In-vitro and In-vivo Efficacy of Zinc Acetate against Propionibacteria Alone and in Combination with Erythromycin

AbstractTo be effective, chemotherapy against tuberculosis (TB) must kill the intracellular population of the pathogen, Mycobacterium tuberculosis. However, how host cell microenvironments affect antibiotic accumulation and efficacy remains unclear. Here, we use correlative light, electron, and ion microscopy to investigate how various microenvironments within human macrophages affect the activity of pyrazinamide (PZA), a key antibiotic against TB. We show that PZA accumulates heterogeneously among individual bacteria in multiple host cell environments. Crucially, PZA accumulation and efficacy is maximal within acidified phagosomes. Bedaquiline, another antibiotic commonly used in combined TB therapy, enhances PZA accumulation via a host cell-mediated mechanism. Thus, intracellular localisation and specific microenvironments affect PZA accumulation and efficacy. Our results may explain the potent in vivo efficacy of PZA, compared to its modest in vitro activity, and its critical contribution to TB combination chemotherapy.

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P074 In vitro and in vivo efficacy of linezolid on Treponema pallidum, the syphilis agent

10.1136/sextrans-2021-sti.208 ◽

2021 ◽

Author(s):

L Giacani ◽

A Haynes ◽

M Vall Mayans ◽

M Ubals Cazorla ◽

C Nieto ◽

...

Keyword(s):

Treponema Pallidum ◽

In Vivo Efficacy

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Efficacy of a novel lantibiotic, CMB001, against MRSA

Journal of Antimicrobial Chemotherapy ◽

10.1093/jac/dkab040 ◽

2021 ◽

Author(s):

Jerzy Karczewski ◽

Christine M Brown ◽

Yukari Maezato ◽

Stephen P Krasucki ◽

Stephen J Streatfield

Keyword(s):

Antibacterial Activity ◽

Pharmacokinetic Analysis ◽

Maximum Tolerable Dose ◽

In Vivo Efficacy ◽

Clostridioides Difficile ◽

Alternative Treatment Option ◽

Significant Damage ◽

Tolerable Dose

Abstract Objectives To evaluate the efficacy of a novel lantibiotic, CMB001, against MRSA biofilms in vitro and in an in vivo experimental model of bacterial infection. Methods Antibacterial activity of CMB001 was measured in vitro after its exposure to whole blood or to platelet-poor plasma. In vitro efficacy of CMB001 against a Staphylococcus aureus biofilm was studied using scanning electron microscopy. The maximum tolerable dose in mice was determined and a preliminary pharmacokinetic analysis for CMB001 was performed in mice. In vivo efficacy was evaluated in a neutropenic mouse thigh model of infection. Results CMB001 maintained its antibacterial activity in the presence of blood or plasma for up to 24 h at 37°C. CMB001 efficiently killed S. aureus within the biofilm by causing significant damage to the bacterial cell wall. The maximum tolerable dose in mice was established to be 10 mg/kg and could be increased to 30 mg/kg in mice pretreated with antihistamines. In neutropenic mice infected with MRSA, treatment with CMB001 reduced the bacterial burden with an efficacy equivalent to that of vancomycin. Conclusions CMB001 offers potential as an alternative treatment option to combat MRSA. It will be of interest to evaluate the in vivo efficacy of CMB001 against infections caused by other pathogens, including Clostridioides difficile and Acinetobacter baumannii, and to expand its pharmacokinetic/pharmacodynamic parameters and safety profile.

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From plants to phospholipid vesicles: A comprehensive review on the incorporation of phytochemicals into phospholipid vesicles designed for skin applications with special focus on scalability and in vitro and in vivo efficacy

Journal of Drug Delivery Science and Technology ◽

10.1016/j.jddst.2021.103049 ◽

2021 ◽

pp. 103049

Author(s):

Mohamad Allaw ◽

Maria Letizia Manca ◽

Ines Castangia ◽

Maria Manconi

Keyword(s):

Phospholipid Vesicles ◽

Special Focus ◽

In Vivo Efficacy ◽

Comprehensive Review

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In vitro and in vivo Efficacy of New Blue Light Emitting Diode Phototherapy Compared to Conventional Halogen Quartz Phototherapy for Neonatal Jaundice

Journal of Korean Medical Science ◽

10.3346/jkms.2005.20.1.61 ◽

2005 ◽

Vol 20 (1) ◽

pp. 61 ◽

Cited By ~ 23

Author(s):

Yun Sil Chang ◽

Jong Hee Hwang ◽

Hyuk Nam Kwon ◽

Chang Won Choi ◽

Sun Young Ko ◽

...

Keyword(s):

Blue Light ◽

Neonatal Jaundice ◽

Light Emitting Diode ◽

In Vivo Efficacy ◽

Light Emitting

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Correlation of In Vitro Activity, Serum Levels, and In Vivo Efficacy of Posaconazole against Rhizopus microsporus in a Murine Disseminated Infection

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01026-09 ◽

2009 ◽

Vol 53 (12) ◽

pp. 5022-5025 ◽

Cited By ~ 26

Author(s):

M. Mar Rodríguez ◽

F. Javier Pastor ◽

Enrique Calvo ◽

Valentina Salas ◽

Deanna A. Sutton ◽

...

Keyword(s):

Serum Levels ◽

Rhizopus Microsporus ◽

In Vitro Susceptibility ◽

In Vivo Efficacy ◽

Susceptibility Data ◽

Microdilution Method ◽

Drug Concentrations ◽

Broth Microdilution Method

ABSTRACT A broth microdilution method was used to evaluate the in vitro activities of seven antifungal agents against 15 clinical strains of Rhizopus microsporus. Amphotericin B (AMB) and posaconazole (POS) were the most active drugs. In a model of disseminated R. microsporus infection in immunosuppressed mice, we studied the efficacy of POS administered once or twice daily against four of the strains previously tested in vitro and compared it with that of liposomal AMB (LAMB). LAMB was the most effective treatment for the two strains with intermediate susceptibility to POS. For the two POS-susceptible strains, LAMB and POS at 20 mg/kg of body weight twice a day orally showed similar efficacies. The in vivo efficacy of POS administered twice a day orally correlated with the in vitro susceptibility data and the serum drug concentrations.

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Are Platelet Aggregation Tests the Best Way to Assess New Drugs for Arterial Disease

General medicine and Clinical Practice ◽

10.31579/2639-4162/003 ◽

2018 ◽

Vol 1 (1) ◽

pp. 01-03

Author(s):

Mark I. M. Noble

Keyword(s):

Platelet Aggregation ◽

Platelet Function ◽

Platelet Rich Plasma ◽

New Drugs ◽

In Vitro Test ◽

In Vivo Efficacy ◽

Experimental Animals ◽

Stenosed Artery

Over many years, laboratory testing of platelet aggregability have been carried out in attempts to develop drugs that would prevent thrombosis in arteries. The problems encountered included the question of methodology. Blood samples have to be anticoagulated in order to study the platelets. Anti-coagulation with citrate and tests on derived platelet rich plasma did not correlate at all well with thrombus growth in the stenosed coronary arteries of experimental animals and citrate removes the calcium ions which are vital for platelet function. Anticoagulation with heparin also interfered with platelet function, so that now, hirudins are the preferred anticoagulant. However it was observed that if, instead of stimulating platelet aggregation with adrenaline or ADP, serotonin was applied to the preparation, very little aggregation took place in spite of serotonin 5HT2A antagonists being the most potent inhibitors of thrombus growth in experimental animals. Another indicator that primary platelet agggregation is not a predictor of in vivo efficacy was the finding that 5HT2A antagonism inhibited aggregate growth. In a stenosed artery the platelets are activated by increased shear stress and blood turbulence with release of platelet serotonin causing positive feedback activation of more platelets. At present, there does not seem to be a bench in vitro test that accurately predicts in vivo efficacy in stenosed artery occlusive thrombosis.

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