Assessment of the Additional Value of Verapamil to a Moxifloxacin and Linezolid Combination Regimen in a Murine Tuberculosis Model

Pieterman, Elise D.; Brake, Lindsey H.M. te; Knegt, Gerjo J. de; Meijden, Aart van der; Alffenaar, Jan‐Willem C.; Bax, Hannelore I.; Aarnoutse, Rob E.; Steenwinkel, Jurriaan E.M. de

doi:10.1128/aac.01354-18

Cited by 9 publications

(2 citation statements)

References 46 publications

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“…The formation of zone of inhibition indicates the development of antibacterial susceptibility of CQ against P. aeruginosa when combined with VRP in a 1:4 ratio. The study by Pieterman et al ( 2018 ), reported the use of VRP to enhance the antimicrobial activity of moxifloxacin and linezolid against mycobacterial infection in murine model. The study showed significant effect of VRP-mediated efflux pump inhibition that resulted in enhancement of the antimicrobial effects.…”

Section: Resultsmentioning

confidence: 99%

Study of chloroquine susceptibility potential of plants using pseudomonas aeruginosa as in vitro model

2022

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Chloroquine (CQ) is mainly known for antimalarial activity but due to lower sensitivity, it has not been well explored in the microbial disease treatment. In the present investigation, we attempted to enhance the CQ sensitivity in Pseudomonas aeruginosa . Presence of efflux pump is well demonstrated in bacterial system which plays an important role in drug sensitivity and resistance in bacteria and also serves other functions. Taking the advantage of presence of efflux pump in Pseudomonas aeruginosa , we made an attempt to sensitize the Pseudomonas aeruginosa with various plant extracts and phytochemicals for the development of CQ sensitivity. Ten rationally selected plant extracts were screened for the development of chloroquine sensitivity in P. aeruginosa . The chloroquine susceptibility assay was demonstrated by combining CQ and verapamil (a known efflux pump inhibitor) as a standard in an in vitro assay system. Results were quite encouraging as methanolic extracts of Syzygium aromaticum, Zingiber officinale and Curcuma longa were able to enhance chloroquine sensitivity in P. aeruginosa by increasing the zone of inhibition in well-defined assay system. These plant extracts were finally analysed for the presence of various phytochemicals. The Syzygium aromaticum extract showed the presence of phytochemicals, such as quinones, phenol, triterpenoid, saponins, tannins, alkaloids and flavonoids. On the other hand, the methanolic extract of Zingiber officinale and Curcuma longa showed the presence of saponins, tannins, alkaloids and flavonoids in the extract. Towards the identification of active principle of selected plant extract for CQ sensitivity enhancement, thin-layer chromatography was performed and various phytocomponent bands were isolated. Flavonoid ( R f 0.44) in Syzygium aromaticum, alkaloid ( R f 0.43) in Zingiber officinale and phenol ( R f 0.62) in Curcuma longa were found responsible for the enhancement of CQ susceptibility in P. aeruginosa . This interesting finding confirmed the concept that a prior course or combination of plant extracts or phytochemicals with chloroquine can be effective against P. aeruginosa . Present investigation successfully presented the proof of concept for the enhancement of chloroquine sensitivity in bacterial system by modulating an efflux pump. Concept can be explored for repurposing chloroquine for new applications. Supplementary Information The online version contains supplementary material available at 10.1007/s13205-022-03382-1.

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Section: Resultsmentioning

confidence: 99%

Study of chloroquine susceptibility potential of plants using pseudomonas aeruginosa as in vitro model

2022

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“…MICs were determined according to Clinical and Laboratory Standards Institute standards [13]. The antibiotic drugs used were prepared as described elsewhere (Supplement 1) [5,14].…”

Section: Bacterial Strain and Tuberculosis Drugsmentioning

confidence: 99%

Superior Efficacy of a Bedaquiline, Delamanid, and Linezolid Combination Regimen in a Mouse Tuberculosis Model

Pieterman

Keutzer

Meijden

et al. 2021

The Journal of Infectious Diseases

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Background The treatment success rate of drug-resistant tuberculosis (DR-TB) is alarmingly low. Therefore, more effective and less complex regimens are urgently required. Methods We compared the efficacy of an all oral DR-TB drug regimen consisting of bedaquiline (25 mg/kg), delamanid (2.5 mg/kg) and linezolid (100 mg/kg) (BDL) on the mycobacterial load in the lungs and spleen of TB infected mice during a treatment period of 24 weeks. This treatment was compared to the standard regimen of isoniazid, rifampicin, pyrazinamide and ethambutol (HRZE). Relapse was assessed 12 weeks post-treatment. Two logistic regression models were developed to compare the efficacy of both regimens. Results Culture negativity in the lungs was achieved at 8 and 20 weeks of treatment with BDL and HRZE, respectively. After 14 weeks of treatment only one mouse relapsed in the BDL group, while in the HRZE group relapse was still observed at 24 weeks of treatment. Predictions from the final mathematical models showed that a 95% cure rate was reached after 20.5 and 28.5 weeks of treatment with BDL and HRZE, respectively. Conclusion The BDL regimen was observed to be more effective than HRZE and could be a valuable option for the treatment of DR-TB.

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Tuberculosis: Experimental Models, Innovations, and Challenges

Jhamb,

Singh,

Singh

2023

Recent Advances in Pharmaceutical Innovation and Research

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Assessment of the Additional Value of Verapamil to a Moxifloxacin and Linezolid Combination Regimen in a Murine Tuberculosis Model

Cited by 9 publications

References 46 publications

Study of chloroquine susceptibility potential of plants using pseudomonas aeruginosa as in vitro model

Study of chloroquine susceptibility potential of plants using pseudomonas aeruginosa as in vitro model

Superior Efficacy of a Bedaquiline, Delamanid, and Linezolid Combination Regimen in a Mouse Tuberculosis Model

Tuberculosis: Experimental Models, Innovations, and Challenges

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