A New Hope for Fighting Multi-Drug Resistant Pseudomonas Aeruginosa Nosocomial Infections

Pseudomonas aeruginosa is a gram negative bacterial pathogen that is commonly associated with nosocomial, or hospital-acquired infections. Pseudomonas infrequently afflicts those with a healthy immune system and more commonly causes an opportunistic infection in immuno-compromised patients, such as those on immunosuppressive drugs or with full blown AIDS. Pseudomonas infection is not a rare occurrence; it is estimated to be involved in 10.1% of hospital-acquired infections (1).

Compounding this problem is the emergence of drug resistant Pseudomonas. Drug resistance can be acquired by this particular pathogen through both plasmid (acquired through transfer from other bacteria) and chromosomal (mutation of the bacteria genome itself) mediated means. Resistance is associated with increased mortality and length of hospital stay (2). With the current health care system already strapped and health insurance benefits dwindling, Pseudomonas is a major public health concern in this country.

A new study published in the journal Science looked to develop a new class of antibiotics to specifically target Pseudomonas (3). The authors produced peptidomimetic antibiotics that resemble peptide protegrin 1 (PG-1). PG-1 has a broad spectrum of activity against an array of pathogens and can cause hemolysis of red blood cells. The goal was to optimize PG-1 such that it was specific for Psedudomonas, but with less red blood cell lysis.

The authors developed several libraries of mimetics and screened them for activity against Pseudomonas aeruginosa. The best mimetic from each library was then further developed and optimized. This led to the development of several mimetics with a minimum inhibitory concentration (MIC) in the nanomolar range that was specific for Pseudomonas aeruginosa and not other bacteria. The mimetics inhibited Pseudomonas aeruginosa independently of membrane lysis of the bacteria. Red blood cell lysis activity was absent with the mimetics, even with high concentrations.

The authors assessed the ability of the mimetics to control Pseudomonas aeruginosa in infected mice at bacterial concentrations that would normally be lethal. Mimetics were effective in controlling infection in these mice similarly to drugs already known to rescue Pseudomonas aeruginosa infection.

These mimetics may ultimately prove useful against Pseudomonas aeruginosa nosocomial infections. Although effective in mice, the mimetics will ultimately need to be tested in humans for their effectiveness in real world patients and to assess potential side effects. This study provides another potential therapeutic intervention for Pseudomonas aeruginosa infections that develop multi-drug resistance with standard care.

References:

1. Samer, A., and Burke, AC., Pseudomonas aeruginosa Infections. http://emedicine.medscape.com/article/226748-overview. accessed 2/26/2010.
2. Page MG and Heim J. Curr Opin Pharmacol. 2009 Oct;9(5):558-65
3. Srinivas, N.; et, al. 2010. Science. 327 : 1010-1013.