c> <c ca="left"> <p>1 (1.8)</p> </c> <c ca="left"> <p>9 (81.8)</p> </c> <c ca="left"> <p>10 (14.7)</p> </c> </r> <r> <c ca="left"> <p>Tetracycline</p> </c> <c ca="left"> <p>27 (47.4)</p> </c> <c ca="left"> <p>11 (100)</p> </c> <c ca="left"> <p>38 (55.9)</p> </c> </r> <r> <c ca="left"> <p>Ciprofloxacin</p> </c> <c ca="left"> <p>12 (21.1)</p> </c> <c ca="left"> <p>8 (72.7)</p> </c> <c ca="left"> <p>20 (29.4)</p> </c> </r> <r> <c ca="left"> <p>Moxifloxacin</p> </c> <c ca="left"> <p>0 (0)</p> </c> <c ca="left"> <p>7 (63.6)</p> </c> <c ca="left"> <p>7 (10.3)</p> </c> </r> <r> <c ca="left"> <p>Trimethoprim/sulfamethoxazole</p> </c> <c ca="left"> <p>39 (68.4)</p> </c> <c ca="left"> <p>10 (90.9)</p> </c> <c ca="left"> <p>49 (72.1)</p> </c> </r> <r> <c ca="left"> <p>Phosphomycin</p> </c> <c ca="left"> <p>0 (0)</p> </c> <c ca="left"> <p>0 (0)</p> </c> <c ca="left"> <p>0 (0)</p> </c> </r> <r> <c ca="left"> <p>Fusidic acid</p> </c> <c ca="left"> <p>0 (0)</p> </c> <c ca="left"> <p>0 (0)</p> </c> <c ca="left"> <p>0 (0)</p> </c> </r> <r> <c ca="left"> <p>Erythromycin</p> </c> <c ca="left"> <p>2 (3.5)</p> </c> <c ca="left"> <p>6 (54.5)</p> </c> <c ca="left"> <p>8 (11.8)</p> </c> </r> <r> <c ca="left"> <p>Clindamycin</p> </c> <c ca="left"> <p>0 (0)</p> </c> <c ca="left"> <p>6 (54.5)</p> </c> <c ca="left"> <p>6 (8.8)</p> </c> </r> <r> <c ca="left"> <p>Rifampicin</p> </c> <c ca="left"> <p>0 (0)</p> </c> <c ca="left"> <p>0 (0)</p> </c> <c ca="left"> <p>0 (0)</p> </c> </r> <r> <c ca="left"> <p>Daptomycin</p> </c> <c ca="left"> <p>0 (0)</p> </c> <c ca="left"> <p>0 (0)</p> </c> <c ca="left"> <p>0 (0)</p> </c> </r> <r> <c ca="left"> <p>Mupirocin</p> </c> <c ca="left"> <p>0 (0)</p> </c> <c ca="left"> <p>0 (0)</p> </c> <c ca="left"> <p>0 (0)</p> </c> </r> <r> <c ca="left"> <p>Linezolid</p> </c> <c ca="left"> <p>0 (0)</p> </c> <c ca="left"> <p>0 (0)</p> </c> <c ca="left"> <p>0 (0)</p> </c> </r> <r> <c ca="left"> <p>Tigecycline</p> </c> <c ca="left"> <p>0 (0)</p> </c> <c ca="left"> <p>0 (0)</p> </c> <c ca="left"> <p>0 (0)</p> </c> </r> </tblbdy> </tbl> <p>Conclusions</p> <p>The use of phenotypic and molecular methods provided useful information on antibiotic resistance and molecular diversity of <it>S. aureus </it>in Nigeria. The high proportion of PVL-positive MSSA isolates affiliated to various clonal complexes and detected in all the health institutions is a major concern, both as a source of severe infections and as a potential reservoir that could lead to the emergence of PVL-positive MRSA. This study presents the first baseline information on the nature of the antibiotic resistance genes from <it>S. aureus </it>isolates in Nigeria. There is the need to curtail the spread and establishment of MRSA and PVL-positive MSSA clones in Nigerian health care institutions.</p

Silence as a way of niche adaptation: mecC-MRSA with variations in the accessory gene regulator (agr) functionality express kaleidoscopic phenotypes

Functionality of the accessory gene regulator (agr) quorum sensing system is an important factor promoting either acute or chronic infections by the notorious opportunistic human and veterinary pathogen Staphylococcus aureus. Spontaneous alterations of the agr system are known to frequently occur in human healthcare-associated S. aureus lineages. However, data on agr integrity and function are sparse regarding other major clonal lineages. Here we report on the agr system functionality and activity level in mecC-carrying methicillin resistant S. aureus (MRSA) of various animal origins (n = 33) obtained in Europe as well as in closely related human isolates (n = 12). Whole genome analysis assigned all isolates to four clonal complexes (CC) with distinct agr types (CC599 agr I, CC49 agr II, CC130 agr III and CC1943 agr IV). Agr functionality was assessed by a combination of phenotypic assays and proteome analysis. In each CC, isolates with varying agr activity levels were detected, including the presence of completely non-functional variants. Genomic comparison of the agr I-IV encoding regions associated these phenotypic differences with variations in the agrA and agrC genes. The genomic changes were detected independently in divergent lineages, suggesting that agr variation might foster viability and adaptation of emerging MRSA lineages to distinct ecological niches

Comparison of Different Phenotypic Approaches to Screen and Detect mecC-Harboring Methicillin-Resistant Staphylococcus aureus

Similar to mecA, mecC confers resistance against beta-lactams, leading to the phenotype of methicillin-resistant Staphylococcus aureus (MRSA). However, mecC-harboring MRSA strains pose special difficulties in their detection. The aim of this study was to assess and compare different phenotypic systems for screening, identification, and susceptibility testing of mecC-positive MRSA isolates. A well-characterized collection of mecC-positive S. aureus isolates (n 111) was used for evaluation. Routinely used approaches were studied to determine their suitability to correctly identify mecC-harboring MRSA, including three (semi)automated antimicrobial susceptibility testing (AST) systems and five selective chromogenic agar plates. Additionally, a cefoxitin disk diffusion test and an oxacillin broth microdilution assay were examined. All mecC-harboring MRSA isolates were able to grow on all chromogenic MRSA screening plates tested. Detection of these isolates in AST systems based on cefoxitin and/or oxacillin testing yielded overall positive agreements with the mecC genotype of 97.3% (MicroScan WalkAway; Siemens), 91.9% (Vitek 2; bioMérieux), and 64.9% (Phoenix, BD). The phenotypic resistance pattern most frequently observed by AST devices was “cefoxitin resistance/oxacillin susceptibility,” ranging from 54.1% (Phoenix) and 83.8% (Vitek 2) to 92.8% (WalkAway). The cefoxitin disk diffusion and oxacillin broth microdilution assays categorized 100% and 61.3% of isolates to be MRSA, respectively. The chromogenic media tested confirmed their suitability to reliably screen for mecC-harboring MRSA. The AST systems showed false-negative results with varying numbers, misidentifying mecC-harboring MRSA as methicillin-susceptible S. aureus. This study underlines cefoxitin’s status as the superior surrogate mecC-positive MRSA marker.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Mutations in the gdpP gene are a clinically relevant mechanism for β-lactam resistance in meticillin-resistant Staphylococcus aureus lacking mec determinants

In Staphylococcus aureus, resistance to β-lactamase stable β-lactam antibiotics is mediated by the penicillinbinding protein 2a, encoded by mecA or by its homologues mecB or mecC. However, a substantial number of meticillin-resistant isolates lack known mec genes and, thus, are called meticillin resistant lacking mec (MRLM). This study aims to identify the genetic mechanisms underlying the MRLM phenotype. A total of 141 MRLM isolates and 142 meticillin-susceptible controls were included in this study. Oxacillin and cefoxitin minimum inhibitory concentrations were determined by broth microdilution and the presence of mec genes was excluded by PCR. Comparative genomics and a genome-wide association study (GWAS) approach were applied to identify genetic polymorphisms associated with the MRLM phenotype. The potential impact of such mutations on the expression of PBP4, as well as on cell morphology and biofilm formation, was investigated. GWAS revealed that mutations in gdpP were significantly associated with the MRLM phenotype. GdpP is a phosphodiesterase enzyme involved in the degradation of the second messenger cyclic-di-AMP in S. aureus. A total of 131 MRLM isolates carried truncations, insertions or deletions as well as amino acid substitutions, mainly located in the functional DHH-domain of GdpP. We experimentally verified the contribution of these gdpP mutations to the MRLM phenotype by heterologous complementation experiments. The mutations in gdpP had no effect on transcription levels of pbp4; however, cell sizes of MRLM strains were reduced. The impact on biofilm formation was highly strain dependent. We report mutations in gdpP as a clinically relevant mechanism for β-lactam resistance in MRLM isolates. This observation is of particular clinical relevance, since MRLM are easily misclassified as MSSA (meticillin-susceptible S. aureus), which may lead to unnoticed spread of β-lactam-resistant isolates and subsequent treatment failure.Peer Reviewe

Novel Lineage of Methicillin-Resistant Staphylococcus aureus, Hong Kong

To determine whether spa type of methicillin-resistant Staphylococcus aureus in pigs belonged to sequence type (ST) 398, we analyzed nasal swabs from pig carcasses at Hong Kong markets in 2008. ST9 belonging to spa type t899 was found for 16/100 samples, which indicates that a distinct lineage has emerged in pigs

Global distribution and diversity of ovine-associated Staphylococcus aureus

Staphylococcus aureus is an important pathogen of many species, including sheep, and impacts on both human and animal health, animal welfare, and farm productivity. Here we present the widest global diversity study of ovine-associated S. aureus to date. We analysed 97 S. aureus isolates from sheep and sheep products from the UK, Turkey, France, Norway, Australia, Canada and the USA using multilocus sequence typing (MLST) and spa typing. These were compared with 196 sheep isolates from Europe (n = 153), Africa (n = 28), South America (n = 14) and Australia (n = 1); 172 bovine, 68 caprine and 433 human S. aureus profiles. Overall there were 59 STs and 87 spa types in the 293 ovine isolates; in the 97 new ovine isolates there were 22 STs and 37 spa types, including three novel MLST alleles, four novel STs and eight novel spa types. Three main CCs (CC133, CC522 and CC700) were detected in sheep and these contained 61% of all isolates. Four spa types (t002, t1534, t2678 and t3576) contained 31% of all isolates and were associated with CC5, CC522, CC133 and CC522 respectively. spa types were consistent with MLST CCs, only one spa type (t1403) was present in multiple CCs. The three main ovine CCs have different but overlapping patterns of geographical dissemination that appear to match the location and timing of sheep domestication and selection for meat and wool production. CC133, CC522 and CC700 remained ovine-associated following the inclusion of additional host species. Ovine isolates clustered separately from human and bovine isolates and those from sheep cheeses, but closely with caprine isolates. As with cattle isolates, patterns of clonal diversification of sheep isolates differ from humans, indicative of their relatively recent host-jump