Antibiofilm Antibiotic Research Articles

Do Anti-Biofilm Antibiotics Have a Place in the Treatment of Diabetic Foot Osteomyelitis?

The choice of antibiotic regimens for use in patients presenting with diabetic foot osteomyelitis and their duration differs according to the situation. Antibiotics play a more important role in the medical option where no infected bone has been resected, while their role is reduced but not negligible in the case of surgical options. Some studies have reported the presence of biofilm structures in bone samples taken from patients with diabetic foot osteomyelitis, which raises the question of the place of anti-biofilm antibiotic regimens in this setting. During the last two decades, clinical studies have suggested a potential benefit for anti-biofilm antibiotics, mainly rifampicin against staphylococci and fluoroquinolones against gram-negative bacilli. However, no data from randomized controlled studies have been reported so far. The present work provides a summary of the available data on the question of the place of anti-biofilm antibiotics for the treatment of diabetic foot osteomyelitis, but also the potential limitations of such treatments.

Smart Nanomaterials for Treatment of Biofilm in Orthopedic Implants.

Biofilms refer to complex bacterial communities that are attached to the surface of animate or inanimate objects, which highly resist the antibiotics or the host immune defense mechanisms. Pathogenic biofilms in medicine are general, chronic, and even costly, especially on medical devices and orthopedic implants. Bacteria within biofilms are the cause of many persistent infections, which are almost impossible to eradicate. Though some progress has been made in comprehending the mechanisms of biofilm formation and persistence, novel alternative compounds or strategies and effective anti-biofilm antibiotics are still lacking. Smart materials of nano size which are able to respond to an external stimulus or internal environment have a great range of applications in clinic. Recently, smart nanomaterials with or without carriage of antibiotics, targeting specific bacteria and biofilm under some stimuli, have shown great potential for pathogenic biofilm and resident bacteria eradication. First, this review briefly summarizes and describes the significance of biofilms and the process of biofilm formation. Then, we focus on some of the latest research studies involving biofilm elimination, which probably could be applied in orthopedic implants. Finally, some outstanding challenges and limitations that need to be settled urgently in order to make smart nanomaterials effectively target and treat implant biofilms are also discussed. It is hoped that there will be more novel anti-biofilm strategies for biofilm infection in the prospective future.

Examination of a first-in-class bis-dialkylnorspermidine-terphenyl antibiotic in topical formulation against mono and polymicrobial biofilms.

Biofilm-impaired tissue is a significant factor in chronic wounds such as diabetic foot ulcers. Most, if not all, anti-biotics in clinical use have been optimized against planktonic phenotypes. In this study, an in vitro assessment was performed to determine the potential efficacy of a first-in-class series of antibiofilm antibiotics and compare outcomes to current clinical standards of care. The agent, CZ-01179, was formulated into a hydrogel and tested against mature biofilms of a clinical isolate of methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa ATCC 27853 using two separate methods. In the first method, biofilms were grown on cellulose discs on an agar surface. Topical agents were spread on gauze and placed over the biofilms for 24 h. Biofilms were quantified and imaged with confocal and scanning electron microscopy. In the second method, biofilms were grown on bioabsorbable collagen coupons in a modified CDC biofilm reactor. Coupons were immersed in treatment for 24 h. The first method was limited in its ability to assess efficacy. Efficacy profiles against biofilms grown on collagen were more definitive, with CZ-01179 gel eradicating well-established biofilms to a greater degree compared to clinical standards. In conclusion, CZ-01179 may be a promising topical agent that targets the biofilm phenotype. Pre-clinical work is currently being performed to determine the translatable potential of CZ-01179 gel.

Bacteriophage–antibiotic combinations against ciprofloxacin/ceftriaxone-resistant Escherichia coli in vitro and in an experimental Galleria mellonella model

Escherichia coli is the most common cause of Gram-negative prosthetic joint infections (PJIs) and ciprofloxacin is the first-line antibiofilm antibiotic. Due to the emergence of fluoroquinolone resistance, management of E. coli PJIs has become challenging and is associated with high treatment failure rates. We evaluated the efficacy of a newly isolated bacteriophage ɸWL-3 as a therapeutic agent in combination with ciprofloxacin, fosfomycin, gentamicin, meropenem or ceftriaxone against biofilm of a ciprofloxacin/ceftriaxone-resistant E. coli strain and the ATCC 25922 reference strain. ɸWL-3 was first characterised in terms of virion morphology, absorption rate, burst size and killing kinetics against both E. coli strains. The tested antibiotics presented high inhibitory concentrations (ranging from 16 to >1024 μg/mL) when tested alone against biofilms. Co-administration of ɸWL-3 with antibiotics improved the antibiotic efficacy against biofilm, especially after staggered exposure, reducing the minimum biofilm bactericidal concentration (MBBC) up to 512 times. The in vivo antimicrobial activity of ɸWL-3/fosfomycin combination against both E. coli strains was assessed in a Galleria mellonella invertebrate infection model. Treatment of infected larvae after lethal doses of E. coli resulted in enhanced survival rates when combinatorial therapy with ɸWL-3/fosfomycin was applied on E. coli ATCC 25922-infected larvae compared with monotherapy, but not for EC1-infected larvae, which we speculated could be due to higher release of endotoxins in a shorter period in EC1-infected larvae exposed to ɸWL-3. Our study provides new insights into the use of bacteriophages and antibiotics in the treatment of biofilm-associated infections caused by antibiotic-resistant bacteria.

In vivo efficacy of a unique first-in-class antibiofilm antibiotic for biofilm-related wound infections caused by Acinetobacter baumannii

Wounds complicated by biofilms challenge even the best clinical care and can delay a return to duty for service members. A major component of treatment in wounded warriors includes infected wound management. Yet, all antibiotic therapy options have been optimized against planktonic bacteria, leaving an important gap in biofilm-related wound care. We tested the efficacy of a unique compound (CZ-01179) specifically synthesized to eradicate biofilms. CZ-01179 was formulated as the active agent in a hydrogel, and tested in vitro and in vivo in a pig excision wound model for its ability to treat and prevent biofilm-related wound infection caused by Acinetobacter baumannii. Data indicated that compared to a clinical standard—silver sulfadiazine—CZ-01179 was much more effective at eradicating biofilms of A. baumannii in vitro and up to 6 days faster at eradicating biofilms in vivo. CZ-01179 belongs to a broader class of newly-synthesized antibiofilm agents (referred to as CZ compounds) with reduced risk of resistance development, specific efficacy against biofilms, and promising formulation potential for clinical applications. Given its broad spectrum and biofilm-specific nature, CZ-01179 gel may be a promising agent to increase the pipeline of products to treat and prevent biofilm-related wound infections.

Extended Release Combination Antibiotic Therapy from a Bone Void Filling Putty for Treatment of Osteomyelitis.

In spite of advances in Total Joint Replacements (TJR), infection remains a major concern and a primary causative factor for revision surgery. Current clinical standards treat these osteomyelitis infections with antibiotic-laden poly(methyl methacrylate) (PMMA)-based cement, which has several disadvantages, including inadequate local drug release kinetics, antibiotic leaching for a prolonged period and additional surgical interventions to remove it, etc. Moreover, not all antibiotics (e.g., rifampicin, a potent antibiofilm antibiotic) are compatible with PMMA. For this reason, treatment of TJR-associated infections and related complications remains a significant concern. The objective of this study was to develop a polymer-controlled dual antibiotic-releasing bone void filler (ABVF) with an underlying osseointegrating substrate to treat TJR implant-associated biofilm infections. An ABVF putty was designed to provide sustained vancomycin and rifampicin antibiotic release for 6 weeks while concurrently providing an osseointegrating support for regrowth of lost bone. The reported ABVF showed efficient antibacterial and antibiofilm activity both in vitro and in a rat infection model where the ABVF both showed complete bacterial elimination and supported bone growth. Furthermore, in an in vivo k-wire-based biofilm infection model, the ABVF putty was also able to eliminate the biofilm infection while supporting osseointegration. The retrieved k-wire implants were also free from biofilm and bacterial burden. The ABVF putty delivering combination antibiotics demonstrated that it can be a viable treatment option for implant-related osteomyelitis and may lead to retention of the hardware while enabling single-stage surgery.

Foot and ankle infections: Debridement, early fixation and rifampicin provide earlier recovery of function and quality of life

BackgroundInfection after foot and ankle fractures is a major concern for orthopedic surgeons. It is widely believed that final osteosynthesis should be delayed until the infection is cured. However, there is no literature that supports this practice. In addition, the delay impairs patient function and quality of life (QoL). MethodsIn the present study, four cases of ankle infection treated with aggressive debridement, early fixation and antibiofilm antibiotics are described. It is thought that, like other implant related infections, ankle infections can be rapidly treated with the definitive fixation and by curing the infection to make for a fast recovery of QoL and function. ResultsThe infections were caused by MSSA and Pseudomonas aeruginosa in case 1, MSSA in case 2 and MRSA as well as K. pneumonia in case 3. Case 4 was a culture negative infection. They were susceptible to antibiofilm antibiotics (the gram-negative bacilli susceptible to ciprofloxacin and the gram-positive cocci susceptible to rifampicin). Cases 1, 3 and 4 were treated with a tibio-talo-calcaneal arthrodesis and case 2 was treated with a de-rotational fibular osteotomy and a medial closing wedge supramalleolar osteotomy. All cases improved at a median time of 4 weeks in terms of quality of life (SF-36) and function (AOFAS). At 2-years follow-up, no recurrence of infection was observed in any of the cases. All the cases achieved fusion or osteotomy healing at final follow-up. ConclusionsEarly fixation after debridement combined with antibiofilm antibiotics can be performed in foot and ankle inflections to provide early recovery of QoL and function in patients.

Silver nanoparticles as an alternative strategy against bacterial biofilms.

Biofilms are complex bacterial communities that resist the action of antibiotics and the human immune system. Bacteria within biofilms are the cause of numerous, almost impossible to eradicate, persistent infections. Biofilms can form on many medical devices and implants, and so have an enormous impact on medicine. Due to the lack of effective anti-biofilm antibiotics, novel alternative compounds or strategies are urgently required. This review describes some of the latest approaches in the field of biofilm treatment. New anti-biofilm technologies target different stages in the biofilm formation process. Some act to modify the colonized biomaterials to make them resistant to biofilm formation. One potentially important candidate treatment uses silver nanoparticles that show anti-bacterial and anti-biofilm activity. The biological action of nano-silver is complex and seems to involve a number of pathways. However, there have been few reports on the anti-biofilm activity of silver nanoparticles and the precise mechanism underlying their action remains unresolved. Here, we describe some anti-biofilm approaches employing AgNPs and consider the challenges and problems that need to be addressed in order to make silver nanoparticles a part of an effective anti-biofilm strategy.