Role of Artesunate in Potentiation of β-lactam Against Methicillin Resistant Staphylococcus aureus (MRSA) Isolated from Bovine Mastitis and its Histopathology Impact In-Vivo Study

2020 ◽  
Keyword(s):  
Clavulanic Acid ◽  
Resistance Mechanism ◽  
Bovine Mastitis ◽  
Lethal Challenge ◽  
Experimental Procedure ◽  
Appropriate Treatment ◽  
Amoxicillin Clavulanic Acid ◽  
Mrsa Infection

This article discusses the augmenting influence of Artesunate (ART) in combination with β-lactams (amoxicillin/clavulanic acid) antibiotic in sepsis mice models infected by a lethal challenge dose of live coagulase positive enterotoxigenic (Sec) MRSA that was isolated from a case of chronic bovine mastitis. The main goal is to find an appropriate treatment to overcome resistance mechanism of MRSA towards β-lactams antibiotic. Fifty healthy adult Swiss mice divided into 5 equal groups were used in the experimental procedure. The infected group that treated with both ART and β-lactams (amoxicillin/clavulanic acid) antibiotic revealed complete inhibition of MRSA count with complete normal macroscopic and histopathological features. We suggest that ART can potentiate the antibacterial action of β-lactams (amoxicillin/Clavulanic) acid against MRSA infection. The combination of ART and antibiotic can overcome MRSA resistance mechanism and so could be considered a novel candidate to overcome mastitis and/or sepsis caused by MRSA.

scholarly journals Achromobacter Xylosoxidans Bloodstream Infection in Elderly Patient with Hepatocellular Carcinoma: Case Report and Review of Literature

2015 ◽  
Vol 7 (02) ◽  
pp. 124-127 ◽  
Author(s):  
Kausalya Raghuraman ◽  
Nishat H Ahmed ◽  
Frincy K Baruah ◽  
Rajesh K Grover
Keyword(s):  
Hepatocellular Carcinoma ◽  
Clavulanic Acid ◽  
Bloodstream Infection ◽  
Acid Treatment ◽  
Achromobacter Xylosoxidans ◽  
Review Of Literature ◽  
Gram Negative ◽  
Antimicrobial Susceptibility Pattern ◽  
Amoxicillin Clavulanic Acid

ABSTRACT Achromobacter xylosoxidans is a nonfermentative Gram-negative organism, known to cause opportunistic infection in humans. We report a case of septicemia in a 76-year-old male patient with underlying hepatocellular carcinoma due to A. xylosoxidans, which showed a different antimicrobial susceptibility pattern from what is usually reported. From aerobic blood culture of the patient, A. xylosoxidans was isolated which was found to be sensitive to amoxicillin-clavulanic acid, piperacillin-tazobactam, ceftazidime, cefoperazone-sulbactam, meropenem, minocycline, tigecycline, and trimethoprim/sulfamethoxazole. The patient recovered with amoxicillin-clavulanic acid treatment, which was given empirically to the patient. The present case highlights the possible role of amoxicillin-clavulanic acid for treatment of bloodstream infection with A. xylosoxidans.

Extended-spectrum resistance to β-lactams/β-lactamase inhibitors (ESRI) evolved from low-level resistant Escherichia coli

2019 ◽  
Author(s):  
Ángel Rodríguez-Villodres ◽  
María Luisa Gil-Marqués ◽  
Rocío Álvarez-Marín ◽  
Rémy A Bonnin ◽  
María Eugenia Pachón-Ibáñez ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Clavulanic Acid ◽  
Genomic Analysis ◽  
E Coli ◽  
Extended Spectrum ◽  
Copy Numbers ◽  
Resistance Patterns ◽  
Amoxicillin Clavulanic Acid

Abstract Objectives Escherichia coli is characterized by three resistance patterns to β-lactams/β-lactamase inhibitors (BLs/BLIs): (i) resistance to ampicillin/sulbactam and susceptibility to amoxicillin/clavulanic acid and piperacillin/tazobactam (RSS); (ii) resistance to ampicillin/sulbactam and amoxicillin/clavulanic acid, and susceptibility to piperacillin/tazobactam (RRS); and (iii) resistance to ampicillin/sulbactam, amoxicillin/clavulanic acid and piperacillin/tazobactam (RRR). These resistance patterns are acquired consecutively, indicating a potential risk of developing resistance to piperacillin/tazobactam, but the precise mechanism of this process is not completely understood. Methods Clinical isolates incrementally pressured by piperacillin/tazobactam selection in vitro and in vivo were used. We determined the MIC of piperacillin/tazobactam in the presence and absence of piperacillin/tazobactam pressure. We deciphered the role of the blaTEM genes in the new concept of extended-spectrum resistance to BLs/BLIs (ESRI) using genomic analysis. The activity of β-lactamase was quantified in these isolates. Results We show that piperacillin/tazobactam resistance is induced in E. coli carrying blaTEM genes. This resistance is due to the increase in copy numbers and transcription levels of the blaTEM gene, thus increasing β-lactamase activity and consequently increasing piperacillin/tazobactam MICs. Genome sequencing of two blaTEM-carrying representative isolates showed that piperacillin/tazobactam treatment produced two types of duplications of blaTEM (8 and 60 copies, respectively). In the clinical setting, piperacillin/tazobactam treatment of patients infected by E. coli carrying blaTEM is associated with a risk of therapeutic failure. Conclusions This study describes for the first time the ESRI in E. coli. This new concept is very important in the understanding of the mechanism involved in the acquisition of resistance to BLs/BLIs.

scholarly journals The Role of Chronic Exposure to Amoxicillin/Clavulanic Acid on the Developmental Enamel Defects in Mice

2015 ◽  
Vol 44 (1) ◽  
pp. 61-70 ◽  
Author(s):  
Eugeniu Mihalaş ◽  
Lavinia Matricala ◽  
Alina Chelmuş ◽  
Nicolae Gheţu ◽  
Ana Petcu ◽  
...  
Keyword(s):  
Clavulanic Acid ◽  
Chronic Exposure ◽  
Enamel Defects ◽  
Amoxicillin Clavulanic Acid

Acute Generalized Exanthematous Pustulosis Induced by Amoxicillin/Clavulanic Acid

2015 ◽  
Vol 19 (6) ◽  
pp. 592-594 ◽  
Author(s):  
Ekaterini Syrigou ◽  
Dimitra Grapsa ◽  
Andriani Charpidou ◽  
Konstantinos Syrigos
Keyword(s):  
Clavulanic Acid ◽  
Patch Testing ◽  
Clinical Presentation ◽  
Drug Induced ◽  
Acute Generalized Exanthematous Pustulosis ◽  
Amoxicillin Clavulanic Acid ◽  
Exanthematous Pustulosis ◽  
Histopathologic Features

Drug-induced acute generalized exanthematous pustulosis is a rare pustular skin reaction, most commonly triggered by antibiotics. Although its diagnosis is based primarily on the presence of specific clinical and histopathologic features, additional in vivo (patch testing) or in vitro testing may be required, especially in atypical cases, to more accurately determine the causative agent. The authors report a histologically confirmed case of acute generalized exanthematous pustulosis that was induced by amoxicillin/clavulanic acid, as documented by subsequent patch testing, and presented with generalized painful lymphadenopathy, mimicking an acute infectious process. This is a very rare and diagnostically challenging clinical presentation of acute generalized exanthematous pustulosis, which has been reported, to the best of our knowledge, only once previously.

In vivo Experimental Study on the Influence of Sodium Fluoride and Amoxicillin/Clavulanic Acid on the Minerals Composition of Dental Enamel

2017 ◽  
Vol 68 (2) ◽  
pp. 269-272
Author(s):  
Eugeniu Mihalas ◽  
Alexandru Ogodescu ◽  
Adriana Balan ◽  
Liana Aminov ◽  
Yllka Decolli ◽  
...  
Keyword(s):  
Clavulanic Acid ◽  
Sodium Fluoride ◽  
Morphological Changes ◽  
Dental Enamel ◽  
Weight Percentage ◽  
Treatment Groups ◽  
Edx Analysis ◽  
Amoxicillin Clavulanic Acid ◽  
Group 2

The aim of this study was to assess the morphological and chemical composition changes induced by the chronic intake of sodium fluoride (NaF) and Amoxicillin in mice enamel. 35 C57BL/6 adult male mice, were randomly divided into a control and 4 treatment groups (n = 7). After acclimatization, the experimental groups were simultaneously treated with 25 ppm (group 2 and 3) and 50ppm (group 4 and 5) of NaF, and 50mg/kg BW (group 2 and 4) and 100 mg/kg BW (group 3 and 5) of Amoxicillin as Amoxicillin/clavulanic acid (AMC). NaF was supplied through drinking water without restricting access, and AMC administered through subcutaneous injection, once per day, for 60 days. After harvesting, lower incisors� enamel was subjected to a scanning electron microscope (SEM) and to an energy dispersive X-ray analysis (EDX). In the treatment groups, SEM and EDX analysis in treatment groups showed an increasing trend of weight percentage (wt%) for C, N, O, F, Na and C/O, F/Fe ratio, and also a decreasing trend of wt% for P, Cl, Ca, Fe and Ca/P ratio. Morphological changes ranged from fissures and short grooves with pits-like appearance, in group 2 sometimes associated with limited demineralized areas looking like irregular scratches, up to demineralized areas extended in the outer enamel, which in group 5 gives the enamel the corroded look. The severity of the morphological changes in the mice enamel varied with the supplied dose of NaF and AMC, and had a uniform pattern in each experimental group. SEM analysis revealed a hypoplasia on the outer enamel and EDX analysis showed a hypomineralisation at the level of the outer enamel.

scholarly journals The linear ubiquitin assembly complex (LUBAC) is essential for NLRP3 inflammasome activation

2014 ◽  
Vol 211 (7) ◽  
pp. 1333-1347 ◽  
Author(s):  
Mary A. Rodgers ◽  
James W. Bowman ◽  
Hiroaki Fujita ◽  
Nicole Orazio ◽  
Mude Shi ◽  
...  
Keyword(s):  
Nlrp3 Inflammasome ◽  
Inflammasome Activation ◽  
Lethal Challenge ◽  
Protein Substrates ◽  
Molecular Events ◽  
Nlrp3 Inflammasome Activation ◽  
Primary Bone ◽  
Primary Bone Marrow

Linear ubiquitination is a newly discovered posttranslational modification that is currently restricted to a small number of known protein substrates. The linear ubiquitination assembly complex (LUBAC), consisting of HOIL-1L, HOIP, and Sharpin, has been reported to activate NF-κB–mediated transcription in response to receptor signaling by ligating linear ubiquitin chains to Nemo and Rip1. Despite recent advances, the detailed roles of LUBAC in immune cells remain elusive. We demonstrate a novel HOIL-1L function as an essential regulator of the activation of the NLRP3/ASC inflammasome in primary bone marrow–derived macrophages (BMDMs) independently of NF-κB activation. Mechanistically, HOIL-1L is required for assembly of the NLRP3/ASC inflammasome and the linear ubiquitination of ASC, which we identify as a novel LUBAC substrate. Consequently, we find that HOIL-1L−/− mice have reduced IL-1β secretion in response to in vivo NLRP3 stimulation and survive lethal challenge with LPS. Together, these data demonstrate that linear ubiquitination is required for NLRP3 inflammasome activation, defining the molecular events of NLRP3 inflammasome activation and expanding the role of LUBAC as an innate immune regulator. Furthermore, our observation is clinically relevant because patients lacking HOIL-1L expression suffer from pyogenic bacterial immunodeficiency, providing a potential new therapeutic target for enhancing inflammation in immunodeficient patients.

scholarly journals Role of Anthrax Toxins in Dissemination, Disease Progression, and Induction of Protective Adaptive Immunity in the Mouse Aerosol Challenge Model

2008 ◽  
Vol 77 (1) ◽  
pp. 255-265 ◽  
Author(s):  
Crystal L. Loving ◽  
Taruna Khurana ◽  
Manuel Osorio ◽  
Gloria M. Lee ◽  
Vanessa K. Kelly ◽  
...  
Keyword(s):  
Lymph Nodes ◽  
Disease Progression ◽  
Anthrax Lethal Toxin ◽  
Lethal Challenge ◽  
In Vivo Experiments ◽  
Secondary Challenge ◽  
Anthrax Toxins ◽  
Disseminated Disease

ABSTRACT Anthrax toxins significantly contribute to anthrax disease pathogenesis, and mechanisms by which the toxins affect host cellular responses have been identified with purified toxins. However, the contribution of anthrax toxin proteins to dissemination, disease progression, and subsequent immunity after aerosol infection with spores has not been clearly elucidated. To better understand the role of anthrax toxins in pathogenesis in vivo and to investigate the contribution of antibody to toxin proteins in protection, we completed a series of in vivo experiments using a murine aerosol challenge model and a collection of in-frame deletion mutants lacking toxin components. Our data show that after aerosol exposure to Bacillus anthracis spores, anthrax lethal toxin was required for outgrowth of bacilli in the draining lymph nodes and subsequent progression of infection beyond the lymph nodes to establish disseminated disease. After pulmonary exposure to anthrax spores, toxin expression was required for the development of protective immunity to a subsequent lethal challenge. However, immunoglobulin (immunoglobulin G) titers to toxin proteins, prior to secondary challenge, did not correlate with the protection observed upon secondary challenge with wild-type spores. A correlation was observed between survival after secondary challenge and rapid anamnestic responses directed against toxin proteins. Taken together, these studies indicate that anthrax toxins are required for dissemination of bacteria beyond the draining lymphoid tissue, leading to full virulence in the mouse aerosol challenge model, and that primary and anamnestic immune responses to toxin proteins provide protection against subsequent lethal challenge. These results provide support for the utility of the mouse aerosol challenge model for the study of inhalational anthrax.

scholarly journals The Antistaphylococcal Activity of Amoxicillin/Clavulanic Acid, Gentamicin, and 1,8-Cineole Alone or in Combination and Their Efficacy through a Rabbit Model of Methicillin-Resistant Staphylococcus aureus Osteomyelitis

2020 ◽  
Vol 2020 ◽  
pp. 1-9 ◽  
Author(s):  
Soukayna Hriouech ◽  
Ahmed A. Akhmouch ◽  
Aouatef Mzabi ◽  
Hanane Chefchaou ◽  
Mariam Tanghort ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Bone Marrow ◽  
Synergistic Effect ◽  
Clavulanic Acid ◽  
Rabbit Model ◽  
Methicillin Resistant ◽  
Antistaphylococcal Activity ◽  
Amoxicillin Clavulanic Acid

The aim of this research paper is to test the antistaphylococcal effect of 1,8-cineole, amoxicillin/clavulanic acid (AMC), and gentamicin, either separately or in combination against three Staphylococcus aureus strains isolated from patients suffering from osteomyelitis. This activity was tested in vitro by using the microdilution method and the checkerboard assay. The efficacy of these three antibacterial agents was then tested in vivo by using an experimental model of methicillin-resistant S. aureus osteomyelitis in rabbits. This efficacy was assessed after four days of treatment by counting the number of bacteria in the bone marrow. The obtained results in vitro showed that the combination of the AMC with gentamicin did not induce a synergistic effect, whereas the combination of the two antibiotics with 1,8-cineole did. This effect is stronger when AMC is combined with 1,8-cineole as a total synergistic effect was obtained on the three strains used (FIC ≤ 0.5). In vivo, a significant reduction was noted in the number of colonies in the bone marrow when rabbits were treated with AMC associated with either 1,8-cineole or gentamicin compared to rabbits treated with AMC, gentamicin, or 1,8-cineole alone. These results demonstrated that 1,8-cineole showed a synergistic effect in combination with both AMC and gentamicin, which offer possibilities for reducing antibiotic usage. Also, the AMC associated with 1,8-cineole could be used to treat MRSA osteomyelitis.

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