Quinolone Antibiotics: Resistance and Therapy

Abstract

The clinical application of quinolone antibiotics is particularly extensive. In addition to their high efficiency in infectious diseases, the treatment process brings multiple hidden dangers or side effects. In this regard, drug resistance becomes a major challenge and is almost unavoidable in the clinical application of quinolones. Both genetic and phenotypic variations contribute to bacterial survival resistance under antibiotic therapy. This review is focusing on the drug discovery history, compound structure, and bactericidal mechanism of quinolone antibiotics. Recent studies bring a more in-depth insight into the research progress of quinolone antibiotics in the causes of death, drug resistance formation, and closely related SOS response after disease treatment at this stage. Combined with the latest clinical studies, we summarize the clinical application of quinolone antibiotics and further lay a theoretical foundation for the mechanism study of resistant or sensitive bacteria in response to quinolone treatment.

Keywords: SOS response; bacteria; disease treatment; lethality; quinolone antibiotics.

Figure 1

Core structure of quinolone antibiotics. (A) Six important modification positions include R1, R5, R6, R7, R8, and X for improving the drug activity. X=C defines quinolones and X=N defines naphthenes. (B) Each modification position has different effects such as antibacterial, affecting pharmacokinetics, enhancing activity and enzymatic binding.

Figure 2

Classification and features of quinolone antibiotics. Quinolone antibiotics are developed from generations to generations, and a wider spectrum of activity is obtained by adding different substituents at different positions in the core structure. Substituent positions and groups are outlined in red.

Figure 3

Global distribution of major quinolone resistant bacteria. Yellow represents Escherichia coli, green represents Klebsiella pneumoniae, red represents Staphylococcus aureus, blue represents Streptococcus pneumoniae and purple represents Neisseria Gonorrhoeae. Light green represents no data report.

Figure 4

MIC comparison of quinolones. The potency of each drug presented in the MIC90 (mg L⁻¹) of different Gram-negative and Gram-positive strains.

Figure 5

Schematic of a gene interaction network related to the SOS response in E. coli based on literature. The figure represents the inducible genes/proteins in the SOS response for repairing DNA damage. Black lines indicate pathways during normal repair and red lines indicate arrows activated/induced due to exposure to damaging substances. Recombination and repair, DNA damage-inducible protein, nucleotide excision repair, error-prone repair, and stationary-phase regulator have family molecules in each box.