Pharmacodynamic evaluation of extending the administration time of meropenem using a Monte Carlo simulation.
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A Monte Carlo simulation demonstrated that 1 g of meropenem (MEM) every 8 h (q8h) (3-h infusion) has a higher target attainment rate against Pseudomonas aeruginosa than either 500 mg of MEM q8h (3-h infusion) or 0.5 g of imipenem-cilastatin (I-C) q6h (1-h infusion). For other pathogens, 500 mg of MEM q8h was equivalent or superior to I-C. (+info)
Quinolones for treatment of nosocomial pneumonia: a meta-analysis.
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Although quinolones are often used to treat nosocomial pneumonia (NP), there have been few trials documenting their efficacy in treating NP. Given the growing use of quinolones and issues regarding resistance, we conducted a meta-analysis of all trials of quinolones for treatment of NP. We identified 5 randomized trials comparing quinolones with other agents used to treat NP. The studies varied in both quality and sample size and included a total of nearly 1200 subjects. Four of the 5 trials used ciprofloxacin, administered every 8 h, whereas the fifth used levofloxacin administered daily. In 3 trials, the comparator agent was imipenem-cilistatin, whereas, in 2 trials, ceftazadime was the comparator agent. The efficacy of quinolones and comparator antibiotics was similar, with a pooled odds ratio for clinical cure of 1.12 (95% confidence interval, 0.80-1.55). Neither microbiological eradication rates nor mortality rates varied on the basis of antimicrobial selection. (+info)
Levofloxacin for treatment of ventilator-associated pneumonia: a subgroup analysis from a randomized trial.
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Ventilator-associated pneumonia (VAP) remains a significant challenge in critical care. We conducted a secondary analysis of a multicenter, prospective, randomized trial comparing levofloxacin (750 mg iv q24h) with imipenem-cilastatin (500-1000 mg iv q6-8h) for treatment of nosocomial pneumonia and focused on the subgroup of patients with VAP. The study cohort included 222 patients, with half (111) of the patients assigned to each treatment group. The patients in both groups were similar with respect to age, severity of illness, and duration of mechanical ventilation before the onset of VAP. Among the intention-to-treat population, clinical success was achieved in 58.6% of patients receiving levofloxacin, compared with 63.1% of patients receiving imipenem-cilastatin (P=.49; 95% confidence interval for the difference, -8.77% to 17.79%). Microbiological success and 28-day mortality rates were also comparable. Multivariate analysis demonstrated that assignment to antibiotic treatment (i.e., levofloxacin vs. imipenem-cilastatin) was not predictive of outcomes, thus suggesting that the treatment regimens were equivalent. Both levofloxacin and imipenem-cilastatin regimens were well tolerated and had similar adverse event profiles. (+info)
Pharmacokinetics and pharmacodynamics of imipenem during continuous renal replacement therapy in critically ill patients.
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The pharmacokinetics of imipenem were studied in adult intensive care unit (ICU) patients during continuous venovenous hemofiltration (CVVH; n=6 patients) or hemodiafiltration (CVVHDF; n=6 patients). Patients (mean+/-standard deviation age, 50.9+/-15.9 years; weight, 98.5+/-15.9 kg) received imipenem at 0.5 g every 8 to 12 h (total daily doses of 1 to 1.5 g/day) by intravenous infusion over 30 min. Pre- and postmembrane blood (plasma) and corresponding ultrafiltrate or dialysate samples were collected 1, 2, 4, and 8 or 12 h (depending on dosing interval) after completion of the drug infusion. Drug concentrations were measured using validated high-performance liquid chromatography methods. Mean systemic clearance (CL(S)) and elimination half-life (t1/2) of imipenem were 145+/-18 ml/min and 2.7+/-1.3 h during CVVH versus 178+/-18 ml/min and 2.6+/-1.6 h during CVVHDF, respectively. Imipenem clearance was substantially increased during both CVVH and CVVHDF, with membrane clearance representing 25% and 32% of CL(S), respectively. The results of this study indicate that CVVH and CVVHDF contribute to imipenem clearance to a greater degree than previously reported. Imipenem doses of 1.0 g/day appear to achieve concentrations adequate to treat most common gram-negative pathogens (MIC up to 2 microg/ml) during CVVH or CVVHDF, but doses of 2.0 g/day or more may be required to adequately treat and prevent resistance in pathogens with higher MICs (MIC=4 to 8 microg/ml). Higher doses should only be used after consideration of potential central nervous system toxicities or other risks of therapy in these severely ill patients. (+info)
The efficacy and safety of tigecycline for the treatment of complicated intra-abdominal infections: analysis of pooled clinical trial data.
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This pooled analysis includes 2 phase 3, double-blind trials designed to evaluate the safety and efficacy of tigecycline, versus that of imipenem-cilastatin, in 1642 adults with complicated intra-abdominal infections. Patients were randomized to receive either tigecycline (initial dose of 100 mg, followed by 50 mg intravenously every 12 h) or imipenem-cilastatin (500/500 mg intravenously every 6 h) for 5-14 days. The primary end point was the clinical response at the test-of-cure visit (12-42 days after therapy) in the co-primary end point microbiologically evaluable and microbiological modified intent-to-treat populations. For the microbiologically evaluable group, clinical cure rates were 86.1% (441/512) for tigecycline, versus 86.2% (442/513) for imipenem-cilastatin (95% confidence interval for the difference, -4.5% to 4.4%; P < .0001 for noninferiority). Clinical cure rates in the microbiological modified intent-to-treat population were 80.2% (506/631) for tigecycline, versus 81.5% (514/631) for imipenem-cilastatin (95% confidence interval for the difference, -5.8% to 3.2%; P < .0001 for noninferiority). Nausea (24.4% tigecycline, 19.0% imipenem-cilastatin [P = .01]), vomiting (19.2% tigecycline, 14.3% imipenem-cilastatin [P = .008]), and diarrhea (13.8% tigecycline, 13.2% imipenem-cilastatin [P = .719]) were the most frequently reported adverse events. This pooled analysis demonstrates that tigecycline was efficacious and well tolerated in the treatment of patients with complicated intra-abdominal infections. (+info)
A multicenter trial of the efficacy and safety of tigecycline versus imipenem/cilastatin in patients with complicated intra-abdominal infections [Study ID Numbers: 3074A1-301-WW; ClinicalTrials.gov Identifier: NCT00081744].
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BACKGROUND: Complicated intra-abdominal infections (cIAI) remain challenging to treat because of their polymicrobial etiology including multi-drug resistant bacteria. The efficacy and safety of tigecycline, an expanded broad-spectrum glycylcycline antibiotic, was compared with imipenem/cilastatin (IMI/CIS) in patients with cIAI. METHODS: A prospective, double-blind, multinational trial was conducted in which patients with cIAI randomly received intravenous (IV) tigecycline (100 mg initial dose, then 50 mg every 12 hours [q12h]) or IV IMI/CIS (500/500 mg q6h or adjusted for renal dysfunction) for 5 to14 days. Clinical response at the test-of-cure (TOC) visit (14-35 days after therapy) for microbiologically evaluable (ME) and microbiological modified intent-to-treat (m-mITT) populations were the co-primary efficacy endpoint populations. RESULTS: A total of 825 patients received >or= 1 dose of study drug. The primary diagnoses for the ME group were complicated appendicitis (59%), and intestinal (8.8%) and gastric/duodenal perforations (4.6%). For the ME group, clinical cure rates at TOC were 80.6% (199/247) for tigecycline versus 82.4% (210/255) for IMI/CIS (95% CI -8.4, 5.1 for non-inferiority tigecycline versus IMI/CIS). Corresponding clinical cure rates within the m-mITT population were 73.5% (227/309) for tigecycline versus 78.2% (244/312) for IMI/CIS (95% CI -11.0, 2.5). Nausea (31.0% tigecycline, 24.8% IMI/CIS [P = 0.052]), vomiting (25.7% tigecycline, 19.4% IMI/CIS [P = 0.037]), and diarrhea (21.3% tigecycline, 18.9% IMI/CIS [P = 0.435]) were the most frequently reported adverse events. CONCLUSION: This study demonstrates that tigecycline is as efficacious as imipenem/cilastatin in the treatment of patients with cIAI. (+info)
Comparison of piperacillin/tazobactam and imipenem/cilastatin, both in combination with tobramycin, administered every 6 h for treatment of nosocomial pneumonia.
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This randomized, double-blind, multicenter study compared the efficacy and safety of piperacillin/tazobactam (P/T) and imipenem/cilastatin (IMP), both in combination with an aminoglycoside, in hospitalized patients with acute nosocomial pneumonia (NP). Patients with acute NP, defined as pneumonia with symptoms > or = 48 h after admission or < or =7 days after hospital discharge, received infusions of 4 g/500 mg P/T or 500 mg/500 mg IMP every 6 h. Endpoints were clinical cure and microbiological response rates; pathogen eradication rates; length of hospital stay; hospital readmissions; and adverse events (AEs). Of 437 patients in the intent-to-treat population, 197 were efficacy evaluable. At test-of-cure, response rates were similar between groups. Within the efficacy evaluable population, 68% of P/T patients and 61% of IMP patients were clinically cured (P = 0.256). Microbiological responses for P/T and IMP patients were: eradication, 64% versus 59%; persistence, 29% versus 21%; relapse, 0% versus 5%; and superinfection, 7% versus 15%, respectively. Gram-positive isolates were eradicated in 83% of P/T patients and 75% of IMP patients; Gram-negative pathogens were eradicated in 72% of P/T patients and 77% of IMP patients. Treatment groups had similar number of mean hospital days, readmission rates, and frequency of AEs. This study showed that P/T administered four times per day was as safe and efficacious as IMP in treating hospitalized patients with NP. (+info)
Comparison of efficacy of cefoperazone/sulbactam and imipenem/cilastatin for treatment of Acinetobacter bacteremia.
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Multiple antibiotic resistance threatens successful treatment of Acinetobacter baumannii infections worldwide. Increasing interest in the well-known activity of sulbactam against the genus Acinetobacter has been aroused. The purpose of this study was to compare the outcomes for patients with Acinetobacter bacteremia treated with cefoperazone/sulbactam versus imipenem/cilastatin. Forty-seven patients with Acinetobacter baumannii bacteremia were analyzed through a retrospective review of their medical records for antibiotic therapy and clinical outcome. Thirty-five patients were treated with cefoperazone/sulbactam, and twelve patients with imipenem/cilastatin. The percentage of favorable response after 72 hours was not statistically different between cefoperazone/sulbactam group and imipenem/cilastatin group. The mortality rate was not statistically different, too. Cefoperazone/sulbactam was found to be as useful as imipenem/cilastatin for treating patients with Acinetobacter bacteremia. (+info)