In-vitro and in-vivo antibacterial activity of imipenem against clinical isolates of bacteria

1983 ◽  
Vol 12 (suppl D) ◽  
pp. 53-64 ◽  
Author(s):  
S. Mitsuhashi
Keyword(s):  
Antibacterial Activity ◽  
Clinical Isolates

scholarly journals The Multifunctional Sactipeptide Ruminococcin C1 Displays Potent Antibacterial Activity In Vivo as Well as Other Beneficial Properties for Human Health

2021 ◽  
Vol 22 (6) ◽  
pp. 3253
Author(s):  
Clarisse Roblin ◽  
Steve Chiumento ◽  
Cédric Jacqueline ◽  
Eric Pinloche ◽  
Cendrine Nicoletti ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Human Health ◽  
Biological Activities ◽  
Resistant Bacteria ◽  
Modified Peptides ◽  
The 1960S ◽  
Conventional Antibiotics ◽  
Clinical Potential

The world is on the verge of a major antibiotic crisis as the emergence of resistant bacteria is increasing, and very few novel molecules have been discovered since the 1960s. In this context, scientists have been exploring alternatives to conventional antibiotics, such as ribosomally synthesized and post-translationally modified peptides (RiPPs). Interestingly, the highly potent in vitro antibacterial activity and safety of ruminococcin C1, a recently discovered RiPP belonging to the sactipeptide subclass, has been demonstrated. The present results show that ruminococcin C1 is efficient at curing infection and at protecting challenged mice from Clostridium perfringens with a lower dose than the conventional antibiotic vancomycin. Moreover, antimicrobial peptide (AMP) is also effective against this pathogen in the complex microbial community of the gut environment, with a selective impact on a few bacterial genera, while maintaining a global homeostasis of the microbiome. In addition, ruminococcin C1 exhibits other biological activities that could be beneficial for human health, as well as other fields of applications. Overall, this study, by using an in vivo infection approach, confirms the antimicrobial clinical potential and highlights the multiple functional properties of ruminococcin C1, thus extending its therapeutic interest.

scholarly journals 1293. Sulbactam-durlobactam is active against recent, multi-drug resistant Acinetobacter baumannii clinical isolates from the Middle East

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S662-S662
Author(s):  
Alita Miller ◽  
Sarah McLeod ◽  
Samir Moussa ◽  
Meredith Hackel
Keyword(s):  
Antibacterial Activity ◽  
Middle East ◽  
Acinetobacter Baumannii ◽  
United Arab Emirates ◽  
Blood Stream ◽  
Multidrug Resistant ◽  
Clinical Isolates ◽  
Surveillance Systems ◽  
Spectrum Activity

Abstract Background The incidence of infections caused by multidrug-resistant (MDR) Acinetobacter baumannii (Ab) is increasing at an alarming rate in certain regions of the world, including the Middle East. Sulbactam (SUL) has intrinsic antibacterial activity against Ab; however, the prevalence of β-lactamases in Ab has limited its therapeutic utility. Durlobactam (DUR, formerly ETX2514) is a diazabicyclooctenone β-lactamase inhibitor with broad-spectrum activity against Ambler class A, C and D β-lactamases that restores SUL activity in vitro against MDR Ab. SUL-DUR is an antibiotic designed to treat serious infections caused by Acinetobacter, including multidrug-resistant strains, that is currently in Phase 3 clinical development. In global surveillance studies of >3600 isolates from 2012-2017, the MIC90 of SUL-DUR was 2 mg/L. Although surveillance systems to monitor MDR infections in the Middle East are currently being established, quantitative, prevalence-based data are not yet available. Therefore, the potency of SUL-DUR was determined against 190 recent, diverse Ab clinical isolates from this region. Methods 190 Ab isolates were collected between 2016 - 2018 from medical centers located in Israel (N = 47), Jordan (N = 36), Qatar (N = 13), Kuwait (N = 42), Lebanon (N = 8), Saudi Arabia (N = 24) and United Arab Emirates (N = 20). Seventy-five percent and 20.5% of these isolates were from respiratory and blood stream infections, respectively. Susceptibility to SUL-DUR and comparator agents was performed according to CLSI guidelines, and data analysis was performed using CLSI and EUCAST breakpoint criteria where available. Results This collection of isolates was 86% carbapenem-resistant and 90% sulbactam-resistant (based on a breakpoint of 4 mg/L). The addition of SUL-DUR (fixed at 4 mg/L) decreased the sulbactam MIC90 from 64 mg/L to 4 mg/L. Only 3 isolates (1.6%) had SUL-DUR MIC values of > 4 mg/L. This potency was consistent across countries, sources of infection and subsets of resistance phenotypes. Conclusion SUL-DUR demonstrated potent antibacterial activity against recent clinical isolates of Ab from the Middle East, including MDR isolates. These data support the global development of SUL-DUR for the treatment of MDR Ab infections. Disclosures Alita Miller, PhD, Entasis Therapeutics (Employee) Sarah McLeod, PhD, Entasis Therapeutics (Employee) Samir Moussa, PhD, Entasis Therapeutics (Employee)

scholarly journals Efficacy of a novel lantibiotic, CMB001, against MRSA

2021 ◽  
Author(s):  
Jerzy Karczewski ◽  
Christine M Brown ◽  
Yukari Maezato ◽  
Stephen P Krasucki ◽  
Stephen J Streatfield
Keyword(s):  
Antibacterial Activity ◽  
Pharmacokinetic Analysis ◽  
Maximum Tolerable Dose ◽  
In Vivo Efficacy ◽  
Clostridioides Difficile ◽  
Alternative Treatment Option ◽  
Significant Damage ◽  
Tolerable Dose

Abstract Objectives To evaluate the efficacy of a novel lantibiotic, CMB001, against MRSA biofilms in vitro and in an in vivo experimental model of bacterial infection. Methods Antibacterial activity of CMB001 was measured in vitro after its exposure to whole blood or to platelet-poor plasma. In vitro efficacy of CMB001 against a Staphylococcus aureus biofilm was studied using scanning electron microscopy. The maximum tolerable dose in mice was determined and a preliminary pharmacokinetic analysis for CMB001 was performed in mice. In vivo efficacy was evaluated in a neutropenic mouse thigh model of infection. Results CMB001 maintained its antibacterial activity in the presence of blood or plasma for up to 24 h at 37°C. CMB001 efficiently killed S. aureus within the biofilm by causing significant damage to the bacterial cell wall. The maximum tolerable dose in mice was established to be 10 mg/kg and could be increased to 30 mg/kg in mice pretreated with antihistamines. In neutropenic mice infected with MRSA, treatment with CMB001 reduced the bacterial burden with an efficacy equivalent to that of vancomycin. Conclusions CMB001 offers potential as an alternative treatment option to combat MRSA. It will be of interest to evaluate the in vivo efficacy of CMB001 against infections caused by other pathogens, including Clostridioides difficile and Acinetobacter baumannii, and to expand its pharmacokinetic/pharmacodynamic parameters and safety profile.

scholarly journals C3 Promotes Clearance of Klebsiella pneumoniae by A549 Epithelial Cells

2004 ◽  
Vol 72 (3) ◽  
pp. 1767-1774 ◽  
Author(s):  
Beatriz de Astorza ◽  
Guadalupe Cortés ◽  
Catalina Crespí ◽  
Carles Saus ◽  
José María Rojo ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Klebsiella Pneumoniae ◽  
Alveolar Epithelial Cells ◽  
Clinical Isolates ◽  
Complement Components ◽  
Innate Defense ◽  
Alveolar Epithelial

ABSTRACT The airway epithelium represents a primary site for contact between microbes and their hosts. To assess the role of complement in this event, we studied the interaction between the A549 cell line derived from human alveolar epithelial cells and a major nosocomial pathogen, Klebsiella pneumoniae, in the presence of serum. In vitro, we found that C3 opsonization of poorly encapsulated K. pneumoniae clinical isolates and an unencapsulated mutant enhanced dramatically bacterial internalization by A549 epithelial cells compared to highly encapsulated clinical isolates. Local complement components (either present in the human bronchoalveolar lavage or produced by A549 epithelial cells) were sufficient to opsonize K. pneumoniae. CD46 could competitively inhibit the internalization of K. pneumoniae by the epithelial cells, suggesting that CD46 is a receptor for the binding of complement-opsonized K. pneumoniae to these cells. We observed that poorly encapsulated strains appeared into the alveolar epithelial cells in vivo but that (by contrast) they were completely avirulent in a mouse model of pneumonia compared to the highly encapsulated strains. Our results show that bacterial opsonization by complement enhances the internalization of the avirulent microorganisms by nonphagocytic cells such as A549 epithelial cells and allows an efficient innate defense.

scholarly journals Carbapenem-Resistant Klebsiella pneumoniae Clinical Isolates: In Vivo Virulence Assessment in Galleria mellonella and Potential Therapeutics by Polycationic Oligoethyleneimine

Antibiotics ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 56
Author(s):  
Dalila Mil-Homens ◽  
Maria Martins ◽  
José Barbosa ◽  
Gabriel Serafim ◽  
Maria J. Sarmento ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Galleria Mellonella ◽  
Multidrug Resistant ◽  
In Vitro Models ◽  
Clinical Isolates ◽  
In Vivo Model ◽  
Virulence Potential ◽  
Hospital Acquired

Klebsiella pneumoniae, one of the most common pathogens found in hospital-acquired infections, is often resistant to multiple antibiotics. In fact, multidrug-resistant (MDR) K. pneumoniae producing KPC or OXA-48-like carbapenemases are recognized as a serious global health threat. In this sense, we evaluated the virulence of K. pneumoniae KPC(+) or OXA-48(+) aiming at potential antimicrobial therapeutics. K. pneumoniae carbapenemase (KPC) and the expanded-spectrum oxacillinase OXA-48 isolates were obtained from patients treated in medical care units in Lisbon, Portugal. The virulence potential of the K. pneumonia clinical isolates was tested using the Galleria mellonella model. For that, G. mellonella larvae were inoculated using patients KPC(+) and OXA-48(+) isolates. Using this in vivo model, the KPC(+) K. pneumoniae isolates showed to be, on average, more virulent than OXA-48(+). Virulence was found attenuated when a low bacterial inoculum (one magnitude lower) was tested. In addition, we also report the use of a synthetic polycationic oligomer (L-OEI-h) as a potential antimicrobial agent to fight infectious diseases caused by MDR bacteria. L-OEI-h has a broad-spectrum antibacterial activity and exerts a significantly bactericidal activity within the first 5-30 min treatment, causing lysis of the cytoplasmic membrane. Importantly, the polycationic oligomer showed low toxicity against in vitro models and no visible cytotoxicity (measured by survival and health index) was noted on the in vivo model (G. mellonella), thus L-OEI-h is foreseen as a promising polymer therapeutic for the treatment of MDR K. pneumoniae infections.

scholarly journals In vivo and in vitro antibacterial activity of neomycin against plant pathogenic bacteria

2011 ◽  
Vol 6 (34) ◽  
pp. 6829-6834, ◽  
Author(s):  
Tao Ke ◽  
Fan Jieyu ◽  
Shi Guanying ◽  
Zhang Xingang ◽  
Zhao Haoyu ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Pathogenic Bacteria ◽  
Plant Pathogenic Bacteria ◽  
In Vitro Antibacterial Activity

scholarly journals In vitro antibacterial activity and in vivo therapeutic effect of Sesbania grandiflora in bacterial infected silkworms

2017 ◽  
Vol 55 (1) ◽  
pp. 1256-1262 ◽  
Author(s):  
Pimporn Anantaworasakul ◽  
Hiroshi Hamamoto ◽  
Kazuhisa Sekimizu ◽  
Siriporn Okonogi
Keyword(s):  
Antibacterial Activity ◽  
Therapeutic Effect ◽  
Sesbania Grandiflora ◽  
In Vitro Antibacterial Activity

scholarly journals In vitro and in vivo evaluation of antibacterial activity of Bridelia ferruginea extracts on some clinical isolates

2018 ◽  
Vol 7 (4) ◽  
pp. 392-398
Author(s):  
B.T Yunana ◽  
◽  
B. B Bukar ◽  
J. C Aguiyi ◽  
◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Staphylococcus Aureus ◽  
Antibacterial Activity ◽  
Bark Extract ◽  
Root Extract ◽  
Root Bark ◽  
Zone Of Inhibition ◽  
Bridelia Ferruginea

The ethanol extracts of root, bark and leaf of Bridelia ferruginea was investigated for antibacterial activity against clinical isolate of Staphylococcus aureus and Escherichia coli. The extracts had significant antibacterial activity in vitro at concentration of 25 mg/ml, 50 mg/ml, 100 mg/ml and 200 mg/ml and in vivo at dose of 50 mg/kg and 100 mg/kg. The root extract in vitro had the highest zone of inhibition, followed by the bark extract for both Staphylococcus aureus and Escherichia coli. The concentration of 200 mg/ml had the highest zone of inhibition in vitro. The minimum inhibitory concentration (MIC) showed a decreasing inhibitory effect of the plant extracts for both Staphylococcus aureus and Escherichia coli as the concentration decreases with root having 3.125 mg/ml, bark having 6.25 mg/ml and leaf having 25 mg/ml for Staphylococcus aureus and Escherichia coli. Likewise, the minimum bactericidal concentration (MBC) showed decreasing bactericide effects with decrease concentration with root having 12.5 mg/ml, bark having 12.5 mg/ml and leaf having 25 mg/ml for Escherichia coli while root had 6.25mg/ml, bark had 12.5mg/ml and leaf had 25mg/ml for Staphylococcus aureus. The in vivo investigation showed that the root and bark extract exhibited antibacterial activity on both Staphylococcus aureus and Escherichia coli at doses of 100mg/kg and 50mg/kg; the root extract had higher activity than the bark and root/bark combined. The dose of 100 mg/kg had the highest colonies reduction for Staphylococcus aureus and Escherichia coli in vivo. Preliminary phytochemical screening of root, bark and leaves of Bridelia ferruginea revealed the presence of tannins, flavonoids, carbohydrates, cardiac glycoside (root, bark and leaves), saponins (root and bark). The presence of tannins, saponins, flavonoid, cardiac glycoside and carbohydrate in the bark and root extracts of the plant indicates that the bark and root extracts were pharmacological importance

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