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Biofilm on artificial pacemaker: fiction or reality?

Abstracts

Cardiac pacing through cardiac pacemaker is one of the most promising alternatives in the treatment of arrhythmias, but it can cause reactions natural or complex reactions, either early or late. This study aimed to describe the scientific evidence on the risk of infection and biofilm formation associated with cardiac pacemaker. This is a study of integrative literature review. It included 14 publications classified into three thematic categories: diagnosis (microbiological and/or clinical), complications and therapy of infections. Staphylococcus epidermidis and Staphylococcus aureus were the microorganisms most frequently isolated. It was not possible to determine the incidence of infection associated with pacemakers, since the studies were generally of prevalence. In terms of therapy, the complete removal of pacemakers stood out, especially in cases of suspected biofilm. Still controversial is the use of systemic antibiotic prophylaxis in reducing the incidence of infection associated with implantation of a pacemaker

Pacemaker; artificial; biofilms; prosthesis-related infections


A estimulação cardíaca artificial por meio de marca-passo cardíaco representa uma das alternativas mais promissoras no tratamento das arritmias, entretanto pode ocasionar reações singulares ou complexas, precoces ou tardias. Neste estudo, objetivou-se descrever as evidências científicas sobre o risco de infecção e formação de biofilme associado ao marca-passo cardíaco. Trata-se de um estudo de revisão integrativa da literatura. Totalizaram-se 14 publicações classificadas em três categorias temáticas: diagnóstico (microbiológico e/ou clínico), complicações e terapêutica das infecções. Os Staphylococcus epidermidis e os Staphylococcus aureus foram os microrganismos mais frequentemente isolados. Não foi possível determinar a incidência da infecção associada aos marca-passos, uma vez que os estudos eram em geral de prevalência. Em termos de terapêutica destacou-se a remoção completa dos marca-passos, especialmente nos casos de suspeita de biofilme. Ainda é controverso o uso da profilaxia antibiótica sistêmica na redução da incidência da infecção associada ao implante de marca-passo

Marca-passo artificial; biofilmes; infecções relacionadas à prótese


La estimulación cardíaca artificial por medio de marcapaso cardíaco representa una de las alternativas más promisorias en el tratamiento de las arritmias, sin embargo, puede ocasionar reacciones singulares o complejas, precoces o tardías. En este estudio, el objetivo fue describir las evidencias científicas sobre el riesgo de infección y formación de biofilm asociado al marcapaso cardíaco. Se trata de un estudio de revisión integrante de la literatura. Se totalizaron 14 publicaciones clasificadas en tres categorías temáticas: diagnóstico (microbiológico y/o clínico), complicaciones y terapéutica de las infecciones. Los Staphylococcus epidermidis y los Staphylococcus aureus fueron los microorganismos más a menudo aislados. No se pudo determinar la incidencia de la infección asociada a los marcapasos, pues los estudios eran en general de prevalencia. En términos de terapéutica se destacó la retirada completa de los marcapasos, especialmente en los casos en que se sospechaba de biofilm. Todavía es algo controvertido el uso de la profilaxis antibiótica sistémica para la reducción de la incidencia de la infección asociada al implante de marcapaso

Marcapaso artificial; biofilms; infecciones relacionadas con la prótesis


CLINICAL UPDATE

IEscola de Enfermagem de Ribeirão Preto - Universidade de São Paulo

IIFaculdade de Odontologia de Ribeirão Preto - Universidade de São Paulo, São Paulo, SP, Brasil

Mailing address

ABSTRACT

Cardiac pacing through cardiac pacemaker is one of the most promising alternatives in the treatment of arrhythmias, but it can cause reactions natural or complex reactions, either early or late. This study aimed to describe the scientific evidence on the risk of infection and biofilm formation associated with cardiac pacemaker. This is a study of integrative literature review. It included 14 publications classified into three thematic categories: diagnosis (microbiological and/or clinical), complications and therapy of infections. Staphylococcus epidermidis and Staphylococcus aureus were the microorganisms most frequently isolated. It was not possible to determine the incidence of infection associated with pacemakers, since the studies were generally of prevalence. In terms of therapy, the complete removal of pacemakers stood out, especially in cases of suspected biofilm. Still controversial is the use of systemic antibiotic prophylaxis in reducing the incidence of infection associated with implantation of a pacemaker.

Keywords: Pacemaker, artificial/trends; biofilms; prosthesis-related infections.

Introduction

Cardiac pacing was introduced into clinical practice in the 50s with the primary objective of eliminating the symptoms and reducing mortality of patients with advanced atrioventricular blocks. Advances in pacemaker manufacturing and implantation technology, plus the electrophysiology knowledge of cardiac conduction disorders, enabled a consistent progress in cardiac pacing, extremely diverse in its mode of operation, with high physiological reliability and safety1.

Although pacemaker implantation surgery is considered less complex, it is important to observe that, for being an invasive procedure and representing a foreign body, it puts the patient at risk for various complications, sometimes due to failures of generators, tissue damage or due to the implantation technique2,3. The diversity of techniques and conducts has provided improvement in surgical technique, however, there is limited information on the implications and effects of these improvements4.

One concern among professionals is the risk of biofilm formation and, consequently, infection. In recent decades, biofilms have been widely blamed for nosocomial infections, especially in prosthetic implants, tubes, probes and catheters5-7. It is speculated that the presence of pacemakers is conducive to microbial colonization, contributing greatly to the development of biofilm, which could explain the occurrence of endocarditis6-10.

It is worth noting that the biofilm consists of a structured community of microbial cells adhered to a solid surface surrounded by a matrix of extracellular polymeric substances. This microbial association is a form of protection against its development, encouraging symbiotic relationships and tolerance to antimicrobials. The literature on biofilm as a risk factor for health progressed from the 90s5. The biofilm formation involves a sequence of events, such as the initial reversible adherence of microorganisms to the surface of the solid substrate, microbial growth, matrix production of extracellular polymeric substances and detachment of sessile cells, which in planktonic form may cause infection or biofilm formation in other locations.

In biofilms, microcolonies are heterogeneous, consisting of microbial cells of one (monomicrobial) or more species (polymicrobial), functionally organized, where the organisms are protected from the action of macrophages and antibiotics. Moreover, the biofilm is roughly composed of 10 to 25% microorganisms, and 75 to 90% extracellular polymeric substances11.

One concern among scholars is the infection that the biofilm triggers, and in many cases of implants, device replacement is the alternative indicated11. Accordingly, it is worth noting that it is crucial to investigate the biofilm when there is persistence of infection12.

Particularly, the implantation of pacemakers is a procedure characterized by a low complication rate, however, infections, mainly that of pacemaker generator pocket is one of the most common complications with incidences ranging from 1-5%3-17. Despite the low incidence, such infections have a worrying development mostly often with high morbidity and potentially fatal.

Several conducts have been described for the treatment of infection of pacemaker pocket. More conservative therapeutic approaches seem to produce higher rates of relapse or failure of treatment2-18, and the best results relate to more aggressive approaches, with complete removal and implantation of new endocardial systems3-8, which is usually associated with high hospitalization rates and high costs3.

Given the above, this study aimed to describe the scientific evidence about the biofilm formation and occurrence of infection associated with pacemakers in order to identify key recommendations for the prevention and control. It also aims to evaluate in the studies the incidence of infection and the microbial flora in pacemakers. Evidence-Based Practice was the theoretical reference which, in a medical problem, allows evaluating critically the production of scientific knowledge to support the decision19.

Methods

The method used was an integrative literature review, which is part of the Evidence-Based Practice, which allows the synthesis of evidence available on a defined issue, contributing to the deepening of knowledge on the subject investigated19.

The articles select was based on the following question: What has been published on biofilm formation and infection related to cardiac pacemakers?

To search for articles, we used the data bases Medical Literature Analysis and Retrieval System (MEDLINE), Latin American and Caribbean Center on Health Sciences (LILACS), Cumulative Index to Nursing and Allied Health Literature (CINAHL) and Cochrane Library, with Internet access. The descriptors were biofilms, pacemaker, artificial cardiac and infection, selected from the definitions in the Medical Subject Headings (MESH) and Descriptors in Health Sciences (DeCS) from the Virtual Library on Health (BVS).

The studies selected were classified according to level of evidence: 01) systematic review or meta-analysis of randomized controlled trials; 02) at least one well-designed randomized controlled clinical trial; 03) well-designed clinical trials without randomization; 04) from well-designed cohort and case-controls; 05) systematic review of qualitative and descriptive studies; 06) single descriptive or qualitative study; and 07) opinion of authorities or reports of specialist committees20.

The publications on the subject collected in full, in Portuguese, English and Spanish were included. The following exclusion criteria were established: structured studies in animal models and those related exclusively to the technique of implantation of pacemaker. Thus, through the careful reading of the title and abstract of the article in order to check consistency with the guiding question, 14 publications were collected, 05 in MEDLINE, two in LILACS, 05 in CINAHL and three in Cochrane Library. Two articles were found in two databases.

Results and discussion

We have found 14 publications since 1984, of which 06 were conducted in the USA, two in Spain, and only one in Austria, one in Brazil, one in Canada, one in Finland, one in France and one in Sweden. Accordingly, 12 were in English, one in Portuguese and one in Spanish. Box 1 shows the different designs of the studies and the levels of evidence. Thus, no systematic review study or meta-analysis of randomized controlled trials was evident, only two (14.3%) with level of evidence 02, 08 (57.1%) at level 04 (well-designed cohort and case-control) and 04 (28.6%) with levels 06 and 07.


Box 2 presented a synopsis of publications concerning the infections resulting from implants of pacemakers. It shows that the focus of attention of researchers permeated aspects related to microbiology, clinics, complications and treatment. Especially on the subject of biofilm in pacemakers, there were only two (14.3%) studies. It is speculated that the occurrence of biofilm formation is inevitable, but its confirmation in pacemakers involves removal of the implanted device, as well as advanced technology for scanning electron microscopy.


With regard to aspects of microbial etiology, there was a concern focused on species and susceptibility profile or multidrug resistance of strains to antibiotics. The emphasis is on the appropriateness of antimicrobial therapy. Out of the total, only two (14.3%) studies were clinical trials of prophylactic antibiotics. This topic is still controversial among surgeons and infectious disease physicians, whether in the prophylaxis and/or therapy.

It is noteworthy that the findings from this research do not determine the real situation of occurrence of infection associated with pacemakers, since the studies relate to a few situations. In this sense, data on the occurrence of biofilms in pacemakers are scarce, considering that this is a complex injury that is difficult to diagnose. Besides this, the population likely to use this device, in general, are the elderly with a history of arrhythmias, older age groups, and therefore with greater likelihood of infectious complications. Another aspect that makes it difficult to report the disease is that the appearance of symptoms of infection may be late, often not associated nor treated as a biofilm.

However, the incidence of infections related to cardiac devices has been reported between 0.5% and 12%. In recent publications, the incidence is smaller than 5%8 or close to 721. Endocarditis associated with pacemaker lead is rare, but it is considered a serious infection. It was estimated that the incidence of endocarditis is 19.9%, however, this rate has probably been overestimated due to the absence of stringent criteria for diagnosis. Endocarditis associated with pacemaker lead was described in 16 patients in the transvenous removal group and 11 in the cardiopulmonary bypass group10.

In the United States, each year about one million cases of nosocomial infections are associated with devices and about two thirds are caused by Staphylococcus aureus or Staphylococcus epidermidis12. Although approximately 1% of patients with endocardial pacemakers developed sepsis22. Infections associated with pacemakers are usually caused by S. epidermidis or S. aureus4,9,12,24,26,27, and there was only one case of infection with Aspergillus spp23. Greenspon et al9 showed that S. aureus was the most common cause of endocarditis associated with pacemaker (53%), followed by S. epidermidis (22%) and streptococci (12%). Early infections occurred within 06 months and late infections in about 32 months. They also noted that the skin flora is the probable origin of endocarditis associated with pacemaker lead9. These data leads us to the studies on biofilm formation that justifies the prolonged time to the onset of the first symptoms of infection.

In another study, S. epidermidis was the microorganism that caused most infections related to pacemakers24. The infection may involve any part of the pacemaker: the pocket, leads and the area of implantation of leads in the endocardium21. Moreover, biofilm formation by S. epidermidis may be influenced by the metal surface18.

Infections associated with surgical implants are generally more difficult to treat because they require a long period of antibiotic therapy and repeated surgical procedures, with dramatic clinical and economic consequences. Mortality is higher among patients with cardiovascular implants and the cost of the device is a small fraction compared to the amount for the treatment of implant-related infection. The most important clinical goals in the treatment of these infections are to treat the infection, prevent recurrence, preserve function, set aside the risk of endocarditis and reduce the risk of death. Most often, these goals can be achieved by antimicrobial therapy and surgical intervention. And, perhaps, manufacturing and using cardiac pacemakers impregnated with antimicrobial agents. The diagnosis of infection from implant requires the presence of clinical manifestations and pathogens in surgical specimens, and blood cultures may be negative in cases of infection related to pacemakers, except in endocarditis associated12.

A study of different treatment modalities of 38 patients with cardiac device-related infection, had 12 patients treated only with antibiotics, 19 had the device removed, reimplantation followed by antibiotics for short periods (10-14 days) and 07 patients received a longer period of 06 weeks of antimicrobial agent. The first group had recurrence of infection and in the other two, patients had the infection completely solved. This demonstrates the importance of removing the device in the treatment of infections21.

According to Darouiche12, most implants contaminated with S. aureus or Candida spp. require surgical removal. The author justifies that it should be fully removed even if the contamination is only in the pacemaker pocket, because other parts of the device may also be contaminated. In the patients who respond to drug therapy, the implant should not be removed.Although removal of the implant is associated with the solution of the infection, it has to be authorized in patients at risk for complications during surgery and post-surgery12.

As mentioned, treatment of infection associated with the system of artificial cardiac pacemaker is diverse. In cases with systemic sepsis or endocarditis, there is still a tendency to more aggressive approaches with prolonged intravenous antibiotic therapy (04 - 12 weeks), removal and complete replacement of endocardial systems.

The result of the microbial culture is another aspect that defines the therapy, that is, conservative approach in cases of S. epidermidis or aggressive intervention for S. aureus have been recommended. Thus, we use the antibiotic therapy associated with the repositioning of the generator or the complete removal of endocardial systems and implantation of a new one, antibiotic therapy associated with local measures and irrigation, among others. All of these are coordinated with long periods of hospitalization, high costs and controversial results. The subpectoral implantation technique proved to be a feasible alternative in the treatment of pacemaker generator pocket infection, showing 100% effectiveness, a shorter hospital stay and a lower cost. However, further studies and follow-up are necessary for a definitive conclusion3-12.

Scholars have shown that the synergy of different combinations of antibiotics against biofilms of S. epidermidis varied with the time of biofilm formation (06, 24, 48 hours). In general, all combinations of antibiotics were effective in new biofilms. The combination of vancomycin and rifampin had a bactericidal effect in 06 hours, and in old biofilms, the combinations with tetracycline were more effective. The difficulty of eradicating older biofilms was evident21,23.

There are genes of biofilm formation mediation, such as genes of attachment (fbe and atlE) and adhesion (ica), which were observed in most strains of isolated S. epidermidis of patients with pacemaker. These data indicate an important role of adhesion genes in infections in pacemakers24.

In the study by Marrie et al22, scanning electron microscopy revealed a different colonization in the pacemaker lead and the microorganism S. aureus was isolated at several sites. An extensive biofilm on the inner surface of the lead was then exposed and the external surface had a huge mass of biofilm with a population of bacterial cells adhered.All areas with cracks accumulated biofilm, which may justify the difficulty of action of therapy with antibiotics22. Therefore, in most cases, the removal of endocardial systems is indicated2-10,12,22.

In a controversial manner, Bluhm et al4 state that the use of a modern surgical technique combined with a meticulous aseptic practice excludes the use of systemic antibiotic prophylaxis in the implantation of pacemaker.

There are reasons to expect that the development of pacemaker technologies has an impact on reducing rates of complications. Aspects such as the reduced size of the generator, increased quality and durability of leads, improved implantation techniques and aseptic procedures. However, dual-chamber stimulators, with the introduction of two leads, result in a longer implantation time, increasing the rate of complications. In 27-month follow-up after implantation, approximately 14% of patients had a complication. In most cases, complications from a clinical standpoint were low and with no deaths. In this study, infection rates were similar in patients receiving antibiotics (1.2%) and those who did not (1.7%), but there was no randomization of participants in the groups25. The benefit of administering antibiotics to reduce the risk of infection is still controversial.

It is still worth noting the following facts:

• The formation of extracellular polysaccharide by S. epidermidis was significantly higher in pacemakers than in intravenous catheters, which makes the threat by biofilm even higher26.

• The difficulties inherent in the safety of reprocessing devices also represents a high risk of contamination. There are reports of reprocessing of pacemakers that were removed from patients with infection2.

• Antibiotic prophylaxis, although controversial, seems to be promising in the prevention of infectious complications after pacemaker implantation8,10,27.

• In terms of sensitivity profile, researchers found that 67% of infections were associated with S. aureus resistant to methicillin, suggesting that this is an important pathogen of endocarditis associated with pacemaker lead9.

• A new technique for the management of pacemaker pocket infection without the removal of endocardial systems proved, in principle, a feasible low-cost alternative, however, we still need follow-up studies for a definitive conclusion3. This was the only study that proposed an alternative for the treatment of infection related to the pacemaker and has had good results.

• From complications related to pacemakers, 6.7% were early and 7.2% were late, and 3.1% related to implantation25. In the study by Maduro Maytin et al2, pacemaker pocket infection was a complication related to late re-interventions (0.4%).

• Regarding the biofilm, adhesion genes were almost always present in species recovered from patients with pacemakers, indicating the important role of these genes in the pathogenic mechanisms of pacemaker-related infection24. Differences in biofilm morphology may reflect the degree to which the fibrin and other materials become embedded in the developing biofilm26. The age of the biofilm may interfere with the action of antibiotics, because they are more effective in younger biofilms. They also predict that the resistance of microorganisms to antibiotics will make the treatment of cardiovascular infections harder21.

Systemic antibiotic prophylaxis significantly reduces the incidence of infectious complications after implantation of a permanent pacemaker8,10,27. In another study, there was no recurrence of infection after removal of the pacemaker lead; this is an effective procedure that can be applied even in patients with biofilms larger than one centimeter. Therefore, in pacemakers with biofilms larger than two centimeters in diameter, the recommendation was removal10. Maduro Maytin et al2 performed antibiotic prophylaxis within 24 hours before the implantation of a pacemaker and 05 days after, with a total of 0.4% of late infections in reoperations. In particular, researchers found that infections occurred in patients who did not receive antibiotic prophylaxis27. That said, there is strong evidence that the best approach for eradication of infection associated with biomaterial implants and reduction in mortality is the surgical intervention2-10,12,26. It seems consensus that all endocardial systems should be completely removed to eradicate infection from biofilm formation.

Conclusion

The biofilm is a current and little studied topic in the field of cardiology and even less when connected to the pacemaker. The conditions concerning the nature of the biomaterial, added to factors of risks to patients, such as extremes of age, immunocompromise due to multiple causes, underlying diseases, characterize the profile of the situation that deserves attention. In particular, additional research is needed to determine the current status of complications from the use of pacemakers in different patient populations, because studies examined individually signaled no statistically significant differences in the rates of infection.

On the other hand, no study has explored the nature of biomaterials that compose the pacemakers and biofilm formation. Thus, the question is: will pacemakers impregnated with antimicrobial agents reduce or inhibit biofilm formation?

In summary, the data analyzed show that the topic is of great importance and has been little studied, since in 24 years only 14 articles were published. With regard to professional nursing, even if it plays a key role in direct and/or indirect assistance to patients subject to the use of a pacemaker, both in implantation and in follow-up, especially in detecting signs and symptoms of infection, their participation was zero in these studies. Given the risk of infection associated with invasive procedures, it is worth noting the value of preventive measures.

It also makes us think about the importance of measures of surveillance of infections, mainly in Brazil, a country marked by cultural diversity, socioeconomic inequalities, heterogeneous patterns of health care in terms of physical structure, type of patients and infections. Besides that, the Brazilian health system has historically faced the serious problem of social expansion, which is combined to a lack of human resources and inappropriate technology. Undoubtedly, these are fertile conditions for rising infection rates.

Potential Conflict of Interest

No potential conflict of interest relevant to this article was reported.

Sources of Funding

There were no external funding sources for this study.

Study Association

This study is not associated with any post-graduation program.

References

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  • Biofilm on artificial pacemaker: fiction or reality?

    Ana Paula Azevedo SantosI; Evandro WatanabeII; Denise de AndradeI
  • Publication Dates

    • Publication in this collection
      20 Dec 2011
    • Date of issue
      Nov 2011

    History

    • Accepted
      13 Jan 2011
    • Reviewed
      12 Jan 2011
    • Received
      27 Aug 2010
    Sociedade Brasileira de Cardiologia - SBC Avenida Marechal Câmara, 160, sala: 330, Centro, CEP: 20020-907, (21) 3478-2700 - Rio de Janeiro - RJ - Brazil, Fax: +55 21 3478-2770 - São Paulo - SP - Brazil
    E-mail: revista@cardiol.br