Repurposed Antimicrobial Combination Therapy: Tobramycin-Ciprofloxacin Hybrid Augments Activity of the Anticancer Drug Mitomycin C Against Multidrug-Resistant Gram-Negative Bacteria

The lack of therapeutic options to treat infections caused by recalcitrant multidrug-resistant pathogens, especially Gram-negative bacteria, is apparent. Therefore, it is imperative to develop new strategies to address the problem of antimicrobial resistance. Repurposing non-antibiotic commercial drugs for antimicrobial therapy presents a viable option. We screened six anticancer drugs for their potential use in antimicrobial therapy. Here, we provide in vitro evidence that suggests feasibility to repurpose the anticancer drug mitomycin C against multidrug-resistant Gram-negative bacteria. We also demonstrated that mitomycin C, etoposide and doxorubicin were affected by drug efflux in Pseudomonas aeruginosa. In combination with a tobramycin-ciprofloxacin antibiotic hybrid (TOB-CIP), the antibacterial activity of mitomycin C was enhanced against multidrug-resistant clinical isolates of P. aeruginosa, Acinetobacter baumannii, Escherichia coli, Klebsiella pneumoniae and Enterobacter cloacae. In fact, 4 µg/mL (3 µM) TOB-CIP reduced the minimum inhibitory concentration of mitomycin C to ≤1 µg/mL against multidrug-resistant Gram-negative bacteria, except A. baumannii. We showed that synergy was inherent to TOB-CIP and that neither tobramycin nor ciprofloxacin individually synergized with mitomycin C. Our finding supports identifying adjuvant partners for mitomycin C, such as TOB-CIP, to enhance suitability for antimicrobial therapy.
Source: Frontiers in Microbiology - Category: Microbiology Source Type: research

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Conclusion: New carbapenem/βLI combinations may be viable alternatives to antimicrobial combination therapy as they displayed high efficacy in vitro and in vivo. Meropenem/Avibactam and Meropenem/Relebactam should be tested on larger sample sizes with different carbapenemases before progressing further in its preclinical development. Introduction Carbapenem resistant Gram-negative bacteria have been gradually increasing in prevalence in recent years. In the United States, the latest CDC Antibiotic Resistance Threat Report indicates that Carbapenem-Resistant Enterobacteriaceae (CREs) are responsible for 9,000 a...
Source: Frontiers in Microbiology - Category: Microbiology Source Type: research
Application of Antimicrobial Peptides of the Innate Immune System in Combination With Conventional Antibiotics—A Novel Way to Combat Antibiotic Resistance? Maria S. Zharkova1, Dmitriy S. Orlov1, Olga Yu. Golubeva2, Oleg B. Chakchir3, Igor E. Eliseev3, Tatyana M. Grinchuk4 and Olga V. Shamova1* 1Laboratory of Design and Synthesis of Biologically Active Peptides, Department of General Pathology and Pathophysiology, FSBSI Institute of Experimental Medicine, Saint Petersburg, Russia 2Laboratory of Nanostructures Research, Institute of Silicate Chemistry of the Russian Academy of Sciences, Saint Petersburg, Russia ...
Source: Frontiers in cellular and infection microbiology - Category: Microbiology Source Type: research
Conclusion The results of our study demonstrate that robenidine is not suitable as a sole antimicrobial agent for the treatment of Gram-negative pathogen infections due to the lack of activity against the majority of Gram-negative isolates except for A. baumannii and A. calcoaceticus. However, we demonstrated in vitro efficacy against all selected Gram-negative organisms when robenidine was tested in combination with EDTA or PMBN, including against multidrug-resistant strains. Therefore, robenidine may be an appropriate candidate as a component of a combination preparation for the treatment of otitis externa in dogs. This...
Source: Frontiers in Microbiology - Category: Microbiology Source Type: research
In this study, the effects of manure spiked with or without doxycycline on the prokaryotic community composition as well as on the relative abundance of ARGs and MGEs in lettuce rhizosphere and bulk soil were investigated by means of a polyphasic cultivation-independent approach. Samples were taken 42 days after manure application, and total community DNA was extracted. Besides a pronounced manure effect, doxycycline spiking caused an additional enrichment of ARGs and MGEs. High-throughput quantitative PCR revealed an increase in tetracycline, aminoglycoside, and macrolide–lincosamide–streptogramin B (MLSB) res...
Source: Frontiers in Microbiology - Category: Microbiology Source Type: research
Conclusion The present results demonstrated that Chilean salmon farms play an important role as reservoirs of sulfonamide- and trimethoprim-resistant bacteria. The prevalence of conjugative plasmids and integrons among sul-carrying bacteria suggests these bacteria, mainly belonging to the Pseudomonas genus may contribute to high spread of bacterial resistance to sulfonamides and other antibacterials in environments associated with Chilean salmon farms. This is the first study reporting the occurrence of transferable sul and dfr genes and integrons among the antimicrobial resistant bacteria associated with Chilean salmonid...
Source: Frontiers in Microbiology - Category: Microbiology Source Type: research
In this study, a BER homolog encoded by cj0595c (named nth) in C. jejuni was analyzed for endonuclease III activity and for its role in maintaining genomic stability. It was found that inactivation of nth resulted in elevated frequencies of spontaneous fluoroquinolone-resistant (FQR) and oxidative stress resistant (OXR) mutants, compared with the wild-type strain in C. jejuni. Sequencing analysis of the FQR and OXR mutants revealed that the elevated mutation rates were associated with C → T or G → A transition in gyrA (FQR mutants) or perR (for OXR mutants). In an in vitro assay, a purified recombinant C. jejuni ...
Source: Frontiers in Microbiology - Category: Microbiology Source Type: research
Abstract There is an urgent need for new therapies to overcome antimicrobial resistance especially in Gram-negative bacilli (GNB). Repurposing old U.S. Food and Drug Administration-approved drugs as complementary agents to existing antibiotics in a synergistic combination presents an attractive strategy. Here, we demonstrate that the anthelmintic drug niclosamide selectively synergized with the lipopeptide antibiotic colistin against colistin-susceptible but more importantly against colistin-resistant GNB, including clinical isolates that harbor the mcr-1 gene. Breakpoints for colistin susceptibility in resistant ...
Source: Antimicrobial Agents and Chemotherapy - Category: Microbiology Authors: Tags: Antimicrob Agents Chemother Source Type: research
Authors: Wang M, Wei H, Zhao Y, Shang L, Di L, Lyu C, Liu J Abstract The frequency of antimicrobial resistance has increased globally due to misuse and overuse of antibiotics, and multi-drug resistant (MDR) bacteria are now recognized as a major cause of hospital-acquired infections (HAI). Our aim was to investigate the prevalence, distribution, and antimicrobial susceptibility rates of MDR bacteria in patients with HAI from a tertiary hospital in China. We retrospectively evaluated all patients with a confirmed diagnosis of bacterial infection at a tertiary general hospital in Jining, for the period between Januar...
Source: Bosnian Journal of Basic Medical Sciences - Category: General Medicine Tags: Bosn J Basic Med Sci Source Type: research
ConclusionThis study shows low resistance to meropenem and tigecycline among the Enterobacteriaceae, and continued activity of linezolid, vancomycin and tigecycline against Gram-positive organisms. However, antimicrobial resistance continues to be problematic in Eastern Europe and requires continued surveillance.
Source: Journal of Global Antimicrobial Resistance - Category: Infectious Diseases Source Type: research
AbstractBackgroundTreatment and prevention of wound infection continues to be a challenging issue in clinical settings of Nepal especially in the context of globally growing problem of antimicrobial resistance. Study on opportunistic pathogens and sensitivity to commonly prescribed local antimicrobial agents are cardinal to reduce the disease burden of wound infections. The aim of this study was to determine the prevalence and antimicrobial susceptibility pattern of methicillin resistantStaphylococcus aureus (MRSA) and extended spectrum β-lactamase (ESBL) producing bacteria from wound infections of patients at a terti...
Source: Antimicrobial Resistance and Infection Control - Category: Infectious Diseases Source Type: research
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