Dissimilar Fitness Associated with Resistance to Fluoroquinolones Influences Clonal Dynamics of Various Multiresistant Bacteria

Abstract

Fitness cost associated with resistance to fluoroquinolones was recently shown to vary across clones of methicillin-resistant Staphylococcus aureus and extended-spectrum β-lactamase-producing Klebsiella pneumoniae. The resulting dissimilar fitness should have influenced the clonal dynamics and thereby the rates of resistance for these pathogens. Moreover, a similar mechanism was recently proposed for the emergence of the H30 and H30R lineages of ESBL-producing E. coli and the major international clone (ribotype 027) of Clostridium difficile. Furthermore, several additional international clones of various multiresistant bacteria are suspect to have been selected by an analogous process. An ability to develop favorable mutations in the gyrase and topoisomerase IV genes seems to be a prerequisite for pathogens to retain fitness while showing high-level resistance to fluoroquinolones. Since, the consumption of other “non-fluoroquinolone” groups of antibiotics have also contributed to the rise in resistance rates a more judicious use of antibiotics in general and of fluoroquinolones in particular could ameliorate the international resistance situation.

Simulating multi-level dynamics of antimicrobial resistance in a membrane computing model

“…We show that the speed and intensity of this process depends on the global resistance landscape and the density and phenotype of the bacterial subpopulations. Our model predicts that previous mutational ciprofloxacin-resistance facilitates fast evolution of multi-resistance by horizontal acquisition of resistance genes (14,15). We also show that the long-term dissemination of chromosomally-encoded genes is by far less effective than the spread of traits encoded in transferable plasmids, even though some limitations are detectable because of plasmid incompatibility.…”

“…The overall success of the plasmid PL1 (blue line) benefits from the fact that this mobile element is selected by two different antibiotics (AbA and AbC, resistance shown in red and green lines respectively). Interestingly, resistance to AbFR (violet) is selected from early stages of the experiment, and after 4,000 steps it converges with the AbCR, a plasmid-mediated trait, meaning that this plasmid is maintained almost exclusively in strains harboring AbFR gene, similar to empirical findings (14,15). If the conjugation rate of PL1 was increased, the main effect…”

ECDC, EFSA and EMA Joint Scientific Opinion on a list of outcome indicators as regards surveillance of antimicrobial resistance and antimicrobial consumption in humans and food‐producing animals

“…Antimicrobials used for the treatment of Gram‐negative bacterial infections may impact resistance in Gram‐positive bacteria. This has been shown for fluoroquinolone use (mostly used for Gram‐negative bacteria, including E. coli ) and MRSA (Fuzi, ). In particular, high levels of fluoroquinolone use have been correlated with high proportions of MRSA and vice versa (Fuzi, ).…”

Delafloxacin: design, development and potential place in therapy

“…However, and in spite of the double target that makes difficult the selection of resistant mutants and its good activity against MRSA, beta-lactamase-producing enterobacteria (ESBL) and fluoroquinolone-resistant isolates, we must not forget the close relationship between the massive use of fluoroquinolones and the selection of specific clones of MRSA, ESBL and ribotype 027 C. difficile strains 51. In the absence of clinical and epidemiological data that can only be obtained once the antibiotic is marketed, the most reasonable approach is to be cautious and avoid indiscriminate use.…”