Current and Emergent Control Strategies for Medical Biofilms - Antibiofilm Agents: From Diagnosis to Treatment and Prevention - page 116

4 Novel Strategies to Combat Biofilm-Associated Infections

Efforts to develop successful treatments for biofilm-associated infections are
urgently needed in clinical practice. These new strategies must take into account
the differences in physiology and antibiotic/host defense susceptibility of biofilm
embedded microorganisms. The genetic and phenotypic versatility of the cells
within biofilms represent a challenge for discovering new methods of treatment
and prevention of biofilm-associated infections. Biofilm penetration by biocides or
antibiotics is typically strongly hindered. To increase the efficiency of new treat-
ment strategies against bacterial and fungal infections, factors that lead to inhibition
of biofilm growth, disruption, or eradication of biofilms are being sought
(Francolini and Donelli 2010 ). These factors include microbial products, enzymes,
sodium salts, metal nanoparticles, antibiotics, acids, chitosan and its derivatives, or
plant products. All of these factors influence biofilm structure via various mecha-
nisms and with different efficiencies.

4.1 Use of Combination Therapy

Conventional therapies target individual microbial species without consideration
that most biofilms are polymicrobial. However, a careful attempt should be made to
identify the causative microorganisms in a biofilm community. Appropriate man-
agement of mixed infections requires the administration of antimicrobials that are
effective against all the components of the biofilms. Many nosocomial infections
involve microbial biofilms and persistence of chronic infections is attributed to the
persistence of polymicrobial biofilms (Brogden and Guthmiller 2002 ; Hall-
Stoodley and Stoodley 2009 ). The standard treatment for such infections involves
two or more antibiotics, referred to as combination therapy (Brook 2002 ). The use
of novel antibiotic combinations may increase the effectiveness of antibiotic
therapies.
Another potential strategy could be to sensitize the bacteria or fungal biofilms by
synthetic or natural compounds (other than antibiotics). For example, Jabra-Rizk
et al. ( 2006 ) reported the sensitization of S. aureus bioflms by farnesol, a fungal QS
molecule. The combined effect of gentamicin at 2.5 times the MIC and farnesol at
100 g/mL) was able to reduce bacterial populations by more than 2 log

units and demonstrated a synergy between the two agents. This observed sensiti-
zation of resistant strains to antimicrobials and the observed synergistic effect with
gentamicin indicates a potential application for farnesol as an adjuvant therapeutic
agent for the prevention of biofilm-related infections. Using a combination
approach we have demonstrated that the phenolic compounds eugenol and phenyl
aldehyde cinnamdehyde potentiate the activity of flucoanzole against biofilm
forming drug-resistant strains of C. albicans (Khan and Ahmad 2012a ).

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