Telavancin-associated acute kidney injury

Cavanaugh, Corey; Moeckel, Gilbert; Perazella, Mark A.

doi:10.5414/cn109651

Cited by 8 publications

(6 citation statements)

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“…Although the side effects of these compounds are mild, their effectiveness against drug-resistant Gram-positive organisms and for long-term treatment remains ambiguous [103][104][105]. Telavancin, another derivative of vancomycin, is more effective for treating a range of drug-resistant Gram-positive bacteria, but it has been reported that it may induce acute kidney injury and have a higher death rate than vancomycin [106,107]. Colistin may cause damage to the kidneys and the central nervous system in adult patients, and heavy use of colistin can result in the occurrence of colistin-resistant bacteria, making it problematic for regular use [108][109][110].…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

Development and Challenges of Antimicrobial Peptides for Therapeutic Applications

2020

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More than 3000 antimicrobial peptides (AMPs) have been discovered, seven of which have been approved by the U.S. Food and Drug Administration (FDA). Now commercialized, these seven peptides have mostly been utilized for topical medications, though some have been injected into the body to treat severe bacterial infections. To understand the translational potential for AMPs, we analyzed FDA-approved drugs in the FDA drug database. We examined their physicochemical properties, secondary structures, and mechanisms of action, and compared them with the peptides in the AMP database. All FDA-approved AMPs were discovered in Gram-positive soil bacteria, and 98% of known AMPs also come from natural sources (skin secretions of frogs and toxins from different species). However, AMPs can have undesirable properties as drugs, including instability and toxicity. Thus, the design and construction of effective AMPs require an understanding of the mechanisms of known peptides and their effects on the human body. This review provides an overview to guide the development of AMPs that can potentially be used as antimicrobial drugs.

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Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

Development and Challenges of Antimicrobial Peptides for Therapeutic Applications

2020

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“…Lung drug levels were reduced to 45% of the Cmax one day post-dose and then to 15% of the Cmax over the three-week monitoring period yet remained significantly above the MIC, pointing to the potential durability of the therapeutic to combat chronic pulmonary MRSA infection. Furthermore, Cmax plasma drug levels (also occurring 3 h post-dose) were 0.1% of lung Cmax, demonstrating that inhaled RV94 DPI results in markedly low systemic levels when given in a single dose by inhalation which could translate to a low probability for harmful off-target side effects such as renal toxicity that have been observed with parenteral lipoglycopeptide therapy [ 18 , 20 ].…”

Section: Discussionmentioning

confidence: 99%

“…However, in future work, a model that more accurately represents CF MRSA lung disease, where a chronic dosing paradigm could be investigated, would be desirable. Moreover, while the benefits of local delivery can be appreciated on the basis of reducing the potential for renal toxicity observed with systemically administered MRSA therapies such as vancomycin and telavancin [ 5 , 18 ], it is unknown at this time whether local toxicities could persist from chronic dosing of RV94 DPI; follow up studies would have to be conducted to better understand how this drug product would perform in repeat dosing regimen.…”

Section: Discussionmentioning

confidence: 99%

“…Lipoglycopeptides, hydrophobic derivatives of glycopeptides, have demonstrated potent activity against MRSA owing to their multiple bactericidal mechanisms and have been reported to efficiently penetrate and kill bacteria in biofilms and cells [ 15 , 16 , 17 ]. Drawbacks to clinical lipoglycopeptide use involve poor elimination kinetics in vivo, the requirement to be administered parenterally in a hospital setting, and renal toxicity for certain compounds (e.g., telavancin) [ 18 , 19 , 20 ]. To improve upon these shortcomings, we synthesized and reported on a new subclass of next generation lipoglycopeptide compounds designed specifically for pulmonary delivery [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

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Preclinical Investigation of a Lipoglycopeptide Dry Powder Inhalation Therapy for the Treatment of Pulmonary MRSA Infection

Konicek,

Plaunt,

Gharse

et al. 2023

Pharmaceutics

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The increased prevalence of pulmonary methicillin-resistant Staphylococcus aureus (MRSA) infection in patients living with cystic fibrosis (CF) is concerning due to a correlation with reduced life expectancy and lack of available treatment options. RV94 is a next generation lipoglycopeptide designed for pulmonary delivery that preclinically demonstrated high potency against MRSA in planktonic and protected colonies and improved pulmonary clearance relative to same class molecules. Here, RV94 was formulated into a dry powder for inhalation (DPI) to investigate the localized treatment of pulmonary MRSA presented in a potentially more convenient dosage form. RV94 DPI was generated using a spray-drying process with 12.5 wt% trileucine and demonstrated aerosol characteristics (2.0 μm MMAD and 73% FPF) predictive of efficient pulmonary deposition. In vivo PK from a single dose of RV94 DPI delivered by inhalation to rats yielded lung levels (127 μg/g) much greater than the MRSA minimum inhibitory concentration (0.063 μg/mL), low systemic levels (0.1 μg/mL), and a lung t1/2 equal to 3.5 days. In a rat acute pulmonary MRSA model, a single dose of RV94 DPI delivered by inhalation either up to seven days prior to or 24 h after infection resulted in a statistically significant reduction in lung MRSA titer.

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“…The www.videleaf.com antimicrobial peptide (AMP) database (https://aps.unmc.edu) encompasses a large collection of natural AMPs (~3,000) [30]. Notably, only seven AMPs are clinically used: daptomycin (natural and synthetic cyclic lipopeptide, 13 amino acids, inhibition of bacterial growth), gramicidin S (natural cyclic peptide, 12 amino acids, membrane disruption, and depolarization) [63], colistin (natural cyclic peptide, 10 amino acids, membrane lysis) [64], oritavancin (nature-inspired lipoglycopeptide, 7 amino acids, membrane lysis and inhibition of cell wall synthesis) [65], dalbavancin (naturally-inspired lipoglycopeptide, 7 amino acids, inhibition of cell wall synthesis) [66], telavancin (nature-inspired, lipoglycopeptide, 7 amino acids, membrane lysis and inhibition of cell wall synthesis) [67], and vancomycin (natural, 7 amino acids, inhibition of cell wall synthesis) [68]. Colistin was first approved for acute and chronic Gram-negative bacterial infections, and despite its significant renal and neurologic toxicity, it remains the last resort treatment for some multi-drug resistant (MDR) species such as Pseudomonas aeruginosa and Acinetobacter spp.…”

Section: Hdpsmentioning

confidence: 99%

nature inspired and medicinally relevant short peptides

Ciulla,

Civera,

Sattin

2023

Updates in Pharmacology

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Peptides constitute an important component of Nature's pharmacy and they play a significant role in several signaling pathways acting as natural biological messengers. While nature has mastered the cycle of creation, application, and destruction of large and short peptides to the benefit of the host organism, organic and medicinal chemists have in their capacity and small steps, made big developments in the field of peptide synthesis as well as in developing them as therapeutics. In comparison to their big counterparts, i.e. proteins, short peptides encompass several advantages, from the ease of synthesis to their physicochemical properties. However, the real challenge for in vivo application of therapeutic peptides is to overcome their low plasma availability and their fast enzymatic degradation. This review briefly covers the relevant areas of medicinally important short peptides and the recent developments made to turn these peptides into therapeutics. Also presented in this article are important efforts and strategies used to overcome some of the inherent limitations of peptidic molecules and thereby facilitate their progression in the clinical phases towards approved drugs.

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Telavancin-associated acute kidney injury

Cited by 8 publications

References 0 publications

Development and Challenges of Antimicrobial Peptides for Therapeutic Applications

Development and Challenges of Antimicrobial Peptides for Therapeutic Applications

Preclinical Investigation of a Lipoglycopeptide Dry Powder Inhalation Therapy for the Treatment of Pulmonary MRSA Infection

nature inspired and medicinally relevant short peptides

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