Pharmacodynamics of Daptomycin

Wenzler, Eric; Liao, Siyun; Rodvold, Keith A.

doi:10.1007/978-1-4939-3323-5_13

Cited by 3 publications

(1 citation statement)

References 109 publications

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“…Daptomycin was reported to be an antibacterial approximately 100 times more effective than Vancomycin on a hamster model of Clostridium difficile (Dong et al, 1987 ). Its antibacterial activity is strictly concentration‐dependent (Wenzler et al, 2016 ), and requires complexation with calcium (Gregoire et al, 2021 ). Because it is not absorbed from the gastrointestinal tract, it has to be administered parentally.…”

Section: Molecular Structure‐based Classification Of Antibacterialsmentioning

confidence: 99%

Structure–activity relationships of antibacterial peptides

Ciulla

Gelain

2023

Microbial Biotechnology

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Antimicrobial peptides play a crucial role in innate immunity, whose components are mainly peptide‐based molecules with antibacterial properties. Indeed, the exploration of the immune system over the past 40 years has revealed a number of natural peptides playing a pivotal role in the defence mechanisms of vertebrates and invertebrates, including amphibians, insects, and mammalians. This review provides a discussion regarding the antibacterial mechanisms of peptide‐based agents and their structure–activity relationships (SARs) with the aim of describing a topic that is not yet fully explored. Some growing evidence suggests that innate immunity should be strongly considered for the development of novel antibiotic peptide‐based libraries. Also, due to the constantly rising concern of antibiotic resistance, the development of new antibiotic drugs is becoming a priority of global importance. Hence, the study and the understanding of defence phenomena occurring in the immune system may inspire the development of novel antibiotic compound libraries and set the stage to overcome drug‐resistant pathogens. Here, we provide an overview of the importance of peptide‐based antibacterial sources, focusing on accurately selected molecular structures, their SARs including recently introduced modifications, their latest biotechnology applications, and their potential against multi‐drug resistant pathogens. Last, we provide cues to describe how antibacterial peptides show a better scope of action selectivity than several anti‐infective agents, which are characterized by non‐selective activities and non‐targeted actions toward pathogens.

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Section: Molecular Structure‐based Classification Of Antibacterialsmentioning

confidence: 99%

Structure–activity relationships of antibacterial peptides

Ciulla

Gelain

2023

Microbial Biotechnology

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Antibiotic Distribution into Cerebrospinal Fluid: Can Dosing Safely Account for Drug and Disease Factors in the Treatment of Ventriculostomy-Associated Infections?

et al. 2017

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Ventriculostomy-associated infections, or ventriculitis, in critically ill patients are associated with considerable morbidity. Efficacious antibiotic dosing for the treatment of these infections may be complicated by altered antibiotic concentrations in the cerebrospinal fluid due to variable meningeal inflammation and antibiotic properties. Therefore, doses used to treat infections with a higher degree of meningeal inflammation (such as meningitis) may often fail to achieve equivalent exposures in patients with ventriculostomy-associated infections such as ventriculitis. This paper aims to review the disease burden, infection rates, and common pathogens associated with ventriculostomy-associated infections. This review also seeks to describe the disease- and drug-related factors that influence antibiotic distribution into cerebrospinal fluid and provide a critical appraisal of current dosing of antibiotics commonly used to treat these types of infections. A Medline search of relevant articles was conducted and used to support a review of cerebrospinal fluid penetration of vancomycin, including critical appraisal of the recent paper by Beach et al. recently published in this journal. We found that in the intensive care unit, ventriculostomy-associated infections are the most common and serious complication of external ventricular drain insertion and often result in prolonged patient stay and increased healthcare costs. Reported infection rates are extremely variable (between 0 and 45%), hindered by the inherent diagnostic difficulty. Both Gram-positive and Gram-negative organisms are associated with such infections and the rise of multi-drug-resistant pathogens means that effective treatment is an ongoing challenge. Disease factors that may need to be considered are reduced meningeal inflammation and the presence of critical illness; drug factors include physiochemical properties, degree of plasma-protein binding, and affinity to active transporter proteins present in the blood-cerebrospinal fluid barrier. The relationship between cerebrospinal fluid antibiotic exposures in the setting of ventriculostomy-associated infection and clinical response has not been fully elucidated for many of the antibiotics commonly used in its treatment. More thorough and clinically relevant investigations are needed to better define blood pharmacokinetic/pharmacodynamics targets and optimal therapeutic exposures for treatment of ventriculostomy-associated infections. It is hoped that this future research will be able to provide clearer recommendations for clinicians frequently faced with dosing-related dilemmas when treating patients with these challenging infections.

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A facile and selective derivatization approach on kynurenine-NH2 in daptomycin, leading to the discovery of hexakynomycin to combat multidrug-resistant Gram-positive pathogens especially daptomycin-resistant bacteria

Guan

Chen

et al. 2023

European Journal of Medicinal Chemistry

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Pharmacodynamics of Daptomycin

Cited by 3 publications

References 109 publications

Structure–activity relationships of antibacterial peptides

Structure–activity relationships of antibacterial peptides

Antibiotic Distribution into Cerebrospinal Fluid: Can Dosing Safely Account for Drug and Disease Factors in the Treatment of Ventriculostomy-Associated Infections?

A facile and selective derivatization approach on kynurenine-NH2 in daptomycin, leading to the discovery of hexakynomycin to combat multidrug-resistant Gram-positive pathogens especially daptomycin-resistant bacteria

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