Impact of Probiotics for Reducing Infections in Veterans: The IMPROVE Study

Reducing infections caused by S. aureus is essential. The knowledge that colonization at a
few key body sites such as the nose and the gastrointestinal tract is a prerequisite for
infection2 ,3 offers an opportunity for therapeutic intervention. Thirty percent of the
population has nasal colonization with S. aureus. In the last few years, decolonization
agents such as mupirocin topical ointment and oral antibiotics such as doxycycline and
rifampin have been studied for their utility in reducing colonization. However, these options
have limitations in that recolonization is common, the impact of these interventions on
multiple sites of colonization has not been assessed and resistance develops frequently to
any of these, especially the oral antibiotics. Resistance in S. aureus has been designated a
public health crisis. Methicillin-resistant S. aureus (MRSA) now accounts for 60% of all S.
aureus infections. As an example of the growing crisis in S. aureus resistance, it should be
noted that the number of MRSA infections rose from 2000 in 1993 to 368,000 in 2005. MRSA
infections pose an even greater health and economic burden on the population than those
caused by methicillin-sensitive S. aureus.4-8 S. aureus and MRSA infection trends in the VA
health system mirror national trends5 and are associated with considerable morbidity and
mortality in Veterans. A treatment that reduces S. aureus and MRSA colonization, without a
risk of promoting antibiotic resistance could represent a breakthrough in decolonization
therapy. Probiotics may be one such treatment option.

Probiotics are live microorganisms that are available over the counter, widely used as
dietary supplements or nutritional foods and represent a low-cost, well tolerated, safe,
non-antibiotic based strategy that may have efficacy for decolonization without the attendant
risks of promoting antimicrobial resistance.9 Certain probiotics, including Lactobacillus
rhamnosus HN001, have demonstrated ability to stimulate systemic immune functions, possibly
enhancing the body's ability to eradicate S. aureus in the gastrointestinal tract and at
sites remote from the gastrointestinal tract such as the nose.10 ,11 The long-term goal of
this research is to identify and test novel interventions for reducing infections caused by
resistant bacteria. The investigators propose a Phase II randomized, double-blind,
placebo-controlled clinical trial in Veterans to evaluate the efficacy of an oral probiotic,
Lactobacillus rhamnosus HN001, for reducing S. aureus colonization. This study will produce
data, methods, and tools that have widespread relevance and portability, with the potential
to reduce healthcare-associated infections.

Inclusion Criteria:

- Colonized at nasal or gastrointestinal source by S. aureus including MRSA

- Age 18 years or older

- Able to take oral medications

- Able to provide informed consent

Exclusion Criteria:

Uncontrolled psychiatric illness

- On a decolonization protocol for MRSA (e.g mupirocin, tea tree oil)

- Current involvement in another investigational trial

- Pregnancy

- Persistent diarrhea (> 3 loose stools per day for at least 2 days)

- Active infection with S.aureus or MRSA