Precision Medicine and Mysteries in Clinical Microbiology: Rationalizing Epidemiology, Genotype, and Phenotype To Guide Therapeutics

Pérez, Federico

doi:10.1128/aac.02264-19

Cited by 7 publications

(2 citation statements)

References 11 publications

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“…A weighted distribution of drug susceptibility could also be incorporated based on recent local/regional surveillance data to guide the use of empiric therapy [ 67 ]. When actual PK (eg, drug exposure, penetration) and drug susceptibility patterns (eg, MIC, resistance genotypes) are known, these factors may pave the way toward precision dosing of antimicrobial therapy [ 68 , 69 ].…”

Section: Monte Carlo Simulations To Evaluate Dosing Strategiesmentioning

confidence: 99%

Optimizing Clinical Outcomes Through Rational Dosing Strategies: Roles of Pharmacokinetic/Pharmacodynamic Modeling Tools

Chua

Tam

2022

Open Forum Infectious Diseases

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Significant progress in previous decades has led to several methodologies developed to facilitate the design of optimal antimicrobial dosing. In this review, we highlight common pharmacokinetic/pharmacodynamic (PKPD) modeling techniques and their roles in guiding rational dosing regimen design. In the early drug development phases, dose fractionation studies identify the PKPD index most closely associated with bacterial killing. Once discerned, this index is linked to clinical efficacy end points, and classification and regression tree analysis can be used to define the PKPD target goal. Monte Carlo simulations integrate PKPD and microbiological data to identify dosing strategies with a high probability of achieving the established PKPD target. Results then determine dosing regimens to investigate and/or validate the findings of randomized controlled trials. Further improvements in PKPD modeling could lead to an era of precision dosing and personalized therapeutics.

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Section: Monte Carlo Simulations To Evaluate Dosing Strategiesmentioning

confidence: 99%

Optimizing Clinical Outcomes Through Rational Dosing Strategies: Roles of Pharmacokinetic/Pharmacodynamic Modeling Tools

Chua

Tam

2022

Open Forum Infectious Diseases

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“…This unfortunate combination of antimicrobial resistance, lack of clinical data and clinician experience, and the dearth of available effective treatment options presents a unique opportunity for collaboration between clinicians and researchers. These collaborations have been employed successfully, especially recently, against a variety of difficult-to-treat pathogens in complex clinical scenarios, highlighting the need for these types of partnerships to optimize therapy and achieve precision medicine [ 4 , 7 , 8 , 9 , 10 ]. Herein, we present a case of an immunocompromised stem cell transplant patient with persistent, extremely drug resistant VREf bacteremia and meningitis treated in collaboration between clinicians and scientists via the use of unique therapeutic drug monitoring and in vitro pharmacokinetic/pharmacodynamic (PK/PD) analyses.…”

Section: Introductionmentioning

confidence: 99%

Inadequate Cerebrospinal Fluid Concentrations of Available Salvage Agents Further Impedes the Optimal Treatment of Multidrug-Resistant Enterococcus faecium Meningitis and Bacteremia

Wenzler

Adeel

et al. 2021

Infectious Disease Reports

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Background: Vancomycin-resistant Enterococcus faecium (VRE) in particular has evolved as an important cause of hospital acquired infection, especially in immunocompromised hosts. Methods: We present a complex case of a patient with relapsed acute myeloid leukemia who underwent allogenic hematopoietic stem cell transplantation complicated by persistent VRE bacteremia and meningitis. To optimize therapy, various blood and cerebrospinal fluid (CSF) samples were sent to a research laboratory for extensive susceptibility testing, pharmacokinetic analyses, and time-kill experiments. Results: In vitro testing revealed resistance to all first-line treatment options and CSF sampling demonstrated sub-optimal central nervous system concentrations achieved by each antimicrobial agent administered in relation to their respective MIC value. Time-kill analyses at observed CSF concentrations confirmed the lack of bactericidal activity despite use of a four-drug combination regimen. Conclusions: This work is the first to report CSF concentrations of oritavancin and tedizolid in humans and adds to the limited data regarding in vitro susceptibility of new antimicrobial agents such as eravacycline, omadacycline, and lefamulin against VRE. Our study provides new insights into various aspects of treatment of extensively drug-resistant Enterococcus faecium meningitis and bacteremia and supports the continued pursuit of precision medicine for these challenging cases.

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Combatting the Rising Tide of Antimicrobial Resistance: Pharmacokinetic/Pharmacodynamic Dosing Strategies for Maximal Precision

Chua

Tse

Smith

et al. 2021

International Journal of Antimicrobial Agents

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Precision Medicine and Mysteries in Clinical Microbiology: Rationalizing Epidemiology, Genotype, and Phenotype To Guide Therapeutics

Cited by 7 publications

References 11 publications

Optimizing Clinical Outcomes Through Rational Dosing Strategies: Roles of Pharmacokinetic/Pharmacodynamic Modeling Tools

Optimizing Clinical Outcomes Through Rational Dosing Strategies: Roles of Pharmacokinetic/Pharmacodynamic Modeling Tools

Inadequate Cerebrospinal Fluid Concentrations of Available Salvage Agents Further Impedes the Optimal Treatment of Multidrug-Resistant Enterococcus faecium Meningitis and Bacteremia

Combatting the Rising Tide of Antimicrobial Resistance: Pharmacokinetic/Pharmacodynamic Dosing Strategies for Maximal Precision

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