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Antimicrobial resistance of biofilms in medical devices

J. Malheiro, M. Simoes University of Porto, Porto, Portugal


The first recorded evidence of a biofilm existence was probably given by Henrici in 1933. Henrici noticed that water bacteria were not free floating, but instead they grew on submerged surfaces (Bose and Ghosh, 2011; Henrici, 1933). In fact, a biofilm can be described as a community of microorganisms that are attached to a surface or to each other and are embedded in an exopolysaccharide matrix (Bose and Ghosh, 2011; Taraszkiewicz et al., 2013). The matrix is also composed of extracellular polymeric substances that are produced by the cells. The bacteria within a biofilm exhibit a modified phenotype when compared with the corresponding planktonic cells, especially considering growth, gene transcription, protein production, and intercellular interactions (Otter et al., 2015). Additionally, the cells within the biofilm exhibit a low metabolic activity, which limits the action of the antimicrobials (Taraszkiewicz et al., 2013; Donlan, 2001b).

The formation of biofilms in healthcare settings is extremely problematic since it is known that they are involved in 65% of nosocomial infections and are commonly detected in medical devices and prosthesis, water lines and tubing, and on endoscopes and wounds (Otter et al., 2015; Taraszkiewicz et al., 2013).

Independent of the immune system of the person who has the medical device, biofilm infections are rarely controlled. Even antibiotics are only effective against the planktonic cells that are released from the biofilm. Therefore, the most common medical treatment for biofilm infection control is the removal of the implanted device or the removal of the biofilm formed in the living tissue (Taraszkiewicz et al., 2013). Healthcare-associated infections (HCAIs) occur as a result of infection by a number of microorganism, such as the Gram-positive bacteria (Staphylococcus aureus, Staphylococcus epidermidis, and Enterococcus faecalis) and the Gram-negative bacteria (Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, and Pseudomonas aeruginosa) (Donlan, 2001b; Percival et al., 2015). However, the most critical is the methicillin-resistant S. aureus (MRSA) that causes several septicemia or bacteremia in clinical settings (Percival et al., 2015). Several medical devices-related infections were considered as being monomicrobial. However, advances in biofilm studies revealed that most infections are polymicrobial. Those biofilms were already found in intravenous and urinary catheters, implants, stents, ventilator tubes, cerebrospinal shunts, and heart valves (Peters et al., 2012; Desai et al., 2014). One of the major

Biofilms and Implantable Medical Devices.

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examples of polymicrobial contamination is the parenteral nutrition feeding tubes (Peters et al., 2012).

The availability of methods to evaluate medical device contamination is based on microorganisms culture or even advanced microscopy methods such as confocal laser scanning microscopy (CLSM), scanning electron microscopy (SEM), and atomic force microscopy (AFM) (Donlan, 2001a; Mihai et al., 2015). Alternative techniques can also be used such as fluorescence in situ hybridization and matrix-assisted laser absorption coupled with time-of-flight analysis mass spectrometry (MALDI-TOF) (Suleman et al., 2014).

The formation of biofilms in medical devices is an increasing concern due to the observed antimicrobial resistance of colonizing microorganisms. Nowadays, some bacteria are already known for their multiresistance to antimicrobials and are considered superbugs. The major clinically relevant superbugs are S. aureus, enterococci, Enterobacteriaceae, P. aeruginosa, and Acinetobacter baumannii (Niveditha et al., 2012). To overcome this problem, new strategies are being developed that prioritize prevention of biofilm formation, such as device surface modification or coating (Cochis et al., 2016).

This chapter is a contextualization of the problem of antimicrobial resistance that is observed in the microorganisms of a biofilm formed in medical devices. Initially, an overview of biofilm formation and structure is assessed followed by the most important and accepted mechanisms of biofilm resistance. The medical devices classification is presented taking into consideration the level of contamination that they are exposed to. Furthermore, the most common pathogens that are responsible for the majority of hospital infections, especially infections associated with medical devices are detailed. The final section of this chapter is the state of the art on the knowledge that the scientific community has acquired on biofilm resistance associated with medical devices.

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