Biomedical Implications of the Porosity of Microbial Biofilms - Porous Media: Applications in Biological Systems and Biotechnology - page 145

radiofrequency electric current (Caubet et al. 2004), electromagnetic fields
(McLeod et al. 1999), and ultrasound (Rediske et al. 2000), in combination
with antimicrobial therapy.
Guidelines for the clinical evaluation of antibiotic treatments are now avail-
able for the CRBSI setting only; comparative studies have rarely been under-
taken in any medical-device infections (Lynch and Robertson 2008). Out of
all agents investigated, a rifampin-antibiotic combination for staphylococcal
medical-device infections has perhaps been most thoroughly evaluated in clin-
ical trials. In these studies, rifampin was combined with quinolones (Isiklar
et al. 1999; Schrenzel et al. 2004), -lactams (Widmer et al. 1992) or fusidic

acid (Drancourt et al. 1997), and rifampin-containing regimens are now estab-
lished as standard therapies for a range of device-associated infections (Karch-
mer 2000; Steckelberg and Osmon 2000; Yogev and Bisno 2000; Zimmerli et al.
2004; Trampuz and Widmer 2006).
Fungal biofilm-associated infections are notoriously dicult to treat sys-
temically with antifungal agents. This poor in vivo ecacy is not surprising,
given the in vitro demonstrated resistance of biofilms formed by C. albicans
and related species to various classes of antifungal agents (Chandra and Ghan-
noum 2004; Kojic and Darouiche 2004; Hawser and Islam 2006). It appears,
however, that agents of the echinocandin class exhibited in vitro fungici-
dal activity on established biofilms (Ramage et al. 2005) and in suppressing
biofilm colonization on biomaterials (Soustre et al. 2004; Shuford et al. 2006).
Lipid-based formulations of amphotericin B have also proven effective in in
vitro assays of biofilm activity. The management of fungal biofilm-associated
medical-device infections involved exchange of the infected device, whenever
possible, combined with systemic antifungal therapy (Chandra and Ghan-
noum 2004). Data accumulating from in vitro and preclinical animal studies
suggest that antifungals of the echinocandin class (caspofungin, micafungin,
anildafungin) and amphotericin B lipid formulations represent the currently
known, best available options for the management of infections caused by
fungal biofilms.

β

4.4.2 The Impact of Porosity and Diffusional Limitations
on Treatment Ecacy
Though the details of development of antimicrobial biofilm resistance is only
partially understood, recent studies have already used a variety of model sys-
tems to determine how and why biofilms are so resistant to commonly used
antimicrobial agents (see above). As the importance of biofilms in nosoco-
mial infections has increased, efforts are being directed toward the study of
the impact of antimicrobial agents on these surface-attached communities.
Four leading hypotheses explain the reduced susceptibility of biofilms: poor
antimicrobial penetration, deployment of adaptive stress responses, physiolog-
ical heterogeneity in the biofilm population; and the presence of phenotypic
variants or persister cells (Stewart 2002; Davies 2003). It seems likely that