combined-vivo-optical-ct-imaging-to-monitor-infection-inflammation

Combined <em>In vivo</em> Optical and &#181;CT Imaging to Monitor Infection, Inflammation, and Bone Anatomy in an Orthopaedic Implant Infection in Mice

Multimodality imaging has emerged as a common technological approach used in both preclinical and clinical research. Advanced techniques that combine in ...

David Geffen School of Medicine at University of California, Los Angeles (UCLA)

Eph receptor tyrosine kinases and their ligands, ephrins, mediate neurodevelopmental processes such as boundary formation, axon guidance, vasculogenesis, and cell migration. We determined the expression profiles of the Eph family members in five glioma cell lines under migrating and nonmigrating conditions. EphB2 mRNA was overexpressed in all five during migration (1.2-2.8-fold). We found abundant EphB2 protein as well as strong phosphorylation of EphB2 in migrating U87 cells. Confocal imaging showed EphB2 localized in lamellipodia of motile U87 cells. Treatment with ephrin-B1/Fc chimera stimulated migration and invasion of U87, whereas treatment with a blocking EphB2 antibody significantly inhibited migration and invasion. Forced expression of EphB2 in U251 cells stimulated cell migration and invasion and diminished adhesion concomitant with the tyrosine phosphorylation of EphB2. U251 stably transfected with EphB2 showed more scattered and more pronounced invasive growth in an ex vivo rat brain slice. In human brain tumor specimens, EphB2 expression was higher in glioblastomas than in low-grade astrocytomas or normal brain; patterns of phosphorylated EphB2 matched the expression levels. Laser capture microdissection of invading glioblastoma cells revealed elevated EphB2 mRNA (1.5-3.5-fold) in 7 of 7 biopsy specimens. Immunohistochemistry demonstrated EphB2 localization primarily in glioblastoma cells (56 of 62 cases) and not in normal brain. This is the first demonstration that migrating glioblastoma cells overexpress EphB2 in vitro and in vivo; glioma migration and invasion are promoted by activation of EphB2 or inhibited by blocking EphB2. Dysregulation of EphB2 expression or function may underlie glioma invasion.

The phosphorylation of EphB2 receptor regulates migration and invasion of human glioma cells.

Developing vertebrates increase both their locomotory power output and endurance due to ontogenetic improvements in anaerobic and aerobic metabolic capacities. Do similar patterns hold for insect locomotion, or do longer tracheal lengths create problems for oxygen delivery in older animals? We forced developing American locust grasshoppers (Schistocerca americana) to jump repeatedly and examined the effect of development on power output, endurance, lactate concentration, oxygen consumption and the oxygen sensitivity of jump performance. As previously shown, power outputs, relative leg lengths and leg cuticular content increased with age. A key finding of this study is that both lactate concentration and aerobic metabolic rate of the jumping muscle increase with age, explaining how the increased leg cuticular stiffness can result in increased power output. After two minutes of jumping, grasshoppers rely completely on aerobic ATP production. The rise in mass-specific, active aerobic metabolic rates with age indicates that problems with longer tracheae can be overcome; however, the reduced endurance, higher lactate concentrations and increased oxygen sensitivity of locomotory performance in older animals indicate that larger/older grasshoppers have smaller safety margins for oxygen delivery during hopping.

Ontogenetic effects on aerobic and anaerobic metabolism during jumping in the American locust, Schistocerca americana.

Eph receptor tyrosine kinases mediate neurodevelopmental processes such as boundary formation, vasculogenesis, and cell migration. Recently, we found that overexpression of EphB2 in glioma cells results in reduced cell adhesion and increased cell invasion. Since R-Ras has been shown to play a critical role in EphB2 regulation of integrin activity, we explored whether the biological role of EphB2 in glioma invasion is mediated by downstream R-Ras activation. On EphB2 activation, R-Ras associated with the receptor and became highly phosphorylated. Depletion of endogenous R-Ras expression by siRNA abrogated EphB2 effects on glioma cell adhesion, proliferation, and invasion in ex vivo rat brain slices. Anti-proliferative responses to EphB2 activation were consistent with suppressed mitogen-activated protein kinase activity. Moreover, R-Ras was highly phosphorylated in the invading glioma cells. In human brain tumor specimens, R-Ras expression and phosphorylation correlated with increasing grade of gliomas. Laser capture microdissection of invading glioblastoma cells revealed elevated R-Ras mRNA (1.5- to 26-fold) in 100% (eight of eight) of biopsy specimens, and immunohistochemistry revealed high R-Ras localization primarily in glioblastoma cells. The phosphorylation ratio of R-Ras positively correlated with the phosphorylation ratio of EphB2 in glioblastoma tissues. These results demonstrate that R-Ras plays an important role in glioma pathology, further suggesting the EphB2/R-Ras signaling pathway as a potential therapeutic target.

EphB2/R-Ras signaling regulates glioma cell adhesion, growth, and invasion.

Eph receptor tyrosine kinases are involved in nervous system development. Eph ligands, termed ephrins, are transmembrane proteins that bind to Eph receptors, the mutual activation of which causes repulsive effects in reciprocally contacting cells. Previously, we showed that overexpression of EphB2 in glioma cells increases cell invasion. Here, expression profiles of ephrin-B family members were determined in four glioma cell lines and in invading glioblastoma cells collected by laser capture microdissection. Ephrin-B3 mRNA was up-regulated in migrating cells of four of four glioma cell lines (1.3- to 1.7-fold) and in invading tumor cells of eight of eight biopsy specimens (1.2- to 10.0-fold). Forced expression of ephrin-B3 in low expressor cell lines (U87, T98G) stimulated cell migration and invasion in vitro and ex vivo, concomitant with tyrosine phosphorylation of ephrin-B3. In high expressor cell lines (U251, SNB19), ephrin-B3 colocalized with Rac1 to lamellipodia of motile wild-type cells. Cells transfected with ephrin-B3 small interfering RNA (siRNA) showed significant morphologic change and decreased invasion in vitro and ex vivo. Depletion of endogenous ephrin-B3 expression abrogated the increase of migration and invasion induced by EphB2/Fc, indicating increased invasion is dependent on ephrin-B3 activation. Furthermore, using a Rac1-GTP pull-down assay, we showed that ephrin-B3 is associated with Rac1 activation. Reduction of Rac1 by siRNA negated the increased invasion by addition of EphB2/Fc. In human glioma specimens, ephrin-B3 expression and phosphorylation correlated with increasing tumor grade. Immunohistochemistry revealed robust staining for phosphorylated ephrin-B and ephrin-B3 in invading glioblastoma cells. These data show that ephrin-B3 expression and signaling through Rac1 are critically important to glioma invasion.

Ephrin-B3 ligand promotes glioma invasion through activation of Rac1.

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Vancomycin is widely used for intravenous prophylaxis against surgical implant infections. However, it is unclear whether alternative antibiotics used to treat methicillin-resistant Staphylococcus aureus (MRSA) infections are effective as prophylactic agents. The aim of this study was to compare the efficacies of vancomycin, daptomycin, and tigecycline as prophylactic therapy against a methicillin-sensitive S. aureus (MSSA) or MRSA surgical implant infection in mice. MSSA or MRSA was inoculated into the knee joints of mice in the presence of a surgically placed medical-grade metallic implant. The efficacies of low- versus high-dose vancomycin (10 versus 110 mg/kg), daptomycin (1 versus 10 mg/kg), and tigecycline (1 versus 10 mg/kg) intravenous prophylaxis were compared using in vivo bioluminescence imaging, ex vivo bacterial counts, and biofilm formation. High-dose vancomycin, daptomycin, and tigecycline resulted in similar reductions in bacterial burden and biofilm formation. In contrast, low-dose daptomycin and tigecycline were more effective than low-dose vancomycin against the implant infection. In this mouse model of surgical implant MSSA or MRSA infection, daptomycin and tigecycline prophylaxis were effective over a broader dosage range than vancomycin. Future studies in humans will be required to determine whether these broader effective dose ranges for daptomycin and tigecycline in mice translate to improved efficacy in preventing surgical implant infections in clinical practice.

Daptomycin and tigecycline have broader effective dose ranges than vancomycin as prophylaxis against a Staphylococcus aureus surgical implant infection in mice.

La vancomycine est largement utilis&eacute;e pour la prophylaxie contre les infections de l&#39;implant chirurgical par voie intraveineuse. Toutefois, on ignore si les antibiotiques utilis&eacute;s pour traiter la methicillin-resistant Staphylococcus aureus (MRSA) infections sont efficaces comme agents prophylactiques. Le but de cette &eacute;tude &eacute;tait de comparer l&#39;efficacit&eacute; de la vancomycine, daptomycine et tig&eacute;cycline comme traitement prophylactique contre un Staphylococcus aureus sensible &agrave; la m&eacute;thicilline (MSSA) ou un implant chirurgical de SARM chez la souris. MSSA ou SARM a &eacute;t&eacute; inocul&eacute; dans les articulations de genou de souris en pr&eacute;sence d&#39;un implant m&eacute;tallique plac&eacute; chirurgicalement de qualit&eacute; m&eacute;dicale. L&#39;efficacit&eacute; des bas-par rapport &agrave; forte dose de vancomycine (10 contre 110 mg/kg), daptomycine (1 contre 10 mg/kg) et la prophylaxie par voie intraveineuse tig&eacute;cycline (1 contre 10 mg/kg) ont &eacute;t&eacute; compar&eacute;es &agrave; l&#39;aide de bioluminescence in vivo d&#39;imagerie, ex vivo la num&eacute;ration bact&eacute;rienne et la formation de biofilm. Tig&eacute;cycline daptomycine et vancomycine dose &eacute;lev&eacute;e a entra&icirc;n&eacute; des r&eacute;ductions similaires formation de fardeau et le biofilm bact&eacute;rienne. En revanche, la tig&eacute;cycline et faible dose daptomycine &eacute;taient plus efficaces que la vancomycine faible dose contre l&#39;infection de l&#39;implant. Dans ce mod&egrave;le de souris de l&#39;implant chirurgical la prophylaxie de l&#39;infection, la daptomycine et tig&eacute;cycline MSSA ou SARM ont &eacute;t&eacute; efficaces sur une plage de dosage plus large que la vancomycine. Futures &eacute;tudes chez les humains devront d&eacute;terminer si ces gammes de dose efficace plus larges pour la daptomycine et tig&eacute;cycline chez les souris se traduisent par une efficacit&eacute; am&eacute;lior&eacute;e pour pr&eacute;venir les infections dans la pratique clinique implant chirurgical.

Daptomycine et tig&eacute;cycline ont plus larges gammes de dose efficace que la vancomycine en prophylaxie contre un Staphylococcus aureus chirurgicale d&#39;implant infection chez la souris.

Vancomycin wird f&uuml;r intraven&ouml;sen Prophylaxe gegen Infektionen chirurgische Implantat eingesetzt. Es ist jedoch unklar, ob alternative Antibiotika zur Behandlung von Methicillin-resistenter Staphylococcus Aureus (MRSA) Infektionen effektiv als prophylaktische Bevollm&auml;chtigte sind. Das Ziel dieser Studie war es, die Leistungsnachteile Vancomycin, Daptomycin und Tigecyclin als prophylaktische Therapie gegen eine Methicillin-sensible S. Aureus (MSSA) oder MRSA chirurgische Implantat Infektion bei M&auml;usen zu vergleichen. MSSA oder MRSA wurde in die Kniegelenke von M&auml;usen in Anwesenheit einer chirurgisch platzierte medizinisches metallischen Implantat verimpft. Die Leistungsnachteile der niedrig-im Vergleich zu hoch dosierten Vancomycin (10 gegen&uuml;ber 110 mg/kg), Daptomycin (1 im Vergleich zu 10 mg/kg) und Tigecyclin (1 im Vergleich zu 10 mg/kg) intraven&ouml;sen Prophylaxe wurden verglichen mit in-vivo imaging, ex Vivo Keimzahlen und Biofilm-Bildung Biolumineszenz. Hochdosierte Vancomycin, Daptomycin und Tigecyclin f&uuml;hrte zu &auml;hnlichen Senkung der bakteriellen Belastung und Biofilm-Bildung. Im Gegensatz dazu waren niedrig dosierte Daptomycin und Tigecyclin effektiver als niedrig dosierte Vancomycin gegen die Implantat-Infektion. In diesem Mausmodell der chirurgische Implantat MSSA oder MRSA-Infektion, Daptomycin und Tigecyclin-Prophylaxe waren &uuml;ber eine umfassendere der Dosierung als Vancomycin wirksam. Zuk&uuml;nftige Studien beim Menschen werden ben&ouml;tigt, um festzustellen, ob dieser breiteren effektive Dosis reicht f&uuml;r Daptomycin und Tigecyclin bei M&auml;usen die verbesserte Wirksamkeit bei der Verhinderung chirurgische Implantat-Infektionen in der klinischen Praxis &uuml;bersetzen.

Daptomycin und Tigecyclin haben breitere effektive Dosis reicht als Vancomycin als Prophylaxe gegen einen Staphylococcus-Aureus-chirurgische Implantat Infektion in den M&auml;usen.

Vancomicina &egrave; ampiamente usato per endovena profilassi contro le infezioni dell&#39;impianto chirurgico. Tuttavia, non &egrave; chiaro se sono efficaci come profilattici agenti antibiotici alternativi usati per trattare meticillina-resistenti Staphylococcus aureus (MRSA) infezioni. Lo scopo di questo studio era di confrontare l&#39;efficacia della vancomicina, daptomicina e tigecycline come terapia profilattica contro una meticillino-sensibili di Staphylococcus aureus (MSSA) o infezione da MRSA chirurgica implantare nei topi. MSSA o MRSA &egrave; stato inoculato in ginocchi di topi in presenza di un impianto di metallico medicale chirurgicamente posizionato. L&#39;efficacia di basso-versus vancomicina ad alte dosi (10 contro 110 mg/kg), daptomicina (1 contro 10 mg/kg) e profilassi endovenosa tigecycline (1 contro 10 mg/kg) sono stati confrontati mediante bioluminescenza in vivo imaging, ex vivo conta batterica e la formazione di biofilm. Tigecycline, daptomicina e alte dosi di vancomicina ha provocato riduzioni simili nella formazione degli oneri e biofilm batterica. Al contrario, tigecycline e low-dose daptomicina erano pi&ugrave; efficaci di basse dosi di vancomicina contro l&#39;infezione dell&#39;impianto. In questo modello del mouse dell&#39;impianto chirurgico MSSA o MRSA infezione, la daptomicina e tigecycline profilassi erano efficaci su una gamma pi&ugrave; vasta di dosaggio vancomicina. Futuri studi negli esseri umani sar&agrave; richiesti per determinare se questi intervalli di dose efficace pi&ugrave; ampi per la daptomicina e tigecycline nei topi traducono per una migliore efficacia nella prevenzione delle infezioni nella pratica clinica chirurgica implantare.

Daptomicina e tigecycline sono pi&ugrave; ampie gamme di dose efficace rispetto a vancomicina come profilassi contro un Staphylococcus aureus chirurgica implantare infezione nei topi.

&#x30D0;&#x30F3;&#x30B3;&#x30DE;&#x30A4;&#x30B7;&#x30F3;&#x306F;&#x5E83;&#x304F;&#x5916;&#x79D1;&#x30A4;&#x30F3;&#x30D7;&#x30E9;&#x30F3;&#x30C8;&#x611F;&#x67D3;&#x75C7;&#x306B;&#x5BFE;&#x3059;&#x308B;&#x9759;&#x8108;&#x5185;&#x6295;&#x4E0E;&#x306E;&#x4E88;&#x9632;&#x306E;&#x305F;&#x3081;&#x306B;&#x4F7F;&#x7528;&#x3055;&#x308C;&#x307E;&#x3059;&#x3002;&#x3057;&#x304B;&#x3057;&#x3001;&#x305D;&#x308C;&#x30E1;&#x30C1;&#x30B7;&#x30EA;&#x30F3;&#x8010;&#x6027;&#x9EC4;&#x8272;&#x30D6;&#x30C9;&#x30A6;&#x7403;&#x83CC; (MRSA) &#x611F;&#x67D3;&#x3092;&#x6CBB;&#x7642;&#x3059;&#x308B;&#x305F;&#x3081;&#x306B;&#x4F7F;&#x7528;&#x3055;&#x308C;&#x308B;&#x4EE3;&#x66FF;&#x306E;&#x6297;&#x751F;&#x7269;&#x8CEA;&#x304C;&#x611F;&#x67D3;&#x4E88;&#x9632;&#x85AC;&#x3068;&#x3057;&#x3066;&#x6709;&#x52B9;&#x3067;&#x3042;&#x308B;&#x304B;&#x3069;&#x3046;&#x304B;&#x660E;&#x78BA;&#x3067;&#x306F;&#x306A;&#x3044;&#x3067;&#x3059;&#x3002;&#x30E1;&#x30C1;&#x30B7;&#x30EA;&#x30F3;&#x611F;&#x53D7;&#x6027;&#x9EC4;&#x8272;&#x30D6;&#x30C9;&#x30A6;&#x7403;&#x83CC; &#xFF08;&#x9EC4;&#x8272;&#x30D6;&#x30C9;&#x30A6;&#x7403;&#x83CC;&#xFF09; &#x3084; MRSA &#x5916;&#x79D1;&#x30A4;&#x30F3;&#x30D7;&#x30E9;&#x30F3;&#x30C8;&#x611F;&#x67D3;&#x30DE;&#x30A6;&#x30B9;&#x306B;&#x5BFE;&#x3059;&#x308B;&#x4E88;&#x9632;&#x7684;&#x6CBB;&#x7642;&#x3068;&#x3057;&#x3066;&#x30C0;&#x30D7;&#x30C8;&#x30DE;&#x30A4;&#x30B7;&#x30F3;&#x3001;&#x30D0;&#x30F3;&#x30B3;&#x30DE;&#x30A4;&#x30B7;&#x30F3;&#x3068;&#x30C1;&#x30B2;&#x30B5;&#x30A4;&#x30AF;&#x30EA;&#x30F3;&#x306E;&#x52B9;&#x80FD;&#x3092;&#x6BD4;&#x8F03;&#x3057;&#x305F;.&#x9EC4;&#x8272;&#x30D6;&#x30C9;&#x30A6;&#x7403;&#x83CC;&#x3084; MRSA &#x306F;&#x5916;&#x79D1;&#x7684;&#x306B;&#x7F6E;&#x304B;&#x308C;&#x305F;&#x533B;&#x7642;&#x30B0;&#x30EC;&#x30FC;&#x30C9;&#x306E;&#x91D1;&#x5C5E;&#x30A4;&#x30F3;&#x30D7;&#x30E9;&#x30F3;&#x30C8;&#x306E;&#x5B58;&#x5728;&#x4E0B;&#x3067;&#x306E;&#x30DE;&#x30A6;&#x30B9;&#x306E;&#x819D;&#x95A2;&#x7BC0;&#x306B;&#x63A5;&#x7A2E;&#x3057;&#x307E;&#x3057;&#x305F;&#x3002;&#x4F4E; - vs &#x9AD8;&#x7528;&#x91CF;&#x30D0;&#x30F3;&#x30B3;&#x30DE;&#x30A4;&#x30B7;&#x30F3; &#xFF08;110 mg/kg &#x5BFE; 10&#xFF09;&#x3001;&#x30C0;&#x30D7;&#x30C8;&#x30DE;&#x30A4;&#x30B7;&#x30F3; (1) 10 mg/kg &#x5BFE;&#x30C1;&#x30B2;&#x30B5;&#x30A4;&#x30AF;&#x30EA;&#x30F3; (10 mg/kg &#x5BFE; 1) &#x9759;&#x8108;&#x5185;&#x6295;&#x4E0E;&#x306E;&#x4E88;&#x9632;&#x306E;&#x52B9;&#x80FD;&#x306F; in vivo &#x306E;&#x751F;&#x7269;&#x767A;&#x5149;&#x30A4;&#x30E1;&#x30FC;&#x30B8;&#x30F3;&#x30B0;&#x3001;&#x751F;&#x4F53;&#x5185;&#x306E;&#x7D30;&#x83CC;&#x6570;&#x3068;&#x30D0;&#x30A4;&#x30AA; &#x30D5;&#x30A3;&#x30EB;&#x30E0;&#x5F62;&#x6210; ex &#x3092;&#x4F7F;&#x7528;&#x3057;&#x3066;&#x6BD4;&#x8F03;&#x3057;&#x307E;&#x3057;&#x305F;&#x3002;&#x9AD8;&#x7528;&#x91CF;&#x30D0;&#x30F3;&#x30B3;&#x30DE;&#x30A4;&#x30B7;&#x30F3;&#x3001;&#x30C0;&#x30D7;&#x30C8;&#x30DE;&#x30A4;&#x30B7;&#x30F3;&#x3068;&#x30C1;&#x30B2;&#x30B5;&#x30A4;&#x30AF;&#x30EA;&#x30F3;&#x7D30;&#x83CC;&#x8CA0;&#x62C5;&#x3068;&#x30D0;&#x30A4;&#x30AA; &#x30D5;&#x30A3;&#x30EB;&#x30E0;&#x5F62;&#x6210;&#x3068;&#x540C;&#x69D8;&#x524A;&#x6E1B;&#x306E;&#x7D50;&#x679C;&#x3002;&#x5BFE;&#x7167;&#x7684;&#x306B;&#x3001;&#x4F4E;&#x7DDA;&#x91CF;&#x30C0;&#x30D7;&#x30C8;&#x30DE;&#x30A4;&#x30B7;&#x30F3;&#x3068;&#x30C1;&#x30B2;&#x30B5;&#x30A4;&#x30AF;&#x30EA;&#x30F3; &#x30A4;&#x30F3;&#x30D7;&#x30E9;&#x30F3;&#x30C8;&#x611F;&#x67D3;&#x75C7;&#x306B;&#x5BFE;&#x3059;&#x308B;&#x4F4E;&#x7528;&#x91CF;&#x30D0;&#x30F3;&#x30B3;&#x30DE;&#x30A4;&#x30B7;&#x30F3;&#x3088;&#x308A;&#x52B9;&#x679C;&#x7684;&#x3060;&#x3063;&#x305F;&#x3002;&#x3053;&#x306E;&#x5916;&#x79D1;&#x30A4;&#x30F3;&#x30D7;&#x30E9;&#x30F3;&#x30C8;&#x306E;&#x30DE;&#x30A6;&#x30B9; &#x30E2;&#x30C7;&#x30EB;&#x3067;&#x9EC4;&#x8272;&#x30D6;&#x30C9;&#x30A6;&#x7403;&#x83CC;&#x3084; MRSA &#x611F;&#x67D3;&#x3001;&#x30C0;&#x30D7;&#x30C8;&#x30DE;&#x30A4;&#x30B7;&#x30F3;&#x3068;&#x30C1;&#x30B2;&#x30B5;&#x30A4;&#x30AF;&#x30EA;&#x30F3;&#x4E88;&#x9632;&#x6709;&#x52B9;&#x8D85;&#x3048;&#x3066;&#x3044;&#x305F;&#x3088;&#x308A;&#x30D0;&#x30F3;&#x30B3;&#x30DE;&#x30A4;&#x30B7;&#x30F3;&#x7528;&#x91CF;&#x5E83;&#x7BC4;&#x3002;&#x30D2;&#x30C8;&#x306B;&#x304A;&#x3051;&#x308B;&#x4ECA;&#x5F8C;&#x306E;&#x7814;&#x7A76;&#x306F;&#x3001;&#x3053;&#x308C;&#x3089;&#x306E;&#x3088;&#x308A;&#x5E83;&#x7BC4;&#x306A;&#x5B9F;&#x52B9;&#x7DDA;&#x91CF;&#x306E;&#x7BC4;&#x56F2;&#x30C0;&#x30D7;&#x30C8;&#x30DE;&#x30A4;&#x30B7;&#x30F3;&#x3068;&#x30C1;&#x30B2;&#x30B5;&#x30A4;&#x30AF;&#x30EA;&#x30F3; &#x30DE;&#x30A6;&#x30B9;&#x306B;&#x304A;&#x3051;&#x308B;&#x81E8;&#x5E8A;&#x5916;&#x79D1;&#x30A4;&#x30F3;&#x30D7;&#x30E9;&#x30F3;&#x30C8;&#x611F;&#x67D3;&#x4E88;&#x9632;&#x6539;&#x5584;&#x52B9;&#x679C;&#x3092;&#x7FFB;&#x8A33;&#x304B;&#x3069;&#x3046;&#x304B;&#x3092;&#x6C7A;&#x5B9A;&#x3059;&#x308B;&#x5FC5;&#x8981;&#x304C;&#x3042;&#x308A;&#x307E;&#x3059;&#x3002;

&#x30C0;&#x30D7;&#x30C8;&#x30DE;&#x30A4;&#x30B7;&#x30F3;&#x3068;&#x30C1;&#x30B2;&#x30B5;&#x30A4;&#x30AF;&#x30EA;&#x30F3; &#x30A4;&#x30F3;&#x30D7;&#x30E9;&#x30F3;&#x30C8;&#x611F;&#x67D3;&#x30DE;&#x30A6;&#x30B9;&#x3088;&#x308A;&#x5E83;&#x7BC4;&#x306A;&#x5B9F;&#x52B9;&#x7DDA;&#x91CF;&#x7BC4;&#x56F2;&#x3088;&#x308A;&#x30D0;&#x30F3;&#x30B3;&#x30DE;&#x30A4;&#x30B7;&#x30F3;&#x624B;&#x8853;&#x9EC4;&#x8272;&#x30D6;&#x30C9;&#x30A6;&#x7403;&#x83CC;&#x306B;&#x5BFE;&#x3059;&#x308B;&#x4E88;&#x9632;&#x3068;&#x3057;&#x3066;&#x3082;&#x3042;&#x308A;&#x307E;&#x3059;&#x3002;

Vancomycin&#xC740; &#xC218;&#xC220; &#xC784; &#xD50C; &#xB780; &#xD2B8; &#xAC10;&#xC5FC;&#xC5D0; &#xB300; &#xD55C; &#xC815; &#xB9E5; &#xC8FC;&#xC0AC; &#xC608;&#xBC29; &#xCE58;&#xB8CC;&#xC5D0; &#xB110;&#xB9AC; &#xC0AC;&#xC6A9; &#xB429;&#xB2C8;&#xB2E4;. &#xADF8;&#xB7EC;&#xB098;, &#xC544;&#xB2C8;&#xB2E4; &#xBA85;&#xD655; &#xC5EC;&#xBD80; &#xBA54; &#xD2F0; &#xC2E4;&#xB9B0; &#xB0B4;&#xC131; &#xD669;&#xC0C9; &#xD3EC;&#xB3C4; &#xC0C1; &#xAD6C; &#xADE0; (MRSA) &#xAC10;&#xC5FC;&#xC744; &#xCE58;&#xB8CC; &#xD558;&#xB294; &#xB370; &#xC0AC;&#xC6A9; &#xD558;&#xB294; &#xB300;&#xCCB4; &#xD56D;&#xC0DD;&#xC81C; &#xC608;&#xBC29; &#xC694;&#xC6D0;&#xC73C;&#xB85C; &#xD6A8;&#xACFC;&#xC801;&#xC785;&#xB2C8;&#xB2E4;. &#xC774; &#xC5F0;&#xAD6C;&#xC758; &#xBAA9;&#xD45C;&#xB294; &#xBA54; &#xD2F0; &#xC2E4;&#xB9B0;&#xC5D0; &#xBBFC;&#xAC10;&#xD55C; S. &#xAD6C; &#xADE0; (MSSA) &#xB610;&#xB294; MRSA &#xC218;&#xC220; &#xC784; &#xD50C; &#xB780; &#xD2B8; &#xC950;&#xC5D0; &#xAC10;&#xC5FC;&#xC5D0; &#xB300; &#xD55C; &#xC608;&#xBC29; &#xD55C; &#xCE58;&#xB8CC;&#xB85C; vancomycin, daptomycin, &#xBC0F; tigecycline &#xC2E0;&#xC9C4;&#xB300;&#xC0AC;&#xB97C; &#xBE44;&#xAD50; &#xD588;&#xB2E4;. MSSA &#xB610;&#xB294; MRSA &#xC218;&#xC220;&#xB85C; &#xBC30;&#xCE58; &#xC758;&#xB8CC; &#xC218;&#xC900;&#xC758; &#xAE08;&#xC18D; &#xC784; &#xD50C; &#xB780; &#xD2B8;&#xC758; &#xC874;&#xC7AC;&#xB294; &#xC950;&#xC758; &#xBB34;&#xB98E; &#xAD00;&#xC808;&#xC5D0; &#xC8FC;&#xC0AC; &#xD588;&#xB2E4;. &#xB0AE;&#xC740;-&#xB192;&#xC740; &#xBCF5;&#xC6A9;&#xB7C9; vancomycin (110 mg/kg &#xB300; 10), daptomycin (10 mg/kg &#xB300; 1), &#xBC0F; tigecycline (10mg/kg &#xB300; 1) &#xC815; &#xB9E5; &#xC8FC;&#xC0AC; &#xC608;&#xBC29; &#xC2E0;&#xC9C4;&#xB300;&#xC0AC; &#xC804; &#xBE44;&#xBCF4; &#xC138;&#xADE0; &#xC218;&#xC640; biofilm &#xD615;&#xC131; &#xC774;&#xBBF8;&#xC9D5; in vivo &#xC0DD;&#xBB3C; &#xBC1C;&#xAD11;&#xC744; &#xC0AC;&#xC6A9; &#xD558; &#xC5EC; &#xBE44;&#xAD50; &#xD588;&#xB2E4;. &#xB192;&#xC740; &#xBCF5;&#xC6A9;&#xB7C9; vancomycin, daptomycin, &#xBC0F; tigecycline &#xC138;&#xADE0;&#xC131; &#xBD80;&#xB2F4;&#xACFC; biofilm &#xD615;&#xC131;&#xC5D0; &#xBE44;&#xC2B7;&#xD55C; &#xAC10;&#xC18C; &#xADC0;&#xCC29;&#xB418; &#xC5C8; &#xB2E4;. &#xB300;&#xC870;&#xC801;&#xC73C;&#xB85C;, &#xB0AE;&#xC740; &#xBCF5;&#xC6A9;&#xB7C9; daptomycin&#xC640; tigecycline &#xC774;&#xC2DD; &#xAC10;&#xC5FC;&#xC5D0; &#xB300; &#xD55C; &#xB0AE;&#xC740; &#xBCF5;&#xC6A9;&#xB7C9; vancomycin &#xBCF4;&#xB2E4; &#xB354; &#xD6A8;&#xACFC;&#xC801; &#xC774;&#xC5C8;&#xB2E4;. &#xC774; &#xB9C8;&#xC6B0;&#xC2A4; &#xBAA8;&#xB378; &#xC218;&#xC220; &#xC784; &#xD50C; &#xB780; &#xD2B8;&#xC758; MSSA &#xB610;&#xB294; MRSA &#xAC10;&#xC5FC;, daptomycin &#xBC0F; tigecycline &#xC608;&#xBC29; vancomycin &#xBCF4;&#xB2E4; &#xAD11;&#xBC94;&#xC704; &#xD55C; &#xBCF5;&#xC6A9;&#xB7C9; &#xBC94;&#xC704; &#xD6A8;&#xACFC;&#xC801;&#xC778; &#xD588;&#xB2E4;. &#xC778;&#xAC04;&#xC758; &#xBBF8;&#xB798; &#xC5F0;&#xAD6C; daptomycin &#xBC0F; tigecycline &#xC950;&#xC5D0; &#xB300; &#xD55C; &#xC774;&#xB7EC;&#xD55C; &#xAD11;&#xBC94;&#xC704; &#xD55C; &#xD6A8;&#xACFC;&#xC801;&#xC778; &#xBCF5;&#xC6A9;&#xB7C9; &#xBC94;&#xC704; &#xC784;&#xC0C1; &#xC5F0;&#xC2B5;&#xC5D0; &#xC788;&#xB294; &#xC218;&#xC220; &#xC784; &#xD50C; &#xB780; &#xD2B8; &#xAC10;&#xC5FC;&#xC744; &#xC608;&#xBC29; &#xAC1C;&#xC120;&#xB41C; &#xD6A8;&#xB2A5;&#xC744; &#xBC88;&#xC5ED; &#xC5EC;&#xBD80;&#xB97C; &#xACB0;&#xC815; &#xD558;&#xB294; &#xB370; &#xD544;&#xC694;&#xD55C; &#xAC83;&#xC785;&#xB2C8;&#xB2E4;.

Daptomycin &#xBC0F; tigecycline &#xC0DD;&#xC950;&#xC5D0; &#xAC10;&#xC5FC; &#xC784; &#xD50C; &#xB780; &#xD2B8; &#xC218;&#xC220; &#xD3EC;&#xB3C4; &#xC0C1; &#xAD6C; &#xADE0;&#xC5D0; &#xB300; &#xD55C; &#xC608;&#xBC29;&#xC73C;&#xB85C; vancomycin &#xBCF4;&#xB2E4; &#xAD11;&#xBC94;&#xC704; &#xD55C; &#xD6A8;&#xACFC;&#xC801;&#xC778; &#xBCF5;&#xC6A9;&#xB7C9; &#xBC94;&#xC704;&#xB294;.

La vancomicina es ampliamente utilizada para la profilaxis intravenosa contra infecciones de implante quir&uacute;rgico. Sin embargo, no est&aacute; claro si son eficaces como agentes profil&aacute;cticos alternativos antibi&oacute;ticos para infecciones resistentes a la meticilina Staphylococcus aureus (MRSA). El objetivo de este estudio fue comparar la eficacia de la vancomicina y daptomicina tigeciclina como terapia profil&aacute;ctica contra un sensible a la meticilina S. aureus (MSSA) o infecci&oacute;n del implante quir&uacute;rgico de MRSA en ratones. MSSA o MRSA se inocul&oacute; en las articulaciones de la rodilla de ratones en presencia de un implante met&aacute;lico colocado quir&uacute;rgicamente de grado m&eacute;dico. Las eficacias de baja-frente a altas dosis de vancomicina (10 frente a 110 mg/kg), daptomicina (1 contra 10 mg/kg) y la profilaxis intravenosa tigeciclina (1 contra 10 mg/kg) se compararon mediante bioluminiscencia in vivo imaging, ex vivo conteos bacterianos y formaci&oacute;n de biopel&iacute;culas. Tigeciclina, altas dosis de vancomicina y daptomicina dio lugar a reducciones similares en la formaci&oacute;n de carga y biofilm bacteriana. Por el contrario, tigeciclina y dosis bajas daptomicina fueron m&aacute;s eficaces que dosis bajas vancomicina contra la infecci&oacute;n del implante. En este modelo de rat&oacute;n de implante quir&uacute;rgico la profilaxis de la infecci&oacute;n, daptomicina y tigeciclina MSSA o MRSA fueron efectivos sobre una gama m&aacute;s amplia de la dosis de vancomicina. Los estudios futuros en los seres humanos ser&aacute; necesarios para determinar si estos rangos de dosis efectiva m&aacute;s amplios para la daptomicina y tigeciclina en ratones se traducen en mayor eficacia en la prevenci&oacute;n de infecciones de implante quir&uacute;rgico en la pr&aacute;ctica cl&iacute;nica.

Daptomicina y tigeciclina tienen rangos de dosis efectiva m&aacute;s amplias que vancomicina como profilaxis contra un estafilococo &aacute;ureo quir&uacute;rgica implante infecci&oacute;n en ratones.

J&uuml;ngste Fortschritte in der nicht-invasiven optisch, radiologischen und &Mu;ct Imaging bieten Gelegenheit, biologische Prozesse in L&auml;ngsrichtung in einem anatomischen Kontext zu &uuml;berwachen. Eine besonders relevante Anwendung f&uuml;r die Kombination dieser Modalit&auml;ten ist orthop&auml;dische Implantate Infektionen zu studieren. Diese Infektionen zeichnen sich durch die Bildung von persistente bakterielle Biofilme auf den implantierten Materialien, verursacht Entz&uuml;ndungen, Periprosthetic Osteolyse, Osteomyelitis, und Sch&auml;den im Implantat Lockerung und Ausfall die Knochendichte.

&Uuml;berwachung bakterielle Belastung, Schaden Entz&uuml;ndung und Knochen in L&auml;ngsrichtung mit optischen und &Mu;ct-Imaging in einer orthop&auml;dischen Implantat Infektion bei M&auml;usen.

I recenti progressi nella non-invasiva ottici, radiografici e &mu;CT imaging offrono la possibilit&agrave; di monitorare i processi biologici longitudinalmente in un contesto anatomico. Una applicazione particolarmente rilevante per la combinazione di queste modalit&agrave; &egrave; quello di studiare le infezioni di protesi ortopediche. Queste infezioni sono caratterizzate dalla formazione di biofilm batterici persistente sui materiali impiantati, provocando infiammazione, osteolisi PERIPROTESICHE, osteomielite e danni, con conseguente allentamento dell&#39;impianto e il fallimento dell&#39;osso.

Controllo carica batterica, infiammazione e danno osseo longitudinalmente utilizzando ottiche e &mu;CT Imaging in un ortopedico dell&#39;impianto infezione nei topi.

&#x6700;&#x65B0;&#x8FDB;&#x5C55;&#x975E;&#x4FB5;&#x5165;&#x5F0F;&#x5149;&#x5B66;&#x3001; &#x7167;&#x76F8;&#x548C; &mu;CT &#x6210;&#x50CF;&#x63D0;&#x4F9B;&#x673A;&#x4F1A;&#x76D1;&#x6D4B;&#x7EB5;&#x5411;&#x5728;&#x89E3;&#x5256;&#x5B66;&#x65B9;&#x9762;&#x7684;&#x751F;&#x7269;&#x8FC7;&#x7A0B;&#x3002;&#x7279;&#x522B;&#x662F;&#x6709;&#x5173;&#x7533;&#x8BF7;&#xFF0C;&#x7ED3;&#x5408;&#x8FD9;&#x4E9B;&#x65B9;&#x5F0F;&#x662F;&#x7814;&#x7A76;&#x9AA8;&#x79D1;&#x690D;&#x5165;&#x7269;&#x611F;&#x67D3;&#x3002;&#x8FD9;&#x4E9B;&#x611F;&#x67D3;&#x7684;&#x7279;&#x70B9;&#x662F;&#x5BF9;&#x690D;&#x5165;&#x6750;&#x6599;&#xFF0C;&#x9020;&#x6210;&#x708E;&#x75C7;&#x3001; &#x5047;&#x4F53;&#x5468;&#x56F4;&#x9AA8;&#x6EB6;&#x89E3;&#x3001; &#x9AA8;&#x9AD3;&#x708E;&#x3001; &#x6301;&#x4E45;&#x6027;&#x7EC6;&#x83CC;&#x751F;&#x7269;&#x819C;&#x7684;&#x5F62;&#x6210;&#x548C;&#x9AA8;&#x79CD;&#x690D;&#x4F53;&#x677E;&#x52A8;&#x548C;&#x6545;&#x969C;&#x6240;&#x9020;&#x6210;&#x7684;&#x635F;&#x5BB3;&#x3002;

&#x76D1;&#x6D4B;&#x7EC6;&#x83CC;&#x7684;&#x8D1F;&#x62C5;&#x3001; &#x708E;&#x75C7;&#x548C;&#x9AA8;&#x7834;&#x574F;&#x7EB5;&#x5411;&#x4F7F;&#x7528;&#x5149;&#x5B66;&#x548C; &mu;CT &#x6210;&#x50CF;&#x5728;&#x9AA8;&#x79D1;&#x690D;&#x5165;&#x7269;&#x611F;&#x67D3;&#x5C0F;&#x9F20;&#x3002;

Recent advances in non-invasive optical, radiographic and Î¼CT imaging provide an opportunity to monitor biological processes longitudinally in an anatomical context. One particularly relevant application for combining these modalities is to study orthopaedic implant infections. These infections are characterized by the formation of persistent bacterial biofilms on the implanted materials, causing inflammation, periprosthetic osteolysis, osteomyelitis, and bone damage, resulting in implant loosening and failure.

Monitoring Bacterial Burden, Inflammation and Bone Damage Longitudinally Using Optical and Î¼CT Imaging in an Orthopaedic Implant Infection in Mice.

Recent advances in non invasif optiques, radiographiques et imagerie &mu;CT permettent de surveiller des processus biologiques longitudinalement dans un contexte anatomique. Une application particuli&egrave;rement pertinente pour la combinaison de ces modalit&eacute;s est d&#39;&eacute;tudier les infections implant orthop&eacute;dique. Ces infections sont caract&eacute;ris&eacute;es par la formation des biofilms bact&eacute;riens persistants sur les mat&eacute;riaux implant&eacute;s, provoquant une inflammation, ost&eacute;olyse p&eacute;riprosth&eacute;tique, ost&eacute;omy&eacute;lite et dommage, r&eacute;sultant en desserrant implant et l&#39;&eacute;chec d&#39;os.

Surveillance de la charge bact&eacute;rienne, l&#39;Inflammation et l&#39;OS endommagent longitudinalement l&#39;aide optique et imagerie &mu;CT dans une Infection de l&#39;Implant orthop&eacute;dique chez la souris.

&#x5149;&#x5B66;&#x3001;x &#x7DDA;&#x64AE;&#x5F71;&#x306E;&#x6700;&#x8FD1;&#x306E;&#x975E;&#x4FB5;&#x8972;&#x7684;&#x9032;&#x6B69;&#x3068; &mu; CT &#x30A4;&#x30E1;&#x30FC;&#x30B8;&#x30F3;&#x30B0;, &#x7E26;&#x65AD;&#x7684;&#x306B;&#x89E3;&#x5256;&#x5B66;&#x7684;&#x6587;&#x8108;&#x306E;&#x751F;&#x7269;&#x5B66;&#x7684;&#x30D7;&#x30ED;&#x30BB;&#x30B9;&#x3092;&#x76E3;&#x8996;&#x3059;&#x308B;&#x6A5F;&#x4F1A;&#x3092;&#x63D0;&#x4F9B;&#x3057;&#x307E;&#x3059;&#x3002;&#x3053;&#x308C;&#x3089;&#x306E;&#x30E2;&#x30C0;&#x30EA;&#x30C6;&#x30A3;&#x3092;&#x7D44;&#x307F;&#x5408;&#x308F;&#x305B;&#x308B;&#x305F;&#x3081;&#x306B; 1 &#x3064;&#x306E;&#x7279;&#x306B;&#x95A2;&#x9023;&#x30A2;&#x30D7;&#x30EA;&#x30B1;&#x30FC;&#x30B7;&#x30E7;&#x30F3;&#x306F;&#x3001;&#x6574;&#x5F62;&#x5916;&#x79D1;&#x30A4;&#x30F3;&#x30D7;&#x30E9;&#x30F3;&#x30C8;&#x611F;&#x67D3;&#x3092;&#x52C9;&#x5F37;&#x3059;&#x308B;&#x3053;&#x3068;&#x3067;&#x3059;&#x3002;&#x3053;&#x308C;&#x3089;&#x306E;&#x611F;&#x67D3;&#x75C7;&#x708E;&#x75C7;, &#x30D7;&#x30ED;&#x30B9;&#x30C6;&#x30FC;&#x30B7;&#x30B9;&#x878D;&#x89E3;, &#x9AA8;&#x9AC4;&#x708E;&#x3092;&#x5F15;&#x304D;&#x8D77;&#x3053;&#x3057;&#x3066;&#x6CE8;&#x5165;&#x6750;&#x6599;&#x306B;&#x95A2;&#x3059;&#x308B;&#x6C38;&#x7D9A;&#x7684;&#x306A;&#x7D30;&#x83CC;&#x30D0;&#x30A4;&#x30AA; &#x30D5;&#x30A3;&#x30EB;&#x30E0;&#x306E;&#x5F62;&#x6210;&#x306B;&#x3088;&#x3063;&#x3066;&#x7279;&#x5FB4;&#x4ED8;&#x3051;&#x3089;&#x308C;&#x308B;&#x3057;&#x3001;&#x9AA8;&#x306E;&#x640D;&#x50B7;&#x3001;&#x30A4;&#x30F3;&#x30D7;&#x30E9;&#x30F3;&#x30C8;&#x3092;&#x7DE9;&#x3081;&#x308B;&#x3068;&#x5931;&#x6557;&#x306E;&#x7D50;&#x679C;&#x3057;&#x307E;&#x3059;&#x3002;

&#x76E3;&#x8996;&#x7D30;&#x83CC;&#x8CA0;&#x62C5;&#x3001;&#x708E;&#x75C7;&#x3001;&#x9577;&#x624B;&#x65B9;&#x5411;&#x5149;&#x5B66;&#x3092;&#x7528;&#x3044;&#x305F;&#x9AA8;&#x306E;&#x640D;&#x50B7;&#x304A;&#x3088;&#x3073; &mu; CT &#x30A4;&#x30E1;&#x30FC;&#x30B8;&#x30F3;&#x30B0;&#x3001;&#x6574;&#x5F62;&#x5916;&#x79D1;&#x9818;&#x57DF;&#x306B;&#x304A;&#x3051;&#x308B;&#x30A4;&#x30F3;&#x30D7;&#x30E9;&#x30F3;&#x30C8;&#x611F;&#x67D3;&#x30DE;&#x30A6;&#x30B9;&#x3002;

&#xAD11;&#xD559;, &#xBC29;&#xC0AC;&#xC120; &#xBE44; &#xCE68;&#xB7B5; &#xC801;&#xC758; &#xCD5C;&#xADFC; &#xBC1C;&#xC804; &#xBC0F; &mu;CT &#xC774;&#xBBF8;&#xC9D5; &#xD574;&#xBD80;&#xD559; &#xCEE8;&#xD14D;&#xC2A4;&#xD2B8;&#xC5D0;&#xC11C; longitudinally &#xC0DD;&#xBB3C; &#xD559;&#xC801; &#xD504;&#xB85C;&#xC138;&#xC2A4;&#xB97C; &#xBAA8;&#xB2C8;&#xD130;&#xB9C1; &#xD558;&#xB294; &#xAE30;&#xD68C;&#xB97C; &#xC81C;&#xACF5; &#xD569;&#xB2C8;&#xB2E4;. &#xC774;&#xB7EC;&#xD55C; &#xD615;&#xC2DD;&#xC740; &#xACB0;&#xD569; &#xD55C; &#xD2B9;&#xD788; &#xAD00;&#xB828; &#xC751;&#xC6A9; &#xD504;&#xB85C;&#xADF8;&#xB7A8; &#xC815;&#xD615; &#xC678;&#xACFC; &#xC784; &#xD50C; &#xB780; &#xD2B8; &#xAC10;&#xC5FC;&#xC744; &#xC5F0;&#xAD6C; &#xD558;&#xB294;. &#xC774;&#xB7EC;&#xD55C; &#xAC10;&#xC5FC; &#xC77C;&#xC73C;&#xD0A4;&#xB294; &#xC5FC;&#xC99D;, periprosthetic osteolysis, osteomyelitis, &#xC774;&#xC2DD;&#xB41C; &#xC7AC;&#xB8CC;&#xC5D0; &#xC601;&#xAD6C;&#xC801;&#xC778; &#xC138;&#xADE0;&#xC131; biofilms&#xC758; &#xD615;&#xC131;&#xC5D0; &#xC758;&#xD574; &#xD2B9;&#xC9D5; &#xBC0F; &#xBF08; &#xC190;&#xC0C1;, &#xC784; &#xD50C; &#xB780; &#xD2B8; &#xC644;&#xD654; &#xBC0F; &#xC2E4;&#xD328;&#xC758; &#xACB0;&#xACFC;.

&#xC138;&#xADE0;&#xC131; &#xBD80;&#xB2F4; &#xBAA8;&#xB2C8;&#xD130;&#xB9C1;, &#xC5FC;&#xC99D;&#xACFC; &#xBF08; &#xC190;&#xC0C1; Longitudinally &#xAD11;&#xD559;&#xB97C; &#xC0AC;&#xC6A9; &#xD558; &#xACE0; &mu;CT &#xC774;&#xBBF8;&#xC9D5;&#xC5D0; &#xC950;&#xC5D0; &#xC788;&#xB294; &#xC815;&#xD615; &#xC678;&#xACFC; &#xC784; &#xD50C; &#xB780; &#xD2B8; &#xAC10;&#xC5FC;.

Avances recientes en invasiva &oacute;pticos, radiogr&aacute;ficos y proyecci&oacute;n de imagen de &mu;CT proporcionan una oportunidad para supervisar procesos biol&oacute;gicos longitudinalmente en un contexto anat&oacute;mico. Una aplicaci&oacute;n particularmente relevante para combinar estas modalidades es el estudio de infecciones de implantes ortop&eacute;dicos. Estas infecciones se caracterizan por la formaci&oacute;n de biofilms bacterianos persistentes en los materiales implantados, causando inflamaci&oacute;n, osteolisis periprot&eacute;sica, osteomielitis y da&ntilde;os, en falta y aflojamiento del implante del hueso.

Monitoreo de carga bacteriana, inflamaci&oacute;n y hueso da&ntilde;an longitudinalmente con &oacute;ptica y proyecci&oacute;n de imagen de &mu;CT en una infecci&oacute;n del implante ortop&eacute;dico en ratones.

Treatment of prosthetic joint infections often involves a 2-stage exchange with implant removal and antibiotic spacer placement followed by systemic antibiotic therapy and delayed reimplantation. However, if antibiotic therapy can be improved, 1-stage exchange or implant retention may be more feasible, thereby decreasing morbidity and preserving function. In this study, a mouse model of prosthetic joint infection was used in which Staphylococcus aureus was inoculated into a knee joint containing a surgically placed metallic implant extending from the femur. This model was used to evaluate whether combination therapy of vancomycin plus rifampin has increased efficacy compared with vancomycin alone against these infections. On postoperative day 7, vancomycin Â± rifampin was administered for 6 weeks with implant retention. In vivo bioluminescence imaging, ex vivo CFUs, X-ray imaging and histologic analysis were evaluated. We found that there was a marked therapeutic benefit when vancomycin was combined with rifampin compared with vancomycin alone. Taken together, our results suggest that the mouse model used could serve as a valuable in vivo preclinical model system to evaluate and compare efficacies of antibiotics and combinatory therapy for prosthetic joint infections before more extensive studies are carried out in human subjects.

Vancomycin plus Rifampin Combination Therapy has Enhanced Efficacy Against an Experimental Staphylococcus aureus Prosthetic Joint Infection.

Periprosthetic joint infections are devastating complications for patients and for our health system. With growing demand for arthroplasty, the incidence of these infections is projected to increase exponentially. This paper is a review of existing animal models to study periprosthetic infection aimed at providing scientists with a succinct presentation of strengths and weaknesses of available in vivo systems. These systems represent the tools available to investigate novel antimicrobial therapies and reduce the clinical and economic impact of implant infections.

Understanding infection: a primer on animal models of periprosthetic joint infection.

The incidence of infections related to cardiac devices (such as permanent pacemakers) has been increasing out of proportion to implantation rates. As management of device infections typically requires explantation of the device, optimal prophylactic strategies are needed. Cefazolin and vancomycin are widely used as single agents for surgical prophylaxis against cardiac device-related infections. However, combination antibiotic prophylaxis may further reduce infectious complications. To model a localized subcutaneous implant-related infection, a bioluminescent strain of Staphylococcus epidermidis was inoculated onto a medical-procedure-grade titanium disc, which was placed into a subcutaneous pocket in the backs of mice. In vivo bioluminescence imaging, quantification of ex vivo CFU from the capsules and implants, variable-pressure scanning electron microscopy (VP-SEM), and neutrophil enhanced green fluorescent protein (EGFP) fluorescence in LysEGFP mice were employed to monitor the infection. This model was used to evaluate the efficacies of low- and high-dose cefazolin (50 and 200 mg/kg of body weight) and vancomycin (10 and 110 mg/kg) intravenous prophylaxis with or without rifampin (25 mg/kg). High-dose cefazolin and high-dose vancomycin treatment resulted in almost complete bacterial clearance, whereas both low-dose cefazolin and low-dose vancomycin reduced the in vivo and ex vivo bacterial burden only moderately. The addition of rifampin to low-dose cefazolin and vancomycin was highly effective in further reducing the CFU harvested from the implants. However, vancomycin-rifampin was more effective than cefazolin-rifampin in further reducing the CFU harvested from the surrounding tissue capsules. Future studies in humans will be required to determine whether the addition of rifampin has improved efficacy in preventing device-related infections in clinical practice.

Combination prophylactic therapy with rifampin increases efficacy against an experimental Staphylococcus epidermidis subcutaneous implant-related infection.

Article	Year
The phosphorylation of EphB2 receptor regulates migration and invasion of human glioma cells. Cancer research\| PubMed ID: 15126357	2004
Ontogenetic effects on aerobic and anaerobic metabolism during jumping in the American locust, Schistocerca americana. The Journal of experimental biology\| PubMed ID: 16043604	2005
EphB2/R-Ras signaling regulates glioma cell adhesion, growth, and invasion. The American journal of pathology\| PubMed ID: 16049340	2005
Ephrin-B3 ligand promotes glioma invasion through activation of Rac1. Cancer research\| PubMed ID: 16951161	2006
Daptomycin and tigecycline have broader effective dose ranges than vancomycin as prophylaxis against a Staphylococcus aureus surgical implant infection in mice. Antimicrobial agents and chemotherapy\| PubMed ID: 22371896	2012
Monitoring Bacterial Burden, Inflammation and Bone Damage Longitudinally Using Optical and Î¼CT Imaging in an Orthopaedic Implant Infection in Mice. PloS one\| PubMed ID: 23082163	2012
Vancomycin plus Rifampin Combination Therapy has Enhanced Efficacy Against an Experimental Staphylococcus aureus Prosthetic Joint Infection. Antimicrobial agents and chemotherapy\| PubMed ID: 23917317	2013
Understanding infection: a primer on animal models of periprosthetic joint infection. TheScientificWorldJournal\| PubMed ID: 24174919	2013
Combination prophylactic therapy with rifampin increases efficacy against an experimental Staphylococcus epidermidis subcutaneous implant-related infection. Antimicrobial agents and chemotherapy\| PubMed ID: 24514089	2014

Jared A. Niska

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