Pharmacokinetics and Pharmacodynamics (PK/PD) of Corallopyronin A against Methicillin-Resistant Staphylococcus aureus

Becker, Tim; Schiefer, Andrea; Grosse, Miriam; Ehrens, Alexandra; Jansen, Rolf; Aden, Tilman; Kehraus, Stefan; König, Gabriele M.; Krome, Anna K.; Hübner, Marc P.; Wagner, Karl G.; Stadler, Marc; Pfarr, Kenneth; Hoerauf, Achim

doi:10.3390/pharmaceutics15010131

Cited by 10 publications

(8 citation statements)

References 38 publications

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“…Furthermore, compound concentrations were determined in target compartments, such as lung, kidney and thigh tissue, using LC-MS/ MS. Based on the pharmacokinetic results, the pharmacodynamic profile of Myxopyronin B was assessed utilizing the standard neutropenic thigh and lung infection models. [44] Estimation of pharmacodynamic and pharmacokinetic effects of Myxopyronin B in randomized human clinical trials phases 1/2:…”

Section: Estimation Of Pharmacodynamic and Pharmacokinetic Effects Of...mentioning

confidence: 99%

Screening and the Industry of Myxopyronin B Antibiotic from Different Soil Environments in Egypt

Kassab

2024

Preprint

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Background: Across the world, antibiotic resistance is a grave problem. To address this issue, it is necessary to investigate new antibiotic sources. Aim of the study: Egypt's diverse soil habitats were used to produce bacterial Myxopyronin B, which was then tested for antimicrobial activity in preclinical animal studies and randomized human clinical trials stages 1/2. Type of the study: Screening experimental study. Methodology: Egypt's various soil conditions were examined for the development of bacterial isolates that produced the antibiotic compound Myxopyronin B. Reversed phase HPLC was used to purify Myxopyronin B. To determine the test antibiotic's minimum inhibitory concentration( MIC) and invitro antibacterial activity, the Broth microdilution method and the Paper disc diffusion assay were utilized. Moreover, in vivo antibacterial spectrum, adverse medication responses, and pharmacokinetics were found in preclinical animal testing stages and phases 1/2 of randomized clinical studies involving volunteer humans. Results: Myxopyronin B was generated from the culture supernatant of Myxococcus SDU36, the main soil bacterial isolate cultured on a Casein yeast peptone plate. With MICs less than 100 mcg/ml, the test antibiotic prevented the growth of several Gram +ve bacteria, whereas, at MICs higher than 100 mcg/ml, it inhibited the development of a small number of Gram -ve bacteria, including Escherichia coli. However, eukaryotic cells—such as those found in fungi and humans—were unaffected. The test antibiotic was seen to inhibit prokaryotic DNA-dependent RNA polymerase( RNLP), indicating its bactericidal activity. Mean Cmax was 9-10 mcg/ ml at mean Tmax 1 hour when 600 mg dose was orally administered in randomized human clinical trials phases 1/2, and T1/2 reached 2.25 hours following first-order kinetics of elimination. Duration of its action was nearly 8 hours after oral administration. Rare toxicity was detected during preclinical and randomized human clinical trials phases 1/2 in the form of mild diarrhea and GI upset in less than 7 % of experimental candidates. It exhibited approximately 90% plasma protein binding, especially with albumin which resulted in prolonged therapeutic action. It showed a concentration dependant antibiotic killing effect. With the concentration-dependent killing pattern, the higher the drug concentration relative to the pathogen minimum inhibitory concentration( MIC), the greater the rate and extent of antimicrobial activity. Conclusion: The present study was promising due to the production of the bactericidal antibiotic Myxopyronin B from Myxococcus sp. SDU36 isolated from different soil environments in Egypt.

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Section: Estimation Of Pharmacodynamic and Pharmacokinetic Effects Of...mentioning

confidence: 99%

Screening and the Industry of Myxopyronin B Antibiotic from Different Soil Environments in Egypt

Kassab

2024

Preprint

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“…Furthermore, compound concentrations were determined in target compartments, such as lung, kidney and thigh tissue, using LC-MS/ MS. Based on the pharmacokinetic results, the pharmacodynamic profile of Corallopyronin A was assessed victimizing the standard neutropenic thigh and lung infection models. [44] Estimation of pharmacodynamic and pharmacokinetic effects of Corallopyronin A in randomized human clinical trials phases 1/2:…”

Section: Procedures Of Broth Dilution Assay For Determination Of Mics...mentioning

confidence: 99%

Exhibition of Corallopyronin A an Antibiotic from Different Soil Environments in Egypt

Kassab

2024

Preprint

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Background: Across the world, antibiotic resistance is a critical challenge. To address such a problem, it has to be done to investigate new antibiotic sources. Aim of the study: Study of the antibacterial activity of Corallopyronin A in preclinical animal testing and randomized human clinical trials stages 1/2, as well as investigating the purification of Corallopyronin A from different soil conditions in Egypt. Type of the study: Screening experimental study. Methodology: Egypt's various soil conditions were tested to develop bacterial isolates that produced the antibiotic compound Corallopyronin A. Reversed phase HPLC was used to purify Myxopyronin A. The broth microdilution method and the paper disc diffusion assay determined the test antibiotic's minimum inhibitory concentration( MIC) and in vitro antibacterial activity. Moreover, in vivo antibacterial spectrum, adverse medication responses, and pharmacokinetics were found in phases 1/2 of randomized clinical studies involving humans and animal models. Results: Corallopyronin A was generated from the culture supernatant of the soil bacterial isolate Corallococcus coralloides M2, cultivated on a Casein yeast peptone( CYP) plate. The test antibiotic prevented the growth of several Gram-ve bacteria, including Escherichia coli, at MICs higher than 100 mcg/ ml; while blocking the development of many Gram +ve bacteria, with MICs ranging from 3 to 15 mcg/ ml. However, eukaryotic cells—such as those found in fungi and humans—were unaffected. A bactericidal consequence of the test antibiotic was detected in the inhibition of prokaryotic DNA-dependent RNA polymerase( RNLP). Conclusion: The synthesis of the bactericidal antibiotic Corallopyronin A from Corallococcus coralloides M2 isolated from different soil settings in Egypt intrigued the current investigation.

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“…In the present study, the pharmacokinetics and the pharmacodynamics of Myxopyronin A were evaluated after dosing in male rabbit animal models weighing about 2 kg. Furthermore, compound concentrations were determined in target compartments, such as lung, kidney and thigh tissue, using LC-MS/ MS. Based on the pharmacokinetic results, the pharmacodynamic profile of Myxopyronin A was assessed victimizing the standard neutropenic thigh and lung infection models [44].…”

Section: Sucrose Fermentation Testmentioning

confidence: 99%

Screening and the Production of Myxopyronin A Antibiotic from different Soil Environments in Egypt

Kassab

2024

Preprint

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Background: Antibiotic resistance is an overwhelming serious difficulty globally. This necessitates the exploration of novel sources of antibiotics to overcome this challenge. Aim of the study: Bacterial Myxopyronin A production from various soil environments Egypt; as well as testing its antimicrobial activity in preclinical animal testing and randomized human clinical trials phases 1/2. Type of the study: Screening experimental study. Methodology: Different soil environments in Egypt were screened for the growth of bacterial isolates producing Myxopyronin A as an antimicrobial agent. Purification of Myxopyronin A was performed via reversed-phase HPLC. Paper disc diffusion assay, as well as broth dilution technique, were exploited to assess the invitro antimicrobial and minimum inhibitory concentration( MIC) of the test antibiotic. Furthermore, in vivo antimicrobial spectrum, adverse drug reactions, and pharmacokinetics were detected during animal model testing stages and human randomized clinical trials phases 1/2. Results: From the culture supernatant of the Myxobacterium Myxococcus fulvus 124B02 which was the predominant soil bacterial isolate grown on the Casein yeast peptone plate, Myxopyronin A was produced. The test antibiotic blocked the growth of many Gram +ve bacteria with MICs less than 100 mcg/ ml; whereas it inhibited the growth of a few Gram -ve bacteria such as Escherichia coli at MICs greater than 100 mcg/ ml. On the other hand, Eukaryotic cells such as fungal and human cells were not affected. Prokaryotic DNA-dependant-RNA polymerase( RNLP) was noticed to be inhibited via the test antibiotic suggesting its bactericidal action. Cmax was 7-8 mcg/ ml at Tmax 2 hours when 600 mg dose was orally administered in randomized human clinical trials phases 1/2; as well as T1/2 reached 2.5 hours following first-order kinetics of elimination. The duration of its action was nearly 12 hours after oral administration. Rare toxicity was detected during preclinical and randomized human clinical trials phases 1/2 in the form of mild diarrhea and cholestatic jaundice in less than 5 % of experimental candidates. Conclusion: The present study was promising due to the production of the bactericidal antibiotic Myxopyronin A from Myxococcus fulvus 124B02 isolated from different soil environments in Egypt.

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Pharmacokinetics and Pharmacodynamics (PK/PD) of Corallopyronin A against Methicillin-Resistant Staphylococcus aureus

Cited by 10 publications

References 38 publications

Screening and the Industry of <em>Myxopyronin B</em> Antibiotic from Different Soil Environments in Egypt

Screening and the Industry of <em>Myxopyronin B</em> Antibiotic from Different Soil Environments in Egypt

Exhibition of <em>Corallopyronin A </em>an Antibiotic from Different Soil Environments in Egypt

Screening and the Production of <em>Myxopyronin A</em> Antibiotic from different Soil Environments in Egypt

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