scholarly journals The Myth of Septic Complications of Acute Pneumonia

2021 ◽  
Vol 2 (8) ◽  
pp. 741-744
Author(s):  
Igor Klepikov
Keyword(s):  
Conventional Treatment ◽  
Modern Medicine ◽  
New Drugs ◽  
Septic Complications ◽  
Practical Medicine ◽  
New Era ◽  
Treatment Regimens ◽  
Acute Pneumonia ◽  
Inflammatory Processes ◽  
Radical Revision

A new era in the treatment of Acute Pneumonia (AP) began with the introduction of antibiotics into medical practice. The first successes of the use of new drugs were accompanied by a gradual simplification of views on the nature of AP with an emphasis on the characteristics of the pathogen and its suppression. A huge layer of scientific materials that allow us to understand the features of the development and course of inflammatory processes in the lungs, remained unclaimed. The focus on the etiology of the disease has led to a distorted view of its mechanisms and an exaggerated diagnosis of septic complications that do not have a reasoned confirmation. The current pandemic with a large number of COVID-19 pneumonias has radically changed the etiology of AP and deprived practical medicine of conventional treatment regimens. The unpreparedness of modern medicine for such a challenge and the preservation of the previous ideology of the disease are the reason for a radical revision of the AP doctrine.

Permeability Through Bacterial Porins Dictates Whole Cell Compound Accumulation

2020 ◽  
Author(s):  
Silvia Acosta Gutiérrez ◽  
Igor Bodrenko ◽  
Matteo Ceccarelli
Keyword(s):  
Cell Envelope ◽  
Scoring Function ◽  
Modern Medicine ◽  
New Drugs ◽  
Prediction Ability ◽  
Whole Cell ◽  
Virtual Libraries ◽  
Major Bottleneck ◽  
Global Threat ◽  
Bacterial Porins

The lack of new drugs for Gram-negative pathogens is a global threat to modern medicine. The complexity of their cell envelope, with an additional outer membrane, hinders internal accumulation and thus, the access of molecules to targets. Our limited understanding of the molecular basis for compound influx and efflux from these pathogens is a major bottleneck for the discovery of effective antibacterial compounds. Here we analyse the correlation between the whole-cell compound accumulation of ~200 molecules and their predicted porin permeability coefficient (influx), using a recently developed scoring function. We found a strong linear relationship (75%) between the two, confirming porins key role in compound penetration. Further, the remarkable prediction ability of the scoring function demonstrates its potentiality to guide the optimization of hits to leads as well as the possibility of screening ultra-large virtual libraries. Eventually, the analysis of false positives, molecules with high-predicted influx but low accumulation, provides new hints on the molecular properties behind efflux.<br>

New Drugs and Treatment Regimens

2013 ◽  
Vol 9 (3) ◽  
pp. 200-210 ◽  
Author(s):  
Derek Sloan ◽  
Geraint Davies ◽  
Saye Khoo
Keyword(s):  
New Drugs ◽  
Treatment Regimens

scholarly journals Benznidazole Treatment: Time- and Dose-Dependence Varies with the Trypanosoma cruzi Strain

Pathogens ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 729
Author(s):  
Kátia da Silva Fonseca ◽  
Luísa Perin ◽  
Nívia Carolina Nogueira de Paiva ◽  
Beatriz Cristiane da Silva ◽  
Thays Helena Chaves Duarte ◽  
...  
Keyword(s):  
Treatment Adherence ◽  
Treatment Efficacy ◽  
Treatment Time ◽  
Standard Dose ◽  
Acute Infection ◽  
Chronic Phase ◽  
Disease Status ◽  
Dose Dependence ◽  
New Drugs ◽  
Treatment Regimens

As the development of new drugs for Chagas disease is not a priority due to its neglected disease status, an option for increasing treatment adherence is to explore alternative treatment regimens, which may decrease the incidence of side effects. Therefore, we evaluated the efficacy of different therapeutic schemes with benznidazole (BNZ) on the acute and chronic phases of the disease, using mice infected with strains that have different BNZ susceptibilities. Our results show that the groups of animals infected by VL-10 strain, when treated in the chronic phase with a lower dose of BNZ for a longer period of time (40 mg/kg/day for 40 days) presented better treatment efficacy than with the standard protocol (100 mg/kg/day for 20 days) although the best result in the treatment of the animals infected by the VL-10 strain was with100 mg/kg/day for 40 days. In the acute infection by the Y and VL-10 strains of T. cruzi, the treatment with a standard dose, but with a longer time of treatment (100 mg/kg/day for 40 days) presented the best results. Given these data, our results indicate that for BNZ, the theory of dose and time proportionality does not apply to the phases of infection.

scholarly journals Tuberculosis: Development of New Drugs and Treatment Regimens

2021 ◽  
Vol 7 (1) ◽  
pp. 36
Author(s):  
Soedarsono Soedarsono
Keyword(s):  
Treatment Guidelines ◽  
New Drugs ◽  
World Health ◽  
Health Crisis ◽  
Treatment Regimens ◽  
Tb Treatment ◽  
Repurposed Drugs ◽  
Latent Tb Infection ◽  
Health Organization ◽  
Who Guideline

Tuberculosis (TB) still becomes a public health crisis. Drug-resistant TB (DR-TB) becomes a concern as the increasing DR-TB cases in countries with high TB burden. The 2017 World Health Organization (WHO) guideline recommended a combination of TB treatment consisting of 2 months of intensive phase with isoniazid (H), rifampisin (R), pyrazinamid (Z), and ethambutol (E), followed by 4 months of continuation phase with HR daily. WHO has updated DR-TB treatment guidelines several times. In 2016, WHO recommended shorter regimen and individual regimen based on certain conditions. The most updated 2020 WHO guideline recommended the short regimen consisting of all oral drugs as well as changes in the grouping of medicines used in DR-TB regimens in longer/individual regimens. Bedaquiline, delamanid, pretomanid, and sutezolid are new drugs which have been studied for their uses as anti-TB drugs (ATD). Bedaquilin and delamanid, which have passed phase 3 trials, have been approved and recommended by WHO for DR-TB treatment. Repurposed drugs have been used for DR-TB treatment during the time of evaluation of drugs list and regimens for DR-TB treatment. Fluoroquinolones, clofazimine, linezolid, carbapenem, amoxicillin/clavulanic acid are repurposed drugs. TB and DR-TB management will be updated at any time, based on the latest findings in studies, to evaluate and improve the effectiveness of current treatments. Prevention of active TB disease by the treatment of latent TB infection (LTBI) is also a critical component of the end TB strategy by WHO. Therefore, the development of new drugs for the LTBI treatment is also needed.

Ponatinib, Lestaurtinib and mTOR/PI3K inhibitors are promising repurposing candidates against Entamoeba histolytica

2021 ◽  
Author(s):  
Monica M. Kangussu-Marcolino ◽  
Upinder Singh
Keyword(s):  
Entamoeba Histolytica ◽  
Current Treatment ◽  
Clinical Development ◽  
New Drugs ◽  
Phase Iii ◽  
Significant Advance ◽  
Pi3k Inhibitors ◽  
Treatment Regimens ◽  
Clinical Resistance ◽  
Tk Inhibitors

Dysentery caused by Entamoeba histolytica affects millions of people annually. Current treatment regimens are based on metronidazole to treat invasive parasites combined with paromomycin for luminal parasites. Issues with treatment include significant side effects, inability to easily treat breastfeeding and pregnant women, the use of two sequential agents, and concern that all therapy is based on nitroimidazole agents with no alternatives if clinical resistance emerges. Thus, the need for new drugs against amebiasis is urgent. To identify new therapeutic candidates, we screened the ReFRAME library (11,948 compounds assembled for Repurposing, Focused Rescue, and Accelerated Medchem) against E. histolytica trophozoites. We identified 159 hits in the primary screen at 10 μM and 46 compounds were confirmed in secondary assays. Overall, 26 were selected as priority molecules for further investigation including 6 FDA approved, 5 orphan designation, and 15 which are currently in clinical trials (3 phase III, 7 phase II and 5 phase I). We found that all 26 compounds are active against metronidazole resistant E. histolytica and 24 are able to block parasite recrudescence after drug removal. Additionally, 14 are able to inhibit encystation and 2 (lestaurtinib and LY-2874455) are active against mature cysts. Two classes of compounds are most interesting for further investigations: the Bcr-Abl TK inhibitors, with the ponatinib (EC 50 0.39) as most potent and mTOR or PI3K inhibitors with 8 compounds in clinical development, of which 4 have nanomolar potency. Overall, these are promising candidates and represent a significant advance for drug development against E. histolytica .

Multidisciplinary advisory teams to manage multidrug-resistant tuberculosis: the example of the French Consilium

2019 ◽  
Vol 23 (10) ◽  
pp. 1050-1054
Author(s):  
L. Guglielmetti ◽  
J. Jaffré ◽  
C. Bernard ◽  
F. Brossier ◽  
N. El Helali ◽  
...  
Keyword(s):  
Multidrug Resistant ◽  
New Drugs ◽  
World Health ◽  
Advisory Committees ◽  
Treatment Regimens ◽  
Tb Treatment ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Mdr Tb ◽  
Health Organization

SETTING: The World Health Organization (WHO) recommends that multidrug-resistant tuberculosis (MDR-TB) treatment should be managed in collaboration with multidisciplinary advisory committees (consilia). A formal national Consilium has been established in France since 2005 to provide a centralised advisory service for clinicians managing MDR-TB and extensively drug-resistant (XDR-TB) cases.OBJECTIVE: Review the activity of the French TB Consilium since its establishment.DESIGN: Retrospective description and analysis of the activity of the French TB Consilium.RESULTS: Between 2005 and 2016, 786 TB cases or contacts of TB cases were presented at the French TB Consilium, including respectively 42% and 79% of all the MDR-TB and XDR-TB cases notified in France during this period. Treatment regimens including bedaquiline and/or delamanid were recommended for 42% of the cases presented at the French TB Consilium since 2009. Patients were more likely to be presented at the French TB Consilium if they were born in the WHO Europe Region, had XDR-TB, were diagnosed in the Paris region, or had resistance to additional drugs than those defining XDR-TB.CONCLUSION: The French TB Consilium helped supervise appropriate management of MDR/XDR-TB cases and facilitated implementation of new drugs for MDR/XDR-TB treatment.

Tuberculosis treatment and management—an update on treatment regimens, trials, new drugs, and adjunct therapies

2015 ◽  
Vol 3 (3) ◽  
pp. 220-234 ◽  
Author(s):  
Alimuddin Zumla ◽  
Jeremiah Chakaya ◽  
Rosella Centis ◽  
Lia D'Ambrosio ◽  
Peter Mwaba ◽  
...  
Keyword(s):  
New Drugs ◽  
Tuberculosis Treatment ◽  
Treatment Regimens

Structure, function and biosynthesis of the Mycobacterium tuberculosis cell wall: arabinogalactan and lipoarabinomannan assembly with a view to discovering new drug targets

2007 ◽  
Vol 35 (5) ◽  
pp. 1325-1328 ◽  
Author(s):  
L.J. Alderwick ◽  
H.L. Birch ◽  
A.K. Mishra ◽  
L. Eggeling ◽  
G.S. Besra
Keyword(s):  
Cell Wall ◽  
Drug Targets ◽  
Infectious Agent ◽  
Multidrug Resistant ◽  
Resistance Mechanisms ◽  
New Drugs ◽  
New Era ◽  
New Drug ◽  
Site Of Action ◽  
Wall Components

In spite of effective antibiotics to treat TB (tuberculosis) since the early 1960s, we enter the new millennium with TB, currently the leading cause of death from a single infectious agent, killing more than three million people worldwide each year. Thus an understanding of drug-resistance mechanisms, the immunobiology of cell wall components to elucidate host–pathogen interactions and the discovery of new drug targets are now required for the treatment of TB. Above the plasma membrane is a classical chemotype IV PG (peptidoglycan) to which is attached the macromolecular structure, mycolyl-arabinogalactan, via a unique diglycosylphosphoryl bridge. This review will discuss the assembly of the mAGP (mycolyl-arabinogalactan-peptidoglycan), its associated glycolipids and the site of action of EMB (ethambutol), bringing forward a new era in TB research and focus on new drugs to combat multidrug resistant TB.

scholarly journals DIFFERENTIAL DIAGNOSIS OF STERILE AND I NFECTED PANCREONECROSIS

2021 ◽  
pp. 31-35
Author(s):  
V. V. Boyko ◽  
V. M. Lykhman ◽  
A. O. Merkulov ◽  
D. O. Myroshnychenko ◽  
S. V. Tkach ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Differential Diagnosis ◽  
Pancreatic Necrosis ◽  
Clinical Laboratory ◽  
Practical Importance ◽  
Modern Medicine ◽  
Infectious Complications ◽  
Infected Pancreatic Necrosis ◽  
Septic Complications ◽  
Great Practical Importance

Summary. Introduction. The search for objective methods for diagnosing the form and severity of acute pancreatitis, accurate prediction and timely prevention of infectious complications in this surgical pathology is of great practical importance for modern medicine. Materials and methods. According to clinical, morphological and bacteriological data, groups of patients were selected. The first group included 33 patients with sterile pancreatic necrosis (SP), the second group consisted of 29 patients with infected pancreatic necrosis (IP). Results and discussion. The program of differential diagnosis of sterile and infected pancreatic necrosis with calculation of the index of differential diagnosis (IDD) for each clinical-laboratory and instrumental indicator used in this system is developed. The development and evaluation of diagnostic possibilities of the method of verification of purulent-septic complications of acute pancreatitis and the transition of a sterile form of pancreatic necrosis to an infected one was carried out. Conclusions. The use of the developed method of diagnosis of sterile and infected pancreatic necrosis with the calculation of the index of differential diagnosis allowed in 93% of cases to distinguish sterile pancreatic necrosis from infected and timely determine the scope and tactics of treatment.

scholarly journals Alternative Medicine: A Recent Overview

2021 ◽  
Author(s):  
Salima Akter ◽  
Mohammad Nazmul Hasan ◽  
Begum Rokeya ◽  
Hajara Akhter ◽  
Mohammad Shamim Gazi ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Alternative Medicine ◽  
Public Interest ◽  
Modern Medicine ◽  
New Drugs ◽  
Future Perspectives ◽  
Analgesic Effects ◽  
Alternative Medicines ◽  
Pharmacologically Active ◽  
Over Time

Alternative medicine has renewed its growing public interest in recent times due to inequality of patients and healthcare professionals’ ratios with increased workload for the latter, various side effects of modern medicine, lack of complete remission from chronic diseases, high cost of new drugs, and emerging new diseases. Hence, people have become more dependent on treatment systems replying on alternative medicine or herbal medicine from traditional medicinal practitioners. Alternative medicine has grown substantially over time and encompasses several millennia of therapeutic systems. The significant areas of alternative medicine include mind–body therapies, body manipulation, and the therapies based on biological systems. Natural products based biological treatment is the most popular of them as nature has endowed us with abundance of effective pharmacologically active phytochemicals. These phytochemicals possess numerous specific clinical health benefits including antioxidant, antidiabetic, anti-inflammatory, anticancer, anti-infectious and analgesic effects. In addition, alternative medicine is easily accessible, affordable, most often noninvasive, and provides favorable benefits during terminal periods of some diseases. However, due to the lack of well-designed clinical trials, the safety and effectiveness of many alternative medicines/therapies remains elusive. This chapter will critically discuss major areas, uses, safety and regulation, current challenges & future perspectives of alternative medicine.

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