Journal ArticleDOI
Antibiotic resistance : What's dosing got to do with it?
Jason A. Roberts,Peter Kruger,David L. Paterson,David L. Paterson,Jeffrey Lipman,Jeffrey Lipman +5 more
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TLDR
Antibiotic dosing must aim to address not only the bacteria isolated, but also the most resistant subpopulation in the colony, to prevent the advent of further resistant infections because of the inadvertent selection pressure of current dosing regimens.Abstract:
Objective: This review seeks to identify original research articles that link antibiotic dosing and the development of antibiotic resistance for different antibiotic classes. Using this data, we seek to apply pharmacodynamic principles to assist clinical practice for suppressing the emergence of resistance. Concepts such as mutant selection window and mutant prevention concentration will be discussed. Data Sources: PubMed, EMBASE, and the Cochrane Controlled Trial Register. Study Selection: All articles that related antibiotic doses and exposure to the formation of antibiotic resistance were reviewed. Data Synthesis: The escalation of antibiotic resistance continues worldwide, most prominently in patients in intensive care units. Data are emerging from in vitro and in vivo studies that suggest that inappropriately low antibiotic dosing may be contributing to the increasing rate of antibiotic resistance. Fluoroquinolones have widely been researched and publications on other antibiotic classes are emerging. Developing dosing regimens that adhere to pharmacodynamic principles and maximize antibiotic exposure is essential to reduce the increasing rate of antibiotic resistance. Conclusions: Antibiotic dosing must aim to address not only the bacteria isolated, but also the most resistant subpopulation in the colony, to prevent the advent of further resistant infections because of the inadvertent selection pressure of current dosing regimens. This may be achieved by maximizing antibiotic exposure by administering the highest recommended dose to the patient.read more
Citations
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Journal ArticleDOI
DALI: Defining Antibiotic Levels in Intensive Care Unit Patients: Are Current β-Lactam Antibiotic Doses Sufficient for Critically Ill Patients?
Jason A. Roberts,Sanjoy K. Paul,Murat Akova,Matteo Bassetti,Jan J. De Waele,George Dimopoulos,Kirsi-Maija Kaukonen,Despoina Koulenti,Claude Martin,Philippe Montravers,Jordi Rello,Andrew Rhodes,Therese Starr,Steven C. Wallis,Jeffrey Lipman,Dali Study +15 more
TL;DR: Infected critically ill patients may have adverse outcomes as a result of inadeqaute antibiotic exposure; a paradigm change to more personalized antibiotic dosing may be necessary to improve outcomes for these most seriously ill patients.
Journal ArticleDOI
Pharmacokinetic issues for antibiotics in the critically ill patient.
Jason A. Roberts,Jeffrey Lipman +1 more
TL;DR: Knowledge of antibiotic pharmacodynamic properties and the potential altered antibiotic pharmacokinetics in critically ill patients can allow the intensivist to develop individualized dosing regimens.
Journal ArticleDOI
Subtherapeutic initial β-lactam concentrations in select critically ill patients: association between augmented renal clearance and low trough drug concentrations.
Andrew A. Udy,Julie M. Varghese,Mahdi Altukroni,Scott Briscoe,Brett C. McWhinney,Jacobus P.J. Ungerer,Jeffrey Lipman,Jason A. Roberts +7 more
TL;DR: Elevated CLCR appears to be an important predictor of subtherapeutic β-lactam concentrations and suggests an important role in identifying such patients in the ICU.
Journal ArticleDOI
Continuous infusion of beta-lactam antibiotics in severe sepsis: a multicenter double-blind, randomized controlled trial
Joel M. Dulhunty,Jason A. Roberts,Joshua S. Davis,Steven A R Webb,Rinaldo Bellomo,Charles D. Gomersall,Charudatt Shirwadkar,Glenn M Eastwood,John Myburgh,David L. Paterson,Jeffrey Lipman +10 more
TL;DR: Continuous administration of beta-lactam antibiotics achieved higher plasma antibiotic concentrations than intermittent administration with improvement in clinical cure, providing a strong rationale for further multicenter trials with sufficient power to identify differences in patient-centered endpoints.
Journal ArticleDOI
Augmented renal clearance: implications for antibacterial dosing in the critically ill
Andrew A. Udy,Andrew A. Udy,Jason A. Roberts,Jason A. Roberts,Robert J. Boots,Robert J. Boots,David L. Paterson,David L. Paterson,Jeffrey Lipman,Jeffrey Lipman +9 more
TL;DR: Augmented renal clearance (ARC) refers to enhanced renal elimination of circulating solute and is being described with increasing regularity in the critically ill, and current evidence suggests that young patients without preexisting co-morbidity or organ dysfunction who present with trauma are most likely to manifest ARC.
References
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Journal ArticleDOI
Pharmacokinetic/Pharmacodynamic Parameters: Rationale for Antibacterial Dosing of Mice and Men
TL;DR: The potential value of using pharmacokinetic/pharmacodynamic parameters as guides for establishing optimal dosing regimens for new and old drugs and for new emerging pathogens and resistant organisms should make the continuing search for the therapeutic rationale of antibacterial dosing of mice and men worthwhile.
Journal ArticleDOI
Daptomycin versus Standard Therapy for Bacteremia and Endocarditis Caused by Staphylococcus aureus
Vance G. Fowler,Helen W. Boucher,G. Ralph Corey,Elias Abrutyn,Adolf W. Karchmer,Mark E. Rupp,Donald P. Levine,Henry F. Chambers,Francis P. Tally,Gloria Vigliani,Christopher H. Cabell,Arthur Stanley Link,Ignace DeMeyer,Scott G. Filler,Marcus J. Zervos,Paul P. Cook,Jeffrey Parsonnet,Jack M. Bernstein,Connie S. Price,Graeme N. Forrest,Gerd Fätkenheuer,Marcelo Gareca,Susan J. Rehm,Hans Reinhardt Brodt,Alan D. Tice,Sara E. Cosgrove +25 more
TL;DR: Daptomycin (6 mg per kilogram daily) is not inferior to standard therapy for S. aureus bacteremia and right-sided endocarditis and met prespecified criteria for the noninferiority of daptomecin.
Journal ArticleDOI
Molecular genetics of aminoglycoside resistance genes and familial relationships of the aminoglycoside-modifying enzymes.
TL;DR: A preliminary assessment of the amino acids which may be important in binding aminoglycosides was obtained from data and from the results of mutational analysis of several of the genes encoding am inoglycoside-modifying enzymes.
Journal ArticleDOI
Pharmacodynamics of intravenous ciprofloxacin in seriously ill patients.
TL;DR: The rationale and tools needed for targeting the dosage of intravenous ciprofloxacin to individual patients' pharmacokinetics and their bacterial pathogens' susceptibilities are provided and shown to be more precise than current guidelines.
Journal ArticleDOI
Bad Bugs Need Drugs: An Update on the Development Pipeline from the Antimicrobial Availability Task Force of the Infectious Diseases Society of America
George H. Talbot,John S. Bradley,John S. Bradley,John E. Edwards,David N. Gilbert,Michael Scheld,John G. Bartlett +6 more
TL;DR: The AATF has prepared this review to highlight pathogens that are frequently resistant to licensed antimicrobials and for which few, if any, potentially effective drugs are identifiable in the late-stage development pipeline.
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