LTX-109 is a novel agent for nasal decolonization of methicillin-resistant and -sensitive Staphylococcus aureus.

Abstract

Nasal decolonization has a proven effect on the prevention of severe Staphylococcus aureus infections and the control of methicillin-resistant S. aureus (MRSA). However, rising rates of resistance to antibiotics highlight the need for new substances for nasal decolonization. LTX-109 is a broad-spectrum, fast-acting bactericidal antimicrobial drug for topical treatment, which causes membrane disruption and cell lysis. This mechanism of action is not associated with cross-resistance and has a low propensity for development of resistance. In the present study, persistent nasal MRSA and methicillin-sensitive S. aureus (MSSA) carriers were treated for 3 days with vehicle or with 1%, 2%, or 5% LTX-109. A significant effect on nasal decolonization was observed already after 2 days of LTX-109 treatment in subjects treated with 2% or 5% LTX-109 compared to vehicle (P ≤ 0.0012 by Dunnett's test). No safety issues were noted during the 9-week follow-up period. Minimal reversible epithelial lesions were observed in the nasal cavity. The systemic exposure was very low, with a maximum concentration of drug in plasma (Cmax) at 1 to 2 h postdosing (3.72 to 11.7 ng/ml). One week after treatment initiation, LTX-109 was not detectable in any subject. Intranasal treatment of S. aureus with LTX-109 is safe and reduces the bacterial load already after a single day of treatment. Hence, LTX-109 has potential as a new and effective antimicrobial agent with a low propensity of resistance development that can prevent infections by MSSA/MRSA during hospitalization. (This study has been registered at ClinicalTrials.gov under registration no. NCT01158235.).

• Authors: Anna C Nilsson, Håkan Janson, Hedda Wold, Anders Fugelli, Karin Andersson, Camilla Håkangård, Pernilla Olsson, Wenche Marie Olsen
• Journal: Antimicrobial agents and chemotherapy (Antimicrob Agents Chemother) Vol. 59 Issue 1 Pg. 145-51 (Jan 2015) ISSN: 1098-6596 [Electronic] United States
• PMID: 25331699 (Publication Type: Clinical Trial, Phase I, Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Chemical References

• Anti-Bacterial Agents
• Oligopeptides
• L-arginyl-2,5,7-tris(1,1-dimethylethyl)-L-tryptophyl-N-(2-phenylethyl)-L-argininamide

Topics

• Administration, Intranasal
• Adolescent
• Adult
• Aged
• Anti-Bacterial Agents (adverse effects, therapeutic use)
• Bacterial Load (drug effects)
• Double-Blind Method
• Female
• Humans
• Male
• Methicillin-Resistant Staphylococcus aureus (drug effects)
• Middle Aged
• Nasal Cavity (microbiology)
• Oligopeptides (adverse effects, pharmacokinetics, therapeutic use)
• Staphylococcal Infections (drug therapy)
• Young Adult