LTX-109 Is a Novel Agent for Nasal Decolonization of Methicillin-Resistant and -Sensitive Staphylococcus aureus

• Published in: Antimicrobial agents and chemotherapy Vol. 59; no. 1; pp. 145 - 151
• Main Authors: Nilsson, Anna C., Janson, Håkan, Wold, Hedda, Fugelli, Anders, Andersson, Karin, Håkangård, Camilla, Olsson, Pernilla, Olsen, Wenche Marie
• Format: Journal Article
• Language: English
• Published: United States American Society for Microbiology 01.01.2015
• Subjects: Administration, Intranasal; Adolescent; Adult; Aged; Anti-Bacterial Agents; Anti-Bacterial Agents - adverse effects; Anti-Bacterial Agents - therapeutic use; Bacterial Load - drug effects; Clinical Therapeutics; Double-Blind Method; Female; Humans; Male; Methicillin-Resistant Staphylococcus aureus; Methicillin-Resistant Staphylococcus aureus - drug effects; Middle Aged; Nasal Cavity; Nasal Cavity - microbiology; Oligopeptides; Oligopeptides - adverse effects; Oligopeptides - pharmacokinetics; Oligopeptides - therapeutic use; Staphylococcal Infections; Staphylococcal Infections - drug therapy; Staphylococcus aureus; Young Adult
• ISSN: 0066-4804; 1098-6596; 1098-6596
• DOI: 10.1128/AAC.03513-14

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 ( C max ) 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.)