Biomedical Engineering Reference
In-Depth Information
prophylaxis is controversial because of its potential to increase antimicrobial
resistance, it is increasingly common in high-risk patient groups. With regard
to device coatings, a recent and comprehensive meta-analysis of randomized-
controlled trials of rifampin-impregnated central venous catheters (CVCs) sug-
gest that they are both safe and effective in reducing the rate of catheter
colonization and CRBSIs (Falagas et al. 2007). Similarly, on six independent
studies of the ecacy of antibiotic lock therapy in the prevention of CRBSIs
in hemodialysis patients, an overall reduction of 64%-100% in CRBSIs was
observed (Manierski and Besarab 2006).
Replacement or removal of an infected medical device, combined with sys-
temic antibiotic and/or antifungal therapy, is the most effective treatment in
most settings. Standard practice involves either a one-stage or a two-stage
procedure (Trampuz and Zimmerli 2006, 2008). For managing medical-device
infections without surgical intervention, long-term antimicrobial suppressive
therapy remains the only option, and current salvage rates are highest with
early diagnosis (Stein et al. 2000). Recommendations of antibiotic therapies
for the management of biofilm-associated infections have been driven largely
by empiric observations and typically involve the use of combinations over
extended periods.
The biofilm intercellular matrix is essential for biofilm structure. Sub-
stances capable of depolymerizing, dissolving, or inhibiting the synthesis of
this matrix may thus convert the status of biofilm cells to planktonic, fully
exposed to the impact of environmental conditions and access of antibiotic. In
vitro treatment of clarithromycin-resistant S. epidermidis and P. aeruginosa
biofilms with a relatively low concentration of clarithromycin resulted in the
decrease of the quantity of biofilm matrix and in an increased penetration of
other antimicrobial agents (Yasuda et al. 1994). Furthermore, an equal com-
bination of streptokinase and ofloxacin had an additive effect on S. aureus
biofilms in vitro (Nemoto et al. 2000).
A major component of the extracellular matrix of several bacteria,
for example, S. aureus , S. epidermidis , E. coli , is a linear polymer com-
posed of N -acetylglucosamine residues in
-(1,6)-linkage called polysac-
charide intercellular adhesin . Kaplan and colleagues (2003) reported that
Actinobacillus actinomycetemcomitans produces a soluble glycoside hydro-
lase called dispersin B , which degrades polysaccharide intercellular adhesin.
It seems possible that dispersin B may be used to detach polysaccha-
ride intercellular adhesin-containing biofilms from the surface of colonized
biomaterials.
New approaches to antimicrobial activity against persistent biofilms are
crucial to effective control and eradication of infections. New compounds or
effective new modes need to be developed and tested for their penetration
into biofilms. Genes responsible for persistence may be considered as targets
for new drugs. Development of drugs that disable the persistent phenotype is
likely to provide an effective therapy for biofilm-associated infections. Ideally,
an inhibitor of persistence development may be combined with a conventional
antimicrobial agent to achieve biofilm eradication (Lewis 2001).
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