In vitro assessment of antibacterial activity of Salicornia herbacea L. seed extracts against multidrug resistant grampositive and gram-negative bacteria

ABSTRACT Cefiderocol (S-649266) is a novel siderophore cephalosporin with potent in vitro activity against clinically encountered multidrug-resistant (MDR) Gram-negative isolates; however, its spectrum of antibacterial activity against these difficult-to-treat isolates remains to be fully explored in vivo. Here, we evaluated the efficacy of cefiderocol humanized exposures in a neutropenic murine thigh model to support a suitable MIC breakpoint. Furthermore, we compared cefiderocol's efficacy with humanized exposures of meropenem and cefepime against a subset of these phenotypically diverse isolates. Ninety-five Gram-negative isolates were studied. Efficacy was determined as the change in log10 CFU at 24 h compared with 0-h controls. Bacterial stasis or ≥1 log reduction in 67 isolates with MICs of ≤4 μg/ml was noted in 77, 88, and 85% of Enterobacteriaceae, Acinetobacter baumannii, and Pseudomonas aeruginosa, respectively. For isolates with MICs of ≥8 μg/ml, bacterial stasis or ≥1 log10 reduction was observed in only 2 of 28 (8 Enterobacteriaceae, 19 A. baumannii, and 1 P. aeruginosa) strains. Against highly resistant meropenem and cefepime organisms, cefiderocol maintained its in vivo efficacy. Overall, humanized exposures of cefiderocol produced similar reductions in bacterial density for organisms with MICs of ≤4 μg/ml, whereas isolates with MICs of ≥8 μg/ml generally displayed bacterial growth in the presence of the compound. Data derived in the current study will assist with the delineation of MIC susceptibility breakpoints for cefiderocol against these important nosocomial Gram-negative pathogens; however, additional clinical data are required to substantiate these observations.

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Microbial Enzymatic Synthesis of Amikacin Analogs With Antibacterial Activity Against Multidrug-Resistant Pathogens

Frontiers in Microbiology ◽

10.3389/fmicb.2021.725916 ◽

2021 ◽

Vol 12 ◽

Author(s):

Yeon Hee Ban ◽

Myoung Chong Song ◽

Joong Ho Jeong ◽

Min Seok Kwun ◽

Chang Rae Kim ◽

...

Keyword(s):

Antibacterial Activity ◽

Resistance Mechanism ◽

Multidrug Resistant ◽

Amino Group ◽

Gram Negative Bacteria ◽

Gram Negative ◽

Structural Modifications ◽

New Antibiotics ◽

Pharmacological Potential

With the constant emergence of multidrug-resistant gram-negative bacteria, interest in the development of new aminoglycoside (AG) antibiotics for clinical use has increased. The regioselective modification of AG scaffolds could be an efficient approach for the development of new antibiotics with improved therapeutic potency. We enzymatically synthesized three amikacin analogs containing structural modifications in the amino groups and evaluated their antibacterial activity and cytotoxicity. Among them, 6′-N-acyl-3″-N-methylated analogs showed improved antibacterial activity against the multidrug-resistant gram-negative bacteria tested, while exhibiting reduced in vitro nephrotoxicity compared to amikacin. This study demonstrated that the modifications of the 6′-amino group as well as the 3″-amino group have noteworthy advantages for circumventing the AG-resistance mechanism. The regiospecific enzymatic modification could be exploited to develop novel antibacterial agents with improved pharmacological potential.

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In Vitro antibacterial activity of lactic acid bacteria isolated from goatâ€™s raw milk of Mostaganem (West Algeria) against Gram negative bacteria responsible for urinary tract infections

South Asian Journal of Experimental Biology ◽

10.38150/sajeb.6(1).p15-22 ◽

2016 ◽

Vol 6 (1) ◽

pp. 15-22

Author(s):

Zergoug Amina ◽

Cheriguene Abderrahim ◽

Chougrani Fadela

Keyword(s):

Antibacterial Activity ◽

Lactic Acid ◽

Urinary Tract ◽

Lactic Acid Bacteria ◽

Raw Milk ◽

Gram Negative Bacteria ◽

Gram Negative ◽

Tract Infections ◽

West Algeria

Urinary tract infections (UTI) are a serious bacterial pathological challenges all over the world, leading to respiratory infections, that’s why new strategies don’t cease to develop. Lactic acid bacteria having shown beneficial effects for years in various areas, may prove to be excellent candidates in medical field. The current research focused on the selection of lactic acid bacteria having the potential of an antibacterial activity against Gram negative bacteria responsible for UTI, for an eventual use as a therapeutic agent. A total of 40 isolates were isolated from goat’s raw milk of Mostaganem (West Algeria). In vitro tests were conducted in order to determine the efficiency of the isolates to produce antibacterial agents in interaction with uropathogens. Among 40 isolates, only 10 isolates identified as Lactobacilli and Lactococci were performant. The Screening showed that the inhibitor agent was proteinaceous substance. Therfore, it is noted that a treatment with presence of LAB is very encouraging as a result of the production of bacteriocin-like substance. On the other hand, LAB can be considered as a good alter-native to the large extent to the antibiotics in the treatment of UTI.

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Case Commentary: the Need for Cefiderocol Is Clear, but Are the Supporting Clinical Data?

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00059-20 ◽

2020 ◽

Vol 64 (4) ◽

Cited By ~ 4

Author(s):

Ryan K. Shields

Keyword(s):

Clinical Trials ◽

Clinical Practice ◽

Salvage Therapy ◽

Randomized Clinical Trials ◽

Treatment Options ◽

Multidrug Resistant ◽

Gram Negative Bacteria ◽

Potential Utility ◽

Gram Negative

ABSTRACT Cefiderocol is a newly approved siderophore cephalosporin that demonstrates expanded in vitro activity against multidrug-resistant Gram-negative bacteria. In two challenging cases reported here, cefiderocol shows potential utility as salvage therapy against difficult-to-treat pathogens with limited or no treatment options; however, two multicenter, randomized clinical trials have yielded mixed results among cefiderocol-treated patients. Taken together, clinicians must balance a clear need for cefiderocol in clinical practice with the uncertainties that have stemmed from the available data.

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Chemical Composition and in Vitro Antibacterial Activity of the Essential Oil of Minthostachys Mollis (Kunth) Griseb Vaught from the Venezuelan Andes

Natural Product Communications ◽

10.1177/1934578x0900400726 ◽

2009 ◽

Vol 4 (7) ◽

pp. 1934578X0900400 ◽

Cited By ~ 2

Author(s):

Flor D. Mora ◽

María Araque ◽

Luis B. Rojas ◽

Rosslyn Ramírez ◽

Bladimiro Silva ◽

...

Keyword(s):

Antibacterial Activity ◽

Essential Oil ◽

Chemical Constituents ◽

Salmonella Typhi ◽

Inhibitory Effect ◽

Gram Negative Bacteria ◽

Gram Negative ◽

Significant Inhibitory Effect ◽

In Vitro Antibacterial Activity

Chemical constituents of the essential oil from the leaves of Minthostachys mollis (Kunth) Griseb Vaught var. mollis collected in January 2008 at Tuñame, Trujillo State, Venezuela, were separated and identified by GCMS analysis. The essential oil was obtained by hydrodistillation and thirteen components (98.5% of the sample) were identified by comparison with the Wiley GCMS library data base. The two major components were pulegone (55.2%) and trans-menthone (31.5%). The essential oil showed a significant inhibitory effect against Gram-positive and Gram-negative bacteria, especially Bacillus subtilis and Salmonella typhi (4 μg/mL).

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Antibacterial Activity and Chemical Composition of the Essential Oil of Grammosciadium platycarpum Boiss. from Iran

Zeitschrift für Naturforschung C ◽

10.1515/znc-2005-1-206 ◽

2005 ◽

Vol 60 (1-2) ◽

pp. 30-34 ◽

Cited By ~ 26

Author(s):

Ali Sonboli ◽

Fereshteh Eftekhar ◽

Morteza Yousefzadi ◽

Mohammad Reza Kanani

Keyword(s):

Pseudomonas Aeruginosa ◽

Antibacterial Activity ◽

Chemical Composition ◽

Essential Oil ◽

Essential Oils ◽

Antibacterial Activities ◽

Gram Negative Bacteria ◽

Gram Negative ◽

Two Samples

The chemical composition of the essential oils obtained from two samples (GP1 and GP2) of Grammosciadium platycarpum Boiss. was analyzed by GC and GC-MS. The analysis of the oils resulted in the identification of twenty-two constituents. Linalool (79.0% - GP1, 81.8% - GP2) and limonene (10.0%, 5.8%) were found to be the major components, respectively. The in vitro antibacterial activities of these oils and their main compounds against seven Gram-positive and Gram-negative bacteria were investigated. The results exhibited that the total oils and their major components possess strong to moderate activities against all the tested bacteria except for Pseudomonas aeruginosa.

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

mBio ◽

10.1128/mbio.00674-17 ◽

2017 ◽

Vol 8 (4) ◽

Cited By ~ 13

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.

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Clinical Experience of Colistin-Glycopeptide Combination in Critically Ill Patients Infected with Gram-Negative Bacteria

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00871-13 ◽

2013 ◽

Vol 58 (2) ◽

pp. 851-858 ◽

Cited By ~ 62

Author(s):

Nicola Petrosillo ◽

Maddalena Giannella ◽

Massimo Antonelli ◽

Mario Antonini ◽

Bruno Barsic ◽

...

Keyword(s):

Protective Factor ◽

Multidrug Resistant ◽

Gram Negative Bacteria ◽

Gram Negative ◽

Content Type ◽

Carbapenem Resistant ◽

Causative Agents ◽

Treatment Onset ◽

Cox Analysis

ABSTRACTA colistin-glycopeptide combination (CGC) has been shownin vitroto be synergistic against multidrug-resistant Gram-negative bacteria (MDR GNB), especiallyAcinetobacter baumannii, and to prevent further resistance. However, clinical data are lacking. We carried out a retrospective multicenter study of patients hospitalized in intensive care units (ICUs) who received colistin for GNB infection over a 1-year period, to assess the rates of nephrotoxicity and 30-day mortality after treatment onset among patients treated with and without CGC for ≥48 h. Of the 184 patients treated with colistin, GNB infection was documented for 166. The main causative agents were MDRA. baumannii(59.6%), MDRPseudomonas aeruginosa(18.7%), and carbapenem-resistantKlebsiella pneumoniae(14.5%); in 16.9% of patients, a Gram-positive bacterium (GPB) coinfection was documented. Overall, 68 patients (40.9%) received CGC. Comparison of patients treated with and without CGC showed significant differences for respiratory failure (39.7% versus 58.2%), ventilator-associated pneumonia (54.4% versus 71.4%), MDRA. baumanniiinfection (70.6% versus 52%), and GPB coinfection (41.2% versus 0%); there were no differences for nephrotoxicity (11.8% versus 13.3%) and 30-day mortality (33.8% versus 29.6%). Cox analysis performed on patients who survived for ≥5 days after treatment onset showed that the Charlson index (hazard ratio [HR], 1.26; 95% confidence interval [CI], 1.01 to 1.44;P= 0.001) and MDRA. baumanniiinfection (HR, 2.51; 95% CI, 1.23 to 5.12;P= 0.01) were independent predictors of 30-day mortality, whereas receiving CGC for ≥5 days was a protective factor (HR, 0.42; 95% CI, 0.19 to 0.93;P= 0.03). We found that CGC was not associated with higher nephrotoxicity and was a protective factor for mortality if administered for ≥5 days.

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