scholarly journals New Antibiotics for Multidrug-Resistant Bacterial Strains: Latest Research Developments and Future Perspectives

Molecules ◽  
2021 ◽  
Vol 26 (9) ◽  
pp. 2671
Author(s):  
Marco Terreni ◽  
Marina Taccani ◽  
Massimo Pregnolato
Keyword(s):  
Antibiotic Resistance ◽  
Chemical Compounds ◽  
Multidrug Resistant ◽  
Phase Iii ◽  
Fourth Generation ◽  
Careful Examination ◽  
Bacterial Strains ◽  
New Agents ◽  
Pharmacological Interest ◽  
New Antibiotics

The present work aims to examine the worrying problem of antibiotic resistance and the emergence of multidrug-resistant bacterial strains, which have now become really common in hospitals and risk hindering the global control of infectious diseases. After a careful examination of these phenomena and multiple mechanisms that make certain bacteria resistant to specific antibiotics that were originally effective in the treatment of infections caused by the same pathogens, possible strategies to stem antibiotic resistance are analyzed. This paper, therefore, focuses on the most promising new chemical compounds in the current pipeline active against multidrug-resistant organisms that are innovative compared to traditional antibiotics: Firstly, the main antibacterial agents in clinical development (Phase III) from 2017 to 2020 are listed (with special attention on the treatment of infections caused by the pathogens Neisseria gonorrhoeae, including multidrug-resistant isolates, and Clostridium difficile), and then the paper moves on to the new agents of pharmacological interest that have been approved during the same period. They include tetracycline derivatives (eravacycline), fourth generation fluoroquinolones (delafloxacin), new combinations between one β-lactam and one β-lactamase inhibitor (meropenem and vaborbactam), siderophore cephalosporins (cefiderocol), new aminoglycosides (plazomicin), and agents in development for treating drug-resistant TB (pretomanid). It concludes with the advantages that can result from the use of these compounds, also mentioning other approaches, still poorly developed, for combating antibiotic resistance: Nanoparticles delivery systems for antibiotics.

scholarly journals Antibacterial Compounds from Mushrooms: A Lead to Fight ESKAPEE Pathogenic Bacteria?

Planta Medica ◽  
2020 ◽  
Author(s):  
Violette Hamers ◽  
Clément Huguet ◽  
Mélanie Bourjot ◽  
Aurélie Urbain
Keyword(s):  
Antibiotic Resistance ◽  
Global Health ◽  
Pathogenic Bacteria ◽  
Resistance Mechanisms ◽  
Pathogenic Microorganisms ◽  
Bacterial Strains ◽  
Antibacterial Compounds ◽  
New Antibiotics ◽  
Hospital Stays ◽  
Antibacterial Potential

AbstractInfectious diseases are among the greatest threats to global health in the 21st century, and one critical concern is due to antibiotic resistance developed by an increasing number of bacterial strains. New resistance mechanisms are emerging with many infections becoming more and more difficult if not impossible to treat. This growing phenomenon not only is associated with increased mortality but also with longer hospital stays and higher medical costs. For these reasons, there is an urgent need to find new antibiotics targeting pathogenic microorganisms such as ESKAPEE bacteria. Most of currently approved antibiotics are derived from microorganisms, but higher fungi could constitute an alternative and remarkable reservoir of anti-infectious compounds. For instance, pleuromutilins constitute the first class of antibiotics derived from mushrooms. However, macromycetes still represent a largely unexplored source. Publications reporting the antibacterial potential of mushroom extracts are emerging, but few purified compounds have been evaluated for their bioactivity on pathogenic bacterial strains. Therefore, the aim of this review is to compile up-to-date data about natural products isolated from fruiting body fungi, which significantly inhibit the growth of ESKAPEE pathogenic bacteria. When available, data regarding modes of action and cytotoxicity, mandatory when considering a possible drug development, have been discussed in order to highlight the most promising compounds.

scholarly journals Production of β-Lactamase Inhibitors by Streptomyces Species

Antibiotics ◽  
2018 ◽  
Vol 7 (3) ◽  
pp. 61 ◽  
Author(s):  
Daniela Viana Marques ◽  
Suellen Machado ◽  
Valéria Ebinuma ◽  
Carolina Duarte ◽  
Attilio Converti ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Cost Effective ◽  
Multidrug Resistant ◽  
Bacterial Strains ◽  
Streptomyces Species ◽  
Innovative Strategies ◽  
New Antibiotics ◽  
Microbial Products ◽  
Type Strains ◽  
Streptomyces Genus

β-Lactamase inhibitors have emerged as an effective alternative to reduce the effects of resistance against β-lactam antibiotics. The Streptomyces genus is known for being an exceptional natural source of antimicrobials and β-lactamase inhibitors such as clavulanic acid, which is largely applied in clinical practice. To protect against the increasing prevalence of multidrug-resistant bacterial strains, new antibiotics and β-lactamase inhibitors need to be discovered and developed. This review will cover an update about the main β-lactamase inhibitors producers belonging to the Streptomyces genus; advanced methods, such as genetic and metabolic engineering, to enhance inhibitor production compared with wild-type strains; and fermentation and purification processes. Moreover, clinical practice and commercial issues are discussed. The commitment of companies and governments to develop innovative strategies and methods to improve the access to new, efficient, and potentially cost-effective microbial products to combat the antimicrobial resistance is also highlighted.

scholarly journals Biosynthetic Origin of Hygromycin A

2003 ◽  
Vol 47 (7) ◽  
pp. 2065-2071 ◽  
Author(s):  
El-Sayed E. Habib ◽  
J. Neel Scarsdale ◽  
Kevin A. Reynolds
Keyword(s):  
Polyketide Synthase ◽  
Multidrug Resistant ◽  
Hydroxyl Group ◽  
Transferase Activity ◽  
Hydroxybenzoic Acid ◽  
Peptidyl Transferase ◽  
New Agents ◽  
New Antibiotics ◽  
Directed Biosynthesis ◽  
Chorismic Acid

ABSTRACT Hygromycin A, an antibiotic produced by Streptomyces hygroscopicus, is an inhibitor of bacterial ribosomal peptidyl transferase. The antibiotic binds to the ribosome in a distinct but overlapping manner with other antibiotics and offers a different template for generation of new agents effective against multidrug-resistant pathogens. Reported herein are the results from a series of stable-isotope-incorporation studies demonstrating the biosynthetic origins of the three distinct structural moieties which comprise hygromycin A. Incorporation of [1-13C]mannose and intact incorporation of d-[1,2-13C2]glucose into the 6-deoxy-5-keto-d-arabino-hexofuranose moiety are consistent with a pathway in which mannose is converted to an activated l-fucose, via a 4-keto-6-deoxy-d-mannose intermediate, with a subsequent unusual mutation of the pyranose to the corresponding furanose. The aminocyclitol moiety was labeled by d-[1,2-13C2]glucose in a manner consistent with formation of myo-inositol and a subsequent unprecedented oxidation and transamination of the C-2 hydroxyl group to generate neo-inosamine-2. Incorporation of [carboxy- 13C]-4-hydroxybenzoic acid and intact incorporation of [2,3-13C2]propionate are consistent with a polyketide synthase-type decarboxylation condensation to generate the 3,4-dihydroxy-α-methylcinnamic acid moiety of hygromycin A. No labeling of hygromycin A was observed when [3-13C]tyrosine, [3-13C]phenylalanine, or [carboxy- 13C]benzoic acid was used, suggesting that the 4-hydroxybenzoic acid is derived directly from chorismic acid. Consistent with this hypothesis was the observation that hygromycin A titers could be reduced by addition of N-(phosphonomethyl)-glycine (an inhibitor of chorismic acid biosynthesis) and restored by coaddition of 4-hydroxybenzoic acid. The convergent biosynthetic pathway established for hygromycin A offers significant versatility for applying the techniques of combinatorial and directed biosynthesis to production of new antibiotics which target the ribosomal peptidyl transferase activity.

scholarly journals Metabolic profiling and antibacterial activity of Eryngium pristis Cham. & Schltdl. - prospecting for its use in the treatment of bacterial infections

2021 ◽  
Vol 5 (1) ◽  
pp. 020-028
Author(s):  
Fernandes Laura Silva ◽  
da Costa Ygor Ferreira Garcia ◽  
de Bessa Martha Eunice ◽  
Ferreira Adriana Lucia Pires ◽  
do Amaral Corrêa José Otávio ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Bioactive Compounds ◽  
Metabolic Profile ◽  
Bacterial Infections ◽  
Ethanolic Extract ◽  
Multidrug Resistant ◽  
Gas Chromatography Mass Spectrometry ◽  
Resistant Bacteria ◽  
Bacterial Strains ◽  
New Antibiotics

Morbidity and mortality of the infected patients by multidrug-resistant bacteria have increased, emphasizing the urgency of fight for the discovery of new innovative antibiotics. In this sense, natural products emerge as valuable sources of bioactive compounds. Among the biodiversity, Eryngium pristis Cham. & Schltdl. (Apiaceae Lindl.) is traditionally used to treat thrush and ulcers of throat and mouth, as diuretic and emmenagogue, but scarcely known as an antimicrobial agent. With this context in mind, the goals of this study were to investigate the metabolic profile and the antibacterial activity of ethanolic extract (EE-Ep) and hexane (HF-Ep), dichloromethane (DF-Ep), ethyl acetate (EAF-Ep) and butanol (BF-Ep) fractions from E. pristis leaves. Gas Chromatography-Mass Spectrometry (GC-MS) was performed to stablish the metabolic profile and revealed the presence of 12 and 14 compounds in EAF-Ep and HF-Ep, respectively. β-selinene, spathulenol, globulol, 2-methoxy-4-vinylphenol, α-amyrin, β-amyrin, and lupeol derivative were some of phytochemicals identified. The antibacterial activity was determined by Minimal Inhibitory Concentration (MIC) using the broth micro-dilution against eight ATCC® and five methicillin-resistant Staphylococcus aureus (MRSA) clinical strains. HF-Ep was the most effective (MIC ≤ 5,000 µg/µL), being active against the largest part of tested Gram-positive and Gram-negative bacterial strains, including MRSA, with exception of Escherichia coli (ATCC 25922) and Pseudomonas aeruginosa (ATCC 9027) and (ATCC 27853). These results suggest that E. pristis is a natural source of bioactive compounds for the search of new antibiotics which can be an interesting therapeutic approach to recover patients mainly infected by MRSA strains.

scholarly journals Identification of antibiotic resistance proteins via MiCId's augmented workflow. A mass spectrometry-based proteomics approach

2021 ◽  
Author(s):  
Gelio Alves ◽  
Aleksey Y Ogurtsov ◽  
Roger Karlsson ◽  
Daniel Jaen-Luchoro ◽  
Beatriz Pineiro-Iglesias ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Antibiotic Resistance ◽  
Pathogenic Bacteria ◽  
High Sensitivity ◽  
Multidrug Resistant ◽  
Bacterial Strains ◽  
Resistance Proteins ◽  
Proteomics Approach ◽  
Resistance Protein ◽  
Microorganism Classification

Fast and accurate identifications of pathogenic bacteria along with their associated antibiotic resistance proteins are of paramount importance for patient treatments and public health. While mass spectrometry has become an important, technique for diagnostics of infectious disease, there is a need for mass spectrometry workflows offering this capability. To meet this need, we have augmented the previously published Microorganism Classification and Identification (MiCId) workflow for this capability. To evaluate the performance of the newly augmented MiCId workflow, we have used MS/MS datafiles from samples of 10 antibiotic resistance bacterial strains belonging to three different species: Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa. The evaluation results show that MiCId's workflow has a sensitivity value around 85% (with a lower bound at about 72%) and a precision greater than 95% in the identification of antibiotic resistance proteins. Using MS/MS datasets from samples of two bacterial clonal isolates, one being antibiotic-sensitive while the other (obtained from the same patient at different times) being multidrug-resistant, we applied MiCId's workflow to investigate possible mechanisms of antibiotic resistance in these pathogenic bacteria; the results showed that MiCId's conclusions are in agreement with the published study. Furthermore, we show that MiCId's workflow is fast. It provides microorganismal identifications, protein identifications, sample biomass estimates, and antibiotic resistance protein identifications in 6-17 minutes per MS/MS sample using computing resources that are available in most desktop and laptop computers, making it a highly portable workflow. This study demonstrated that MiCId's workflow is fast, portable, and with high sensitivity and high precision, making it a valuable tool for rapid identifications of bacteria as well as detection of their antibiotic resistance proteins. The new version of MiCId (v.07.01.2021) is freely available for download at https://www.ncbi.nlm.nih.gov/CBBresearch/Yu/downloads.html.

scholarly journals MULTIDRUG-RESISTANT AND EXTREMELY DRUG-RESISTANT BACTERIA: ARE WE FACING THE END OF THE ANTIBIOTIC ERA?

2016 ◽  
Vol 7 (1) ◽  
Author(s):  
G.M. Rossolini
Keyword(s):  
Antibiotic Resistance ◽  
Bacterial Infections ◽  
Multidrug Resistant ◽  
Modern Medicine ◽  
Infectious Complications ◽  
Future Perspective ◽  
Resistant Bacteria ◽  
Bacterial Strains ◽  
Public Health Agencies ◽  
Drug Resistant Bacteria

Antibiotics are one of the most significant advancements of modern medicine. They have changed the prognosis of several bacterial infections, and made possible advanced medical practices associated with a high risk of infectious complications. Unfortunately, antibiotics are affected by the phenomenon of antibiotic resistance, which jeopardizes their efficacy. In recent years, antibiotic discovery and development has been lagging, due to a lower appeal of this sector for the pharmaceutical industry, while antibiotic resistance has continued to evolve with the eventual emergence and dissemination of bacterial strains which are resistant to most available antibiotics and pose a major challenge to antimicrobial chemotherapy. This worrisome scenario, indicated as the “antibiotic resistance crisis”, has been acknowledged by Scientific Societies and Public Health Agencies, and is now gathering an increasing attention from the Media and Governments. This article reviews the antibiotic-resistant pathogens which currently pose major problems in terms of clinical and epidemiological impact, and briefly discuss future perspective in this field.

scholarly journals Oxygen-ozone activity in making factory farms antibiotic-free for prevention of antibiotic resistance

Ozone Therapy ◽  
2016 ◽  
Vol 1 (2) ◽  
pp. 42 ◽  
Author(s):  
Luigi Valdenassi ◽  
Marianno Franzini ◽  
Pierpaolo Garbelli ◽  
Manuele Camolese
Keyword(s):  
Antibiotic Resistance ◽  
Pharmaceutical Industry ◽  
Bacterial Strains ◽  
Inappropriate Use ◽  
Chemotherapy Drugs ◽  
Factory Farms ◽  
New Antibiotics

For some years an increasing number of bacterial strains have shown resistance to common antibiotics and chemotherapy drugs. The excessive and inappropriate use of antibiotics is at the root of this problem, which could develop to a devastating extent if not controlled properly. It should not be forgotten that the pharmaceutical industry itself appears to be unable to offer the necessary countermeasures in terms of advanced research within tight deadlines because of the objective difficulties with synthesis of new antibiotics. The use of oxygen-ozone appears to give a concrete answer to the problem through application in the dietary and environment process of livestock.

scholarly journals Antistaphylococcal and Antibiotic Resistance Modulatory Activities of Thirteen Cameroonian Edible Plants against Resistant Phenotypes

2018 ◽  
Vol 2018 ◽  
pp. 1-12
Author(s):  
Brice E. N. Wamba ◽  
Armelle T. Mbaveng ◽  
Paul Nayim ◽  
Joachim K. Dzotam ◽  
Ornella J. T. Ngalani ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Efflux Pump ◽  
Efflux Pumps ◽  
Antibacterial Activities ◽  
Multidrug Resistant ◽  
Edible Plants ◽  
Bacterial Strains ◽  
Efflux Pump Inhibitor ◽  
Dacryodes Edulis

Background. In this study, 18 methanol extracts from Cameroonian edible plants were tested for their antibacterial activities against 26 strains ofS. aureus; the role of efflux pumps in the resistance of tested bacteria and the antibiotic resistance-modulating activities against selected multidrug-resistant (MDR) phenotypes were also investigated.Methods. Broth microdilution assay was used to evaluate the antibacterial activity, the role of efflux pumps, and the antibiotic resistance-modulating effects of plant extracts.Results. Extracts fromDacryodes edulisseeds (DES) andDacryodes edulisbark (DEB) were active against all 26 tested bacterial strains, within the minimal inhibitory concentration (MIC) range of 256–1024 µg/mL. MIC values varied from 64 to 1024 µg/mL against 96.2% of the 26 tested bacteria forPhaseolus vulgarisleaves (PVL), 92.3% forAzadirachta indicabark (AIB),Dacryodes edulisleaves (DEL), andRicinodendron heudelotiileaves (RHL). The lowest MIC value of 64 µg/mL was obtained with the extract fromCucurbita maximabeans (CMB) against MRSA4 strain and fromUapaca guineensisbark (UGB) against MRSA9 strain. Bacterial efflux pump inhibitor (EPI), carbonyl cyanidem-chlorophenyl hydrazone (CCCP), improved the activity of DES and UGB as well as that of extracts fromHibiscus esculentusleaves (HEL) andUapaca guineensisleaves (UGL) against resistantS. aureusstrains. Antibiotic-modulating effects against more than 70% of theS. aureusstrains tested were obtained when RHL (at MIC/2) was combined with CIP, ERY, and KAN (88.89%), CHL (88.89%), TET (77.78%), and STR (88.89%).Conclusion. The present study demonstrated that the 13 tested plants had antistaphylococcal effects and that DES, HEL, UGL, and UGB could be used in combination with EPI to combat resistance toStaphylococcus aureus. Also, it demonstrated that some studied extracts and mostly RHL could be used as antibiotic resistance modulators to fight against resistant strains ofS. aureus.

scholarly journals Comparison of Antibiotic Resistance Profile and Biofilm Production of Staphylococcus aureus Isolates Derived from Human Specimens and Animal-Derived Samples

Antibiotics ◽  
2019 ◽  
Vol 8 (3) ◽  
pp. 97 ◽  
Author(s):  
Maria Vitale ◽  
Paola Galluzzo ◽  
Patrizia Giuseppina Buffa ◽  
Eleonora Carlino ◽  
Orazio Spezia ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Antibiotic Resistance ◽  
Antimicrobial Resistance ◽  
Meca Gene ◽  
Multidrug Resistant ◽  
Animal Origin ◽  
Antibiotic Resistance Profile ◽  
Biofilm Production ◽  
New Antibiotics ◽  
Resistant Strains

Background: The diffusion of antimicrobial resistance is a significant concern for public health worldwide. Staphylococcus aureus represents a paradigm microorganism for antibiotic resistance in that resistant strains appear within a decade after the introduction of new antibiotics. Methods: Fourteen S. aureus isolates from human specimens and twenty-one from samples of animal origin, were compared for their antimicrobial resistance and biofilm capability. In addition, they were characterized at the molecular level to detect the antimicrobial resistance mecA gene and genes related with enterotoxin, toxin, and biofilm production. Results: Both phenotypic and molecular analysis showed main differences among human- and animal-derived isolates. Among the human-derived isolates, more multidrug-resistant isolates were detected and mecA gene, enterotoxin, and toxin genes were more prevalent. Different genes involved in biofilm production were detected with bap present only in animal-derived isolates and sasC present in both isolates, however, with a higher prevalence in the human-derived isolates. Biofilm capability was higher in human-derived isolates mainly associated to the sasC gene. Conclusions: The overall results indicate that human S. aureus isolates are more virulent and resistant than the isolates of animal origin randomly selected with no infection anamnesis. This study confirms that selection for more virulent and resistant S. aureus strains is related to the clinical practice.

An Update for Community-Acquired Bacterial Pneumonia Pharmacotherapy

2012 ◽  
Vol 25 (6) ◽  
pp. 569-575
Author(s):  
Heather F. DeBellis ◽  
Melissa C. Jones ◽  
Scott E. Kincaid
Keyword(s):  
Bacterial Pneumonia ◽  
The United States ◽  
Multidrug Resistant ◽  
Patient Factors ◽  
New Agents ◽  
Ceftaroline Fosamil ◽  
The Us ◽  
Multidrug Resistant Organisms ◽  
New Antibiotics ◽  
Disease Community

In 2007, 1.2 million people in the United States were hospitalized with pneumonia, and more than 52 000 died from the disease. Community-acquired bacterial pneumonia (CABP) can be caused by a variety of organisms as a result of patient factors such as comorbidities, epidemiologic conditions, or the setting in which the infection was contracted. Treatment of CABP differs depending on the types of bacteria that are suspected. In the last several years, due to the concern regarding multidrug-resistant organisms (MDROs), 2 new antibiotics have been developed and approved for use in CABP. Ceftaroline fosamil (Teflaro) was approved by the US Food and Drug Administration (FDA) in October 2010 and tigecycline (Tygacil) in March 2009. In clinical trials, both agents have been shown to be efficacious and are generally well tolerated. Although these agents have received approval as therapy for CABP, it is the responsibility of physicians and pharmacists to prudently use these antimicrobials where they are truly needed. Until these agents show superiority over conventional therapy for selected patient populations, given the wide variety of pharmacotherapy that can prove efficacious for pneumonia, the new agents should be reserved for patients who have known risk factors for MDROs. Further studies are warranted for these agents in the setting of CABP.

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