Antimicrobial Drug Resistance

Abstract

This 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 mechanism of drug action, the pharmacokinetics (PK) of the antimicrobial agent in the targeted patient population, the pharmacodynamics (PD) of the bacterial response to the antimicrobial agent, the PK/PD relationship that will influence dose selection, and the integrity of the host immune system. Finally, the differences between bacterial tolerance and bacterial resistance are considered, and the potential for non-traditional anti-infective therapies is discussed.

Antibacterial Drugs in Fish Farms: Application and Its Effects

“…The excessive use of antibacterials in fish aquaculture is increasing the resistance in bacteria that can infect both humans and animals (Burridge et al, 2010;Kümmerer, 2010;Defoirdt et al, 2011). It is not only the direct therapeutic use of antibacterials, but also their indirect contact with them which might enhance the resistance of bacteria: not taking into account the bacteria's origins, resistance genes have been isolated from human pathogens, bacteria of animal origin and even environmental bacteria (Kemper, 2008;Martinez & Silley, 2010;Martinez, 2009). The consequences of increasing resistance in bacteria and the diminishing impact of therapeutic drugs reach far beyond the geographic origins of antibacterial compounds and are, therefore, of global concern (Kemper, 2008).…”

“…PK and PD data has allowed the design of therapeutic regimens, with the PK/PD variable providing the most appropriate surrogate for drug effectiveness being dependent upon several factors (Rigos & Troisi, 2005;Martinez & Silley, 2010;Toutain et al, 2010). Within some species there may be considerable differences both within and between breeds in PK and PD profiles; veterinary pharmacogenetics aims to identify genetic variations (polymorphisms) as the origin of differences in the drug response of individuals within a given species.…”

“…There is a considerable amount of information available on the PK of various antibacterials delivered by different routes to different species of fish, but little information about the plasma levels of antibacterials that are required to be of benefit for the implanted fish or the calculation of the dosage of antibacterial required to obtain a positive benefit (Mulcahy, 2011). It is important to remember that it is the host immune system that is ultimately responsible for success in combating bacterial disease (Martinez & Silley, 2010). If one is unsure about the dose to use, it is usually best to start with the lower recommended dose.…”

“…If no response is seen by that time, both the diagnosis and treatment should be reconsidered (Walker & Giguére, 2008). It is important to remember that it is the host immune system that is ultimately responsible for any success in combating bacterial diseases (Martinez & Silley, 2010).…”

Dosing Regimen Matters: the Importance of Early Intervention and Rapid Attainment of the Pharmacokinetic/Pharmacodynamic Target

“…A summary of drug classes versus generalizations regarding the corresponding PK/PD parameter(s), the type of antimicrobial activity (i.e., bactericidal and/or bacteriostatic), and the mechanism(s) of action is provided in Table 1 (42).…”