All Journals > The Journal of Infectious Diseases > 15 June 2007 > Therapy Duration and Resistance Emergence

Article Tools

Search for Related Articles

  • By Author
  • Search In

Announcements

Science Watch logo

JID Article Named "New Hot Paper" by ScienceWatch.com

Dr. Lauri Hicks' 2007 article on pneumococcal disease has been named a "hot new paper" by Thompson Reuters' ScienceWatch.com. Read a Q&A about the article with Dr. Hicks here. 

Press Release

Unique Collaboration Charts the Migrations of a Parasite that Affected History
Researchers Sequence Louse DNA from Mummies and Propose New Model for its Development


In the News

Featured in Grist
"Another symptom of swine flu: instant amnesia" May 11, 2009
Swine Influenza Virus: Zoonotic Potential and Vaccination Strategies for the Control of Avian and Swine Influenzas
Eileen Thacker and Bruce Janke
Read the veterinary literature on swine flu and you get a strong sense of what might be called vaccination treadmill: the hog industry is literally scrambling to generate new vaccines for the rapidly evolving flu strains that sweep through CAFOs. Writing in the Journal of Infectious Diseases [PDF] in 2008, Eileen Thacker and Bruce Janke of Iowa State University paint a stark picture: “A number of genetically diverse viruses are circulating in swine herds throughout the world and are a major cause of concern to the swine industry,” they write. “Influenza virus infections in swine and poultry are potential sources of viruses for the next pandemic among humans.”

Featured in New York Times
"Fear of a Swine Flu Epidemic in 1976 Offers Some Lessons, and Concerns, Today" May 8, 2009
Anti‐Ganglioside Antibody Induction by Swine (A/NJ/1976/H1N1) and Other Influenza Vaccines: Insights into Vaccine‐Associated Guillain‐Barré Syndrome
Irving Nachamkin, Sean V. Shadomy, Anthony P. Moran, Nancy Cox, Collette Fitzgerald, Huong Ung, Adrian T. Corcoran, John K. Iskander, Lawrence B. Schonberger, and Robert T. Chen
Irving Nachamkin, a professor of pathology and laboratory medicine at the University of Pennsylvania, examined some 1976 vaccine that had been saved by a scientist in Texas. In a paper published last year in The Journal of Infectious Diseases, he and colleagues reported that mice given the vaccine made antibodies that reacted with gangliosides, which are components of nerve cells. An antibody attack on gangliosides is part of the disease mechanism of Guillain-Barré.

Featured in AFP
"Swine flu vaccine 'could be ready soon'" May 7, 2009
A Broadly Protective Vaccine against Globally Dispersed Clade 1 and Clade 2 H5N1 Influenza Viruses
Mary A. Hoelscher, Neetu Singh, Sanjay Garg, Lakshmi Jayashankar, Vic Veguilla, Aseem Pandey, Yumi Matsuoka, Jacqueline M. Katz, Ruben Donis, Suresh K. Mittal, and Suryaprakash Sambhara
The vaccine Mittal created for the bird flu worked on three different strains isolated over a seven-year period and was described in papers for the Journal of Infectious Diseases and the journal Clinical Pharmacology and Therapeutics.

Featured in Newsweek
"The Path of a Pandemic" http://www.newsweek.com/id/195692
Swine Influenza Virus: Zoonotic Potential and Vaccination Strategies for the Control of Avian and Swine Influenzas
Eileen Thacker and Bruce Janke
Last year researchers from Iowa State University in Ames warned that pigs located in industrial-scale farms were being subjected to influenza infections from farm poultry, wild birds and their human handlers. Writing in The Journal of Infectious Diseases, Eileen Thacker and Bruce Janke said, "As a result of the constantly changing genetic makeup of individual influenza viruses in pigs, the U.S. swine industry is continually scrambling to respond to the influenza viruses circulating within individual production systems."

15 June 2007

Volume 195, Number 12
The Journal of Infectious Diseases 2007;195:1818–1827
© 2007 by the Infectious Diseases Society of America. All rights reserved.
0022-1899/2007/19512-0013$15.00
DOI: 10.1086/518003
MAJOR ARTICLE

Impact of Drug‐Exposure Intensity and Duration of Therapy on the Emergence of Staphylococcus aureus Resistance to a Quinolone Antimicrobial

V. H. Tam,1,a

A. Louie,1

T. R. Fritsche,2

M. Deziel,1,b

W. Liu,1

D. L. Brown,1

L. Deshpande,2

R. Leary,3,a

R. N. Jones,2 and

G. L. Drusano1

1Emerging Infections and Host Defense Laboratory, Ordway Research Institute, Albany, New York; 2JMI Laboratories, North Liberty, Iowa; 3University of California, San Diego, Supercomputer Center

We have shown previously in animal model and in vitro systems that antimicrobial therapy intensity has a profound influence on subpopulations of resistant organisms. Little attention has been paid to the effect of therapy duration on resistant subpopulations. We examined the influence of therapy intensity (area under the concentration/time curve for 24 h:minimum inhibitory concentration [AUC24:MIC] ratio) and therapy duration on resistance emergence using an in vitro model of Staphylococcus aureus infection. AUC24:MIC ratios of 100 were necessary to kill a substantial portion of the total population. Importantly, we demonstrated that therapy duration is a critical parameter. As the duration increased beyond 5 days, the intensity needed to suppress the antibiotic‐resistant subpopulations increased, even when the initial bacterial kill was >4 log10 (cfu/mL). These findings were prospectively validated in an independent experiment in which exposures were calculated from the results of fitting a large mathematical model to all data simultaneously. All of the prospectively determined predictions were fulfilled in this validation experiment.

Received 12 October 2006; accepted 6 January 2007; electronically published 2 May 2007.

Reprints or correspondence: Dr. G. L. Drusano, Codirector, Ordway Research Institute, 150 New Scotland Ave., Albany, NY ().

Cited by

R. Singh, K. R. Ledesma, K.-T. Chang, J.-G. Hou, R. A. Prince, V. H. Tam. (2009) Pharmacodynamics of moxifloxacin against a high inoculum of Escherichia coli in an in vitro infection model. Journal of Antimicrobial Chemotherapy
Online publication date: 9-Aug-2009.
CrossRef
G. L. Drusano, W. Liu, D. L. Brown, L. B. Rice, and A. Louie. (2009) Impact of Short‐Course Quinolone Therapy on Susceptible and Resistant Populations of Staphylococcus aureus. The Journal of Infectious Diseases 199:2, 219-226
Online publication date: 15-Jan-2009.
Abstract-Full Text-PDF Version (457 kB)

  • Potential conflicts of interest: none reported (garenoxacin is no longer owned by Bristol‐Myers Squibb but is licensed to Schering‐Plough).

    Financial support: Bristol‐Myers Squibb.

    This article is dedicated to the memory and career of Dr. Theodore E. Woodward, a treasured mentor.

  • Present affiliations: Department of Clinical Sciences and Administration, University of Houston College of Pharmacy, Houston, Texas (V.H.T.); Pharsight Corporation, Cary, North Carolina (R.L.).

  • Deceased.

Back to Top
Close Popup