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Infectious complications in implant based breast surgery and implications for plastic surgeons

Infektiöse Komplikationen bei alloplastischen Brustoperationen und Implikationen für Plastische Chirurgen

Abstract

Implantation of breast prosthesis is still one of the most frequently performed breast reconstructing or contouring procedures.

Raymund E. Horch

1,2

Gregory Schultz

3

Infectious complications and capsular contracture are inherent problems

that may have different causes which are not clearly defined yet in terms

Dirk W. Schubert

2,4

Marweh Schmitz

1,2

of pathophysiology. Recent findings showed bacterial contamination as a major cause of implant failure. Since this has direct implications for the surgical management we report on biofilm development on allo-

1 Plastisch- und

Handchirurgische Klinik, plastic breast prostheses, characteristics and effects after implantation

of medical devices in general. This article gives a review of the current

Universitätsklinikum literature and discusses possible issues to solve the problem of infection

after implantation of breast prosthesis. Erlangen, Friedrich-Alexander

Universität Erlangen- Nürnberg, Erlangen, Germany In conclusion the reinsertion of single-use devices should not be recom-

mended and should be strictly avoided when a device related infection

2 Center for Breast Prosthesis Research, Friedrich- has occured. According to current knowledge contaminated implants

should be removed, the infection then be cured and if necessary, a new Alexander Universität prosthesis may be implanted after a regeneration period. Alternatively Erlangen-Nürnberg, Erlangen,

Germany a change in therapy towards autologous tissue reconstruction should

be considered if previous attempts with alloplastic prostheses have

3 Institute for Wound Research, Department of failed and if radiation therapy has worsened the local tissue situation

in the recipient area. Obstetrics and Gynecology,

Zusammenfassung

Implantationen von Brust-Prothesen sind für Brustrekonstruktionen oder Konturierungen noch immer die am häufigsten durchgeführten

University of Florida, Gainesville, USA 4 Lehrstuhl für

Polymerwerkstoffe, Friedrich- Alexander Universität Verfahren. Typische inhärente Probleme sind dabei neben infektiösen Erlangen-Nürnberg, Erlangen,

Germany Komplikationen die Kapselkontrakturen, deren unterschiedliche Ursa-

chen bezüglich der Pathophysiologie noch nicht eindeutig geklärt sind.

Neuere Erkenntnisse weisen auf bakterielle Kontamination als eine der Hauptursachen von Implantatversagen hin. Da dies direkte Auswirkun- gen auf die chirurgische Behandlung hat, berichten wir über das Problem der Biofilmentwicklung auf alloplastischen Brustimplantaten sowie über deren Effekte nach Einsetzen von medizinischen Implantaten allgemein.

Dieser Artikel gibt einen Überblick über die aktuelle Literatur und disku- tiert mögliche Fragen der Problematik der Infektion nach der Implanta- tion von Brust-Prothesen.

Zusammenfassend kann das Wiedereinsetzen von Implantaten für den Einmalgebrauch nicht empfohlen werden und sollte daher bei Verdacht auf eine Infektion unbedingt unterlassen werden. Nach derzeitigem Kenntnisstand sollten kontaminierte Implantate entfernt, eine beste- hende Infektion zunächst ausgeheilt und, falls erforderlich, erst nach einer Regenerationsphase ein neues Implantat eingesetzt werden. Al- ternativ sollte immer auch ein Verfahrenswechsel auf eine Eigengewebs- rekonstruktion in Betracht gezogen werden, insbesondere wenn vorhe- rige alloplastische Verfahren versagt haben und die lokale Gewebesi- tuation im Empfängergebiet etwa durch eine Strahlentherapie ungünstig ist.

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Introduction

In recent literature there is a growing body of scientific evidence that bacteriae could be a major cause for im- plant failure [1], [2]. We have previously reviewed the biofilm problem with regard to late seroma and revisional breast surgery [3] and want to highlight this issue because not only in aesthetic procedures but also in breast recon- struction implants still play a considerable role [4]. In contrast to this procedure, usually no long term infectious problems are seen when restoring the breast mound with the patient’s own tissue. Through an increased standard- ization of autologous breast reconstruction surgery this alternative has become a routine procedure in the hands of experienced reconstructive surgeons and it is available to many patients in Europe when amputation of the breast or partial loss of breast tissue as a consequence of cancer therapy is experienced. In addition, when performed in high volume centers, free microsurgical transplantation of suitable tissue has been optimized rendering reliable results with a high rate of safety, even in previously irra- diated patients [5], [6], [7]. Other future options, such as creating replacement tissue by means of tissue engineer- ing and regenerative medicine seem highly promising but are not clinically available yet [8], [9], [10], [11], [12], [13], [14], [15], [16], [17]. Nevertheless on a worldwide perspective implant based alloplastic breast reconstruc- tions with or without skin expansion is believed to account for the majority of procedures to restore breast shape and volume. Moreover despite the undoubtable benefits of autologous breast repair authors have even proclaimed a shift of paradigm towards increasing alloplastic recon- structions recently [18].

Breast implants are also used for aesthetic reasons, malformation of the breast, expanders followed by definitive implants in reconstructive surgery, prophylactic mastectomy due to BRCA 1 mutations. After skin sparing mastectomy (with still approximately 5% of remaining breast tissue) often a critical perfusion of the skin enve- lope is experienced. In these patients it is questionable if less perfused tissue may present a sufficient mechan- ical barrier against microorganisms. If the skin is irradi- ated this problem might become even more significant.

Patients who had radiotherapy have a significantly higher incidence of subclinical infection than patients who did not [19], Oposite after a risk-reducing mastectomy with approximately 20–30% of remaining breast tissue a ro- bust skin envelope remains that could act as a good mechanical barrier of microorganisms.

Among other well known side effects of breast implants, such as displacement, double bubble deformity, undue scarring, implant rupture, systemic spreading of silicone into the body [20] etc., the event of a capsular contracture remains an unsolved but serious clinical problem [21], [22], [23], [24], [25]. Up to now numerous attempts to prevent capsular contracture failed and did not achieve a reliable effect for clinical use [23], [26]. Following the so called PIP scandal numerous questions were brought up again whether we do know enough about the material

properties and longevity of alloplastic breast implants, the mechanisms of capsular contracture [27], and the involvement of subclinical infectious processes, long term side effects such as the occurance of anaplastic large cell lymphoma cells in the periprosthetic fluid etc. [28], [29], [30], [31], [32], [33], [34], [35], [36].

Anecdotally it has been reported that bacterial coloniza- tion was detected in the seroma fluid of patients with capsular contracture [37], [38], but even when infection was clinically seen bacterial counts were not positive in all cases [1], [2], [39], [40], [41], [42], [43]. Researchers removed breast prostheses from capsular contracture grade III and IV, and sonication detected bacteria in 41%

of removed breast implants. The identified bacteria be- longed to normal skin flora [2]. Although further investi- gations will be needed to determine a true causal relation between biofilms and capsular fibrosis, the infectious hypothesis has gained widespread acceptance as one major cause of capsular contracture [1], [44]. According to Jacobs et al. this is based on both clinical and research studies that have shown an association between the presence of bacteria and high grade capsular contracture [45]. With a better understanding of the complex interac- tions of planctonic bacteria in biofilms [46] an increasing number of publications now focuses on the problems of bacterial contamination of chronic wounds and infected implants of any type [47]. Knowledge about the behavior of various bacteria within biofilms, their diagnosis and treatment options in dental medicine and in microbiology is constantly growing, but data on biofilms in breast im- plants are still scarce [47], [48], [49], [50], [51], [52], [53], [54], [55], [56]. In the literature there is no clear description of a correlation of the grade of capsular con- tractures and microbiological structures found in biofilms so far.

Biofilm development on devices

The detrimental effects of bacterial biofilms on medical devices have been established within the scientific liter- ature to be responsible for persisting infections in con- cerned implants and recently have been shown to be re- sponsible for non-healing chronic wounds too.

Electron microscopy of biopsies from chronic wounds found that 60% of the specimens contained biofilm structures in comparison with only 6% of biopsies from acute wounds. According to Philips et al. [57] biofilms are complex microbial communities that contain bacteria and fungi. The microorganisms synthesize and secrete a protective matrix that attaches the biofilm firmly to a vital or non-vital surface. Bacteria within biofilms interact with each other and exchange signals. This phenomenon has been termed “quorum sensing”. Cell-to-cell communica- tion is pivotal to the development and maintenance of biofilm structures [45]. This system confers several ad- vantages to these microorganisms, including protection from the host immune system and antibiotic treatment.

Biofilms are considered to be dynamic heterogeneous

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communities which are continuously changing their composition [45]. They may consist of a single bacterial or fungal species, or more commonly, may be polymicro- bial [58], [59], [60], [61], [62]. At the most basic level a biofilm can be described as bacteria embedded in a thick, slimy barrier of sugars and proteins. The biofilm barrier protects the microorganisms from external threats [57].

They have been for long time known to form on surfaces of medical devices, such as central venous lines, urinary catheters, endotracheal tubes, dental replacement ma- terials and teeth, orthopaedic and breast implants, con- tact lenses, intrauterine devices sutures and dialysis catheters [63], [64], [65].

Biofilms were mainly found in aqueous systems, which are based on a water surface or on a boundary surface to a solid phase [35], [46]. Biofilms on teeth are well known under the term “plaque” [47]. They are assumed to be a major contributor to diseases that are character- ized by an underlying bacterial infection and chronic in- flammation, e.g. periodontal disease, cystic fibrosis, chronic acne and osteomyelitis. Microorganisms in biofilms excrete extracellular polymeric substances and form hydrogels in combination with water. Essentially, there are polysaccharides, proteins, lipids and nucleic acids that compose the film. The product can be seen as a slimy matrix in which nutrients and other substances are dissolved, and that gives a stable form to the biofilm.

Several steps have been characterized that are typical for the timing of biofilm formation. Various terms have been published to describe typical states of biofilm devel- opment and among them three time periods have been commonly accepted. These include an induction phase, agglomeration phase and the phase of existence (see Figure 1).

Biofilm formation is a very complex, multistep process with microorganisms attraction and adhesion, with pluri- stratification of bacteria onto the artificial surface as the first and decisive step to a given surface [53] (Figure 1).

The first step requires the mediation of bacterial surface proteins, in which the main bacterium isS. aureusauto- lysin [38]. Free-floating microorganisms are attracted to dirty, wet surfaces and initially adhere to these surfaces using weak intermolecular van der Waals forces. If not physically separated from the surface immediately, these microorganisms “permanently” attach to such surfaces using cell adhesion molecules such as pili. Water coated surfaces provide better attachment conditions than dry surfaces. As the biofilm begins to form, an increasing number of microorganisms is attracted to cell adhesion sites [56], [57].

The second step is dominated by the growth period. As the biofilm grows, the structure is held together and pro- tected by an excreted EPS (extracellular polymeric sub- stance). As already mentioned biofilm molecules, often consist of many different Bacteria, and they communicate with one another using “quorum sensing” [56]. Quorum sensing, an interbacterial communication mechanism it- self is dependent on population densit. The EPS protects the microorganisms living within and provides pathways

for efficient communication between cells and microor- ganisms also undergo a genetic change when living within biofilms [57]. Several studies suggest that some cells such asE. colibecome virtually immune to antibiot- ics due to a low level of metabolic activity. In their study from 2001 Stewart and Costerton have estimated that antibiotic resistance of sessile bacteria living within biofilms can be 1000 fold greater than that of free-floating planktonic bacteria [63]. The biofilm matrix forms both mechanical stability and the possibility that the individual organisms build synergistic interactions among them- selves, to survive periods of starvation and remain extra- cellular enzymes get into the mucus layer [38], [66].

The third phase is characterized by detachment. This is seen when biofilms grow into large macroscopic three- dimensional structures. This is when shear forces may cause large sections of the biofilm to detach – releasing millions of organisms [57], [67].

Biofilm and the “re”-use of medical implants

Historically implant sizers (implants with smooth surfaces to find out the appropriate size of the definitive prosthe- sis) were routinely and repeatedly resterilized until the early 1990s. Also anecdotally it was reported that im- plants had been washed in antibacterial disinfectants or antibiotics and then were reinserted during revisional surgery when they macroscopically looked intact. How- ever, when recommendations had been issued that no implant may be reinserted once it had been taken out, in Germany the regulation for medical products and inter- pretations of the appropriate laws has been discussed by various authors and institutions, among them by a special task force for questions of hygiene in medicine by the AWMF (Arbeitsgemeinschaft der Wissenschaft- lichen Medizinischen Fachgesellschaften/working group of scientific medical associations) [66]. Since then it has been considered common knowledge and has become a standard that breast implants may not be used twice, being designed as one way products. Since at the time of implant exchange one cannot definitely know the result of bacterial swabs (which have to be processed for several days) it seems clear that the existence of a biofilm on a prosthesis cannot be ruled out visually, even when there were no typical clinical signs. Biofilms may not be visible by inspection. According to the current data it is not pos- sible to reliably remove a biofilm on a breast implant in situ and under clinical conditions. Methods to eliminate biofilms on implant currently rely on harsh procedures that can be applied only outside the human body, such as plasma sterilization, ultrasonic treatment, oxidants, chlorine/ sodium hypochlorite, hydrolysis with microbub- bling, bacteriophage therapy, x-ray or UV/ozone-irradi- ation, electroporation and application of electric fields in combination with biocides, laser radiation etc., to name the most frequently discussed options [68]. Necessarily, for these interventions implants will have to be removed

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Figure 1: Schematic depiction of biofilm development and growth (mod. after [57], [92])

from the body. This applies also for the use of other allo- plastic or biological materials that are inserted or im- planted into the human organism, such as “fillers” for instance [56], [69]. Ideas to protectively coat prostheses with antibactericidal surfaces have been investigated, but are not clinically available yet [70].

Because on the one hand the rapidly evolving knowledge about biofilms in this context is not yet generally recog- nized, and on the other hand, however, plastic surgeons may get into considerable and potentially avoidable legal conflicts when they deviate from current guidelines, we want to reflect on this topic against the background of current insights with regard to the biofilm problem on breast implants [2], [71].

Infectious complications after breast implants and biofilms

Infection after breast implant surgery occurs in 1.1% to 2.5% of procedures performed for augmentation and up to 35% of procedures performed for reconstruction after mastectomy. Most infections result from skin organisms and occur in the immediate postoperative period, al- though infections can occasionally present after many years [72]. Many product recalls and product contamina- tion issues are caused by biofilm detachment. Generally there is a consensus that despite all safety measures

local complications cannot be completely avoided after breast implant surgery. Devices such as sterile funnels to prevent skin contact during insertion of breast pros- theses have been developed for this reason. Similar to infections of other medical devices the removal of the potentially contaminated implant is the cornerstone of treatment. Bacterial cells which detach from these biofilms can enter the circulatory system. This can lead to severe systemic side effects such as sepsis. For in- stance, in patients with catheter sepsis, sepsis has been described to occur in 6%, and endocarditis in 1% [73].

In general, in current reviews any device in place is con- siderd to bacterially contaminated during its life span in around 7% [74].

For any exposed or infected implant the main aim is to cure the infection in the first step before reinsertion of another implant can be considered. A time frame of 3–6 months is generally accepted to be sufficient before re- peating the device implantation [75], [76], [77], [78].

Failed post cancer breast reconstructions frequently are converted into autologous reconstructive procedures [79], [80], [81], [82] to get rid of the alloplastic material.

Only within the last years the impact of bacterial biofilms on the pathogenesis and maintenance of chronic inflam- mation processes could be shown as the most frequent reason for implant failure, which is why the strict removal of potentially infected breast prosthesis is essential [83].

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Figure 2: 3D electron scanning micsroscopical image of textured breast prostehesis surface explanted from a grade IV Baker capsular contracture; visibly broken polymer structure with sharp edges and growth of bacteriae seen in left lower corner

In contrast to the scientific aspects especially for Plastic Surgeons the legal aspects have to be taken into consid- eration when dealing with one way products and devices.

Due to economic needs in modern medicine the repeated use or “re-use” of single-use products has become an increasingly contentious issue. Obviously this is not primarily a pure medical problem. But if surgeons deviate from the standard regulations concerning medical devices lawful they take over the responsibility of delivering a certified product. This usually would be the task of the manufacturer who has to oblige certain laws and regula- tions in order to get permission to distribute medical devices for implantation into a human body which have been shown to cause no harm. There has been consider- able debate if medical devices that are intended for single use may be recycled or not. In Germany the Robert Koch Institute and the Association of Scientific Medical Socie- ties (AWMF) have issued a consensus statement that covers also the handling of silicone implants for breast surgery [66].

European Union member states have propagated certain steps to tighten regulatory controls over medical devices and technologies in the wave of revelations that French breast implant manufacturer Poly Implant Prothèse Company (PIP) used non-medical-grade silicone in its products. Coordinated efforts have been initiated at na- tional levels to ensure full implementation and enforce- ment of existing medical device legislation to guarantee safety and improve patient confidence in the EU regula- tory system. On a regulatory level verification of notified body designations needs to be evaluated whether these entities are truly designated only for assessment of medical devices and technologies, as well as making sure that Notified Bodies fully leverage their authority being

laid out in conformity assessments, including their power to conduct unannounced inspections. In any respect it seems advisable for Plastic Surgeons to be informed about the legal implications of deviating from common standards and how to perform safely during revisional breast implant surgery. Infections after breast implants and the role of potential biofilms are a common cause for legal cases. As long as the microscopically thin biofilms containing bacteria or fungi are not visible by pure inspec- tion an implant that may look otherwise intact the implant should be considered to be potentially afflicted with biofilm once it has been exposed. It should be clear that washing breast implants in bactericidal solutions or in antibiotics intra-operatively in order to get rid of biofilm is not sufficient to ensure product safety. Given the complex 3D surface structure of breast prosthesis (Figure 2, Figure 3) it can easily be perceived that a full penetration of any antimicrobial agent into the deepest holes and spaces of the surface is almost impossible.

Case reports in the literature about successful retainment of exposed silicone breast implants were based on clinical experience and did not discuss the removal of a biofilm or the problems of incomplete microbicidal action and penetration into the structure [20], [73], preventing complete removement of the biofilm [74].

Furthermore on it has been suggested that aggressive biocides may well alter the surface of a silicone implant and could lead to implant failure by destroying the original material properties of the membrane. Testing potential side effects of antimicrobial agents and various disinfect- ants on the material properties of breast implants is ne- cessary and is currently envisioned by researchers to clarify these questions.

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Figure 3: Prosthesis removed from a a patient with grade IV Baker capsular contracture and firm attachment of capsule

suspicisous of a chronic inflammatory process

It seems currently common sense, although various ex- perimental methods to prevent or combat biofilms have been published, that all of these measures are not applic- able to the patient in the clinical situation yet. In particu- lar, the high-frequency ultrasound treatment of implants or the plasma treatment of implants outside the body or the introduction of selected metals into a biofilm, such as silver, platinum or bismuth, coatings of urinary cathet- ers with non-pathogenic Escherichia coli bacteria, elec- trical current, Chlorine or UV- and X-ray irradiation are unsuitable for intraoperative removal of biofilms [20], [71], [72], [73], [74], [75], [76], [77], [84]. Even if some major bacterial load of biofilms could be removed, disin- fectants will probably not penetrate deep enough into the biofilm. Remaining bacteria can be quiescent for years.

These are termed “persisters”.

According to our current understanding, the chemical composition of the biofilm can also offer unfavorable conditions that render bactericides effectless. Moreover, the different cells or groups of cells within a biofilm can behave very differently. For example bacterial biofilm can grow in the aerobic and/or anaerobic zone. Thus, different parts of the biofilm vary by the distance to nutrients or oxygen or antibiotics or reactions of the immune system.

In addition, microbes within a biofilm show a reduced metabolism and rate of growth up to extended periods of quiescence [85], [86], [87], [88], [89]. Such bacteria frequently cannot be propagated in culture and hence are not detected in swabs [43]. They do ingest cytotoxins and protect themselve by their failure to respond to anti- biotics or bactericides. This special phenomenon has been accused to cause the so called “late seroma” in breast prosthesis [40]. It is one reason why perioperative antibiotic prophylaxis is recommended when breast im- plants are inserted [90]. There is no clear evidence yet if the use of sterile plastic bags to protect contact between implants and skin definitely decreases this complication risk. One reason might be the contamination possibility by the contact to glandula/ducts [47], [91].

Conclusion

In conlusion our current knowledge about biofilms and breast implants implicate that a reliable elimination of biofilm on breast implants during operative revisions is not safely possible so far. Moreover, exposed prostheses need to be replaced by new ones to make sure that any risk of persisting biofilm is excluded. It seems obvious and is highly advisable to not reuse single-use products when an infection might have occurred. The safest resol- ution is first of all to remove the implant, then cure the infect and either come back to reinsert another prosthesis or change the procedure to an autologous reconstruction.

Notes

Competing interests

The authors declare that they have no competing in- terests.

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Corresponding author:

Prof. Dr. Raymund E. Horch

Plastisch- und Handchirurgische Klinik,

Universitätsklinikum Erlangen, Friedrich-Alexander Universität Erlangen-Nürnberg, Krankenhausstrasse 12, 91054 Erlangen

Irma.goldberg@uk-erlangen.de

Please cite as

Horch RE, Schultz G, Schubert DW, Schmitz M. Infectious complications in implant based breast surgery and implications for plastic

surgeons. GMS Ger Plast Reconstr Aesthet Surg. 2013;3:Doc04.

DOI: 10.3205/gpras000014, URN: urn:nbn:de:0183-gpras0000146

This article is freely available from

http://www.egms.de/en/journals/gpras/2013-3/gpras000014.shtml Published:2013-07-04

Copyright

©2013 Horch et al. This is an Open Access article distributed under the terms of the Creative Commons Attribution License

(http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share — to copy, distribute and transmit the work, provided the original author and source are credited.

Abbildung

Figure 1: Schematic depiction of biofilm development and growth (mod. after [57], [92])
Figure 2: 3D electron scanning micsroscopical image of textured breast prostehesis surface explanted from a grade IV Baker capsular contracture; visibly broken polymer structure with sharp edges and growth of bacteriae seen in left lower corner
Figure 3: Prosthesis removed from a a patient with grade IV Baker capsular contracture and firm attachment of capsule

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