Journal_1_2014_final_WEB

Scientific Communication
strategies and novel models of wound infection involving
disruption of the biofilm alone or in combination with
antimicrobial agents.
Disruption of biofilms has been demonstrated with
ultrasound waves. Although the endpoint of most studies
has been surface release from young biofilms (i.e., not
necessarily equal to a reduced infection); some studies have
managed to prove that ultrasound waves can effectively enhance
the efficacy of antimicrobials (45-50 . Clinical studies
of ultrasound wound debridement have also shown good
effects 51,52 ; however, the decrease in bacterial counts were
not significant 51 . This non-significant decrease in bacterial
burden could be explained by the difficulties in detecting
biofilms, but it has also been suggested that the positive
effect arises from a multitude of factors such as cellular
recruitment and stimulation, collagen synthesis, angiogenesis,
and fibrinolysis (53,54 . However, non-published data
from our laboratory and the recent knowledge of biofilms
in non-healing wounds has led to the hypothesis that ultrasound,
in addition to the above mentioned parameters,
aids biofilm disruption and thereby wound healing 55 .
Maggot debridement therapy of non-healing wounds
was approved in 2004 by the FDA and has been shown to
possess an antibacterial effect in combination with other
wound healing properties 56-59 . An interesting study has
recently shown that larvae actually combine physical
disruption with enzymatic destabilization of wound biofilms
60 . As mentioned in the introduction, DNA stabilizes
all biofilms. Apparently, in addition to physically grazing,
the biofilm larvae secrete DNases that degrade DNA and
thereby further weaken the biofilm structure. As with the
ultrasound, larvae also have secondary positive effects on
wound healing immunomodulation, angiogenesis, and
tissue remodelling and regeneration, and this may explain
their beneficial effects on wound healing. Another
example of combining disruption of biofilms with positive
secondary effects is negative pressure therapy 61-63 . The
authors found that negative pressure disrupted the matrix
of biofilms on porcine skin implants, making them more
susceptible to antiseptics 61 .
As observed with other biofilm infections, targeting
several factors in wound biofilms seems to be a solid strategy
worth investigating. In the case of wound healing, the
secondary effects as discussed above might even be more
pronounced and thus constitute a promising strategy.
The tasks
From the above discussion of the impact of biofilms, it is
clear that we have a number of tasks to solve. First of all,
in order to prove that biofilm plays the role it is believed
to do, we need to improve diagnostic methods. This task
is also paramount when evaluating anti-biofilm strategies
in vivo. Secondly, the study of possible treatment strategies
for biofilm infections needs to be expanded and the
in vitro models need to be aligned to simulate the wound
in the best possible way.
For these tasks to be solved, it is important that scientists,
doctors, and wound healing specialists communicate
and share their thoughts and concerns on the issue. If
we combine the knowledge of wound care professionals
and basic scientists, we can hopefully take a giant leap
towards turning non-healing wounds into healing wounds.
Such multidisciplinary communication between doctors
and biofilm researchers has contributed significantly to
the treatment of chronic lung infections in patients with
the genetic disorder cystic fibrosis 64,65 . Communication
through research journals is significant; however, it is our
experience that the most fruitful results and collaborations
come from live discussions and consensus debates at conferences.
At the EWMA conference in 2013, the topic of
biofilms was for the first time denoted in an EWMA document;
furthermore, a number of abstracts dealt with biofilms
in addition to the popular workshop. In particular,
at the workshop, we had a great discussion on the future
of biofilm research. It is our hope that even more people,
from all branches of wound care, will attend the biofilm
workshops at EWMA GNEAUPP 2014 in Madrid, so
we can discuss the best approach to finding better ways
to study, diagnose, and treat biofilm-infected wounds.m
References
1. Costerton, J. W., P. S. Stewart, and E. P. Greenberg.
1999. Bacterial biofilms: a common cause of
persistent infections. Science 284:1318-1322.
2. Costerton, J. W., K. J. Cheng, G. G. Geesey, T. I.
Ladd, J. C. Nickel, M. Dasgupta, and T. J. Marrie.
1987. Bacterial biofilms in nature and disease.
ANNU REV MICROBIOL 41:435-464.
3. Davey, M. E., and A. O’Toole G. 2000. Microbial
biofilms: from ecology to molecular genetics.
Microbiol Mol Biol Rev 64:847-867.
4. Costerton, J. W., G. G. Geesey, and K. J. Cheng.
1978. How bacteria stick. Sci Am 238:86-95.
5. Costerton, W., R. Veeh, M. Shirtliff, M. Pasmore, C.
Post, and G. Ehrlich. 2003. The application of
biofilm science to the study and control of chronic
bacterial infections. J Clin Invest 112:1466-1477.
6. Bjarnsholt, T., P. Ø. Jensen, M. J. Fiandaca,
J. Pedersen, C. R. Hansen, C. B. Andersen, T.
Pressler, M. Givskov, and N. Høiby. 2009. Pseudomonas
aeruginosa biofilms in the respiratory tract
of cystic fibrosis patients. Pediatr Pulmonol 44:547-
558.
7. Høiby, N., T. Bjarnsholt, M. Givskov, S. Molin, and
O. Ciofu. 2010. Antibiotic resistance of bacterial
biofilms. Int J Antimicrob Agents 35:322-332.
8. Kirketerp-Møller, K., P. Ø. Jensen, M. Fazli, K. G.
Madsen, J. Pedersen, C. Moser, T. Tolker-Nielsen,
N. Høiby, M. Givskov, and T. Bjarnsholt. 2008.
Distribution, organization, and ecology of bacteria in
chronic wounds. J Clin Microbiol 46:2717-2722.
9. Fazli, M., T. Bjarnsholt, K. Kirketerp-Moller, B.
Jorgensen, A. S. Andersen, K. A. Krogfelt, M.
Givskov, and T. Tolker-Nielsen. 2009. Nonrandom
distribution of Pseudomonas aeruginosa and
Staphylococcus aureus in chronic wounds. J Clin
Microbiol 47:4084-4089.
10. Bjarnsholt, T., T. Tolker-Nielsen, M. Givskov, M.
Janssen, and L. H. Christensen. 2009. Detection of
bacteria by fluorescence in situ hybridization in
culture-negative soft tissue filler lesions. Dermatol
Surg 35 Suppl 2:1620-1624.
11. Høiby, N., O. Ciofu, and T. Bjarnsholt. 2010.
Pseudomonas aeruginosa biofilms in cystic fibrosis.
Future microbiology 5:1663-1674.
12. Nickel, J. C., I. Ruseska, J. B. Wright, and J. W.
Costerton. 1985. Tobramycin resistance of
Pseudomonas aeruginosa cells growing as a biofilm
on urinary catheter material. Antimicrob Agents
Chemother 27:619-624.
13. Whitchurch, C. B., T. Tolker-Nielsen, P. C. Ragas,
and J. S. Mattick. 2002. Extracellular DNA required
for bacterial biofilm formation. Science 295:1487.
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