Antimicrobial Activity and Resistance: Influencing Factors

Abstract

Rational use of antibiotic is the key approach to improve the antibiotic performance and tackling of the antimicrobial resistance. The efficacy of antimicrobials are influenced by many factors: (1) bacterial status (susceptibility and resistance, tolerance, persistence, biofilm) and inoculum size; (2) antimicrobial concentrations [mutant selection window (MSW) and sub-inhibitory concentration]; (3) host factors (serum effect and impact on gut micro-biota). Additional understandings regarding the linkage between antimicrobial usages, bacterial status and host response offers us new insights and encourage the struggle for the designing of antimicrobial treatment regimens that reaching better clinical outcome and minimizing the emergence of resistance at the same time.

Keywords: antibiotic concentration; gut microbiota; inoculum size effect; persistence; resistance; serum effect.

Figure 1

Time-kill curves of susceptibility, tolerance and persistence (modified from Brauner et al., 2016). A persistent strain of bacteria has a similar MIC and a similar MDK99 to a susceptible strain; however, the MDK for 99.99% of bacterial cells in the population (MDK99.99) is substantially higher for a persistent strain than the MDK99.99 for a susceptible strain. The minimum duration for killing [MDK; for example for 99% of bacterial cells in the population (MDK99)] for a tolerant strain is substantially higher than the MDK99 for a susceptible strain.

Figure 2

Growth of the susceptible and the isogenic resistant bacteria in the sub-MIC selective window and traditional MSW (modified from Gullberg et al., 2011). For antibiotic concentrations lower than MSC, the susceptible strain (green line) will outcompete the resistant strain (orange line). However, for the antibiotic concentrations between sub-MIC selective window and traditional mutant selective window, the resistant strain will outcompete the susceptible strain.