Skip directly to site content Skip directly to page options Skip directly to A-Z link Skip directly to A-Z link Skip directly to A-Z link
Volume 12, Number 2—February 2006
Perspective

Antimicrobial Drug Resistance, Regulation, and Research1

Joshua P. Metlay*†Comments to Author , John H. Powers‡, Michael N. Dudley§, Keryn Christiansen¶, Roger G. Finch#**, on behalf of the Second Colloquium of the International Forum on Antibiotic Resistance
Author affiliations: *VA Medical Center, Philadelphia, Pennsylvania, USA; †University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA; ‡US Food and Drug Administration, Rockville, Maryland, USA; §Diversa Corporation, San Diego, California, USA; ¶Royal Perth Hospital, Perth, Western Australia, Australia; #Nottingham City Hospital, Nottingham, United Kingdom; **University of Nottingham, Nottingham, United Kingdom

Main Article

Figure 4

Relationship between the dominant pharmacokinetic/pharmacodynamic (PK/PD) index, efficacy, and resistance emergence in vitro (both quantified by the number of bacterial colony-forming units). The PK/PD index is related to efficacy in a sigmoid curve and the resistance emergence by an inverted U-shaped curve (21).

Figure 4. Relationship between the dominant pharmacokinetic/pharmacodynamic (PK/PD) index, efficacy, and resistance emergence in vitro (both quantified by the number of bacterial colony-forming units). The PK/PD index is related to efficacy in a sigmoid curve and the resistance emergence by an inverted U-shaped curve (21).

Main Article

References
  1. Commission of the European Communities. Communication from the commission on a community strategy against antimicrobial resistance. Brussels: The Commission; 2001.
  2. Interagency Task Force on Antimicrobial Resistance. Public health action plan to combat antimicrobial resistance. Atlanta: Centers for Disease Control and Prevention; 2001.
  3. World Health Organization. WHO global strategy for the containment of antimicrobial resistance. Geneva: The Organization; 2001.
  4. Powers  JH. Antimicrobial drug development—the past, present and future. Clin Microbiol Infect. 2004;10(Suppl 4):23–31. DOIPubMedGoogle Scholar
  5. Infectious Diseases Society of America. Bad bugs, no drugs. Alexandria (VA): The Society; 2004.
  6. Nordberg  P, Monnet  DL, Cars  O. Antibacterial resistance. Background document for the WHO project: priority medicines for Europe and the World—a public health approach to innovation. 2005 Aug 9 [cited 2005 Nov 22]. Available from http://mednet3.who.int/prioritymeds/report/index.htm
  7. Norrby  SR, Nord  CE, Finch  R. Lack of development of new antimicrobial drugs: a potential serious threat to public health. Lancet Infect Dis. 2005;5:115–9.PubMedGoogle Scholar
  8. Metlay  JM, Singer  DE. Outcomes in lower respiratory tract infections and the impact of antimicrobial drug resistance. Clin Microbiol Infect. 2002;8(Suppl 2):1–11. DOIPubMedGoogle Scholar
  9. Food and Drug Administration, Center for Drug Evaluation and Research, Center for Biologics Evaluation and Research. Guidance for industry. E9 statistical principles for clinical trials. Rockville (MD): The Administration; 1998.
  10. Dudley  MN, Ambrose  PG. Pharmacodynamics in the study of drug resistance and establishing in vitro susceptibility breakpoints: ready for prime time. Curr Opin Microbiol. 2000;3:515–21. DOIPubMedGoogle Scholar
  11. Andes  D, Craig  WA. Animal model pharmacokinetics and pharmacodynamics: a critical review. Int J Antimicrob Agents. 2002;19:261–8. DOIPubMedGoogle Scholar
  12. MacGowan  A, Bowker  K. Developments in PK/PD: optimising efficacy and prevention of resistance. A critical review of PK/PD in in vitro models. Int J Antimicrob Agents. 2002;19:291–8. DOIPubMedGoogle Scholar
  13. MacGowan  AP. Elements of design: the knowledge on which we build. Clin Microbiol Infect. 2004;10(Suppl 2):6–11. DOIPubMedGoogle Scholar
  14. MacGowan  A, Rogers  C, Holt  A, Wootton  M, Bowker  K. Assessment of different antibacterial effect measures used in in vitro models of infection and subsequent use in pharmacodynamic correlations for moxifloxacin. J Antimicrob Chemother. 2000;46:73–8. DOIPubMedGoogle Scholar
  15. Craig  WA, Kiem  S, Andes  D, Ambrose  P, Jones  R. Impact of ESBLs on in vivo activity of four cephalosporins in the neutropenic mouse-thigh infection model [abstract A-1318]. In: Abstracts of the 43rd Interscience Conference on Antimicrobial Agents and Chemotherapy; Chicago; 2003 Sep 14–17. Washington; American Society for Microbiology; 2003.
  16. Jumbe  N, Louie  A, Leary  R, Liu  W, Deziel  MR, Tam  VH, Application of a mathematical model to prevent in vivo amplification of antibiotic-resistant bacterial populations during therapy. J Clin Invest. 2003;112:275–85.PubMedGoogle Scholar
  17. Bradley  JS, Dudley  MN, Drusano  GL. Predicting efficacy of antiinfectives with pharmacodynamics and Monte Carlo simulation. Pediatr Infect Dis J. 2003;22:982–92. DOIPubMedGoogle Scholar
  18. Dudley  MN. Commentary on dual individualization with antibiotics. In: Evans WE, Schentag JJ, Jusko WJ, editors. Applied pharmacokinetics-principles of therapeutic drug monitoring. 3rd ed. Vancouver (WA): Applied Therapeutics; 1992. p. 18-1–18-13.
  19. National Committee for Clinical Laboratory Standards. Performance standards for antimicrobial susceptibility testing. Eleventh informational supplement. NCCLS Document M100-S11. Wayne (PA): The Committee; 2001.
  20. Ambrose  PG, Bhavnani  SM, Jones  RN, Jones  RN, Craig  WA, Dudley  MN. Use of pharmacokinetics-pharmacodynamics and Monte Carlo simulation as decision support for the re-evaluation of NCCLS cephem susceptibility breakpoints for Enterobacteriaceae [abstract A-138]. In: Abstracts of the 44th Interscience Conference on Antimicrobial Agents and Chemotherapy; Washington; 2004 Oct 30-Nov 2. Washington; American Society for Microbiology; 2004.
  21. Craig  WA, Kiem  S. Pharmacodynamic requirements to prevent the emergence of quinolone-resistant Streptococcus pneumoniae in an animal model [abstract 81]. In: Abstracts of the 40th Infectious Diseases Society of America; Chicago; 2002 Oct 24–27; Alexandria (VA): Infectious Disease Society of America.
  22. Knudsen  JD, Odenholt  I, Erlendsdottir  H, Gottfredsson  M, Cars  O, Frimodt-Moller  N, Selection of resistant Streptococcus pneumoniae during penicillin treatment in vitro and in three animal models. Antimicrob Agents Chemother. 2003;47:2499–506. DOIPubMedGoogle Scholar
  23. Odenholt  I, Gustafsson  I, Lowdin  E, Cars  O. Suboptimal antibiotic dosage as a risk factor for selection of penicillin-resistant Streptococcus pneumoniae: in vitro kinetic model. Antimicrob Agents Chemother. 2003;47:518–23. DOIPubMedGoogle Scholar
  24. Zinner  S, Gilbert  DS, Simmons  K, Lubenko  I, Zhao  X, Drlica  K, Emergence of resistant Streptococcus pneumoniae in an in vitro dynamic model that simulates moxifloxacin concentrations in and out of the mutant selection window: related changes in susceptibility and resistance frequency [abstract A-1149]. In: Abstracts of the 43rd Interscience Conference on Antimicrobial Agents and Chemotherapy; Chicago; 2003 Sep 14–17. Washington: American Society for Microbiology; 2003.
  25. Blaser  J, Stone  BB, Groner  MC, Zinner  S. Comparative study with enoxacin and netilmicin in pharmacodynamic model to determine importance of the ratio of antibiotic peak concentration to MIC for bactericidal activity and emergence of resistance. Antimicrob Agents Chemother. 1987;31:1054–60.PubMedGoogle Scholar
  26. MacGowan  AP, Rogers  CA, Holt  HA, Bowker  KE. Activities of moxifloxacin against, and emergence of resistance in, Streptococcus pneumoniae and Pseudomonas aeruginosa in an in vitro pharmacokinetic model. Antimicrob Agents Chemother. 2003;47:1088–95. DOIPubMedGoogle Scholar
  27. Thomas  JK, Forrest  A, Bhavnani  SM, Hyatt  JM, Cheng  A, Ballow  CH, Pharmacodynamic evaluation of factors associated with the development of bacterial resistance in acutely ill patients during therapy. Antimicrob Agents Chemother. 1998;42:521–7.PubMedGoogle Scholar
  28. Pallares  R, Linares  J, Vadillo  M, Cabellos  C, Manresa  F, Viladrich  PF, Resistance to penicillin and cephalosporin and mortality from severe pneumococcal pneumonia in Barcelona, Spain. N Engl J Med. 1995;333:474–80. DOIPubMedGoogle Scholar
  29. Yu  VL, Chiou  CC, Feldman  C, Ortqvist  A, Rello  J, Morris  AJ, An international prospective study of pneumococcal bacteremia: correlation with in vitro resistance, antibiotics administered, and clinical outcome. Clin Infect Dis. 2003;37:230–7. DOIPubMedGoogle Scholar
  30. Powers  JH, Moncada  V, Johann-Liang  R. Disease severity (DS) assessment in community-acquired pneumonia (CAP) antimicrobial clinical trials: a comparison of the PORT criteria with the original and revised ATS criteria [abstract L-655]. In: Abstracts of the 44th Interscience Conference on Antimicrobial Agents and Chemotherapy; Washington; 2004 Oct 30–Nov 2. Washington: American Society for Microbiology; 2004.
  31. Ambrose  PG, Anon  JB, Owen  JS, Wan Wart  S, McPhee  ME, Bhavnani  SM, Use of pharmacokinetic endpoints in the evaluation of gatifloxacin for the treatment of acute maxillary sinusitis. Clin Infect Dis. 2004;38:1513–20. DOIPubMedGoogle Scholar
  32. Committee for Proprietary Medicinal Products. Note for guidance on evaluation of medicinal products for the treatment of bacterial infection. Document CPMP/EWP/558/95. London: European Agency for the Evaluation of Medicinal Products; 2004.
  33. Committee for Proprietary Medicinal Products. Points to consider on pharmacokinetics and pharmacodynamics in the development of antibacterial medicinal products. Document CPMP/EWP/2655/99. London: European Agency for the Evaluation of Medicinal Products; 2000.
  34. Committee for Proprietary Medicinal Products. Points to consider on pharmacokinetics and pharmacodynamics in the development of antibacterial medicinal products. Document CPMP/EWP/2655/99. London: European Agency for the Evaluation of Medicinal Products; 2000.
  35. Turnidge  JD, Bell  JM; Sentry Asia-Pacific Participants. Reduced quinolone susceptibility is common in Salmonella species from the Asia-Pacific region: results from the Sentry Asia-Pacific Surveillance program 2001 [abstract C2-1284]. In: Abstracts of the 42nd Interscience Conference on Antimicrobial Agents and Chemotherapy; San Diego; 2002 Sep 27–30. Washington: American Society for Microbiology; 2002.
  36. McCaig  LF, Besser  RE, Hughes  JM. Antimicrobial drug prescription in ambulatory care settings, United States, 1992–2000. Emerg Infect Dis. 2003;9:432–7.PubMedGoogle Scholar
  37. Beilby  J, Marley  J, Walker  D, Chamberlain  N, Burke  M; FIESTA Study Group. Effect of changes in antibiotic prescribing on patient outcomes in a community setting: a natural experiment in Australia. Clin Infect Dis. 2002;34:55–64. DOIPubMedGoogle Scholar
  38. Food and Drug Administration. Labeling requirements for systemic antibacterial drug products intended for human use. Document 21CFR, part 201. Rockville (MD): The Administration; 2003.

Main Article

1This article is based on presentations and discussions held at the Second Colloquium of the International Forum on Antibiotic Resistance (IFAR), held on September 13, 2003, in Chicago, Illinois, USA. IFAR is a multidisciplinary, international group concerned with evaluating current knowledge regarding antimicrobial drug resistance and the means for its control. This article represents the opinions of the participants at the second IFAR colloquium and not necessarily those of the institutions for whom they work.

Page created: February 02, 2012
Page updated: February 02, 2012
Page reviewed: February 02, 2012
The conclusions, findings, and opinions expressed by authors contributing to this journal do not necessarily reflect the official position of the U.S. Department of Health and Human Services, the Public Health Service, the Centers for Disease Control and Prevention, or the authors' affiliated institutions. Use of trade names is for identification only and does not imply endorsement by any of the groups named above.
file_external