SPECIAL TOPIC

Soft-Tissue Filler Complications: The Important

Role of Biofilms
Rod J. Rohrich, M.D.
Gary Monheit, M.D.
Alexander T. Nguyen, M.D.
Spencer A. Brown, Ph.D.
Steven Fagien, M.D.
Dallas, Texas; Birmingham, Ala.; and
Boca Raton, Fla.

iofilms are defined as a structured community of microorganisms encapsulated within

a self-developed polymeric matrix and irreversibly adherent to a living or inert surface.
The first observations of biofilms were made on
dental plaque by Anthony van Leeuwenhoek,
who noted the limited ability to kill microorganisms adherent to his teeth.1 Biofilms were
first theorized by Costerton et al. in 1978, but
visualization of biofilms was not possible until
the use of scanning electron microscopy.2 The
enhanced ability for bacteria to grow on a surface was described in 1940.3 Biofilms are also
often characterized by surface attachment,
structural heterogeneity, genetic diversity, complex community interactions, and an extracellular matrix of polymeric substances.4 The
extracellular matrix of polymeric substances is
composed primarily of polysaccharides that may
be neutral or polyanionic. This matrix is strong
enough to become fossilized and appeared as
early as 3.25 billion years ago.5
Biofilm Characteristics
The architecture of biofilms may make the
term a misnomer because it is not a continuous
monolayer. Instead, they are heterogeneous and
unique structures of bacterial colonies, extracellular matrix of polymeric substances, and interstitial voids. Figure 1 displays the heterogeneity and channels of a mature biofilm of
From the Department of Plastic Surgery, University of Texas
Southwestern Medical Center; the Departments of Dermatology and Ophthalmology, University of Alabama at Birmingham; and Aesthetic Oculoplastic Surgery (private practice).
Received for publication May 1, 2009; accepted September
14, 2009.
Copyright 2010 by the American Society of Plastic Surgeons
DOI: 10.1097/PRS.0b013e3181cb4620

1250

Pseudomonas aeruginosa, Klebsiella pneumoniae,

and Flavobacterium.6
The characteristics of biofilms essentially
make them their own organism, if not superorganism. They respond to stimuli, grow, and maintain a homeostatic environment.7 Biofilms have
impaired immune system penetration, reduced
growth rates/susceptibility by quorum sensing, altered microenvironment, and altered gene expression and display.8 They are less conspicuous to
the immune system and produce substances that
individual bacteria are unable to produce alone.
The extracellular matrix of polymeric substances
of biofilms may interfere with macrophage
phagocytosis.9 Biofilms allow for up to 1000-fold
improved resistance to antibiotics.10,11 This may be
attributable to the biofilm environment allowing
for more ready exchange of extrachromosomal
DNA plasmids, which may encode antimicrobial
resistance.12 Quorum sensing is cell-to-cell signaling that has been shown to be involved in biofilm
production and differentiation.13
Bacteria are the underlying source of biofilms
and are the most successful form of life on earth
by biomass. Bacteria may account for 95 percent
of the biomass of biofilms.14 Biofilms form when
planktonic, free-floating bacteria adhere to surfaces and become sessile. Evidence of mature biofilms has been found as early as 10 hours after
infection.15,16 Once biofilms are established, they
are extremely difficult, if not impossible, to completely eradicate.

Disclosures: Gary Monheit, M.D., is a consultant

for Allergan, Dermik, Genzyme, Colbar LifeScience,
Contura, Ipsen/Medicis, Stiefel, Melafind, Revance,
Kythera, Galderma, and Mentor. None of the other
authors has a financial interest regarding the contents
of this article.

www.PRSJournal.com

Volume 125, Number 4 Soft-Tissue Filler Complications

if exposed to the bloodstream.19 As with all other
indwelling foreign bodies, biofilms are suspected
to be the underlying cause of delayed complications for soft-tissue fillers.

SOFT-TISSUE FILLER COMPLICATIONS

Fig. 1. Polymicrobic biofilm examined by epifluorescence microscopy. Bar 20 m. (Reprinted with permission from Donlan
RM. Biofilms: Microbial life on surfaces. Emerg Infect Dis. 2002;8:
881 890.)

Current culture techniques fail to identify biofilms. Frequently, the offending bacteria are not
found in clinically infected abscesses and will be
labeled as sterile abscesses because of the lack of
growth from culture specimens. This can be attributable to ongoing patient antibiotic coverage.
Initiating bacteria may already be dead and gone,
leaving an ongoing inflammatory response along
with the resistant biofilm colony. Also, current
methods of collection and culture evaluation may
not be adequate to identify the offending organism. Specimens frequently do not arrive at the
laboratories immediately and are not routinely
placed in gas packs. Not doing so immediately may
kill sensitive anaerobes. In addition, most laboratories do not routinely culture for extended periods of time, as 2 to 3 weeks are required to
culture atypical microorganisms. Finally, some
pathogens require specific culture media for optimal growth that are not routinely used.
Biofilms in Medicine
Biofilms are omnipresent and are found in
streams, corroding pipes, showers, countertops,
and sewer treatment plants. The most common
example is dental plaque. Biofilms cost greater
than $1 billion per year in the United States.17
They are estimated to account for up to 80 percent
of all infections.4,18 In medicine, biofilms have
been associated with urinary tract infections, endocarditis, otitis media, biliary disease, osteomyelitis, all surgical implants, and cystic fibrosis. In
cystic fibrosis, biofilms of Pseudomonas aeruginosa
exist in the lungs at normally fatal concentrations

With the increasing use of injectable agents for

cosmetic facial rejuvenation and reshaping, biofilm-related soft-tissue filler complications will
concomitantly rise.20,21 Soft-tissue filler injections
increased 130 percent between 2005 and 2007,
including 174,000 collagen and over 1 million hyaluronic acid injections.22,23 These numbers do
not include the growing popularity of longer lasting soft-tissue fillers. We choose to identify these
products as soft-tissue fillers, as opposed to dermal
fillers, as these various compounds are not placed
exclusively into the dermis. In fact, they are presently injected into all levels of facial soft tissue in
variable volumes.
Currently available filling agents in the United
States have excellent safety profiles with rare, minor, and easily treated side effects.24,25 Soft-tissue
fillers are classified by their duration of effect as a
function of time: temporary, long-lasting, semipermanent, and permanent. These durations may
be roughly defined as less than 6 months, 6
months to 2 years, 2 to 5 years, and greater than
5 years, respectively (Table 1).7 All of these fillers
except autologous fat are composed of materials
that are foreign to the host and a potential source
for biofilm formation.
Soft-tissue fillers approved in the United
States have been tested extensively and are extremely safe substances.26 The more common
adverse outcomes are procedural or techniquerelated as opposed to product-based, such as
inappropriate placement (region or soft-tissue
plane) of fillers.27,28 Although rare, all fillers have
been associated with adverse reactions.29,30 These
adverse reactions are usually transient and mild.
Many of the more serious complications may be
infectious reactions diagnosed as foreign-body
granulomas.31 The incidence of foreign-body
granuloma is noted to be 0.01 to 0.1 percent.28,32
Table 1. Classification of Soft-Tissue Implants*
Longevity
Temporary
Long-lasting
Semipermanent
Permanent

06 mo
6 mo2 yr
25 yr
5 yr

*From Rohrich RJ, Nguyen AT, Kenkel JM. Lexicon for soft tissue
implants. Dermatol Surg. 2009;35:16051611.

1251

Plastic and Reconstructive Surgery April 2010

This is likely greatly underestimated because of
the lack of physician reporting, skewed company/
industry estimates, and may even be attributed to
the lack of patient reporting because of personal
embarrassment. With the increasing use of fillers,
especially permanent, this adverse outcome will
become more prevalent. The mechanism of delayed foreign-body granuloma formation has been
previously suggested to be caused by biofilms.21
Complication Classification
The timing of the onset of complications in
relation to the time of injection of products may
be classified to assist in patient management, as
most have commonly been classified as early and
late. We suggest that they be classified as early, late,
and delayed (Table 2). Recognizing the range of
overlapping disease processes, these time frames
may be roughly defined as less than 14 days, 14
days to 1 year, and more than 1 year, respectively.
These time frames also correlate with the potential
cause. Early complications are commonly inflammatory in nature; late complications are usually
secondary to granuloma formation; and both of
these may be infectious in cause and may be complicated by biofilms.7
Early Complications
Early complications are the most common adverse events and are generally inflammatory or
technical in nature and may be seen immediately
after treatment. Redness and swelling have been
noted to occur in approximately 80 percent of
injections.33 The local effects of traumatic puncture may last several hours for redness or several
days for swelling. Inadvertent injury to blood vessels may result in bruising that may last approximately 1 week. Intraarterial injection can cause
injection-site necrosis.34 This has been reported in
both the supraorbital artery during glabellar injection and the angular artery with injection of the
nasolabial folds.35 Except for autologous fat, allergic reactions may occur with any filler. Hypersensitivity can be as severe as angioedema and
anaphylaxis.36 The immediate appearance of
lumps and bumps is a technical error of product
Table 2. Complication Timing and Potential Cause*
Early
Late
Delayed

Timing

Potential Cause

14 days
14 days1 yr
1 yr

Inflammatory
Granuloma formation
Biofilms

*From Rohrich RJ, Nguyen AT, Kenkel JM. Lexicon for soft tissue
implants. Dermatol Surg. 2009;35:16051611.

1252

placement, such as filler placement that is too

superficial.
Angry red bumps are described in case reports with and without tenderness to describe delayed erythema in the sites of injection of various
products that are associated with visible or palpable nodules. These have been more often associated with permanent fillers or collagen. The cause
has been thought to vary from a host of causes,
including hypersensitivity, infections, and foreign
body reactions.37 In all of these situations, these
angry red bumps can be more appropriately categorized as painful or nonpainful inflammatory
nodules.
Late Complications: Foreign-Body Granuloma
A granuloma is an organized focus of chronic
inflammation. It is characterized by aggregated
chronic inflammatory cells, macrophages transformed into epithelium-like cells surrounded by
mononuclear leukocytes. These epithelium-like
cells fuse to form giant cells that may attain diameters of 40 to 50 m. They are the bodys response to relatively inert foreign bodies or chronic
indolent infection. These foreign bodies are too
large for phagocytosis by a single macrophage.
Giant cells form on the surface and encompass the
foreign body in an effort to isolate it. The foreign
material can oftentimes be identified in the center
of the granuloma.38 Characteristics of the foreignbody granuloma may even be specific to the filler
material used.31,39
The diagnosis of filler foreign-body granuloma
should be based on clinical findings. All soft-tissue
fillers can stimulate a foreign-body reaction and become encapsulated, but the foreign-body granuloma will present with ongoing inflammation. Patients will have an uneventful period after injection,
usually ranging from 6 to 24 months, followed by
swelling, erythema, or discoloration.28
Delayed Complications: Biofilms and Their
Relationship to Soft-Tissue Fillers
The cause of foreign-body granuloma after
soft-tissue filler injection has been hypothesized to
be attributable to implantation in one session of
volumes that are too large, impurities in the agent,
or irregularities of the filler surface, but the impact
of biofilms has yet to be established.40 Reports of
delayed complications temporally related to systemic infections support the infectious cause.41 43
All fillers, especially longer lasting products, have
the potential for biofilm complications.

Volume 125, Number 4 Soft-Tissue Filler Complications

RECOMMENDATIONS FOR FUTURE
CARE AS IT RELATES TO BIOFILM
Given that biofilms are difficult to eradicate or
detect, current care should be focused on preventative measures, defining and avoiding risk factors,
management of complications, future research,
and regulation.
Preventative Measures
The causes of biofilms relate to both the types
of filler materials injected or present from previous treatments and/or a breach in technique as it
relates to sufficient reduction in the biological
burden before treatment; simple preventative
measures may reduce this risk. A good history is
always important to reveal which previous fillers
have been injected into the patient, possible
bleeding disorders, immunocompromised state,
and previous infections. Adherence to aseptic
technique should be followed, even more so for
permanent fillers. Alcohol cleansing is commonly
used, but chlorhexidine may have the benefit of a
residual antibacterial effect. It is important to remember to spread the skin during cleansing to get
into wrinkles. Prophylactic antibiotics have been
suggested to prevent biofilms in situations where
semipermanent or permanent fillers are used initially or later during significant infections. Smaller
gauge needles should be used to minimize trauma
and access for bacteria. Patients should be advised
to avoid makeup immediately before and after
injection.
Avoiding Risk Factors
Other known risk factors should be avoided if
possible. Stacking of fillers, especially permanent
on top of permanent, and large-volume injections
have been associated with more inflammation and
granuloma formation.40 Inappropriate plane of
placement is the most common error.27 Avoid in-

jecting during active acne or any other infections.

Skin-related problem areas should be approached
with caution. Injections of the tear trough may be
problematic if lymphatics are blocked. The lips
may actually be the highest risk area for potential
biofilm because of the proximity of the oral flora,
with over 500 species of bacteria.
Management of Complications
Complications should be approached in an
algorithmic manner with early recognition (Fig.
2). If possible, one should make every attempt to
determine what was injected into the site. If the
wound is fluctuant, it should be needle-drained
and cultured. Cultures should be sent to the laboratory immediately for appropriate handling.
They also should be monitored for up to 21 days
for routine culture and atypical infections. The
initial antibiotic regimen should consist of at least
two-drug therapy, such as a quinolone and a thirdgeneration macrolide, to prevent further biofilm
deposition. Macrolides have been shown to be
uniquely effective, which appears to be related to
improved accumulation in the subcutaneous fat
(where the filler material typically resides) and
may also block quorum sensing.44
After a trial of antibiotics, intralesional highdose steroids should be considered.28 If hyaluronic
acid was used, hyaluronidase should also be
considered.45 Excision should be the last step. This
algorithm is exemplified in Figure 3. This patient
presented with nonfluctuant inflammation following hyaluronic acid to the lips. She was successfully
treated sequentially with an antibiotic regimen,
hyaluronidase, intralesional steroids, and eventual
transoral excision.
Future Research
Future research should focus on biofilm identification in association with soft-tissue filler com-

Fig. 2. Management algorithm of late and delayed complications of soft-tissue fillers. HA, hyaluronic acid.

1253

Plastic and Reconstructive Surgery April 2010

sistance of industry, authorities, and key opinion
leaders in the field of filling agents. Manufacturers
should support a uniform filler passport or central registry. This can be coded for privacy and
provide practitioners with important information
of what was previously injected, exactly where it
was injected, and the volumes used. In addition,
this may minimize unqualified practitioners and
unregulated products that occur at places such as
salons or spas.

CONCLUSIONS

Fig. 3. Delayed complications. (Above) The patient exhibits

nonfluctuant inflammation following hyaluronic acid to the
lips. (Below) Appearance of the patient 6 months after algorithmic treatment.

plications, defense, control strategies, and, lastly,

the individual organisms.46 Much of this research
has been a response to the growing knowledge of
the pathophysiology of biofilms in various disease
states. For instance, enzymes are already being
used against biofilms for contact lenses. Mixtures
of enzymes may be necessary for sufficient degradation of bacterial biofilms.47 Quorum sensing interference research is also promising.48 Surface
engineering of roughness, charge density, and
polyelectrolyte multilayers have been shown to
correlate with the number of bacterial colonies.49
Surface impregnation with silver has been shown
to decrease infections.50 Antibiotic coating is being studied extensively in the orthopedic literature. The use of lasers to destroy bacteria and
biofilms should be investigated further. Future
research may identify specific genes expressed by
biofilm organisms.
Regulations
Regulations should be implemented to better
provide care and track complications with the as-

1254

With the increased use of soft-tissue fillers,

especially longer lasting products, we expect the
prevalence of all complications to increase, including the more devastating delayed complications. We have separated early, late, and delayed complications based on the underlying
cause. Delayed granulomas are postulated to be
caused by biofilms, an omnipresent and extremely difficult problem to eradicate of which
we are now more acutely aware. We have proposed an algorithmic approach to the prevention and management of these complications.
Immediate recommendations should be focused on prevention, prophylaxis, effective
treatment, and regulation while further research is developed to identify, defend against,
and control these complications of biofilms.
Rod J. Rohrich, M.D.
Department of Plastic Surgery
University of Texas Southwestern Medical Center
1801 Inwood Road
Dallas, Texas 75390-9132
rod.rohrich@utsouthwestern.edu

ACKNOWLEDGMENTS

The authors thank the participants of the Summit on

Filler Complications, August 23, 2008, Dallas, Texas,
for supporting the conference: Spencer Brown, Daniel
Cassuto, Lise Christensen, Joel Cohen, Bill Coleman, Sue
Ellen Cox, David Duffy, Steve Fagien, Rick Glogau,
Jeffrey Kenkel, Gary Monheit, Rhoda Narins, Norbert
Pallua, Stefano Piccolo, Jim Richardson, Rod J. Rohrich,
Tony Sclafani, Michael Tvede, Luitgard Wiest, and
Contura.
REFERENCES
1. von Leeuwenhoek A. An abstract of a letter from Mr. Anthony Leevvenhoek at Delft, dated Sepember 17, 1683, Containing Some Microscopical Observations, about Animals in
the Scurf of the Teeth, the Substance Calld Worms in the
Nose, the Cuticula Consisting of Scales. Philosophical Transactions 1684;14:568574.
2. Costerton JW, Geesey GG, Cheng KJ. How bacteria stick. Sci
Am. 1978;238:8695.

Volume 125, Number 4 Soft-Tissue Filler Complications

3. Heukelekian H, Heller A. Relation between food concentration and surface for bacterial growth. J Bacteriol. 1940;40:
547558.
4. Biofim (Wikipedia web site). Available at: http://en.wikipedia.
org/wiki/Biofilm. Accessed January 25, 2009.
5. Hall-Stoodley L, Costerton JW, Stoodley P. Bacterial biofilms:
From the natural environment to infectious diseases. Nat Rev
Microbiol. 2004;2:95108.
6. Donlan R. Biofilms: Microbial life on surfaces. Emerg Infect
Dis. 2002;8:891890.
7. Rohrich RJ, Nguyen AT, Kenkel JM. Lexicon for soft tissue
implants. Dermatol Surg. 2009;35:16051611.
8. Costerton JW, Stewart PS, Greenberg EP. Bacterial biofilms:
A common cause of persistent infections. Science 1999;284:
13181322.
9. Shiau AL, Wu CL. The inhibitory effect of Staphylococcus
epidermidis slime on the phagocytosis of murine peritoneal
macrophages is interferon-independent. Microbiol Immunol.
1998;42:3340.
10. Ceri H, Olson ME, Stremick C, Read RR, Morck D, Buret A.
The Calgary Biofilm Device: New technology for rapid determination of antibiotic susceptibilities of bacterial biofilms.
J Clin Microbiol. 1999;37:17711776.
11. Anwar H, Strap JL, Chen K, Costerton JW. Dynamic interactions of biofilms of mucoid Pseudomonas aeruginosa with
tobramycin and piperacillin. Antimicrob Agents Chemother.
1992;36:12081214.
12. Ghigo JM. Natural conjugative plasmids induce bacterial
biofilm development. Nature 2001;412:442445.
13. Stickler DJ, Morris NS, McLean RJ, Fuqua C. Biofilms on
indwelling urethral catheters produce quorum-sensing signal molecules in situ and in vitro. Appl Environ Microbiol.
1998;64:34863490.
14. Flemming HC. Biofouling in water systems: Cases, causes and
countermeasures. Appl Microbiol Biotechnol. 2002;59:629640.
15. Davis SC, Ricotti C, Cazzaniga A, Welsh E, Eaglstein WH,
Mertz PM. Microscopic and physiologic evidence for biofilmassociated wound colonization in vivo. Wound Repair Regen.
2008;16:2329.
16. Harrison-Balestra C, Cazzaniga AL, Davis SC, Mertz PM. A
wound-isolated Pseudomonas aeruginosa grows a biofilm in
vitro within 10 hours and is visualized by light microscopy.
Dermatol Surg. 2003;29:631635.
17. Archibald LK, Gaynes RP. Hospital-acquired infections in the
United States: The importance of interhospital comparisons.
Infect Dis Clin North Am. 1997;11:245255.
18. Mah TF, OToole GA. Mechanisms of biofilm resistance to
antimicrobial agents. Trends Microbiol. 2001;9:3439.
19. Parsek MR, Singh PK. Bacterial biofilms: An emerging link
to disease pathogenesis. Annu Rev Microbiol. 2003;57:677
701.
20. Rohrich RJ, Rios JL, Fagien S. Role of new fillers in facial
rejuvenation: A cautious outlook. Plast Reconstr Surg. 2003;
112:18991902.
21. Christensen L, Breiting V, Janssen M, Vuust J, Hogdall E.
Adverse reactions to injectable soft tissue permanent fillers.
Aesthetic Plast Surg. 2005;29:3448.
22. American Society of Plastic Surgeons. National Clearinghouse of Plastic Surgery Statistics. Available at: http://www.
plasticsurgery.org/media/press_releases/injectables-at-aglance.cfm. Accessed January 25, 2009.
23. American Society for Dermatologic Surgery. American Society
for Dermatologic Surgery procedure survey data. Available at:
http://www.asds.net/TheAmericanSocietyforDermatologic
SurgeryReleasesNewProcedureSurveyData.aspx. Accessed January 25, 2009.

24. Broder KW, Cohen SR. An overview of permanent and semipermanent fillers. Plast Reconstr Surg. 2006;118:7S14S.
25. Matarasso SL. Injectable collagens: Lost but not forgotten. A
review of products, indications, and injection techniques.
Plast Reconstr Surg. 2007;120:17S26S.
26. Alam M, Dover JS. Management of complications and sequelae with temporary injectable fillers. Plast Reconstr Surg.
2007;120:98S105S.
27. Cohen JL. Understanding, avoiding, and managing dermal
filler complications. Dermatol Surg. 2008;34(Suppl 1):S92
S99.
28. Lemperle G, Rullan PP, Gauthier-Hazan N. Avoiding and
treating dermal filler complications. Plast Reconstr Surg. 2006;
118:92S107S.
29. Lowe NJ, Maxwell CA, Patnaik R. Adverse reactions to dermal
fillers: Review. Dermatol Surg. 2005;31:16161625.
30. Andre P, Lowe NJ, Parc A, Clerici TH, Zimmermann U.
Adverse reactions to dermal fillers: A review of European
experiences. J Cosmet Laser Ther. 2005;7:171176.
31. Parada MB, Michalany NS, Hassun KM, Bagatin E, Talarico
S. A histologic study of adverse effects of different cosmetic
skin fillers. Skinmed 2005;4:345349.
32. Lemperle G, Morhenn V, Charrier U. Human histology and
persistence of various injectable filler substances for soft
tissue augmentation. Aesthetic Plast Surg. 2003;27:354366;
discussion 367.
33. Narins RS, Brandt F, Leyden J, Lorenc ZP, Rubin M, Smith
S. A randomized, double-blind, multicenter comparison of
the efficacy and tolerability of Restylane versus Zyplast for the
correction of nasolabial folds. Dermatol Surg. 2003;29:588
595.
34. Glaich AS, Cohen JL, Goldberg LH. Injection necrosis of the
glabella: Protocol for prevention and treatment after use of
dermal fillers. Dermatol Surg. 2006;32:276281.
35. McCleve DE, Goldstein JC. Blindness secondary to injections
in the nose, mouth, and face: Cause and prevention. Ear Nose
Throat J. 1995;74:182188.
36. Mullins RJ, Richards C, Walker T. Allergic reactions to oral,
surgical and topical bovine collagen: Anaphylactic risk for
surgeons. Aust N Z J Ophthalmol. 1996;24:257260.
37. Narins RS, Jewell M, Rubin M, Cohen J, Strobos J. Clinical
conference: Management of rare events following dermal
fillers: Focal necrosis and angry red bumps. Dermatol Surg.
2006;32:426434.
38. Kumar V, Abbas AK, Fausto N, et al. Robbins and Cotran
Pathologic Basis of Disease . 7th ed. Philadelphia: Elsevier Saunders, 2005.
39. Dadzie OE, Mahalingam M, Parada M, El Helou T, Philips T,
Bhawan J. Adverse cutaneous reactions to soft tissue fillers:
A review of the histological features. J Cutan Pathol. 2008;
35:536548.
40. Gelfer A, Carruthers A, Carruthers J, Jang F, Bernstein SC.
The natural history of polymethylmethacrylate microspheres
granulomas. Dermatol Surg. 2007;33:614620.
41. Achauer BM. A serious complication following medicalgrade silicone injection of the face. Plast Reconstr Surg. 1983;
71:251254.
42. Rongioletti F, Cattarini G, Sottofattori E, Rebora A. Granulomatous reaction after intradermal injections of hyaluronic
acid gel. Arch Dermatol. 2003;139:815816.
43. Lemperle G, Romano JJ, Busso M. Soft tissue augmentation
with artecoll: 10-year history, indications, techniques, and
complications. Dermatol Surg. 2003;29:573587; discussion
587.
44. Hoffmann N, Lee B, Hentzer M, et al. Azithromycin blocks
quorum sensing and alginate polymer formation and in-

1255

Plastic and Reconstructive Surgery April 2010

creases the sensitivity to serum and stationary-growth-phase
killing of Pseudomonas aeruginosa and attenuates chronic P.
aeruginosa lung infection in Cftr(/) mice. Antimicrob
Agents Chemother. 2007;51:36773687.
45. Lambros V. The use of hyaluronidase to reverse the effects
of hyaluronic acid filler. Plast Reconstr Surg. 2004;114:277.
46. Wolcott RD, Ehrlich GD. Biofilms and chronic infections.
JAMA. 2008;299:26822684.
47. Johansen C, Falholt P, Gram L. Enzymatic removal and disinfection of bacterial biofilms. Appl Environ Microbiol. 1997;
63:37243728.

48. Smith KM, Bu Y, Suga H. Induction and inhibition of Pseudomonas aeruginosa quorum sensing by synthetic autoinducer
analogs. Chem Biol. 2003;10:8189.
49. Lichter JA, Thompson MT, Delgadillo M, Nishikawa T, Rubner MF, Van Vliet KJ. Substrata mechanical stiffness can
regulate adhesion of viable bacteria. Biomacromolecules 2008;
9:15721578.
50. Kollef MH, Afessa B, Anzueto A, et al. Silver-coated endotracheal tubes and incidence of ventilator-associated pneumonia: The NASCENT randomized trial. JAMA. 2008;300:
805813.

e-TOCs and e-Alerts

Receive the latest developments in plastic and reconstructive surgery.
Request the delivery of Plastic and Reconstructive Surgerys e-Alerts directly to your email address. This is a fast,
easy, and free service to all subscribers. You will receive:
Notice of all new issues of Plastic and Reconstructive Surgery, including the posting of a new issue on the
PRS-Online Web site
Complete Table of Contents for all new issues
Visit www.PRSJournal.com and click on e-Alerts.

1256