Recent Advances in the Development of Macrolide Antibiotics as Antimicrobial Agents

2020 ◽  
Vol 20 (7) ◽  
pp. 601-625
Author(s):  
Yinhui Qin ◽  
Shutao Ma
Keyword(s):  
Infectious Diseases ◽  
Chemical Modification ◽  
Respiratory System ◽  
Bacterial Resistance ◽  
Antimicrobial Agents ◽  
Synthetic Methods ◽  
Macrolide Antibiotics ◽  
Urinary System ◽  
Erythromycin A ◽  
Clinical Candidate

The chemical modification of natural products has been a major method in the discovery and synthesis of new macrolide antibiotics (MA) to treat a variety of infectious diseases. However, a lot of MA obtained in the above methods are no longer effective, because the bacteria quickly develop their resistance to these new macrolides, which has become a great threat to successful treatment of infectious diseases, such as infections of the respiratory system and urinary system. In this paper, total synthetic methods for MA that include erythromycin A (ERY), azithromycin (AZM), the clinical candidate solithromycin (CEM-101), as well as 14-membered and 15-membered azaketolides have been systematically reviewed on the basis of the literature reported previously. The total synthetic methods we describe here helps to accelerate the discovery of newer MA to deal with the serious problem of bacterial resistance.

scholarly journals The Lactococcal dgkB (yecE) and dxsA Genes for Lipid Metabolism Are Involved in the Resistance to Cell Envelope-Acting Antimicrobials

2021 ◽  
Vol 22 (3) ◽  
pp. 1014
Author(s):  
Aleksandra Tymoszewska ◽  
Tamara Aleksandrzak-Piekarczyk
Keyword(s):  
Antimicrobial Peptides ◽  
Bacterial Resistance ◽  
Antimicrobial Agents ◽  
Cytoplasmic Membrane ◽  
Cross Resistance ◽  
Resistant Bacteria ◽  
Membrane Targeting ◽  
Nucleotide Polymorphisms ◽  
Next Generation ◽  
Lipid Ii

The emergence of antibiotic-resistant bacteria led to an urgent need for next-generation antimicrobial agents with novel mechanisms of action. The use of positively charged antimicrobial peptides that target cytoplasmic membrane is an especially promising strategy since essential functions and the conserved structure of the membrane hinder the development of bacterial resistance. Aureocin A53- and enterocin L50-like bacteriocins are highly cationic, membrane-targeting antimicrobial peptides that have potential as next-generation antibiotics. However, the mechanisms of resistance to these bacteriocins and cross-resistance against antibiotics must be examined before application to ensure their safe use. Here, in the model bacterium Lactococcus lactis, we studied the development of resistance to selected aureocin A53- and enterocin L50-like bacteriocins and its correlation with antibiotics. First, to generate spontaneous resistant mutants, L.lactis was exposed to bacteriocin BHT-B. Sequencing of their genomes revealed single nucleotide polymorphisms (SNPs) in the dgkB (yecE) and dxsA genes encoding diacylglycerol kinase and 1-deoxy-D-xylulose 5-phosphate synthase, respectively. Then, selected mutants underwent susceptibility tests with a wide array of bacteriocins and antibiotics. The highest alterations in the sensitivity of studied mutants were seen in the presence of cytoplasmic membrane targeting bacteriocins (K411, Ent7, EntL50, WelM, SalC, nisin) and antibiotics (daptomycin and gramicidin) as well as lipid II cycle-blocking bacteriocins (nisin and Lcn972) and antibiotics (bacitracin). Interestingly, decreased via the SNPs accumulation sensitivity to membrane-active bacteriocins and antibiotics resulted in the concurrently increased vulnerability to bacitracin, carbenicillin, or chlortetracycline. It is suspected that SNPs may result in alterations to the efficiency of the nascent enzymes rather than a total loss of their function as neither deletion nor overexpression of dxsA restored the phenotype observed in spontaneous mutants.

scholarly journals Economic Impacts of Banning Subtherapeutic Use of Antibiotics in Swine Production

2002 ◽  
Vol 34 (3) ◽  
pp. 489-500 ◽  
Author(s):  
B. Wade Brorsen ◽  
Terry Lehenbauer ◽  
Dasheng Ji ◽  
Joe Connor
Keyword(s):  
Public Health ◽  
Bacterial Resistance ◽  
Antimicrobial Agents ◽  
Economic Effects ◽  
Swine Production ◽  
Livestock Feed ◽  
Long Run ◽  
Short Run ◽  
Public Health Officials ◽  
Growth Promotants

Public health officials and physicians are concerned about possible development of bacterial resistance and potential effects on human health that may be related to the use of antimicrobial agents in livestock feed. The focus of this research is aimed at determining the economic effects that subtherapeutic bans of antimicrobials would have on both swine producers and consumers. The results show that a ban on growth promotants for swine would be costly, totaling $242.5 million annually, with swine producers sharing the larger portion in the short run and consumers sharing the larger portion in the long run.

Handbuch der Kinderheilkunde

PEDIATRICS ◽  
1967 ◽  
Vol 39 (5) ◽  
pp. 803-804
Author(s):  
HEINZ F. EICHENWALD
Keyword(s):  
United States ◽  
Infectious Diseases ◽  
The United States ◽  
Urinary System ◽  
Cardiopulmonary Function ◽  
Entire Field ◽  
Social Pediatrics

Volume III of the Handbuch der Kinderheilkunde contributes another significant segment to the encyclopedic exposition of the entire field of pediatrics, which eventually will occupy nine large volumes. Volumes II and IV have previously been reviewed in this journal. Also available at this time are Volume V (Infectious Diseases) and Volume VII (The Lungs, The Heart, Cardiopulmonary Function, The Kidneys, and The Urinary System). Volume III deals with two separate fields, immunology and social pediatrics. It contains contributions by 67 authors; most authors are from Germany but some are also from Switzerland Poland, and the United States.

An Update on the Synthesis and Applications of Bis(Naphthoquinones): An Important Class of Molecules against Infectious Diseases and Other Conditions

2021 ◽  
Vol 21 ◽  
Author(s):  
Luana da S. M. Forezi ◽  
Acácio S. de Souza ◽  
Carolina G. S. Lima ◽  
Amanda A. Borges ◽  
Patricia G. Ferreira ◽  
...  
Keyword(s):  
Infectious Diseases ◽  
General Class ◽  
Biological Activities ◽  
Pharmaceutical Market ◽  
Synthetic Methods ◽  
Important Class ◽  
Biological Targets ◽  
Valuable Compounds ◽  
Synthetic Approaches

: Naphthoquinones are important molecules belonging to the general class of quinones, and many of these compounds have become drugs that are in the pharmaceutical market for the treatment of several diseases. A special subclass of compounds is that of the bis(naphthoquinones), which have two linked naphthoquinone units. In the last few years, several synthetic approaches toward such valuable compounds have been described, as well as their evaluation against numerous important biological targets. In this review, we provide a thorough discussion on the various synthetic methods reported for the synthesis of bis(naphthoquinone) analogues, also highlighting the biological activities of these substances.

2015 Nelson's Pediatric Antimicrobial Therapy

2015 ◽  
Keyword(s):  
Health Care ◽  
Infectious Diseases ◽  
Health Care Providers ◽  
Antimicrobial Therapy ◽  
Antimicrobial Agents ◽  
Complete Information ◽  
Care Providers ◽  
Dosing Regimens

New! This bestselling and widely used resource on pediatric antimicrobial therapy provides instant access to reliable, up-to-the-minute recommendations for treatment of all infectious diseases in children. For each disease, the authors provide a commentary to help health care providers select the best of all antimicrobial choices. Drug descriptions cover all antimicrobial agents available today, and include complete information about dosing regimens. In response to growing concerns about overuse of antibiotics, the book includes guidelines on when not to prescribe antimicrobials. Key 21st edition features! Contents

scholarly journals Pregnancy Outcome Following Gestational Exposure to Fluoroquinolones: a Multicenter Prospective Controlled Study

1998 ◽  
Vol 42 (6) ◽  
pp. 1336-1339 ◽  
Author(s):  
Ronen Loebstein ◽  
Antonio Addis ◽  
Elaine Ho ◽  
Roseann Andreou ◽  
Suzanne Sage ◽  
...  
Keyword(s):  
Relative Risk ◽  
Confidence Interval ◽  
Pregnancy Outcome ◽  
Bacterial Resistance ◽  
Antimicrobial Agents ◽  
In Utero ◽  
Controlled Study ◽  
Control Group ◽  
Increased Risk ◽  
Clinically Significant

ABSTRACT Concerns regarding the teratogenicity of fluoroquinolones have resulted in their restricted use during gestation. This is despite an increasing need for their use due to emerging bacterial resistance. The objectives of the present investigation were to evaluate pregnancy and fetal outcomes following maternal exposure to fluoroquinolones and to examine whether in utero exposure to quinolones is associated with clinically significant musculoskeletal dysfunctions. We prospectively enrolled and followed up 200 women exposed to fluoroquinolones (norfloxacin, ciprofloxacin, ofloxacin) during gestation. Pregnancy outcome was compared with that for 200 controls matched for age and for smoking and alcohol consumption habits. Controls were exposed to nonteratogenic, nonembryotoxic antimicrobial agents matched by indication, duration of therapy (±3 days), and trimester of exposure. Rates of major congenital malformations did not differ between the group exposed to quinolones in the first trimester (2.2%) and the control group (2.6%) (relative risk, 0.85; 95% confidence interval, 0.21 to 3.49). Women treated with quinolones had a tendency for an increased rate of therapeutic abortions compared with the rate among women exposed to nonteratogens (relative risk, 4.50; 95% confidence interval, 0.98 to 20.57), resulting in lower live-birth rates (86 versus 94%; P = 0.02). The rates of spontaneous abortions, fetal distress, and prematurity and the birth weight did not differ between the groups. Gross motor developmental milestone achievements did not differ between the children of the mothers in the two groups. We concluded that the use of fluoroquinolones during embryogenesis is not associated with an increased risk of major malformations. There were no clinically significant musculoskeletal dysfunctions in children exposed to fluoroquinolones in utero. The higher rate of therapeutic abortions observed in quinolone-exposed women compared to that for their controls may be secondary to the misperception of a major risk related to quinolone use during pregnancy.

scholarly journals Light and Phages on Tackle of Infectious Diseases

2021 ◽  
Author(s):  
Felipe de Paula Nogueira Cruz ◽  
Andréa Cristina Bogas ◽  
Cristina Paiva de Sousa
Keyword(s):  
Infectious Diseases ◽  
Antimicrobial Agents ◽  
Microbial Inactivation ◽  
Resistant Bacteria ◽  
Bacteriophage Therapy ◽  
Drug Resistant Bacteria ◽  
Evolutionary Trajectories ◽  
Efficient Alternative ◽  
Emergence Of Resistance ◽  
Inducing Resistance

There has been an important increase in the emergence of resistance in microbial population worldwide. This trajectory needs, necessarily new approaches to treat infectious diseases. The ability to detect and prevent the evolutionary trajectories of microbial resistance would be of value. Photodynamic inactivation (PDI) represents an efficient alternative treatment for diseases caused by viruses, which can cause infections well documented in various mammals. PDI can kill cells after exposure with the appropriate photosensitizer (PS), light of adequate wavelength combined with the presence of oxygen, without inducing resistance. Cytotoxic reactive species formed interaction with vital biomolecules leading to irreversible microbial inactivation. Bacteriophages can act on delivering antimicrobial agents into bacteria, which consist in a likely instrument for the treatment of infectious diseases. Non-enveloped bacteriophages are more difficult to tolerate photoinactivation than enveloped phages, which makes them an important model tool to evaluate the efficiency of PDI therapy against viruses that cause diseases in humans. Combination of photosensitizers and bacteriophage therapy can be employed to eradicate biofilms, contributing to control of infections also caused by drug-resistant bacteria.

scholarly journals The Principles of Antibody Therapy for Infectious Diseases with Relevance for COVID-19

mBio ◽  
2021 ◽  
Vol 12 (2) ◽  
Author(s):  
Arturo Casadevall ◽  
Liise-anne Pirofski ◽  
Michael J. Joyner
Keyword(s):  
Infectious Diseases ◽  
Antimicrobial Agents ◽  
Severe Disease ◽  
Antibody Therapy ◽  
Course Of Disease ◽  
Medical Practitioners ◽  
History Of ◽  
Serum Therapy ◽  
Effective Lessons ◽  
Further Development

ABSTRACT Antibody therapies such as convalescent plasma and monoclonal antibodies have emerged as major potential therapeutics for coronavirus disease 2019 (COVID-19). Immunoglobulins differ from conventional antimicrobial agents in that they mediate direct and indirect antimicrobial effects that work in concert with other components of the immune system. The field of infectious diseases pioneered antibody therapies in the first half of the 20th century but largely abandoned them with the arrival of conventional antimicrobial therapy. Consequently, much of the knowledge gained from the historical development and use of immunoglobulins such as serum and convalescent antibody therapies was forgotten; principles and practice governing their use were not taught to new generations of medical practitioners, and further development of this modality stalled. This became apparent during the COVID-19 pandemic in the spring of 2020 when convalescent plasma was initially deployed as salvage therapy in patients with severe disease. In retrospect, this was a stage of disease when it was less likely to be effective. Lessons of the past tell us that antibody therapy is most likely to be effective when used early in respiratory diseases. This article puts forth three principles of antibody therapy, namely, specificity, temporal, and quantitative principles, connoting that antibody efficacy requires the administration of specific antibody, given early in course of disease in sufficient amount. These principles are traced to the history of serum therapy for infectious diseases. The application of the specificity, temporal, and quantitative principles to COVID-19 is discussed in the context of current use of antibody therapy against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

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