Novel Compound from Flowers of Moringa oleifera Active Against Multi- Drug Resistant Gram-negative Bacilli

2020 ◽  
Vol 20 (1) ◽  
pp. 69-75
Author(s):  
Santi M. Mandal ◽  
Subhanil Chakraborty ◽  
Santanu Sahoo ◽  
Smritikona Pyne ◽  
Samaresh Ghosh ◽  
...  
Keyword(s):  
Acetic Acid ◽  
Moringa Oleifera ◽  
Aqueous Acetic Acid ◽  
Phytochemical Analysis ◽  
Hydroxyl Groups ◽  
Drug Resistant ◽  
Gram Negative ◽  
Isolated Compound ◽  
Conventional Antibiotics

Background: The need for suitable antibacterial agents effective against Multi-drug resistant Gram-negative bacteria is acknowledged globally. The present study was designed to evaluate the possible antibacterial potential of an extracted compound from edible flowers of Moringa oleifera. Methods: Five different solvents were used for preparing dried flower extracts. The most effective extract was subjected to fractionation and further isolation of the active compound with the highest antibacterial effect was obtained using TLC, Column Chromatography and reverse phase- HPLC. Approaches were made for characterization of the isolated compound using FTIR, NMR and Mass spectrometry. Antibacterial activity was evaluated according to the CLSI guidelines. Results: One fraction of aqueous acetic acid extract of M. oleifera flower was found highly effective and more potent than conventional antibiotics of different classes against Multi-drug resistant Gram-negative bacilli (MDR-GNB) when compared. The phytochemical analysis of the isolated compound revealed the presence of hydrogen-bonded amine and hydroxyl groups attributable to unsaturated amides. Conclusion: The present study provided data indicating a potential for use of the flowers extract of M. oleifera in the fight against infections caused by lethal MDR-GNB. Recommendations: Aqueous acetic acid flower extract of M. oleifera is effective, in-vitro, against Gram-negative bacilli. This finding may open a scope in pharmaceutics for the development of new classes of antibiotics.

scholarly journals In Vitro Activity of Imipenem-Relebactam and Ceftolozane-Tazobactam against Resistant Gram-Negative Bacilli

2018 ◽  
Vol 62 (8) ◽  
Author(s):  
Suzannah M. Schmidt-Malan ◽  
Avisya J. Mishra ◽  
Ammara Mushtaq ◽  
Cassandra L. Brinkman ◽  
Robin Patel
Keyword(s):  
Antimicrobial Agents ◽  
Empirical Therapy ◽  
Drug Resistant ◽  
Rapid Diagnostics ◽  
In Vitro Activity ◽  
Gram Negative ◽  
Content Type ◽  
Inhibitor Combination ◽  
Selection Of

ABSTRACT Understanding which antimicrobial agents are likely to be active against Gram-negative bacilli can guide selection of antimicrobials for empirical therapy as mechanistic rapid diagnostics are adopted. In this study, we determined the MICs of a novel β-lactam–β-lactamase inhibitor combination, imipenem-relebactam, along with ceftolozane-tazobactam, imipenem, ertapenem, meropenem, ceftriaxone, and cefepime, against 282 drug-resistant isolates of Gram-negative bacilli. For isolates harboring blaKPC (n = 110), the addition of relebactam to imipenem lowered the MIC50/MIC90 from 16/>128 μg/ml for imipenem alone to 0.25/1 μg/ml. For isolates harboring blaCTX-M (n = 48), the MIC50/MIC90 of ceftolozane-tazobactam were 0.5/16 μg/ml (83% susceptible). For isolates harboring blaCMY-2 (n = 17), the MIC50/MIC90 of ceftolozane-tazobactam were 4/8 μg/ml (47% susceptible). Imipenem-relebactam was active against most KPC-producing (but not NDM- or IMP-producing) Enterobacteriaceae and is an encouraging addition to the present antibiotic repertoire.

Rifampicin

1970 ◽  
Vol 8 (3) ◽  
pp. 11-12
Keyword(s):  
Messenger Rna ◽  
Viral Infections ◽  
Drug Resistant ◽  
Gram Positive ◽  
Gram Negative ◽  
Low Concentrations ◽  
Resistant Mutants ◽  
Gram Negative Organisms

Rifampicin (Rifadin-Lepetit; Rimactane-Ciba) is a semi-synthetic antibiotic derived from Streptomyces mediterranei which inhibits the synthesis of bacterial messenger-RNA. In vitro it is active against Gram-positive organisms and mycobacteria in low concentrations (0.0002 – 0.5 mcg/ml); and against Gram-negative organisms in higher concentrations (1 – 10 mcg/ml). Drug-resistant mutants readily emerge if rifampicin is used alone.1 It is already established as an important agent in the treatment of tuberculosis. Its usefulness in other bacterial and in viral infections is uncertain.

scholarly journals Curative Treatment of Severe Gram-Negative Bacterial Infections by a New Class of Antibiotics Targeting LpxC

mBio ◽  
2017 ◽  
Vol 8 (4) ◽  
Author(s):  
Nadine Lemaître ◽  
Xiaofei Liang ◽  
Javaria Najeeb ◽  
Chul-Jin Lee ◽  
Marie Titecat ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Biosynthetic Pathway ◽  
Lipid A ◽  
Multidrug Resistant ◽  
Gram Negative Bacteria ◽  
Drug Resistant ◽  
Bubonic Plague ◽  
Gram Negative ◽  
New Class

ABSTRACT The infectious diseases caused by multidrug-resistant bacteria pose serious threats to humankind. It has been suggested that an antibiotic targeting LpxC of the lipid A biosynthetic pathway in Gram-negative bacteria is a promising strategy for curing Gram-negative bacterial infections. However, experimental proof of this concept is lacking. Here, we describe our discovery and characterization of a biphenylacetylene-based inhibitor of LpxC, an essential enzyme in the biosynthesis of the lipid A component of the outer membrane of Gram-negative bacteria. The compound LPC-069 has no known adverse effects in mice and is effective in vitro against a broad panel of Gram-negative clinical isolates, including several multiresistant and extremely drug-resistant strains involved in nosocomial infections. Furthermore, LPC-069 is curative in a murine model of one of the most severe human diseases, bubonic plague, which is caused by the Gram-negative bacterium Yersinia pestis. Our results demonstrate the safety and efficacy of LpxC inhibitors as a new class of antibiotic against fatal infections caused by extremely virulent pathogens. The present findings also highlight the potential of LpxC inhibitors for clinical development as therapeutics for infections caused by multidrug-resistant bacteria. IMPORTANCE The rapid spread of antimicrobial resistance among Gram-negative bacilli highlights the urgent need for new antibiotics. Here, we describe a new class of antibiotics lacking cross-resistance with conventional antibiotics. The compounds inhibit LpxC, a key enzyme in the lipid A biosynthetic pathway in Gram-negative bacteria, and are active in vitro against a broad panel of clinical isolates of Gram-negative bacilli involved in nosocomial and community infections. The present study also constitutes the first demonstration of the curative treatment of bubonic plague by a novel, broad-spectrum antibiotic targeting LpxC. Hence, the data highlight the therapeutic potential of LpxC inhibitors against a wide variety of Gram-negative bacterial infections, including the most severe ones caused by Y. pestis and by multidrug-resistant and extensively drug-resistant carbapenemase-producing strains. IMPORTANCE The rapid spread of antimicrobial resistance among Gram-negative bacilli highlights the urgent need for new antibiotics. Here, we describe a new class of antibiotics lacking cross-resistance with conventional antibiotics. The compounds inhibit LpxC, a key enzyme in the lipid A biosynthetic pathway in Gram-negative bacteria, and are active in vitro against a broad panel of clinical isolates of Gram-negative bacilli involved in nosocomial and community infections. The present study also constitutes the first demonstration of the curative treatment of bubonic plague by a novel, broad-spectrum antibiotic targeting LpxC. Hence, the data highlight the therapeutic potential of LpxC inhibitors against a wide variety of Gram-negative bacterial infections, including the most severe ones caused by Y. pestis and by multidrug-resistant and extensively drug-resistant carbapenemase-producing strains.

scholarly journals In vitro antimicrobial activity of five essential oils on multi-drug resistant Gram-negative clinical isolates

2016 ◽  
Vol 5 (3) ◽  
pp. 212 ◽  
Author(s):  
Hercules Sakkas ◽  
Panagiota Gousia ◽  
Vangelis Economou ◽  
Vassilios Sakkas ◽  
Stefanos Petsios ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Essential Oils ◽  
Clinical Isolates ◽  
Drug Resistant ◽  
Gram Negative ◽  
In Vitro Antimicrobial Activity

scholarly journals In Vitro Activity of Cefiderocol against Multi-Drug Resistant Carbapenemase-Producing Gram-Negative Pathogens

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S376-S376 ◽  
Author(s):  
Sandra Boyd ◽  
Karen Anderson ◽  
Valerie Albrecht ◽  
Davina Campbell ◽  
Maria S Karlsson ◽  
...  
Keyword(s):  
Vitro Activity ◽  
Burkholderia Cepacia Complex ◽  
Uptake System ◽  
Drug Resistant ◽  
In Vitro Activity ◽  
Gram Negative ◽  
Class A ◽  
Class D ◽  
Class B

Abstract Background Few options remain for treatment of infections caused by multi-drug resistant (MDR), carbapenemase-producing gram-negative pathogens. Cefiderocol (CFDC; Shionogi & Co. Ltd), is a novel parenteral siderophore cephalosporin that enters the bacterial cell through the iron–siderophore uptake system. Here we report on the in vitro activity of CFDC against a set of well-characterized MDR gram-negative isolates collected by the Centers for Disease Control and Prevention. Methods Minimum inhibitory concentrations (MIC) values for CFDC in iron-depleted cation-adjusted Mueller Hinton broth were determined using reference broth microdilution. Study isolates (n = 315) included Enterobacteriaceae (59%), Pseudomonas aeruginosa (19%), Acinetobacter baumannii (17%), Stenotrophomonas maltophilia (4%), and Burkholderia cepacia complex (1%). Of these, 229 (73%) were carbapenemase-producers including Ambler Class A- (37%), Class B- (29%) and Class D- type (29%) enzymes. The remaining isolates included 51 β-lactam-resistant isolates that were non-carbapenemase-producers, and 35 β-lactam-susceptible isolates. Results were interpreted using suggested CFDC breakpoints of Sensitive ≤4 μg/mL and Resistant ≥16 μg/mL. Results The majority of the isolates (90.8%) were categorized as CFDC susceptible; the percentage of isolates with a CFDC MIC ≤4 μg/mL among Enterobacteriaceae, P. aeruginosa, and A. baumannii was 87.5%, 100%, and 89%, respectively. Percentage of isolates with a CFDC MIC ≤4 μg/mL that harbored a carbapenemase of the Class A-, Class B-, and Class D-type was 91.8%, 74.8%, 98.0%, respectively. By applying suggested breakpoints, 12 isolates were categorized as intermediate and 17 as resistant. The resistant isolates included 11 NDM-, 2 OXA-23- and 4 KPC-positive organisms. Conclusion Cefiderocol showed potent activity against MDR gram-negative pathogens including Class A, B, and D carbapenemase-producing isolates. Of note, all P. aeruginosa, including Class B metallo-β-lactamase producers, were susceptible to CFDC. Disclosures All authors: No reported disclosures.

scholarly journals Tristemma hirtumand Five Other Cameroonian Edible Plants with Weak or No Antibacterial Effects Modulate the Activities of Antibiotics against Gram-Negative Multidrug-Resistant Phenotypes

2018 ◽  
Vol 2018 ◽  
pp. 1-12
Author(s):  
Gaëlle S. Nguenang ◽  
Armelle T. Mbaveng ◽  
Aimé G. Fankam ◽  
Hermione T. Manekeng ◽  
Paul Nayim ◽  
...  
Keyword(s):  
Antibacterial Activities ◽  
Multidrug Resistant ◽  
Phytochemical Analysis ◽  
Edible Plants ◽  
Phytochemical Screening ◽  
Antibacterial Effects ◽  
Gram Negative ◽  
Microdilution Method ◽  
Raphia Hookeri

In order to contribute to the fight against infectious diseases, thein vitroantibacterial activity and the antibiotic-potentiating effects ofTristemma hirtumand five other Cameroonian edible plants have been evaluated against Gram-negative multidrug-resistant (MDR) phenotypes. The microdilution method was used to evaluate the bacterial susceptibility of the extracts and their combination to common antibiotics. The phytochemical screening of the extracts was carried out according to standard methods. Phytochemical analysis of the extracts revealed the presence of alkaloids, triterpenes, steroids, and polyphenols, including flavonoids in most of the tested extracts. The entire tested extracts showed moderate (512 μg/mL ≤ MIC ≤ 2048 μg/mL) to weak (MIC > 2048 μg/mL) antibacterial activities against the tested bacteria. Furthermore, extracts of leaf ofTristemma hirtumand pericarpsofRaphia hookeri(at their MIC/2 and MIC/4) strongly potentiated the activities of all antibiotics used in the study, especially those of chloramphenicol (CHL), ciprofloxacin (CIP), kanamycin (KAN), and tetracycline (TET) against 70% (7/10) to 100% (10/10) of the tested MDR bacteria, with the modulating factors ranging from 2 to 128. The results of this study suggest that extracts from leaves ofTristemma hirtumand pericarps ofRaphia hookerican be sources of plant-derived products with antibiotic modifying activity.

scholarly journals A3, a Scorpion Venom Derived Peptide Analogue with Potent Antimicrobial and Antibiofilm Activity against Clinical Isolates of Multi-Drug Resistant Gram Positive Bacteria

2018 ◽  
Author(s):  
Ammar Almaaytah ◽  
Ahmad Farajallah ◽  
Ahmad Abualhaijaa ◽  
Qosay Al-balas
Keyword(s):  
Host Defense ◽  
Mammalian Cells ◽  
Scorpion Venom ◽  
Clinical Isolates ◽  
Drug Resistant ◽  
Gram Positive ◽  
Peptide Analogue ◽  
Gram Positive Bacteria ◽  
Conventional Antibiotics

Current research in the field of antimicrobials is focused on the development of novel antibiotics and antimicrobial agents to counteract the huge dilemma that the human population is mainly facing in regards to the rise of bacterial resistance and biofilm infections. Host Defense peptides (HDPs) are a promising group of molecules for antimicrobial development as they share unique characteristics suitable for antimicrobial activity including their broad spectrum of activity and potency against bacteria. AamAP1 is a novel HDP that was identified through molecular cloning from the venom of the North African scorpion Androctonus amoeruxi. In vitro antimicrobial assays revealed that the peptide displays moderate activity against different strains of Gram-positive and Gram-negative bacteria. Additionally, the peptide proved to be highly hemolytic and displaying significantly high toxicity against mammalian cells. In our study, a novel synthetic peptide analogue named A3 was designed from the naturally occurring scorpion venom host defense peptide. The design strategy depended on modifying the amino acid sequence of the parent peptide in order to increase its net positive charge, percentage helicity and optimize other physico-chemical parameters involved theoretically in HDPs activity. Accordingly, A3 was evaluated for its in vitro antimicrobial and anti-biofilm activity individually and in combination with four different types of conventional antibiotics against clinical isolates of multi-drug resistant (MDR) Gram-positive bacteria. A3 was also evaluated for its cytotoxicity against mammalian cells. A3 displayed potent and selective in vitro antimicrobial activities against a wide range of MDR Gram-positive bacteria. Our results also showed that combining A3 with conventional antibiotics displayed a synergistic mode of action which resulted in decreasing the MIC value for A3 peptide as low as 0.125 µM. These effective concentrations were associated with negligible toxicities on mammalian cells. In conclusion, A3 exhibits enhanced activity and selectivity when compared with the parent natural scorpion venom peptide. The combination of A3 with conventional antibiotics may be pursued as a potential novel treatment strategy against MDR and biofilm forming bacteria.

scholarly journals Antimicrobial Essential Oil Formulation: Chitosan Coated Nanoemulsions for Nose to Brain Delivery

Pharmaceutics ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 678 ◽  
Author(s):  
Federica Rinaldi ◽  
Alessandra Oliva ◽  
Manuela Sabatino ◽  
Anna Imbriano ◽  
Patrizia N. Hanieh ◽  
...  
Keyword(s):  
Thymus Vulgaris ◽  
Syzygium Aromaticum ◽  
Drug Resistant ◽  
Bacterial Strains ◽  
Onset Of Action ◽  
Gram Negative ◽  
Efficient Delivery ◽  
Oil Formulation ◽  
The Brain

Brain infections as meningitis and encephalitis are attracting a great interest. Challenges in the treatment of these diseases are mainly represented by the blood brain barrier (BBB) that impairs the efficient delivery of even very potent drugs to reach the brain. The nose to the brain administration route, is a non-invasive alternative for a quick onset of action, and enables the transport of numerous medicinal agents straight to the brain thus workarounding the BBB through the highly vascularized olfactory region. In this report, Thymus vulgaris and Syzygium aromaticum essential oils (EOs) were selected to be included in chitosan coated nanoemulsions (NEs). The EOs were firstly analyzed to determine their chemical composition, then used to prepare NEs, that were deeply characterized in order to evaluate their use in intranasal administration. An in vitro evaluation against a collection of clinical isolated bacterial strains was carried out for both free and nanoemulsioned EOs. Chitosan coated NEs showed to be a potential and effective intranasal formulation against multi-drug resistant Gram-negative bacteria such as methicillin-susceptible Staphylococcus aureus and multi-drug resistant Gram-negative microorganisms including carbapenem-resistant Acinetobacter baumannii and Klebsiella pneumoniae.

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