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

• DOI: 10.1128/aac.03513-14
• Publication Date: 2014-10-21T02:43:11Z
• Authors: Anna C. Nilsson; Håkan Janson; Hedda Wold; Anders Fugelli; Karin Andersson; Camilla Håkangård; Pernilla Olsson; Wenche Marie Olsen
• Keywords: Adult; Male; Methicillin-Resistant Staphylococcus aureus; 0301 basic medicine; 0303 health sciences; Adolescent; Middle Aged; Staphylococcal Infections; Bacterial Load; Anti-Bacterial Agents; 3. Good health; Young Adult; 03 medical and health sciences; Double-Blind Method; 13. Climate action; Humans; Female; Nasal Cavity; Oligopeptides; Administration, Intranasal; Aged

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 ( 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.)