scholarly journals In Vitro Assessment of 17 Antimicrobial Agents Against Clinical Mycobacterium Avium Complex Isolates

2021 ◽  
Author(s):  
Siran Lin ◽  
Wenya Hua ◽  
Shiyong Wang ◽  
Yu Zhang ◽  
Xinchang Chen ◽  
...  
Keyword(s):  
Mycobacterium Avium ◽  
Antimicrobial Agents ◽  
Resistance Rate ◽  
New Drugs ◽  
Health Concern ◽  
Subspecies Level ◽  
Current Usage ◽  
In Vitro Assessment

Abstract Background: Recently, Mycobacterium avium complex (MAC) infections have been increasing, especially in immunocompromised and older adults. The rapid increase has triggered a global health concern due to limited therapeutic strategies and adverse effects caused by long-term medication. To provide more evidence for the treatment of MAC, we studied the in vitro inhibitory activities of 17 antimicrobial agents against clinical MAC isolates.Results: A total of 111 clinical MAC isolates were enrolled in the study and they were identified as M. intracellulare, M. avium, M. marseillense, M. colombiense, M. yongonense, M. arosience, and one isolate was undifferentiated at subspecies level. MAC strains had relatively low (0–21.6%) resistance to clarithromycin, amikacin, bedaquiline, rifabutin, streptomycin, and clofazimine, and the resistant rates to isoniazid, rifampin, linezolid, doxycycline, and ethionamide were very high (72.1–100%). In addition, M. avium and M. intracellulare had different resistance profiles for clarithromycin, ethambutol, trimethoprim/sulfamethoxazole, amikacin, linezolid, clofazimine, cycloserine, and ethionamide. Conclusions: Our results supported the current usage of macrolides, rifabutin, and aminoglycosides in the regimens for MAC infection, and also demonstrated the low resistance rate against new drugs, such as clofazimine, tedizolid, and bedaquiline, suggesting the possible implementation of these drugs in MAC treatment.

Medicinal Au(i) compounds targeting urease as prospective antimicrobial agents: unveiling the structural basis for enzyme inhibition

2021 ◽  
Author(s):  
Luca Mazzei ◽  
Lara Massai ◽  
Michele Cianci ◽  
Luigi Messori ◽  
Stefano Ciurli
Keyword(s):  
Antibiotic Resistance ◽  
Enzyme Inhibition ◽  
Antimicrobial Agents ◽  
Antimicrobial Properties ◽  
New Drugs ◽  
Structural Basis ◽  
Great Promise ◽  
Gold Compounds

A few gold compounds were recently found to show antimicrobial properties in vitro, holding great promise for the discovery of new drugs to overcome antibiotic resistance.

Synthesis, in silico pharmacokinetics and biological evaluation of some new thiazolidinedione as PPAR-γ agonists and antibacterial agents

2021 ◽  
Vol 18 ◽  
Author(s):  
Zohor Mohammad Mahdi Alzhrani ◽  
Mohammad Mahboob Alam ◽  
Syed Nazreen
Keyword(s):  
Antibacterial Agents ◽  
Antimicrobial Agents ◽  
Antibacterial Activities ◽  
Biological Evaluation ◽  
New Drugs ◽  
Diabetic Patients ◽  
Spectroscopic Techniques ◽  
Standard Drug ◽  
Ppar Γ

Background: The frequent uses of antimicrobial agents to treat infections in diabetic patients make them more drug resistance than non diabetic patients which accounts for higher mortality rate of diabetic patients. Therefore, it is a necessity today to synthesize new drugs with dual mode of action as antidiabetic and antibacterial agents. In the present work, new derivatives containing thiazolidinedione and 1,3,4-oxadiaozle have been synthesized and screened for PPAR-γ and antibacterial activities. Methods: Compound 5-12 have been synthesized from 2-methoxy benzaldehyde and thiazolidinedione and characterized using different spectroscopic techniques such as IR, NMR and mass spectrometry. These compounds were tested for in vitro PPAR-γ transactivation, PPAR-γ gene expression and antibacterial activities. Finally molecular docking was carried out to see the binding interactions of molecules with the target protein. Results: All the compounds follow Lipinski rule suggesting the synthesized derivatives have good drug likeness properties. Compound 11 and 12 exhibited promising PPAR-γ transactivation with 73.69% and 76.50%, respectively as well as showed significant antibacterial activity with comparable MIC of 3.12 μg/disc to standard drug amoxicillin. The docking result was found to be in consistent with the in vitro PPAR-γ transactivation results. Conclusion: Compounds 11 and 12 can be further investigated as lead molecules for the development of new and effective antidiabetic and antibacterial agents.

scholarly journals In Vitro and In Vivo Activities of Novel Fluoroquinolones Alone and in Combination with Clarithromycin against Clinically Isolated Mycobacterium avium Complex Strains in Japan

2007 ◽  
Vol 51 (11) ◽  
pp. 4071-4076 ◽  
Author(s):  
Yoshihisa Kohno ◽  
Hideaki Ohno ◽  
Yoshitsugu Miyazaki ◽  
Yasuhito Higashiyama ◽  
Katsunori Yanagihara ◽  
...  
Keyword(s):  
Infectious Disease ◽  
Mycobacterium Avium ◽  
Antimicrobial Agents ◽  
Histopathological Examination ◽  
Bacterial Counts ◽  
Viable Bacteria ◽  
The Individual ◽  
Combination Regimens

ABSTRACT The recommended treatments for Mycobacterium avium complex (MAC) infectious disease are combination regimens of clarithromycin (CLR) or azithromycin with ethambutol and rifamycin. However, these chemotherapy regimens are sometimes unsuccessful. Recently developed antimicrobial agents, such as newer fluoroquinolones (FQs) containing C-8 methoxy quinolone (moxifloxacin [MXF] and gatifloxacin [GAT]), are expected to be novel antimycobacterial agents. Here, we evaluated the in vitro and in vivo antimycobacterial activities of three FQs (MXF, GAT, and levofloxacin) and CLR against clinically isolated MAC strains. Subsequently, the in vitro and in vivo synergic activities of FQ-CLR combinations against MAC strains were investigated. CLR and the individual FQs alone showed promising activity against MAC strains in vitro, and the bacterial counts in organs (lungs, liver, and spleen) of MAC-infected mice treated with single agents were significantly reduced compared to control mice. CLR showed the best anti-MAC effect in vivo. When the three FQs were individually combined with CLR in vitro, mild antagonism was observed for 53 to 57% of the tested isolates. Moreover, mice were infected with MAC strains showing mild antagonism for FQ-CLR combinations in vitro, and the anti-MAC effects of the FQ-CLR combinations were evaluated by counting the viable bacteria in their organs and by histopathological examination after 28 days of treatment. Several FQ-CLR combinations exhibited bacterial counts in organs significantly higher than those in mice treated with CLR alone. Our results indicate that the activity of CLR is occasionally attenuated by combination with an FQ both in vitro and in vivo and that this effect seems to be MAC strain dependent. Careful combination chemotherapy using these agents against MAC infectious disease may be required.

Infection of the Subcutis and Skin of Cats with Rapidly Growing Mycobacteria: A Review of Microbiological and Clinical Findings

2000 ◽  
Vol 2 (1) ◽  
pp. 35-48 ◽  
Author(s):  
R Malik ◽  
D I Wigney ◽  
D Dawson ◽  
P Martin ◽  
G B Hunt ◽  
...  
Keyword(s):  
Oral Therapy ◽  
Antimicrobial Agents ◽  
Susceptibility Testing ◽  
Inhibitory Concentration ◽  
Clinical Findings ◽  
Disc Diffusion ◽  
In Vitro Susceptibility ◽  
In Vitro Susceptibility Testing

Mycobacteria were isolated and characterised from 49 cats with extensive infections of the subcutis and skin. Cats were generally between 3 and 10 years of age, and female cats were markedly over-represented. All isolates were rapid-growers and identified as either Mycobacteria smegmatis (40 strains) or M fortuitum (nine strains). On the basis of Etest for minimum inhibitory concentration and/or disc diffusion susceptibility testing, all strains of M smegmatis were susceptible to trimethoprim while all strains of M fortuitum were resistant. M smegmatis strains were typically susceptible to doxycycline, gentamicin and fluoroquinolones but not clarithromycin. All M fortuitum strains were susceptible to fluoroquinolones, and often also susceptible to gentamicin, doxycycline and clarithromycin. Generally, M smegmatis strains were more susceptible to antimicrobial agents than M fortuitum strains. Treatment of mycobacterial panniculitis involves long courses of antimicrobial agents, typically of 3–6 months, chosen on the basis of in vitro susceptibility testing and often combined with extensive surgical debridement and wound reconstruction. These therapies will result in effective cure of the disease. One or a combination of doxycycline, ciprofloxacin/enrofloxacin or clarithromycin are the drugs of choice for long-term oral therapy.

scholarly journals Nano-biofilm Arrays as a Novel Universal Platform for Microscale Microbial Culture and High-Throughput Downstream Applications

2019 ◽  
Vol 26 (14) ◽  
pp. 2529-2535 ◽  
Author(s):  
Anand Srinivasan ◽  
Anand K. Ramasubramanian ◽  
José L. Lopez-Ribot
Keyword(s):  
High Throughput ◽  
High Throughput Screening ◽  
Antimicrobial Agents ◽  
Microarray Platform ◽  
New Drugs ◽  
Microbial Culture ◽  
Phenotypic Properties ◽  
Microbial Biofilms ◽  
Antibiotic Drug

Biofilms are the predominant mode of microbial growth and it is now fully accepted that a majority of infections in humans are associated with a biofilm etiology. Biofilms are defined as attached and structured microbial communities surrounded by a protective exopolymeric matrix. Importantly, sessile microorganisms growing within a biofilm are highly resistant to antimicrobial agents. Thus, there is an urgent need to develop new and improved anti-biofilm therapies. Unfortunately, most of the current techniques for in-vitro biofilm formation are not compatible with high throughput screening techniques that can speed up discovery of new drugs with anti-biofilm activity. To try to overcome this major impediment, our group has developed a novel technique consisting of micro-scale culture of microbial biofilms on a microarray platform. Using this technique, hundreds to thousands of microbial biofilms, each with a volume of approximately 30-50 nanolitres, can be simultaneously formed on a standard microscope slide. Despite more than three orders of magnitude of miniaturization over conventional biofilms, these nanobiofilms display similar growth, structural and phenotypic properties, including antibiotic drug resistance. These nanobiofilm chips are amenable to automation, drastically reducing assay volume and costs. This technique platform allows for true high-throughput screening in search for new anti-biofilm drugs.

scholarly journals Prevalence of fosfomycin resistance and gene mutations in clinical isolates of methicillin-resistant Staphylococcus aureus

2020 ◽  
Author(s):  
Yi-Chien Lee ◽  
Pao-Yu Chen ◽  
Jann-Tay Wang ◽  
Shan-Chwen Chang
Keyword(s):  
Staphylococcus Aureus ◽  
Antimicrobial Agents ◽  
Genetic Relatedness ◽  
Protein A ◽  
Gene Mutations ◽  
Resistance Rate ◽  
Staphylococcal Protein A ◽  
Methicillin Resistant ◽  
Fosfomycin Resistance

Abstract Background: Fosfomycin exhibits excellent in vitro activity against multidrug-resistant pathogens, including methicillin-resistant Staphylococcus aureus (MRSA). Increasing fosfomycin resistance among clinical MRSA isolates was reported previously, but little is known about the genetic mechanisms of fosfomycin resistance.Methods: All MRSA isolates, collected in 2002 and 2012 by the Taiwan Surveillance of Antimicrobial Resistance (TSAR) program, were used in this study. Susceptibility to various antimicrobial agents, including fosfomycin, was determined by broth microdilution. Genetic determinants of fosfomycin resistance, including fosB carriage and murA, glpT and uhpT mutations, were investigated using PCR and sequencing of amplicons. Staphylococcal protein A (spa) typing was also performed to determine the genetic relatedness of MRSA isolates.Results: A total of 969 MRSA strains, 495 in the year 2002 and 474 in the year 2012, were analyzed. The overall in vitro susceptibility was 8.2% to erythromycin, 18.0% to clindamycin, 29.0% to tetracycline, 44.6% to ciprofloxacin, 57.5% to trimethoprim/sulfamethoxazole, 86.9% to rifampicin, 92.9% to fosfomycin and 100% to linezolid and vancomycin. A significant increase in the fosfomycin resistance rate was observed from 3.4% in 2002 to 11.0% in 2012. Of 68 fosfomycin-resistant MRSA isolates, 12 harbored the fosB gene, and expression of murA, uhpT, and glpT mutations was noted in 11, 59, and 66 isolates, respectively. Combination of mutations of uhpT and glpT genes (58 isolates) was the most prevalent resistant mechanism. The vast majority of the fosfomycin-resistant MRSA isolates belonged to spa type t002.Conclusions: An increased fosfomycin resistance rate of MRSA isolates was observed in our present study, mostly due to mutations in the glpT and uhpT genes. Clonal spread probably contributed to the increased fosfomycin resistance.

scholarly journals 611. Fosfomycin Resistance of Multidrug-Resistant Escherichia coli and Mechanisms of Fosfomycin Resistance

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S285-S285
Author(s):  
Hyeri Seok ◽  
Ji Hoon Jeon ◽  
Hee Kyoung Choi ◽  
Won Suk Choi ◽  
Dae Won Park ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Antimicrobial Agents ◽  
Multidrug Resistant ◽  
Resistance Rate ◽  
Coli Strain ◽  
Resistant Bacteria ◽  
E Coli ◽  
Broth Microdilution Method ◽  
Fosfomycin Resistance

Abstract Background Fosfomycin is one of the antibiotics that may be a candidate for the next-generation antimicrobial agents againt multidrug-resistant bacteria. To date, it is known that the resistance rate is not high for Escherichia coli. However, it is necessary to update the fosfomycin resistance rates in E. coli according to the studies that extended spectrum β-lactamase (ESBL) producing E. coli strains are highly resistance to fosfomycin. We evaluated the resistance rate of fosfomycin, the resistant mechanism of fosfomycin in E. coli, and the activity of fosfomycin against susceptible and resistant strains of E. coli. Methods A total of 283 clinical isolates was collected from patients with Escherichia coli species during the period of January 2018 to June 2018, in three tertiary hospitals of Republic of Korea. In vitro antimicrobial susceptibility tests were performed in all E. coli isolates using the broth microdilution method according to the Clinical and Laboratory Standard Institute (CLSI). Multilocus sequence typing (MLST) of the Oxford scheme was conducted to determine the genotypes of E. coli isolated. Fosfomycin genes were investigated for all fosfomycin-resistant E. coli strains. Results The overall resistance rate to fosfomycin was 10.2%, compared with 53.4%, 46.3%, 41.3%, 31.1%, 10.6%, 2.5%, and 2.1% for ciprofloxacin, cefixime, cefepime, piperacillin/tazobactam, colistin, ertapenem, and amikacin, respectively. The 29 fosfomycin-resistant isolates did not show a clonal pattern on the phylogenetic tree. MurA and glp genes were identified in all strains. FosA3 were identified in two strains and uhp gene were identified in 4 strains. In time-kill curve studies, fosfomycin was more bactericidal than cefixime against all sensitive E. coli strain. Morever, fosfomycin was more bactericidal than piperacillin/tazobactam against ESBL-producing E. coli strain. Conclusion The resistant rate of fosfomycin to E. coli is still low. Fosfomycin was active against E. coli including ESBL producing strains. Disclosures All authors: No reported disclosures.

In vitro sensitivity to 5-FU and gemcitabine in pancreatic cancer.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 312-312
Author(s):  
J. Franko ◽  
M. M. Bilimoria ◽  
S. Chalikonda ◽  
D. A. Iannitti
Keyword(s):  
Pancreatic Cancer ◽  
Drug Sensitivity ◽  
Resistance Rate ◽  
Response Curves ◽  
Chemosensitivity Assay ◽  
In Vitro Sensitivity ◽  
In Vitro Chemosensitivity ◽  
In Vitro Assessment ◽  
Precision Therapeutics

312 Background: Gemcitabine and 5-fluorouracil (5-FU) represent the mainstay of chemotherapeutic options for pancreatic cancer. Currently, approximately 40% of patients with pancreatic cancer receive chemotherapy. Relapse is common after resection and adjuvant therapy, and response rates are low in patients with advanced/metastatic disease. The purpose of this study was to describe the prevalence of in vitro drug sensitivity or resistance to these agents in pancreatic cancer and explore the clinical implication of in vitro assessment. Methods: From August 2006 to January 2010, 74 specimens from patients with primary/metastatic pancreatic cancer were tested for response to gemcitabine, 5-FU, and their combination using an in vitro chemosensitivity assay (ChemoFx, Precision Therapeutics, Pittsburgh, PA). Tumors were classified as sensitive or resistant based on in vitro dose response curves. Results: Thirty-four of the 74 tumor specimens (46%) exhibited in vitro chemosensitivity to gemcitabine, 5-FU, or their combination. Fourteen tumors (19%) were sensitive to gemcitabine, and 12 (16%) to 5-FU. Of the 60 patient specimens resistant to gemcitabine, 4 (7%) were sensitive to 5-FU. Conversely, of the 62 specimens resistant to 5-FU, 6 (10%) were sensitive to gemcitabine. Eight of the 74 specimens (11%) were sensitive to both gemcitabine and 5-FU and 56 (76%) were resistant to both agents. Of these 56 specimens, 16 (29%) showed sensitivity to the gemcitabine/5-FU combination. Conclusions: The ChemoFx data indicates a high (76%) in vitro resistance rate to traditional chemotherapy. In vitro chemosensitivity to gemcitabine only partially overlaps with that of 5-FU and the gemcitabine/5-FU combination. Thus, tumors resistant to one drug, were not necessarily resistant to the other and vice versa. Further correlation with clinical outcomes is needed to determine the clinical efficacy of the ChemoFx assay. [Table: see text]

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