scholarly journals Multidrug and Pan-Antibiotic Resistance—The Role of Antimicrobial and Synergistic Essential Oils: A Review

2020 ◽  
Vol 15 (10) ◽  
pp. 1934578X2096259
Author(s):  
Karen Boren ◽  
AliceAnn Crown ◽  
Richard Carlson
Keyword(s):  
Essential Oils ◽  
Bacterial Resistance ◽  
Fungal Infections ◽  
Multidrug Resistant ◽  
World Health ◽  
Resistant Bacteria ◽  
Bacterial Membranes ◽  
New Antibiotics ◽  
Clinical Benefits

Bacterial resistance to antibiotics continues to be a grave threat to human health. Because antibiotics are no longer a lucrative market for pharmaceutical companies, the development of new antibiotics has slowed to a crawl. The World Health Organization reported that the 8 new bacterial agents approved since July 2017 had limited clinical benefits. While a cohort of biopharmaceutical companies recently announced plans to develop 2-4 new antibiotics by 2030, we needn’t wait a decade to find innovative antibiotic candidates. Essential oils (EOs) have long been known as antibacterial agents with wide-ranging arsenals. Many are able to penetrate the bacterial membrane and may also be effective against bacterial defenses such as biofilms, efflux pumps, and quorum sensing. EOs have been documented to fight drug-resistant bacteria alone and/or combined with antibiotics. This review will summarize research showing the significant role of EOs as nonconventional regimens against the worldwide spread of antibiotic-resistant pathogens. The authors conducted a 4-year search of the US National Library of Medicine (PubMed) for relevant EO studies against methicillin-resistant Staphylococcus aureus, multidrug-resistant (MDR) Escherichia coli, EO combinations/synergy with antibiotics, against MDR fungal infections, showing the ability to permeate bacterial membranes, and against the bacterial defenses listed above. EOs are readily available and are a needed addition to the arsenal against resistant pathogens.

scholarly journals Gold Nanoparticles: Can They Be the Next Magic Bullet for Multidrug-Resistant Bacteria?

Nanomaterials ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 312
Author(s):  
Mohammad Okkeh ◽  
Nora Bloise ◽  
Elisa Restivo ◽  
Lorenzo De Vita ◽  
Piersandro Pallavicini ◽  
...  
Keyword(s):  
Gold Nanoparticles ◽  
Bacterial Resistance ◽  
Multidrug Resistant ◽  
World Health ◽  
Resistant Bacteria ◽  
Magic Bullet ◽  
Global Challenge ◽  
Gold Silver ◽  
Inorganic Nanomaterials ◽  
Health Organization

In 2017 the World Health Organization (WHO) announced a list of the 12 multidrug-resistant (MDR) families of bacteria that pose the greatest threat to human health, and recommended that new measures should be taken to promote the development of new therapies against these superbugs. Few antibiotics have been developed in the last two decades. Part of this slow progression can be attributed to the surge in the resistance acquired by bacteria, which is holding back pharma companies from taking the risk to invest in new antibiotic entities. With limited antibiotic options and an escalating bacterial resistance there is an urgent need to explore alternative ways of meeting this global challenge. The field of medical nanotechnology has emerged as an innovative and a powerful tool for treating some of the most complicated health conditions. Different inorganic nanomaterials including gold, silver, and others have showed potential antibacterial efficacies. Interestingly, gold nanoparticles (AuNPs) have gained specific attention, due to their biocompatibility, ease of surface functionalization, and their optical properties. In this review, we will focus on the latest research, done in the field of antibacterial gold nanoparticles; by discussing the mechanisms of action, antibacterial efficacies, and future implementations of these innovative antibacterial systems.

scholarly journals Multidrug-Resistant Bacteria Isolated from Different Aquatic Environments in the North of Spain and South of France

2020 ◽  
Vol 8 (9) ◽  
pp. 1425
Author(s):  
Lara Pérez-Etayo ◽  
David González ◽  
José Leiva ◽  
Ana Isabel Vitas
Keyword(s):  
Wastewater Treatment Plants ◽  
Multidrug Resistant ◽  
World Health ◽  
Resistant Bacteria ◽  
Aquatic Environments ◽  
Multidrug Resistant Bacteria ◽  
Antibiotic Resistant ◽  
The North ◽  
New Antibiotics ◽  
Health Organization

Due to the global progress of antimicrobial resistance, the World Health Organization (WHO) published the list of the antibiotic-resistant “priority pathogens” in order to promote research and development of new antibiotics to the families of bacteria that cause severe and often deadly infections. In the framework of the One Health approach, the surveillance of these pathogens in different environments should be implemented in order to analyze their spread and the potential risk of transmission of antibiotic resistances by food and water. Therefore, the objective of this work was to determine the presence of high and critical priority pathogens included in the aforementioned list in different aquatic environments in the POCTEFA area (North Spain–South France). In addition to these pathogens, detection of colistin-resistant Enterobacteriaceae was included due its relevance as being the antibiotic of choice to treat infections caused by multidrug resistant bacteria (MDR). From the total of 80 analyzed samples, 100% of the wastewater treatment plants (WWTPs) and collectors (from hospitals and slaughterhouses) and 96.4% of the rivers, carried antibiotic resistant bacteria (ARB) against the tested antibiotics. Fifty-five (17.7%) of the isolates were identified as target microorganisms (high and critical priority pathogens of WHO list) and 58.2% (n = 32) of them came from WWTPs and collectors. Phenotypic and genotypic characterization showed that 96.4% were MDR and resistance to penicillins/cephalosporins was the most widespread. The presence of bla genes, KPC-type carbapenemases, mcr-1 and vanB genes has been confirmed. In summary, the presence of clinically relevant MDR bacteria in the studied aquatic environments demonstrates the need to improve surveillance and treatments of wastewaters from slaughterhouses, hospitals and WWTPs, in order to minimize the dispersion of resistance through the effluents of these areas.

scholarly journals Complex effects of macrolide venturicidins on bacterial F-ATPases likely contribute to their action as antibiotic adjuvants

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yakov M. Milgrom ◽  
Thomas M. Duncan
Keyword(s):  
Atpase Activity ◽  
Atp Synthase ◽  
Critical Factor ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Adjuvant Activity ◽  
Bacterial Membranes ◽  
Resistant Tuberculosis ◽  
Key Factor ◽  
New Antibiotics

AbstractBacterial energy metabolism is now recognized as a critical factor for the efficacy of antibiotics. The F-type ATPase/ATP synthase (FOF1) is a central player in cellular bioenergetics of bacteria and eukaryotes, and its potential as a selective antibiotic target has been confirmed by the success of bedaquiline in combatting multidrug-resistant tuberculosis. Venturicidin macrolides were initially identified for their antifungal properties and were found to specifically inhibit FOF1 of eukaryotes and bacteria. Venturicidins alone are not effective antibacterials but recently were found to have adjuvant activity, potentiating the efficacy of aminoglycoside antibiotics against several species of resistant bacteria. Here we discovered more complex effects of venturicidins on the ATPase activity of FOF1 in bacterial membranes from Escherichia coli and Pseudomonas aeruginosa. Our major finding is that higher concentrations of venturicidin induce time– and ATP–dependent decoupling of F1-ATPase activity from the venturicidin-inhibited, proton-transporting FO complex. This dysregulated ATPase activity is likely to be a key factor in the depletion of cellular ATP induced by venturicidins in prior studies with P. aeruginosa and Staphylococcus aureus. Further studies of how this functional decoupling occurs could guide development of new antibiotics and/or adjuvants that target the F-type ATPase/ATP synthase.

scholarly journals Antimicrobial Stewardship Program: Reducing Antibiotic’s Spectrum of Activity Is not the Solution to Limit the Emergence of Multidrug-Resistant Bacteria

Antibiotics ◽  
2022 ◽  
Vol 11 (1) ◽  
pp. 70
Author(s):  
Rindala Saliba ◽  
Assaf Mizrahi ◽  
Péan de Ponfilly Gauthier ◽  
Le Monnier Alban ◽  
Jean-Ralph Zahar ◽  
...  
Keyword(s):  
Bacterial Resistance ◽  
Multidrug Resistant ◽  
Resistance Mechanisms ◽  
Resistant Bacteria ◽  
Stewardship Program ◽  
Intestinal Dysbiosis ◽  
Pharmacokinetic Properties ◽  
Multidrug Resistant Organisms ◽  
New Antibiotics ◽  
The Impact

Overconsumption of antibiotics in hospitals has led to policy implementation, including the control of antibiotic prescriptions. The impact of these policies on the evolution of antimicrobial resistance remains uncertain. In this work, we review the possible limits of such policies and focus on the need for a more efficient approach. Establishing a causal relationship between the introduction of new antibiotics and the emergence of new resistance mechanisms is difficult. Several studies have demonstrated that many resistance mechanisms existed before the discovery of antibiotics. Overconsumption of antibiotics has worsened the phenomenon of resistance. Antibiotics are responsible for intestinal dysbiosis, which is suspected of being the source of bacterial resistance. The complexity of the intestinal microbiota composition, the impact of the pharmacokinetic properties of antibiotics, and the multiplicity of other factors involved in the acquisition and emergence of multidrug-resistant organisms, lead us to think that de-escalation, in the absence of studies proving its effectiveness, is not the solution to limiting the spread of multidrug-resistant organisms. More studies are needed to clarify the ecological risk caused by different antibiotic classes. In the meantime, we need to concentrate our efforts on limiting antibiotic prescriptions to patients who really need it, and work on reducing the duration of these treatments.

scholarly journals Membrane-Activating Triphenylphosphonium Functionalized Ciprofloxacin for Multidrug Resistant Bacteria

2020 ◽  
Author(s):  
Sangrim Kang ◽  
Kyoung Sunwoo ◽  
Yuna Jung ◽  
Junho Hur ◽  
Ki-Ho Park ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Morphological Changes ◽  
Antibacterial Activities ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Severe Problem ◽  
Bacterial Membranes ◽  
High Antibacterial Activity ◽  
New Antibiotics ◽  
Mrsa Strains

Multidrug resistant (MDR) bacteria have become a severe problem for public health. Developing new antibiotics for MDR bacteria is difficult, from inception to the clinically approved stage. Here, we have used a new approach; we have modified the antibiotic, ciprofloxacin (CFX), with triphenylphosphonium (TPP, PPh3) moiety via ester- (CFX-ester-PPh3) and amide-coupling (CFX-ester-PPh3), to target bacterial membranes. In this study, we have evaluated the antibacterial activities of CFX and its derivatives against 16 species of bacteria, including MDR bacteria, using minimum inhibitory concentration (MIC) assay, morphological monitoring, and expression of resistance-related genes. TPP-conjugated CFX, CFX-ester-PPh3 and CFX-amide-PPh3 showed significantly improved antibacterial activity against Gram-positive bacteria, Staphylococcus aureus, including MDR S. aureus (MRSA) strains. The MRSA ST5 5016 strain showed high antibacterial activity, with an MIC values of 11.12 µg/mL for CFX-ester-PPh3 and 2.78 µg/mL for CFX-amide-PPh3. The CFX derivatives inhibited biofilm formation in MRSA by more than 74.9% of CFX-amide-PPh3. In the sub-MIC, CFX derivates induced significant morphological changes in MRSA, including irregular deformation and membrane disruption, accompanied by a decrease in the level of resistance-related gene expression. With these promising results, this method is very likely to combat MDR bacteria, through a simple TPP moiety modification of known antibiotics, which can be readily prepared at clinical sites.

Complex Effects of Macrolide Venturicidins on Bacterial F-ATPases Likely Contribute to Their Action as Antibiotic Adjuvants

2021 ◽  
Author(s):  
Yakov M. Milgrom ◽  
Thomas M. Duncan
Keyword(s):  
Atpase Activity ◽  
Atp Synthase ◽  
Critical Factor ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Adjuvant Activity ◽  
Bacterial Membranes ◽  
Resistant Tuberculosis ◽  
Key Factor ◽  
New Antibiotics

Abstract Bacterial energy metabolism is now recognized as a critical factor for the efficacy of antibiotics. The F-type ATPase/ATP synthase (FOF1) is a central player in cellular bioenergetics of bacteria and eukaryotes, and its potential as a selective antibiotic target has been confirmed by the success of bedaquiline in combatting multidrug-resistant tuberculosis. Venturicidin macrolides were initially identified for their antifungal properties and were found to specifically inhibit FOF1 of eukaryotes and bacteria. Venturicidins alone are not effective antibacterials but recently were found to have adjuvant activity, potentiating the efficacy of aminoglycoside antibiotics against several species of resistant bacteria. Here we discovered more complex effects of venturicidins on the ATPase activity of FOF1 in bacterial membranes from Escherichia coli and Pseudomonas aeruginosa. Our major finding is that higher concentrations of venturicidin induce time– and ATP–dependent decoupling of F1-ATPase activity from the venturicidin-inhibited, proton-transporting FO complex. This dysregulated ATPase activity is likely to be a key factor in the depletion of cellular ATP induced by venturicidins in prior studies with P. aeruginosa and Staphylococcus aureus. Further studies of how this functional decoupling occurs could guide development of new antibiotics and/or adjuvants that target the F-type ATPase/ATP synthase.

scholarly journals Taking Bacteriophage Therapy Seriously: A Moral Argument

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Gilbert Verbeken ◽  
Isabelle Huys ◽  
Jean-Paul Pirnay ◽  
Serge Jennes ◽  
Nina Chanishvili ◽  
...  
Keyword(s):  
Pharmaceutical Industry ◽  
Western Europe ◽  
Bacterial Resistance ◽  
Multidrug Resistant ◽  
Shared Responsibility ◽  
Resistant Bacteria ◽  
Bacteriophage Therapy ◽  
Bacterial Populations ◽  
Improper Use ◽  
New Antibiotics

The excessive and improper use of antibiotics has led to an increasing incidence of bacterial resistance. In Europe the yearly number of infections caused by multidrug resistant bacteria is more than 400.000, each year resulting in 25.000 attributable deaths. Few new antibiotics are in the pipeline of the pharmaceutical industry. Early in the 20th century, bacteriophages were described as entities that can control bacterial populations. Although bacteriophage therapy was developed and practiced in Europe and the former Soviet republics, the use of bacteriophages in clinical setting was neglected in Western Europe since the introduction of traditional antibiotics. Given the worldwide antibiotic crisis there is now a growing interest in making bacteriophage therapy available for use in modern western medicine. Despite the growing interest, access to bacteriophage therapy remains highly problematic. In this paper, we argue that the current state of affairs is morally unacceptable and that all stakeholders (pharmaceutical industry, competent authorities, lawmakers, regulators, and politicians) have the moral duty and the shared responsibility towards making bacteriophage therapy urgently available for all patients in need.

scholarly journals Multidrug Resistence Prevalence in COVID Area

Life ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 601
Author(s):  
Caterina Aurilio ◽  
Pasquale Sansone ◽  
Antonella Paladini ◽  
Manlio Barbarisi ◽  
Francesco Coppolino ◽  
...  
Keyword(s):  
Bacterial Resistance ◽  
Respiratory Infections ◽  
Prolonged Mechanical Ventilation ◽  
Viral Disease ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Antimicrobial Drugs ◽  
Infected People ◽  
Therapeutic Procedures ◽  
Viral Respiratory Infections

Coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, is often complicated by severe acute respiratory syndrome. The new coronavirus outbreak started in China in December 2019 and rapidly spread around the world. The high diffusibility of the virus was the reason for the outbreak of the pandemic viral disease, reaching more than 100 million infected people globally by the first three months of 2021. In the various treatments used up to now, the use of antimicrobial drugs for the management, especially of bacterial co-infections, is very frequent in patients admitted to intensive care. In addition, critically ill patients with SARS-CoV-2 infection are subjected to prolonged mechanical ventilation and other therapeutic procedures often responsible for developing hospital co-infections due to multidrug-resistant bacteria. Co-infections contribute to the increase in the morbidity–mortality of viral respiratory infections. We performed this study to review the recent articles published on the antibiotic bacterial resistance and viruses to predict risk factors of coronavirus disease 2019 and to assess the multidrug resistance in patients hospitalized in the COVID-19 area.

scholarly journals Antibiotic Pipeline Coordinators

2018 ◽  
Vol 46 (S1) ◽  
pp. 25-31 ◽  
Author(s):  
Enrico Baraldi ◽  
Olof Lindahl ◽  
Miloje Savic ◽  
David Findlay ◽  
Christine Årdal
Keyword(s):  
Research And Development ◽  
World Health ◽  
Resistant Bacteria ◽  
Antibiotic Resistant ◽  
Priority List ◽  
Non Profit ◽  
Global Priority ◽  
The World ◽  
New Antibiotics ◽  
Health Organization

The World Health Organization (WHO) has published a global priority list of antibiotic-resistant bacteria to guide research and development (R&D) of new antibiotics. Every pathogen on this list requires R&D activity, but some are more attractive for private sector investments, as evidenced by the current antibacterial pipeline. A “pipeline coordinator” is a governmental/non-profit organization that closely tracks the antibacterial pipeline and actively supports R&D across all priority pathogens employing new financing tools.

scholarly journals Independent Behavior of Commensal Flora for Carriage of Fluoroquinolone-Resistant Bacteria in Patients at Admission

2010 ◽  
Vol 54 (12) ◽  
pp. 5193-5200 ◽  
Author(s):  
Victoire de Lastours ◽  
Françoise Chau ◽  
Florence Tubach ◽  
Blandine Pasquet ◽  
Etienne Ruppé ◽  
...  
Keyword(s):  
Risk Factors ◽  
Bacterial Resistance ◽  
Care Facility ◽  
Health Care Facility ◽  
Epidemiological Data ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
E Coli ◽  
Commensal Flora ◽  
Resistant Strains

ABSTRACT The important role of commensal flora as a natural reservoir of bacterial resistance is now well established. However, whether the behavior of each commensal flora is similar to that of other floras in terms of rates of carriage and risk factors for bacterial resistance is unknown. During a 6-month period, we prospectively investigated colonization with fluoroquinolone-resistant bacteria in the three main commensal floras from hospitalized patients at admission, targeting Escherichia coli in the fecal flora, coagulase-negative Staphylococcus (CNS) in the nasal flora, and α-hemolytic streptococci in the pharyngeal flora. Resistant strains were detected on quinolone-containing selective agar. Clinical and epidemiological data were collected. A total of 555 patients were included. Carriage rates of resistance were 8.0% in E. coli, 30.3% in CNS for ciprofloxacin, and 27.2% in streptococci for levofloxacin; 56% of the patients carried resistance in at least one flora but only 0.9% simultaneously in all floras, which is no more than random. Risk factors associated with the carriage of fluoroquinolone-resistant strains differed between fecal E. coli (i.e., colonization by multidrug-resistant bacteria) and nasal CNS (i.e., age, coming from a health care facility, and previous antibiotic treatment with a fluoroquinolone) while no risk factors were identified for pharyngeal streptococci. Despite high rates of colonization with fluoroquinolone-resistant bacteria, each commensal flora behaved independently since simultaneous carriage of resistance in the three distinct floras was uncommon, and risk factors differed. Consequences of environmental selective pressures vary in each commensal flora according to its local specificities (clinical trial NCT00520715 [http://clinicaltrials.gov/ct2/show/NCT00520715 ]).

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