minocycline and Endocarditis

Though the increased resistance to antibiotics observed worldwide is not a major concern in France, treatment of methicillin-resistant S. aureus has important limitations. New antibiotics have recently been marketed or will soon be (quinupristin-dalfopristin, linelozide, tigecyclin, daptomycin, ceftobiprole, dalbavancin). Their role, which has been documented in several forms of acute infections, remains to be established in infective endocarditis. At present, only treatment of methicillin-resistant S. aureus right-sided endocarditis justifies the use of daptomycin, preferably in association with rifampicin, when the use of vancomycin is not possible or contraindicated.

Topics: Acetamides; Anti-Bacterial Agents; Daptomycin; Drug Resistance, Bacterial; Endocarditis; Gram-Positive Bacterial Infections; Humans; Linezolid; Minocycline; Oxazolidinones; Tigecycline; Virginiamycin

The treatment of recurrent prosthetic valve endocarditis is extremely difficult. Heart transplantation (HT) may save the patient's life. Recurrent endocarditis, however, can occur after HT. This report described a patient who had under gone four conventional valve surgeries and three HTs successfully. In May 2000, a 14-year-old boy suffered from endocarditis with severe aortic valve regurgitation. He underwent aortic valve replacement (AVR) at another hospital. Due to prosthetic valve endocarditis, he displayed a severe paravalvular leakage and was transferred to our hospital where he underwent Bentall's operation in October 2000. Despite a full antibiotic course, he experienced a relapse of the prosthetic endocarditis with significant deterioration of the heart function and a progressively more severe paravalvular leak. Considering the difficulties of repair and the poor heart function, he underwent an HT in June 2003 and recovered well. Unfortunately, endocarditis with aortic valve regurgitation attacked him again after 3 years. Remarkably, all blood cultures were negative. A second AVR was performed in October 2006 with a Second Bentall's procedure 1 year later in 2007. In November 2009, the patient suddenly displayed cardiogenic shock with collapse. He was transferred to our hospital and needed extracorporcal membrane oxygenation (ECMO) support. Two days later, he underwent a second HT. However, the donor heart was nonfunctional due to the prolonged ischemia time. ECMO support was continuously needed after the HT. A third HT was performed successfully 10 days later. Due to previous reported experiences of culture-negative endocarditis, minocycline was prescribed twice daily continuously after the third HT/seventh cardiac surgery. The patient was discharged 2 months later. To date he takes minocycline every day and lives a healthy life.

Topics: Adolescent; Anti-Bacterial Agents; Aortic Valve Insufficiency; Drug Administration Schedule; Endocarditis; Heart Transplantation; Heart Valve Prosthesis; Heart Valve Prosthesis Implantation; Humans; Male; Minocycline; Prosthesis-Related Infections; Recurrence; Reoperation; Time Factors; Treatment Outcome

The activity of tigecycline (GAR-936), a novel glycylcycline, was investigated in vitro and in experimental endocarditis due to the susceptible Enterococcus faecalis JH2-2 strain, its VanA type transconjugant BM4316, and a clinical VanA type strain, E. faecium HB217 resistant to tetracycline. MICs of GAR-936 were 0.06 micro g/ml for the three strains. In vitro pharmacodynamic studies demonstrated a bacteriostatic effect of GAR-936 that was not enhanced by increasing concentrations to more than 1 micro g/ml and a postantibiotic effect ranging from 1 to 4.5 h for concentrations of 1- to 20-fold the MIC. Intravenous injection of [(14)C]GAR-936 to five rabbits with enterococcal endocarditis sacrificed 30 min, 4 h, or 12 h after the end of the infusion evidenced a lower clearance of GAR-936 from aortic vegetations than from serum and a homogeneous diffusion of GAR-936 into the vegetations. In rabbits with endocarditis, GAR-936 (14 mg/kg of body weight twice a day [b.i.d.]) given intravenously for 5 days was bacteriostatic against both strains of E. faecalis. Against E. faecium HB217, bacterial counts in vegetations significantly decreased during therapy (P < 0.01), and the effect was similar with GAR-936 at 14 mg/kg b.i.d., 14 mg/kg once a day (o.d.), and 7 mg/kg o.d., which provided concentrations in serum constantly above the MIC. Mean serum elimination half-life ranged from 3.3 to 3.6 h. No GAR-936-resistant mutants were selected in vivo with any regimen. We concluded that the combination of prolonged half-life, significant postantibiotic effect, and good and homogeneous diffusion into the vegetations may account for the in vivo activity of GAR-936 against enterococci susceptible or resistant to glycopeptides and tetracyclines, even when using a o.d. regimen in rabbits.

Topics: Animals; Area Under Curve; Autoradiography; Endocarditis; Enterococcus faecalis; Enterococcus faecium; Half-Life; Metabolic Clearance Rate; Microbial Sensitivity Tests; Minocycline; Rabbits; Tigecycline; Tissue Distribution

To determine the efficacy of antibiotic catheter lock solution in preventing catheter-related infections, silicone catheters were tunneled and inserted into the jugular veins of 18 rabbits. The catheters were challenged with an intraluminal injection of 10(5) CFU of slime-producing Staphylococcus epidermidis in 0.1 ml of water. The catheters were maintained on heparin (100 IU/ml) flush for the first 3 days. On day 3, quantitative blood samples for culture were obtained from the catheters and ear veins, which documented catheter-related bacteremia, and the rabbits were randomized to have their catheters flushed as follows: five animals were continued on heparin (100 IU/ml), five animals received vancomycin (3 mg/ml) with heparin (100 IU/ml), and eight animals received 3 mg of minocycline per ml with 30 mg of EDTA per ml (M-EDTA). All animals were killed at day 7. Blood, catheters, jugular veins, and heart valves were cultured quantitatively. Animals maintained on heparin developed catheter-related colonization, bacteremia, septic phlebitis, and endocarditis. Vancomycin-heparin partially prevented catheter colonization, bacteremia, and phlebitis (P = 0.2). M-EDTA completely prevented catheter colonization, catheter-related bacteremia, and phlebitis in all of the animals (P < 0.01). Tricuspid endocarditis was equally prevented by vancomycin-heparin and M-EDTA (P < or = 0.06). In conclusion, the M-EDTA catheter flush solution was highly efficacious in preventing catheter-related colonization, bacteremia, septic phlebitis, and endocarditis in rabbits.

Topics: Animals; Anti-Bacterial Agents; Bacteremia; Catheterization; Disease Models, Animal; Edetic Acid; Endocarditis; Male; Minocycline; Phlebitis; Prosthesis-Related Infections; Rabbits