title: 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.affiliation: Department of Clinical Sciences, Infectious Diseases Research Unit, Lund University, Malmö, Sweden anna.nilsson@med.lu.se.
authors.forename: Anna C
authors.initials: AC
authors.lastname: Nilsson
authors.affiliation: Department of Laboratory Medicine, Medical Microbiology Unit, Lund University, Malmö, Sweden.
authors.forename: Håkan
authors.initials: H
authors.lastname: Janson
authors.affiliation: Lytix Biopharma AS, Oslo, Norway.
authors.forename: Hedda
authors.initials: H
authors.lastname: Wold
authors.affiliation: Lytix Biopharma AS, Oslo, Norway.
authors.forename: Anders
authors.initials: A
authors.lastname: Fugelli
authors.affiliation: Department of Clinical Sciences, Infectious Diseases Research Unit, Lund University, Malmö, Sweden.
authors.forename: Karin
authors.initials: K
authors.lastname: Andersson
authors.affiliation: Department of Clinical Sciences, Infectious Diseases Research Unit, Lund University, Malmö, Sweden.
authors.forename: Camilla
authors.initials: C
authors.lastname: Håkangård
authors.affiliation: Department of Clinical Sciences, Infectious Diseases Research Unit, Lund University, Malmö, Sweden.
authors.forename: Pernilla
authors.initials: P
authors.lastname: Olsson
authors.affiliation: Lytix Biopharma AS, Oslo, Norway.
authors.forename: Wenche Marie
authors.initials: WM
authors.lastname: Olsen
mesh_terms: D000281:Administration, Intranasal; D000293:Adolescent; D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000627:therapeutic use*; D058491:Bacterial Load / Q000187:drug effects; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects*; D008875:Middle Aged; D009296:Nasal Cavity / Q000382:microbiology*; D009842:Oligopeptides / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D013203:Staphylococcal Infections / Q000188:drug therapy*; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D009842:Oligopeptides; C568461:L-arginyl-2,5,7-tris(1,1-dimethylethyl)-L-tryptophyl-N-(2-phenylethyl)-L-argininamide