Emergence and spread of antibiotic resistance following exposure to antibiotics

Abstract

Within a susceptible wild-type population, a small fraction of cells, even <10(-9) , is not affected when challenged by an antimicrobial agent. This subpopulation has mutations that impede antimicrobial action, allowing their selection during clinical treatment. Emergence of resistance occurs in the frame of a selective compartment termed a mutant selection window (MSW). The lower margin corresponds to the minimum inhibitory concentration of the susceptible cells, whereas the upper boundary, named the mutant prevention concentration (MPC), restricts the growth of the entire population, including that of the resistant mutants. By combining pharmacokinetic/pharmacodynamic concepts and an MPC strategy, the selection of resistant mutants can be limited. Early treatment avoiding an increase of the inoculum size as well as a regimen restricting the time within the MSW can reduce the probability of emergence of the resistant mutants. Physiological and, possibly, genetic adaptation in biofilms and a high proportion of mutator clones that may arise during chronic infections influence the emergence of resistant mutants. Moreover, a resistant population can emerge in a specific selective compartment after acquiring a resistance trait by horizontal gene transfer, but this may also be avoided to some extent when the MPC is reached. Known linkage between antimicrobial use and resistance should encourage actions for the design of antimicrobial treatment regimens that minimize the emergence of resistance. Emergence of a resistant bacterial subpopulation within a susceptible wild-type population can be restricted with a regimen using an antibiotic dose that is sufficiently high to inhibit both susceptible and resistant bacteria.

Extended-spectrum β-lactamase/AmpC-producing uropathogenic Escherichia coli from HIV patients: do they have a low virulence score?

“…Exposure to antibiotics has been considered as a significant factor that strongly influences the emergence and spread of antibiotic resistance (Cantó n & Morosini, 2011;Andersson & Hughes, 2010). Currently, FQs and b-lactams are the broad-spectrum antimicrobials widely used in clinical medicine.…”

GC-MS Analysis of Bioactive Compounds and Hosttoxicity Studies of Azolla caroliniana Symbiotic with the Cyanobacterium Anabaena azollae

“…Additionally, the ability of the fern to produce an array of secondary metabolites, like several higher plants [13][14][15][16] is considered important for the use against bacterial pathogens as a non-microbial antimicrobial agent against the array of bacterial self defense mechanisms, i.e., shenanigans in achieving resistance over applied antibacterials 17 since the symbiotic fern has a higher litany of chemicals that could never be won upon by any prokaryote, equipped with armamentaria of multiresistance 18 The present finding of the absence of hosttoxicity similar to the medicinal plants, Woodfordia fruticosa 13 and Combretum albidum 16 with human lymphocyte culture supported the use of the fern as complementary and alternative medicine (CAM), along with mainstream antibiotics. The concept of CAM of using phyto-drugs is now widely held, being promoted by World Health Organization…”

Comparative Study of the Mutant Prevention Concentrations of Sulfamethoxazole-Trimethoprim Alone and in Combination with Levofloxacin against &lt;i&gt;Stenotrophomonas maltophilia&lt;/i&gt;

“…One of them is combination therapy, the method that had been studied by our team completely [19]. Another is using Maria-Isabel point out that resistance mechanisms involving horizontal gene transfer can be researched by MPC and MSW [22]. In their opinion the MPC concept also can be used in variety of antibiotics, including fluoroquinolones, glycopeptides, mcrolide, and tetracycline and so on.…”