Progress in the Fight Against Multidrug-Resistant Bacteria 2005–2016: Modern Noninferiority Trial Designs Enable Antibiotic Development in Advance of Epidemic Bacterial Resistance

Hospital environments constitute the main reservoir of multidrug-resistant bacteria. In this study we aimed to investigate the presence of Gram-negative bacteria in one Northwestern Tunisian hospital environment, and characterize the genes involved in bacterial resistance. A total of 152 environmental isolates were collected from various surfaces and isolated using MacConkey medium supplemented with cefotaxime or imipenem, with 81 fermenter bacteria (27 Escherichia coli, and 54 Enterobacter spp., including 46 Enterobacter cloacae), and 71 non-fermenting bacteria (69 Pseudomonas spp., including 54 Pseudomonas aeruginosa, and 2 Stenotrophomonas maltophilia) being identified by the MALDI-TOF-MS method. Antibiotic susceptibility testing was performed by disk diffusion method and E-Test was used to determine MICs for imipenem. Several genes implicated in beta-lactams resistance were characterized by PCR and sequencing. Carbapenem resistance was detected among 12 isolates; nine E. coli (blaNDM-1 (n = 8); blaNDM-1 + blaVIM-2 (n = 1)) and three P. aeruginosa were carbapenem-resistant by loss of OprD porin. The whole-genome sequencing of P. aeruginosa 97H was determined using Illumina MiSeq sequencer, typed ST285, and harbored blaOXA-494. Other genes were also detected, notably blaTEM (n = 23), blaCTX-M-1 (n = 10) and blaCTX-M-9 (n = 6). These new epidemiological data imposed new surveillance strategies and strict hygiene rules to decrease the spread of multidrug-resistant bacteria in this area.

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Bacteriophages: Protagonists of a Post-Antibiotic Era

Antibiotics ◽

10.3390/antibiotics7030066 ◽

2018 ◽

Vol 7 (3) ◽

pp. 66 ◽

Cited By ~ 34

Author(s):

Pilar Domingo-Calap ◽

Jennifer Delgado-Martínez

Keyword(s):

Bacterial Resistance ◽

Multidrug Resistant ◽

Therapeutic Agents ◽

Point Of View ◽

Resistant Bacteria ◽

Natural Killers ◽

Food Control ◽

Multidrug Resistant Bacteria ◽

Clinical Point ◽

Excellent Tool

Despite their long success for more than half a century, antibiotics are currently under the spotlight due to the emergence of multidrug-resistant bacteria. The development of new alternative treatments is of particular interest in the fight against bacterial resistance. Bacteriophages (phages) are natural killers of bacteria and are an excellent tool due to their specificity and ecological safety. Here, we highlight some of their advantages and drawbacks as potential therapeutic agents. Interestingly, phages are not only attractive from a clinical point of view, but other areas, such as agriculture, food control, or industry, are also areas for their potential application. Therefore, we propose phages as a real alternative to current antibiotics.

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Two Mechanisms of Killing of Pseudomonas aeruginosa by Tobramycin Assessed at Multiple Inocula via Mechanism-Based Modeling

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.04099-14 ◽

2015 ◽

Vol 59 (4) ◽

pp. 2315-2327 ◽

Cited By ~ 47

Author(s):

Jürgen B. Bulitta ◽

Neang S. Ly ◽

Cornelia B. Landersdorfer ◽

Nicholin A. Wanigaratne ◽

Tony Velkov ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Protein Synthesis ◽

Outer Membrane ◽

Bacterial Resistance ◽

Multidrug Resistant ◽

Quantitative Model ◽

Great Promise ◽

Resistant Bacteria ◽

Multidrug Resistant Bacteria ◽

Bacterial Killing

ABSTRACTBacterial resistance is among the most serious threats to human health globally, and many bacterial isolates have emerged that are resistant to all antibiotics in monotherapy. Aminoglycosides are often used in combination therapies against severe infections by multidrug-resistant bacteria. However, models quantifying different antibacterial effects of aminoglycosides are lacking. While the mode of aminoglycoside action on protein synthesis has often been studied, their disruptive action on the outer membrane of Gram-negative bacteria remains poorly characterized. Here, we developed a novel quantitative model for these two mechanisms of aminoglycoside action, phenotypic tolerance at high bacterial densities, and adaptive bacterial resistance in response to an aminoglycoside (tobramycin) against threePseudomonas aeruginosastrains. At low-intermediate tobramycin concentrations (<4 mg/liter), bacterial killing due to the effect on protein synthesis was most important, whereas disruption of the outer membrane was the predominant killing mechanism at higher tobramycin concentrations (≥8 mg/liter). The extent of killing was comparable across all inocula; however, the rate of bacterial killing and growth was substantially lower at the 108.9CFU/ml inoculum than that at the lower inocula. At 1 to 4 mg/liter tobramycin for strain PAO1-RH, there was a 0.5- to 6-h lag time of killing that was modeled via the time to synthesize hypothetical lethal protein(s). Disruption of the outer bacterial membrane by tobramycin may be critical to enhance the target site penetration of antibiotics used in synergistic combinations with aminoglycosides and thereby combat multidrug-resistant bacteria. The two mechanisms of aminoglycoside action and the new quantitative model hold great promise to rationally design novel, synergistic aminoglycoside combination dosage regimens.

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Molecular Mechanisms of Bacterial Resistance to Metal and Metal Oxide Nanoparticles

International Journal of Molecular Sciences ◽

10.3390/ijms20112808 ◽

2019 ◽

Vol 20 (11) ◽

pp. 2808 ◽

Cited By ~ 27

Author(s):

Nereyda Niño-Martínez ◽

Marco Felipe Salas Orozco ◽

Gabriel-Alejandro Martínez-Castañón ◽

Fernando Torres Méndez ◽

Facundo Ruiz

Keyword(s):

Metal Oxide ◽

Molecular Mechanisms ◽

Bacterial Resistance ◽

Bacterial Species ◽

Metal Oxide Nanoparticles ◽

Multidrug Resistant ◽

Resistance Mechanisms ◽

Resistant Bacteria ◽

Oxide Nanoparticles ◽

Multidrug Resistant Bacteria

The increase in bacterial resistance to one or several antibiotics has become a global health problem. Recently, nanomaterials have become a tool against multidrug-resistant bacteria. The metal and metal oxide nanoparticles are one of the most studied nanomaterials against multidrug-resistant bacteria. Several in vitro studies report that metal nanoparticles have antimicrobial properties against a broad spectrum of bacterial species. However, until recently, the bacterial resistance mechanisms to the bactericidal action of the nanoparticles had not been investigated. Some of the recently reported resistance mechanisms include electrostatic repulsion, ion efflux pumps, expression of extracellular matrices, and the adaptation of biofilms and mutations. The objective of this review is to summarize the recent findings regarding the mechanisms used by bacteria to counteract the antimicrobial effects of nanoparticles.

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Antibacterial activity of total flavonoids from Ilex rotunda Thunb. and different antibacterials on different multidrug-resistant bacteria alone or in combination

10.1101/457911 ◽

2018 ◽

Author(s):

Yongji Wu ◽

Beibei Chai ◽

Lizhen Wang ◽

Weijia Jiang ◽

Mei Hu ◽

...

Keyword(s):

Antibacterial Activity ◽

Bacterial Resistance ◽

Antimicrobial Agents ◽

Combined Therapy ◽

Multidrug Resistant ◽

Resistant Bacteria ◽

Total Flavonoids ◽

Multidrug Resistant Bacteria ◽

Minimal Inhibitory Concentrations ◽

Ilex Rotunda

AbstractThe problem of bacterial resistance is becoming more and more serious, which has become an urgent problem to be solved in human and veterinary. One approach to control and delay bacterial resistance is combination therapy in which antibiotics are given together with other antimicrobial or non-antimicrobial agents. Studies have shown that flavonoids from Traditional Chinese medicine (TCM) possess a high level of antibacterial activity against antibiotic resistant strains. The aim of this study was to evaluate the antibacterial effects of a combined therapy of total flavonoids from Ilex rotunda Thunb. and antibiotics against seven kinds of veterinary bacteria which were multidrug resistance bacteria. A microdilution checkerboard method was used to determine the minimal inhibitory concentrations of both types of antimicrobials, alone and in combination. The fractional inhibitory concentration index was calculated and used to classify observed collective antibacterial activity as synergistic, additive, indifferent or antagonistic.From the performed tests, the total flavonoids and antimicrobial agents were combined to inhibit different multidrug-resistant bacteria, such as Escherichia coli, Streptococcus, Pseudomonas aeruginosa, Enterococcus faecalis, Proteus vulgaris, Staphylococcus aureus, Acinetobacter baumannii. For these bacteria, total flavonoids from Ilex Rotunda Thunb. presented synergistic or additive with different antibiotics and had a certain antibacterial effect on the separated multidrug-resistant bacteria. The study shows total flavonoids from Ilex rotunda Thunb. have potential as adjuvants for the treatment of animal bacterial diseases.

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