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Drugs Sep 2021Contezolid (Youxitai ), an orally administered oxazolidinone antibacterial agent, is being developed by Shanghai MicuRx Pharmaceutical Co., Ltd. for the treatment of... (Review)
Review
Contezolid (Youxitai ), an orally administered oxazolidinone antibacterial agent, is being developed by Shanghai MicuRx Pharmaceutical Co., Ltd. for the treatment of multidrug-resistant (MDR) Gram-positive bacterial infections, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci. In June 2021, it was approved by the National Medical Products Administration of China for the treatment of complicated skin and soft tissue infections (cSSTI), including, but not limited to, methicillin-susceptible S. aureus, MRSA, Streptococcus pyogenes and Streptococcus agalactiae. The recommended dosage of contezolid is 800 mg (i.e. two 400 mg tablets) every 12 h for 7-14 days. Contezolid is also undergoing clinical development for acute bacterial skin and skin structure infections (ABSSSI) in the USA, and for diabetic foot infections. This article summarizes the milestones in the development of contezolid leading to this first approval for the treatment of cSSTI.
Topics: Anti-Bacterial Agents; China; Drug Approval; Drug Resistance, Multiple, Bacterial; Gram-Positive Bacterial Infections; Humans; Methicillin-Resistant Staphylococcus aureus; Oxazolidinones; Pyridones; Vancomycin Resistance
PubMed: 34365606
DOI: 10.1007/s40265-021-01576-0 -
Clinical Microbiology and Infection :... Nov 2019Adjunctive systemic antibiotic therapy for treatment of bacterial endophthalmitis is controversial but common practice due to the severity of the disease. In the absence... (Review)
Review
BACKGROUND
Adjunctive systemic antibiotic therapy for treatment of bacterial endophthalmitis is controversial but common practice due to the severity of the disease. In the absence of guidance documents, several antibiotic regimens are being used without applying evidence-based prescribing, leading to inappropriate treatment of this serious eye condition.
OBJECTIVES
To summarize available data on intravitreal penetration of systemically administered antibiotics and to discuss their usefulness from a microbiological and pharmacological point of view.
SOURCES
We performed a systematic PubMed search of studies investigating antibiotic concentrations in the vitreous after systemic administration in humans, and selected animal models.
CONTENT
The best-documented agents achieving therapeutic levels in the vitreous are meropenem, linezolid and moxifloxacin. Vancomycin, cefazoline, ceftriaxone, ceftazidime, imipenem and trimethoprim-sulfamethoxazole reach levels justifying their use in specific situations. Available data do not support the use of ciprofloxacin, levofloxacin, aminoglycosides, aminopenicillins, piperacillin, cefepime and clarithromycin. With very limited but available promising data, the use of daptomycin and rifampicin deserves further investigation.
IMPLICATIONS
The choice of the adjunctive systemic antibiotic agent-in situations where it is considered relevant for treatment-must to date be made on an individual basis, considering microbiological aspects as well as operative status and inflammation of the eye. This review gives a systematic overview of antibiotic options and provides guidance to the clinician striving for optimal systemic antibiotic treatment of bacterial endophthalmitis.
Topics: Administration, Intravenous; Animals; Anti-Bacterial Agents; Bacterial Infections; Disease Models, Animal; Endophthalmitis; Humans; Vitreous Body
PubMed: 30771529
DOI: 10.1016/j.cmi.2019.01.017 -
Drugs Sep 2017Delafloxacin (Baxdela™) is a fluoroquinolone antibacterial with activity against both gram-positive and gram-negative pathogens being developed by Melinta... (Review)
Review
Delafloxacin (Baxdela™) is a fluoroquinolone antibacterial with activity against both gram-positive and gram-negative pathogens being developed by Melinta Therapeutics. The drug is being investigated or considered as a treatment for various bacterial infections and in June 2017 received approval in the USA for the treatment of acute bacterial skin and skin structure infections. This article summarizes the milestones in the development of delafloxacin leading to this first global approval for the treatment of acute bacterial skin and skin structure infections.
Topics: Anti-Bacterial Agents; Bacterial Infections; Dose-Response Relationship, Drug; Drug Approval; Drug Compounding; Fluoroquinolones; Humans; Skin Diseases, Bacterial; United States; United States Food and Drug Administration
PubMed: 28748399
DOI: 10.1007/s40265-017-0790-5 -
Cold Spring Harbor Perspectives in... Jul 2016Rifamycins inhibit RNA polymerase of most bacterial genera. Rifampicin remains part of combination therapy for treating tuberculosis (TB), and for treating Gram-positive... (Review)
Review
Rifamycins inhibit RNA polymerase of most bacterial genera. Rifampicin remains part of combination therapy for treating tuberculosis (TB), and for treating Gram-positive prosthetic joint and valve infections, in which biofilms are prominent. Rifabutin has use for AIDS patients in treating mycobacterial infections TB and Mycobacterium avium complex (MAC), having fewer drug-drug interactions that interfere with AIDS medications. Rifabutin is occasionally used in combination to eradicate Helicobacter pylori (peptic ulcer disease). Rifapentine has yet to fulfill its potential in reducing time of treatment for TB. Rifaximin is a monotherapeutic agent to treat gastrointestinal (GI) disorders, such as hepatic encephalopathy, irritable bowel syndrome, and travelers' diarrhea. Rifaximin is confined to the GI tract because it is not systemically absorbed on oral dosing, achieving high local concentrations, and showing anti-inflammatory properties in addition to its antibacterial activity. Resistance issues are unavoidable with all the rifamycins when the bioburden is high, because of mutations that modify RNA polymerase.
Topics: Anti-Bacterial Agents; Antibiotics, Antitubercular; Drug Resistance, Bacterial; Drug Therapy, Combination; Gastrointestinal Diseases; Humans; Rifabutin; Rifampin; Rifamycins; Rifaximin; Tuberculosis
PubMed: 27270559
DOI: 10.1101/cshperspect.a027011 -
Indian Pediatrics Nov 2004Linezolid is an oxazolidinone antibacterial agent that acts by inhibiting the initiation of bacterial protein synthesis. Linezolid has a wide spectrum of activity...
Linezolid is an oxazolidinone antibacterial agent that acts by inhibiting the initiation of bacterial protein synthesis. Linezolid has a wide spectrum of activity against gram-positive organisms including methicillin resistant staphylococci, penicillin resistant pneumococci and vancomycin resistant enterococcus faecalis and E. faecium. Linezolid has a good bio-availability orally and could be switched from parenteral to oral therapy while treating serious infections. Linezolid is well tolerated in children.
Topics: Acetamides; Adult; Anti-Bacterial Agents; Child; Gram-Positive Bacterial Infections; Humans; Linezolid; Oxazolidinones; Protein Biosynthesis; Protein Synthesis Inhibitors
PubMed: 15591662
DOI: No ID Found -
Journal of Traditional Chinese Medicine... Aug 2021To investigate the anti-bacterial and anti-viral effects of Fengreqing oral liquid (, FRQ) in vitro and in vivo.
OBJECTIVE
To investigate the anti-bacterial and anti-viral effects of Fengreqing oral liquid (, FRQ) in vitro and in vivo.
METHODS
The minimum inhibitory concentrations of Fengreqing Oral Liquid against six gram-positive bacteria (Staphylococcus aureus, Streptococcus mutans, Peptostreptococcus anaerobius, Hemolytic streptococcus, Streptococcus pneumoniae, Klebsiella pneumoniae), seven gram-negative bacteria (Escherichia coli, Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, Haemophilus influenzae, Helicobacter pylori, Pseudomonas aeruginosa, Gardnerella vaginalis) and Candida albicans were detected by the paper disc diffusion method. The inhibition rate of A/PuertoRico/8/34(H1N1) (PR8) influenza virus in different concentrations of Fengreqing oral solution was detected by chicken embryo method. CCK8 method was used to detect the half-cell infection of RSV, VSV and CVB3. The effect of FRQ on the survival curve of mice was detected by using co-infection model of Streptococcus pneumoniae and influenza virus.
RESULTS
In vitro, FRQ can inhibit Actinobacillus actinomycetemcomitans, Helicobacter pylori, Gardnerella vaginalis, Staphylococcus aureus, Streptococcus mutans and Streptococcus pneumoniae and has an antiviral effect on the envelope virus H1N1. In vivo, Fengreqing oral solution had therapeutic effect on influenza-Streptococcus pneumoniae co-infection in mice, significantly improving the survival rate of mice. The medium dose and low dose FRQ significantly prolonged the survival time of mice.
CONCLUSION
FRQ has good anti-bacterial and anti-viral effectsin vivo and in vitro.
Topics: Animals; Anti-Bacterial Agents; Antiviral Agents; Chick Embryo; Helicobacter pylori; Influenza A Virus, H1N1 Subtype; Mice; Microbial Sensitivity Tests; Staphylococcus aureus
PubMed: 34392645
DOI: 10.19852/j.cnki.jtcm.2021.03.005 -
Molecules (Basel, Switzerland) Aug 2023Rakicidin B1 was isolated and purified from the culture broth of a marine sp. as a potent anti-cancer agent, and lately the compound and its derivatives have firstly...
Rakicidin B1 was isolated and purified from the culture broth of a marine sp. as a potent anti-cancer agent, and lately the compound and its derivatives have firstly been found to possess anti- (CD) activity but with high cytotoxicity. Herein, following our previous discovery on anti-CD activity of Rakicidin B1, structure modification was performed at the OH position of Rakicidin B1 and a new Rakicidin B1-PEG hybrids FIMP2 was facilely designed and synthesized by conjugating the PEG2000 with the scaffolds of Rakicidin B1 via the linkage of carbamate. The cytotoxicity of the FIMP2 was first evaluated against three different cancer cell lines, including HCT-8 cells, PANC-1, and Caco-2, with IC values at 0.519 μM, 0.815 μM, and 0.586 μM, respectively. Obviously, as compared with a positive control group treated with Rakicidin B1, the IC value of FIMP2 increased by nearly 91-fold, 50-fold, and 67-fold, suggesting that the PEGylation strategy significantly reduced the cytotoxicity of FIMP2. Thus, this preliminary result may be beneficial to increase its safety index (SI) value due to the decreased cytotoxicity of FIMP2. In addition, this decreased cytotoxicity of FIMP2 was further confirmed based on a zebrafish screening model in vivo. Thereafter, the anti-CD activity of FIMP2 was evaluated in vivo, and its efficacy to treat CDI was found to be better than that of vancomycin. The mortality and recurrence rate of FIMP2 is not as low compared with that of vancomycin; these results demonstrated that compound FIMP2 is a new, promising anti-CD agent with significant efficacy against CD recurrence with low cytotoxicity towards bodies.
Topics: Humans; Animals; Anti-Bacterial Agents; Vancomycin; Caco-2 Cells; Zebrafish; Clostridioides difficile
PubMed: 37630404
DOI: 10.3390/molecules28166152 -
International Journal of Molecular... Sep 2019resistance to current antibiotics has become the greatest global challenge facing public health. The development of new antimicrobial agents is urgent and important and...
resistance to current antibiotics has become the greatest global challenge facing public health. The development of new antimicrobial agents is urgent and important and is needed to provide additional therapeutic options. In our previous study, we found out that pterostilbene exhibited potent antibacterial activity, especially against methicillin-resistant (MRSA). According to previous studies, 1,2,3-triazole, with the characteristic of increasing the interaction with the target readily and enhancing water solubility, were widely used in the approved anti-bacterial drugs. Therefore, these results attract our interest to use the structure of pterostilbene as a scaffold for the hybrid 1,2,3-triazole moiety to develop a novel anti-MRSA infection agent. In this study, we demonstrated the design and synthesis of a series of triazolylpterostilbene derivatives. Among these compounds, compound exhibited the most potent anti-MRSA activity with a minimum inhibitory concentration (MIC) value of 1.2-2.4 μg/mL and a minimum bactericidal concentration (MBC) value of 19.5-39 μg/mL. The structure-activity relationship and antibacterial mechanism were investigated in this study. Molecular docking studies were carried out to verify and rationalize the biological results. In this study, the results confirmed that our design could successfully increase the inhibitory activity and specificity against MRSA. Compound could be used as a candidate for anti-bacterial agents and in depth vivo studies should be further investigated.
Topics: Anti-Bacterial Agents; DNA Polymerase III; Methicillin-Resistant Staphylococcus aureus; Molecular Docking Simulation; Stilbenes; Structure-Activity Relationship; Triazoles
PubMed: 31540106
DOI: 10.3390/ijms20184564 -
Journal of Infection and Chemotherapy :... May 2016Fosfomycin was discovered over four decades ago, yet has drawn renewed interest as an agent active against a range of multidrug-resistant (MDR) and extensively... (Review)
Review
Fosfomycin was discovered over four decades ago, yet has drawn renewed interest as an agent active against a range of multidrug-resistant (MDR) and extensively drug-resistant (XDR) pathogens. Its unique mechanism of action and broad spectrum of activity makes it a promising candidate in the treatment of various MDR/XDR infections. There has been a surge of in vitro data on its activity against MDR/XDR organisms, both when used as a single agent and in combination with other agents. In the United States, fosfomycin is only approved in an oral formulation for the treatment of acute uncomplicated urinary tract infections (UTIs), whereas in some countries both oral and intravenous formulations are available for various indications. Fosfomycin has minimal interactions with other medications and has a relatively favorable safety profile, with diarrhea being the most common adverse reaction. Fosfomycin has low protein binding and is excreted primarily unchanged in the urine. The clinical outcomes of patients treated with fosfomycin are favorable for uncomplicated UTIs, but data are limited for use in other conditions. Fosfomycin maintains activity against most Enterobacteriaceae including Escherichia coli, but plasmid-mediated resistance due to inactivation have appeared in recent years, which has the potential to compromise its use in the future. In this review, we summarize the current knowledge of this resurgent agent and its role in our antimicrobial armamentarium.
Topics: Anti-Bacterial Agents; Bacteria; Bacterial Infections; Drug Resistance, Multiple, Bacterial; Fosfomycin; Humans; Microbial Sensitivity Tests
PubMed: 26923259
DOI: 10.1016/j.jiac.2016.01.010 -
Journal of Nanobiotechnology Dec 2022Despite significant progress in synthetic polymer chemistry and in control over tuning the structures and morphologies of nanoparticles, studies on morphologic design of... (Review)
Review
Despite significant progress in synthetic polymer chemistry and in control over tuning the structures and morphologies of nanoparticles, studies on morphologic design of nanomaterials for the purpose of optimizing antimicrobial activity have yielded mixed results. When designing antimicrobial materials, it is important to consider two distinctly different modes and mechanisms of activity-those that involve direct interactions with bacterial cells, and those that promote the entry of nanomaterials into infected host cells to gain access to intracellular pathogens. Antibacterial activity of nanoparticles may involve direct interactions with organisms and/or release of antibacterial cargo, and these activities depend on attractive interactions and contact areas between particles and bacterial or host cell surfaces, local curvature and dynamics of the particles, all of which are functions of nanoparticle shape. Bacteria may exist as spheres, rods, helices, or even in uncommon shapes (e.g., box- and star-shaped) and, furthermore, may transform into other morphologies along their lifespan. For bacteria that invade host cells, multivalent interactions are involved and are dependent upon bacterial size and shape. Therefore, mimicking bacterial shapes has been hypothesized to impact intracellular delivery of antimicrobial nanostructures. Indeed, designing complementarities between the shapes of microorganisms with nanoparticle platforms that are designed for antimicrobial delivery offers interesting new perspectives toward future nanomedicines. Some studies have reported improved antimicrobial activities with spherical shapes compared to non-spherical constructs, whereas other studies have reported higher activity for non-spherical structures (e.g., rod, discoid, cylinder, etc.). The shapes of nano- and microparticles have also been shown to impact their rates and extents of uptake by mammalian cells (macrophages, epithelial cells, and others). However, in most of these studies, nanoparticle morphology was not intentionally designed to mimic specific bacterial shape. Herein, the morphologic designs of nanoparticles that possess antimicrobial activities per se and those designed to deliver antimicrobial agent cargoes are reviewed. Furthermore, hypotheses beyond shape dependence and additional factors that help to explain apparent discrepancies among studies are highlighted.
Topics: Animals; Nanoparticles; Anti-Infective Agents; Anti-Bacterial Agents; Polymers; Biological Transport; Nanostructures; Mammals
PubMed: 36539809
DOI: 10.1186/s12951-022-01733-x