scholarly journals CSE (Ceftriaxone+ Sulbactam+ Disodium Edta): A Possible Solution to the Global Antimicrobial Resistance Pandemic

2020 ◽  
Vol 14 (3) ◽  
pp. 2039-2045
Author(s):  
Shalini Upadhyay ◽  
Anita Chakravarti ◽  
Tanisha Bharara ◽  
Sushmita Yadav
Keyword(s):  
Bacterial Infections ◽  
Ethylenediaminetetraacetic Acid ◽  
Beta Lactamase ◽  
Global Public Health ◽  
Bacterial Strains ◽  
First Line ◽  
Significant Treatment ◽  
Mortality And Morbidity ◽  
Disodium Ethylenediaminetetraacetic Acid

The menace of multidrug resistance among bacterial infections is an issue of global public health. Treatment of these superbugs with first line antibiotics is associated with significant treatment failure leading to increased mortality and morbidity. Carbapenems and polymyxins are the saviour antibiotics in case of such infections. But the problem is compounded when these antimicrobials also fail. The addition of beta-lactamase inhibitor like sulbactam and disodium ethylenediaminetetraacetic acid broaden the in vitro antibacterial action of ceftriaxone. This novel combination has been found to be effective in most of the drug resistant bacterial strains.

Repurposing of auranofin against bacterial infections: An In silico and In vitro study

2020 ◽  
Vol 16 ◽  
Author(s):  
Nidhi Sharma ◽  
Arti Singh ◽  
Ruchika Sharma ◽  
Anoop Kumar
Keyword(s):  
Broad Spectrum ◽  
In Silico ◽  
Antibacterial Agent ◽  
Bacterial Infections ◽  
In Vitro Assays ◽  
Infection Model ◽  
Synergistic Activity ◽  
Bacterial Strains ◽  
Molecular Docking Study

Aim: The aim of the study was to find out the role of auranofin as a promising broad spectrum antibacterial agent. Methods: In-vitro assays (Percentage growth retardation, Bacterial growth kinetics, Biofilm formation assay) and In-silico study (Molegro virtual docker (MVD) version 6.0 and Molecular operating environment (MOE) version 2008.10 software). Results: The in vitro assays have shown that auranofin has good antibacterial activity against Gram positive and Gram negative bacterial strains. Further, auranofin has shown synergistic activity in combination with ampicillin against S. aureus and B. subtilis whereas in combination with neomycin has just shown additive effect against E. coli, P. aeruginosa and B. pumilus. In vivo results have revealed that auranofin alone and in combination with standard drugs significantly decreased the bioburden in zebrafish infection model as compared to control. The molecular docking study have shown good interaction of auranofin with penicillin binding protein (2Y2M), topoisomerase (3TTZ), UDP-3-O-[3- hydroxymyristoyl] N-acetylglucosaminedeacetylase (3UHM), cell adhesion protein (4QRK), β-lactamase (5CTN) and arylsulphatase (1HDH) enzyme as that of reference ligand which indicate multimodal mechanism of action of auranofin. Finally, MTT assay has shown non-cytotoxic effect of auranofin. Conclusion: In conclusion, auranofin in combination with existing antibiotics could be developed as a broad spectrum antibacterial agent; however, further studies are required to confirm its safety and efficacy. This study provides possibility of use of auranofin apart from its established therapeutic indication in combination with existing antibiotics to tackle the problem of resistance.

scholarly journals 1564. Activity of bacteriophage against multidrug resistant Klebsiella pneumoniae

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S782-S782
Author(s):  
Sailaja Puttagunta ◽  
Maya Kahan-Haanum ◽  
Sharon Kredo-Russo ◽  
Eyal Weinstock ◽  
Efrat Khabra ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Unmet Need ◽  
Multidrug Resistant ◽  
Beta Lactamase ◽  
Bacterial Strains ◽  
Antibiotic Resistant ◽  
Extended Spectrum Beta Lactamase ◽  
Novel Approach ◽  
Infection Types

Abstract Background The prevalence of extended-spectrum beta-lactamase (ESBL) producing and carbapenem resistant (CR) Klebsiella pneumoniae (KP) has significantly risen in all geographic regions. Infections due to these bacteria are associated with high mortality across different infection types. Even with newer options, there remains an unmet need for safe and effective therapeutic options to treat infections caused by ESBL and CR KP. Phage therapy offers a novel approach with an unprecedented and orthogonal mechanism of action for treatment of diseases caused by pathogenic bacterial strains that are insufficiently addressed by available antibiotics. Phage-based therapies confer a high strain-level specificity and have a strong intrinsic safety profile. Here we describe the identification of novel phages that can effectively target antibiotic resistant KP strains. Host range of the 21 phages on 33 strain KP panel via solid culture infectivity assays. Red marks resistance to infection while sensitivity to phage is marked in green Methods KP clinical strains were isolated from human stool specimens preserved in glycerol. Selective culturing was carried, followed by testing of individual colonies for motility, indole and urease production, sequenced and analyzed by Kleborate tool to determine antibiotic resistant genes. Natural phages were isolated from plaques that developed on susceptible bacterial targets, sequenced and characterized. Results Antibiotic-resistant KP strains encoding beta lactamase genes or a carbapenemase (n=33) were isolated from healthy individuals (n=3), and patients with inflammatory bowel disease (n=26) or primary sclerosing cholangitis (n=3). Isolates sequencing revealed bla CTX-M15 and/or bla SHV encoding strains and carbapenamase KPC-2. A panel of 21 phages targeting the beta-lactamase- and carbapenemase-producing KP strains were identified. Phage sequencing revealed that all phages belong to the Caudovirales order and include 6 Siphoviridae, 14 Myoviridae, and 1 Podoviridae. In vitro lytic activity of the phages was tested on the isolated bacteria and revealed a coverage of 70% of the 33 isolated antibiotic resistant strains, >50% of which were targeted by multiple phages. Conclusion Collectively, these results demonstrate the feasibility of identifying phage with potent activity against antibiotic resistant KP strains, and may provide a novel therapeutic approach for treatment of ESBL and CR KP infections. Disclosures All Authors: No reported disclosures

scholarly journals Polymeric Nanoparticles Active against Dual-Species Bacterial Biofilms

Molecules ◽  
2021 ◽  
Vol 26 (16) ◽  
pp. 4958
Author(s):  
Jessa Marie V. Makabenta ◽  
Jungmi Park ◽  
Cheng-Hsuan Li ◽  
Aritra Nath Chattopadhyay ◽  
Ahmed Nabawy ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Laser Scanning ◽  
Polymeric Nanoparticles ◽  
Bacterial Species ◽  
Laser Scanning Microscopy ◽  
Confocal Laser ◽  
Bacterial Biofilms ◽  
Global Public Health ◽  
Bacterial Strains

Biofilm infections are a global public health threat, necessitating new treatment strategies. Biofilm formation also contributes to the development and spread of multidrug-resistant (MDR) bacterial strains. Biofilm-associated chronic infections typically involve colonization by more than one bacterial species. The co-existence of multiple species of bacteria in biofilms exacerbates therapeutic challenges and can render traditional antibiotics ineffective. Polymeric nanoparticles offer alternative antimicrobial approaches to antibiotics, owing to their tunable physico-chemical properties. Here, we report the efficacy of poly(oxanorborneneimide) (PONI)-based antimicrobial polymeric nanoparticles (PNPs) against multi-species bacterial biofilms. PNPs showed good dual-species biofilm penetration profiles as confirmed by confocal laser scanning microscopy. Broad-spectrum antimicrobial activity was observed, with reduction in both bacterial viability and overall biofilm mass. Further, PNPs displayed minimal fibroblast toxicity and high antimicrobial activity in an in vitro co-culture model comprising fibroblast cells and dual-species biofilms of Escherichia coli and Pseudomonas aeruginosa. This study highlights a potential clinical application of the presented polymeric platform.

scholarly journals Imaging Sensitive and Drug-Resistant Bacterial Infection with [11C]-TMP: In Vitro and First-in-Human Evaluation

2021 ◽  
Author(s):  
Iris K Lee ◽  
Daniel A Jacome ◽  
Joshua K Cho ◽  
Vincent Tu ◽  
Anthony Young ◽  
...  
Keyword(s):  
Bacterial Infection ◽  
Mammalian Cells ◽  
Bacterial Infections ◽  
The Body ◽  
Response Monitoring ◽  
Drug Resistant ◽  
Bacterial Strains ◽  
Critical Question ◽  
In Vitro Uptake

Recently, several molecular imaging strategies have developed to image bacterial infections in humans. Nuclear approaches, specifically positron emission tomography (PET), affords sensitive detection and the ability to non-invasively locate infections deep within the body. Two key radiotracer classes have arisen: metabolic approaches targeting bacterial specific biochemical transformations, and antibiotic-based approaches that have inherent selectivity for bacteria over mammalian cells. A critical question for clinical application of antibiotic radiotracers is whether resistance to the template antibiotic abrogates specific uptake, thus diminishing the predictive value of the diagnostic test. We recently developed small-molecule PET radiotracers based on the antibiotic trimethoprim (TMP), including [11C]-TMP, and have shown their selectivity for imaging bacteria in preclinical models. Here, we measure the in vitro uptake of [11C]-TMP in pathogenic susceptible and drug-resistant bacterial strains. Both resistant and susceptible bacteria showed similar in vitro uptake, which led us to perform whole genome sequencing of these isolates to identify the mechanisms of TMP resistance that permit retained radiotracer binding. By interrogating these isolate genomes and a broad panel of previously sequenced strains, we reveal mechanisms where uptake or binding of TMP radiotracers can potentially be maintained despite the annotation of genes conferring antimicrobial resistance. Finally, we present several examples of patients with both TMP-sensitive and drug-resistant infections in our first-in-human experience with [11C]-TMP. This work underscores the ability of an antibiotic radiotracer to image bacterial infection in patients, which may allow insights into human bacterial pathogenesis, infection diagnosis, and antimicrobial response monitoring.

scholarly journals Investigation of Metallo-Beta-Lactamases in Carbapenem Resistant Pseudomonas aeruginosa Strains by Phenotypic and Genotypic Methods

2020 ◽  
Vol 25 (3) ◽  
pp. 301-307
Author(s):  
M. Duygu Aksoy ◽  
H. Murat Tuğrul
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Ethylenediaminetetraacetic Acid ◽  
Carbapenem Resistance ◽  
Beta Lactamase ◽  
Bacterial Strains ◽  
Beta Lactamases ◽  
Carbapenem Resistant ◽  
Synergy Test ◽  
Phenotypic Tests ◽  
Positive Controls

Introduction: Carbapenem resistant Pseudomonas aeruginosa strains cause serious problems in treatment. A large number of identified metallo-beta-lactamase (MBL) enzymes produced by P. aeruginosa are one of the most important mechanisms in resistance to carbapenems. MBL genes are located on the chromosome or plasmid, and they can easily spread between different bacterial strains. The activities of these enzymes are zinc-dependent, and they are inhibited by ethylenediaminetetraacetic acid (EDTA). Therefore, this advantage is used in MBL identification tests. In this study, it was aimed to determine MBL among P. aeruginosa strains. Materials and Methods: MBL existence was investigated in 35 P. aeruginosa strains accepted to be mildly susceptible/resistant to any of the carbapenem group of antibiotics through phenotypic and genotypic methods. Phenotypic tests were performed as double disk synergy test (DDST), combined disk diffusion tests (CDDT) by using 0.1 M and 0.5 M EDTA, MBL E-test, and modified Hodge test (MHT). blaIMP, blaVIM, blaGIM, blaSIM, blaSPM genes and blaNDM gene were investigated by multiplex polimerase chain reaction (PCR) and PCR, respectively. Escherichia coli ATCC 25922 and P. aeruginosa ATCC 27853 standard bacteria were used in tests. VIM-1, VIM-2, IMP-13, SPM-1, NDM-1 type MBL-producing P. aeruginosa strains were used as positive controls. Results: Among the carbapenems resistant P. aeruginosa isolates, positivity of MBL was found as 54.2% by MBL E-test, 42.8% by DDST, 94.2% and 37.1% by CDDT method using 0.5 M and 0.1 M EDTA, respectively. Modified Hodge test and genotypic method did not detect MBL. Conclusion: In order to correctly evaluate the results of the phenotypic method, the investigation of resistance genes by molecular methods is also required. The most common metallo-beta-lactamase enzymes responsible for resistance to carbapenem in Pseudomonas were not observed. It was thought that different mechanisms might be responsible for the identified carbapenem resistance.

scholarly journals Antibiotic Use and Resistance Pattern in Ethiopia: Systematic Review and Meta-Analysis

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Oumer Abdu Muhie
Keyword(s):  
Multidrug Resistance ◽  
Bacterial Infections ◽  
Detection Rate ◽  
Public Health Problem ◽  
Antibiotic Use ◽  
Multidrug Resistant ◽  
Resistance Pattern ◽  
Global Public Health ◽  
Bacterial Strains ◽  
Bacterial Detection

Background. In the last decades, medicines have had an unprecedented positive effect on health, leading to reduced mortality and disease burden and consequently to an improved quality of life. The rapid and ongoing spread of antimicrobial-resistant organisms threatens our ability to successfully treat a growing number of infectious diseases. In the absence of the development of new generations of antibiotic drugs, appropriate use of existing antibiotics is needed to ensure the long-term availability of effective treatment for bacterial infections. Irrational use of antibiotics is an ongoing global public health problem that deserves more attention. This review is conducted to evaluate the prevalence of inappropriate antibiotic utilization and resistance to antibiotics in Ethiopia. Methods. Electronic search in PubMed/MEDLINE and Google was used to find published literature with reference lists of relevant articles searched manually. Titles and abstracts were initially screened for eligibility. The full texts of articles judged to be eligible were reviewed if they meet the inclusion criteria. Data were extracted on important variables like the sample size, region of the study, the inappropriate antibiotic use, bacterial detection rate, multidrug resistance pattern, and more other variables. Microsoft Excel was used for data extraction. Quantitative analysis was performed using STATA version 11. Results. The electronic searches identified 193 articles of which 33 were found eligible. The random-effects model was used to provide point estimates (with 95% confidence interval (CI)) of bacterial detection rate, inappropriate antibiotic use, and multidrug resistance rate to account for heterogeneity. The pooled bacteria detection rate was 29.1 with 95% CI (16.6–41.7). The pooled prevalence of multidrug resistant strains identified was 59.7% (95% CI: 43.5–75.9). The pooled estimate of inappropriate antibiotic use was 49.2% (95% CI: 32.2–66.2). The pooled proportion of self-antibiotic prescription was 43.3% (95% CI: 15.7–70.9). Other reasons for inappropriate antibiotic use included a wrong indication, wrong duration, improper route of administration, use of leftover antibiotics from a family member, and immature discontinuation of antibiotics. Conclusion and Recommendations. Inappropriate antibiotic use is a huge problem in Ethiopia, and many bacteria were resistant to commonly used antibiotics and similarly, multidrug-resistant bacterial strains are numerous. Appropriate antibiotic use should be ensured by prohibiting over-the-counter sale of antibiotics and strengthening antimicrobial stewardship.

scholarly journals Antibacterial properties of capsaicin and its derivatives and their potential to fight antibiotic resistance – A literature survey

2021 ◽  
Author(s):  
Samuel Füchtbauer ◽  
Soraya Mousavi ◽  
Stefan Bereswill ◽  
Markus M. Heimesaat
Keyword(s):  
Antibiotic Resistance ◽  
Bacterial Infections ◽  
Molecular Mechanisms ◽  
Antibacterial Properties ◽  
Treatment Strategies ◽  
Natural Compounds ◽  
Literature Survey ◽  
Bacterial Strains ◽  
Antibacterial Effects

AbstractAntibiotic resistance is endangering public health globally and gives reason for constant fear of virtually intractable bacterial infections. Given a limitation of novel antibiotic classes brought to market in perspective, it is indispensable to explore novel, antibiotics-independent ways to fight bacterial infections. In consequence, the antibacterial properties of natural compounds have gained increasing attention in pharmacological sciences. We here performed a literature survey regarding the antibacterial effects of capsaicin and its derivatives constituting natural compounds of chili peppers. The studies included revealed that the compounds under investigation exerted i.) both direct and indirect antibacterial properties in vitro depending on the applied concentrations and the bacterial strains under investigation; ii.) synergistic antibacterial effects in combination with defined antibiotics; iii.) resistance-modification via inhibition of bacterial efflux pumps; iv.) attenuation of bacterial virulence factor expression; and v.) dampening of pathogen-induced immunopathological responses. In conclusion, capsaicin and its derivatives comprise promising antimicrobial molecules which could complement or replace antibiotic treatment strategies to fight bacterial infections. However, a solid basis for subsequent clinical trials requires future investigations to explore the underlying molecular mechanisms and in particular pharmaceutical evaluations in animal infection models.

In-vitro evaluation of cisplatin nanoparticles encompass natural polymer

2020 ◽  
Vol 3 (1) ◽  
pp. 1-6
Author(s):  
Bhavani J ◽  
Sunil Kumar Prajapati ◽  
Ravichandran S
Keyword(s):  
Antibacterial Activity ◽  
Bacterial Infections ◽  
Pathogenic Bacteria ◽  
Bacterial Species ◽  
Research Work ◽  
Dilution Method ◽  
Bacterial Strains ◽  
Active Components ◽  
Synthetic Drugs

Opportunistic bacterial infections are common in the various parts of human body. In recent years bacterial species have shown resistance against a number of synthetic drugs. This study measured the antibacterial activity of bacterial strains against five common pathogenic bacteria related strains. Cup plate method and two fold serial dilution method were used to evaluated by antibacterial activity by the help of different bacterial related strains. The results revealed that Cisplatin (CIP) using natural as a polymer showed a minimum inhibitory concentration (MIC) at 250 mg/ml to 500 mg/ml of the broth against all bacterial strains. CIP using natural as a polymer was prepared different doses1000 μg/ml and 2000 μg/ ml and measured zone of inhibition dose dementedly reduced when compared to standard. The CIP using natural as a polymer exhibited strong anti-bacterial activity against five different species of bacteria and this may be attributed to various active components. Our research work has been indicated Nanoparticles containing CIP using natural as a polymer formulated for the enhanced anti-cancer activity through antimicrobial mechanism. 

Synthesis, Antimicrobial Evaluation and In silico Studies of Novel 2,4- disubstituted-1,3-thiazole Derivatives

2018 ◽  
Vol 16 (2) ◽  
pp. 160-173 ◽  
Author(s):  
Mir Mohammad Masood ◽  
Mohammad Irfan ◽  
Shadab Alam ◽  
Phool Hasan ◽  
Aarfa Queen ◽  
...  
Keyword(s):  
In Silico ◽  
Bacterial Infections ◽  
Antimicrobial Agents ◽  
Docking Studies ◽  
Bacterial Strains ◽  
Thiazole Derivatives ◽  
Standard Drug ◽  
Hek 293 ◽  
In Silico Studies

Background: 2,4-disubstituted-1,3-thiazole derivatives (2a–j), (3a–f) and (4a–f) were synthesized, characterized and screened for their potential as antimicrobial agents. In the preliminary screening against a panel of bacterial strains, nine compounds showed moderate to potent antibacterial activity (IC50 = 13.7-90.8 μg/ml). </P><P> Methods: In the antifungal screening, compound (4c) displayed potent antifungal activity (IC50 = 26.5 &#181;g/ml) against Candida tropicalis comparable to the standard drug, fluconazole (IC50 = 10.5 &#181;g/ml). Based on in vitro antimicrobial results, compounds 2f, 4c and 4e were selected for further pharmacological investigations. Hemolytic activity using human red blood cells (hRBCs) and cytotoxicity by MTT assay on human embryonic kidney (HEK-293) cells revealed non-toxic nature of the selected compounds (2f, 4c and 4e). To ascertain their possible mode of action, docking studies with the lead inhibitors (2f, 4c and 4e) were performed using crystal structure coordinates of bacterial methionine aminopeptidases (MetAPs), an enzyme involved in bacterial protein synthesis and maturation. Results: The results of in vitro and in silico studies provide a rationale for selected compounds (2f, 4c and 4e) to be carried forward for further structural modifications and structure-activity relationship (SAR) studies against these bacterial infections. Conclusion: The study suggested binding with one or more key amino acid residues in the active site of Streptococcus pneumoniae MetAP (SpMetAP) and Escherichia coli MetAP (EcMetAP). In silico physicochemical properties using QikProp confirmed their drug likeliness.

scholarly journals Novel Lytic Phages Protect Cells and Mice against Pseudomonas aeruginosa Infection

2021 ◽  
Author(s):  
Feng Chen ◽  
Xingjun Cheng ◽  
Jianbo Li ◽  
Xiefang Yuan ◽  
Xiuhua Huang ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Mouse Models ◽  
Bacterial Infections ◽  
Phage Therapy ◽  
Inflammatory Responses ◽  
Multi Drug Resistance ◽  
Bacterial Strains ◽  
Genetic Traits

With the fast emergence of serious antibiotic resistance and the lagged discovery of novel antibacterial drugs, phage therapy for pathogenic bacterial infections has acquired great attention in the clinics. However, development of therapeutic phages also faces tough challenges, such as laborious screening and time to generate effective phage drugs since each phage may only lyse a narrow scope of bacterial strains. Identifying highly effective phages with broad host ranges is crucial for improving phage therapy. Here, we isolated and characterized several lytic phages from various environments specific for Pseudomonas aeruginosa by testing their growth, invasion, host ranges, and potential for killing targeted bacteria. Importantly, we identified several therapeutic phages (HX1, PPY9, and TH15) with broad host ranges to lyse laboratory strains and clinical isolates of P. aeruginosa with multi-drug resistance (MDR) both in vitro and in mouse models. In addition, we analyzed critical genetic traits related to the high-level broad host coverages by genome sequencing and subsequent computational analysis against known phages. Collectively, our findings establish that these novel phages may have potential for further development as therapeutic options for patients who fail to respond to conventional treatments. IMPORTANCE Novel lytic phages isolated from various environmental settings were systematically characterized for their critical genetic traits, morphology structures, host ranges against laboratory strains and clinical multi-drug resistant (MDR) Pseudomonas aeruginosa, and antibacterial capacity both in vitro and in mouse models. First, we characterized the genetic traits and compared with other existing phages. Furthermore, we utilized acute pneumonia induced by laboratorial strain PAO1, and W19, an MDR clinical isolate and chronic pneumonia by agar beads laden with FDR1, a mucoid phenotype strain isolated from the sputum of a cystic fibrosis (CF) patient. Consequently, we found that these phages not only suppress bacteria in vitro but also significantly reduce the infection symptom and disease progression in vivo, including lowered bug burdens, inflammatory responses and lung injury in mice, suggesting that they may be further developed as therapeutic agents against MDR P. aeruginosa.

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