Novel Targets for Treatment of Pseudomonas aeruginosa Biofilms - Antibiofilm Agents: From Diagnosis to Treatment and Prevention - page 256

6 Silver

The antibacterial effect of silver has been known and utilized since the nineteenth
century but was “forgotten” with the introduction of antibiotics. With the emer-
gence of multiple resistant bacteria, silver is facing its revival (Chopra 2007 ). The
main focus of silver as an antimicrobial agent has been in the topical treatment of
infected wounds. The mode of action of silver is multiple, unlike most antibiotics.
Silver interferes with several components of bacterial cell structures and functions,
including cell membrane integrity, respiratory chains, transmembranous energy and
electrolyte transport, and enzyme activities (Lansdown 2002 ).
In general it is very difficult to compare the antimicrobial efficiency of silver
containing products (i.e., dressings) because of a complete lack of standardized test
methods, and the fact that silver is used in many different formulations (e.g., silver
nitrate, silver sulfadiazine (SSD), and nano crystalline silver). Most silver dressings
exploit the highly reactive silver cation to achieve their antimicrobial effect.
Manufacturers are then distinguished by how the silver is incorporated into the
dressing and the amount of silver that is released (Toy and Macera 2011 ).
Silver's multiple of modes of action are proposed to be less affected by the
microenvironmental variations found in biofilms than are antibiotics (Bjarnsholt
et al. 2007 ). Furthermore, silver is known to decrease bacterial adhesion and
destabilize the biofilm matrix (Klueh et al. 2000 ; Chaw et al. 2005 ). Hence, silver
could prove to be an efficient antibiofilm drug. Many silver-containing wound
dressings have shown very promising results against P. aeruginosa when they are
growing in dilute solutions (Parsons et al. 2005 ; Castellano et al. 2007 ); however,
few studies have examined its efficacy against biofilms (Kostenko et al. 2010 ;
Bowler et al. 2012 ). As is the case with all other antimicrobials, we have found
that silver containing dressings loose their effect as the biofilm matures
(unpublished data). Bjarnsholt et al. demonstrated that to eradicate a mature
in vitro biofilm (4 day old) with silver sulfadiazine, concentrations as high as 5-
10

g/mL were needed. This concentration is 10-100 times higher than that used to
eradicate planktonic bacteria. These observations indicate that the concentration of
silver in currently available wound dressings is too low for treatment of chronic
biofilm wound infections (i.e., mature biofilms) (Bjarnsholt et al. 2007 ) (See Fig. 2 ).
In another study, it was found that cells in some regions of a 24-h-old biofilm
survived 7 days of silver treatment, but that the surviving cells were highly
susceptible to tobramycin and ciprofloxacin. The antimicrobial efficacy of the
dressings was correlated to the type of base material of the dressing and the silver
species loaded (Kostenko et al. 2010 ).
As stated above, silver containing products are used in wound treatment to
combat a broad spectrum of pathogens. However, evidence of their effectiveness
in preventing wound infection or promoting healing is lacking. Furthermore,
standardized tests are also lacking, so direct comparisons are not possible. In
spite of this, a large survey of 26 randomized trials investigated the effects of
silver-containing wound dressings and topical agents in preventing wound infection

ʼ