Colistin-resistant multidrug-resistant (MDR), extensively drug-resistant (XDR), and pan-drug-resistant (PDR) bacteria are highly lethal and many researchers have tried hard to combat these microorganisms around the world. Infections caused by these bacteria are resistant to the last resort of antibiotic therapy and have posed a major challenge in clinical and public health. Since the production of new antibiotics is very expensive and also very slow compared to the increasing rate of antibiotic resistance, researchers are suggesting the use of natural substances with high antibacterial potential. Bacteriophages are one of the most effective therapeutic measures that are known to exist for use for incurable and highly resistant infections. Phages are highly taken into consideration due to the lack of side effects, potential spread to various body organs, distinct modes of action from antibiotics, and proliferation at the site of infection. Although the effects of phages on MDR and XDR bacteria have been demonstrated in various studies, only a few have investigated the effect of phage therapy on colistin-resistant isolates. Therefore, in this review, we discuss the problems caused by colistin-resistant MDR and XDR bacteria in the clinics, explain the different mechanisms associated with colistin resistance, introduce bacteriophage therapy as a powerful remedy, and finally present new studies that have used bacteriophages against colistin-resistant isolates.

Introduction: The extensive drug-resistant (XDR) Pseudomonas aeruginosa (P. aeruginosa) causes a range of infections with high mortality rate, which inflicts additional costs on treatment. The use of nano-biotechnology-based methods in medicine has opened a new perspective against drug-resistant bacteria. The aim of this study was to evaluate the effectiveness of the AgNO3 nanoparticles alone and conjugated with imipenem (IMI) to combat extensively drug-resistant P. aeruginosa. Methods: Antibiotic susceptibility was carried out using disc diffusion method. Detection of different resistant genes was performed using standard polymerase chain reaction (PCR). The chemically synthesized AgNO 3 particles were characterized using scanning electron microscope (SEM), dynamic light scattering (DLS) and X-ray diffraction (XRD) methods. Fourier transform infrared spectroscopy (FTIR) was accomplished to confirm the binding of AgNO 3 with IMI. The microdilution broth method was used to obtain minimum inhibitory concentration (MIC) of AgNO 3 and IMI-conjugated AgNO 3. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay was carried out on L929 cell line to study the cytotoxicity of nanoparticles. The data were analyzed by Eta correlation ratio and chisquare (X 2) test. Results: Analysis of the antibiotic resistance pattern showed that 12 (24%) isolates were XDR, and MIC values of IMI were between 64 and 128 μg/mL. Frequency of SHV, TEM, CTX M, IMP, VIM, OPR, SIM, SPM, GIM, NDM, VEB, PER, KPC, OXA, intI, intII, and intIII genes were 29 (58%), 26 (52%), 26 (52%), 32 (64%), 23 (46%), 43 (86%), 3 (6%), 6 (12%), 3 (6%), 4 (8%), 7 (14%), 6 (12%), 18 (36%), 4 (8%), 19 (38%), 16 (32%), and 2 (4%), respectively. The XRD, SEM, DLS, and FTIR analysis confirmed the synthesis of AgNO 3 nanoparticles and their conjugation with IMI. The AgNO 3 nanoparticles had antimicrobial activity, and their conjugation with IMI showed enhanced effectiveness against XDR isolates. The synthesized AgNO 3 showed no cytotoxic effects. Conclusion: The results suggest that IMI-conjugated AgNO 3 has a strong potency as a powerful antibacterial agent against XDR P. aeruginosa.

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