scholarly journals Evaluation of Benzguinols as Next-Generation Antibiotics for the Treatment of Multidrug-Resistant Bacterial Infections

Antibiotics ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 727
Author(s):  
Hang Thi Nguyen ◽  
Mahmud T. Morshed ◽  
Daniel Vuong ◽  
Andrew Crombie ◽  
Ernest Lacey ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Inhibitory Concentration ◽  
Specific Treatment ◽  
Multidrug Resistant ◽  
Survival Times ◽  
Fungal Natural Products ◽  
Serious Bacterial Infections ◽  
Further Development ◽  
Reference Strains

Our recent focus on the “lost antibiotic” unguinol and related nidulin-family fungal natural products identified two semisynthetic derivatives, benzguinols A and B, with unexpected in vitro activity against Staphylococcus aureus isolates either susceptible or resistant to methicillin. Here, we show further activity of the benzguinols against methicillin-resistant isolates of the animal pathogen Staphylococcus pseudintermedius, with minimum inhibitory concentration (MIC) ranging 0.5–1 μg/mL. When combined with sub-inhibitory concentrations of colistin, the benzguinols demonstrated synergy against Gram-negative reference strains of Acinetobacter baumannii, Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa (MICs of 1–2 μg/mL in the presence of colistin), whereas the benzguinols alone had no activity. Administration of three intraperitoneal (IP) doses of 20 mg/kg benzguinol A or B to mice did not result in any obvious adverse clinical or pathological evidence of acute toxicity. Importantly, mice that received three 20 mg/kg IP doses of benzguinol A or B at 4 h intervals exhibited significantly reduced bacterial loads and longer survival times than vehicle-only treated mice in a bioluminescent S. aureus murine sepsis challenge model. We conclude that the benzguinols are potential candidates for further development for specific treatment of serious bacterial infections as both stand-alone antibiotics and in combination with existing antibiotic classes.

Repurposing of escitalopram oxalate and clonazepam in combination with ciprofloxacin and sulfamethoxazole/trimethoprim for treatment of multidrug-resistant microorganisms and evaluation of the cleavage capacity of plasmid DNA

2021 ◽  
Author(s):  
Taciéli Fagundes da Rosa ◽  
Catrine de Souza Machado ◽  
Marissa Bolson Serafin ◽  
Angelita Bottega ◽  
Silvana Silveira Coelho ◽  
...  
Keyword(s):  
Plasmid Dna ◽  
Bacterial Infections ◽  
Bacterial Resistance ◽  
Inhibitory Concentration ◽  
Drug Repurposing ◽  
Multidrug Resistant ◽  
Culture Collection ◽  
Bacterial Strains ◽  
Gram Positive

Bacterial resistance has propelled one of the most serious public health problems in the world. In this sense, drug repurposing has emerged for faster identification of effective drugs. The aim of this study was to investigate the repurposing of escitalopram oxalate and clonazepam drugs individually and in combination with antibiotics ciprofloxacin and sulfamethoxazole-trimethoprim to treat multidrug-resistant microorganisms (MDR) and to evaluate the chemical nuclease capacity. The minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), fractional inhibitory concentration index (FICI) and tolerance level were determined against each microorganism tested. In vitro antibacterial activity was evaluated against forty-seven multidrug-resistant clinical isolates and eleven standard bacterial strains of the American Type Culture Collection (ATCC). Escitalopram oxalate was active mainly against Gram-positive and clonazepam against Gram-positive and Gram-negative bacteria. When associated with the two antibiotics mentioned, they had a significant synergistic effect. Clonazepam was able to cleave plasmid DNA and the mechanisms involved were oxidative and hydrolytic. These results allow us to suggest repurposing these non-antibiotic drugs to treat bacterial infections. However, further studies on the mechanism of action of these drugs should be performed, including to increase safety in use.

scholarly journals IN VITRO STUDY OF URSOLIC ACID COMBINATION FIRST-LINE ANTITUBERCULOSIS DRUGS AGAINST DRUG-SENSITIVE AND DRUG-RESISTANT STRAINS OF Mycobacterium tuberculosis

2017 ◽  
Vol 10 (4) ◽  
pp. 216 ◽  
Author(s):  
Dian Ayu Eka Pitaloka ◽  
Elin Yulinah Sukandar
Keyword(s):  
Ursolic Acid ◽  
Drug Combination ◽  
Resistant Strain ◽  
Inhibitory Concentration ◽  
In Vitro Study ◽  
Antimycobacterial Activity ◽  
Multidrug Resistant ◽  
Minimum Concentration ◽  
Different Strains

Objective: The resurgence of tuberculosis (TB) caused by Mycobacterium TB (MTB) is associated with the rapid spread of multidrug-resistant,therefore, the development of new antimycobacterial agents is necessary. The aim of this study was to evaluate the antimycobacterial activity ofursolic acid (UA) when it using alone and combination with TB drugs.Methods: MTB H37Rv strain, streptomycin-rifampicin resistant strain, and isoniazid-ethambutol resistant strain were evaluated by susceptibility testusing a serial number of UA (25-150 µg/mL). Minimum inhibitory concentration (MIC) was read as minimum concentration of drugs that completelyinhibit visible growth of organism. Activities of drug combination of UA with TB drug were determined in Lowenstein-Jensen media by calculatingthe fractional inhibitory concentration index.Results: The results showed that MIC of UA was 50 µg/mL against three different strains of MTB. The combination of UA and TB drugs displayedsynergistic interaction, and no antagonism result from the combination was observed for strains of MTB.Conclusion: These results indicate that UA may serve as a promising lead compound for future antimycobacterial drug development.Keywords: Ursolic acid, Tuberculosis, Drug combination, Susceptibility test

scholarly journals Evaluation of the Efficacy of a Bacteriophage in the Treatment of Pneumonia Induced by Multidrug ResistanceKlebsiella pneumoniaein Mice

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Fang Cao ◽  
Xitao Wang ◽  
Linhui Wang ◽  
Zhen Li ◽  
Jian Che ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Burst Size ◽  
Multidrug Resistant ◽  
Lung Lesion ◽  
Lytic Bacteriophage ◽  
Short Latent Period ◽  
Dose Dependent ◽  
Antibiotic Control

Multidrug-resistantKlebsiella pneumoniae(MRKP) has steadily grown beyond antibiotic control. However, a bacteriophage is considered to be a potential antibiotic alternative for treating bacterial infections. In this study, a lytic bacteriophage, phage 1513, was isolated using a clinical MRKP isolate KP 1513 as the host and was characterized. It produced a clear plaque with a halo and was classified as Siphoviridae. It had a short latent period of 30 min, a burst size of 264 and could inhibit KP 1513 growthin vitrowith a dose-dependent pattern. Intranasal administration of a single dose of 2 × 109 PFU/mouse 2 h after KP 1513 inoculation was able to protect mice against lethal pneumonia. In a sublethal pneumonia model, phage-treated mice exhibited a lower level ofK. pneumoniaeburden in the lungs as compared to the untreated control. These mice lost less body weight and exhibited lower levels of inflammatory cytokines in their lungs. Lung lesion conditions were obviously improved by phage therapy. Therefore, phage 1513 has a great effectin vitroandin vivo, which has potential to be used as an alternative to an antibiotic treatment of pneumonia that is caused by the multidrug-resistantK. pneumoniae.

scholarly journals In Vitro Activity of the Novel Pleuromutilin Lefamulin (BC-3781) and Effect of Efflux Pump Inactivation on Multidrug-Resistant and Extensively Drug-Resistant Neisseria gonorrhoeae

2017 ◽  
Vol 61 (11) ◽  
Author(s):  
Susanne Jacobsson ◽  
Susanne Paukner ◽  
Daniel Golparian ◽  
Jörgen S. Jensen ◽  
Magnus Unemo
Keyword(s):  
Efflux Pump ◽  
Multidrug Resistant ◽  
Cross Resistance ◽  
Drug Resistant ◽  
The Novel ◽  
Extensively Drug Resistant ◽  
Optimal Dosing ◽  
And Performance ◽  
Reference Strains

ABSTRACT We evaluated the activity of the novel semisynthetic pleuromutilin lefamulin, inhibiting protein synthesis and growth, and the effect of efflux pump inactivation on clinical gonococcal isolates and reference strains (n = 251), including numerous multidrug-resistant and extensively drug-resistant isolates. Lefamulin showed potent activity against all gonococcal isolates, and no significant cross-resistance to other antimicrobials was identified. Further studies of lefamulin are warranted, including in vitro selection and mechanisms of resistance, pharmacokinetics/pharmacodynamics, optimal dosing, and performance in randomized controlled trials.

scholarly journals Isolation and Characterization of Novel Phages Targeting Pathogenic Klebsiella pneumoniae

2021 ◽  
Vol 11 ◽  
Author(s):  
Na Li ◽  
Yigang Zeng ◽  
Rong Bao ◽  
Tongyu Zhu ◽  
Demeng Tan ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Bacterial Infections ◽  
Antimicrobial Agents ◽  
Multidrug Resistant ◽  
S1 Nuclease ◽  
Isolation And Characterization ◽  
Comprehensive Knowledge ◽  
Future Challenges ◽  
Lactamase Gene

Klebsiella pneumoniae is a dominant cause of community-acquired and nosocomial infections, specifically among immunocompromised individuals. The increasing occurrence of multidrug-resistant (MDR) isolates has significantly impacted the effectiveness of antimicrobial agents. As antibiotic resistance is becoming increasingly prevalent worldwide, the use of bacteriophages to treat pathogenic bacterial infections has recently gained attention. Elucidating the details of phage-bacteria interactions will provide insights into phage biology and the better development of phage therapy. In this study, a total of 22 K. pneumoniae isolates were assessed for their genetic and phenotypic relatedness by multi-locus sequence typing (MLST), endonuclease S1 nuclease pulsed-field gel electrophoresis (S1-PFGE), and in vitro antibiotic susceptibility testing. In addition, the beta-lactamase gene (blaKPC) was characterized to determine the spread and outbreak of K. pneumoniae carbapenemase (KPC)-producing enterobacterial pathogens. Using these ST11 carbapenem-resistant K. pneumoniae isolates, three phages (NL_ZS_1, NL_ZS_2, and NL_ZS_3) from the family of Podoviridae were isolated and characterized to evaluate the application of lytic phages against the MDR K. pneumoniae isolates. In vitro inhibition assays with three phages and K. pneumoniae strain ZS15 demonstrated the strong lytic potential of the phages, however, followed by the rapid growth of phage-resistant and phage-sensitive mutants, suggesting several anti-phage mechanisms had developed in the host populations. Together, this data adds more comprehensive knowledge to known phage biology and further emphasizes their complexity and future challenges to overcome prior to using phages for controlling this important MDR bacterium.

scholarly journals In Vitro Antifungal Combination of Flucytosine with Amphotericin B, Voriconazole, or Micafungin against Candida auris Shows No Antagonism

2019 ◽  
Vol 63 (12) ◽  
Author(s):  
A. L. Bidaud ◽  
F. Botterel ◽  
A. Chowdhary ◽  
E. Dannaoui
Keyword(s):  
Amphotericin B ◽  
Inhibitory Concentration ◽  
Geometric Mean ◽  
Multidrug Resistant ◽  
Candida Auris ◽  
Content Type ◽  
Hospital Acquired Infections ◽  
Resistant Mutants ◽  
Hospital Acquired

ABSTRACT Candida auris is an emerging, multidrug-resistant pathogen responsible for invasive hospital-acquired infections. Flucytosine is an effective anti-Candida species drug, but which cannot be used as a monotherapy because of the risk of development of resistant mutants during treatment. It is, therefore, noteworthy to test possible combinations with flucytosine that may have a synergistic interaction. In this study, we determined the in vitro interaction between flucytosine and amphotericin B, micafungin, or voriconazole. These combinations have been tested against 15 C. auris isolates. The MIC ranges (geometric mean [Gmean]) of flucytosine, amphotericin B, micafungin, and voriconazole were 0.125 to 1 μg/ml (0.42 μg/ml), 0.25 to 1 μg/ml (0.66 μg/ml), 0.125 to 0.5 μg/ml (0.3 μg/ml), and 0.03 to 4 μg/ml (1.05 μg/ml), respectively. When tested in combination, indifferent interactions were mostly observed with fractional inhibitory concentration index values from 0.5 to 1, 0.31 to 1.01, and 0.5 to 1.06 for the combinations of flucytosine with amphotericin B, micafungin, and voriconazole, respectively. A synergy was observed for the strain CBS 10913 from Japan. No antagonism was observed for any combination. The combination of flucytosine with amphotericin B or micafungin may be relevant for the treatment of C. auris infections.

scholarly journals Volatile Oils ofNepeta tenuifolia(Jing Jie) as an Alternative Medicine against Multidrug-Resistant Pathogenic Microbes

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Yi-Hsuan Lee ◽  
Chao-Min Wang ◽  
Po-Yu Liu ◽  
Ching-Chang Cheng ◽  
Zong-Yen Wu ◽  
...  
Keyword(s):  
Essential Oils ◽  
In Vitro Study ◽  
Multidrug Resistant ◽  
Clinical Isolates ◽  
Gram Negative ◽  
E Coli ◽  
Wide Range ◽  
Main Component ◽  
Reference Strains

Essential oils from the dried spikes ofNepeta tenuifolia(Benth) are obtained by steam distillation. Pulegone was identified as the main component in the spikes ofN. tenuifoliathrough analysis, with greater than 85% purity obtained in this study. The essential oils are extremely active against all Gram-positive and some Gram-negative reference bacteria, particularlySalmonella enterica,Citrobacter freundii, andEscherichia coli. The minimum inhibitory concentration was found to be between 0.08 and 0.78% (againstS. enterica), 0.39 and 0.78% (againstC. freundii), and 0.097 and 0.39% (againstE. coli), whereas the minimum bactericidal concentration varied in range from 0.097% to 1.04%. In general, the essential oils show a strong inhibitory action against all tested reference strains and clinical isolates. However, the antibacterial activity of EOs against bothPseudomonas aeruginosareference strains and clinical isolates was relatively lower than other Gram-negative pathogens. The essential oils ofN. tenuifoliaalso displayed bactericidal activities (MBC/MIC < 4) in this study. These findings reflect the bactericidal activity of the essential oils against a wide range of multidrug-resistant clinical pathogens in an in vitro study. In addition, we propose the fragmentation pathways of pulegone and its derivatives by LC-ESI-MS/MS in this study.

scholarly journals Preliminary Evaluation of In Vitro Bacteriostatic and Bactericidal Effect of Salt on Leptospira spp.

2020 ◽  
Vol 7 (4) ◽  
pp. 154
Author(s):  
Giovanni Cilia ◽  
Filippo Fratini ◽  
Elena della Buona ◽  
Fabrizio Bertelloni
Keyword(s):  
Marine Mammals ◽  
Inhibitory Concentration ◽  
Chloride Concentration ◽  
Bactericidal Effect ◽  
Preliminary Evaluation ◽  
Environmental Resistance ◽  
Leptospira Spp ◽  
Vitro Effect ◽  
Reference Strains

Environmental resistance is an important factor for understanding the epidemiology of leptospirosis. Recently, new Leptospira hosts were identified, including also marine mammals. Moreover, halotolerant Leptospira strain, isolated from the environment and animals, highlighted the capability of this microorganism to persist in the seawater. The aim of this research was to investigate the bacteriostatic and bactericidal effect of salt on Leptospira strains belonging to 16 different serovars. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values were verified through the microdilutions method starting from a 20% sodium chloride concentration. MIC values obtained were between 0.3125% and 10% of salt, while MBC values between 0.625% and >20%. Icterohaemorrhagiae (MIC: 0.3125%; MBC: 0.625%) resulted the most inhibited serovar, while the most resistant was Tarassovi (MIC: 10%; MBC: >20%). Interestingly, trends were reported for Pomona (MIC: 1.25%; MBC: >20%) and Bratislava (MIC: 0.625%; MBC: 20%), highlighting low MIC values but high MBC values. This is the first investigation aimed at the in vitro effect of salt on the growth of Leptospira spp. reference strains.

scholarly journals Screening and Application of Chitin Synthase Inhibitors

Processes ◽  
2020 ◽  
Vol 8 (9) ◽  
pp. 1029
Author(s):  
Xiaozai Shi ◽  
Shuo Qiu ◽  
Yingling Bao ◽  
Hanchi Chen ◽  
Yuele Lu ◽  
...  
Keyword(s):  
Antifungal Activity ◽  
Inhibitory Concentration ◽  
Inhibitory Effect ◽  
Chitin Synthase ◽  
Fungal Cell ◽  
Ic50 Value ◽  
Further Development ◽  
Fungicide Target ◽  
Better Than

Chitin is an important part of the fungal cell wall, but is not found in plants and mammals, so chitin synthase (CHS) can be a green fungicide target. In this paper, 35 maleimide compounds were designed and synthesized as CHS inhibitors. All the screened compounds showed different degrees of CHS inhibitory activity and antifungal activity in vitro. In particular, the half–inhibitory concentration (IC50) value of compound 20 on CHS was 0.12 mM, and the inhibitory effect was better than that of the control polyoxin B (IC50 = 0.19 mM). At the same time, this compound also showed good antifungal activity and has further development value.

scholarly journals In Vitro Interactions of Echinocandins with Triazoles against Multidrug-Resistant Candida auris

2017 ◽  
Vol 61 (11) ◽  
Author(s):  
Hamed Fakhim ◽  
Anuradha Chowdhary ◽  
Anupam Prakash ◽  
Afsane Vaezi ◽  
Eric Dannaoui ◽  
...  
Keyword(s):  
Concentration Index ◽  
Inhibitory Concentration ◽  
Multidrug Resistant ◽  
Fractional Inhibitory Concentration ◽  
Candida Auris ◽  
Fractional Inhibitory Concentration Index ◽  
Synergistic Interactions ◽  
In Vitro Interactions

ABSTRACT We determined the in vitro interactions between echinocandins and azoles against 10 multidrug-resistant Candida auris strains by use of a microdilution checkerboard technique. Our results suggest synergistic interactions between micafungin and voriconazole with fractional inhibitory concentration index (FICI) values of 0.15 to 0.5, and we observed indifferent interactions when micafungin was combined with fluconazole (FICI, 0.62 to 1.5). Combinations of caspofungin with fluconazole or voriconazole exhibited indifferent interactions. No antagonism was observed for any combination.

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