Antimicrobial Drug Resistance
Marilyn Martinez and Peter Silley
Contents
1 Introduction ............................................................................... 228
2 Antimicrobial Mechanisms of Action ..................................................... 229
3 Resistance ................................................................................. 233
3.1 Resistance Mechanisms ............................................................. 233
3.2 Defining the Term “Resistance” .................................................... 233
3.3 Monitoring Programmes: Points to Consider ....................................... 237
3.4 Impact of Antibiotic Use on Resistance ............................................ 239
4 Pharmacokinetic Considerations .......................................................... 241
4.1 General Considerations ............................................................. 241
4.2 Mutation Selection Window ........................................................ 244
4.3 Duration of Dosing ................................................................. 245
4.4 PK/PD is More Than MICs ......................................................... 247
4.5 Clinical Susceptibility Breakpoints ................................................. 249
5 Tolerance Versus Resistance .............................................................. 250
6 New Approaches in Antimicrobial Therapy .............................................. 255
7 Conclusions ............................................................................... 257
References .................................................................................... 258
AbstractThis chapter provides an overview of our current understanding of the
mechanisms associated with the development of antimicrobial drug resistance,
international differences in definitions of resistance, ongoing efforts to track shifts
in drug susceptibility, and factors that can influence the selection of therapeutic
intervention. The latter presents a matrix of complex variables that includes the
M. Martinez (*)
Office of New Animal Drug Evaluation (HFV-130), Center for Veterinary Medicine Food and
Drug Administration, 7500 Standish Place, Rockville, MD 20855, USA
e-mail: [email protected]
P. Silley
MB Consult Limited, Enterprise House, Ocean Village, Southampton, Hampshire, SO14 3XB, UK
e-mail: [email protected]
F. Cunningham et al. (eds.),Comparative and Veterinary Pharmacology,
Handbook of Experimental Pharmacology 199,
DOI 10.1007/978-3-642-10324-7_10,#Springer-Verlag Berlin Heidelberg 2010
227