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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.).

SUBMITTER: Nilsson AC

PROVIDER: S-EPMC4291342 | biostudies-literature | 2015 Jan

REPOSITORIES: biostudies-literature

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LTX-109 is a novel agent for nasal decolonization of methicillin-resistant and -sensitive Staphylococcus aureus.

Nilsson Anna C AC Janson Håkan H Wold Hedda H Fugelli Anders A Andersson Karin K Håkangård Camilla C Olsson Pernilla P Olsen Wenche Marie WM

Antimicrobial agents and chemotherapy 20141020 1

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 ...[more]

PMID: 25331699

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Project description:BACKGROUND:Skin and soft tissue infections (SSTIs) due to community-acquired methicillin-resistant Staphylococcus aureus (MRSA) can lead to a number of significant known medical outcomes including hospitalization, surgical procedures such as incision and drainage (I&D), and the need for decolonization procedures to remove the bacteria from the skin and nose and prevent recurrent infection. Little research has been done to understand patient and caregiver-centered outcomes associated with the successful treatment of MRSA infection. OBJECTIVE:This study aimed to uncover MRSA decolonization outcomes that are important to patients and their parents in order to create a set of prototype measures for use in the MRSA Eradication and Decolonization in Children (MEDiC) study. METHODS:A 4-hour, human-centered design (HCD) workshop was held with 5 adolescents (aged 10-18 years) who had experienced an I&D procedure and 11 parents of children who had experienced an I&D procedure. The workshop explored the patient and family experience with skin infection to uncover patient-centered outcomes of MRSA treatment. The research team analyzed the audio and artifacts created during the workshop and coded for thematic similarity. The final themes represent patient-centered outcome domains to be measured in the MEDiC comparative effectiveness trial. RESULTS:The workshop identified 9 outcomes of importance to patients and their parents: fewer MRSA outbreaks, improved emotional health, improved self-perception, decreased social stigma, increased amount of free time, increased control over free time, fewer days of school or work missed, decreased physical pain and discomfort, and decreased financial burden. CONCLUSIONS:This study represents an innovative HCD approach to engaging patients and families with lived experience with MRSA SSTIs in the study design and trial development to determine meaningful patient-centered outcomes. We were able to identify 9 major recurrent themes. These themes were used to develop the primary and secondary outcome measures for MEDiC, a prospectively enrolling comparative effectiveness trial. TRIAL REGISTRATION:ClinicalTrials.gov NCT02127658; https://clinicaltrials.gov/ct2/show/NCT02127658.

Project description:BACKGROUND:Community-acquired methicillin-resistant Staphylococcus aureus (MRSA) skin and soft tissue infections affect many healthy children. A significant number of these children are hospitalized and require surgical incision and drainage (I&D). Once sent home, these children and families are asked to complete burdensome home decolonization and hygiene procedures in an effort to prevent the high rate of recurrent infections. OBJECTIVE:This component of the Methicillin-resistant Staphylococcus aureus Eradication and Decolonization in Children (MEDiC) study aimed to develop a toolkit to assist MEDiC study participants in completing MRSA decolonization and hygiene procedures at home (the MEDiC kit). METHODS:In all, 5 adolescents (aged 10-18 years) who had undergone an I&D procedure for a skin infection and 11 parents of children who had undergone an I&D procedure for a skin infection were engaged in a 4-hour group workshop using a human-centered design approach. The topics covered in this workshop and analyzed for this paper were (1) attitudes about MRSA decolonization procedures and (2) barriers to the implementation of MRSA decolonization and hygiene procedures. The team analyzed the audio and artifacts created during the workshop and synthesized their findings to inform the creation of the MEDiC kit. RESULTS:The workshop activities uncovered barriers to successful completion of the decolonization and hygiene procedures: lack of step-by-step instruction, lack of proper tools in the home, concerns about adverse events, lack of control over some aspects of the hygiene procedures, and general difficulty coordinating all the procedures. Many of these could be addressed as part of the MEDiC kit. In addition, the workshop revealed that effective communication about decolonization would have to address concerns about the effects of bleach, provide detailed information, give reasons for the specific decolonization and hygiene protocol steps, and include step-by-step instructions (preferably through video). CONCLUSIONS:Through direct engagement with patients and families, we were able to better understand how to support families in implementing MRSA decolonization and hygiene protocols. In addition, we were able to better understand how to communicate about MRSA decolonization and hygiene protocols. With this knowledge, we created a robust toolkit that uses patient-driven language and visuals to help support patients and families through the implementation of these protocols. TRIAL REGISTRATION:ClinicalTrials.gov NCT02127658; https://clinicaltrials.gov/ct2/show/NCT02127658.

Project description:ImportanceChlorhexidine gluconate (CHG) and mupirocin are widely used to decolonize patients with methicillin-resistant Staphylococcus aureus (MRSA) and reduce risks associated with infection in hospitalized populations. Quantifying the association of an application of CHG alone or in combination with mupirocin with risk of MRSA infection is important for studies evaluating alternative decolonization strategies or schedules and for identifying whether there is room for improved decolonizing agents.ObjectiveTo estimate the proportion of patients with MRSA decolonized per application of CHG and mupirocin from existing population-level studies.Design, setting, and participantsA stochastic mathematical model of an 18-bed intensive care unit (ICU) in an academic medical center operating over 1 year was used to estimate parameters for the proportion of simulated patients with MRSA decolonized per application of CHG and mupirocin. The model was conducted using approximate bayesian computation with data from an existing meta-analysis of studies conducted from February 2005 through January 2015. Data were analyzed from January 2018 through November 2019.ExposureA universal decolonization protocol for colonized patients in the ICU using CHG or CHG and mupirocin in combination was simulated.Main outcomes and measuresThe proportion of patients with MRSA decolonized per application of CHG and mupirocin was estimated.ResultsThe estimated proportion of patients with MRSA decolonized per application of CHG was 0.15 (95% credible interval, 0.01-0.42), and the estimated proportion per application of mupirocin in conjunction with CHG was 0.15 (95% credible interval, 0.01-0.54). A lag in colonization detection was associated with decreases in the CHG estimate (0.11; 95% credible interval, 0.01-0.30) and mupirocin estimate (0.10; 95% credible interval, 0.00-0.34), which were sensitive to the value of the modeled contact rate between nurses and patients. A 1% increase in the value of this parameter was associated with a 0.73% increase in the estimated combined outcomes associated with CHG and mupirocin (95% CI: 0.71, 0.75). Gaps longer than 24 hours in the administration of decolonizing agents were associated with a decrease of within-ICU MRSA transmission. Compared with a mean (SD) of 1.23 (0.27) acquisitions per 1000 patient-days in scenarios with no decolonizing bathing, a bathing protocol administering CHG and mupirocin every 120 hours was associated with a mean (SD) acquisition rate of 1.03 (0.24) acquisitions per 1000 patient days, a 16.3% decrease (95% CI, 14.7%-18.0%; P > .001).Conclusions and relevanceThese findings suggest that there may be room for significant improvement in anti-MRSA disinfectants, including the compounds themselves and their delivery mechanisms. Despite the decolonization estimates found in this study, these agents are associated with robust outcomes after delays in administration, which may help in alleviating concerns over patient comfort and toxic effects.

Dataset Information

LTX-109 is a novel agent for nasal decolonization of methicillin-resistant and -sensitive Staphylococcus aureus.

Publications

LTX-109 is a novel agent for nasal decolonization of methicillin-resistant and -sensitive Staphylococcus aureus.

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