Jan Verhaegen

Inhibition of staphylothrombin by dabigatran reduces Staphylococcus aureus virulence

Summary.u2002 Background:u2002Staphylocoagulase and von Willebrand binding protein (VWbp) bind to prothrombin to form the staphylothrombin complex that converts fibrinogen into fibrin. Objectives:u2002To study the role of staphylothrombin and its inhibition by dabigatran on Staphylococcus aureus virulence. Methods:u2002We studied the effect of staphylothrombin inhibition on bacterial attachment to polystyrene surfaces, leukocyte activation and bactericidal activity for S. aureus ATCC 25923, S. aureus Newman, and staphylocoagulase‐ and VWbp‐negative S. aureus Newman mutants in the presence or absence of prothrombin and fibrinogen. We measured the abscess size after subcutaneous (s.c.) injection of S. aureus ATCC 25923 and S. aureus Newman, as well as an S. aureus Newman mutant strain lacking staphylocoagulase and VWbp, in mice treated with either dabigatran or placebo. Results:u2002Staphylothrombin‐mediated fibrin increased the association of S. aureus to polystyrene surfaces and reduced the bactericidal activity of leukocytes. The absence or inhibition of staphylothrombin decreased the bacterial association, enhanced leukocyte activation and reduced bacterial survival in vitro. Abscess size was smaller in mice treated with dabigatran or infected with a coagulase‐negative mutant. Conclusion:u2002Inhibition or the absence of staphylothrombin reduced S. aureus virulence in in vitro and in vivo models.

Capsular types and antibiotic sensitivity of pneumococci isolated from patients with serious infections in Belgium 1980 to 1988

A total of 2,765 strains ofStreptococcus pneumoniae isolated in more than 60 Belgian laboratories from blood or normally sterile body fluids between 1 November 1980 and 31 December 1988 were serotyped. From January 1983 onwards susceptibility of the strains to antimicrobial agents was also tested. The 2,765 isolates belonged to 57 of the 84 currently identified serotypes. Overall, 94 % of the strains were represented in the current 23-valent vaccine. The remaining 6 % of strains were distributed among 18 serotypes. More than 84 % of the middle ear fluid isolates came from children under ten years. Meningitis was commonest in children under five years and in adults over sixty years. Two-thirds of pneumococcal bacteremia isolates came from patients over 50 years. Of 1,933 isolates tested for susceptibility to antibiotics, 335 (17 %) were resistant to one or more of the agents tested (tetracycline, erythromycin, chloramphenicol, penicillin). Only 19 strains were relatively resistant to penicillin, while six were fully resistant. Resistance to erythromycin increased significantly from 5.2 % in 1986 to 11.5 % in 1988. The resistance ofStreptococcus pneumoniae to other antimicrobial agents did not change significantly during the study period. There was no relationship between age group and resistance to any of the agents tested.

Kosteneffectiviteit Van Vaccinatie Tegen Pneumokokkenbacteriëmie Bij Bejaarden: Resultaten Voor België

Abstract Background: Several studies have shown that pneumococcal vaccination of older persons would be cost-effective in preventing pneumococcal pneumonia, but evidence of clinical protection for this condition is uncertain. Given much better evidence of vaccination effectiveness against invasive disease, studies showing that vaccination is cost-effective in preventing invasive disease alone could provide strong support for public policies to vaccinate older persons. Methods: We examined the cost-effectiveness of preventing invasive pneumococcal infection by vaccination with the 23-valent pneumococcal polysaccharide vaccine of persons ≥ 65 years in age in Belgium. The direct medical costs expressed per quality adjusted life year (QALYs) of a cohort of vaccinated persons was compared with the costs per QALY in a cohort of persons who are not vaccinated. Results: Preventing invasive pneumococcal infections by vaccinating elderly persons clearly benefits peoples health. By vaccinating 10,000 persons over 65 years of age, approximately eight QALYs can be gained compared with no vaccination. Achieving these health benefits however requires additional costs,: 30,000 ECU per QALY gained. The cost-effectiveness ratio is slightly better (i.e. 25,000 ECU per QALY) for the age group 65-75 years, and slightly worse (i.e. 35,000 ECU per QALY ) for the age group 75-84 years. It increases sharply to 77,000 ECU per QALY for the persons over 85 years of age. An extensive one-dimensional sensitivity analysis did not greatly affect these results. If vaccination is also clinically effective in preventing pneumococcal pneumonia, vaccinating all elderly persons is cost saving. Conclusion: Using empirical epidemiological data, pneumococcal vaccination to prevent invasive pneumococcal disease is acceptably to moderately cost-effective in Belgium. On the basis of our findings, we believe public health authorities should consider policies for encouraging pneumococcal vaccination for all persons ≥ 65 years in age.

In vitro activity of the new ketolide telithromycin and other antibiotics against Streptococcus pneumoniae in Belgium

Abstract In Belgium more than 17 % of the invasive pneumococci are not susceptible to penicillin, and more than 38 % not to macrolides. The most prevalent mechanism of macrolide resistance in Europe is modification of the drug target site leading to cross-resistance to lincosamides and group B streptogramines (MLSB resistance). Telithromycin is the first antibiotic of the family of ketolides, which differ from erythromycin by having a 3-keto group instead of the neutral sugar L-cladinose. We tested the susceptibility of 637 pneumococci, recently isolated from patients in Belgium, to telithromycin and five other antibiotics. Data generated by this study show that telithromycin inhibits 98.4 % of pneumococci at a breakpoint concentration of 1 mg/L in spite of a high percentage ( >30 %) of strains with the MLSB constitutive type of resistance. Susceptibilities to the five comparator drugs were : penicillin (81.8 %), tetracycline (67.0 %), levofloxacin (98.9 %), erythromycin (61.5 %) and clindamycin (66.6 %). Consequently telithromycin looks to have considerable potential for the empiric treatment of community-acquired respiratory tract infections.