Warfarin maintenance dose prediction for Chinese after heart valve replacement by a feedforward neural network with equal stratified sampling.

Patients requiring low-dose warfarin are more likely to suffer bleeding due to overdose. The goal of this work is to improve the feedforward neural network model's precision in predicting the low maintenance dose for Chinese in the aspect of training data construction. We built the model from a resampled dataset created by equal stratified sampling (maintaining the same sample number in three dose-groups with a total of 3639) and performed internal and external validations. Comparing to the model trained from the raw dataset of 19,060 eligible cases, we improved the low-dose group's ideal prediction percentage from 0.7 to 9.6% and maintained the overall performance (76.4% vs. 75.6%) in external validation. We further built neural network models on single-dose subsets to invest whether the subsets samples were sufficient and whether the selected factors were appropriate. The training set sizes were 1340 and 1478 for the low and high dose subsets; the corresponding ideal prediction percentages were 70.2% and 75.1%. The training set size for the intermediate dose varied and was 1553, 6214, and 12,429; the corresponding ideal prediction percentages were 95.6, 95.1%, and 95.3%. Our conclusion is that equal stratified sampling can be a considerable alternative approach in training data construction to build drug dosing models in the clinic.

Zinc ameliorates human aortic valve calcification through GPR39 mediated ERK1/2 signalling pathway.

AIMS: Calcific aortic valve disease (CAVD) is the most common heart valve disease in the Western world. It has been reported that zinc is accumulated in calcified human aortic valves. However, whether zinc directly regulates CAVD is yet to be elucidated. The present study sought to determine the potential role of zinc in the pathogenesis of CAVD. METHODS AND RESULTS: Using a combination of a human valve interstitial cell (hVIC) calcification model, human aortic valve tissues, and blood samples, we report that 20 µM zinc supplementation attenuates hVIC in vitro calcification, and that this is mediated through inhibition of apoptosis and osteogenic differentiation via the zinc-sensing receptor GPR39-dependent ERK1/2 signalling pathway. Furthermore, we report that GPR39 protein expression is dramatically reduced in calcified human aortic valves, and there is a significant reduction in zinc serum levels in patients with CAVD. Moreover, we reveal that 20 µM zinc treatment prevents the reduction of GPR39 observed in calcified hVICs. We also show that the zinc transporter ZIP13 and ZIP14 are significantly increased in hVICs in response to zinc treatment. Knockdown of ZIP13 or ZIP14 significantly inhibited hVIC in vitro calcification and osteogenic differentiation. CONCLUSIONS: Together, these findings suggest that zinc is a novel inhibitor of CAVD, and report that zinc transporter ZIP13 and ZIP14 are important regulators of hVIC in vitro calcification and osteogenic differentiation. Zinc supplementation may offer a potential therapeutic strategy for CAVD.

[Application of cream formula in treatment of severe heart failure].

Cream formula has been mostly used to treat deficiency syndrome. Currently,it has been used to recuperate the body,promote health against aging,and prevent and treat chronic disease. In modern medicine,there are only treatment concepts and methods of diseases,but lack of concepts of " deficiency syndrome" and " restoring deficiency". The concepts of " deficiency syndrome" and " restoring deficiency" could effectively supplement and improve the diagnosis and treatment scheme of some modern diseases. Refractory heart failure,dilated cardiomyopathy,ischemic cardiomyopathy,and valvular heart disease belong to the traditional category of " consumptive disease". The cream formula with the efficacy of restoring deficiency can not only alleviate symptoms and improve the quality of life,but also improve the structure and function of the heart,reduce the dosage of diuretics and the number of hospitalizations,and achieve the purpose of secondary prevention in the treatment of severe heart failure,dilated cardiomyopathy,ischemic cardiomyopathy and valvular heart disease. The cream formula for treating chronic heart failure include Shenqi Pills,Zhenwu Decoction,Yougui Pills,Wuling Powder,Linggui Zhugan Decoction,Danggui Shaoyao Powder,Lizhong Decoction,Buzhong Yiqi Decoction,Guipi Decoction,Yupingfeng Powder,Guizhi Decoction. Long-term administration of cream formula could not only resist aging,but also play an irreplaceable role in the secondary prevention of acute and critical diseases.

Regulation of calcific vascular and valvular disease by nuclear receptors.

PURPOSE OF REVIEW: This review addresses recent developments in studies of lipid regulation of calcific disease of arteries and cardiac valves, including the role of nuclear receptors. The role of lipid-soluble signals and their receptors is timely given the recent evidence and concerns that lipid-lowering treatment may increase the rate of progression of coronary artery calcification, which has been long associated with increased cardiovascular risk. Understanding the mechanisms will be important for interpreting such clinical information. RECENT FINDINGS: New findings support regulation of calcific vascular and valvular disease by nuclear receptors, including the vitamin D receptor, glucocorticoid receptor, nutrient-sensing nuclear receptors (liver X receptor, farnesoid X receptor, and peroxisome proliferator-activated receptors), and sex hormone (estrogen and androgen) receptors. There were two major unexpected findings: first, vitamin D supplementation, which was previously believed to prevent or reduce vascular calcification, showed no cardiovascular benefit in large randomized, controlled trials. Second, both epidemiological studies and coronary intravascular ultrasound studies suggest that treatment with HMG-CoA reductase inhibitors increases progression of coronary artery calcification, raising a question of whether there are mechanically stable and unstable forms of coronary calcification. SUMMARY: For clinical practice and research, these new findings offer new fundamental mechanisms for vascular calcification and provide new cautionary insights for therapeutic avenues.

Interactive and Multifactorial Mechanisms of Calcific Vascular and Valvular Disease.

Calcific vascular and valvular disease (CVVD) is widespread and has major health consequences. Although coronary artery calcification has long been associated with hyperlipidemia and increased mortality, recent evidence suggests that its progression is increased in association with cholesterol-lowering HMG-CoA reductase inhibitors ('statins') and long-term, high-intensity exercise. A nationwide trial showed no cardiovascular benefit of vitamin D supplements. Controversy remains as to whether calcium deposits in plaque promote or prevent plaque rupture. CVVD appears to occur through mechanisms similar to those of intramembranous, endochondral, and osteophytic skeletal bone formation. New evidence implicates autotaxin, endothelial-mesenchymal transformation, and microRNA and long non-coding RNA (lncRNA) as novel regulatory factors. New therapeutic options are being developed.

Stroke in a young man: a late complication of radiation therapy.

This 37-year-old man presented with left sided facial warmth and numbness associated with new sudden-onset right hemiparesis. The patient first developed sudden numbness of his left lip and warmth in left ear which travelled to the rest of left face. His past medical history was significant for hypertension, Hodgkin lymphoma treated with radiation therapy at the age of 10, and sleeve gastrectomy for obesity 1 year ago complicated by bilateral ischaemic cerebral infarctions with residual left hemiparesis. No acute infarcts were found on MRI. Transesophageal echocardiography revealed a complex atheroma near the sinotubular junction in ascending aorta.

Therapeutic Effect and Mechanism of Action of Abnormal Savda Munziq in Development of Degenerative Atherosclerotic Aortic Valve Disease.

BACKGROUND The aim of this study was to investigate the therapeutic effect of abnormal Savda Munziq (ASMq) on the development of degenerative atherosclerotic aortic valve disease and its underlying mechanisms. MATERIAL AND METHODS We randomly divided 80 rabbits into 4 groups: a normal control group (group N, n=20); a high-fat diet group (group HC, n=20); a high-fat diet and Atorvastatin calcium intervention group (group AI, n=20); and a high-fat diet and ASMq intervention group (group MI, n=20). For evaluation of blood lipid profiles, blood samples were collected at week 0 and at the end of week 8. Aortic valve samples were taken at weeks 0, 2, 4, 6, and 8 for atomic force microscopy (AFM) examination of endothelial cell nanostructures, and at week 8 for pathological examinations. RESULTS Triglyceride (TG), cholesterol (TC), low-density lipoprotein (LDL), and high-density lipoprotein HDL levels of rabbits in group HC were significantly different from those in group N (P<0.01). TG, TC, LDL, and HDL values of rabbits in group MI were significantly different from rabbits in group HC (P<0.05). Pathological examination revealed that the aortic valves from rabbits in group MI were visibly clear, with strong endothelial cell continuity. No infiltration of macrophages or other inflammatory cells nor subendothelial calcium deposition was found when compared with rabbits in group HC. CONCLUSIONS ASMq therapy can delay the onset of degenerative calcific aortic valve disease, and its effects are similar to those of Atorvastatin.

Stroke, Bleeding, and Mortality Risks in Elderly Medicare Beneficiaries Treated With Dabigatran or Rivaroxaban for Nonvalvular Atrial Fibrillation.

Importance: Dabigatran and rivaroxaban are non-vitamin K oral anticoagulants approved for stroke prevention in patients with nonvalvular atrial fibrillation (AF). There are no randomized head-to-head comparisons of these drugs for stroke, bleeding, or mortality outcomes. Objective: To compare risks of thromboembolic stroke, intracranial hemorrhage (ICH), major extracranial bleeding including major gastrointestinal bleeding, and mortality in patients with nonvalvular AF who initiated dabigatran or rivaroxaban treatment for stroke prevention. Design, Setting, and Participants: Retrospective new-user cohort study of 118 891 patients with nonvalvular AF who were 65 years or older, enrolled in fee-for-service Medicare, and who initiated treatment with dabigatran or rivaroxaban from November 4, 2011, through June 30, 2014. Differences in baseline characteristics were adjusted using stabilized inverse probability of treatment weights based on propensity scores. The data analysis was performed from May 7, 2015, through June 30, 2016. Exposures: Dabigatran, 150 mg, twice daily; rivaroxaban, 20 mg, once daily. Main Outcomes and Measures: Adjusted hazard ratios (HRs) for the primary outcomes of thromboembolic stroke, ICH, major extracranial bleeding including major gastrointestinal bleeding, and mortality, with dabigatran as reference. Adjusted incidence rate differences (AIRDs) were also estimated. Results: A total of 52 240 dabigatran-treated and 66 651 rivaroxaban-treated patients (47% female) contributed 15 524 and 20 199 person-years of on-treatment follow-up, respectively, during which 2537 primary outcome events occurred. Rivaroxaban use was associated with a statistically nonsignificant reduction in thromboembolic stroke (HR, 0.81; 95% CI, 0.65-1.01; P = .07; AIRD = 1.8 fewer cases/1000 person-years), statistically significant increases in ICH (HR, 1.65; 95% CI, 1.20-2.26; P = .002; AIRD = 2.3 excess cases/1000 person-years) and major extracranial bleeding (HR, 1.48; 95% CI, 1.32-1.67; P < .001; AIRD = 13.0 excess cases/1000 person-years), including major gastrointestinal bleeding (HR, 1.40; 95% CI, 1.23-1.59; P < .001; AIRD = 9.4 excess cases/1000 person-years), and with a statistically nonsignificant increase in mortality (HR, 1.15; 95% CI, 1.00-1.32; P = .051; AIRD = 3.1 excess cases/1000 person-years). In patients 75 years or older or with CHADS2 score greater than 2, rivaroxaban use was associated with significantly increased mortality compared with dabigatran use. The excess rate of ICH with rivaroxaban use exceeded its reduced rate of thromboembolic stroke. Conclusions and Relevance: Treatment with rivaroxaban 20 mg once daily was associated with statistically significant increases in ICH and major extracranial bleeding, including major gastrointestinal bleeding, compared with dabigatran 150 mg twice daily.

Cardiovascular Disease Risk in a Large, Population-Based Cohort of Breast Cancer Survivors.

PURPOSE: To conduct a large, population-based study on cardiovascular disease (CVD) in breast cancer (BC) survivors treated in 1989 or later. METHODS AND MATERIALS: A large, population-based cohort comprising 70,230 surgically treated stage I to III BC patients diagnosed before age 75 years between 1989 and 2005 was linked with population-based registries for CVD. Cardiovascular disease risks were compared with the general population, and within the cohort using competing risk analyses. RESULTS: Compared with the general Dutch population, BC patients had a slightly lower CVD mortality risk (standardized mortality ratio 0.92, 95% confidence interval [CI] 0.88-0.97). Only death due to valvular heart disease was more frequent (standardized mortality ratio 1.28, 95% CI 1.08-1.52). Left-sided radiation therapy after mastectomy increased the risk of any cardiovascular event compared with both surgery alone (subdistribution hazard ratio (sHR) 1.23, 95% CI 1.11-1.36) and right-sided radiation therapy (sHR 1.19, 95% CI 1.04-1.36). Radiation-associated risks were found for not only ischemic heart disease, but also for valvular heart disease and congestive heart failure (CHF). Risks were more pronounced in patients aged <50 years at BC diagnosis (sHR 1.48, 95% CI 1.07-2.04 for left- vs right-sided radiation therapy after mastectomy). Left- versus right-sided radiation therapy after wide local excision did not increase the risk of all CVD combined, yet an increased ischemic heart disease risk was found (sHR 1.14, 95% CI 1.01-1.28). Analyses including detailed radiation therapy information showed an increased CVD risk for left-sided chest wall irradiation alone, left-sided breast irradiation alone, and internal mammary chain field irradiation, all compared with right-sided breast irradiation alone. Compared with patients not treated with chemotherapy, chemotherapy used ≥1997 (ie, anthracyline-based chemotherapy) increased the risk of CHF (sHR 1.35, 95% CI 1.00-1.83). CONCLUSION: Radiation therapy regimens used in BC treatment between 1989 and 2005 increased the risk of CVD, and anthracycline-based chemotherapy regimens increased the risk of CHF.

Connections between nutritional status and proton pump inhibitor therapy in patients scheduled for cardiovascular rehabilitation after treatment for ischaemic and valvular heart disease.

BACKGROUND: Multiple and yet uncertain connections exist between cardiovascular diseases and the nutritional status of patients, particularly in relation to cardiovascular treatments. Proton pump inhibitors (PPI) are among the most commonly used group of drugs. AIM: To analyse utilisation of PPI in association with nutritional risk of patients scheduled for rehabilitation after treatment for ischaemic and valvular heart disease. METHODS: Retrospective analyses on a consecutive sample of patients, which included drug utilisation of PPI and nutritional risk screening, using a standardised NRS-2002 tool. The patients (n = 536) were divided into groups based on previous cardiovascular treatments and use of PPI. RESULTS: Nearly half of the patients (244, 46.1%) had PPI in their chronic therapy despite the clinically negligible prevalence of conditions that are their fundamental indications. The odds for using PPI in patients with increased nutritional risk, estimated by logistic regression, were 3.34 (95% confidence intervals [CI] 2.26-4.94), p < 0.001. Receiver operating curve analyses also revealed significant differences of PPI utilisation in connection with NRS-2002 > 3: positive likelihood-ratio (LR) 2.35 (95% CI 2.10-2.60); negative LR 0.46 (95% CI 0.4-0.6); area under the curve (AUC) 0.720; p < 0.001; as well as the percentage weigh loss history > 6.36% (positive LR 2.22 [95% CI 2.00-2.50]; negative LR 0.41 [95% CI 0.30-0.50]; AUC 0.707; p < 0.001). CONCLUSIONS: Utilisation of PPI was found to be of relatively high prevalence and significantly associated with parameters of nutritional risk screening. Furthermore, it was in correlation with the age of patients and the existence of chronic kidney disease, which are well-established predispositions for poor nutritional status. Nutritional risk seems to be additionally negatively challenged by utilisation of PPI due to gastric malabsorption and anaemia.

[Effect of pretreatment with qishen yiqi dropping pills on right cardiac function of patients undergoing valve replacement].

In this study, 120 patients with rheumatic heart disease undergoing valve replacement were randomly divided into the control group and the Qishen group, with 60 cases in each group. Before the operation, the control group was given routine heart and diuretic treatments and placebo of Qishen Yiqi dropping pills for seven days (0.5 g each time, three times a day); While the Qishen group was given Qishen Yiqi dropping pills for seven days (0.5 g each time after meal, three times a day) on the basis of the routine treatments. The right ventricular end-diastolic volume (RVEDV), end-systolic volume (RVESV), stroke volume (SV) and right ventricular ejection fraction (RVEF) were detected after the operation. The results showed that patients in the two groups showed significantly lower right ventricular end diastolic volume (RVEDV), right ventricular end systolic volume (RVESV) and stroke volume (SV) decreased than that before the operation, but with significantly higher Ejection fraction (RVEF) significantly than that before the operation. However, the Qishen group showed a significantly lower right heart function reduction than the control group, with the statistical significance in the differences (P < 0.05). This indicated that the pretreatment with Qishenyiqi Drop Pills showed a remarkable efficacy in the improvement of right ventricular function after valve replacement.

Comparison of six generic vancomycin products for treatment of methicillin-resistant Staphylococcus aureus experimental endocarditis in rabbits.

Concerns have recently emerged about the potency and the quality of generic vancomycin (VAN) products approved for use in humans, based on experiments in a neutropenic mouse thigh infection model. However, other animal models may be more appropriate to decipher the bactericidal activities of VAN generics in vivo and to predict their efficacy in humans. We aimed to compare the bactericidal activities of six generic VAN products currently used in France (Mylan and Sandoz), Spain (Hospira), Switzerland (Teva), and the United States (Akorn-Strides and American Pharmaceutical Products [APP]) in a rabbit model of aortic valve endocarditis induced by 8 × 10(7) CFU of methicillin-resistant Staphylococcus aureus (MRSA) strain COL (VAN MIC, 1.5 µg/ml). In vitro, there were no significant differences in the time-kill curve studies performed with the six generic VAN products. Ten rabbits in each group were treated with intravenous (i.v.) VAN, 60 mg/kg of body weight twice a day (b.i.d.) for 4 days. Mean peak serum VAN levels, measured 45 min after the last injection, ranged from 35.5 (APP) to 45.9 µg/ml (Teva). Mean trough serum VAN levels, measured 12 h after the last injection, ranged from 2.3 (Hospira) to 9.2 (APP) µg/ml. All generic VAN products were superior to controls (no treatment) in terms of residual organisms in vegetations (P < 0.02 for each comparison) and in the spleen (P < 0.005 for each comparison). Pairwise comparisons of generic VAN products found no significant differences. In conclusion, a stringent MRSA endocarditis model found no significant differences in the bactericidal activities of six generic VAN products currently used in Europe and America.

Antithrombotic and thrombolytic therapy for valvular disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines.

BACKGROUND: Antithrombotic therapy in valvular disease is important to mitigate thromboembolism, but the hemorrhagic risk imposed must be considered. METHODS: The methods of this guideline follow those described in Methodology for the Development of Antithrombotic Therapy and Prevention of Thrombosis Guidelines. Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines in this supplement. RESULTS: In rheumatic mitral disease, we recommend vitamin K antagonist (VKA) therapy when the left atrial diameter is > 55 mm (Grade 2C) or when complicated by left atrial thrombus (Grade 1A). In candidates for percutaneous mitral valvotomy with left atrial thrombus, we recommend VKA therapy until thrombus resolution, and we recommend abandoning valvotomy if the thrombus fails to resolve (Grade 1A). In patients with patent foramen ovale (PFO) and stroke or transient ischemic attack, we recommend initial aspirin therapy (Grade 1B) and suggest substitution of VKA if recurrence (Grade 2C). In patients with cryptogenic stroke and DVT and a PFO, we recommend VKA therapy for 3 months (Grade 1B) and consideration of PFO closure (Grade 2C). We recommend against the use of anticoagulant (Grade 1C) and antiplatelet therapy (Grade 1B) for native valve endocarditis. We suggest holding VKA therapy until the patient is stabilized without neurologic complications for infective endocarditis of a prosthetic valve (Grade 2C). In the first 3 months after bioprosthetic valve implantation, we recommend aspirin for aortic valves (Grade 2C), the addition of clopidogrel to aspirin if the aortic valve is transcatheter (Grade 2C), and VKA therapy with a target international normalized ratio (INR) of 2.5 for mitral valves (Grade 2C). After 3 months, we suggest aspirin therapy (Grade 2C). We recommend early bridging of mechanical valve patients to VKA therapy with unfractionated heparin (DVT dosing) or low-molecular-weight heparin (Grade 2C). We recommend long-term VKA therapy for all mechanical valves (Grade 1B): target INR 2.5 for aortic (Grade 1B) and 3.0 for mitral or double valve (Grade 2C). In patients with mechanical valves at low bleeding risk, we suggest the addition of low-dose aspirin (50-100 mg/d) (Grade 1B). In valve repair patients, we suggest aspirin therapy (Grade 2C). In patients with thrombosed prosthetic valve, we recommend fibrinolysis for right-sided valves and left-sided valves with thrombus area < 0.8 cm(2) (Grade 2C). For patients with left-sided prosthetic valve thrombosis and thrombus area ≥ 0.8 cm(2), we recommend early surgery (Grade 2C). CONCLUSIONS: These antithrombotic guidelines provide recommendations based on the optimal balance of thrombotic and hemorrhagic risk.

Association of warfarin use with valvular and vascular calcification: a review.

Vitamin K is required for the activity of various biologically active proteins in our body. Apart from clotting factors, vitamin K-dependent proteins include regulatory proteins like protein C, protein S, protein Z, osteocalcin, growth arrest-specific gene 6 protein, and matrix Gla protein. Glutamic acid residues in matrix Gla protein are γ-carboxylated by vitamin K-dependent γ-carboxylase, which enables it to inhibit calcification. Warfarin, being a vitamin K antagonist, inhibits this process, and has been associated with calcification in various animal and human studies. Though no specific guidelines are currently available to prevent or treat this less-recognized side effect, discontinuing warfarin and using an alternative anticoagulant seems to be a reasonable option. Newer anticoagulants such as dabigatran and rivaroxaban offer promise as future therapeutic options in such cases. Drugs including statins, alendronate, osteoprotegerin, and vitamin K are currently under study as therapies to prevent or treat warfarin-associated calcification. Copyright © 2011 Wiley Periodicals, Inc. The authors have no funding, financial relationships, or conflicts of interest to disclose.

Use of daptomycin in a pregnant patient with Staphylococcus aureus endocarditis.

OBJECTIVE: To report on 6 weeks of daptomycin treatment for tricuspid valve endocarditis caused by Staphylococcus aureus in a pregnant female in her second trimester. CASE SUMMARY: A 24-year-old, 14-week pregnant patient with no significant medical history, but with a history of intravenous drug abuse presented with tricuspid valve endocarditis caused by methicillin-sensitive S. aureus. After initial treatment with vancomycin, the patient continued to have fever and bacteremia and was initiated on daptomycin 6 mg/kg for 6 weeks of therapy. The treatment resulted in the resolution of the endocarditis, and no adverse sequelae were identified in the mother or baby. DISCUSSION: Infective endocarditis is a common infection encountered in the hospital setting and represents an increased cost burden to institutions due to prolonged lengths of treatment. Antimicrobial resistance, antimicrobial failure, inadequate attainment of effective drug concentrations, drug allergies, and adverse reactions may be factors that limit the use of commonly utilized antimicrobial agents. Therefore, newer therapies like daptomycin may need to be employed in these situations. Although daptomycin is pregnancy category B, limited case reports with neonatal outcomes are reported. CONCLUSIONS: This case provides further support for the safety of daptomycin in pregnancy with the dose of 6 mg/kg, the extended duration of therapy (6 weeks), and the primary exposure in the second trimester.

Daptomycin for methicillin-resistant Staphylococcus epidermidis native-valve endocarditis: a case report.

Coagulase-negative staphylococci (CoNS) have been increasing in importance as a cause of native valve endocarditis (NVE). Most cases of NVE caused by CoNS are attributable to Staphylococcus epidermidis. NVE caused by CoNS acquired in a nosocomial setting may differ from cases acquired in the community in several ways. It may be associated with hemodialysis, the presence of a long-term indwelling central catheter or pacemaker, or a recent invasive procedure; nosocomial cases may have a higher rate of methicillin resistance among CoNS isolates, and so be more likely to be treated with vancomycin. Unfortunately, NVE caused by methicillin-resistant CoNS has been associated with significantly higher rates of persistent bacteremia and in-hospital mortality than methicillin-susceptible isolates. The poor outcomes in these cases point to the need for alternative therapies with potent activity against methicillin-resistant CoNS. In our medical center, a 76-year-old man presented with native-valve endocarditis and positive blood cultures for methicillin-resistant Staphylococcus epidermidis (MRSE). During each of three 6-week courses of treatment with vancomycin, blood cultures were negative, but they once again became positive for MRSE when vancomycin was discontinued. The minimum inhibitory concentration of the MRSE isolates for vancomycin remained stable at 2 microg/mL. Eventually, treatment with daptomycin was initiated (500 mg [7 mg/kg]) 3 times/week for 6 weeks. Over the following year, no positive cultures for MRSE were detected.

First case of Pasteurella multocida endocarditis of the tricuspid valve: a favorable outcome following medical treatment.

We describe a rare case of tricuspid valve endocarditis caused by Pasteurella multocida in an elderly woman with no previous history of valvular heart disease. Risk factors included contact with animals and old age. The patient was treated successfully with five days of intravenous ampicillin followed by four weeks of oral ciprofloxacin.

Successful treatment with moxifloxacin of experimental aortic valve endocarditis due to methicillin-resistant Staphylococcus aureus (MRSA).

Moxifloxacin (MXF) is an 8-methoxyquinolone with high activity against Gram-positive bacteria. In an experimental model of aortic valve endocarditis (EAVE), the efficacy of MXF was evaluated against a strain of methicillin-resistant Staphylococcus aureus (MRSA). Rabbits with catheter-induced aortic valve vegetations were randomly assigned to a control group or to groups receiving MXF 20 mg/kg intravenous (i.v.) twice a day (bid) or vancomycin (VAN) 30 mg/kg i.v. bid for a total of eight doses (4 days). Rabbits were sacrificed 15 h after the last dose of antibiotics. In another group, treatment with MXF was extended to 5 days and rabbits were sacrificed 5 days after the last dose (10th dose) of MXF in order to detect possible relapses of endocarditis after the end of treatment (test-of-cure (TOC) study). Both MXF and VAN significantly reduced the bacterial load in vegetations (P < 0.001 vs. controls). All animals in the MXF-TOC group had sterile vegetations. MXF given at a dose of 20 mg/kg i.v. bid for 4 days was equally effective as VAN in the treatment of EAVE due to MRSA. When treatment with MXF was extended to 5 days, the cure rate reached 100% and no relapses of endocarditis were observed.

Daptomycin is effective in treatment of experimental endocarditis due to methicillin-resistant and glycopeptide-intermediate Staphylococcus aureus.

Daptomycin is a lipopeptide antibiotic with potent in vitro activity against gram-positive cocci, including Staphylococcus aureus. This study evaluated the in vitro and in vivo efficacies of daptomycin against two clinical isolates: methicillin-resistant S. aureus (MRSA) 277 (vancomycin MIC, 2 microg/ml) and glycopeptide-intermediate S. aureus (GISA) ATCC 700788 (vancomycin MIC, 8 microg/ml). Time-kill experiments demonstrated that daptomycin was bactericidal in vitro against these two strains. The in vivo activity of daptomycin (6 mg/kg of body weight every 24 h) was evaluated by using a rabbit model of infective endocarditis and was compared with the activities of a high-dose (HD) vancomycin regimen (1 g intravenously every 6 h), the recommended dose (RD) of vancomycin regimen (1 g intravenously every 12 h) for 48 h, and no treatment (as a control). Daptomycin was significantly more effective than the vancomycin RD in reducing the density of bacteria in the vegetations for the MRSA strains (0 [interquartile range, 0 to 1.5] versus 2 [interquartile range, 0 to 5.6] log CFU/g vegetation; P = 0.02) and GISA strains (2 [interquartile range, 0 to 2] versus 6.6 [interquartile range, 2.0 to 6.9] log CFU/g vegetation; P < 0.01) studied. In addition, daptomycin sterilized more MRSA vegetations than the vancomycin RD (13/18 [72%] versus 7/20 [35%]; P = 0.02) and sterilized more GISA vegetations than either vancomycin regimen (12/19 [63%] versus 4/20 [20%]; P < 0.01). No statistically significant difference between the vancomycin HD and the vancomycin RD for MRSA treatment was noted. These results support the use of daptomycin for the treatment of aortic valve endocarditis caused by GISA and MRSA.