George L. Drusano

Publication List Details

Period

1984 - 2007

Number

72

Co-Authors

Probability of Target Attainment for Ceftobiprole as Derived from a Population Pharmacokinetic Analysis of 150 Subjects � (2007)

Thomas P. Lodise, Rienk Pypstra, James B. Kahn, Bindu P. Murthy, Hui C. Kimko, Karen Bush, ...

Ceftobiprole is a broad-spectrum cephalosporin with activity against methicillin-resistant Staphylococcus aureus (MRSA) that is undergoing phase III trials for the treatment of complicated skin and...

Isoniazid Bactericidal Activity and Resistance Emergence: Integrating Pharmacodynamics and Pharmacogenomics To Predict Efficacy in Different Ethnic Populations � (2007)

A Gumbo, Arnold Louie, Weiguo Liu, David Brown, Paul G. Ambrose, Sujata M. Bhavnani, ...

Isoniazid, administered as part of combination antituberculosis therapy, is responsible for most of the early bactericidal activity (EBA) of the regimen. However, the emergence of Mycobacterium...

Standardization of pharmacokinetic/pharmacodynamic (PK/PD) terminology for anti-infective drugs: an update (2005)

Mouton, Johan W., Dudley, Michael N., Cars, Otto, Derendorf, Hartmut, Drusano, George L.

Interest in the relationships between the pharmacokinetics (PK) and pharmacodynamics (PD) of antimicrobial agents has increased over recent years. Since the appearance 2 years ago of our first...

Standardization of pharmacokinetic/pharmacodynamic (PK/PD) terminology for anti-infective drugs: an update (2005)

Mouton, Johan W., Dudley, Michael N., Cars, Otto, Derendorf, Hartmut, Drusano, George L.

Interest in the relationships between the pharmacokinetics (PK) and pharmacodynamics (PD) of antimicrobial agents has increased over recent years. Since the appearance 2 years ago of our first...

Pharmacodynamics of cefepime in patients with Gram-negative infections (2002)

Tam, Vincent H., McKinnon, Peggy S., Akins, Ronda L., Rybak, Michael J., Drusano, George L.

We conducted a prospective, open-label study to delineate a relationship between exposure and outcomes in 36 patients treated with cefepime. Twenty patients had documented Gram-negative infections....

Comparative pharmacokinetics and serum bactericidal activity of mezlocillin, ticarcillin and piperacillin, with and without gentamicin (1985)

Viollier, Anne-Françoise, Standiford, Harold C., Drusano, George L., Tatem, Beverly A., Moody, Marcia R., Schimpff, Stephen C.

We compared the serum levels, pharmacokinetics and serum bactericidal activity after intravenous infusions of 5 g of each of three anti-pseudomonal penicillins—ticarcillin, mezlocillin and...

The serum bactericidal activity of latamoxef (moxalactam), cefoperazone and cefotaxime (1984)

McNamee, William, Drusano, George L., Tatem, Beverly A., Standiford, Harold C.

We determined the serum bactericidal activity 1 h after the end of 2 g, 30 min infusions of latamoxef, cefoperazone and cefotaxime in six volunteers against six strains each of Escherichia coli,...

Optimizing Aminoglycoside Therapy for Nosocomial Pneumonia Caused by Gram-Negative Bacteria

Kashuba, Angela D. M., Nafziger, Anne N., Drusano, George L., Bertino, Joseph S.

Nosocomial pneumonia is a notable cause of morbidity and mortality and leads to increases in lengths of hospital stays and institutional expenditures. Aminoglycosides are used to treat patients with...

Prospective Evaluation of the Effect of an Aminoglycoside Dosing Regimen on Rates of Observed Nephrotoxicity and Ototoxicity

Rybak, Michael J., Abate, Betty J., Kang, S. Lena, Ruffing, Michael J., Lerner, Stephen A., Drusano, George L.

The nephrotoxicity and ototoxicity associated with once-daily versus twice-daily administration of aminoglycosides was assessed in patients with suspected or proven gram-negative bacterial infections...

Pharmacokinetics and Absolute Bioavailability of Ribavirin in Healthy Volunteers as Determined by Stable-Isotope Methodology

Preston, Sandra L., Drusano, George L., Glue, Paul, Nash, Jacqueline, Gupta, S. K., McNamara, P.

Ribavirin has recently been demonstrated to have efficacy in combination with alpha interferon for treatment of relapsed hepatitis C. The marked improvement in the response rate after treatment with...

Interaction between Fluconazole and Amphotericin B in Mice with Systemic Infection Due to Fluconazole-Susceptible or -Resistant Strains of Candida albicans

Louie, Arnold, Banerjee, Partha, Drusano, George L., Shayegani, Mehdi, Miller, Michael H.

The interaction between fluconazole (Flu) and amphotericin B (AmB) was evaluated in a murine model of systemic candidiasis for one Flu-susceptible strain (MIC, 0.5 μg/ml), two strains with...

Pharmacodynamics of Daptomycin in a Murine Thigh Model of Staphylococcus aureus Infection

Louie, Arnold, Kaw, Pamela, Liu, Weiguo, Jumbe, Nelson, Miller, Michael H., Drusano, George L.

Daptomycin is a lipopeptide antibiotic with activity against gram-positive bacteria, including Staphylococcus aureus. We defined the pharmacodynamic parameters that determine the activity of...

Susceptibilities of Human Cytomegalovirus Clinical Isolates to BAY38-4766, BAY43-9695, and Ganciclovir

McSharry, James J., McDonough, Ann, Olson, Betty, Hallenberger, Sabine, Reefschlaeger, Juergen, Bender, Wolfgang, ...

BAY38-4766 and BAY43-9695 are nonnucleosidic compounds with activities against human cytomegalovirus (HCMV). Two phenotypic assays were used to determine the drug susceptibilities of 36 HCMV clinical...

Flow Cytometric Determination of Ganciclovir Susceptibilities of Human Cytomegalovirus Clinical Isolates

McSharry, James M., Lurain, Nell S., Drusano, George L., Landay, Alan, Manischewitz, Jody, Nokta, Mostafa, ...

A flow cytometric assay has been developed for the measurement of susceptibilities to ganciclovir of laboratory strains and clinical isolates of human cytomegalovirus (HCMV). The assay uses...

Mathematical Modeling of the Interrelationship of CD4 Lymphocyte Count and Viral Load Changes Induced by the Protease Inhibitor Indinavir

Drusano, George L., Stein, Daniel S.

While CD4 cell counts are widely used to predict disease progression in human immunodeficiency virus (HIV)-infected patients, they are poorly explanatory of the progression to AIDS or death after the...

Pharmacokinetic Studies of Fluconazole in Rabbits Characterizing Doses Which Achieve Peak Levels in Serum and Area under the Concentration-Time Curve Values Which Mimic Those of High-Dose Fluconazole in Humans

Louie, Arnold, Liu, Qing-Feng, Drusano, George L., Liu, Weiguo, Mayers, Martin, Anaissie, Elias, ...

We conducted steady-state pharmacokinetic studies with high-dose fluconazole with rabbits and human volunteers. We then derived mathematical equations that predict the doses of fluconazole that...

Levofloxacin Population Pharmacokinetics and Creation of a Demographic Model for Prediction of Individual Drug Clearance in Patients with Serious Community-Acquired Infection

Preston, Sandra L., Drusano, George L., Berman, Adam L., Fowler, Cynthia L., Chow, Andrew T., Dornseif, Bruce, ...

Population pharmacokinetic modeling is a useful approach to obtaining estimates of both population and individual pharmacokinetic parameter values. The potential for relating pharmacokinetic...

Pharmacodynamics of Fluconazole in a Murine Model of Systemic Candidiasis

Louie, Arnold, Drusano, George L., Banerjee, Partha, Liu, Qing-Feng, Liu, Weiguo, Kaw, Pamela, ...

In this study we defined the pharmacodynamic parameter that optimizes outcome in deep-seated Candida albicans infections treated with fluconazole. Using a murine model of systemic candidiasis, we...

Rapid Ganciclovir Susceptibility Assay Using Flow Cytometry for Human Cytomegalovirus Clinical Isolates

McSharry, James J., Lurain, Nell S., Drusano, George L., Landay, Alan L., Notka, Mostafa, O’Gorman, Maurice R. G., ...

Rapid, quantitative, and objective determination of the susceptibilities of human cytomegalovirus (HCMV) clinical isolates to ganciclovir has been assessed by an assay that uses a...

Pharmacokinetics and Pharmacodynamics of Cefepime in Patients with Various Degrees of Renal Function

Tam, Vincent H., McKinnon, Peggy S., Akins, Ronda L., Drusano, George L., Rybak, Michael J.

This study evaluated the pharmacokinetics of cefepime in 36 patients with different levels of renal function. Pharmacokinetic and pharmacodynamic parameters were calculated using samples obtained at...

Application of a mathematical model to prevent in vivo amplification of antibiotic-resistant bacterial populations during therapy

Jumbe, Nelson, Louie, Arnold, Leary, Robert, Liu, Weiguo, Deziel, Mark R., Tam, Vincent H., ...

The worldwide increase in the prevalence of multi-antibiotic–resistant bacteria has threatened the physician’s ability to provide appropriate therapy for infections. The relationship between...

In Vitro-In Vivo Model for Evaluating the Antiviral Activity of Amprenavir in Combination with Ritonavir Administered at 600 and 100 Milligrams, Respectively, Every 12 Hours

Preston, Sandra L., Piliero, Peter J., Bilello, John A., Stein, Daniel S., Symonds, William T., Drusano, George L.

The study objective was to evaluate the pharmacodynamics of amprenavir in an in vitro system, develop an exposure target for maximal viral suppression, and determine the likelihood of target...

Phenotypic Drug Susceptibility Assay for Influenza Virus Neuraminidase Inhibitors

McSharry, James J., McDonough, Ann C., Olson, Betty A., Drusano, George L.

A flow cytometric (fluorescence-activated cell sorter [FACS]) assay was developed for analysis of the drug susceptibilities of wild-type and drug-resistant influenza A and B virus laboratory strains...

Pharmacodynamic Profiling of Piperacillin in the Presence of Tazobactam in Patients through the Use of Population Pharmacokinetic Models and Monte Carlo Simulation

Lodise, Thomas P., Lomaestro, Ben, Rodvold, Keith A., Danziger, Larry H., Drusano, George L.

The primary objectives of this analysis were to determine which pharmacokinetic model most accurately describes the elimination pathways for piperacillin in the presence of tazobactam through...

Evaluation by Monte Carlo Simulation of the Pharmacokinetics of Two Doses of Meropenem Administered Intermittently or as a Continuous Infusion in Healthy Volunteers

Krueger, Wolfgang A., Bulitta, Jurgen, Kinzig-Schippers, Martina, Landersdorfer, Cornelia, Holzgrabe, Ulrike, Naber, Kurt G., ...

Meropenem is a broad-spectrum carbapenem antibacterial agent. In order to optimize levels in plasma relative to the MICs, the ideal dose level and dosage regimen need to be determined. The...

Pharmacodynamic Evidence that Ciprofloxacin Failure against Tuberculosis Is Not Due to Poor Microbial Kill but to Rapid Emergence of Resistance

Gumbo, Tawanda, Louie, Arnold, Deziel, Mark R., Drusano, George L.

Studies of early bactericidal activity provide a fast and economic way to evaluate the clinical efficacy of potential agents for the treatment of tuberculosis. Based on good early bactericidal...

Pharmacodynamics of Caspofungin in a Murine Model of Systemic Candidiasis: Importance of Persistence of Caspofungin in Tissues to Understanding Drug Activity

Louie, Arnold, Deziel, Mark, Liu, Weiguo, Drusano, Michael F., Gumbo, Tawanda, Drusano, George L.

Pharmacokinetic and pharmacodynamic studies were conducted in a murine model of systemic candidiasis to determine the pharmacodynamic parameter linked with caspofungin efficacy. Additional studies...

Quinolone Efflux Pumps Play a Central Role in Emergence of Fluoroquinolone Resistance in Streptococcus pneumoniae

Jumbe, Nelson L., Louie, Arnold, Miller, Michael H., Liu, Weiguo, Deziel, Mark R., Tam, Vincent H., ...

The preferential use of older antimicrobial agents is, in general, sound public health policy and is meant to maintain susceptibility to newer agents. In the case of fluoroquinolones, however, this...

Optimizing Aminoglycoside Therapy for Nosocomial Pneumonia Caused by Gram-Negative Bacteria

Kashuba, Angela D. M., Nafziger, Anne N., Drusano, George L., Bertino, Joseph S.

Nosocomial pneumonia is a notable cause of morbidity and mortality and leads to increases in lengths of hospital stays and institutional expenditures. Aminoglycosides are used to treat patients with...

Prospective Evaluation of the Effect of an Aminoglycoside Dosing Regimen on Rates of Observed Nephrotoxicity and Ototoxicity

Rybak, Michael J., Abate, Betty J., Kang, S. Lena, Ruffing, Michael J., Lerner, Stephen A., Drusano, George L.

The nephrotoxicity and ototoxicity associated with once-daily versus twice-daily administration of aminoglycosides was assessed in patients with suspected or proven gram-negative bacterial infections...

Pharmacokinetics and Absolute Bioavailability of Ribavirin in Healthy Volunteers as Determined by Stable-Isotope Methodology

Preston, Sandra L., Drusano, George L., Glue, Paul, Nash, Jacqueline, Gupta, S. K., McNamara, P.

Ribavirin has recently been demonstrated to have efficacy in combination with alpha interferon for treatment of relapsed hepatitis C. The marked improvement in the response rate after treatment with...

Interaction between Fluconazole and Amphotericin B in Mice with Systemic Infection Due to Fluconazole-Susceptible or -Resistant Strains of Candida albicans

Louie, Arnold, Banerjee, Partha, Drusano, George L., Shayegani, Mehdi, Miller, Michael H.

The interaction between fluconazole (Flu) and amphotericin B (AmB) was evaluated in a murine model of systemic candidiasis for one Flu-susceptible strain (MIC, 0.5 μg/ml), two strains with...

Pharmacodynamics of Daptomycin in a Murine Thigh Model of Staphylococcus aureus Infection

Louie, Arnold, Kaw, Pamela, Liu, Weiguo, Jumbe, Nelson, Miller, Michael H., Drusano, George L.

Daptomycin is a lipopeptide antibiotic with activity against gram-positive bacteria, including Staphylococcus aureus. We defined the pharmacodynamic parameters that determine the activity of...

Susceptibilities of Human Cytomegalovirus Clinical Isolates to BAY38-4766, BAY43-9695, and Ganciclovir

McSharry, James J., McDonough, Ann, Olson, Betty, Hallenberger, Sabine, Reefschlaeger, Juergen, Bender, Wolfgang, ...

BAY38-4766 and BAY43-9695 are nonnucleosidic compounds with activities against human cytomegalovirus (HCMV). Two phenotypic assays were used to determine the drug susceptibilities of 36 HCMV clinical...

Flow Cytometric Determination of Ganciclovir Susceptibilities of Human Cytomegalovirus Clinical Isolates

McSharry, James M., Lurain, Nell S., Drusano, George L., Landay, Alan, Manischewitz, Jody, Nokta, Mostafa, ...

A flow cytometric assay has been developed for the measurement of susceptibilities to ganciclovir of laboratory strains and clinical isolates of human cytomegalovirus (HCMV). The assay uses...

Mathematical Modeling of the Interrelationship of CD4 Lymphocyte Count and Viral Load Changes Induced by the Protease Inhibitor Indinavir

Drusano, George L., Stein, Daniel S.

While CD4 cell counts are widely used to predict disease progression in human immunodeficiency virus (HIV)-infected patients, they are poorly explanatory of the progression to AIDS or death after the...

Pharmacokinetic Studies of Fluconazole in Rabbits Characterizing Doses Which Achieve Peak Levels in Serum and Area under the Concentration-Time Curve Values Which Mimic Those of High-Dose Fluconazole in Humans

Louie, Arnold, Liu, Qing-Feng, Drusano, George L., Liu, Weiguo, Mayers, Martin, Anaissie, Elias, ...

We conducted steady-state pharmacokinetic studies with high-dose fluconazole with rabbits and human volunteers. We then derived mathematical equations that predict the doses of fluconazole that...

Levofloxacin Population Pharmacokinetics and Creation of a Demographic Model for Prediction of Individual Drug Clearance in Patients with Serious Community-Acquired Infection

Preston, Sandra L., Drusano, George L., Berman, Adam L., Fowler, Cynthia L., Chow, Andrew T., Dornseif, Bruce, ...

Population pharmacokinetic modeling is a useful approach to obtaining estimates of both population and individual pharmacokinetic parameter values. The potential for relating pharmacokinetic...

Pharmacodynamics of Fluconazole in a Murine Model of Systemic Candidiasis

Louie, Arnold, Drusano, George L., Banerjee, Partha, Liu, Qing-Feng, Liu, Weiguo, Kaw, Pamela, ...

In this study we defined the pharmacodynamic parameter that optimizes outcome in deep-seated Candida albicans infections treated with fluconazole. Using a murine model of systemic candidiasis, we...

Rapid Ganciclovir Susceptibility Assay Using Flow Cytometry for Human Cytomegalovirus Clinical Isolates

McSharry, James J., Lurain, Nell S., Drusano, George L., Landay, Alan L., Notka, Mostafa, O’Gorman, Maurice R. G., ...

Rapid, quantitative, and objective determination of the susceptibilities of human cytomegalovirus (HCMV) clinical isolates to ganciclovir has been assessed by an assay that uses a...

Pharmacokinetics and Pharmacodynamics of Cefepime in Patients with Various Degrees of Renal Function

Tam, Vincent H., McKinnon, Peggy S., Akins, Ronda L., Drusano, George L., Rybak, Michael J.

This study evaluated the pharmacokinetics of cefepime in 36 patients with different levels of renal function. Pharmacokinetic and pharmacodynamic parameters were calculated using samples obtained at...

Application of a mathematical model to prevent in vivo amplification of antibiotic-resistant bacterial populations during therapy

Jumbe, Nelson, Louie, Arnold, Leary, Robert, Liu, Weiguo, Deziel, Mark R., Tam, Vincent H., ...

The worldwide increase in the prevalence of multi-antibiotic–resistant bacteria has threatened the physician’s ability to provide appropriate therapy for infections. The relationship between...

In Vitro-In Vivo Model for Evaluating the Antiviral Activity of Amprenavir in Combination with Ritonavir Administered at 600 and 100 Milligrams, Respectively, Every 12 Hours

Preston, Sandra L., Piliero, Peter J., Bilello, John A., Stein, Daniel S., Symonds, William T., Drusano, George L.

The study objective was to evaluate the pharmacodynamics of amprenavir in an in vitro system, develop an exposure target for maximal viral suppression, and determine the likelihood of target...

Phenotypic Drug Susceptibility Assay for Influenza Virus Neuraminidase Inhibitors

McSharry, James J., McDonough, Ann C., Olson, Betty A., Drusano, George L.

A flow cytometric (fluorescence-activated cell sorter [FACS]) assay was developed for analysis of the drug susceptibilities of wild-type and drug-resistant influenza A and B virus laboratory strains...

Pharmacodynamic Profiling of Piperacillin in the Presence of Tazobactam in Patients through the Use of Population Pharmacokinetic Models and Monte Carlo Simulation

Lodise, Thomas P., Lomaestro, Ben, Rodvold, Keith A., Danziger, Larry H., Drusano, George L.

The primary objectives of this analysis were to determine which pharmacokinetic model most accurately describes the elimination pathways for piperacillin in the presence of tazobactam through...

Evaluation by Monte Carlo Simulation of the Pharmacokinetics of Two Doses of Meropenem Administered Intermittently or as a Continuous Infusion in Healthy Volunteers

Krueger, Wolfgang A., Bulitta, Jurgen, Kinzig-Schippers, Martina, Landersdorfer, Cornelia, Holzgrabe, Ulrike, Naber, Kurt G., ...

Meropenem is a broad-spectrum carbapenem antibacterial agent. In order to optimize levels in plasma relative to the MICs, the ideal dose level and dosage regimen need to be determined. The...

Pharmacodynamic Evidence that Ciprofloxacin Failure against Tuberculosis Is Not Due to Poor Microbial Kill but to Rapid Emergence of Resistance

Gumbo, Tawanda, Louie, Arnold, Deziel, Mark R., Drusano, George L.

Studies of early bactericidal activity provide a fast and economic way to evaluate the clinical efficacy of potential agents for the treatment of tuberculosis. Based on good early bactericidal...

Pharmacodynamics of Caspofungin in a Murine Model of Systemic Candidiasis: Importance of Persistence of Caspofungin in Tissues to Understanding Drug Activity

Louie, Arnold, Deziel, Mark, Liu, Weiguo, Drusano, Michael F., Gumbo, Tawanda, Drusano, George L.

Pharmacokinetic and pharmacodynamic studies were conducted in a murine model of systemic candidiasis to determine the pharmacodynamic parameter linked with caspofungin efficacy. Additional studies...

Quinolone Efflux Pumps Play a Central Role in Emergence of Fluoroquinolone Resistance in Streptococcus pneumoniae

Jumbe, Nelson L., Louie, Arnold, Miller, Michael H., Liu, Weiguo, Deziel, Mark R., Tam, Vincent H., ...

The preferential use of older antimicrobial agents is, in general, sound public health policy and is meant to maintain susceptibility to newer agents. In the case of fluoroquinolones, however, this...

Anidulafungin Pharmacokinetics and Microbial Response in Neutropenic Mice with Disseminated Candidiasis▿

Gumbo, Tawanda , Drusano, George L., Liu, Weiguo, Ma, Lei, Deziel, Mark R., Drusano, Michael F. , ...

Candidemia is often fatal, especially in patients with persistent neutropenia. New therapies are needed. We performed 24-h pharmacodynamic studies to compare the efficacies of anidulafungin,...

Pharmacokinetic Considerations and Efficacy of Levofloxacin in an Inhalational Anthrax (Postexposure) Rhesus Monkey Model

Kao, L. Mark , Bush, Karen, Barnewall, Roy, Estep, James, Thalacker, Frederic W., Olson, Pamela H. , ...

Because the treatment of inhalational anthrax cannot be studied in human clinical trials, it is necessary to conduct efficacy studies using a rhesus monkey model. However, the half-life of...

Derivation of an In Vivo Drug Exposure Breakpoint for Flucytosine against Candida albicans and Impact of the MIC, Growth Rate, and Resistance Genotype on the Antifungal Effect▿

Hope, William W., Warn, Peter A., Sharp, Andrew, Howard, Susan, Kasai, Miki, Louie, Arnold, ...

Drug exposure or pharmacodynamic breakpoints refer to a magnitude of drug exposure which separates a population into groups with high and low probabilities of attaining a desired outcome. We used a...

Effect of Neutropenia and Treatment Delay on the Response to Antifungal Agents in Experimental Disseminated Candidiasis▿

Hope, William W., Drusano, George L., Moore, Caroline B., Sharp, Andrew, Louie, Arnold, Walsh, Thomas J., ...

Disseminated candidiasis is associated with a high rate of morbidity and mortality. The presence of neutrophils and the timely administration of antifungal agents are likely to be critical factors...

The Relationship between Quinolone Exposures and Resistance Amplification Is Characterized by an Inverted U: a New Paradigm for Optimizing Pharmacodynamics To Counterselect Resistance▿

Tam, Vincent H., Louie, Arnold, Deziel, Mark R., Liu, Weiguo, Drusano, George L.

We determined the relationship between garenoxacin exposure and quinolone-resistant subpopulations for three bacterial isolates in an in vitro hollow-fiber infection model. An “inverted-U”...

Once-Weekly Micafungin Therapy Is as Effective as Daily Therapy for Disseminated Candidiasis in Mice with Persistent Neutropenia▿

Gumbo, Tawanda, Drusano, George L., Liu, Weiguo, Kulawy, Robert W., Fregeau, Christine, Hsu, Vasha, ...

The effect of micafungin dose scheduling on the treatment of candidemia is unknown. Neutropenic mice with disseminated Candida glabrata infection were treated with single intraperitoneal micafungin...

Isoniazid Bactericidal Activity and Resistance Emergence: Integrating Pharmacodynamics and Pharmacogenomics To Predict Efficacy in Different Ethnic Populations▿

Gumbo, Tawanda, Louie, Arnold, Liu, Weiguo, Brown, David, Ambrose, Paul G., Bhavnani, Sujata M., ...

Isoniazid, administered as part of combination antituberculosis therapy, is responsible for most of the early bactericidal activity (EBA) of the regimen. However, the emergence of Mycobacterium...

Probability of Target Attainment for Ceftobiprole as Derived from a Population Pharmacokinetic Analysis of 150 Subjects▿

Lodise, Thomas P., Pypstra, Rienk, Kahn, James B., Murthy, Bindu P., Kimko, Hui C., Bush, Karen, ...

Ceftobiprole is a broad-spectrum cephalosporin with activity against methicillin-resistant Staphylococcus aureus (MRSA) that is undergoing phase III trials for the treatment of complicated skin and...

Impact of Resistance Selection and Mutant Growth Fitness on the Relative Efficacies of Streptomycin and Levofloxacin for Plague Therapy▿

Louie, Arnold, Deziel, Mark R., Liu, Weiguo, Drusano, George L.

Yersinia pestis, the bacterium that causes plague, is a potential agent of biowarfare and bioterrorism. The aminoglycoside antibiotic streptomycin is the gold standard for treatment. However, this...

Population Pharmacokinetics and Pharmacodynamics of Continuous versus Short-Term Infusion of Imipenem-Cilastatin in Critically Ill Patients in a Randomized, Controlled Trial▿

Sakka, Samir G., Glauner, Anna K., Bulitta, Jürgen B., Kinzig-Schippers, Martina, Pfister, Wolfgang, Drusano, George L., ...

Beta-lactams are regularly administered in intermittent short-term infusions. The percentage of the dosing interval during which free drug concentrations exceed the MIC (fT>MIC) is the measure of...

Population Pharmacokinetics at Two Dose Levels and Pharmacodynamic Profiling of Flucloxacillin▿

Landersdorfer, Cornelia B., Kirkpatrick, Carl M. J., Kinzig-Schippers, Martina, Bulitta, Jürgen B., Holzgrabe, Ulrike, Drusano, George L., ...

Flucloxacillin is often used for the treatment of serious infections due to sensitive staphylococci. The pharmacokinetic (PK)-pharmacodynamic (PD) breakpoint of flucloxacillin has not been determined...

Population Pharmacokinetics of Micafungin in Pediatric Patients and Implications for Antifungal Dosing▿

Hope, William W., Seibel, Nita L., Schwartz, Cindy L., Arrieta, Antonio, Flynn, Patricia, Shad, Aziza, ...

The echinocandins potentially have an important role in treatment of infections caused by Candida spp. and Aspergillus spp. in immunocompromised children. However, there are no population...

Optimization of the Dosage of Flucytosine in Combination with Amphotericin B for Disseminated Candidiasis: a Pharmacodynamic Rationale for Reduced Dosing▿

Hope, William W., Warn, Peter A., Sharp, Andrew, Reed, Paul, Keevil, Brian, Louie, Arnold, ...

Amphotericin B and flucytosine (5FC) have an additive effect when used for disseminated candidiasis. Here, we bridge the results of an experimental pharmacodynamic study to humans and demonstrate...

In Vitro Infection Model Characterizing the Effect of Efflux Pump Inhibition on Prevention of Resistance to Levofloxacin and Ciprofloxacin in Streptococcus pneumoniae▿

Louie, Arnold, Brown, David L., Liu, Weiguo, Kulawy, Robert W., Deziel, Mark R., Drusano, George L.

The prevalence of fluoroquinolone-resistant Streptococcus pneumoniae is slowly rising as a consequence of the increased use of fluoroquinolone antibiotics to treat community-acquired pneumonia. We...

Concentration-Dependent Mycobacterium tuberculosis Killing and Prevention of Resistance by Rifampin▿

Gumbo, Tawanda, Louie, Arnold, Deziel, Mark R., Liu, Weiguo, Parsons, Linda M., Salfinger, Max, ...

Rifampin is a cornerstone of modern antituberculosis therapy. However, rifampin's half-life of 3 h is believed to limit its utility for intermittent therapy, so new congeners with long half-lives are...

Evaluation of Tigecycline Penetration into Colon Wall Tissue and Epithelial Lining Fluid Using a Population Pharmacokinetic Model and Monte Carlo Simulation▿

Rubino, Christopher M., Ma, Lei, Bhavnani, Sujata M., Korth-Bradley, Joan, Speth, John, Ellis-Grosse, Evelyn, ...

The objective of these analyses was to assess the penetration of tigecycline into colon wall tissue and epithelial lining fluid (ELF). The analyses included data from subjects without infection...

Pharmacokinetics-Pharmacodynamics of Gatifloxacin in a Lethal Murine Bacillus anthracis Inhalation Infection Model▿

Ambrose, Paul G., Forrest, Alan, Craig, William A., Rubino, Chistopher M., Bhavnani, Sujata M., Drusano, George L., ...

We determined the pharmacokinetic-pharmacodynamic (PK-PD) measure most predictive of gatifloxacin efficacy and the magnitude of this measure necessary for survival in a murine Bacillus anthracis...

Use of Population Pharmacokinetic Modeling and Monte Carlo Simulation To Describe the Pharmacodynamic Profile of Cefditoren in Plasma and Epithelial Lining Fluid▿

Lodise, Thomas P., Kinzig-Schippers, Martina, Drusano, George L., Loos, Ulrich, Vogel, Friedrich, Bulitta, Jürgen, ...

Cefditoren is a broad-spectrum, oral cephalosporin that is highly active against clinically relevant respiratory tract pathogens, including multidrug-resistant Streptococcus pneumoniae. This study...

Telavancin Penetration into Human Epithelial Lining Fluid Determined by Population Pharmacokinetic Modeling and Monte Carlo Simulation▿

Lodise, Thomas P., Gotfried, Mark, Barriere, Steven, Drusano, George L.

Telavancin is an investigational bactericidal lipoglycopeptide with a multifunctional mechanism of action, as demonstrated against methicillin-resistant Staphylococcus aureus. While the plasma...

Pharmacodynamics of Cidofovir for Vaccinia Virus Infection in an In Vitro Hollow-Fiber Infection Model System▿

McSharry, James J., Deziel, Mark R., Zager, Kris, Weng, Qingmei, Drusano, George L.

Variola major virus remains a potent weapon of bioterror. There is currently an investigational-new-drug application for cidofovir for the therapy of variola major virus infections. Stittelaar and...

Penetration of Moxifloxacin into Bone Evaluated by Monte Carlo Simulation▿

Landersdorfer, Cornelia B., Kinzig, Martina, Hennig, Friedrich F., Bulitta, Jürgen B., Holzgrabe, Ulrike, Drusano, George L., ...

Moxifloxacin is a fluoroquinolone with a broad spectrum of activity and good penetration into many tissues, including bone. Penetration of moxifloxacin into bone has not yet been studied using...