Biofilms and Veterinary Medicine: 6 (Springer Series on Biofilms)

Rather, combinations of biofilm diagnostic tools will be required to identify problematic biofilms, not just biofilms per se.

Biofilms and human health

Biosensors that measure subtle changes in the wound that are induced by a biofilm may be one approach for a biofilm marker. Slough has not yet been adequately defined or analyzed for evidence of biofilms. As slough is composed of devitalized proteinaceous tissue in conjunction with viable tissue, this will provide an ideal environment for microbial adhesion and biofilm development.

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Slough will constitute a potential bioreactor system, which will serve to disseminate microbes further into the wound bed. Consequently, the removal of slough will help to remove the majority of the microbial biofilms before employing antimicrobial interventions. Furthermore, EPS is vital to the nature of the biofilm and may also be useful as a biomarker, in conjunction with microbial genomics, to highlight the evidence of a virulent biofilm in a wound.

Investigations to date have made it clear that the management of biofilms requires further technological and clinical advancements. However, more evidence on the role that pathogenic biofilms play in wound healing is fundamental to guiding anti-biofilm approaches to wound management. Despite this, effective anti-biofilm management practices and technologies must be combined with currently useful clinical practices to attempt to achieve higher rates of healing of chronic wounds.

Biofilm-based wound management should be employed routinely as positive clinical outcomes have been achieved with this approach. Going forward, it is imperative that some new wound dressings being developed have anti-biofilm capabilities or characteristics. However, there is an important balance between necessity and overkill.

In order for a clinician to make a decision as to when more expensive techniques are required to get rid off, or reduce, the pathogenic biofilm, a simple algorithm could be employed. We have offered such an algorithm to help guide clinical practice, but it has not been subjected to validation to date. In conclusion, it is important to realize that biofilms, like microorganisms, are not all bad; some, the commensal biofilm , may actually provide benefit to wound healing.

It is the virulent or pathogenic biofilms that represent a major long-term cause for concern for nonhealing and development of infection in a wound. No competing financial interests exist. The content of this article was expressly written by the authors listed. No ghostwriters were used to write this article. He has written over scientific publications and conference abstracts on biofilms, antimicrobials, wounds, infection control, and has authored or edited seven textbooks.

He joined the faculty of the University of Washington in the Department of Medicine, rising to full Professor of Medicine. Professor Lipsky has authored over peer-reviewed research articles H-index 63 , as well as over other medical articles and textbook chapters, research abstract presentations, and three books on infectious diseases. He has chaired the guideline committees on diabetic foot infections of both the Infectious Diseases Society of American and the International Working Group on the Diabetic Foot since their inception. In he was appointed Director of the Electron Microscopy Unit and in he was the winner of a public competition for a position of Research Director in molecular biology.

Since Professor Donelli's research activity has been mainly focused on biofilm-based healthcare-associated infections and possible strategies to prevent and counteract the development of microbial biofilms in the human body. Claudia Vuotto is currently a Ph. During her theses work she applied microbial methods to grow bacteria in biofilm, ultrastructural techniques SEM for biofilm surface characterization, and molecular techniques DGGE to identify biofilm-growing bacterial species isolated from biliary stents.

In she obtained a fellowship at the Department of Technology and Health, ISS, in the field of biofilm-based infections related to the insertion of prosthetic implants. From to the present, she is research assistant at the Microbial Biofilm Laboratory, Fondazione Santa Lucia Research Hospital in Rome, where she performs further investigations on the microbial biofilms. Vuotto is co-author of 10 original full-length articles and 1 Springer book chapter. National Center for Biotechnology Information , U. Advances in Wound Care. Adv Wound Care New Rochelle.

Find articles by Steven L. Find articles by Claudia Vuotto. Find articles by Gianfranco Donelli. Find articles by Benjamin A. Author information Article notes Copyright and License information Disclaimer. Received Jul 1; Accepted Aug 4. Copyright , Mary Ann Liebert, Inc. This article has been cited by other articles in PMC. Open in a separate window.

Translational Relevance Biofilms have been observed to date in a variety of different anatomical areas. Clinical Relevance Many published articles provide evidence of the role of biofilms in wounds, in both animals and humans. Identification of a biofilm Abiotic surfaces The visualization of biofilms by the naked eye on nonbiological surfaces is relatively easy when the biofilm has grown to a certain size, especially if it contains color. Biotic surfaces Unlike abiotic surfaces, the macroscopic identification of biofilms on biotic surfaces, particularly chronic wounds, is speculative and often based on a color induced by the overpopulating dominant sessile or planktonic aggregates of microbes.

Proposed visual markers for wound biofilm A relatively small number of researchers and clinicians suggest that biofilms may reveal themselves as a slimy, translucent, and confluent film on a wound. Potential algorithm for biofilms An algorithm to help identify biofilms in chronic wounds may be useful when wound biopsies are available allowing preliminary identification of biofilm , but also when they are not.

Treatment of biofilms To date there are few effective anti-biofilm strategies applied to chronic wounds. Summary We have discussed how two types of biofilm may exist in a chronic wound: Using microscopic appearance as evidence for or against the presence of biofilm can be detrimental to wound care practice. Acknowledgments and Funding Sources No funding sources were obtained for this review article. Author Disclosure and Ghostwriting No competing financial interests exist. About the Authors Steven L. Advanced techniques for in situ analysis of the biofilm matrix structure, composition, dynamics by means of laser scanning microscopy.

Methods Mol Biol ; Trends Microbiol ; Flemming HC, Wingender J. Nat Rev Microbiol ; 8: Emerg Infect Dis ; 8: Colloids Surf B Biointerfaces ; Biofilms and bacterial imbalances in chronic wounds: Int Wound J ; 7: Biofilms in chronic wounds. Wound Repair Regen ; Distribution, organization, and ecology of bacteria in chronic wounds. J Clin Microbiol ; Burns, biofilm and a new appraisal of burn wound sepsis.

Microbiology of equine wounds and evidence of bacterial biofilms. Vet Microbiol ; Biofilm-infected wounds in a dog. J Am Vet Med Assoc ; Biofilm evidence and the microbial diversity of horse wounds. Can J Microbiol ; An in vivo polymicrobial biofilm wound infection model to study interspecies interactions.

PLoS One ; 6: Microscopic and physiologic evidence for biofilm-associated wound colonization in vivo. Increasing the presence of biofilm and healing delay in a porcine model of MRSA-infected wounds. Krom BP, Oskam J. Microbial biofilms and wound healing: Clin Microbiol Rev ; Development of a novel ex vivo porcine skin explant model for the assessment of mature bacterial biofilms. Quantitative analysis of the cellular inflammatory response against biofilm bacteria in chronic wounds.

Detection and identification of specific bacteria in wound biofilms using peptide nucleic acid fluorescent in situ hybridization PNA FISH. Microbiology ; Pt 8: Staphylococcal biofilms impair wound healing by delaying reepithelialization in a murine cutaneous wound model. Treatment of Pseudomonas aeruginosa biofilm-infected wounds with clinical wound care strategies: Plast Reconstr Surg ; 2 ;e—e [ PubMed ]. Interactions of methicillin resistant Staphylococcus aureus USA and Pseudomonas aeruginosa in polymicrobial wound infection.

PLoS One ; 8: Development of a novel, highly quantitative in vivo model for the study of biofilm-impaired cutaneous wound healing. Quantitative comparison and analysis of species-specific wound biofilm virulence using an in vivo, rabbit ear model. J Am Coll Surg ; Comparative analysis of single-species and polybacterial wound biofilms using a quantitative, in vivo, rabbit ear model. PLoS One ; 7: Deficient cytokine expression and neutrophil oxidative burst contribute to impaired cutaneous wound healing in diabetic, biofilm-containing chronic wounds.

Wound Repair Regen ; 21 6: Clinical presentation and treatment of orthopaedic implant-associated infection. J Intern Med ; Multiple drug resistant bacterial biofilms on implanted catheters - a reservoir of infection. J Assoc Physicians India ; Update on the challenging role of biofilms in peritoneal dialysis. A comparison of microbial plaque disclosants after personal oral hygiene instruction and prophylaxis. J Prev Dent ; 2: Expert Rev Anti Infect Ther ; 1: Biofilms in chronic diabetic foot ulcers—a study of 2 cases. Acta Orthop ; Annu Rev Microbiol ; Wound healing, immunology and biofilms.

Biofilms and human health - Semantic Scholar

Percival SL, editor; , Cutting K, editor. Br J Community Nurs ; 8: In vitro evaluation of tobramycin and aztreonam versus Pseudomonas aeruginosa biofilms on cystic fibrosis-derived human airway epithelial cells. J Antimicrob Chemother ; Extending the TIME concept: What have we learned in the past 10 years? Int Wound J ; 9: A study of biofilm-based wound management in subjects with critical limb ischaemia. J Wound Care ; Adv Skin Wound Care ; Biofilms have also been shown to develop on contact lens storage cases 46 , , In fact, the lens case has been implicated as the primary source of organisms for contaminated lens disinfectant solutions and lenses These investigators found that bacterial biofilms were present on 17 of 20 storage cases examined, a significantly greater percentage than the percentage of lenses containing biofilms.

They also isolated the identical organism from the lens case and the corneas of infected patients for 9 of 12 samples examined. Additionally, studies have found that the protozoan Acanthamoeba may be a component of these biofilms 46 , These organisms feed on the biofilm bacteria and may also be a cause of microbial keratitis. Two types of intrauterine devices IUDs are commonly used: IUDs made of a nonabsorbable material, such as polyethylene, impregnated with barium sulfate, and IUDs that release a chemically active substance, such as copper or a progestational agent.

IUDs generally have a tail that facilitates locating the device for removal. These tails are composed of a plastic monofilament surrounded by a nylon sheath. One particular model, the Dalkon Shield, has a tail composed of a bundle of to such monofilaments surrounded by a sheath IUD use has been shown to result in pelvic inflammatory disease 31 , , IUDs removed from asymptomatic women have been shown to be heavily contaminated with S. Marrie and Costerton also isolated Lactobacillus plantarum , S. In addition, IUDs removed from women with pelvic inflammatory disease may also contain beta-hemolytic streptococci, S.

Evidence for biofilms on IUDs has been demonstrated by scanning electron microscopy and transmission electron microscopy 12 , 89 , and by culture on complex media , , Using the scanning electron microscope, Marrie and Costerton also demonstrated the presence of human leukocytes and cellular debris in the biofilms The tail portion of the IUD may be a primary source of contamination.

One study found that approximately half of the IUD samples that had no tail protruding into the cervix were sterile. Another study determined that contamination was heaviest on the distal portions of the tail, which is directly exposed to the vaginal flora They showed, using dye uptake and bacterial cultures in vitro, that this could happen. An interesting finding of a study by Bank and Williamson 12 was that no PMNs were observed within multifilament tails collected from asymptomatic women. PMNs will rapidly attach to nylon fibers and quickly become immobilized, significantly limiting their ability to travel up the interfibrillar spaces of the Dalkon Shield tail.

The implication is that the bacteria, once inside the tail, would be relatively protected from attack by phagocytes, which normally maintain sterility in the uterus. This may explain why organisms readily populate IUD tails, even in asymptomatic patients. However, Jaques et al. Devices inserted through the vagina were colonized rapidly within 2 weeks , while those inserted surgically remained uncolonized even after 8 weeks. Development of a reproducible nonanimal model system for growing and evaluating IUD biofilms might allow a clearer understanding of the rate of biofilm formation and the importance of different materials, contaminating organisms, and treatments which could control the process.

Unlike other medical devices discussed previously, dental water systems are not indwelling devices, and the public health significance of biofilms in these systems is unclear. However, because dental procedures may expose patients and dental professionals to opportunistic and pathogenic organisms originating from the various components of the dental unit, there may be potential for human impact.

Hence, we include a discussion of biofilms in these systems. Dental units are equipped with small-bore flexible plastic tubing that supplies water to different hand pieces, such as the air-water syringe, the ultrasonic scaler, and the high-speed hand piece. Units may be supplied with municipal water or from separate reservoirs containing either distilled or sterile water Elevated bacterial counts have been found in water collected from these systems 13 , 70 , , For example, Furuhashi and Miyamae 70 found that bacterial counts increased from usually less than 40 per ml in the incoming municipal water supply to between 10 3 and 10 5 per ml in water collected from the three-way syringe.

They noted that the air-turbine hand piece and cup water filler also had elevated counts. Organisms generally isolated from these units include Pseudomonas spp. Legionella pneumophila has also been isolated from these systems 8 , 23 , Evidence for biofilms in these systems has come from a number of studies, using both scanning electron microscopy , , and viable plating of organisms isolated from the dental unit components They also cultured the same organisms from both tubing biofilm samples and water samples, and numbers were similar in both types of samples.

Using plate count techniques following mechanical removal of biofilms from tubing sections, Tall et al. They also found a positive correlation between biofilm and water counts. They showed that by days of exposure, the entire surface of the dental unit water line was covered by a thick, multiple layer of extracellular polymeric substances. Dental suction systems such as saliva ejectors have also been shown to harbor biofilms containing both mixed skin flora and aquatic bacteria. Fortunately, water-borne outbreaks as a result of contamination have been very few.

One exception was a case cited in which two cancer patients undergoing dental work contracted a P. In both cases, infection swelling occurred in the area where the matrix band had been used. Pyocin typing demonstrated that the organisms cultured from the patient and water lines were identical. However, the authors noted the possibility that the organisms of concern may have originated from the patient and not the water system Important issues remain, such as survival and transmission of pathogens other than Legionella , e.

H7, and Cryptosporidium sp. It is clear from epidemiologic evidence that biofilms have a role in infectious diseases, both for specific conditions such as cystic fibrosis and periodontitis and in bloodstream and urinary tract infections as a result of indwelling medical devices. The process may be particularly relevant for immunocompromised patients, who lack the ability to combat invading organisms.

Beyond the evidence, however, the exact processes by which biofilm-associated organisms elicit disease in the human host are only poorly understood at best. Suggested mechanisms include the following: A basis for each of these proposed mechanisms follows. Cells may detach individually from biofilms as a result of cell growth and division within the biofilms, or cell aggregates or clusters may detach or be sloughed from the biofilm. Though detachment has not been well characterized for medical device biofilms, some aspects of the process can be considered universal for all biofilms.

Laboratory studies have shown that an increase in shear stress, as would occur during changes in direction or rate of flow, will result in an increase in the rate of cell erosion from the biofilm It has also been shown that detachment of cells or aggregates may be related to changes in substrate concentration Regardless of the reason, detached cells could conceivably cause an infection. Bloodstream and urinary tract infections could conceivably result from very small numbers of bacteria.

In addition to the direct effects of cell detachment or antimicrobial resistance, gram-negative bacteria within biofilms of indwelling medical devices will produce endotoxins, which may in turn elicit an immune response in the patient. Several studies have measured endotoxin levels of biofilms 82 , , However, none of these studies documented the levels or kinetics of endotoxin release from the biofilms. Shiau and Wu found that extracellular slime produced by S. The vaccinated animals had a 1,fold-higher titer of the antibody, but it appears that the antibodies did not reach the surface of bacterial cells within the biofilms.

They hypothesized that the increase in resistance was the result of an increase in resistance of the biofilm bacteria to killing by active oxygen species in the polymorphonuclear leukocytes.

INTRODUCTION

These results lead to the conclusion that organisms detaching from a biofilm on a medical device or other infection could overcome the immune system more readily to cause an infection. It has been shown that bacteria can exchange plasmids by conjugation within biofilms, and resistance factors may be carried on a plasmid. Hausner and Wuertz 80 showed plasmid transfer between E.

The physical proximity of cells within microcolonies in biofilms would be expected to favor conjugation over the same process among suspended planktonic organisms. This could be especially relevant in the case of indwelling medical device biofilms, where resistant organisms could be spread from patient to patient on the hands of health care workers.

When the inherent resistance of biofilms to industrial biocides was first discovered, this property was attributed to a limitation in mass transfer conferred by the matrix material However, it was soon revealed that the matrix of a biofilm limits diffusion only when the diffusing molecule actually reacts with the matrix material The biofilm phenotype is remarkably resistant to antibacterial agents, including antibiotics , and biofilm cells are also remarkably resistant to the bactericidal effects of metal ions, including copper and silver.

Wild strains of many different species of bacteria colonize the surfaces of these metals very avidly, and some of the thickest and most luxuriant clinically relevant biofilms have formed naturally on the copper wires of IUDs Extensive attempts to control biofilm formation in industrial systems by manipulation of the metallurgy and the surface characteristics of pipes and vessels have all failed. We can expect an equal lack of success if we take this approach with medical devices. Industry currently relies on mechanical cleaning and oxidative biocides; the former removes biofilms, and the latter gradually dissolves the biofilm matrix material and eventually kills the sessile cells.

That being said, intervention strategies currently used for biofilm control will either i prevent initial device contamination, ii minimize initial microbial cell attachment to the device, iii penetrate the biofilm matrix and kill the biofilm-associated cells, or iv remove the device. The following specific treatments have been proposed for several of the medical devices already discussed.

Generally, antibiotics are prescribed for prolonged periods up to 8 weeks, depending on the antimicrobial agent prescribed and organism to be treated 55 , though it has been noted that relatively few patients can be cured by antimicrobial therapy alone Jude mechanical heart valve which was designed to prevent microorganism attachment and colonization.

The coating termed silzone was a dense layer of metallic silver deposited on the individual fibrils designed to inhibit attachment. These authors implanted this fabric material into a guinea pig artificially infected with Staphylococcus epidermidis. By measuring inflammation, they showed that the silzone-coated fabric produced less inflammation than uncoated fabric. To document the efficacy of this approach, Carrel et al. However, Kjaergard et al. Jude silver-coated valves and ultimately replaced the patient's infected valve with an aortic homograph.

They noted that the St. Jude silver-coated valve may be effective in vitro but that it does not protect the tissues surrounding the prosthesis; this position was supported by Cook et al. Several strategies for controlling biofilms on CVCs have been suggested, including using topical antimicrobial ointments, minimizing the length of catheterization, using in-line filtration of intravenous fluids, using a surgically implanted cuff to the catheter, coating the inner lumen with antimicrobial agents, and as a last resort removing the device Maki and Band found that topical antimicrobial agents provided only modest protection against catheter-related infections, and this protective effect was primarily for peripheral venous catheters in place for more than 4 days.

Freeman and Gould 69 found that 0. The same basic approach was used by Wiernikowski et al. A subcutaneous collagen cuff impregnated with silver has been tested and found in some studies to prevent bloodstream infection 68 , , , though Raad noted that this treatment was ineffective for catheters in place for more than 10 days. The silver acts as a biocidal agent to prevent the attachment and growth of bacteria. Another approach for controlling biofilms on CVCs has been to impregnate the catheter with either silver salts or antibiotics.

They concluded that central venous catheters impregnated with chlorhexidine combined with silver sulfadiazine were effective in reducing the incidence of catheter colonization and catheter-related bloodstream infections in patients at high risk for catheter-related infections. Darouiche 44 reviewed the various CVC treatments incorporating silver and found that silver-chelated collagen cuffs were threefold less likely to be colonized and fourfold less likely to cause bloodstream infection than uncuffed catheters, that CVCs coated with silver alone were clinically ineffective, that CVCs coated with chlorhexidine and silver sulfadiazine provide short-lived protection, since the internal lumen of the catheter is not treated, and that silver ionophoretic CVCs have been shown to be protective against Staphylococcus aureus in a rabbit model system, though clinical studies have yet to be done.

Antimicrobial coating treatments that have been evaluated for the control of biofilms on central venous catheters CVCs. Control strategies that have been used to inhibit biofilm formation on urinary catheters include antimicrobial ointments and lubricants, bladder instillation or irrigation, antimicrobial agents in the collection bags, impregnating the catheter with antimicrobial agents silver oxide , and using systemic antibiotics for prophylaxis in catheterized patients Sedor and Mulholland also noted that the material of catheter construction might also be important; silicone catheters obstruct less often than latex, Teflon, or silicone-coated latex in patients prone to catheter encrustation.

Darouiche 44 reviewed the efficacy of various types of silver-coated indwelling medical devices. Two categories of treated bladder urinary catheters were discussed, those coated with silver oxide and those coated with silver hydrogel. With the silver oxide-coated catheters, there have been mixed results in human clinical trials. Saint and Lipsky reviewed eight different randomized, controlled trials and found that silver alloy catheters were significantly better than untreated catheters, while silver oxide catheters were not.

They opined that silver alloy catheters could be considered for patients at highest risk for developing serious consequences from a urinary tract infection, though other investigators have questioned their conclusions Effect of acetohydroxamic acid, a urease inhibitor, on the encrustation of silicone catheters by Proteus mirabilis biofilms.

Each value is the mean calculated from three replicated experiments. The mean values for the log of the number of viable cells per milliliter of urine at 24 h were 8. Reprinted from reference with permission of Springer-Verlag Co. Several studies have compared the efficacy of contact lens storage and cleaning solutions against bacterial biofilms on lens storage cases. Another study found that sodium salicylate was effective in decreasing initial bacterial adherence to lenses and cases However, one study found that biofilms could be detected on contact lenses removed from patients with microbial keratitis whose lens storage cases were treated according to the manufacturer's instructions with disinfectants such as hydrogen peroxide and chlorine release systems Further research is needed to determine the efficacy of disinfectant solutions against model system biofilms and natural biofilms on contact lenses that have been removed from patients with an active infection.

Flushing has been suggested as one treatment for reducing the planktonic bacterial load that originates from the tubing biofilms ; however, several studies have shown that flushing alone is ineffective in significantly decreasing bacterial contamination , , They demonstrated that treated tubing samples contained between 4 and 5 logs fewer bacteria per ml initially following treatment with povidine iodine, but the levels returned to pretreatment levels within 22 days. Fiehn and Henriksen 67 showed that treatment with 0. When chlorination was discontinued, the counts continued to increase.

However, Murdoch-Kinch et al. The problem may lie in the fact that dental unit water lines are very small in diameter, present a very high surface-to-volume ratio and relatively low flow rates, and are ideal for colonization with aquatic bacteria, leading to biofilm formation. Other methods of treatment, such as use of separate, sterile water supplies and filtration, have also been suggested Numerous biofilm control strategies have been proposed.

Because of concerns with device compatibility or effects on the patient, many such treatments cannot be considered for medical devices. Nevertheless, several merit further investigation. A Effect of a low-strength electric field with a low current density followed by biocide application arrows on P. At 24 h, glutaraldehyde 5 ppm open and solid squares or kathon 1 ppm open and solid triangles was applied to both electrified and control devices. B Effect of biocides on an established h P. The electrified devices are represented by solid symbols.

Reprinted from reference 17 with permission of the American Society for Microbiology. In light of the fact that biofilms comprise both cells and extracellular polymeric substances, treatments that either eradicate or penetrate the extracellular polymeric substances might also be effective. For example, Johansen et al.

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Though the extracellular polymeric substance matrix of biofilms may be highly variable, especially between different organisms, it might be possible to identify the polysaccharides for a specific organism in a biofilm and treat the biofilm with that enzyme. Hatch and Schiller 79 showed that alginate lyase allowed more effective diffusion of gentamicin and tobramycin through alginate, the biofilm polysaccharide of P.

In addition, since younger biofilms are more susceptible to antimicrobial agents than are older biofilms of the same organism as already discussed , development of noninvasive techniques that detect early biofilm formation might result in greater success in their treatment and removal. A number of laboratories are currently attempting to elucidate the genes that are activated or repressed during initial biofilm formation. In the future, treatments that inhibit the transcription of these genes might be able to completely inhibit biofilms. Bacterial cells have grown in the biofilm phenotype for billions of years, as a part of their successful strategy to colonize most of this planet and most of its life forms.

We have only recognized this distinct phenotype as the predominant mode of bacterial growth for the last two decades. Initially, biofilms attracted our attention because we could detect them by direct methods, and our approach to understanding them was necessarily descriptive and somewhat academic.

During the past 5 years, studies of this distinct phenotype have provided a rational explanation for this pattern of gene expression, and biofilms can now be defined in genetic terms. The medical importance of these scientific and engineering studies now resides not in scholarly interest, but in our ability to explain the characteristics of device-related and other chronic infections and to design strategies to counter their refractory nature.

All of the chronic infections described in this review share the fundamental characteristics of all bacterial biofilms. Their distinct phenotype makes them resistant to antibacterial agents, and their matrix makes them resistant to the antibacterial molecules and cells mobilized by the host. This diagnostic feature is unequivocal and useful, but we should now begin to examine any infection that is refractory to antibiotic therapy and to host defenses in terms of the genes that are expressed to produce the refractory bacterial phenotype.

Furthermore, we must begin to use the biofilm phenotype of each chronic pathogen in the development of new vaccines and antibiotics aimed at biofilm-specific targets and in studies of the causes and means of controlling this burgeoning group of diseases. We express our appreciation to J. Michael Miller for helpful suggestions and encouragment and to the following individuals for providing articles or figures for this paper: National Center for Biotechnology Information , U.

Journal List Clin Microbiol Rev v. Author information Copyright and License information Disclaimer. This article has been cited by other articles in PMC. Abstract Though biofilms were first described by Antonie van Leeuwenhoek, the theory describing the biofilm process was not developed until Open in a separate window. Methods that have been used for measurement of biofilms on catheters. Apparatuses that have been used for growing and testing biofilms.

Factors to consider in the development of a model biofilm system. Medium Inoculum Hydrodynamics Substratum Composition, temperature, presence of antimicrobial agents Identity of organism, no.

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Susceptibility of planktonic and biofilm bacteria to selected antibiotics. Delayed Penetration of the Antimicrobial Agent Antimicrobial molecules must diffuse through the biofilm matrix in order to inactivate the encased cells. Altered Growth Rate of Biofilm Organisms Another proposed mechanism for biofilm resistance to antimicrobial agents is that biofilm-associated cells grow significantly more slowly than planktonic cells and, as a result, take up antimicrobial agents more slowly.

Other Physiological Changes Due to Biofilm Mode of Growth Gram-negative bacteria respond to nutrient limitation and other environmental stresses by synthesizing sigma factors. Native Valve Endocarditis Native valve endocarditis NVE is a condition that results from the interaction between the vascular endothelium, generally of the mitral, aortic, tricuspid, and pulmonic valves of the heart, and bacteria or fungi circulating in the bloodstream Otitis Media Otitis media OM is a disease of the middle ear that involves the inflammation of the mucoperiosteal lining.

Chronic Bacterial Prostatitis The prostate gland may become infected by bacteria that have ascended from the urethra or by reflux of infected urine into the prostatic ducts emptying into the posterior urethra Cystic Fibrosis Cystic fibrosis CF , a chronic disease of the lower respiratory system, is the most common inherited disease.

Periodontitis Periodontal diseases, infections involving the supporting tissues of teeth, range from mild and reversible inflammations of the gums gingiva to chronic destruction of periodontal tissues gingiva, periodontal ligament, and alveolar bone. Prosthetic Heart Valves Two major groups of prosthetic heart valves are currently used, mechanical valves and bioprostheses tissue valves Urinary Catheters Urinary catheters are tubular, latex, or silicone devices that are inserted through the urethra into the bladder to measure urine output, collect urine during surgery, prevent urinary retention, or control urinary incontinence Contact Lenses Contact lenses have been classified according to material of construction, design, wear schedule, and frequency of disposal.

Dental Unit Water Lines Unlike other medical devices discussed previously, dental water systems are not indwelling devices, and the public health significance of biofilms in these systems is unclear. Detachment of Cells or Cell Aggregates Cells may detach individually from biofilms as a result of cell growth and division within the biofilms, or cell aggregates or clusters may detach or be sloughed from the biofilm.

Production of Endotoxins In addition to the direct effects of cell detachment or antimicrobial resistance, gram-negative bacteria within biofilms of indwelling medical devices will produce endotoxins, which may in turn elicit an immune response in the patient. Provision of a Niche for the Generation of Resistant Organisms It has been shown that bacteria can exchange plasmids by conjugation within biofilms, and resistance factors may be carried on a plasmid. Prosthetic Heart Valves Generally, antibiotics are prescribed for prolonged periods up to 8 weeks, depending on the antimicrobial agent prescribed and organism to be treated 55 , though it has been noted that relatively few patients can be cured by antimicrobial therapy alone Central Venous Catheters Several strategies for controlling biofilms on CVCs have been suggested, including using topical antimicrobial ointments, minimizing the length of catheterization, using in-line filtration of intravenous fluids, using a surgically implanted cuff to the catheter, coating the inner lumen with antimicrobial agents, and as a last resort removing the device Roll tip method or sonication method used for quantification of catheter colonization.

Controlled Release Bioactive Mat. Urinary Catheters Control strategies that have been used to inhibit biofilm formation on urinary catheters include antimicrobial ointments and lubricants, bladder instillation or irrigation, antimicrobial agents in the collection bags, impregnating the catheter with antimicrobial agents silver oxide , and using systemic antibiotics for prophylaxis in catheterized patients Examples of selected urinary catheter biofilm control treatments. Contact Lenses Several studies have compared the efficacy of contact lens storage and cleaning solutions against bacterial biofilms on lens storage cases.

Dental Unit Water Lines Flushing has been suggested as one treatment for reducing the planktonic bacterial load that originates from the tubing biofilms ; however, several studies have shown that flushing alone is ineffective in significantly decreasing bacterial contamination , , Novel and Unproven Strategies Numerous biofilm control strategies have been proposed. Acknowledgments We express our appreciation to J.

Impact of rpoS deletion on Escherichia coli biofilms. Antibiotic susceptibility assay for Staphylococcus aureus in biofilms developed in vitro. Role of catheter colonization and infrequent hematogenous seeding in catheter-related infections. On line, non-destructive biomass determination of bacterial biofilms by fluorometry. Dynamic interactions of biofilms of mucoid Pseudomonas aeruginosa with tobramycin and piperacillin. Susceptibility of biofilm cells of Pseudomonas aeruginosa to bactericidal actions of whole blood and serum. Does surface heparinisation reduce bacterial colonisation of central venous catheters?

Legionella contamination of dental-unit waters. Routine semiquantitative cultures and central venous catheter-related bacteremia. Efficacy of silver-coating central venous catheters in reducing bacterial colonization. Effect of growth rate on resistance of Candida albicans biofilms to antifungal agents. Scanning electron microscopy of Dalkon Shield tails. Multiparametric analysis of waterline contamination in dental units.

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Introduction to microbial biofilms, p. Bacterial biofilms in nature and disease. Physiological responses induced in bacteria adhering to surfaces. Enzymatic modification of glycocalyx in the treatment of experimental endocarditis due to viridins streptococci. Anti-infective efficacy of silver-coated medical prostheses. A comparison of two antimicrobial-impregnated central venous catheters. Contact lens and prosthesis infections, p.

Regulation of the alginate biosynthesis gene algC in Pseudomonas aeruginosa during biofilm development in continuous culture. The involvement of cell-to-cell signals in the development of a bacterial biofilm. Evolution of microbiology and of microbes, p. Harper and Row, Philadelphia, Pa. Liquid flow in heterogeneous biofilms. Increasing resistance of planktonic and biofilm cultures of Burkholderia cepacia to ciprofloxacin and ceftazidime during exponential growth.

Protocol for the detection of biofilms on needleless connectors attached to central venous catheters. Growing biofilms in intravenous fluids , p. Prosthetic valve endocarditis, p. Growth-rate-dependent killing by ciprofloxacin of biofilm-derived Staphylococcus epidermidis; evidence for cell-cycle dependency. Effect of biofilm culture on the susceptibility of Staphylococcus epidermidis to tobramycin. Experimental bacterial endocarditis II. Survival of bacteria in endocardial vegetations.

Structure and evolution of very early lesions. The predominant cultivable microbiota of active and inactive lesions of destructive periodontal diseases. RP4 plasmid transfer among species of Pseudomonas in a biofilm reactor. Novel approach to investigate a source of microbial contamination of central venous catheters. Effect of growth-rate on resistance of gram-negative biofilms to cetrimide. A novel antibiofilm technology for contact lens solutions. A morphological study of experimental staphylococcal endocarditis and aortitis.

Interrelationship of bacteria, vegetation and cardiovasculature in established infections. Methods of disinfection of the water system of dental units by water chlorination. Efficacy of an attachable subcutaneous cuff for the prevention of intravascular catheter-related infection. Infection and intravenous catheters. Prevention of bacterial contamination of water in dental units. Scanning electron microscopy of bacterial biofilms on indwelling bladder catheters.

Adaptation and growth of Serratia marcescens in contact lens disinfectant solutions containing chlorhexidine gluconate. The bacteriology and cytology of chronic otitis media with effusion. Antibiotic interaction and diffusion through alginate and exopolysaccharide of cystic fibrosis-derived Pseudomonas aeruginosa. Otorrhea after insertion of silver oxide-impregnated silastic tympanostomy tubes. Microbial pathogenesis in cystic fibrosis: Artificial valve disease, p.

Alginate lyase promotes diffusion of aminoglycosides through the extracellular polysaccharide of mucoid Pseudomonas aeruginosa. High rates of conjugation in bacterial biofilms as determined by quantitative in situ analysis. Diffuse lamellar keratitis related to endotoxins released from sterilizer reservoir biofilms. Production of mucoid exopolysaccharide during development of Pseudomonas aeruginosa biofilms.

Effects of ultrasonic treatment on the efficacy of gentamicin against established Pseudomonas aeruginosa biofilms. Colloids Surfaces B Biointerfaces 6: In vivo efficacy of silver-coated silzone infection-resistant polyester fabric against a biofilm-producing bacteria, Staphylococcus epidermidis. Spectrophotometric monitoring of biofouling.

Microbial colonization of tailed and tailless intrauterine contraceptive devices: Human polymorphonuclear leukocyte response to Pseudomonas aeruginosa grown in biofilms. Some bacterial parameters influencing the neutrophil oxidative burst to Pseudomonas aeruginosa biofilms. Effects of tetracycline-containing gel and a mixture of tetracycline and citric acid-containing gel on non-surgical periodontal therapy. Enzymatic removal and disinfection of bacterial biofilm. Activities of a nitrofurazone-containing urinary catheter and a silver hydrogel catheter against multidrug-resistant bacteria characteristic of catheter-associated urinary tract infection.

Activity of a nitrofurazone matrix urinary catheter against catheter-associated uropathogens. Value of antibiotic levels in serum and cardiac vegetations for predicting antibacterial effect of ceftriaxone in experimental Escherichia coli endocarditis. Reduced intravascular catheter infection by antibiotic bonding. A prospective, randomized, controlled trial. Infections of prosthetic heart valves and vascular grafts, p. Infections associated with foreign bodies in the urinary tract, p. Robbins Device in biofilm research. The effect of chlorhexidine on defined, mixed culture oral biofilms grown in a novel model system.

Evaluation of a novel endoluminal brush method for in situ diagnosis of catheter related sepsis. Recurrent endocarditis in silver-coated heart valve prosthesis. Pathogenesis of cystic fibrosis. Adhere today, here tomorrow: Inhibitory effect of macrolide antibiotics on biofilm formation by Pseudomonas aeruginosa.

Nippon Jibiinkoka Gakkai Kaiho Penetration of amoxicillin, cefaclor, erythromycin-sulfisoxazole, and trimethoprim-sulfamethoxazole into the middle ear fluid of patients with chronic serous otitis media. Rapid method for detection of adherent bacteria on Foley urinary catheters. Production of mucoid microcolonies by Pseudomonas aeruginosa within infected lungs in cystic fibrosis. Porphyromonas gingivalis invasion of gingival epithelial cells. Life below gum line: Cambridge University Press, Cambridge, England.

Resistance of Streptococcus sanguis biofilms to antimicrobial agents. Optical sectioning of microbial biofilms. Structure and function of biofilms , p. A review of bacteriological culture of removed intrauterine contraceptive devices. Pathogenesis of infective endocarditis, p. Raven Press, New York, N. The role of fibronectin binding on the rate model of experimental endocarditis caused by Streptococcus sanguis.

Adherence of Streptococcus sanguis to conformationally specific determinants in fibronectin. Relation between the presence of echocardiographic vegetations and the complication rate in infective endocarditis. A comparative study of polyantibiotic and iodophor ointments in prevention of vascular catheter-related infection.

Infections caused by intravascular devices used for infusion therapy: Prevention of central venous catheter-related bloodstream infection by use of an antiseptic-impregnated catheter. A randomized, controlled trial. An attachable silver-impregnated cuff for prevention of infection with central venous catheters: A semiquantitative culture method for identifying intravenous-catheter-related infection.

A scanning and transmission electron microscopic study of the surfaces of intrauterine contraceptive devices. Interfaces in microbial ecology , p. Harvard University Press, Cambridge, Mass. Mucoid conversion of Pseudomonas aeruginosa by hydrogen peroxide: Alginate synthesis by Pseudomonas aeruginosa: Bacterial biofilm on contact lenses and lens storage cases in wearers with microbial keratitis. Biofilm associated urinary tract infections, p. Mucoid Pseudomonas aeruginosa growing in a biofilm in vitro are killed by opsonic antibodies to the mucoid exopolysaccharide capsule but not by antibodies produced during chronic lung infection in cystic fibrosis patients.

Effects of protein, mucin, and human tears on adherence of Pseudomonas aeruginosa to hydrophilic contact lenses. Adherence of Pseudomonas aeruginosa to hydrophilic contact lenses and other substrata. Multipurpose laminar-flow adhesion cells for the study of bacterial colonization and biofilm formation. Bacteriology of moderate chronic periodontitis in mature adult humans.

The effect of urease inhibitors on the encrustation of urethral catheters. Which indwelling urethral catheters resist encrustation by Proteus mirabilis biofilms. Comparison of dental water quality management procedures. Biofilm formation by gram-negative bacteria on central venous catheter connectors: Movement of Pseudomonas aeruginosa along catheter surfaces. Coagulase-negative staphylococcus in chronic prostatitis.

Rat model of experimental bacterial prostatitis. Tobramycin resistance of Pseudomonas aeruginosa cells growing as a biofilm on urinary catheter material. Pathogenesis of chronic bacterial prostatitis in an animal model. Bacterial localization in antibiotic-refractory chronic bacterial prostatitis.

Ultrastructural study of microbiologic colonization of urinary catheters. Amdinocillin treatment of catheter-associated bacteriuria in rabbits. Darkground microscopy of subgingival plaque from the top to the bottom of the periodontal pocket. The efficacy of chlorination and filtration in the control and eradication of Legionella from dental chair water systems. Native valve infective endocarditis caused by Streptococcus bovis.

Efficacy of short-term antibiotic therapy and usefulness of serial echocardiographic evaluation. Antibiotic hydrogel coated Foley catheters for prevention of urinary tract infection in a rabbit model. Ultrastructural analysis of indwelling vascular catheters: Quantitative tip culture methods and the diagnosis of central venous catheter-related infections.

Clinical effects of simultaneous ultrasonic scaling and subgingival scaling and subgingival irrigation with chlorhexidine. Mediating influence of periodontal probing depth. Quantitative determination of endotoxins released by bacterial biofilms. Transfer of a conjugative transposon, Tn , in a model oral biofilm. Examination of biofilm formation and risk of infection associated with the use of urinary catheters with leg bags. Effect of antibiotic treatment on vegetation size and complication rate in infective endocarditis. In vivo resistance to bacterial biofilm formation on tympanostomy tubes as a function of tube material.

Microbial contamination of dental unit waterlines: The efficacy of silver alloy-coated urinary catheters in preventing urinary tract infection. Hospital-acquired urinary tract infections associated with the indwelling catheter. Etiology of periodontal disease, p. Biofilm and the dental office. Three-year experience with sonicated vascular catheter cultures in a clinical microbiology laboratory.

The inhibitory effect of Staphylococcus epidermidis slime on the phagocytosis of murine peritoneal macrophages is interferon-independent. The bacteriology of destructive periodontal disease: Effects of slime produced by clinical isolates of coagulase-negative staphylococci on activities of various antimicrobial agents. Pseudomonas keratitis associated with biofilm formation on a disposable soft contact lens. Bacterial adherence and glycocalyx formation on unworn hydrogel lenses. Quantification of bacteria in middle ear effusions. Echocardiographic documentation of vegetative lesions in infective endocarditis: Theoretical aspects of antibiotic diffusion into microbial biofilms.

Studies on the formation of crystalline bacterial biofilms on urethral catheters. Activity of antiseptics against biofilms of mixed bacterial species growing on silicone surfaces. Bacterial biofilms and the encrustation of urethral catheters. Blockage of urethral catheters by bacterial biofilms. Ability of Proteus mirabilis to swarm over urethral catheters. Proteus mirabilis biofilms and the encrustation of urethral catheters. Biofilms on indwelling urethral catheters produce quorum-sensing signal molecules in situ and in vitro. The structure of urinary catheter encrusting bacterial biofilms.

Simple physical model to study formation and physiology of biofilms on urethral catheters. Bacterial endocarditis with aortic regurgitation: Oscillation characteristics of biofilm streamers in turbulent flowing water as related to drag and pressure drop. Investigation of ciprofloxacin penetration into Pseudomonas aeruginosa biofilms. Bacterial succession within a biofilm in water supply lines of dental air-water syringes. The Dalkon Shield controversy. Efficacy of industrial biocides against bacterial biofilms. University of Birmingham, Birmingham, United Kingdom. Adherent microorganisms on lumenal surfaces of long-term intravenous catheters.

Biofilm and biofilm-related encrustations of urinary tract devices. Efficacy of antiseptic-impregnated central venous catheters in preventing catheter-related bloodstream infection. A bacterial biofilm in a hemodialysis system. Assessment of disinfection and crossing of endotoxin. Resistance of Pseudomonas pseudomallei growing as a biofilm on silastic disks to ceftazidime and cotrimoxazole. Quantitative assessment of biocide control of biofilms including Legionella pneumophila using total viable counts, fluorescence microscopy, and image analysis.

Mechanism of persistent infection associated with peritoneal implants. Treatment of native valve Candida endocarditis with flucanazole. Influence of biofilms on microbial contamination in dental unit water. Bacterial colonization of tunneled right atrial catheters in pediatric oncology: The effects of adherence to silicone surfaces on antibiotic susceptibility in Staphylococcus aureus. Evaluation and use of a low nutrient medium and reduced incubation temperature to study bacterial contamination in the water supply of dental units.

Assessing microbial contamination in clean water dental units and compliance with disinfection protocol. Comparative efficacies of soft contact lens disinfectant solutions against microbial films in lens cases. Bacterial colonization of intrauterine devices IUDs. Interaction between human polymorphonuclear leucocytes and bacteria released from in-vitro bacterial biofilm models. Measuring antimicrobial effects on biofilm bacteria: Management of urinary bladder function in Danish hospitals, nursing homes and home care.

Biofilms: Survival Mechanisms of Clinically Relevant Microorganisms

Ultrasound as a means of detaching biofilms. Simple method for rapid diagnosis of catheter-associated infection by direct acridine orange staining of catheter tips. Support Center Support Center. Please review our privacy policy. Roll the catheter tip over the surface of a blood agar plate.