Download Microbiologic Trends and Biofilm Growth on Explanted Periorbital

Original Investigation
Microbiologic Trends and Biofilm Growth on Explanted
Periorbital Biomaterials: A 30-Year Review
David B. Samimi, M.D.*†, Brett P. Bielory, M.D.*, Darlene Miller, D.H.SC. M.P.H.*,
and Thomas E. Johnson, M.D.*
*Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida; and †Eyesthetica,
Oculofacial and Cosmetic Surgery Associates, Los Angeles, California, U.S.A.
Purpose: To investigate microbiologic trends and role of
biofilm on periorbital biomaterials surgically explanted for
recalcitrant infection.
Methods: A search of the Bascom Palmer Eye Institute,
University of Miami Miller School of Medicine microbiology
laboratory electronic database was conducted from 1980 to
2010. Culture results were analyzed from submitted periorbital
biomaterials explanted for nonresolving infections or exposure.
Random select samples cultured during the study were sent for
electron microscopy.
Results: Twenty-one explanted biomaterials were identified
from 18 patients. Five orbital plate implants included 2 made of
nylon, 1 of porous polyethylene, 1 of silicone, and 1 metallic.
Of 4 anophthalmic socket sphere implants, 2 were silicone,
1 was porous polyethylene, and 1 was poly-2-hydroxyethyl
methacrylate. Lacrimal intubation devices included 10 silicone
stents and 2 pyrex glass Jones tubes. All biomaterials were
culture positive with 40 total isolates identified. The most
common organisms overall were Mycobacterium chelonae
(N = 9), Staphylococcus aureus (N = 8), and Pseudomonas
aeruginosa (N = 3). One hundred percent of orbital spheres
had Gram-positive organisms, 90% of lacrimal silicone stents
grew atypical mycobacterium, and 60% of orbital plates were
culture positive for yeast species. Mixed organism growth was
documented on 58% of the specimens. Ten of 12 implants
(83%) examined with electron microscopy exhibited organisms
encased in glycocalyx, suggestive of biofilm.
Conclusions: A diverse array of microorganisms can colonize
biomaterials implanted within the orbit and lacrimal drainage
system. The authors’ study showed that the majority of infected
periocular and orbital alloplastic implants display biofilm when
studied with electron microscopy (83%). The cultured organism
type depended on the implant location and composition. Most
infected silicone lacrimal stents grew atypical mycobacterium,
whereas infected orbital fracture repair plates demonstrated
yeast species. Biofilms are known to be antibiotic resistant,
explaining the need to explant most infected alloplastic implants.
Further research concerning treatment of biofilms may prevent
explantation and improve surgical outcomes.
(Ophthal Plast Reconstr Surg 2013;29:376–381)
Accepted for publication April 24, 2013.
Presented at the American Society of Ophthalmic Plastic and
Reconstructive Surgery (ASOPRS) 40th Annual Fall Scientific Symposium
on October 21–22, 2009, in San Francisco, CA.
The authors have no financial or conflicts of interest to disclose.
Address correspondence and reprint requests to David B. Samimi, M.D.,
Eyesthetica, 1513 South Grand Avenue, Suite 200, Los Angeles, CA 90015.
E-mail: [email protected]
DOI: 10.1097/IOP.0b013e31829a7313
376
T
he expanding availability of implantable biomaterials
has increased the use of synthetic material in oculofacial
surgery. Biomaterials, such as acrylic, nylon, glass, silicone,
hydroxyapatite, and porous polyethylene, provide the surgeon
with an expanding armamentarium of surgical tools for treating orbital and periocular disease. They also may provide
microorganisms with an immune-privileged, abiotic surface
for growth.
Recalcitrant infections associated with implants have
been described in almost every part of the body where they
have been used. The presence of biofilms on implants in ophthalmology has been documented on corneal sutures, punctal
plugs, lacrimal intubation devices, scleral buckles, and intraocular lenses.1–7
The purpose of this study was to characterize the microbiology of clinically significant periorbital biomaterial infection
and document the presence of biofilm by direct visualization
with electron microscopy.
METHODS
A retrospective review of the electronic Bascom Palmer Eye
Institute Microbiology Laboratory database was conducted between 1980
and 2010. Culture results from periorbital biomaterial submitted to the
microbiology laboratory for culture at the time of explantation were recorded. Clinical charts were reviewed and information regarding demographics, clinical course, and antibiotic usage were collected. The study
was approved by the University of Miami Institutional Review Board.
The culture protocol consisted of vortexing implant material
in thioglycollate broth and inoculating aliquots onto solid (chocolate,
5% sheep blood, sabouraud, Lowenstein-jensen) and liquid (thioglycollate broth and SeptiChek AFB [Becton Dickinson, Franklin Lakes,
NJ, U.S.A.]) culture media. Preliminary identification was confirmed
using Gram stains, acid-fast stains, growth rate, and biochemical profiles. Definitive identification of Mycobacteria was performed by either
MAYO Medical Labs (Rochester, MN, U.S.A.) or Focus Diagnostic
Labs (Cypress, CA, U.S.A.) using polymerase chain reaction or highperformance liquid chromatography.
Biomaterials and aliquots of the microbiology specimen that
were available while conducting this review were placed in formalin
and sent to the Center for Biofilm Engineering in Bozeman Montana or
the University of Miami Center for Advanced Microscopy for scanning
electron microscopy for detection of biofilm. Specimens sent to Miami
Center for Advanced Microscopy were processed by fixing in 10% formalin for at least 1 hour, then post fixed in 1% Osmium Tetroxide in
phosphate-buffered saline buffer for 30 minutes. After 3 progressive
rinses in phosphate-buffered saline for 10 minutes each, the samples
were dehydrated in an ethanol series. The specimens were critically
dried with hexamethyldisilazane, allowed to outgas overnight, and sputter coated with Palladium before imaging. Scanning electron microscopy at Miami Center for Advanced Microscopy used a Phillips XL-30
Ophthal Plast Reconstr Surg, Vol. 29, No. 5, 2013
Ophthal Plast Reconstr Surg, Vol. 29, No. 5, 2013
Periorbital Implant Infection
TABLE 1. Clinical data
Age, mean (range)
Immunosuppression
Diabetes mellitus
Dialysis or HIV
Autoimmune disorder
Age >65 years
Total weeks implanted
Median (range)
Weeks symptomatic before explantation
Median (range)
Postexplant weeks to symptom resolution
Median (range)
Pre-explantation antibiotic treatment attempted
Organisms that should have been sensitive based on culture
Overall
(N = 21)
Plate
(n = 5)
Spheres
(n = 4)
Jones tube
(n = 2)
Stent
(n = 10)
57 (5–81)
58 (38–73)
41 (5–64)
79 (77–81)
58 (32–79)
2 (10%)
0
2 (10%)
10 (48%)
1 (20%)
0
1 (20%)
3 (60%)
0
0
0
0
0
0
0
2 (100%)
1 (10%)
0
1 (10%)
5 (50%)
13 (2–1,924)
60 (24–1,924)
5 (4–208)
36 (12–60)
11 (2–128)
19 (2–105)
63 (8–156)
2 (2–105)
33 (10–55)
4 (1–8)
1 (1–62)
76%
44%
1 (1–4)
100%
40%
1 (1–1)
50%
0
9 (1–16)
100%
50%
9 (1–62)
70%
57%
HIV, human immunodeficiency virus.
ESEM FEG (Phillips, Amsterdam, the Netherlands) at varying kilovolts.
Scanning technique and equipment at Center for Biofilm Engineering
was similar and has been described previously.8 Images were examined
in a masked fashion by one of the authors, the director of the microbiology laboratory (D.M.), for evidence of organisms growing in biofilm.
overall had pre-explantation antibiotic treatment. Of those treated, 44%
of infections should have been sensitive to the given antibiotic based on
postexplantation culture results.
All biomaterials were culture positive with 40 total isolates identified (Table 2). The most common organisms overall were
Mycobacterium chelonae, Staphylococcus aureus, and Pseudomonas
aeruginosa. One hundred percent of orbital spheres had culture-confirmed Gram-positive organisms, 90% of lacrimal silicone stents grew
atypical mycobacterium, and 60% of orbital plates were culture positive
for yeast species (Fig. 1). Multiple organisms were growing on 58% of
the implants.
Twelve implants were imaged with electron microscopy: 4 orbital spheres, 4 plates, and 4 lacrimal stents. Organisms encased in matrix on the surface of the implants suggestive of biofilm was seen on 10
(83%) of the implants imaged (Figs. 2–4).
RESULTS
Twenty-one explanted biomaterials were identified from 18 patients. (Table 1) Five orbital plates included 2 nylon, 1 porous polyethylene, 1 silicone, and 1 metallic. Of 4 anophthalmic socket sphere
implants, 2 were silicone, 1 was porous polyethylene, and 1 was poly2-hydroxyethyl methacrylate. Lacrimal intubation devices included 10
silicone stents and 2 pyrex glass Jones tubes. Fourteen implants (67%)
were from female patients. Nine (43%) patients were Hispanic, 7 (33%)
Caucasian, 0 African American, and 5 (24%) others. Twelve (57%)
specimens were from the OD. Average follow-up period was 65 weeks
(range 0–350 weeks).
Median symptomatic weeks before explantation was longest
among the orbital plate (63) and Jones tube group (33). Postexplantation
time to symptom resolution was greatest in the Jones tube and lacrimal silicone stent groups, both 9 weeks. Seventy-six percent of patients
DISCUSSION
The authors’ study characterized microbiologic trends
from a variety of infected periorbital alloplastic implants needing surgical removal after recalcitrant infection in South Florida.
We discovered the predominance of Gram-positive isolates on
TABLE 2. Microbiology of explanted biomaterials from periorbital infections
Isolates
Gram positive
Staphylococcus aureus
S. epidermidis
Gram negative
Achromobacter xylosoxidans
Pantoea agglomerans
Pseudomonas aeruginosa
Serratia marcescens
Stenotrophomonas maltophilia
Mycobacteria
Mycobacterium chelonae
Fungi
Candida species
Trichosporon species
Total isolates
Orbital plates
(N = 5)
Orbital spheres
(N = 4)
Lacrimal stents
(N = 10)
Jones tubes
(N = 2)
Total
1
1
4
—
2
1
1
—
8
2
2
—
2
—
—
—
1
—
—
—
—
—
—
1
3
—
—
1
1
—
2
1
3
2
3
1
1
8
—
10
2
1
10
—
—
6
—
—
15
—
—
3
2
1
34*
*Forty total isolates, 6 individually occurring isolates excluded from table: Acinetobacter baumannii, Achromobacter xylosoxidans, Streptococcus intermedius,
Corynebacterium diphtheriae, Corynebacterium amycolatum, Enterobacter.
© 2013 The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc.
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D. B. Samimi et al.
FIG. 1. Organism by biomaterial type. Sums equal greater than 100% due to multiple isolates on the majority of implants.
orbital sphere implants, yeast on the majority of orbital plates,
and a high prevalence of atypical mycobacterium on clinically infected lacrimal silicone stents. The longest time period
between implant removal and resolution of infection-related
symptoms occurred with lacrimal implants. This study also
found that the period between implantation and removal was
longest in orbital plate group. Electron microscopic imaging
was suggestive for biofilm in the majority of implants studied.
Many factors predispose certain organisms to colonize
a given class of implants. These include the implant material,
native flora in the region of the implant, and organism compatibility with growth in a biofilm. All infected orbital spheres
exhibited Gram-positive isolate culture results. This likely
relates to the predominance of Gram-positive organisms routinely found on the conjunctival surface.9,10 Staphylococcus
isolates from the conjunctiva have also been shown to exhibit
increased biofilm formation ability in comparison to isolates
from the rest of the face.11 Yeast species were found on 3 of 5
orbital plates and not on any other class of implants. A positive
medical history for immunosuppression or high-risk setting for
infection was evident in all 3 patients: 1 with Wegener granulomatosis on immunosuppressant agents, 1 with diabetes mellitus, and a third with a history of prison incarceration at the
time of infection. Immunosuppression correlates with yeast
growth in the paranasal sinuses adjacent to where orbital plates
are placed.12 Chronic or later onset rhinosinusitis may partially
explain the longer period between implantation and removal
noted with orbital plates. Studies of sinus mucosa have shown
the presence of biofilm that may provide a reservoir for native
flora to infect an implant.13 One of the patients had a silicone
orbital plate that grew S. aureus and a history of chronic rhinosinusitis. He had undergone multiple sinus surgeries after
implant placement and had suffered 5 episodes of orbital cellulitis treated with intravenous antibiotics before explantation
of the plate.
Lacrimal silicone stent infection with atypical mycobacterium was first described by Rootman et al.14 in 1989.
The authors’ study found atypical mycobacterium on 90% of
FIG. 2. Infected porous polyethylene orbital floor implant culture positive with Mycobacterium chelonae, Pseudomonas aeruginosa,
and Trichosporon species in a patient with Wegener granulomatosis. A, Gross image. B, Electron microscopy of porous surface. C, High
power image showing sheets of rod-shaped organisms (blue arrow) and overlying hyphae (yellow arrow) consistent in size and morphology with culture results.
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© 2013 The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc.
Ophthal Plast Reconstr Surg, Vol. 29, No. 5, 2013
Periorbital Implant Infection
FIG. 3. Electron microscopy images. A and B, Metal screws from metal-coated porous polyethylene orbital plate implant removed 6
months after placement, culture positive with Pseudomonas aeruginosa and Candida parapsilosis. Organisms and surrounding deposits
consistent in size and morphology with yeast seen on high power images of surface. C and D, Cocci-shaped organisms encased in
biofilm matrix on the surface of methicillin-resistant Staphylococcus aureus–infected poly-2-hydroxyethyl methacrylate material AlphaSphere implant surgically explanted 1 month after placement.
infected stents. The organism may be subclinically present in
many patients with history of nasolacrimal duct obstruction
necessitating dacryocystorhinostomy surgery or may develop
externally during or after implantation. The majority of dacryocystitis cases are caused by Gram-positive flora.15,16 A study
of microbial growth on lacrimal silicone stents by Kim et al.17
found mostly Gram-positive organisms, but a correlation of
P. aeruginosa with postoperative membranous ostia obstruction.
A high prevalence of underlying mycobacterial infection has
not been documented. Atypical mycobacteria are ubiquitous
throughout the environment and commonly found in municipal
water supplies.18–20 A study by Feazel et al.21 involved swabbing
the interior surface of showerheads from 9 regions across the
country and used rRNA analysis to identify microbial species.
Nontuberculous mycobacterium were the most common class
of organisms found. Theoretically, daily exposure to aerosolized
FIG. 4. Progressively closer images of infected lacrimal silicone stent that caused chronic mucopurulent dacryoconjunctivitis. Culture
isolates included Mycobacterium chelonae, Serratia, and Corynebacteria. A, Sectioned lumen with biofilm plaques. B and C, Depth of 1
plaque (white arrow). D, Tubular-shaped organisms encased within protective matrix seen on surface of plaque (black arrow).
© 2013 The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc.
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D. B. Samimi et al.
mycobacteria, while showering in the presence of a silicone foreign body, may predispose these patients to clinically significant
infection. Other possible explanations include contaminated
tubes or silk sutures at the time of implantation, contaminated
make up, preexisting mycobacterial dacryocystitis, or nasal colonization with atypical mycobacterium.
Patients with infected lacrimal silicone stents and Jones
tubes both had a median of 9 weeks of residual symptoms after
implant removal. Common symptoms were discharge, erythema, and pain. These symptoms may be related to bacterial
reservoirs from lacrimal or nasal biofilm residua or from scarring of the lacrimal system with recurrent nasolacrimal duct
obstruction and dacryocystitis. The longer duration of symptoms may also be related to the extraorbital location of the lacrimal system making residual or resolving infection more evident
to the patient and clinician.
The majority of bodily infections involve biofilm, a heterogeneous collection of microorganisms encased within a protective extracellular polymeric substance matrix derived from
host and bacterial materials.7 Within biofilm exist complex
communities exhibiting cell-to-cell communication, varying
degrees of gene expression, and commonly multiple species acting synergistically to survive harsh environmental conditions.22
Cells near the biofilm surface have the most exposure to nutrients and are the most metabolically active, whereas those deeper
in the biofilm have access to nutrients through intricate channel
networks but are relatively dormant.7 The heterogeneous degree
of metabolic activity and physical extracellular polymeric substance matrix fortification confer microorganism protection
against adverse conditions. Bacteria in biofilm are up to 1,000
times more resistant to antibiotics than those studied in the classic laboratory planktonic form.7,23
Biofilms have previously been described on a wide variety of periorbital implants including punctal plugs, lacrimal
intubation devices, and scleral buckles.1,3–5,7 Electron microscopy examination of most implants in the authors’ study suggested presence of biofilm. The 3 most common organisms
overall, M. chelonae, S. aureus, and P. aeruginosa, are all avid
biofilm producers. Many implants included in the study were
recalcitrant to antibiotic therapy to which the organism isolate
was sensitive in laboratory culture. The widely held paradigm
of treating infection based on laboratory sensitivities does not
fit implant-related infection.24
The definitive treatment strategy for implant-related
infection is implant removal and appropriate antibiotic therapy.23,24 Other intervention strategies include the prevention of
initial device contamination, minimization of initial microbial
cell attachment, and use of antibiotics with increased penetrance and efficacy against microbial biofilm.23,25 Strict aseptic
technique should always be followed when implanting foreign
biomaterial. Once implanted, all foreign bodies are quickly
coated by host matrix molecules such as fibrinogen, fibronectin,
and collagen.7,23 The fate of the available surface is then a contest between tissue cell integration and microbial adhesion and
subsequent biofilm formation.26 Implant design modifications,
such as alteration in surface polarity, surface texture, and antibiotic coating, have been shown to discourage bacterial biofilm
growth.27–29 Design alterations to inhibit microbial growth are
not without their problems. Sufficient antibiotic must be incorporated for the lifetime of the device, and long-term presence
of antimicrobials may promote resistant organisms.25 Although
antibiotic efficacy against biofilm-embedded organisms is limited, some antibiotics demonstrate more efficacy than others.
Daptomycin, minocycline, and tigecycline show increased
efficacy against biofilm-embedded methicillin-resistant S.
aureus when compared with linezolid or vancomycin in vitro.30
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The literature also suggests a synergistic effect when adding
rifampin or N-acetylcysteine.30,31 Further studies regarding the
effective prevention and treatment strategies are needed.
The main weaknesses of the authors’ study relate to the
retrospective nature of their data search. Relevant infections
may have been missed in their microbiology electronic database
review. Many removed implants are sent to pathology instead
of the microbiology laboratory. It would have also have been
useful to report the incidence of successfully treated implantrelated infections in their patient population during the same
period. This data would be difficult to accurately ascertain over
the 30-year interval. Given the relatively small sample size of
the study and referral nature of the patient population at their
institution, the study was also not ideally structured to extrapolate conclusions regarding incidence and risk factors for infection. Comparative controls would be useful to further clarify the
pathogenicity of the organisms and biofilm in their study. Also,
the findings from South Florida may not generalize to other
patient populations.
Biofilm growth likely plays a significant role in clinically significant periorbital implant infection. Further research
in effective biofilm prevention and treatment strategies may
improve surgical outcomes.
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