The beneficial effects of therapy combining an antibiotic and dexamethasone have been reported in human studies on meningitis and in experimental studies on septic arthritis, nephritis, and endophthalmitis. Since most patients with staphylococcal endocarditis need a combination of medical and surgical treatment, the purpose of this study was to determine whether the addition of dexamethasone to vancomycin has any beneficial effect regarding the degree of valve tissue damage or the course of experimental aortic valve endocarditis caused by a methicillin-resistant strain of Staphylococcus aureus. Rabbits with catheter-induced aortic valve vegetations were randomly assigned to a control group and to groups receiving dexamethasone (0.

Using a rabbit model of aortic valve endocarditis, we studied the efficacy of vancomycin alone or in combination with netilmicin and/or rifampin against a methicillin-and gentamicin-resistant strain of Staphylococcus aureus (MGRSA). Antibiotics were given for 6 or 12 days, as follows: vancomycin (15 mg/kg of body weight every 12 h [BID] intravenously), vancomycin plus netilmicin (2.5 mg/kg BID intramuscularly), vancomycin plus rifampin (10 mg/kg BID intramuscularly), and vancomycin plus netilmicin plus rifampin at the same routes, dosages, and schedules mentioned above. Netilmicin was given to two additional groups at a higher dosage (6 mg/kg every 24 h intramuscularly) alone or in combination with vancomycin (15 mg/kg BID intravenously) for 12 days. All regimens resulted in undetectable bacterial counts in a significant proportion of vegetations (except netilmicin alone) or reduced the bacterial counts in the vegetations compared with the counts in the untreated controls (P < 0.01 to P < 0.001). No resistance to rifampin or netilmicin developed during therapy. It is concluded that in the treatment of experimental aortic valve endocarditis caused by MGRSA (i) vancomycin as monotherapy is as efficacious as the triple combination, (ii) the addition of netilmicin (once daily or BID) to vancomycin does not improve the efficacy of the latter antibiotic, even in the presence of rifampin, and (iii) a 12-day course is more effective than a 6-day one, but not at a statistically significant level.Staphylococcus aureus is the second most common cause of infective endocarditis. It affects either native (25 to 35%) or prosthetic valves and is the most common organism (70%) recovered from intravenous drug addicts with endocarditis (23). Methicillin-resistant S. aureus (MRSA) strains have spread worldwide, and the frequency of their isolation has recently increased steeply (5, 12). MRSA isolates should be considered resistant to all ␤-lactams, and very often these organisms are cross resistant to gentamicin; however, they are uniformly susceptible to vancomycin and are usually susceptible to rifampin (5, 23).Vancomycin is clearly the drug of choice for the treatment of infections caused by MRSA as well as an alternative to betalactam antibiotics for the treatment of methicillin-susceptible S. aureus infections, particularly in patients allergic to ␤-lactams (8, 24). Nevertheless, there have been several reports of therapeutic failures in patients with S. aureus endocarditis treated with vancomycin as monotherapy (18,33,35). Even in animal models, vancomycin has been found to be ''surprisingly unsuccessful'' against MRSA endocarditis (9). On the other hand, the therapeutic role of rifampin in MRSA endocarditis is controversial (4), and today the majority of MRSA endocarditis strains are also gentamicin resistant (23). Because netilmicin (i) has been found to be active in vitro against MRSA strains cross resistant to gentamicin (16a), (ii) it possesses decreased nephrotoxic potential in comparison with that of gentamicin (11,22,...

The in vivo efficacies of ceftazidime, aztreonam, and the combinations of ceftazidime with amikacin and aztreonam with amikacin were studied in the rabbit left-sided endocarditis model by using two strains of Pseudomonas aeruginosa, one multisusceptible and one multiresistant, in a total of 156 animals. Antibiotics were given intramuscularly for 10 days, as follows: amikacin, 7 mg/kg of body weight every 8 (12,13,21,22,29

Azithromycin and ampicillin protected 94 and 72% of animals challenged with Streptococcus oralis, respectively (P ‫؍‬ 0.177), while azithromycin and vancomycin protected 59 and 94% of the methicillin-resistant Staphylococcus aureus (MRSA)-challenged animals, respectively (P ‫؍‬ 0.018). Azithromycin is effective in preventing experimental streptococcal endocarditis, but against MRSA it is less effective than vancomycin.Azithromycin (AZM) differs from other macrolide antibiotics in that it has unusual pharmacokinetics characterized by rapid tissue penetration with simultaneous low levels in serum (5). The favorable tissue pharmacokinetics makes AZM a good candidate for prophylaxis against infective endocarditis (IE). This study was designed to evaluate the prophylactic efficacy of AZM against the most common etiologic agents of IE, namely, viridans group streptococci (Streptococcus oralis) and Staphylococcus aureus.The two microorganisms used in this study were isolated from blood cultures of patients with endocarditis and were identified by standard methods. MICs and minimal bactericidal concentrations (MBCs) of AZM, vancomycin (VAN), oxacillin (plus 2% NaCl), and ampicillin (AMP) were determined by a microdilution technique in 0.1-ml volumes, as described previously (12). Nonbacterial thrombotic endocarditis of the aortic valve was induced in female white rabbits weighing 2.3 to 3.5 kg by using the model described by Perlman and Freedman, with the polyethylene catheter left in place throughout the experiment (13). Twenty-four hours after catheterization, rabbits were randomly assigned to a control group, a group receiving a single dose of 50 mg of AZM per kg of body weight per os, a group receiving a single dose of 30 mg of VAN (supplied by Eli Lilly, Indianapolis, Ind.) per kg of body weight intravenously, and a group receiving a single dose of 40 mg of AMP (supplied by Bristol-Myers, Squibb, Athens, Greece) per kg of body weight intravenously. AMP or VAN was given for prophylaxis against S. oralis or S. aureus, respectively. AZM was supplied by Pfizer (Groton, Conn.) as a suspension at a concentration of 40 mg/ml and was given to the animals through an esophageal catheter (Nelaton catheter no. 10; Uno Plast, Denmark) after the intramuscular administration of 25 mg of ketamine HCl per kg. The dose of AZM used was chosen because in pilot studies it was found to achieve peak levels in serum in rabbits similar to those obtained in humans after a single per os dose of 500 mg (5). The doses of VAN and AMP were chosen because they have been used in previous studies of successful endocarditis prophylaxis (11). Animals treated with AZM and animals treated with AMP or VAN were challenged 1 and 0.5 h later, respectively, with an inoculum of ϳ10 7 CFU of S. oralis or of ϳ10 6 CFU of S. aureus. The inocula were suspended in 1-ml volumes of saline and injected via the marginal ear vein. The rabbits were sacrificed 5 days (120 h) after bacterial challenge. The processing of vegetations and criteria for IE were described prev...

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