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Although recent advances in pulmonary valve replacement have enabled excellent hemodynamics, infective endocarditis remains a serious complication, particularly for implanted bovine jugular vein (BJV) conduits. We investigated contributions by platelets and plasma fibrinogen to endocarditis initiation on various grafts used for valve replacement. Thus, adherence of Staphylococcus aureus and platelets to 5 graft tissues was studied quantitatively in perfusion chambers, assisted by microscopic analysis. We also evaluated standard antiplatelet therapy to prevent onset of S aureus endocarditis. Of all tissues, bovine pericardium (BP) showed the greatest fibrinogen binding. Perfusion of all plasma-precoated tissues identified BP and BJV wall with the greatest affinity for S aureus. Perfusions of anticoagulated human blood over all tissues also triggered more platelet adhesion to BP and BJV wall as single platelets. Several controls confirmed that both S aureus and platelets were recruited on immobilized fibrinogen. In addition, perfusions (and controls) over plasma-coated tissues with whole blood, spiked with S aureus , revealed that bacteria exclusively bound to adhered platelets. Both the platelet adhesion and platelet-mediated S aureus recruitment required platelet α IIb β 3 and coated or soluble fibrinogen, respectively, interactions abrogated by the α IIb β 3 -antagonist eptifibatide. Also, standard antiplatelet therapy (aspirin/ticagrelor) reduced the adherence of S aureus in blood to BJV 3-fold. Binding of plasma fibrinogen to especially BJV grafts enables adhesion of single platelets via α IIb β 3. S aureus then attaches from blood to (activated) bound platelet α IIb β 3 via plasma fibrinogen. Dual antiplatelet therapy appears a realistic approach to prevent endocarditis and its associated mortality. General experimental study design and impact of dual anti-platelet treatment on infective endocarditis initiation. Discs of various graft tissues were placed in a microparallel flow chamber, allowing perfusion of bacteria, suspended in whole blood over graft tissue surfaces in laminar flow conditions. The optimized setup enables assessment of bacterial adhesion by fluorescence microscopy and a serial dilution method to determine CFUs. Also, platelet adhesion in the flow chamber was quantitatively measured by a colorimetric assay, based on an acid phosphatase test. In the course of these studies, we uncovered that bacteria are exclusively recruited to graft cardiac tissues by adhered active platelets, bridging their activated α IIb β 3 receptor and bacterial ligands via fibrinogen (Fg). This in vitro flow chamber system, therefore, made it possible to investigate whether inhibiting platelet binding with antiaggregant agents would eradicate the platelet-assisted S aureus recruitment to the graft tissue. We found that bacterial adhesion to bovine jugular vein in citrate anticoagulated blood was eliminated by antiplatelet agents such as ASA and TICA, in combination. These results provide a basis for clinical studies on the use of antiplatelet drugs in prevention of S aureus infections, such as infective endocarditis. ASA , Acetylsalicylic acid; TICA , ticagrelor; CFU , colony-forming unit. [Display omitted] [ABSTRACT FROM AUTHOR]

Streptococcus tigurinus is responsible for systemic infections in humans including infective endocarditis. We investigated whether the invasive trait of S. tigurinus in humans correlated with an increased ability to induce IE in rats. Rats with catheter-induced aortic vegetations were inoculated with 104 CFU/ml of either of four S. tigurinus strains AZ_3aT, AZ_4a, AZ_8 and AZ_14, isolated from patients with infective endocarditis or with the well known IE pathogen Streptococcus gordonii (Challis). Aortic infection was assessed after 24h. S. tigurinus AZ_3aT, AZ_4a and AZ_14 produced endocarditis in ≥80% of rats whereas S. gordonii produced endocarditis in only 33% of animals (P <0.05). S. tigurinus AZ_8 caused vegetation infection in 56% of the animals. The capacity of S. tigurinus to induce aortic infection was not related to their ability to bind extracellular matrix proteins (fibrinogen, fibronectin or collagen) or to trigger platelet aggregation. However, all S. tigurinus isolates showed an enhanced resistance to phagocytosis by macrophages and two of them had an increased ability to enter endothelial cells, key attributes of invasive streptococcal species. [ABSTRACT FROM AUTHOR]

Methicillin-resistant Staphylococcus aureus (MRSA), both hospital-acquired and community-acquired, is a dangerous pathogen that is involved in an increasing number of serious infections with high risk for morbidity and mortality. Community-acquired MRSA strains have epidemic potential and can be particularly virulent. Vancomycin has been the standard hospital treatment for the past 40 years, but vancomycin-resistant isolates of S. aureus have emerged in the USA, and vancomycin-intermediate isolates are increasingly being reported worldwide. New antimicrobial agents with activity against multidrug-resistant S. aureus and other resistant pathogens are urgently needed. Despite great strides, further advances in our understanding of the molecular and biochemical mechanisms responsible for antimicrobial resistance are still required. Several agents have been recently approved for the treatment of serious Gram-positive infections, including linezolid, daptomycin, and tigecycline. The novel investigational cephalosporin, ceftobiprole, is one of the first penicillinase-resistant agents to target penicillin-binding protein 2a (or PBP2a), an acquired PBP with low β-lactam-affinity that confers intrinsic β-lactam resistance to S. aureus and other staphylococci. This mechanism of PBP binding, including inhibition of PBP2a, confers broad-spectrum activity against clinically important Gram-negative and Gram-positive pathogens, including MRSA. Phase III clinical trials comparing ceftobiprole with vancomycin alone and in combination with ceftazidime for the treatment of complicated skin and skin structure infections showed ceftobiprole to have efficacy similar to the efficacy of these comparators as evidenced by non-inferior clinical cure and microbiological eradication rates. [ABSTRACT FROM AUTHOR]

Despite improvements in health care, the incidence of infective endocarditis has not decreased over the past decades. This apparent paradox is explained by a progressive evolution in risk factors; while classic predisposing conditions such as rheumatic heart disease have been all but eradicated, new risk factors for infective endocarditis have emerged. These include intravenous drug use, sclerotic valve disease in elderly patients, use of prosthetic valves, and nosocomial disease. Newly identified pathogens, which are difficult to cultivate—eg, Bartonella spp and Tropheryma whipplei—are present in selected individuals, and resistant organisms are challenging conventional antimicrobial therapy. Keeping up with these changes depends on a comprehensive approach, allying understanding of the pathogenesis of disease with the development of new drugs for infective endocarditis. Infection by staphylococci and streptococci is being dissected at the molecular level. New ideas for antimicrobial agents are being developed. These novel insights should help redefine preventive and therapeutic strategies against infective endocarditis. [Copyright &y& Elsevier]

Examines the risk and benefit of antibiotic resistance on animal experimentation. Contribution of anti-infective chemotherapy to public health advantage and limitation of antibiotic usage; Risk of selecting resistance emergence during treatment.

Staphylococcus aureus is a highly contagious mastitis-causing pathogen infecting dairy cattle worldwide. Previous studies have shown the presence of different genotypes (GT) on farms. In Switzerland, Staph. aureus genotype B (GTB) is contagious, whereas GTC and other genotypes cause sporadic, noncontagious mastitis. In this study, we evaluated the epidemiological properties of Staph. aureus, together with its genotypes and spa types, on Swiss dairy farms. A total of 21 dairy farms were sampled throughout Switzerland; 10 farms were positive for the contagious Staph. aureus GTB and 11 farms were negative for GTB. Samples were taken from milk, body surfaces of dairy cattle and other animals, milkers, milking equipment, and environmental sites (e.g., parlor, washing room, stall floor, manger, and bedding). The epidemiology of Staph. aureus depended markedly on the genotype. Staphylococcus aureus GTB was associated with mammary gland, intramammary infections (IMI), and milking clusters, whereas GTC and other genotypes were related to cow and other animal surfaces and occasionally to environment. Genotype C was by far the most common subtype in cattle and was found on GTB-negative and GTB-positive farms. Each farm had a predominant genotype, such as GTB, GTC, GTA, or GTF, but a few farms were almost free from Staph. aureus. The genotypes and spa types of Staph. aureus detected in the noses of milkers clearly differed from those found in dairy cattle, other animals, milking equipment, and the environment. Exceptions were GTS (spa type t034) and GTF (t899), which crossed the species barrier. In most cases, however, the species barrier was maintained because Staph. aureus is adapted to a particular host and even to particular body sites. As biological properties differ among the genotypes, new guidelines to prevent IMI caused by different genotypes were established: classical measures to prevent IMI caused by contagious pathogens still hold for GTB but not for Staph. aureus genotypes that are opportunistic colonizers of bovine skin (e.g., GTC and GTA). For those genotypes, protection of the skin from minor lesions and wounds, particularly on the hocks, is essential. [ABSTRACT FROM AUTHOR]

Objective To assess the molecular epidemiology and risk factors of predominant clones and sporadic strains of methicillin-resistant Staphylococcus aureus (MRSA) in Swiss hospitals and to compare them with European strains of epidemic clones. Material and methods One-year national survey of MRSA cases. Analysis of epidemiological and molecular typing data (PFGE) of MRSA strains. Results In 1997, 385 cases of MRSA were recorded in the five Swiss university hospitals and in 47 community hospitals. Half of the cases were found in Geneva hospitals where MRSA was already known to be endemic. Molecular typing of 288 isolates (one per case) showed that 186 (65%) belong to four predominant clones, three of which were mostly present in Geneva hospitals. In contrast, the fourth clone (85 cases) was found in 23 hospitals (in one to 16 cases per hospital). The remaining 35% of the strains were clustered into 62 pulsed field gel electrophoresis types. They accounted for one to five patients per hospital and were defined as sporadic. Multivariate analysis revealed no independent risk factors for harboring a predominant versus a sporadic strain, except that transfer from a foreign hospital increases the risk of harboring a sporadic strain (OR, 42; 95% CI, 5–360). Conclusion While cases with predominant clones were due to the local spread of these clones, most sporadic cases appear to be due to the continuous introduction of new strains into the country. With the exception of a transfer from a hospital outside Switzerland, no difference in the clinical or epidemiological characteristics was observed between patients harboring a predominant clone and those with a sporadic strain. [ABSTRACT FROM AUTHOR]