scholarly journals Non-antibiotic pharmaceutical agents as antibiotic adjuvants

2020 ◽  
Vol 64 (1) ◽  
pp. 17-24
Author(s):  
Márió Gajdács
Keyword(s):  
Drug Repurposing ◽  
Multidrug Resistant ◽  
Antimicrobial Treatment ◽  
Public Health Issue ◽  
Resistant Bacteria ◽  
Global Public Health ◽  
Bacterial Strains ◽  
Pharmacological Agents ◽  
Treatment Regimens ◽  
Broth Microdilution Method

The emergence of multidrug-resistant bacteria is a global public health issue, which severely hinders clinicians in providing patients with adequate antimicrobial treatment regimens. The strategy of drug repurposing is an emerging strategy in antimicrobial chemotherapy, during which new pharmacological uses are identified for drugs already approved. The aim of our present study was to assess the adjuvant properties of several existing and widely-used pharmacological agents against bacteria in combination with reference antibiotics. Staphylococcus aureus ATCC 25923, S. epidermidis ATCC 12228, Escherichia coli ATCC 25922 and Klebsiella pneumoniae ATCC 700603 were selected for our experiments. The minimum inhibitory concentrations (MICs) of the tested compounds were determined using the broth microdilution method, while a MIC reduction assay was performed to ascertain the effect of the tested compounds on the MICs of standard antibiotics (ciprofloxacin and gentamicin). Eight tested compounds (namely atorvastatin, celecoxib, clotrimazole, diclofenac-epolamine, ivermectin, lidocaine, mebendazole and terbinafine) showed antibacterial activity on the tested bacterial strains and several agents presented with various degrees of adjuvant (MIC-reducing) properties. Further experiments involving the screening of additional pharmaceutical compounds for their secondary antibacterial and adjuvant properties are warranted.

scholarly journals The Role of Drug Repurposing in the Development of Novel Antimicrobial Drugs: Non-Antibiotic Pharmacological Agents as Quorum Sensing-Inhibitors

Antibiotics ◽  
2019 ◽  
Vol 8 (4) ◽  
pp. 270 ◽  
Author(s):  
Márió Gajdács ◽  
Gabriella Spengler
Keyword(s):  
Antibacterial Activity ◽  
Quorum Sensing ◽  
Drug Repurposing ◽  
Model Systems ◽  
Public Health Issue ◽  
Attractive Alternative ◽  
Pharmacological Agents ◽  
Bacterial Physiology ◽  
Chemical Structures ◽  
Broth Microdilution Method

Background: The emergence of multidrug-resistant organisms (MDROs) is a global public health issue, severely hindering clinicians in administering appropriate antimicrobial therapy. Drug repurposing is a drug development strategy, during which new pharmacological applications are identified for already approved drugs. From the viewpoint of the development of virulence inhibitors, inhibition of quorum sensing (QS) is a promising route because various important features in bacterial physiology and virulence are mediated by QS-dependent gene expression. Methods: Forty-five pharmacological agents, encompassing a wide variety of different chemical structures and mechanisms of action, were tested during our experiments. The antibacterial activity of the compounds was tested using the broth microdilution method. Screening and semi-quantitative assessment of QS-inhibition by the compounds was performed using QS-signal molecule-producing and indicator strains. Results: Fourteen pharmaceutical agents showed antibacterial activity in the tested concentration range, while eight drugs (namely 5-fluorouracil, metamizole-sodium, cisplatin, methotrexate, bleomycin, promethazine, chlorpromazine, and thioridazine) showed dose-dependent QS-inhibitory activity in the in vitro model systems applied during the experiments. Conclusions: Virulence inhibitors represent an attractive alternative strategy to combat bacterial pathogens more efficiently. Some of the tested compounds could be considered potential QS-inhibitory agents, warranting further experiments involving additional model systems to establish the extent of their efficacy.

scholarly journals Multidrug resistance in Shiga toxin-producing Escherichia coli (STEC) isolated from broiler chickens at slaughter

2021 ◽  
Vol 42 (6supl2) ◽  
pp. 3813-3824
Author(s):  
Rodrigo Pacheco Ornellas ◽  
◽  
Hugo Peralva Lopes ◽  
Daniela de Queiroz Baptista ◽  
Thomas Salles Dias ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Multidrug Resistance ◽  
Shiga Toxin ◽  
Broiler Chickens ◽  
Treatment Success ◽  
Multidrug Resistant ◽  
Resistance Pattern ◽  
Public Health Issue ◽  
Resistant Bacteria ◽  
Systemic Complications

Broiler chickens and derived products are a key source of Shiga toxin-producing Escherichia coli (STEC) in humans. This pathotype is responsible for causing severe episodes of diarrhea, which can progress to systemic complications. A rapid and accurate diagnosis of the disease, and early treatment of the infection with antimicrobials, can prevent it worsening. However, multidrug-resistant strains have potentially negative implications for treatment success. In this context, the aim of the present study was to isolate and identify multidrug-resistant STEC strains from broiler chickens and carcasses. Of 171 E. coli strains, isolated by conventional microbiological techniques and submitted to Polymerase Chain Reaction (PCR), for detection of stx1 and stx2 genes, 21.05% (36/171) were STEC pathotype, and most of them (66.67% - 24/36) carried both stx1 and eae genes. The multidrug resistance pattern was observed in 75% (27/36) of STEC strains. The presence of STEC in broiler chickens and carcasses reinforces that these sources may act as reservoirs for this pathotype. Multidrug-resistant bacteria contaminating animal products represent a public health issue because of the possibility of spread of multidrug-resistant determinants in the food chain and a higher risk of failure in human treatment when antimicrobials are needed.

scholarly journals Synthesis, Structure Elucidation, Antibacterial Activities, and Synergistic Effects of Novel Juglone and Naphthazarin Derivatives Against Clinical Methicillin-Resistant Staphylococcus aureus Strains

2021 ◽  
Vol 9 ◽  
Author(s):  
Valentin Duvauchelle ◽  
Chaimae Majdi ◽  
David Bénimélis ◽  
Catherine Dunyach-Remy ◽  
Patrick Meffre ◽  
...  
Keyword(s):  
Synergistic Effects ◽  
Antibacterial Properties ◽  
Clinical Importance ◽  
Antibacterial Activities ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Global Public Health ◽  
Gram Positive ◽  
Drug Resistant Bacteria ◽  
Mrsa Strains

Infections caused by drug-resistant bacteria are a serious threat to human and global public health. Moreover, in recent years, very few antibiotics have been discovered and developed by pharmaceutical companies. Therefore, there is an urgent need to discover and develop new antibacterial agents to combat multidrug-resistant bacteria. In this study, two novel series of juglone/naphthazarin derivatives (43 compounds) were synthesized and evaluated for their antibacterial properties against various clinical and reference Gram-positive MSSA, clinical Gram-positive MRSA, and clinical and reference Gram-negative bacteria E. coli and P. aeruginosa. These strains are of clinical importance because they belong to ESKAPE pathogens. Compounds 3al, 5ag, and 3bg showed promising activity against clinical and reference MSSA (MIC: 1–8 µg/ml) and good efficacy against clinical MRSA (MIC: 2–8 µg/ml) strains. 5am and 3bm demonstrated better activity on both MSSA (MIC: 0.5 µg/ml) and MRSA (MIC: 2 µg/ml) strains. Their MICs were similar to those of cloxacillin against clinical MRSA strains. The synergistic effects of active compounds 3al, 5ag, 5am, 3bg, and 3bm were evaluated with reference antibiotics, and it was found that the antibiotic combination with 3bm efficiently enhanced the antimicrobial activity. Compound 3bm was found to restore the sensitivity of clinical MRSA to cloxacillin and enhanced the antibacterial activity of vancomycin when they were added together. In the presence of 3bm, the MIC values of vancomycin and cloxacillin were lowered up to 1/16th of the original MIC with an FIC index of 0.313. Moreover, compounds 3al, 5ag, 5am, 3bg, and 3bm did not present hemolytic activity on sheep red blood cells. In silico prediction of ADME profile parameter results for 3bm is promising and encouraging for further development.

scholarly journals Multidrug Resistant and Extensively Drug Resistant Bacteria: A Study

2016 ◽  
Vol 2016 ◽  
pp. 1-5 ◽  
Author(s):  
Silpi Basak ◽  
Priyanka Singh ◽  
Monali Rajurkar
Keyword(s):  
Antimicrobial Resistance ◽  
Antibiotic Susceptibility ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Close Monitoring ◽  
Care Hospital ◽  
Drug Resistant ◽  
Bacterial Isolates ◽  
Bacterial Strains ◽  
Extensively Drug Resistant

Background and Objective. Antimicrobial resistance is now a major challenge to clinicians for treating patients. Hence, this short term study was undertaken to detect the incidence of multidrug-resistant (MDR), extensively drug-resistant (XDR), and pandrug-resistant (PDR) bacterial isolates in a tertiary care hospital.Material and Methods. The clinical samples were cultured and bacterial strains were identified in the department of microbiology. The antibiotic susceptibility profile of different bacterial isolates was studied to detect MDR, XDR, and PDR bacteria.Results. The antibiotic susceptibility profile of 1060 bacterial strains was studied. 393 (37.1%) bacterial strains were MDR, 146 (13.8%) strains were XDR, and no PDR was isolated. All (100%) Gram negative bacterial strains were sensitive to colistin whereas all (100%) Gram positive bacterial strains were sensitive to vancomycin.Conclusion. Close monitoring of MDR, XDR, or even PDR must be done by all clinical microbiology laboratories to implement effective measures to reduce the menace of antimicrobial 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 Susceptibility Assessment of Multidrug Resistant Bacteria to Natural Products

Dose-Response ◽  
2020 ◽  
Vol 18 (3) ◽  
pp. 155932582093618
Author(s):  
Essam Hassan Mohamed ◽  
Youssef Saeed Alghamdi ◽  
Salama Mostafa Abdel-Hafez ◽  
Mohamed Mohamed Soliman ◽  
Saad H. Alotaibi ◽  
...  
Keyword(s):  
Inhibitory Concentration ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Syzygium Aromaticum ◽  
Bacterial Strains ◽  
Multidrug Resistant Bacteria ◽  
Scanning Electron Microscope Analysis ◽  
Electron Microscope Analysis ◽  
Holothuria Atra ◽  
Scanning Electron

Objective: The aim of this study was to examine the effect of some natural compounds against multidrug-resistant bacteria. Methods: Forty-three bacterial strains were collected. Disc diffusion and minimum inhibitory concentration (MIC) tests were carried out for natural compounds including quercetin, Acacia nilotica, Syzygium aromaticum, and Holothuria atra. Scanning electron microscope analysis and bacterial DNA apoptosis assays were performed. Results: Staphylococcus aureus strains were resistant to imipenim, ampicillin, and penicillin. Most Escherichia coli strains were resistant to amoxicillin, clavulanat, and ampicillin. Finally, tigecycline was effective with Klebsiella pneumoniae and was resistant to all antibiotics. Only S aromaticum had an antibacterial effect on K pneumoniae. Most S aureus strains were sensitive to S aromaticum, A nilotica, and quercetin. All examined natural extracts had no effect on E coli. Holothuria atra had no effect on any of the strains tested. Minimum inhibitory concentration and minimum bactericidal concentration values for examined plants against S aureus were 6.25 to 12, 1.6 to 3.2, and 9.12 to 18.24 mg/mL, respectively. Syzygium aromaticum was active against K pneumoniae with an MIC of 12.5 mg/mL. Scanning electron microscope analysis performed after 24 and 48 hours of incubation showed bacterial strains with distorted shapes and severe cell wall damage. Syzygium aromaticum, quercetin, and A nilotica showed clear fragmentations of S aureus DNA. Conclusions: Current findings confirmed the beneficial effect of using natural products such as clove (S aromaticum), quercetin, and A nilotica as a promising therapy to overcome multidrug resistant bacteria.

scholarly journals Prevalence of multidrug resistant bacteria in causing community acquired urinary tract infection among the patients attending outpatient department of Seti Zonal Hospital, Dhangadi, Nepal

2015 ◽  
Vol 3 (1) ◽  
pp. 55-59 ◽  
Author(s):  
Tek Raj Awasthi ◽  
Narayan Dutt Pant ◽  
Puspa Raj Dahal
Keyword(s):  
Urinary Tract Infection ◽  
Urinary Tract ◽  
Tract Infection ◽  
Past History ◽  
Multidrug Resistant ◽  
Outpatient Department ◽  
Public Health Issue ◽  
Resistant Bacteria ◽  
Biochemical Tests ◽  
Multidrug Resistant Bacteria

Involvement of multidrug resistant bacteria in causing community acquired infection is very serious public health issue. The main objective of our study was to determine the prevalence of multidrug resistant bacteria in causing community acquired urinary tract infection. In this study we cultured the 384 mid stream urine samples collected aseptically from the patients attending outpatient department of Seti zonal hospital and having no past history of hospitalization. The organisms isolated were identified by using conventional biochemical tests and antimicrobial susceptibility testing was performed by Kirby Bauer disc diffusion technique. Out of total 384 samples 98 (25.52%) samples showed significant bacterial growth. The most prevalent bacterium isolated was Escherichia coli. 42.86% of the bacteria isolated were found to be multidrug resistant (MDR). The involvement of such large numbers of multidrug resistant bacteria in causing community acquired urinary tract infection is very serious issue and cannot be neglected. And some abrupt initiatives should be taken by the responsible authorities to improve or at least avoid the further worsening of the situation.Nepal Journal of Biotechnology. Dec. 2015 Vol. 3, No. 1: 55-59

scholarly journals Assessment of the Antibacterial Efficacy of Halicin against Pathogenic Bacteria

Antibiotics ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1480
Author(s):  
Rayan Y. Booq ◽  
Essam A. Tawfik ◽  
Haya A. Alfassam ◽  
Ahmed J. Alfahad ◽  
Essam J. Alyamani
Keyword(s):  
Pathogenic Bacteria ◽  
Wide Spectrum ◽  
New Technology ◽  
Cost Effective ◽  
Multidrug Resistant ◽  
New Drugs ◽  
Resistant Bacteria ◽  
Antibacterial Drug ◽  
Bacterial Strains ◽  
Zones Of Inhibition

Artificial intelligence (AI) is a new technology that has been employed to screen and discover new drugs. Using AI, an anti-diabetic treatment (Halicin) was nominated and proven to have a unique antibacterial activity against several harmful bacterial strains, including multidrug-resistant bacteria. This study aims to explore the antibacterial effect of halicin and microbial susceptibility using the zone of inhibition and the minimum inhibition concentration (MIC) values while assessing the stability of stored halicin over a period of time with cost-effective and straightforward methods. Linear regression graphs were constructed, and the correlation coefficient was calculated. The new antibacterial agent was able to inhibit all tested gram-positive and gram-negative bacterial strains, but in different concentrations—including the A. baumannii multidrug-resistant (MDR) isolate. The MIC of halicin was found to be 16 μg/mL for S. aureus (ATCC BAA-977), 32 μg/mL for E. coli (ATCC 25922), 128 μg/mL for A. baumannii (ATCC BAA-747), and 256 μg/mL for MDR A. baumannii. Upon storage, the MICs were increased, suggesting instability of the drug after approximately a week of storage at 4 °C. MICs and zones of inhibition were found to be high (R = 0.90 to 0.98), suggesting that halicin has a promising antimicrobial activity and may be used as a wide-spectrum antibacterial drug. However, the drug’s pharmacokinetics have not been investigated, and further elucidation is needed.

scholarly journals NastyBugs: A simple method for extracting antimicrobial resistance information from metagenomes

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 1971
Author(s):  
Hsinyi Tsang ◽  
Matthew Moss ◽  
Greg Fedewa ◽  
Sharif Farag ◽  
Daniel Quang ◽  
...  
Keyword(s):  
Antimicrobial Resistance ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Drug Selection ◽  
Global Public Health ◽  
Simple Method ◽  
Metagenomic Sample ◽  
Clinical Tools ◽  
Efficient Selection ◽  
Selection Of

Multidrug resistant bacteria are becoming a major threat to global public health. While there are many possible causes for this, there have so far been few adequate solutions to this problem. One of the major causes is a lack of clinical tools for efficient selection of an antibiotic in a reliable way. NastyBugs is a new program that can identify what type of antimicrobial resistance is most likely present in a metagenomic sample, which will allow for both smarter drug selection by clinicians and faster research in an academic environment.

scholarly journals Metabolic profiling and antibacterial activity of Eryngium pristis Cham. & Schltdl. - prospecting for its use in the treatment of bacterial infections

2021 ◽  
Vol 5 (1) ◽  
pp. 020-028
Author(s):  
Fernandes Laura Silva ◽  
da Costa Ygor Ferreira Garcia ◽  
de Bessa Martha Eunice ◽  
Ferreira Adriana Lucia Pires ◽  
do Amaral Corrêa José Otávio ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Bioactive Compounds ◽  
Metabolic Profile ◽  
Bacterial Infections ◽  
Ethanolic Extract ◽  
Multidrug Resistant ◽  
Gas Chromatography Mass Spectrometry ◽  
Resistant Bacteria ◽  
Bacterial Strains ◽  
New Antibiotics

Morbidity and mortality of the infected patients by multidrug-resistant bacteria have increased, emphasizing the urgency of fight for the discovery of new innovative antibiotics. In this sense, natural products emerge as valuable sources of bioactive compounds. Among the biodiversity, Eryngium pristis Cham. & Schltdl. (Apiaceae Lindl.) is traditionally used to treat thrush and ulcers of throat and mouth, as diuretic and emmenagogue, but scarcely known as an antimicrobial agent. With this context in mind, the goals of this study were to investigate the metabolic profile and the antibacterial activity of ethanolic extract (EE-Ep) and hexane (HF-Ep), dichloromethane (DF-Ep), ethyl acetate (EAF-Ep) and butanol (BF-Ep) fractions from E. pristis leaves. Gas Chromatography-Mass Spectrometry (GC-MS) was performed to stablish the metabolic profile and revealed the presence of 12 and 14 compounds in EAF-Ep and HF-Ep, respectively. β-selinene, spathulenol, globulol, 2-methoxy-4-vinylphenol, α-amyrin, β-amyrin, and lupeol derivative were some of phytochemicals identified. The antibacterial activity was determined by Minimal Inhibitory Concentration (MIC) using the broth micro-dilution against eight ATCC® and five methicillin-resistant Staphylococcus aureus (MRSA) clinical strains. HF-Ep was the most effective (MIC ≤ 5,000 µg/µL), being active against the largest part of tested Gram-positive and Gram-negative bacterial strains, including MRSA, with exception of Escherichia coli (ATCC 25922) and Pseudomonas aeruginosa (ATCC 9027) and (ATCC 27853). These results suggest that E. pristis is a natural source of bioactive compounds for the search of new antibiotics which can be an interesting therapeutic approach to recover patients mainly infected by MRSA strains.

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