scholarly journals Fight Against Antimicrobial Resistance: We Always Need New Antibacterials but for Right Bacteria

Molecules ◽  
2019 ◽  
Vol 24 (17) ◽  
pp. 3152 ◽  
Author(s):  
Raphaël E. Duval ◽  
Marion Grare ◽  
Béatrice Demoré

Antimicrobial resistance in bacteria is frightening, especially resistance in Gram-negative Bacteria (GNB). In 2017, the World Health Organization (WHO) published a list of 12 bacteria that represent a threat to human health, and among these, a majority of GNB. Antibiotic resistance is a complex and relatively old phenomenon that is the consequence of several factors. The first factor is the vertiginous drop in research and development of new antibacterials. In fact, many companies simply stop this R&D activity. The finding is simple: there are enough antibiotics to treat the different types of infection that clinicians face. The second factor is the appearance and spread of resistant or even multidrug-resistant bacteria. For a long time, this situation remained rather confidential, almost anecdotal. It was not until the end of the 1980s that awareness emerged. It was the time of Vancomycin-Resistance Enterococci (VRE), and the threat of Vancomycin-Resistant MRSA (Methicillin-Resistant Staphylococcus aureus). After this, there has been renewed interest but only in anti-Gram positive antibacterials. Today, the threat is GNB, and we have no new molecules with innovative mechanism of action to fight effectively against these bugs. However, the war against antimicrobial resistance is not lost. We must continue the fight, which requires a better knowledge of the mechanisms of action of anti-infectious agents and concomitantly the mechanisms of resistance of infectious agents.

2020 ◽  
Vol 19 (5) ◽  
pp. 49-60
Author(s):  
K. G. Kosyakova ◽  
N. B. Esaulenko ◽  
O. A. Kameneva ◽  
S. P. Kazakov ◽  
A. Y. Dubinina ◽  
...  

Relevance The World Health Organization has provided a list of resistant bacteria that pose the greatest threat to society. Among them, the most important (critically high priority level) are Pseudomonas aeruginosa and Acinetobacter baumannii strains resistant to carbapenems, as well as enterobacteriaceae producing extended spectrum beta-lactamases and carbapenemases.Aim. To conduct a comparative analysis of the sensitivity to chlorhexidine of multiply-resistant gram-negative bacteria, the causative agents of infectious conditions in patients of various medical organizations, and to study the relationship between the presence of resistance genes and the minimum inhibitory concentration of chlorhexidine.Materials & methods. The study included 138 Gram-negative multidrug-resistant strains isolated during 2018–2019 from various clinical specimens. Susceptibility of the isolates to antibiotics were determined using Vitek-2 compact and Phoenix М50, susceptibility to chlorhexidine were determined by agar dilution method. The resistance genes were detected by the real-time PCR method.Results. The lowest level of resistance to chlorhexidine was determined in E. coli strains (MIC90 16 mg/l), other strains were highly resistant: MIC90 of P. aeruginosa and A. baumannii – 128 mg/l, K. pneumoniae, E. cloacae и P. mirabilis – 256 mg/l. The highest frequency of detection of carbapenemase genes observed in K. pneumoniae strains – 56.0% and P. aeruginosa – 48.1%. High prevalence of cepA gene was found out (the strains of enterobacteria – 47.8%, A. baumannii – 42.9%), genes qacE, qacEΔ1 were more often detected in non-fermenting Gram-negative bacteria then in enterobacteria. Conclusion. According to the results of our study, we did not reveal a significant correlation between the presence or absence of resistance genes and MIC of chlorhexidine in Gram-negative bacteria. However, taking into account complex mechanism of the adaptive response of bacteria to the effects of chlorhexidine, and to implement the concept of preventing health care-associated infections, it is proposed to continue dynamic monitoring of the resistance of microorganisms to antiseptics, disinfectants and antibiotics.


Nanomaterials ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 312
Author(s):  
Mohammad Okkeh ◽  
Nora Bloise ◽  
Elisa Restivo ◽  
Lorenzo De Vita ◽  
Piersandro Pallavicini ◽  
...  

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.


2020 ◽  
Vol 8 (9) ◽  
pp. 1425
Author(s):  
Lara Pérez-Etayo ◽  
David González ◽  
José Leiva ◽  
Ana Isabel Vitas

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.


2019 ◽  
Author(s):  
Jenny Yijian Huang

AbstractBackgroundAccording to the World Health Organization, nearly 15% of all hospitalized patients worldwide acquire nosocomial infections. A particular area of concern for bacterial build up in hospitals is sink drains. The moist, microbiologically active environment of drains promotes the formation of biofilms that are difficult to target with standard chemical disinfectants. Bacteriophages, however, show potential to be used as disinfecting agents in hospital drains. Not only do bacteriophages increase in titer as they infect, spreading to hard-to-reach surfaces, phages have been shown to degrade the extracellular matrix of biofilms and gain access to underlying bacteria. This research explores the potential of bacteriophages to eradicate biofilms in an environment modeling a sink drain by comparing the efficacy, range, and durability of bacteriophage to a chemical disinfectant.MethodsE. coli biofilms were grown in M9 minimal media placed in sink P-traps assigned one of three treatments: chemical disinfectant, bacteriophage, or deionized water (control). Biofilms were quantified at five time points -- 1, 12, 24, 36, and 48 hours -- using the crystal violet assay.ResultsBoth chemical disinfectant and bacteriophage significantly decreased the optical densities of biofilms (p < 0.001***). P-traps treated with bacteriophages showed more uniform destruction of biofilm across P-trap compared to chemical disinfectant (p < 0.01**). A trend may suggest that over time bacteriophage became more effective at reducing biofilm than chemical disinfectant.ConclusionThis work highlights the potential of bacteriophage as an alternative to conventional chemical disinfectants for biofilm control in settings such as hospital drains.ImportanceNosocomial infections prolong hospital stay, costing the U.S. healthcare system $5-10 billion annually. An increasing number of reports demonstrate that sink drains -- reservoirs for multidrug resistant bacteria -- may be a source of hospital-related outbreaks. Recent studies have elucidated the mechanism of dispersal of bacteria from contaminated sinks to patients, but limited data are available identifying disinfecting methods for hospital drains. Not only did this study demonstrate that bacteriophages could reduce biofilms on sink drains just as effectively as a commercial disinfectant, it showed that phages tended to spread more thoroughly across P-traps and may work for longer. With hand-washing an imperative activity for disease prevention, hospital sinks should remain clean. This work explores an alternative disinfecting method for hospital sink drains.


2020 ◽  
Vol 8 (5) ◽  
pp. 639 ◽  
Author(s):  
Alexis Simons ◽  
Kamel Alhanout ◽  
Raphaël E. Duval

Currently, the emergence and ongoing dissemination of antimicrobial resistance among bacteria are critical health and economic issue, leading to increased rates of morbidity and mortality related to bacterial infections. Research and development for new antimicrobial agents is currently needed to overcome this problem. Among the different approaches studied, bacteriocins seem to be a promising possibility. These molecules are peptides naturally synthesized by ribosomes, produced by both Gram-positive bacteria (GPB) and Gram-negative bacteria (GNB), which will allow these bacteriocin producers to survive in highly competitive polymicrobial environment. Bacteriocins exhibit antimicrobial activity with variable spectrum depending on the peptide, which may target several bacteria. Already used in some areas such as agro-food, bacteriocins may be considered as interesting candidates for further development as antimicrobial agents used in health contexts, particularly considering the issue of antimicrobial resistance. The aim of this review is to present an updated global report on the biology of bacteriocins produced by GPB and GNB, as well as their antibacterial activity against relevant bacterial pathogens, and especially against multidrug-resistant bacteria.


Infectio ◽  
2019 ◽  
Vol 23 (2) ◽  
pp. 205 ◽  
Author(s):  
Johanna M. Vanegas Múnera ◽  
J. Natalia Jiménez Quiceno

Antimicrobial resistance worsens the prognosis in patients with chronic diseases. Patients on hemodialysis have infection rates that exceed those reported in other types of patients. Colonization has been suggested as a risk factor for the development of infections. However, the majority of the studies that have evaluated this association have methodological limitations that have called into question the validity of the results; such as the lack of use of molecular methods to confirm that the colonizing species are the same as that which causes infection, the measurement of exposure only at the beginning of the study, the absence of follow-up, the evaluation of bacteremia as the only important outcome and the focus only on Staphylococcus aureus, without including other resistant bacteria of clinical importance such as multidrug-resistant Gram-negative bacteria. This lead to the need to use molecular epidemiology methods for refine the association between colonization and infection in endemic countries like Colombia, where the high rates of antimicrobial resistance demand accurate prevention strategies in susceptible patients.


Materials ◽  
2019 ◽  
Vol 12 (10) ◽  
pp. 1639 ◽  
Author(s):  
Eva Torres Sangiao ◽  
Alina Maria Holban ◽  
Mónica Cartelle Gestal

We are constantly exposed to infectious diseases, and they cause millions of deaths per year. The World Health Organization (WHO) estimates that antibiotic resistance could cause 10 million deaths per year by 2050. Multidrug-resistant bacteria are the cause of infection in at least one in three people suffering from septicemia. While antibiotics are powerful agents against infectious diseases, the alarming increase in antibiotic resistance is of great concern. Alternatives are desperately needed, and nanotechnology provides a great opportunity to develop novel approaches for the treatment of infectious diseases. One of the most important factors in the prognosis of an infection caused by an antibiotic resistant bacteria is an early and rigorous diagnosis, jointly with the use of novel therapeutic systems that can specifically target the pathogen and limit the selection of resistant strains. Nanodiamonds can be used as antimicrobial agents due to some of their properties including size, shape, and biocompatibility, which make them highly suitable for the development of efficient and tailored nanotherapies, including vaccines or drug delivery systems. In this review, we discuss the beneficial findings made in the nanodiamonds field, focusing on diagnosis and treatment of infectious diseases. We also highlight the innovative platform that nanodiamonds confer for vaccine improvement, drug delivery, and shuttle systems, as well as their role in the generation of faster and more sensitive clinical diagnosis.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Victoria L. Barlow ◽  
Shu-Jung Lai ◽  
Chia-Yu Chen ◽  
Cheng-Han Tsai ◽  
Shih-Hsiung Wu ◽  
...  

AbstractAcinetobacter baumannii is a prevalent pathogen that can rapidly acquire resistance to antibiotics. Indeed, multidrug-resistant A. baumannii is a major cause of hospital-acquired infections and has been recognised by the World Health Organization as one of the most threatening bacteria to our society. Resistance-nodulation-division (RND) type multidrug efflux pumps have been demonstrated to convey antibiotic resistance to a wide range of pathogens and are the primary resistance mechanism employed by A. baumannii. A component of an RND pump in A. baumannii, AdeT1, was previously demonstrated to enhance the antimicrobial resistance of Escherichia coli. Here, we report the results of experiments which demonstrate that wild-type AdeT1 does not confer antimicrobial resistance in E. coli, highlighting the importance of verifying protein production when determining minimum inhibitory concentrations (MICs) especially by broth dilution. Nevertheless, using an agar-based MIC assay, we found that propionylation of Lys280 on AdeT1 renders E. coli cells more resistant to erythromycin.


2020 ◽  
pp. 175717742096382
Author(s):  
Frank Günther ◽  
Brigitte Blessing ◽  
Ulrike Dapunt ◽  
Alexander Mischnik ◽  
Nico T Mutters

Purpose: This in vitro study was designed to determine if standard antiseptics used for skin and environmental surface cleansing can disrupt the metabolic activity (as a measure of viability) of multidrug-resistant gram-negative bacteria, methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus isolates within their native biofilms. Methods: Sixty clinical isolates of multidrug-resistant bacteria were selected for testing in different chlorhexidine gluconate, octenidine, polyhexanide and chloroxylenol concentrations. Metabolic inhibition of biofilm for each clinical isolate was analysed using a biofilm viability assay. Results: Chlorhexidine gluconate (mean = 83.8% ± 9.8%) and octenidine (mean = 84.5% ± 6.8%) showed the greatest efficacy against biofilms of the tested microorganisms, with the greatest efficacies against MRSA. The antiseptics demonstrated the least efficacy against biofilms of Pseudomonas aeruginosa. Conclusion: Chlorhexidine gluconate and octenidine showed the greatest level of bacterial metabolic inhibition and were statistically equivalent. Polyhexanide was more effective than chloroxylenol, but both were inferior to chlorhexidine gluconate and octenidine against the tested organisms.


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