International journal of antimicrobial agents
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Int. J. Antimicrob. Agents · Jan 2005
ReviewEvaluation of colistin as an agent against multi-resistant Gram-negative bacteria.
Infections caused by multi-resistant Gram-negative bacteria, particularly Pseudomonas aeruginosa, are increasing worldwide. In patients with cystic fibrosis (CF), resistance in P. aeruginosa to numerous anti-pseudomonal agents is becoming common. The absence since 1995, of new substances active against resistant Gram-negative bacteria, has caused increasing concern. ⋯ Because its use as an anti-pseudomonal agent was displaced by the potentially less toxic aminoglycosides in 1970s, our knowledge of this drug is limited. However, there has been a significant recent increase in the data gathered on colistin, focussing on its chemistry, antibacterial activity, mechanism of action and resistance, pharmacokinetics, pharmacodynamics and new clinical application. It is likely that colistin will be an important antimicrobial option against multi-resistant Gram-negative bacteria, for some years to come.
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Int. J. Antimicrob. Agents · Jan 2005
Randomized Controlled Trial Clinical TrialPharmacokinetics of piperacillin-tazobactam: intermittent dosing versus continuous infusion.
In the present study 24 hospitalized patients requiring empirical antibiotic treatment were randomly assigned to receive the beta-lactam antibiotic/beta-lactamase inhibitor combination piperacillin-tazobactam either as an intermittent or as a continuous infusion. According to pharmacokinetic modelling, the daily dose was reduced by 33% in patients receiving continuous infusion compared with intermittent infusion. Dose reduction because of impaired renal function was required in the intermittent dosing group for 5 of 12 patients compared with 1 of 12 patients in the continuous infusion group. ⋯ The corresponding mean value for tazobactam was 6.3 microg/ml. Pharmacokinetic/pharmacodynamic modelling suggests that both treatment schemes should produce virtually identical anti-infective responses to sensitive, intermediate and resistant strains. In the present study the continuous infusion of piperacillin/tazobactam provided adequate antibacterial activity over the 24-h dosing period and offers the potential for a substantial reduction in the total daily dose.
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Int. J. Antimicrob. Agents · Nov 2004
ReviewCommunity-acquired pneumonia: new management strategies for evolving pathogens and antimicrobial susceptibilities.
Community-acquired pneumonia (CAP) is still one of the leading causes of mortality and morbidity. The most common bacterial cause of CAP is Streptococcus pneumoniae. The increase in antimicrobial resistance has raised concerns about the efficacy of available therapies, and a call for the reassessment of both existing and newer therapeutic agents. ⋯ Within this review, the role of monotherapy versus the need for combination antimicrobial therapy, which often includes a macrolide and an extended spectrum cephalosporin such as ceftriaxone, is discussed. This review also discusses the various aspects of antimicrobial susceptibilities of S. pneumoniae, the drivers and influences of increasing resistance, the clinical relevance of this resistance and possible therapeutic options in the face of changing susceptibilities and mixed bacterial aetiologies. New guidelines from the IDSA attempt to embrace these changes.
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Int. J. Antimicrob. Agents · Nov 2004
Pharmacodynamic target attainment analysis against Streptococcus pneumoniae using levofloxacin 500 mg, 750 mg and 1000 mg once daily in plasma (P) and epithelial lining fluid (ELF) of hospitalized patients with community acquired pneumonia (CAP).
The pharmacokinetics and pharmacodynamics of levofloxacin in patients with respiratory infections such as community-acquired pneumonia (CAP) are poorly documented. This work aimed at assessing the pharmacodynamic target attainment against Streptococcus pneumoniae using levofloxacin 500 mg, 750 mg and 1000 mg administered once daily in plasma (P) and epithelial lining fluid (ELF) of hospitalized patients with community acquired pneumonia. The pharmacokinetics of levofloxacin in elderly (>/=65 years) compared with younger patients (<65 years) hospitalized with CAP were simulated. ⋯ Levofloxacin 750 mg OD provides high probabilities of achieving free-drug AUC(0-24)/MIC(all) of 30 in both plasma and epithelial lining fluid in patients with CAP including younger patients. Levofloxacin 500 mg OD provides high probabilities of achieving free-drug AUC(0-24)/MIC(all) of 30 in elderly patients with CAP, although we favour the 750 mg dosing in these patients as well. Levofloxacin 750 mg OD results in high probability of pharmacodynamic target attainment and improved bacteriological outcome against S. pneumoniae in patients with CAP.
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Int. J. Antimicrob. Agents · Nov 2004
Severity scoring in community-acquired pneumonia caused by Streptococcus pneumoniae: a 5-year experience.
Multiple severity scoring systems have been devised and evaluated in community-acquired pneumonia (CAP), but a simplified set of prognostic indicators has not yet been developed. Streptococcus pneumoniae is the most frequent aetiological agent of CAP. Our aim was to characterise the outcome in the light of different severity scoring systems and to compare the predictive values of different sets of clinical parameters, using available clinical data for pneumococcal CAP patients. ⋯ Neither prior antimicrobial use (or failure) nor antimicrobial resistance contributed to an adverse outcome. S. pneumoniae bacteraemia failed to correlate with need for ICU, length of stay, higher morbidity index or fatal outcome. Low rates of empirical antibiotic use for non-bacterial infections in the local community, implementation of an emergency department protocol for CAP therapy, early recognition of higher risk patients and placement in ICU, use of broad spectrum antibiotics, infectious disease approval or critical pathway restriction for admission orders, could all have combined to effect a good outcome for these patients.