Archive for September 18, 2015

Telavancin for Acute Bacterial Skin and Skin Structure Infections, a Post Hoc Analysis of the Phase 3 ATLAS Trials in Light of the 2013 FDA Guidance

Antimicrobial Agents and Chemotherapy OCT 2015 V.59 N.10

Richard Pushkin, Steven L. Barriere, Whedy Wang, G. Ralph Corey, and Martin E. Stryjewski

aTheravance Biopharma US, Inc., South San Francisco, California, USA

bDuke Clinical Research Institute and Division of Infectious Diseases, Duke University Medical Center, Durham, North Carolina, USA

cDepartment of Medicine, Section of Infectious Diseases, Centro de Educación Médica e Investigaciones Clínicas Norberto Quirno (CEMIC), Buenos Aires, Argentina

Two phase 3 ATLAS trials demonstrated noninferiority of telavancin compared with vancomycin for complicated skin and skin structure infections.

Data from these trials were retrospectively evaluated according to 2013 U.S. Food and Drug Administration (FDA) guidance on acute bacterial skin and skin structure infections.

This post hoc analysis included patients with lesion sizes of ≥75 cm2 and excluded patients with ulcers or burns (updated all-treated population; n = 1,127). Updated day 3 (early) clinical response was defined as a ≥20% reduction in lesion size from baseline and no rescue antibiotic.

Updated test-of-cure (TOC) clinical response was defined as a ≥90% reduction in lesion size, no increase in lesion size since day 3, and no requirement for additional antibiotics or significant surgical procedures.

Day 3 (early) clinical responses were achieved in 62.6% and 61.0% of patients receiving telavancin and vancomycin, respectively (difference, 1.7%, with a 95% confidence interval [CI] of −4.0% to 7.4%).

Updated TOC visit cure rates were similar for telavancin (68.0%) and vancomycin (63.3%), with a difference of 4.8% (95% CI, −0.7% to 10.3%).

Adopting current FDA guidance, this analysis corroborates previous noninferiority findings of the ATLAS trials of telavancin compared with vancomycin.

abstract

http://aac.asm.org/content/59/10/6170.abstract?etoc

PDF

http://aac.asm.org/content/59/10/6170.full.pdf

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September 18, 2015 at 8:17 pm

Successful Treatment of Carbapenemase-Producing Pandrug-Resistant Klebsiella pneumoniae Bacteremia

Antimicrobial Agents and Chemotherapy OCT 2015 V.59 N.10 P.5903-5908

Jose F. Camargo, Jacques Simkins, Thiago Beduschi, Akin Tekin, Laura Aragon, Armando Pérez-Cardona, Clara E. Prado, Michele I. Morris, Lilian M. Abbo, and Rafael Cantón

aDepartment of Medicine, Division of Infectious Diseases, University of Miami Miller School of Medicine, Miami, Florida, USA

bMiami Transplant Institute and Department of Surgery, University of Miami Miller School of Medicine, Miami, Florida, USA

cDepartment of Pharmacy, Jackson Memorial Hospital, Miami, Florida, USA

dDepartment of Microbiology, Jackson Memorial Hospital, Miami, Florida, USA

eDepartment of Microbiology, University of Miami, Miami, Florida, USA

fServicio de Microbiología, Hospital Universitario Ramón y Cajal and Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain

gRed Española de Investigación en Patología Infecciosa (REIPI), Madrid, Spain

New antibiotic options are urgently needed for the treatment of carbapenem-resistant Enterobacteriaceae infections.

We report a 64-year-old female with prolonged hospitalization following an intestinal transplant who developed refractory bacteremia due to a serine carbapenemase-producing pandrug-resistant isolate of Klebsiella pneumoniae.

After failing multiple antimicrobial regimens, the patient was successfully treated.

abstract

http://aac.asm.org/content/59/10/5903.abstract?etoc

PDF

http://aac.asm.org/content/59/10/5903.full.pdf

 

September 18, 2015 at 8:15 pm

Profile of ceftolozane/tazobactam and its potential in the treatment of complicated intra-abdominal infections.

Drug Des Devel Ther. 2015 Jun 4;9:2919-25.

Skalweit MJ1.

1Department of Medicine, Louis Stokes Cleveland Department of Veterans Affairs and Case Western Reserve University School of Medicine, Cleveland, OH, USA ; Department of Biochemistry, Louis Stokes Cleveland Department of Veterans Affairs and Case Western Reserve University School of Medicine, Cleveland, OH, USA.

Abstract

Drug-resistant pathogens have gained a foothold especially in the most vulnerable patient populations, hospitalized and immunocompromised individuals.

Furthermore, extended-spectrum β-lactamase and carbapenemase-producing organisms are finding their way even into the community, with patients presenting to the hospital with established colonization and infection with resistant Enterobacteriaceae in particular.

Recently, a novel antipseudomonal cephalosporin in combination with an established Class A β-lactamase inhibitor, ceftolozane/tazobactam has been approved by the FDA for use in the treatment of complicated urinary tract infections and complicated intra-abdominal infections.

Ceftolozane is a uniquely potent antipseudomonal cephalosporin because of its high affinity for the penicillin-binding proteins of Pseudomonas aeruginosa, its low affinity for the intrinsic Class C β-lactamases of P. aeruginosa, its ability to enter P. aeruginosa through the outer membrane without the utilization of OprD protein, and the fact that it is not a substrate of the often upregulated MexAB/OprM efflux system of P. aeruginosa.

The biological chemistry, pharmacokinetics/pharmacodynamics, microbiologic spectrum, and clinical trials that led to the approval of ceftolozane is reviewed.

A discussion regarding its potential role in the treatment of complicated intra-abdominal infections and other infectious disease syndromes associated with drug-resistant pathogens follows.

PDF

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4461093/pdf/dddt-9-2919.pdf

September 18, 2015 at 3:34 pm

Ceftolozane/Tazobactam: a new option in the treatment of complicated gram-negative infections.

P T. 2014 Dec;39(12):825-32.

Sorbera M, Chung E, Ho CW, Marzella N.

Abstract

Ceftolozane/tazobactam: a new option in the treatment of complicated gram-negative infections.

PDF

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4264669/pdf/ptj3912825.pdf

 

September 18, 2015 at 3:32 pm


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