International journal of antimicrobial agents
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Int. J. Antimicrob. Agents · Aug 2014
Long-term, low-dose erythromycin monotherapy for Mycobacterium avium complex lung disease: a propensity score analysis.
Multidrug regimens are initially withheld in mild cases of pulmonary Mycobacterium avium complex (MAC) disease. Based on the anti-inflammatory effects of macrolides, some patients are treated with erythromycin, which does not appear to exhibit cross-resistance with clarithromycin in MAC. The aim of this study was to evaluate the effects and adverse events of erythromycin monotherapy in patients with pulmonary MAC disease. ⋯ In addition, the rate of response to the multidrug regimens after exacerbation in the erythromycin group (56%; 5/9) was similar to that observed in the control group (62%; 13/21) (P=0.528). Erythromycin monotherapy for patients with pulmonary MAC disease may have the potential to suppress exacerbation without inducing cross-resistance to clarithromycin. However, further prospective studies are needed to microbiologically verify the effectiveness and potential for cross-resistance of these drugs.
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Int. J. Antimicrob. Agents · Aug 2014
Review Meta AnalysisEfficacy and safety of sofosbuvir-based therapy for the treatment of chronic hepatitis C in treatment-naïve and treatment-experienced patients.
Sofosbuvir, a hepatitis C virus (HCV) NS5B polymerase inhibitor, is a new direct-acting antiviral for chronic HCV infection. This systematic review and proportional meta-analysis examined the efficacy and safety of sofosbuvir-based therapy for chronic HCV infection in treatment-naïve and -experienced patients. Medline, Cochrane Database of Systematic Reviews, EMBASE and Web of Science databases were searched. ⋯ Six treatment arms/cohorts met the criteria for analysis in treatment-naïve patients who were treated with sofosbuvir and RBV; the SVR12 was 72% (95% CI 60-81%), relapse was 27% and the SAE rate was 3%. Three treatment arms/cohorts met the criteria for analysis in treatment-experienced patients who were treated with sofosbuvir and RBV; the SVR12 was 51% (95% CI 27-75%), relapse was 46% and the SAE rate was 4%. In conclusion, sofosbuvir-based treatment is effective and safe in treating chronic HCV infection, although the SVR12 of its combination with RBV, especially in treatment-experienced patients, requires improvement.
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Int. J. Antimicrob. Agents · Aug 2014
Observational StudyPopulation pharmacokinetics and dose simulation of vancomycin in critically ill patients during high-volume haemofiltration.
This study aimed to describe the population pharmacokinetics of vancomycin in critically ill patients with refractory septic shock undergoing continuous venovenous high-volume haemofiltration (HVHF) and to define appropriate dosing for these patients. This was a prospective pharmacokinetic study in the ICU of a university hospital. Eight blood samples were taken over one vancomycin dosing interval. ⋯ Simulations indicate that after a loading dose, vancomycin doses required for different HVHF intensities would be 750 mg every 12h (q12h) for 69 mL/kg/h, 1000 mg q12h for 100 mL/kg/h and 1500 mg q12h for 123 mL/kg/h. Continuous infusion would also be a valuable administration strategy. In conclusion, variable and much higher than standard vancomycin doses are required to achieve therapeutic concentrations during different HVHF settings.
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Int. J. Antimicrob. Agents · Jun 2014
Ceftolozane/tazobactam activity tested against Gram-negative bacterial isolates from hospitalised patients with pneumonia in US and European medical centres (2012).
During 2012, a total of 2968 isolates were consecutively collected from 59 medical centres in the USA and 15 European countries from hospitalised patients with pneumonia. Ceftolozane/tazobactam (tazobactam at a fixed concentration of 4mg/L) and comparator agents were tested by reference methods, and MIC endpoints were interpreted by CLSI (2013) and EUCAST (2013) breakpoint criteria. Pseudomonas aeruginosa was the most common isolated pathogen (1019 strains; 34.3%), and ceftolozane/tazobactam was the most active β-lactam tested against P. aeruginosa (MIC50/90, 0.5/4 mg/L; 94.1% inhibited at ≤ 8 mg/L). ⋯ All β-lactams had limited activity against Acinetobacter spp. and Stenotrophomonas maltophilia. Ceftolozane/tazobactam demonstrated greater in vitro activity than currently available cephalosporins, carbapenems and piperacillin/tazobactam when tested against P. aeruginosa. In addition, ceftolozane/tazobactam demonstrated greater activity than contemporary cephalosporins and piperacillin/tazobactam when tested against most Enterobacteriaceae.
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Int. J. Antimicrob. Agents · May 2014
Review Meta Analysis Comparative StudyProlonged infusion versus intermittent boluses of β-lactam antibiotics for treatment of acute infections: a meta-analysis.
The clinical advantages of prolonged (extended/continuous) infusion remain controversial. Previous studies and reviews have failed to show consistent clinical benefits of extending the infusion time. This meta-analysis sought to determine whether prolonged β-lactam infusions were associated with a reduction in mortality and improvement in clinical success. ⋯ Compared with intermittent boluses, use of prolonged infusion appeared to be associated with a significant reduction in mortality [pooled relative risk (RR) = 0.66, 95% confidence interval (CI) 0.53-0.83] and improvement in clinical success (RR = 1.12, 95% CI 1.03-1.21). Statistically significant benefit was supported by non-randomised studies (mortality, RR = 0.57, 95% CI 0.43-0.76; clinical success, RR = 1.34, 95% CI 1.02-1.76) but not by RCTs (mortality, RR = 0.83, 95% CI 0.57-1.21; clinical success, RR = 1.05, 95% CI 0.99-1.12). The positive results from observational studies, especially in the face of increasing antibiotic resistance, serve to justify the imperative need to conduct a large-scale, well-designed, multicentre RCT involving critically ill patients infected with high minimum inhibitory concentration pathogens to clearly substantiate this benefit.