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.).

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Figures

FIG 1

Disposition of subjects in the study.

FIG 2

Nasal decolonization during days 1 to 4 and weeks 2 to 9 after treatment with vehicle or 1%, 2%, or 5% LTX-109. The mean bacterial load, analyzed as CFU/ml, with standard deviation (SD) is shown. The minimum CFU detectable is represented by a horizontal line. At days 3 and day 4 there was a statistically significant reduction in the 2% LTX-109 group (P = 0.0008 and P = 0.0180, respectively) and the 5% LTX-109 group (P = 0.0012 and P = 0.0105, respectively) compared to vehicle (Dunnett's test).