Antimicrobial agents and chemotherapy
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Antimicrob. Agents Chemother. · Nov 1993
Comparative StudyTherapy of experimental murine brucellosis with streptomycin alone and in combination with ciprofloxacin, doxycycline, and rifampin.
The in vivo efficacy of streptomycin (STR), doxycycline (DOX), rifampin (RIF), ciprofloxacin (CIP), and their combinations was evaluated for a Brucella melitensis experimental infection in a mouse model. Animals were infected with 2 x 10(4) to 4 x 10(4) CFU of B. melitensis intraperitoneally on day 0 and were randomized to receive, starting on day 7, STR alone at 75, 150, or 300 mg/kg of body weight per day intraperitoneally or DOX at 6 mg/kg/day orally, RIF at 3 mg/kg/day orally, or CIP at 200 mg/kg/day orally, each of the last three drugs alone or in combination with STR at 75, 150, or 300 mg/kg/day, for 14 days. Therapy failure (defined as nonsterile spleens) was observed in all animals treated with STR at all doses and with CIP given as monotherapy. ⋯ All animals treated with DOX or RIF combined with any STR dose were cured, but none of the animals receiving the STR-CIP combinations was cured, and the splenic CFU remained similar to those in the controls. These results demonstrate that the combinations DOX-STR and RIF-STR are synergistic against B. melitensis, while the combination STR-CIP is indifferent and ineffective in the management of acute murine brucellosis. The results also appear to support the clinical superiority of combination drug therapy over monotherapy.
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Antimicrob. Agents Chemother. · Sep 1993
Activity of a nitrofurazone matrix urinary catheter against catheter-associated uropathogens.
Nitrofurazone-coated urinary catheter segments inhibited 51 (75%) of 70 urinary bacterial isolates from patients with indwelling catheters. Inhibition zones correlated significantly with the nitrofurazone MIC (r2 = 0.79, P = 0.0001). All strains except the Pseudomonas spp. were inhibited by < or = 64 micrograms of nitrofurazone per ml. MICs of nitrofurazone and nitrofurantoin correlated significantly (r2 = 0.93, P = 0.0001).
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Antimicrob. Agents Chemother. · Sep 1993
Randomized Controlled Trial Comparative Study Clinical TrialQuinolones in treatment of human brucellosis: comparative trial of ofloxacin-rifampin versus doxycycline-rifampin.
Quinolones have been reported to be active against Brucella species in vitro. In this prospective randomized study, the efficacy and safety of the combination of ofloxacin plus rifampin were compared with the efficacy and safety of doxycycline plus rifampin, both combinations administered for a 6-week period in treatment of brucellosis. Sixty-one patients were enrolled in the study, and 49 had blood or bone marrow cultures positive for Brucella melitensis. ⋯ There was one therapeutic failure in the ofloxacin-rifampin treatment group, and one patient from each group relapsed (3.3% of those in the doxycycline-rifampin treatment group versus 3.2% of those in the ofloxacin-rifampin treatment group). Gastric discomfort was the major side effect observed in 13 patients (43.3%) who received doxycycline plus rifampin, whereas only 2 patients (6.5%) treated with ofloxacin plus rifampin complained of gastric irritation. These results suggest that the combination of ofloxacin plus rifampin administered for 6 weeks is as effective as doxycycline plus rifampin given for the same period, regardless of the presence of complications of the disease.
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Antimicrob. Agents Chemother. · Mar 1993
Activity of ampicillin-sulbactam and oxacillin in experimental endocarditis caused by beta-lactamase-hyperproducing Staphylococcus aureus.
Using a rat model of aortic valve infective endocarditis, we previously found that oxacillin was equally effective against an oxacillin-susceptible strain of Staphylococcus aureus and a beta-lactamase-hyperproducing borderline oxacillin-susceptible strain of S. aureus; also, ampicillin-sulbactam was less effective than oxacillin against both isolates and at low doses was less effective against the borderline-susceptible strain than against the fully oxacillin-susceptible strain (C. Thauvin-Eliopoulos, L. B. ⋯ However, for any individual sulbactam dosage, the model of administration (continuous versus intermittent infusion) did not affect the activity of the regimen. When additional strains were used in the model, oxacillin and ampicillin-sulbactam (1,000 plus 2,000 mg/kg/day) were equally effective against both oxacillin-susceptible and borderline oxacillin-resistant strains of S. aureus. These results support the predictions that oxacillin would be clinically effective in the treatment of infections caused by borderline oxacillin-susceptible strains of S. aureus and that, except at very low doses, ampicillin-sulbactam would also be as effective against borderline-susceptible strains as against fully oxacillin-susceptible strains of S. aureus.
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Antimicrob. Agents Chemother. · Feb 1993
Comparative StudyTherapeutic effects of a human antiflagella monoclonal antibody in a neutropenic murine model of Pseudomonas aeruginosa pneumonia.
Human immunoglobulin G1 (IgG1) monoclonal antibodies (MAbs) reactive with type-specific Pseudomonas aeruginosa lipopolysaccharide (LPS) and flagella were compared for their protective activities against Fisher immunotype 2 P. aeruginosa pneumonia in neutropenic mice. The activity of the antiflagella MAb at a dose of 500 micrograms per mouse was comparable to that of the anti-LPS MAb at the same dose. In vivo protection was correlated with bacterial density in the lung tissue and blood of infected mice. ⋯ The additive effects between the antiflagella MAb and sparfloxacin at sub-MICs on the inhibitory effects of bacterial motility supported the in vivo effect of the combination. These data suggest that human isotype-matched antiflagella and anti-LPS MAbs have similar protective activities against Pseudomonas pneumonia in neutropenic mice, despite discrete mechanisms of antibody-matched protection. In addition, in vivo synergy was demonstrated between antiflagella MAb and sparfloxacin in this model.