Redox-active cationic organoiron complex: a promising lead structure for developing antimicrobial agents with activity against Gram-positive pathogens including methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecium

RSC Advances ◽  
2015 ◽  
Vol 5 (105) ◽  
pp. 86421-86427 ◽  
Author(s):  
Alaa S. Abd-El-Aziz ◽  
Christian Agatemor ◽  
Nola Etkin ◽  
David P. Overy ◽  
Russell G. Kerr
Keyword(s):  
Antimicrobial Agents ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Multidrug Resistant ◽  
Gram Positive ◽  
Lead Structure ◽  
Gram Positive Bacteria ◽  
Redox Active ◽  
Vancomycin Resistant ◽  
Organoiron Complexes ◽  
Multidrug Resistant Strain

A redox-active, cationic organoiron complexes active against multidrug-resistant strain of Gram-positive bacteria is presented as a potential new lead structure for the design of antimicrobial agents.

scholarly journals Resistance of Gram-Positive Bacteria to Current Antibacterial Agents and Overcoming Approaches

Molecules ◽  
2020 ◽  
Vol 25 (12) ◽  
pp. 2888 ◽  
Author(s):  
Buthaina Jubeh ◽  
Zeinab Breijyeh ◽  
Rafik Karaman
Keyword(s):  
Turning Point ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Gram Positive ◽  
Medical Interventions ◽  
Gram Positive Bacteria ◽  
New Antibiotics ◽  
Vancomycin Resistant ◽  
New Treatments ◽  
Emergence Of Resistance

The discovery of antibiotics has created a turning point in medical interventions to pathogenic infections, but unfortunately, each discovery was consistently followed by the emergence of resistance. The rise of multidrug-resistant bacteria has generated a great challenge to treat infections caused by bacteria with the available antibiotics. Today, research is active in finding new treatments for multidrug-resistant pathogens. In a step to guide the efforts, the WHO has published a list of the most dangerous bacteria that are resistant to current treatments and requires the development of new antibiotics for combating the resistance. Among the list are various Gram-positive bacteria that are responsible for serious healthcare and community-associated infections. Methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus faecium, and drug-resistant Streptococcus pneumoniae are of particular concern. The resistance of bacteria is an evolving phenomenon that arises from genetic mutations and/or acquired genomes. Thus, antimicrobial resistance demands continuous efforts to create strategies to combat this problem and optimize the use of antibiotics. This article aims to provide a review of the most critical resistant Gram-positive bacterial pathogens, their mechanisms of resistance, and the new treatments and approaches reported to circumvent this problem.

scholarly journals Emerging Treatment Options for Infections by Multidrug-Resistant Gram-Positive Microorganisms

2020 ◽  
Vol 8 (2) ◽  
pp. 191 ◽  
Author(s):  
Despoina Koulenti ◽  
Elena Xu ◽  
Andrew Song ◽  
Isaac Yin Sum Mok ◽  
Drosos E. Karageorgopoulos ◽  
...  
Keyword(s):  
Safety Profile ◽  
Bacterial Infections ◽  
Antimicrobial Agents ◽  
Treatment Options ◽  
Multidrug Resistant ◽  
Current Treatment ◽  
Multi Drug Resistance ◽  
Gram Positive ◽  
Treatment Regimens ◽  
Gram Positive Bacteria

Antimicrobial agents are currently the mainstay of treatment for bacterial infections worldwide. However, due to the increased use of antimicrobials in both human and animal medicine, pathogens have now evolved to possess high levels of multi-drug resistance, leading to the persistence and spread of difficult-to-treat infections. Several current antibacterial agents active against Gram-positive bacteria will be rendered useless in the face of increasing resistance rates. There are several emerging antibiotics under development, some of which have been shown to be more effective with an improved safety profile than current treatment regimens against Gram-positive bacteria. We will extensively discuss these antibiotics under clinical development (phase I-III clinical trials) to combat Gram-positive bacteria, such as Staphylococcus aureus, Enterococcus faecium and Streptococcus pneumoniae. We will delve into the mechanism of actions, microbiological spectrum, and, where available, the pharmacokinetics, safety profile, and efficacy of these drugs, aiming to provide a comprehensive review to the involved stakeholders.

Antimicrobial-Resistant Gram-Positive Bacteria in PD Peritonitis and the Newer Antibiotics Used to Treat Them

2005 ◽  
Vol 25 (4) ◽  
pp. 313-319 ◽  
Author(s):  
William Salzer
Keyword(s):  
Methicillin Resistant Staphylococcus Aureus ◽  
Natural Habitat ◽  
Gram Positive ◽  
Gram Positive Bacteria ◽  
The Past ◽  
Vancomycin Resistant Enterococci ◽  
Resistant Strains ◽  
Vancomycin Resistant ◽  
Novel Antibiotics

The incidence of resistant gram-positive bacteria in nosocomial and, more recently, community-acquired infections is increasing. Staphylococci, because of their natural habitat on the skin, have always been the leading cause of peritonitis in patients receiving peritoneal dialysis (PD). These organisms have demonstrated a remarkable ability to develop resistance to antibiotics, first with penicillin, then antistaphylococcal penicillins (methicillin-resistant Staphylococcus aureus), and more recently, strains expressing resistance to vancomycin (vancomycin-intermediate and vancomycin-resistant S. aureus) have emerged. Enterococci are normal inhabitants of the gastrointestinal tract and occasionally cause PD peritonitis. In the past 15 years, vancomycin-resistant enterococci have emerged as significant pathogens in many areas. In the past 5 years, novel antibiotics that have activity on gram-positive bacteria, including vancomycin-resistant strains, have become available. The problem of resistant gram-positive bacteria in PD peritonitis, their therapy, and the role of these newer agents, quinupristin/dalfopristin, linezolid, and daptomycin, are reviewed.

scholarly journals Antimicrobial O-Alkyl Derivatives of Naringenin and Their Oximes Against Multidrug-Resistant Bacteria

Molecules ◽  
2020 ◽  
Vol 25 (16) ◽  
pp. 3642 ◽  
Author(s):  
Anna Duda-Madej ◽  
Joanna Kozłowska ◽  
Paweł Krzyżek ◽  
Mirosław Anioł ◽  
Alicja Seniuk ◽  
...  
Keyword(s):  
Antimicrobial Agents ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Quantitative Measure ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Beta Lactam ◽  
Multidrug Resistant Bacteria ◽  
Alkyl Derivatives ◽  
Vancomycin Resistant ◽  
Derivatives Of

New antimicrobial agents are needed to address infections caused by multidrug-resistant bacteria. Here, we are reporting novel O-alkyl derivatives of naringenin and their oximes, including novel compounds with a naringenin core and O-hexyl chains, showing activity against clinical strains of clarithromycin-resistant Helicobacter pylori, vancomycin-resistant Enterococcus faecalis, methicillin-resistant Staphylococcus aureus, and beta-lactam-resistant Acinetobacter baumannii and Klebsiella pneumoniae. The minimum inhibitory concentrations (MICs), which provide a quantitative measure of antimicrobial activity, were in the low microgram range for the selected compounds. Checkerboard assays for the most active compounds in combination with antibiotics revealed interactions that varied from synergistic to neutral.

scholarly journals Baseline Study To Determine In Vitro Activities of Daptomycin against Gram-Positive Pathogens Isolated in the United States in 2000-2001

2003 ◽  
Vol 47 (5) ◽  
pp. 1689-1693 ◽  
Author(s):  
Ian A. Critchley ◽  
Renée S. Blosser-Middleton ◽  
Mark E. Jones ◽  
Clyde Thornsberry ◽  
Daniel F. Sahm ◽  
...  
Keyword(s):  
United States ◽  
Outpatient Care ◽  
Antimicrobial Agents ◽  
The United States ◽  
Multidrug Resistant ◽  
Gram Positive ◽  
Gram Positive Bacteria ◽  
Oxacillin Resistance ◽  
Positive Spectrum

ABSTRACT The activity of daptomycin was assessed by using 6,973 gram-positive bacteria isolated at 50 United States hospitals in 2000 and 2001. Among the isolates of Streptococcus pneumoniae (n = 1,163) collected, the rate of penicillin resistance was 16.1%; rates of oxacillin resistance among Staphylococcus aureus isolates (n = 1,018) and vancomycin resistance among Enterococcus faecium isolates (n = 368) were 30.0 and 59.5%, respectively. Multidrug-resistant (MDR) phenotypes (isolates resistant to three or more different chemical classes of antimicrobial agents) accounted for 14.2% of S. pneumoniae isolates, 27.1% of S. aureus isolates, and 58.4% of E. faecium isolates. For all gram-positive species tested, MICs at which 90% of the isolates tested were inhibited (MIC90s) and MIC ranges for directed-spectrum agents (daptomycin, quinupristin-dalfopristin, and linezolid) were identical or highly similar for isolates susceptible or resistant to other agents or MDR. Daptomycin had a MIC90 of 0.12 μg/ml for both penicillin-susceptible and -resistant isolates of S. pneumoniae. Against oxacillin-resistant S. aureus daptomycin had a MIC90 of 0.5 μg/ml, and it had a MIC90 of 4 μg/ml against both vancomycin-susceptible and -resistant E. faecium. The MIC90s for daptomycin and other directed-spectrum agents were unaffected by the regional or anatomical origin of isolates or patient demographic parameters (patient age, gender, and inpatient or outpatient care). Our results confirm the gram-positive spectrum of activity of daptomycin and that its activity is independent of susceptibility or resistance to commonly prescribed and tested antimicrobial agents. This study may serve as a baseline to monitor future changes in the susceptibility of gram-positive species to daptomycin following its introduction into clinical use.

scholarly journals In vitro properties of antimicrobial bromotyrosine alkaloids

2006 ◽  
Vol 55 (4) ◽  
pp. 407-415 ◽  
Author(s):  
Neora Pick ◽  
Mamta Rawat ◽  
Dorit Arad ◽  
Jiong Lan ◽  
Junfa Fan ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Antimicrobial Agents ◽  
Lead Compound ◽  
Gram Positive ◽  
Gram Positive Bacteria ◽  
Monocytes And Macrophages ◽  
Natural Inhibitor ◽  
Low Toxicity ◽  
Vancomycin Resistant

A bromotyrosine alkaloid family of antimicrobial agents was synthesized using the known structure of a natural inhibitor of the mycobacterial mycothiol S-conjugate amidase (MCA) as a template. This series of compounds represents a novel class of anti-infective agents against Gram-positive pathogens, including mycobacteria and meticillin- and vancomycin-resistant Staphylococcus aureus. The fact that these compounds are active against mycobacterial strains in which the MCA gene is deleted and against Gram-positive bacteria lacking mycothiol suggests the existence of an alternative target for these compounds. One member of this family, EXEG1706, was identified as the lead compound possessing low MICs (2·5–25 μg ml−1) for several clinical isolates, whilst having low toxicity for THP-1 monocytes and macrophages.

scholarly journals Cerecidins, Novel Lantibiotics from Bacillus cereus with Potent Antimicrobial Activity

2014 ◽  
Vol 80 (8) ◽  
pp. 2633-2643 ◽  
Author(s):  
Jian Wang ◽  
Li Zhang ◽  
Kunling Teng ◽  
Shutao Sun ◽  
Zhizeng Sun ◽  
...  
Keyword(s):  
Bacillus Cereus ◽  
Multidrug Resistant ◽  
Regulator Gene ◽  
Gram Positive ◽  
Content Type ◽  
Pcr Screening ◽  
Gram Positive Bacteria ◽  
Immunity Genes ◽  
Natural Variants ◽  
Vancomycin Resistant

ABSTRACTLantibiotics are ribosomally synthesized and posttranslationally modified antimicrobial peptides that are widely produced by Gram-positive bacteria, including many species of theBacillusgroup. In the present study, one novel gene cluster coding lantibiotic cerecidins was unveiled inBacillus cereusstrain As 1.1846 through genomic mining and PCR screening. The designatedcerlocus is different from that of conventional class II lantibiotics in that it included seven tandem precursorcerAgenes, one modification gene (cerM), two processing genes (cerTandcerP), one orphan regulator gene (cerR), and two immunity genes (cerFandcerE). In addition, one unprecedented quorum sensing component,comQXPA, was inserted betweencerMandcerR. The expression of cerecidins was not detected in this strain ofB. cereus, which might be due to repressed transcription ofcerM. We constitutively coexpressedcerAgenes andcerMinEscherichia coli, and purified precerecidins were proteolytically processed with the endoproteinase GluC and a truncated version of putative serine protease CerP. Thus, two natural variants of cerecidins A1 and A7 were obtained which contained two terminal nonoverlapping thioether rings rarely found in lantibiotics. Both cerecidins A1 and A7 were active against a broad spectrum of Gram-positive bacteria. Cerecidin A7, especially its mutant Dhb13A, showed remarkable efficacy against multidrug-resistantStaphylococcus aureus(MDRSA), vancomycin-resistantEnterococcus faecalis(VRE), and evenStreptomyces.

scholarly journals Quinupristin-Dalfopristin Resistance among Gram-Positive Bacteria in Taiwan

2000 ◽  
Vol 44 (12) ◽  
pp. 3374-3380 ◽  
Author(s):  
Kwen-Tay Luh ◽  
Po-Ren Hsueh ◽  
Lee-Jene Teng ◽  
Hui-Ju Pan ◽  
Yu-Chi Chen ◽  
...  
Keyword(s):  
Antimicrobial Agents ◽  
Animal Husbandry ◽  
Coagulase Negative Staphylococci ◽  
Gram Positive ◽  
In Vitro Susceptibility ◽  
Methicillin Resistant ◽  
Gram Positive Bacteria ◽  
Vancomycin Resistant ◽  
Viridans Group Streptococci

ABSTRACT To understand quinupristin-dalfopristin resistance among clinical isolates of gram-positive bacteria in Taiwan, where this agent is not yet available for clinical use, we evaluated 1,287 nonduplicate isolates recovered from January 1996 to December 1999 for in vitro susceptibility to quinupristin-dalfopristin and other newer antimicrobial agents. All methicillin-susceptible Staphylococcus aureus (MSSA) isolates were susceptible to quinupristin-dalfopristin. High rates of nonsusceptibility to quinupristin-dalfopristin (MICs, ≥2 μg/ml) were demonstrated for the following organisms: methicillin-resistant S. aureus (MRSA) (31%), coagulase-negative staphylococci (CoNS) (16%),Streptococcus pneumoniae (8%), viridans group streptococci (51%), vancomycin-susceptible enterococci (85%), vancomycin-resistantEnterococcus faecalis (100%), vancomycin-resistantEnterococcus faecium (66%), Leuconostoc spp. (100%), Lactobacillus spp. (50%), andPediococcus spp. (87%). All isolates of MSSA, MRSA,S. pneumoniae, and viridans group streptococci were susceptible to vancomycin and teicoplanin. The rates of nonsusceptibility to vancomycin and teicoplanin were 5 and 7%, respectively, for CoNS, ranging from 12 and 18% for S. simulans to 0 and 0% for S. cohnii and S. auricularis. Moxifloxacin and trovafloxacin had good activities against these isolates except for ciprofloxacin-resistant vancomycin-resistant enterococci and methicillin-resistant staphylococci. In Taiwan, virginiamycin has been used in animal husbandry for more than 20 years, which may contribute to the high rates of quinupristin-dalfopristin resistance.

scholarly journals In Vitro Activities of a New Ketolide, ABT-773, against Multidrug-Resistant Gram-Positive Cocci

2001 ◽  
Vol 45 (12) ◽  
pp. 3640-3643 ◽  
Author(s):  
Kavindra V. Singh ◽  
Kumthorn Malathum ◽  
Barbara E. Murray
Keyword(s):  
Staphylococcus Aureus ◽  
Enterococcus Faecium ◽  
Multidrug Resistant ◽  
Gram Positive ◽  
Methicillin Resistant ◽  
Gram Positive Bacteria ◽  
Vancomycin Resistant ◽  
Almost All ◽  
Gram Positive Cocci

ABSTRACT The in vitro activities of ABT-773 were evaluated against 324 strains of gram-positive bacteria, including multidrug-resistantStaphylococcus spp. and Enterococcus spp. ABT-773 had lower MIC ranges, MICs at which 50% of isolates are inhibited (MIC50s), and MIC90s than erythromycin or clindamycin for almost all isolates tested. The MICs of ABT-773 were also lower than those of quinupristin-dalfopristin (Q-D) for methicillin-susceptible Staphylococcus aureus,Rhodococcus spp., and Streptococcus spp., while the MICs of Q-D were lower than those of ABT-773 for methicillin-resistant S. aureus and Enterococcus faecium, including vancomycin-resistant isolates.

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