**1. Introduction**

Group of microbial cells that are surface-attached and embedded within the extracellular matrix (self-produced), and are strikingly resistant to antimicrobials are called biofilms [1]. Biofilms can adhere to almost different types of surfaces like body tissue and plant, plastics, metals, implant objects as well as medical devices [2]. Formation of biofilm on implants and medical equipment and implants, for example, vascular grafts, prosthetic joints, heart valves, catheters, intrauterine devices, pacemakers, and contact lenses can cause infection. Central line-associated bloodstream infection (CLABSI) can occur due to use of intravascular catheters, furthermore,

CLABSI can cause an increased rate of mortality and morbidity, and every year in the USA almost 250,000 cases of bloodstream infections are reported [3].

When cells adhere and attach to surfaces biofilm formation begins. Several factors can promote the attachment of microorganisms to biomaterials including increased shear forces, bacterial motility, and electrostatic as well as hydrodynamic interactions between the surface and microbial cells [4]. It has been observed that adherence of biomaterials to bacteria via biomaterial-surface interactions and cell-surface is facilitated by numerous factors, such as protein autolysin, surface, and adhesion proteins and capsular polysaccharides, etc. For example, '*Staphylococcus* species' show cell-surface proteins that are vital for adherence of '*Staphylococcus epidermidis'* to polystyrene which is named as staphylococcal surface protein-1 and -2 (SSP-1 and SSP-2). After attachment to the extracellular surfaces, microbial cells will start aggregate, multiply, and eventually differentiate into the biofilm network [5]. Such microbial cells can then be separated from mature biofilms, can cause chronic infections and can spread to other organs also [6].

Another worrying characteristic of infections associated with biofilm formation is increased biofilm cell tolerance to biocides. As biofilms provide an excellent niche for exchange of plasmid, so increased resistance to the drug can affect genes containing plasmids which results in multidrug resistance (MDR) phenotypes. Enhanced drug resistance mechanisms include incomplete or slow infiltration of antimicrobials within the extracellular matrix, the formation of dormant cells during the non-dividing phase, reduced cell's growth rate within the biofilm, hence ultimately decreasing total targets for antimicrobial molecules [7]. Furthermore, it is difficult to treat biofilm formation with the traditional antimicrobial approach and the therapy is further inhibited by increased resistance to the antibiotic because under antibiotic selective pressure microbial cells develop resistance. For instance, it has been observed that almost above 70% of hospital isolate of *'Staphylococcus epidermidis'* show resistance to methicillin and surprisingly there are many strategies to prevent infections associated with biofilm formation other than antibiotic treatment [8]. In this chapter, we have focused on anti-biofilm approaches and some promising efforts for controlling these biofilmbased infections.

### **2. The process of biofilm development**

The production and maturation of biofilm are complex, subsequent and dynamic processes, depending upon several factors i.e. cellular metabolism, intrinsic properties of the cells, genetic control, the substratum, and the medium signaling molecules. Biofilm formation is introduced with a conditioning film of inorganic or organic material on the cell surface; furthermore, this layer modifies the surface feature of substratum which ultimately favors microbes for colonization on the cell surface. The formation of biofilm consist of several different steps: (i) initially the reversible attachment of microbial cells with biotic or abiotic surfaces through weak forces for example van der Waals forces, (ii) irreversible attachment to the cell surface with the help of different attachment structure i.e. lipopolysaccharides, flagella, adhesive proteins or fimbriae by hydrophobic or hydrophilic interactions, (iii) and then eventually biofilm architecture development due to the production and proliferation of extracellular polysaccharide (EPS) matrix which is self-produced and is made up of proteins, extracellular deoxyribonucleic acid (DNA) and polysaccharides [9] (iv) in the

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adhesion [18].

*Innovative Strategies for the Control of Biofilm Formation in Clinical Settings*

next step mature biofilm is formed which has water channels that are responsible for distribution of nutrients as well as signaling molecules within the biofilm [10], (v) and then due to extrinsic or intrinsic factors separation of biofilm cells occurs individually or in clumps and finally colonization of other niches and

Biofilm development starts with a reversible weak adhesion of microbial cells to the exterior surface of medical equipment, however, if they are not removed from the exterior of devices, they adhered permanently through their adhesion structures i.e. fimbriae, pili and thereby forming biofilm matrix [12]. Surface charge and hydrophobicity of implant constituents play a significant role in controlling the ability of microbes to anchor to cell surfaces. Therefore, alteration in the hydrophobicity and surface charge of polymeric constituents are proved as efficient for controlling biofilm formation by using numerous antimicrobial agents and backbone compounds [13]. Poly N-vinylpyrrolidone and Hydrophilic polymers i.e. hyaluronic acid [14] on silicone shunt and polyurethane catheters have been widely used to decrease the adherence of '*Staphylococcus epidermidis'*. Furthermore, several hydrogel membranes have been introduced particularly for ureteral stents that decrease bacterial adherence because of their hydrophilic characteristics. It has been observed that due to very low wettability superhydrophobic coatings play a significant role to reduce the biofilm matrix formation and adhesion of bacteria [15]. Later, it has been suggested that *S. aureus* and *Pseudomonas aeruginosa* poorly attached on superhydrophobic fluorinated silica coating as well as on titanium coatings. However, it was demonstrated that *Escherichia coli* and *Staphylococcus aureus* poorly adhered on other superhydrophobic surfaces i.e. (AACVD) aerosol assisted chemical vapor deposition-coated [16]. In some cases, it was observed that hairpin coating affects colonization and adhesion of bacteria because it forms vascular catheter negatively charged, so contribute to reducing the catheter-related infections, inhibiting microbial colonization and thrombosis [17]. It has been described that the surface roughness can modulate hydrophobicity, which ultimately influences the bacterial

*DOI: http://dx.doi.org/10.5772/intechopen.89310*

**3. Inhibition of initial attachment**

**3.1 Altering physical properties of biomaterials**

**3.2 Altering the chemical properties of biomaterials**

There are several chemical approaches used to alter the exterior of biomedical equipment to inhibit the biofilm formation comprising ion coatings, biocides and also antibiotics [19]. Catheters that are impregnated with antibiotics, for example, rifampin and minocycline have been revealed to reduce the occurrence of biofilmbased infections by *Staphylococcus aureus*. Furthermore, catheters are coated with several antibiotics that play a significant role in biofilm production during urinary tract infections (UTI) like norfloxacin, nitrofurazone, and gentamicin [20]. Several chemical molecules are identified through screening of chemical libraries, these molecules are used as potential drugs to control infection and biofilm development. Furthermore, such molecules do not provoke antimicrobial action, and hence reduces the development of resistance due to no selective pressure against biofilm matrix formation. In *Staphylococcus aureus* and *Streptococcus pyogenes* a series of

dispersal of the cells [11].

*Innovative Strategies for the Control of Biofilm Formation in Clinical Settings DOI: http://dx.doi.org/10.5772/intechopen.89310*

next step mature biofilm is formed which has water channels that are responsible for distribution of nutrients as well as signaling molecules within the biofilm [10], (v) and then due to extrinsic or intrinsic factors separation of biofilm cells occurs individually or in clumps and finally colonization of other niches and dispersal of the cells [11].
