Antimicrobial agents and chemotherapy
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Antimicrob. Agents Chemother. · Jun 2002
Comparative StudyEfficacy of colistin versus beta-lactams, aminoglycosides, and rifampin as monotherapy in a mouse model of pneumonia caused by multiresistant Acinetobacter baumannii.
The treatment of life-threatening infections due to carbapenem-resistant Acinetobacter baumannii has become a serious challenge for physicians worldwide. Often, only colistin shows in general good in vitro activity against these carbapenem-resistant strains, but its antibacterial efficacy in comparison with the antibiotics most used in clinical practice is not well known. We studied the efficacy of colistin versus those of imipenem, sulbactam, tobramycin, and rifampin in an experimental pneumonia model with immunocompetent mice. ⋯ On the contrary, colistin showed the weakest antibacterial effect among the antibiotics tested, both in killing curves and in the in vivo model (-2.39 log(10) CFU/ml; P < 0.05). We conclude that colistin did not appear as a good option for treatment of patients with pneumonia due to carbapenem-resistant A. baumannii strains. Other alternatives, including combinations with rifampin, may offer better therapeutic profiles and thus should be studied.
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Antimicrob. Agents Chemother. · Mar 2002
Risk factors for piperacillin-tazobactam-resistant Pseudomonas aeruginosa among hospitalized patients.
Antimicrobial resistance is an emerging problem with Pseudomonas aeruginosa. This study determined risk factors for the recovery of piperacillin-tazobactam-resistant P. aeruginosa from clinical cultures from hospitalized patients. A case-control study design was used to compare two groups of case patients with control patients. ⋯ In this study, antibiotics associated with piperacillin-tazobactam-susceptible P. aeruginosa were different from antibiotics associated with piperacillin-tazobactam-resistant P. aeruginosa. Piperacillin-tazobactam was a strong risk factor for piperacillin-tazobactam-resistant P. aeruginosa. Our results suggest that the nosocomial isolation of piperacillin-tazobactam-resistant P. aeruginosa may be affected by multiple antibiotics.
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Antimicrob. Agents Chemother. · Jan 2002
Antifungal efficacy of caspofungin (MK-0991) in experimental pulmonary aspergillosis in persistently neutropenic rabbits: pharmacokinetics, drug disposition, and relationship to galactomannan antigenemia.
The antifungal efficacy, pharmacokinetics, and safety of caspofungin (CAS) were investigated in the treatment and prophylaxis of invasive pulmonary aspergillosis due to Aspergillus fumigatus in persistently neutropenic rabbits. Antifungal therapy consisted of 1, 3, or 6 mg of CAS/kg of body weight/day (CAS1, CAS3, and CAS6, respectively) or 1 mg of deoxycholate amphotericin B (AMB)/kg/day intravenously for 12 days starting 24 h after endotracheal inoculation. Prophylaxis (CAS1) was initiated 4 days before endotracheal inoculation. ⋯ The CAS1, CAS3, and CAS6 dose regimens demonstrated dose-proportional exposure and maintained drug levels in plasma above the MIC for the entire 24-h dosing interval at doses that were > or =3 mg/kg/day. As serial galactomannan antigen levels may be used for therapeutic monitoring, one should be aware that profoundly neutropenic patients receiving echinocandins for aspergillosis might have persistent galactomannan antigenemia despite clinical improvement. CAS improved survival, reduced pulmonary injury, and caused dose-dependent hyphal damage but with no reduction in residual fungal burden or galactomannan antigenemia in persistently neutropenic rabbits with invasive pulmonary aspergillosis.
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Antimicrob. Agents Chemother. · Dec 2001
Effectiveness of once-weekly rifapentine and moxifloxacin regimens against Mycobacterium tuberculosis in mice.
Mice infected with 1.6 x 10(7) CFU of Mycobacterium tuberculosis were treated 14 days later for 6 months with a regimen of once-weekly 10 mg of rifapentine and 75 mg of isoniazid per kg of body weight supplemented with either 150 mg of streptomycin per kg or 100 mg of moxifloxacin per kg during either both the 2-week daily initial and once-weekly continuation phases or only in the daily 2-week initial phase. On completion of treatment, all lung cultures were negative, except for three mice, each with a single colony: two whose rifapentine-isoniazid regimen was supplemented with streptomycin during the whole course of therapy and one whose rifapentine-isoniazid regimen had no initial daily phase, but was supplemented with streptomycin and moxifloxacin during the whole course of therapy. After 3 months of follow-up, positive lung cultures were obtained from 61 and 56% of mice supplemented with streptomycin during either the full course of therapy or only the daily 2-week initial phase, respectively, and 15 and 50% of mice supplemented with moxifloxacin during either the full course of therapy or only the daily 2-week initial phase, respectively. These results suggest that moxifloxacin has sterilizing activity against M. tuberculosis.
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Antimicrob. Agents Chemother. · Nov 2001
Clinical TrialPharmacokinetics of cefepime during continuous renal replacement therapy in critically ill patients.
The pharmacokinetics of cefepime were studied in 12 adult patients in intensive care units during continuous venovenous hemofiltration (CVVH) or continuous venovenous hemodiafiltration (CVVHDF) with a Multiflow60 AN69HF 0.60-m(2) polyacrylonitrile hollow-fiber membrane (Hospal Industrie, Meyzieu, France). Patients (mean age, 52.0 +/- 13.0 years [standard deviation]; mean weight, 96.7 +/- 18.4 kg) received 1 or 2 g of cefepime every 12 or 24 h (total daily doses of 1 to 4 g/day) by intravenous infusion over 15 to 30 min. Pre- and postmembrane blood (serum) samples and corresponding ultrafiltrate or dialysate samples were collected 1, 2, 4, 8, and 12 or 24 h (depending on dosing interval) after completion of the drug infusion. ⋯ Cefepime clearance was substantially increased during both CVVH and CVVHDF, with membrane clearance representing 40 and 59% of CL(S), respectively. The results of this study confirm that continuous renal replacement therapy contributes substantially to total CL(S) of cefepime and that CVVHDF appears to remove cefepime more efficiently than CVVH. Cefepime doses of 2 g/day (either 2 g once daily or 1 g twice daily) appear to achieve concentrations adequate to treat most common gram-negative pathogens (MIC