Multidrug-Resistant Gram-Negative Bacteria

Mills, John P.; Marchaim, Dror

doi:10.1016/j.idc.2021.08.001

Cited by 33 publications

(28 citation statements)

References 155 publications

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“…With the overuse and misuse of antibiotics in recent decades, antibiotic resistance in bacterial pathogens has become one of the greatest challenges in the public health system with high morbidity and mortality [1–3] . What is even worse is that antibiotic resistance in Gram‐positive and Gram‐negative bacteria has resulted in untreatable infections with conventional antibiotics [4–6] . It is estimated that there will be no effective antibiotics available by 2050, if no new drugs are developed or discovered [7] .…”

Section: Introductionmentioning

confidence: 99%

“…[1 -3] What is even worse is that antibiotic resistance in Gram-positive and Gram-negative bacteria has resulted in untreatable infections with conventional antibiotics. [4][5][6] It is estimated that there will be no effective antibiotics available by 2050, if no new drugs are developed or discovered. [7] Hence, the discovery of new antibiotics is crucial to solving the growing crisis of antibiotic resistance.…”

Section: Introductionmentioning

confidence: 99%

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Azaphilones from the Fungus Penicillium multicolor LZUC‐S2 and Their Antibacterial Activity

Shen

Feng

Jiang

et al. 2023

Chemistry & Biodiversity

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Two new azaphilones, penimultiones A and B, together with seven known analogs were isolated from the culture of Penicillium multicolor LZUC-S2. Their structures were elucidated by detailed spectroscopic data analysis and chemical transformation. Penimultiones A and B belong to a rare class of azaphilones possessing a 1,3dioxolane moiety. In addition, all compounds were evaluated for their antibacterial activity against five clinically bacterial strains in vitro, and three compounds showed potent antibacterial activity with minimum inhibitory concentration (MIC) values ranging from 12.5 to 50.0 μg/mL.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Azaphilones from the Fungus Penicillium multicolor LZUC‐S2 and Their Antibacterial Activity

Shen

Feng

Jiang

et al. 2023

Chemistry & Biodiversity

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“…[1][2][3] This is a particular challenge for infections caused by Gram-negative bacteria, as these organisms possess a protective outer membrane composed of lipopolysaccharides (LPS) that renders them resistant to many antibiotics and other therapeutic agents. [4][5][6] Despite the efficacy of chemically synthesized and conventional natural antibiotics against Gram-negative bacteria, [7][8][9] the emergence of multidrugresistant (MDR) strains and so-called "superbacteria" poses a grave threat to the survival of millions of people worldwide. [10][11][12] Thus, there is an urgent need for more effective antibacterial strategies to combat infections with Gram-negative bacteria.…”

Section: Introductionmentioning

confidence: 99%

Arginine‐Enhanced Antimicrobial Activity of Nanozymes against Gram‐Negative Bacteria

Zhao,

Wen,

Song

et al. 2023

Adv Healthcare Materials

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The continuous reduction of clinically available antibiotics has made it imperative to exploit more effective antimicrobial therapies, especially for difficult‐to‐treat Gram‐negative pathogens. Herein, we showed that the combination of an antimicrobial nanozyme with the clinically compatible basic amino acid L‐arginine affords a potent treatment for infections with Gram‐negative pathogens. In particular, the antimicrobial activity of the antimicrobial nanozyme was dramatically increased by approximately 1000‐fold after L‐arginine stimulation. Specifically, the combination therapy enhanced bacterial outer and inner membrane permeability and promoted intracellular reactive oxygen species (ROS) generation. Moreover, the metabolomic and transcriptomic results revealed that combination treatment led to the increased ROS‐mediated damage by inhibiting the tricarboxylic acid cycle and oxidative phosphorylation, thereby inducing an imbalance of the antioxidant and oxidant systems. Importantly, L‐arginine dramatically significantly accelerated the healing of infected wounds in mouse models of multidrug‐resistant peritonitis‐sepsis and skin wound infection. Overall, this work demonstrates a novel synergistic antibacterial strategy by combining the antimicrobial nanozymes with L‐arginine, which substantively facilitates the nanozyme‐mediated killing of pathogens by promoting ROS production.This article is protected by copyright. All rights reserved

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“…P. aeruginosa has the characteristics of easy colonization, variation, and multi-drug resistance (MDR) ( Miyoshi-Akiyama et al, 2017 ; Liao et al, 2019 ; Al-Orphaly et al, 2021 ). Among Gram-negative strains, the most common MDR pathogens are Acinetobacter baumannii , P. aeruginosa , and Enterobacteriaceae ( Otsuka, 2020 ; Mills and Marchaim, 2021 ). In China, carbapenem-resistant Pseudomonas aeruginosa (CR-PA) has been included in one of the five MDR bacteria targeted for prevention and control, in accordance with the requirements of the National Health Commission.…”

Section: Introductionmentioning

confidence: 99%

Clinical Efficacy and In Vitro Drug Sensitivity Test Results of Azithromycin Combined With Other Antimicrobial Therapies in the Treatment of MDR P. aeruginosa Ventilator-Associated Pneumonia

et al. 2022

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Objective: The aim of the research was to study the effect of azithromycin (AZM) in the treatment of MDR P. aeruginosa VAP combined with other antimicrobial therapies.Methods: The clinical outcomes were retrospectively collected and analyzed to elucidate the efficacy of different combinations involving azithromycin in the treatment of MDR-PA VAP. The minimal inhibitory concentration (MIC) of five drugs was measured by the agar dilution method against 27 isolates of MDR-PA, alone or in combination.Results: The incidence of VAP has increased approximately to 10.4% (961/9245) in 5 years and 18.4% (177/961) caused by P. aeruginosa ranking fourth. A total of 151 cases of MDR P. aeruginosa were included in the clinical retrospective study. Clinical efficacy results are as follows: meropenem + azithromycin (MEM + AZM) was 69.2% (9/13), cefoperazone/sulbactam + azithromycin (SCF + AZM) was 60% (6/10), and the combination of three drugs containing AZM was 69.2% (9/13). The curative effect of meropenem + amikacin (MEM + AMK) was better than that of the meropenem + levofloxacin (MEM + LEV) group, p = 0.029 (p < 0.05). The curative effect of cefoperazone/sulbactam + amikacin (SCF + AMK) was better than that of the cefoperazone/sulbactam + levofloxacin (SCF + LEV) group, p = 0.025 (p < 0.05). There was no significant difference between combinations of two or three drugs containing AZM, p > 0.05 (p = 0.806). From the MIC results, the AMK single drug was already very sensitive to the selected strains. When MEM or SCF was combined with AZM, the sensitivity of them to strains can be significantly increased. When combined with MEM and AZM, the MIC50 and MIC90 of MEM decreased to 1 and 2 ug/mL from 8 to 32 ug/mL. When combined with SCF + AZM, the MIC50 of SCF decreased to 16 ug/mL, and the curve shifted obviously. However, for the combination of SCF + LEV + AZM, MIC50 and MIC90 could not achieve substantive changes. From the FIC index results, the main actions of MEM + AZM were additive effects, accounting for 72%; for the combination of SCF + AZM, the additive effect was 40%. The combination of AMK or LEV with AZM mainly showed unrelated effects, and the combination of three drugs could not improve the positive correlation between LEV and AZM.Conclusion: AZM may increase the effect of MEM or SCF against MDR P. aeruginosa VAP. Based on MEM or SCF combined with AMK or AZM, we can achieve a good effect in the treatment of MDR P. aeruginosa VAP.

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Multidrug-Resistant Gram-Negative Bacteria

Cited by 33 publications

References 155 publications

Azaphilones from the Fungus Penicillium multicolor LZUC‐S2 and Their Antibacterial Activity

Azaphilones from the Fungus Penicillium multicolor LZUC‐S2 and Their Antibacterial Activity

Arginine‐Enhanced Antimicrobial Activity of Nanozymes against Gram‐Negative Bacteria

Clinical Efficacy and In Vitro Drug Sensitivity Test Results of Azithromycin Combined With Other Antimicrobial Therapies in the Treatment of MDR P. aeruginosa Ventilator-Associated Pneumonia

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