LTX-109 Is a Novel Agent for Nasal Decolonization of Methicillin-Resistant and -Sensitive Staphylococcus aureus
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
DOI:
10.1128/aac.03513-14
Publication Date:
2014-10-21T02:43:11Z
AUTHORS (8)
ABSTRACT
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.)
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