Entity

Time filter

Source Type


Nicolau D.P.,Center for Anti Infective Research and Development
Current Opinion in Infectious Diseases | Year: 2011

Purpose of review: Management of hospital-associated infections (HAIs) has been made more challenging by the increasing proportion of immunocompromised or otherwise severely ill patients and increasing prevalence of antibiotic-resistant pathogens in this environment. This review examines strategies to optimize clinical outcomes and lower healthcare costs for patients with HAIs by focusing on patient-related, pathogen-related, and drug-related factors. Recent findings: Factors have converged to increase the risk of infection with antibiotic-resistant pathogens in the current hospital environment, including the increasing prevalence of resistant species and number of hospitalized patients with conditions increasingly susceptible to infection with drug-resistant bacteria. Although the list of bacterial pathogens associated with HAIs has been fairly constant over time, the prevalence and resistance profile of these individual species continues to evolve. Periodic antibiograms should be utilized to access local patterns of resistance within the different hospital wards. Outcomes for patients with HAIs are optimized with early empiric treatment with an appropriate regimen, selected on the basis of patient characteristics and local resistance patterns. Dosing strategies should be utilized to ensure that the efficacy of an appropriate antibiotic is optimized, by achieving the pharmacodynamic target predictive of its efficacy. Using these strategies improves quality of care and is associated with lower overall healthcare costs. Summary: Bacterial resistance is an increasing problem in the hospital environment, and has been associated with poorer clinical outcomes and elevated healthcare costs. By using patient characteristics, local antibiograms, and dosing strategies to achieve an optimal pharmacodynamic profile, early appropriate empiric therapy can be utilized to improve clinical outcomes, minimize the development of resistance, and reduce healthcare costs. © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins. Source


Eagye K.J.,Center for Anti Infective Research and Development | Nicolau D.P.,Center for Anti Infective Research and Development
Journal of Antimicrobial Chemotherapy | Year: 2011

Background: Concern remains that ertapenem use may promote cross-resistance in Pseudomonas aeruginosa to antipseudomonal carbapenems (APCs). This study extends our earlier multicentre investigation of this relationship by an additional 3 years. Methods: Use density ratios (UDRs) for ertapenem, APCs, aminoglycosides, fluoroquinolones and non-carbapenem β-lactams were derived from purchase data for 3 years pre-adoption and up to 6 years post-adoption of ertapenem at 25 hospitals. Hospital antibiograms in corresponding years yielded APC susceptibility data. Mixed model repeated measures ANOVA explored associations between 9 year repeated APC susceptibility and ertapenem UDR while controlling for all other classes. Results: All 25 sites had 4 years of post-adoption data, with 22 of 25 reporting 5 years and 18 of 25 reporting 6 years. Ertapenem UDR rose steadily once adopted, with a mean UDR of 7.27 in year 4 and a mean UDR of 15.93 in year 9. APC UDR increased initially (from 10.39 in year 1 to a peak of 18.77 in year 6) and then declined to 15.27 in year 9. By year 9 ertapenem and APC use were similar. Among other classes, fluoroquinolone UDR increased notably (year/mean UDR): 1/303.84; 4/174.38; and 9/423.32. Mean APC susceptibility declined from 85.4% in year 1 to 81.0% in year 9; this change across time was not significant (P=0.99). Change in 9 year APC susceptibility was not associated with ertapenem UDR (P=0.54), while controlling for all other antibiotic classes (all showed no association at P>0.5). Conclusions: While controlling for utilization of other antibiotic classes, we found no association between change in APC susceptibility and ertapenem use. © The Author 2011. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. Source


Tessier P.R.,Center for Anti Infective Research and Development | Nicolau D.P.,Center for Anti Infective Research and Development
Antimicrobial Agents and Chemotherapy | Year: 2013

Progressively enhanced activity of a humanized tigecycline (TGC) regimen was noted over 3 days against an extended-spectrum-β-lactamase (ESBL)-producing Escherichia coli isolate and an ESBL-producing Klebsiella pneumoniae isolate. Bacterial density reduction approximated 3 log10 approaching bactericidal activity at 72 h. This level of activity has not been previously noted for compounds such as tetracyclines, normally considered bacteriostatic antimicrobials. Extended regimen studies in vivo may aid in better delineation of antimicrobial effects, producing improved correlation with clinical outcomes. Copyright © 2013, American Society for Microbiology. All Rights Reserved. Source


Tessier P.R.,Center for Anti Infective Research and Development | Nicolau D.P.,Center for Anti Infective Research and Development
Antimicrobial Agents and Chemotherapy | Year: 2013

The activity of five novel gyrase inhibitors was evaluated against 303 nonduplicate Pseudomonas aeruginosa strains collected from 53 North American institutions. The most active compound, GP-2, displayed MIC50 and MIC90 values of 1 and 2 μg/ml, respectively. Cross-resistance to other commercially available antipseudomonal compounds was not evident, as no major change was observed in the gyrase inhibitor MIC distribution when stratified by nonsusceptible phenotypes, including the fluoroquinolones and those isolates classified as multidrug resistant (MDR). Copyright © 2013, American Society for Microbiology. All Rights Reserved. Source


Bulik C.C.,Center for Anti Infective Research and Development | Nicolau D.P.,Center for Anti Infective Research and Development
Antimicrobial Agents and Chemotherapy | Year: 2011

The limited treatment options available for carbapenemase-producing Klebsiella pneumoniae (KPC) have made it a formidable pathogen. Previously we have shown the enhanced activity of pharmacodynamically optimized doripenem against KPC. Capitalizing on KPC's increased affinity for ertapenem, we evaluated the efficacy of a combination of ertapenem and doripenem in both an in vitro chemostat and an in vivo murine thigh infection model. Overall, the combination of doripenem plus ertapenem demonstrated enhanced efficacy over either agent alone. Copyright © 2011, American Society for Microbiology. All Rights Reserved. Source

Discover hidden collaborations