This Article  • Full text  • PDF  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Citing articles on Web of Science (346)  • Contact me when this article is cited  Related Content  • Related article  • Similar articles in JAMA  Social Bookmarking   What's this?

A New Paradigm for Early Clinical Trials

Sandra L. Preston, PharmD; George L. Drusano, MD; Adam L. Berman; Cynthia L. Fowler, MD; Andrew T. Chow, PhD; Bruce Dornseif, PhD; Veronica Reichl, RN; Jaya Natarajan, PhD; Michael Corrado, MD

JAMA. 1998;279:125-129.

Context.— One purpose of early clinical trials is to establish the appropriate dose of an antibiotic for phase 3 trials. Development of a relationship between the ratio of drug exposure to organism minimum inhibitory concentration (MIC) and therapeutic response early in the development process would allow an optimal choice of dose to maximize response.

Objective.— To prospectively quantitate the relationship between plasma levels of levofloxacin and successful clinical and/or microbiological outcomes and occurrence of adverse events in infected patients.

Design.— Multicenter open-label trial.

Setting.— Twenty-two enrolling university-affiliated medical centers.

Patients.— A total of 313 patients with clinical signs and symptoms of bacterial infections of the respiratory tract, skin, or urinary tract.

Main Outcome Measures.— Clinical response and microbiological eradication of pathogenic organisms.

Results.— Of 313 patients, 272 had plasma concentration-time data obtained. Of these, 134 patients had a pathogen recovered from the primary infection site and had an MIC of the pathogen to levofloxacin determined. These patients constituted the primary analysis group for clinical outcome. Groups of 116 and 272 patients, respectively, were analyzed for microbiological outcome and incidence of adverse events. In a logistic regression analysis, the clinical outcome was predicted by the ratio of peak plasma concentration to MIC (Peak/MIC) and site of infection (P<.001). Microbiological eradication was predicted by the Peak/MIC ratio (P<.001). Both clinical and microbiological outcomes were most likely to be favorable if the Peak/MIC ratio was at least 12.2.

Conclusions.— Levofloxacin generated clinical and microbiological response rates of 95% and 96%, respectively. These response rates included fluoroquinolone "problem pathogens," such as Streptococcus pneumoniae and Staphylococcus aureus. Exposure to levofloxacin was significantly associated with successful clinical and microbiological outcomes. The principles used in these analyses can be applied to other classes of drugs to develop similar relationships between exposure and outcome. This pharmacokinetic modeling could be used to determine optimal treatment dose in clinical trials in a shorter time frame with fewer patients. This modeling also should be evaluated for its potential to improve outcomes (maximizing therapeutic response, preventing emergence of resistance, and minimizing adverse events) of patients treated with this drug.

From the Division of Clinical Pharmacology, Departments of Medicine and Pharmacology, Albany Medical College, Albany, NY (Drs Preston and Drusano and Mr Berman); Department of Pharmacy Practice, Albany College of Pharmacy (Dr Preston); and R.W. Johnson Pharmaceutical Research Institute, Raritan, NJ (Drs Fowler, Chow, Dornseif, Natarajan, and Corrado and Ms Reichl).

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter     What's this?

RELATED ARTICLE

Antibiotic Dosing—Does One Size Fit All?
Jerome J. Schentag
JAMA. 1998;279(2):159-160.
EXTRACT | FULL TEXT  

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

Impact of Low-Level Resistance to Fluoroquinolones Due to qnrA1 and qnrS1 Genes or a gyrA Mutation on Ciprofloxacin Bactericidal Activity in a Murine Model of Escherichia coli Urinary Tract Infection
Allou et al.
Antimicrob. Agents Chemother. 2009;53:4292-4297.
ABSTRACT | FULL TEXT  

Pharmacodynamic Profiling of Ceftobiprole for Treatment of Complicated Skin and Skin Structure Infections
Kimko et al.
Antimicrob. Agents Chemother. 2009;53:3371-3374.
ABSTRACT | FULL TEXT  

Rational dosing of antimicrobial agents: Pharmacokinetic and pharmacodynamic strategies
Owens and Shorr
Am J Health Syst Pharm 2009;66:S23-S30.
ABSTRACT | FULL TEXT  

Bactericidal Activity of the Combination of Levofloxacin with Rifampin in Experimental Prosthetic Knee Infection in Rabbits Due to Methicillin-Susceptible Staphylococcus aureus
Muller-Serieys et al.
Antimicrob. Agents Chemother. 2009;53:2145-2148.
ABSTRACT | FULL TEXT  

New Drugs against Tuberculosis: Problems, Progress, and Evaluation of Agents in Clinical Development
van den Boogaard et al.
Antimicrob. Agents Chemother. 2009;53:849-862.
FULL TEXT  

Effect of Differences in MIC Values on Clinical Outcomes in Patients with Bloodstream Infections Caused by Gram-Negative Organisms Treated with Levofloxacin
DeFife et al.
Antimicrob. Agents Chemother. 2009;53:1074-1079.
ABSTRACT | FULL TEXT  

Antibiotic Therapy in Critical Illness
Niederman
ACCP Crit Care Med Brd Rev 2009;20:523-538.
FULL TEXT  

Clinical implications of antimicrobial resistance for therapy
MacGowan and on behalf of the BSAC Working Parties on Resistanc
J Antimicrob Chemother 2008;62:ii105-ii114.
ABSTRACT | FULL TEXT  

Antagonistic Effect of Rifampin on the Efficacy of High-Dose Levofloxacin in Staphylococcal Experimental Foreign-Body Infection
Murillo et al.
Antimicrob. Agents Chemother. 2008;52:3681-3686.
ABSTRACT | FULL TEXT  

Quantitative Assessment of Combination Antimicrobial Therapy against Multidrug-Resistant Acinetobacter baumannii
Lim et al.
Antimicrob. Agents Chemother. 2008;52:2898-2904.
ABSTRACT | FULL TEXT  

Use of Population Pharmacokinetic Modeling and Monte Carlo Simulation To Describe the Pharmacodynamic Profile of Cefditoren in Plasma and Epithelial Lining Fluid
Lodise et al.
Antimicrob. Agents Chemother. 2008;52:1945-1951.
ABSTRACT | FULL TEXT  

Clinical Microdialysis in Skin and Soft Tissues: An Update
Schmidt et al.
J Clin Pharmacol 2008;48:351-364.
ABSTRACT | FULL TEXT  

Setting and Revising Antibacterial Susceptibility Breakpoints
Turnidge and Paterson
Clin. Microbiol. Rev. 2007;20:391-408.
ABSTRACT | FULL TEXT  

Clinical Pharmacodynamics of Meropenem in Patients with Lower Respiratory Tract Infections
Li et al.
Antimicrob. Agents Chemother. 2007;51:1725-1730.
ABSTRACT | FULL TEXT  

Levofloxacin Pharmacokinetics in Adult Cystic Fibrosis
Lee et al.
Chest 2007;131:796-802.
ABSTRACT | FULL TEXT  

Efficacy of High Doses of Levofloxacin in Experimental Foreign-Body Infection by Methicillin-Susceptible Staphylococcus aureus
Murillo et al.
Antimicrob. Agents Chemother. 2006;50:4011-4017.
ABSTRACT | FULL TEXT  

Pharmacodynamics of moxifloxacin and levofloxacin against Streptococcus pneumoniae, Staphylococcus aureus, Klebsiella pneumoniae and Escherichia coli: simulation of human plasma concentrations after intravenous dosage in an in vitro kinetic model
Odenholt and Cars
J Antimicrob Chemother 2006;58:960-965.
ABSTRACT | FULL TEXT  

Effect of Treatment Duration on Pharmacokinetic/Pharmacodynamic Indices Correlating with Therapeutic Efficacy of Ceftazidime in Experimental Klebsiella pneumoniae Lung Infection.
Bakker-Woudenberg et al.
Antimicrob. Agents Chemother. 2006;50:2919-2925.
ABSTRACT | FULL TEXT  

Which reliable pharmacodynamic breakpoint should be advised for ciprofloxacin monotherapy in the hospital setting? A TDM-based retrospective perspective
Pea et al.
J Antimicrob Chemother 2006;58:380-386.
ABSTRACT | FULL TEXT  

Applying antimicrobial pharmacodynamics to resistant gram-negative pathogens.
Scheetz et al.
Am J Health Syst Pharm 2006;63:1346-1360.
ABSTRACT | FULL TEXT  

Levofloxacin pharmacokinetics and pharmacodynamics in patients with severe burn injury.
Kiser et al.
Antimicrob. Agents Chemother. 2006;50:1937-1945.
ABSTRACT | FULL TEXT  

Pharmacokinetic-Pharmacodynamic Relationships Describing the Efficacy of Oritavancin in Patients with Staphylococcus aureus Bacteremia
Bhavnani et al.
Antimicrob. Agents Chemother. 2006;50:994-1000.
ABSTRACT | FULL TEXT  

In Vivo Efficacies and Pharmacokinetics of DX-619, a Novel Des-Fluoro(6) Quinolone, against Streptococcus pneumoniae in a Mouse Lung Infection Model
Fukuda et al.
Antimicrob. Agents Chemother. 2006;50:121-125.
ABSTRACT | FULL TEXT  

Effective Antimicrobial Regimens for Use in Humans for Therapy of Bacillus anthracis Infections and Postexposure Prophylaxis
Deziel et al.
Antimicrob. Agents Chemother. 2005;49:5099-5106.
ABSTRACT | FULL TEXT  

Pharmacokinetics and Pharmacodynamics of the New Quinolones
Noreddin et al.
Journal of Pharmacy Practice 2005;18:432-443.
ABSTRACT  

Pharmacokinetics and Pharmacodynamics of a Novel Extended-Release Ciprofloxacin in Healthy Volunteers
Washington et al.
J Clin Pharmacol 2005;45:1236-1244.
ABSTRACT | FULL TEXT  

Evaluating Ciprofloxacin Dosing for Pseudomonas aeruginosa Infection by Using Clinical Outcome-Based Monte Carlo Simulations
Zelenitsky et al.
Antimicrob. Agents Chemother. 2005;49:4009-4014.
ABSTRACT | FULL TEXT  

Pharmacodynamics of Levofloxacin in Patients With Acute Exacerbation of Chronic Bronchitis
Cazzola et al.
Chest 2005;128:2093-2098.
ABSTRACT | FULL TEXT  

Antistaphylococcal Effect Related to the Area under the Curve/MIC Ratio in an In Vitro Dynamic Model: Predicted Breakpoints versus Clinically Achievable Values for Seven Fluoroquinolones
Firsov et al.
Antimicrob. Agents Chemother. 2005;49:2642-2647.
ABSTRACT | FULL TEXT  

Specific Antibodies, Levofloxacin, and Modulation of Capsule-Associated Virulence in Streptococcus pneumoniae
Tarrago et al.
Antimicrob. Agents Chemother. 2005;49:3095-3096.
FULL TEXT  

Patient stratification in the management of acute bacterial exacerbation of chronic bronchitis: the role of levofloxacin 750 mg
Martinez et al.
Eur Respir J 2005;25:1001-1010.
ABSTRACT | FULL TEXT  

Application of an In Vitro Infection Model and Simulation for Reevaluation of Fluoroquinolone Breakpoints for Salmonella enterica Serotype Typhi
Booker et al.
Antimicrob. Agents Chemother. 2005;49:1775-1781.
ABSTRACT | FULL TEXT  

The Effects of Continuous Renal Replacement on Anti-infective Therapy in the Critically Ill
Kubin and Dzierba
Journal of Pharmacy Practice 2005;18:109-117.
ABSTRACT  

Bacteriostatic and bactericidal activities of eight fluoroquinolones against MexAB-OprM-overproducing clinical strains of Pseudomonas aeruginosa
Dupont et al.
J Antimicrob Chemother 2005;55:518-522.
ABSTRACT | FULL TEXT  

Levofloxacin Pharmacokinetics in Children
Chien et al.
J Clin Pharmacol 2005;45:153-160.
ABSTRACT | FULL TEXT  

Pharmacokinetics and Pharmacodynamics of Meropenem in Febrile Neutropenic Patients with Bacteremia
Ariano et al.
The Annals of Pharmacotherapy 2005;39:32-38.
ABSTRACT | FULL TEXT  

Pharmacodynamic Profiling of Piperacillin in the Presence of Tazobactam in Patients through the Use of Population Pharmacokinetic Models and Monte Carlo Simulation
Lodise et al.
Antimicrob. Agents Chemother. 2004;48:4718-4724.
ABSTRACT | FULL TEXT  

Evolution of Ciprofloxacin-Resistant Staphylococcus aureus in In Vitro Pharmacokinetic Environments
Campion et al.
Antimicrob. Agents Chemother. 2004;48:4733-4744.
ABSTRACT | FULL TEXT  

The Changing Face of Antibiotic Prescribing: The Mutant Selection Window
Epstein et al.
The Annals of Pharmacotherapy 2004;38:1675-1682.
ABSTRACT | FULL TEXT  

Novel Pharmacokinetic-Pharmacodynamic Model for Prediction of Outcomes with an Extended-Release Formulation of Ciprofloxacin
Meagher et al.
Antimicrob. Agents Chemother. 2004;48:2061-2068.
ABSTRACT | FULL TEXT  

Towards targeted prescribing: will the cure for antimicrobial resistance be specific, directed therapy through improved diagnostic testing?
Peterson and Dalhoff
J Antimicrob Chemother 2004;53:902-905.
ABSTRACT | FULL TEXT  

Mutant Selection Window in Levofloxacin and Moxifloxacin Treatments of Experimental Pneumococcal Pneumonia in a Rabbit Model of Human Therapy
Croisier et al.
Antimicrob. Agents Chemother. 2004;48:1699-1707.
ABSTRACT | FULL TEXT  

Peritoneal Fluid Titer Test for Peritoneal Dialysis-Related Peritonitis
Strijack et al.
Antimicrob. Agents Chemother. 2004;48:1719-1726.
ABSTRACT | FULL TEXT  

Steady-State Intrapulmonary Concentrations of Moxifloxacin, Levofloxacin, and Azithromycin in Older Adults
Capitano et al.
Chest 2004;125:965-973.
ABSTRACT | FULL TEXT  

In Vitro Pharmacodynamic Activities of ABT-492, a Novel Quinolone, Compared to Those of Levofloxacin against Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis
Gunderson et al.
Antimicrob. Agents Chemother. 2004;48:203-208.
ABSTRACT | FULL TEXT  

In Vivo Efficacy of a New Quinolone, DQ-113, against Streptococcus pneumoniae in a Mouse Model
Otsu et al.
Antimicrob. Agents Chemother. 2003;47:3699-3703.
ABSTRACT | FULL TEXT  

Pharmacodynamics of the New Des-F(6)-Quinolone Garenoxacin in a Murine Thigh Infection Model
Andes and Craig
Antimicrob. Agents Chemother. 2003;47:3935-3941.
ABSTRACT | FULL TEXT  

Pharmacological indices in antibiotic therapy
Barger et al.
J Antimicrob Chemother 2003;52:893-898.
ABSTRACT | FULL TEXT  

Bronchoscopic Sampling of Drug Concentrations: Penetration to Tissue Is the Issue
Fish
Am. J. Respir. Crit. Care Med. 2003;168:1263-1265.
FULL TEXT  

Bronchoscopic Microsampling Method for Measuring Drug Concentration in Epithelial Lining Fluid
Yamazaki et al.
Am. J. Respir. Crit. Care Med. 2003;168:1304-1307.
ABSTRACT | FULL TEXT  

Levofloxacin Disposition in Cerebrospinal Fluid in Patients with External Ventriculostomy
Pea et al.
Antimicrob. Agents Chemother. 2003;47:3104-3108.
ABSTRACT | FULL TEXT  

Pharmacokinetic/Pharmacodynamic Considerations in Community-Acquired Lower Respiratory Tract Infections
Smith
Journal of Pharmacy Practice 2003;16:313-323.
ABSTRACT  

Treatment and outcome of Pseudomonas aeruginosa bacteraemia: an antibiotic pharmacodynamic analysis
Zelenitsky et al.
J Antimicrob Chemother 2003;52:668-674.
ABSTRACT | FULL TEXT  

Fluoroquinolone AUIC Break Points and the Link to Bacterial Killing Rates Part 2: Human Trials
Schentag et al.
The Annals of Pharmacotherapy 2003;37:1478-1488.
ABSTRACT | FULL TEXT  

AUIC in Humans: A Fact-Based Discussion
Amsden et al.
The Annals of Pharmacotherapy 2003;37:1518-1521.
FULL TEXT  

Pharmacodynamics of Levofloxacin and Ciprofloxacin in a Murine Pneumonia Model: Peak Concentration/MIC versus Area under the Curve/MIC Ratios
Scaglione et al.
Antimicrob. Agents Chemother. 2003;47:2749-2755.
ABSTRACT | FULL TEXT  

Characterization of the onset and consequences of pneumonia due to fluoroquinolone-susceptible or -resistant Pseudomonas aeruginosa
Paladino et al.
J Antimicrob Chemother 2003;52:457-463.
ABSTRACT | FULL TEXT  

Lack of Bioequivalence of Levofloxacin When Coadministered with a Mineral-Fortified Breakfast of Juice and Cereal
Amsden et al.
J Clin Pharmacol 2003;43:990-995.
ABSTRACT | FULL TEXT  

Fluoroquinolone AUIC Break Points and the Link to Bacterial Killing Rates: Part 1: In Vitro and Animal Models
Schentag et al.
The Annals of Pharmacotherapy 2003;37:1287-1298.
ABSTRACT | FULL TEXT  

The mutant selection window and antimicrobial resistance
Drlica
J Antimicrob Chemother 2003;52:11-17.
ABSTRACT | FULL TEXT  

Lack of Bioequivalence When Levofloxacin and Calcium-Fortified Orange Juice Are Coadministered to Healthy Volunteers
Wallace et al.
J Clin Pharmacol 2003;43:539-544.
ABSTRACT | FULL TEXT  

Optimizing ceftazidime pharmacodynamics in patients with acute exacerbation of severe chronic bronchitis
Lubasch et al.
J Antimicrob Chemother 2003;51:659-664.
ABSTRACT | FULL TEXT  

Efficacy of liposome-encapsulated ciprofloxacin compared with ciprofloxacin and ceftriaxone in a rat model of pneumococcal pneumonia
Ellbogen et al.
J Antimicrob Chemother 2003;51:83-91.
ABSTRACT | FULL TEXT  

Lack of Bioequivalence of Gatifloxacin When Coadministered with Calcium-Fortified Orange Juice in Healthy Volunteers
Wallace et al.
J Clin Pharmacol 2003;43:92-96.
ABSTRACT | FULL TEXT  

Efficacy and pharmacodynamics of simulated human-like treatment with levofloxacin on experimental pneumonia induced with penicillin-resistant pneumococci with various susceptibilities to fluoroquinolones
Croisier et al.
J Antimicrob Chemother 2002;50:349-360.
ABSTRACT | FULL TEXT  

Ciprofloxacin in Polyethylene Glycol-Coated Liposomes: Efficacy in Rat Models of Acute or Chronic Pseudomonas aeruginosa Infection
Bakker-Woudenberg et al.
Antimicrob. Agents Chemother. 2002;46:2575-2581.
ABSTRACT | FULL TEXT  

Pharmacokinetic/pharmacodynamic modelling of ciprofloxacin 250 mg/12 h versus 500 mg/24 h for urinary infections
Sanchez Navarro et al.
J Antimicrob Chemother 2002;50:67-72.
ABSTRACT | FULL TEXT  

In Vitro Activities of Novel Nonfluorinated Quinolones PGE 9262932 and PGE 9509924 against Clinical Isolates of Staphylococcus aureus and Streptococcus pneumoniae with Defined Mutations in DNA Gyrase and Topoisomerase IV
Jones et al.
Antimicrob. Agents Chemother. 2002;46:1651-1657.
ABSTRACT | FULL TEXT  

Pharmacodynamics of the New Fluoroquinolone Gatifloxacin in Murine Thigh and Lung Infection Models
Andes and Craig
Antimicrob. Agents Chemother. 2002;46:1665-1670.
ABSTRACT | FULL TEXT  

Pharmacodynamics of Moxifloxacin against Streptococcus pyogenes in an In Vitro Kinetic Model
Odenholt et al.
Antimicrob. Agents Chemother. 2002;46:2046-2048.
ABSTRACT | FULL TEXT  

Comparison of Levofloxacin, Alatrofloxacin, and Vancomycin for Prophylaxis and Treatment of Experimental Foreign-Body-Associated Infection by Methicillin-Resistant Staphylococcus aureus
Vaudaux et al.
Antimicrob. Agents Chemother. 2002;46:1503-1509.
ABSTRACT | FULL TEXT  

Resistance to Levofloxacin and Failure of Treatment of Pneumococcal Pneumonia
Davidson et al.
NEJM 2002;346:747-750.
FULL TEXT  

Pharmacodynamic considerations in the treatment of moderate to severe pseudomonal infections with cefepime
Ambrose et al.
J Antimicrob Chemother 2002;49:445-453.
ABSTRACT | FULL TEXT  

Pharmacodynamics of Gatifloxacin against Streptococcus pneumoniae in an In Vitro Pharmacokinetic Model: Impact of Area under the Curve/MIC Ratios on Eradication
Lister
Antimicrob. Agents Chemother. 2002;46:69-74.
ABSTRACT | FULL TEXT  

Antibiotic therapy of community respiratory tract infections: strategies for optimal outcomes and minimized resistance emergence
Ball et al.
J Antimicrob Chemother 2002;49:31-40.
ABSTRACT | FULL TEXT  

Pharmacodynamics of Trovafloxacin and Levofloxacin against Bacteroides fragilis in an In Vitro Pharmacodynamic Model
Peterson et al.
Antimicrob. Agents Chemother. 2002;46:203-210.
ABSTRACT | FULL TEXT  

BTS Guidelines for the Management of Community Acquired Pneumonia in Adults
Thorax 2001;56:iv1-64.
FULL TEXT  

Pharmacodynamics and Bactericidal Activity of Moxifloxacin in Experimental Escherichia coli Meningitis
Rodriguez-Cerrato et al.
Antimicrob. Agents Chemother. 2001;45:3092-3097.
ABSTRACT | FULL TEXT  

Pharmacodynamics of Gemifloxacin against Streptococcus pneumoniae in an In Vitro Pharmacokinetic Model of Infection
MacGowan et al.
Antimicrob. Agents Chemother. 2001;45:2916-2921.
ABSTRACT | FULL TEXT  

Pharmacokinetics of Levofloxacin and Ciprofloxacin during Continuous Renal Replacement Therapy in Critically Ill Patients
Malone et al.
Antimicrob. Agents Chemother. 2001;45:2949-2954.
ABSTRACT | FULL TEXT  

Pharmacodynamic Evaluation of RWJ-270201, a Novel Neuraminidase Inhibitor, in a Lethal Murine Model of Influenza Predicts Efficacy for Once-Daily Dosing
Drusano et al.
Antimicrob. Agents Chemother. 2001;45:2115-2118.
ABSTRACT | FULL TEXT  

Activities of Newer Fluoroquinolones against Ciprofloxacin-Resistant Streptococcus pneumoniae
Coyle et al.
Antimicrob. Agents Chemother. 2001;45:1654-1659.
ABSTRACT | FULL TEXT  

Cerebrospinal fluid penetration and pharmacokinetics of levofloxacin in an experimental rabbit meningitis model
Destache et al.
J Antimicrob Chemother 2001;47:611-615.
ABSTRACT | FULL TEXT  

Tissue penetration of a single dose of levofloxacin intravenously for antibiotic prophylaxis in lung surgery
von Baum et al.
J Antimicrob Chemother 2001;47:729-730.
FULL TEXT  

In Vivo Efficacy of Trovafloxacin against Bacteroides fragilis in Mixed Infection with either Escherichia coli or a Vancomycin-Resistant Strain of Enterococcus faecium in an Established-Abscess Murine Model
Stearne et al.
Antimicrob. Agents Chemother. 2001;45:1394-1401.
ABSTRACT | FULL TEXT  

Improved Efficacy of Ciprofloxacin Administered in Polyethylene Glycol-Coated Liposomes for Treatment of Klebsiella pneumoniae Pneumonia in Rats
Bakker-Woudenberg et al.
Antimicrob. Agents Chemother. 2001;45:1487-1492.
ABSTRACT | FULL TEXT  

In vitro pharmacodynamic modelling simulating free serum concentrations of fluoroquinolones against multidrug-resistant Streptococcus pneumoniae
Zhanel et al.
J Antimicrob Chemother 2001;47:435-440.
ABSTRACT | FULL TEXT  

Steady-State Plasma and Intrapulmonary Concentrations of Levofloxacin and Ciprofloxacin in Healthy Adult Subjects
Gotfried et al.
Chest 2001;119:1114-1122.
ABSTRACT | FULL TEXT  

Comparative Bactericidal Activities of Ciprofloxacin, Clinafloxacin, Grepafloxacin, Levofloxacin, Moxifloxacin, and Trovafloxacin against Streptococcus pneumoniae in a Dynamic In Vitro Model
Klepser et al.
Antimicrob. Agents Chemother. 2001;45:673-678.
ABSTRACT | FULL TEXT  

Pharmacodynamics of Daptomycin in a Murine Thigh Model of Staphylococcus aureus Infection
Louie et al.
Antimicrob. Agents Chemother. 2001;45:845-851.
ABSTRACT | FULL TEXT  

Use of Preclinical Data for Selection of a Phase II/III Dose for Evernimicin and Identification of a Preclinical MIC Breakpoint
Drusano et al.
Antimicrob. Agents Chemother. 2001;45:13-22.
ABSTRACT | FULL TEXT  

Antibacterial Spectrum of a Novel Des-Fluoro(6) Quinolone, BMS-284756
Fung-Tomc et al.
Antimicrob. Agents Chemother. 2000;44:3351-3356.
ABSTRACT | FULL TEXT  

Levofloxacin Pharmacokinetics and Serum Bactericidal Activities against Five Enterobacterial Species
Geerdes-Fenge et al.
Antimicrob. Agents Chemother. 2000;44:3478-3480.
ABSTRACT | FULL TEXT  

Application of fluoroquinolone pharmacodynamics
Wright et al.
J Antimicrob Chemother 2000;46:669-683.
ABSTRACT | FULL TEXT  

The use of in vitro pharmacodynamic models of infection to optimize fluoroquinolone dosing regimens
MacGowan et al.
J Antimicrob Chemother 2000;46:163-170.
FULL TEXT  

Assessment of different antibacterial effect measures used in in vitro models of infection and subsequent use in pharmacodynamic correlations for moxifloxacin
MacGowan et al.
J Antimicrob Chemother 2000;46:73-78.
ABSTRACT | FULL TEXT  

Pharmacodynamics to combat resistance
Woodnutt
J Antimicrob Chemother 2000;46:25-31.
ABSTRACT | FULL TEXT  

Clinafloxacin serum concentrations in a patient on continuous veno-venous haemofiltration
Darley et al.
J Antimicrob Chemother 2000;45:927-928.
FULL TEXT  

Streptococcus pneumoniae in the USA: in vitro susceptibility and pharmacodynamic analysis
Mason et al.
J Antimicrob Chemother 2000;45:623-631.
ABSTRACT | FULL TEXT  

Pharmacokinetics and Pharmacodynamics of Levofloxacin against Streptococcus pneumoniae and Staphylococcus aureus in Human Skin Blister Fluid
Trampuz et al.
Antimicrob. Agents Chemother. 2000;44:1352-1355.
ABSTRACT | FULL TEXT