TAKSTATM (CEM-102)

Fusidic acid (TAKSTATM, CEM-102) is an antibiotic with a long history of safety and efficacy outside the United States. Cempra has exclusive rights to the supply of the compound for the U.S. market. Fusidic acid is orally active against gram-positive bacteria, including all S. aureus strains such as HA-MRSA and CA-MRSA. A novel dosing regimen has been successfully evaluated in a Phase II trial in patients with acute bacterial skin and skin structure infections (aBSSSI). Cempra is conducting a Phase II trial of TAKSTA for patients with prosthetic joint infections.


Profile of TAKSTA (CEM-102)
Prosthetic joint infections (PJI) occur in about 1% of hip replacements and 2% of knee replacements, translating to an incidence rate of about 10,000 per year in the U.S. at current hip and knee arthroplasty rates.  There are few good options to treat these serious staphylococcal, often MRSA infections, which require long-term antibiotic treatment.  Current therapy in the U.S. is with intravenous antibiotics such as vancomycin.  An oral drug that can be safely administered for a long period of time could improve care and quality of life for these patients.

TAKSTA has shown potent activity against a large number of S. aureus strains, including CA-MRSA, HA-MRSA and linezolid-resistant strains, isolated in the U.S over a 10 year period. Its broad S. aureus coverage makes it useful for a broad range of clinical applications. Because of its safety and tolerability profile, TAKSTA could be ideal for patients suffering from staphylococcal infections that require long-term therapy such as patients with PJIs.

Cempra has developed a unique oral loading dose regimen to optimize key pathogen coverage and minimize drug resistance development. This regimen is incorporated in our Phase II trial to treat PJIs with TAKSTA in combination with rifampin, which is commonly used with injectible antibiotics such as vancomycin to treat PJIs.
 

 


Research on TAKSTA

Publications

The links for the articles go to subscription-based sites and may require a fee to view the article.

In Vitro Activity of CEM-102 (Fusidic Acid) Against Prevalent Clones and Resistant Phenotypes of Staphylococcus aureus
DF Sahm, J Deane, CM Pillar, P Fernandes 
Antimicrobial Agents and Chemotherapy. June 2013  57: 4535-4346
http://aac.asm.org/content/57/9/4535

Efforts to Support the Development of Fusidic Acid in the United States
P Fernandes, D Pereira
Clinical Infectious Disease. June 2011 52:S542-6
http://www.ncbi.nlm.nih.gov/pubmed/21546632

Case report: Treatment of Chronic Osteomyelitis 
CR Wolfe
Clinical Infectious Disease. June 2011 52:S538-41
http://cid.oxfordjournals.org/content/52/suppl_7/S538.long

The Safety Record of Fusidic Acid in Non-US markets: A Focus on Skin Infections
CN Kraus, BW Burnstead 
Clinical Infectious Disease. June 2011 52:S527-37
http://cid.oxfordjournals.org/content/52/suppl_7/S527.long

A Randomized, Double-Blind Phase 2 Study Comparing the Efficacy and Safety of an Oral Fusidic Acid Loading-Dose Regimen to Oral Linezolid in the Treatment of Acute Bacterial Skin and Skin Structure Infections 
JC Craft, SR Moriarty, K Clark, D Scott, TP Degenhardt, JG Still, GR Corey, A Das,  P Fernandes
Clinical Infectious Disease. June 2011 52:S520-26
http://cid.oxfordjournals.org/content/52/suppl_7/S520.long

Application of Pharmacokinetic-Pharmacodynamic Modeling and the Justification of a Novel Fusidic Acid Dosing Regimen: Raising Lazarus from the Dead 
BT Tsuji, OO Okusanya, JB Bulitta, A Forrest, SM Bhavnani, P Fernandes, PG Ambrose 
Clinical Infectious Disease. June 2011 52:S513-19
http://cid.oxfordjournals.org/content/52/suppl_7/S513.long

Pharmacokinetics and Safety of Single, Multiple, and Loading Doses of Fusidic Acid in Healthy Subjects 
JG Still,  K Clark, TP Degenhardt, D. Scott, P. Fernandes,  M. J. Gutierrez 
Clinical Infectious Disease. June 2011 52:S504-12
http://cid.oxfordjournals.org/content/52/suppl_7/S504.long

Activity of Fusidic Acid Against Extracellular and Intracellular Staphylococcus aureus: Influence of pH and Comparison with Linezolid and Clindamycin
S Lemaire,  F Van Bambeke, D Pierard, PC Appelbaum,  PM Tulkens
Clinical Infectious Disease. June 2011 52:S493-503
http://cid.oxfordjournals.org/content/52/suppl_7/S493.long

Characterization of Global Patterns and the Genetics of Fusidic Acid Resistance 
DJ Farrell, M Castanheira, I Chopra
Clinical Infectious Disease. June 2011  52:S487-92
http://cid.oxfordjournals.org/content/52/suppl_7/S487.long

In Vitro Antimicrobial Findings for Fusidic Acid Tested Against Contemporary (2008-2009) Gram-Positive Organisms Collected in the United States
RN Jones, RE Mendes, HS Sader, M Castanheira
Clinical Infectious Disease. June 2011 52:S477-86
http://cid.oxfordjournals.org/content/52/suppl_7/S477.long

New Rules for Clinical Trials in Patients with Acute Bacterial Skin and Skin Structure Iinfections: Do not Let the Perfect be the Enemy of the Good 
GR Corey, ME Stryjewski
Clinical Infectious Disease. June 2011 52:S469-76
http://cid.oxfordjournals.org/content/52/suppl_7/S469.long

Introduction: Fusidic Acid Enters the United States
RC Moellering,  GR Corey, ML Grayson
Clinical Infectious Disease. June 2011 52:S467-8
http://cid.oxfordjournals.org/content/52/suppl_7/S467.long

Evaluation of the Pharmacokinetics-Pharmacodynamics of Fusidic Acid Against Staphylococcus aureus and Streptococcus pyogenes Using In Vitro Infection Models: Implications for Dose Selection 
OO Okusanya, BT Tsuji, JB Bulitta, A Forrest, CC Bulik, SM Bhavnani, P Fernandes, PG Ambrose
Diagnostic Microbiology & Infectious Disease. June 2011 70:101-11
http://www.ncbi.nlm.nih.gov/pubmed/21513848

In Vitro Activity of Fusidic Acid (CEM-102, Sodium Fusidate) Against Staphylococcus aureus Isolated from Cystic Fibrosis Patients and its Effect on the Activities of Tobramycin and Amikacin against Pseudomonas aeruginosa and Burkholderia cepacia 
P McGhee, K Credito, L Beachel, PC Appelbaum,  K Kosowaska-Shick
Antimicrobial Agents and Chemotherapy. June 2011 55:2417-19
http://www.ncbi.nlm.nih.gov/pubmed/21343445

Occurrence and Molecular Characterization of Fusidic Acid Resistance Mechanisms Among Staphylococcus spp. From European Countries (2008)
Castanheira, M., AA Watters, RE Mendes, DJ Farrell, RN Jones
Antimicrobial Agents and Chemotherapy. April 2010 65:1353-8
http://jac.oxfordjournals.org/content/65/7/1353.long

Update on Fusidic Acid (CEM-102) Tested Against Neisseria gonorrhoeae and Chlamydia trachomatis
R Jones, D Biedenbach, P Roblin, S Kohlhoff, M Hammerschlag
Antimicrobial Agents and Chemotherapy. October 2010 54: 4518-4519
http://aac.asm.org/cgi/content/citation/54/10/4518

Fusidic Acid Resistance Rates and Prevalence of Resistance Mechanisms Among Staphylococcus spp. Isolated in North America and Australia, 2007-2008
M Castanheira, AA Watters, JM Bell, JD Turnidge, RN Jones
Antimicrobial Agents and Chemotherapy. September 2010 54: 3614-3617
http://www.ncbi.nlm.nih.gov/pubmed/20566766

Spectrum of Activity, Mutation Rates, Synergistic Interactions, and the Effects of pH and Serum Proteins for Fusidic Acid (CEM-102)
D Biedenbach, P Rhomberg, R Mendes, R Jones
Diagnostic Microbiology & Infectious Disease. March 2010 66: 301-307
http://www.dmidjournal.com/article/S0732-8893(09)00424-6/abstract

Performance of Fusidic Acid (CEM-102) Susceptibility Testing Reagents: Broth Microdilution, Disk Diffusion, and Etest Methods as Applied to Staphylococcus aureus
R Jones, M Castanheira, P Rhomberg, L Woosley, M Pfaller
Journal of Clinical Microbiology. March 2010 48: 972-976
http://jcm.asm.org/cgi/content/abstract/48/3/972

Evaluation of the Activity of Fusidic Acid Tested Against Contemporary Gram-Positive Clinical Isolates From the USA and Canada
M Pfaller, M Castaneira, H Sader, R Jones
International Journal of Antimicrobial Agents. March 2010 35: 282-287
http://www.ijaaonline.com/article/S0924-8579(09)00510-X/abstract

 

 

6th ASM Conference on Biofilms 2012 (Sept 29-Oct 4) - Miami, FL 2012
 

Quantitative and qualitative assessment of antibiotic activity against Staphylococcus aureus biofilm.
Siala, W., M. P. Mingeot-Leclercq, P. M. Tulkens, and F. Van Bambeke.
Abstr. 6th Am. Soc. Microbiol. Conf. Biofilms, abstr A-179.
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NACFC 2011
 

Activity of Fusidic Acid Against Methicillin-resistant Staphylococcus Aureus (MRSA) Isolated from CF Patients
Prabhavathi Fernandes, Donald Anderson, K. Kosowska-Shick, P. McGhee, L. Beachel and P.C. Appelbaum
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ECCMID 2011

Evaluation of L6 Ribosomal Protein Alterations in Fusidic Acid-Resistant Staphylococcus aureus: Fitness Cost and Time Kill Analysis
M Castanheira, RN Jones, LN Woosley, RE Mendes, GJ Moet, DJ Farrell
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Fusidic Acid Activity and Coverage of Gram-positive Pathogens Associated with Acute Bacterial Skin and Skin Structure Infections (ABSSSI) in the USA (2008-2010)
RN Jones, DJ Farrell, HS Sader, M Castanheira
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IDSA 2010

Spectrum of Activity

Activity of Fusidic Acid Tested Against Contemporary Staphylococcus aureus Collected from United States Hospitals
M. Castanheira, R.E. Mendes, P.R. Rhomberg, R.N. Jones
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ICAAC 2010

Spectrum of Activity

Pharmacokinetics-Pharmacodynamics (PK-PD) of CEM- 102 (Sodium Fusidate) Against Streptococcus pyogenes Using In Vitro Pharmacodynamic Models (IVPM)
B. T. Tsuji, A. Forrest, P. A. Kelchlin, T. Brown, P. N. Holden, O. O. Okusanya, S. M. Bhavnani, P. Fernandes, P. G. Ambrose
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Activity of CEM-102 (sodium fusidate) against 40 MRSA from Cystic Fibrosis Patients
Cynthia Todd, Pamela Mcghee, and Peter Appelbaum
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Ability of CEM-102 (Fusidic Acid), Linezolid, Daptomycin to Select Resistant S.aureus Mutants at Steady-state Serum Levels
K. Kosowska-Shick, P. Mcghee, L. Beachel, P. C. Appelbaum;
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CEM-102 (Fusidic Acid) Maintains Potency against Resistant MRSA and Prevalent Hospital Acquired, Community Acquired,and Epidemic MRSA Clones
C.M. Pillar, M.K. Torres, D.F. Sahm and P. Fernandes
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In Vitro Activity Of Fusicic Acid (CEM-102) Against Resistant Strains Of Staphylococcus aureus
J. dubois, P. Fernandes
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Clinical Data

Efficacy and Safety of CEM-102 in a Phase 2, Randomized, Double-Blind Study in Patients with Acute Bacterial Skin and Skin Structure Infections (ABSSSI)
S. R. Moriarty, K. Clark, D. Scott, T. P. Degenhardt, P. Fernandes, J.C. Craft, G.R. Corey, J.G. Still; A Das
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ECCMID 2010

Spectrum of Activity

CEM-102 (fusidic acid) in vitro activity and evaluation of molecular resistance mechanisms among European Gram-positive isolates, 2008-2009
M. Castanheira, D. Farrell, M. Janechek, R. Jones
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IDSA 2009

PK-PD

CEM-102 (Sodium Fusidate) Dosage Regimen Decision Support Using Population Pharmacokinetic (PPK) and Mechanism-Based Pharmacokinetic-Pharmacodynamic (PK-PD) Models
OO OKUSANYA, JB. BULITTA, A FORREST, BT TSUJI, SM BHAVNANI, J GORDON STILL, P FERNANDES, PG AMBROSE
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Spectrum of Activity

Contemporary Antimicrobial Activity of CEM-102 (Fusidic Acid [FA)]) Against Canadian Isolates of Staphylococci and Streptococci (2001-2006)
P. R. Rhomberg, L.N. Woosley, H.S. Sader, R. N. Jones
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Update on the Spectrum of CEM-102 (Fusidic Acid [FA)]) Against Contemporary Wildtype (WT) Bacterial Species Including Mutational Resistance (R) Analysis, and Synergy Testing
P. R. Rhomberg, R. E. Mendes, H. K. Becker, K. A. Fedler, H. S. Sader, R. N.
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Assay Standards

Performance of CEM-102 (Fusidic Acid [FA)]) Susceptibility Testing Reagents; Broth Microdilution, Disk Diffusion and Etest Methods.
P. R. Rhomberg, L.N. Woosley, H.S. Sader, R. N. Jones
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ICAAC 2009

Spectrum of Activity

Relevance of Protein Binding of CEM-102 (Fusidic acid) and its pH-dependent Effect on in vitro Activity
TP Degenhardt, PR Rhomberg, RN Jones, P Fernandes, D Johnson
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Contrasting Effect of Acidic pH on the Bactericidal Activities of CEM-102 (Fusidic Acid) vs. Linezolid and Clindamycin Towards Staphylococcus aureus
PM Tulkens, S Lemaire, F Van Bambeke
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Preclinical Models

Pharmacokinetics-Pharmacodynamics (PK-PD) of CEM-102 against Methicillin-Resistant Staphylococcus aureus (MRSA) using an In Vitro PD Model (IVPM) and Mechanism-Based (MB) Modeling
BT Tsuji, JB Bulitta, A Forrest, PA Kelchlin, T Brown, PN Holden, MP Pai, SM Bhavnani, P Fernandes, RN Jones, PG Ambrose
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Low CEM-102 (Fusidic Acid [FA]) Resistance (R) Rates and High Prevalence of Acquired (acq) Genes Among Staphylococcus spp. (SSP) from North America and Australia
M Castanheira, AA Watters, JM Bell, RN Jones, JD Turnidge
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Assay Standards

Assessment of In Vivo Activity of CEM-102 (Fusidic Acid) in Murine Infection Models
T Murphy, S Little, R Wu, A Slee, P Fernandes
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Initial Quality Control (QC) Ranges for Fusidic Acid (FA) Using the CLSI Multi-Laboratory M23-A3 Study Design
RN Jones, JE Ross
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Safety

Population Pharmacokinetics (PPK) of CEM-102 in Healthy Subjects
JB Bulitta, OO Okusanya, A Forrest, SM Bhavnani, D Reynolds, MP Pai, JG Still, PB Fernandes, PG Ambrose
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Pharmacokinetics and Safety of Single, Multiple, and Loading Doses of CEM-102 in Healthy Subjects
JG Still, K Clark, TP Degenhardt, D Scott, P Fernandes, MJ Gutierrez
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From Mouse to Man: The Pharmacokinetics of CEM-102 (Fusidic acid)
TP Degenhardt, JG Still, K Clark, P Fernandes
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