Microbial Resistance to Antibiotics and Effective Antibiotherapy

Abstract

Currently, the efficacy of antibiotics is severely affected by the emergence of the antimicrobial resistance phenomenon, leading to increased morbidity and mortality worldwide. Multidrug-resistant pathogens are found not only in hospital settings, but also in the community, and are considered one of the biggest public health concerns. The main mechanisms by which bacteria develop resistance to antibiotics include changes in the drug target, prevention of entering the cell, elimination through efflux pumps or inactivation of drugs. A better understanding and prediction of resistance patterns of a pathogen will lead to a better selection of active antibiotics for the treatment of multidrug-resistant infections.

Keywords: antibiotherapy; antibiotic resistance; biofilms; mechanism of resistance; multidrug-resistant bacteria; persistence.

Figure 2

The main mechanisms of action of antibiotics [21,22,23,24].

Figure 4

Genetic transfer in AMR—(1) conjugation, transfer of genes from one bacterial cell to another that requires cell-to-cell contact, (2) transformation—uptake of free DNA from the environment, (3) transfer of plasmid genes from one cell to another by viruses. Adapted from [128], published by Pharmaceuticals and Personal Care Products: Waste Management and Treatment Technology, 2019.

Figure 1

The evolution of antibiotics discovery and their resistance (MRSA—methicillin-resistant Staphylococcus aureus, PDR—pan-drug-resistant, VRE—vancomycin-resistant enterococci, VRSA—vancomycin-resistant Staphylococcus aureus, XDR—extensively drug-resistant) [2,5,6,8].

Figure 3

Various elements of bacterial resistance to antibiotics. Adapted from [79], published by Front Microbiol, 2013 and [80], published by Environ Sci Pollut Res, 2019.

Figure 5

Resistance vs. persistence. Adapted from [20], published by AIMS Microbiol, 2018.

Figure 6

Stages of microbial biofilm formation. Adapted from [163], published by Antimicrobial Resist Infect Control, 2019 and [164], published by Front Chem, 2019.

Figure 7

Rate of antimicrobial resistance of K. pneumoniae, E. coli and Enterobacter spp. isolates to different antibiotics (AMK—amikacin, AZT—aztreonam, CAZ—ceftazidime, CFM—cefixime, CFZ—cefazolin, CPM—cefepime, CTX—cefotaxime, ETP—ertapenem, GEN—gentamicin, IMI—imipenem, MEM—meropenem, PTZ—piperacillin-tazobactam, TET—tetracycline, TMT-SMX—trimethoprim-sulfamethoxazole, TOB—tobramycin). Adapted from [255], published by Infect Drug Resist, 2020.

Figure 8

Antibiotics active against P. aeruginosa. Adapted from [254], published by Pathogens, 2021.

Figure 9

Resistance of P. aeruginosa and virulence factors causing extreme pathogenicity. This figure was based on the information provided in [270,271].

Figure 10

Phage replication cycles: a—bacteria lysis; b—infection; c—replication; d—integration; e—induction; f—vertical transfer. Adapted from [289], published by Trends Microbiol, 2018.