Antibiofilm Strategy Research Articles

Novel 2-Substituted 3-Hydroxy-1,6-dimethylpyridin-4(1H)-ones as Dual-Acting Biofilm Inhibitors of Pseudomonas aeruginosa.

2-Heptyl-3-hydroxy-4(1H)-quinolone (PQS), a compound from P. aeruginosa, functions as both a quorum sensing (QS) regulator and a potent iron chelator to induce expression of pyoverdine and pyochelin which are involved in high-affinity iron transport systems. A potential dual-acting antibiofilm strategy requires molecules designed to interfere with iron uptake and the QS system of P. aeruginosa. A series of 2-substituted 3-hydroxy-1,6-dimethylpyridin-4-ones have been designed, synthesized, and tested as biofilm inhibitors of P. aeruginosa. One compound, N-((1,3,6-trimethyl-4-oxo-1,4-dihydropyridin-2-yl)methyl)hexanamide (10d), exhibits 68.67% biofilm inhibitory activity at 20 μM. Further mechanistic studies have confirmed that this compound not only inhibits the QS systems of P. aeruginosa but also acts as an iron chelator to compete strongly with pyoverdine, causing iron deficiency in bacteria. The pyoverdine receptor FpvA was revealed as the target of 10d by the Pvds mutant strain, fpvA-overexpressed strain, and in silico studies.

Inhibiting bacterial cooperation is an evolutionarily robust anti-biofilm strategy

Bacteria commonly form dense biofilms encased in extracellular polymeric substances (EPS). Biofilms are often extremely tolerant to antimicrobials but their reliance on shared EPS may also be a weakness as social evolution theory predicts that inhibiting shared traits can select against resistance. Here we show that EPS of Salmonella biofilms is a cooperative trait whose benefit is shared among cells, and that EPS inhibition reduces both cell attachment and antimicrobial tolerance. We then compare an EPS inhibitor to conventional antimicrobials in an evolutionary experiment. While resistance against conventional antimicrobials rapidly evolves, we see no evolution of resistance to EPS inhibition. We further show that a resistant strain is outcompeted by a susceptible strain under EPS inhibitor treatment, explaining why resistance does not evolve. Our work suggests that targeting cooperative traits is a viable solution to the problem of antimicrobial resistance.

Evaluation of Viable Cells in Pseudomonas aeruginosa Biofilmsby Colony Count and Live/Dead Staining.

Pseudomonas aeruginosa is a human pathogen capable to form robust biofilms. P. aeruginosa biofilms represent a serious problem because of the adverse effects on human health and industry, from sanitary and economic points of view. Typical strategies to break down biofilms have been long used, such as the use of disinfectants or antibiotics, but also, according to their high resistance to standard antimicrobial approaches, alternative strategies employing photocatalysis or control of biofilm formation by modifying surfaces, have been proposed. Colony forming units (cfu) counting and live/dead staining, two classic techniques used for biofilm quantification, are detailed in this work. Both methods assess cell viability, a key factor to analyze the microbial susceptibility to given treatment, then, they represent a good approach for evaluation of an antibiofilm strategy.

Co-delivery of Diverse Therapeutic Compounds Using PEG–PLGA Nanoparticle Cargo against Drug-Resistant Bacteria: An Improved Anti-biofilm Strategy

Controlling biofilms of bacteria is a challenging aspect because of their drug-resistance potentials against a range of antibiotics, demanding the development of active anti-biofilm agents. Rutin(R), a natural antioxidant, and benzamide(B), a synthetic antibacterial agent, have several pharmacological and antibacterial abilities. Herein, we developed PEG-PLGA NPs that synergistically carried rutin and benzamide as drug candidates, while displaying therapeutic and anti-biofilm functions. These drug delivery NPs were synthesized by the oil-in-water emulsion (O/W) solvent evaporation technique. The obtained NPs were characterized by UV-vis, FT-IR, SEM, TEM, and DLS measurements. Confocal laser scanning microscopy was employed to evaluate theanti-biofilmcapabilities against Staphylococcus aureus and Pseudomonas aeruginosa and further quantified the levels of residual biofilm constituents such as protein and exopolysaccharide (EPS). Drug release experiments showed the controlled release of rutin-benzamide (RB)for several days. Antibacterial analyses showed that the minimum inhibitory concentration (MIC) of NPs was at least two times lower than that of the free drugs. RB-PEG-PLGA NPs revealed that they targeted biofilm-forming bacteria through the disruption of the membrane and biofilm surface and were observed to be nontoxic when tested using human erythrocytes and human cell lines. In vivo evaluations in zebrafish showed that the NPs did not alter the antioxidant functions and histological features of tissues. On the basis of results obtained, it is substantiated that the rutin-benzamide-loaded nanocarrier offers potential anti-biofilm therapy due to its high anti-biofilmactivity and biocompatibility.

Minimally invasive salvage of infected breast tissue expanders: A continuous closed irrigation technique based on surface biofilm disruption

Removal of the infected device has been the general treatment for device-associated infection in antibiotic failure. There have been anecdotal attempts to salvage infected medical devices by introducing a continuous closed irrigation system. This study examines whether continuous closed irrigation of an infected device is a successful alternative to removal in patients with recalcitrant device-associated infection. Patients who were diagnosed with recalcitrant periexpander infections during the course of expander-implant breast reconstruction from 2010 to 2018 were enrolled in a retrospective case-control study. Patients who failed antibiotics before 2017 underwent expander removal, but patients since 2017 underwent continuous closed irrigation of the infected expanders. Treatment details and clinical outcomes were compared. Rationale for expander irrigation was based on review of the current literature on biofilm research. During the study period, 21 out of the 1176 patients were diagnosed with periexpander infection recalcitrant to antibiotic therapy. Among the 21 patients, 16 underwent expander removal and five underwent expander irrigation. Clinical outcomes were comparable in terms of resolution of infection signs. The irrigation group showed fewer patients who abandoned reconstruction after infection treatment (removal=11/16, irrigation=1/5). Literature review revealed that expander irrigation might have induced hydrodynamic disruption of the biofilm structure. Expander irrigation was less invasive than removal and effective in suppressing severe recalcitrant periexpander infection. Continuous closed irrigation of infected expander devices may be a successful antibiofilm strategy in treating device-associated infections in select patients.

Magnesium-doped zinc oxide nanoparticles alter biofilm formation of Proteus mirabilis.

Aim:Proteus mirabilis biofilms colonize medical devices, and their role in microbial pathogenesis is well established. Magnesium-doped zinc oxide nanoparticles (ZnO:MgO NPs) have potential antimicrobial properties; thus, we aimed at evaluating the antibiofilm activity of ZnO:MgO NPs against P. mirabilis biofilm. Materials & methods: After synthesis and characterization of ZnO:MgO NPs and their addition to a polymer film, we evaluated the stages of P. mirabilis biofilm development over glass coverslip covered by different concentrations of ZnO:MgO NPs. Results: Low concentrations of ZnO:MgO NPs affect the development of P. mirabilis biofilm. Descriptors showed reduced values in bacterial number, bacterial volume and extracellular material. Conclusion: Our results highlight this new application of ZnO:MgO NPs as a potential antibiofilm strategy in medical devices.

Two to six-year disease resolution and marginal bone stability rates of a modified resective-implantoplasty therapy in 32 peri-implantitis cases.

Different nonsurgical, antibacterial, surgical, and regenerative approaches to treat peri-implantitis have been proposed, but there is no an actual "gold" standard treatment showing the most favorable results to counteract peri-implantitis effects. To evaluate radiographically and clinically the disease resolution and peri-implant marginal bone stability rates of peri-implantitis cases treated through a combined resective-implantoplasty therapy in a moderate to long-term period. Records of patients diagnosed with peri-implantitis and treated through the same protocol applying a combined resective-implantoplasty therapy with minimum 2-year follow-up were screened. Eligible patients were contacted and asked to undergo clinical and radiologic examination. Progressive marginal bone loss, bleeding on probing, suppuration, implant mobility, and implant fracture were considered to establish the disease resolution rate and peri-implant bone stability of the treated implants. Twenty-three patients with 32 treated implants fulfilled the inclusion criteria. Over the 2 to 6-year follow-up, (mean time: 3.4 ± 1.5 years), the disease resolution rate was 83% (patient level) and 87% (implant level). Four implants (13%) were lost or removed due to continuous MBL and osseointegration failure. At follow-up, peri-implant marginal bone remained stable with no further bone loss in 87% of the treated implants. BOP was absent in 89.3% (implant level), suppuration was resolved in all cases, and no pain or implant fracture was reported. Implantoplasty treated cases showed high disease resolution rate and peri-implant marginal bone stability. This surgical antibiofilm strategy can counteract peri-implantitis progression providing an adequate environment for implant function and longevity over a moderate to long-term period.

Fucoidan-Stabilized Gold Nanoparticle-Mediated Biofilm Inhibition, Attenuation of Virulence and Motility Properties in Pseudomonas aeruginosa PAO1.

The emergence of antibiotic resistance in Pseudomonas aeruginosa due to biofilm formation has transformed this opportunistic pathogen into a life-threatening one. Biosynthesized nanoparticles are increasingly being recognized as an effective anti-biofilm strategy to counter P. aeruginosa biofilms. In the present study, gold nanoparticles (AuNPs) were biologically synthesized and stabilized using fucoidan, which is an active compound sourced from brown seaweed. Biosynthesized fucoidan-stabilized AuNPs (F-AuNPs) were subjected to characterization using UV-visible spectroscopy, Fourier transform infrared spectroscopy (FTIR), field emission transmission electron microscopy (FE-TEM), dynamic light scattering (DLS), and energy dispersive X-ray diffraction (EDX). The biosynthesized F-AuNPs were then evaluated for their inhibitory effects on P. aeruginosa bacterial growth, biofilm formation, virulence factor production, and bacterial motility. Overall, the activities of F-AuNPs towards P. aeruginosa were varied depending on their concentration. At minimum inhibitory concentration (MIC) (512 µg/mL) and at concentrations above MIC, F-AuNPs exerted antibacterial activity. In contrast, the sub-inhibitory concentration (sub-MIC) levels of F-AuNPs inhibited biofilm formation without affecting bacterial growth, and eradicated matured biofilm. The minimum biofilm inhibition concentration (MBIC) and minimum biofilm eradication concentration (MBEC) were identified as 128 µg/mL. Furthermore, sub-MICs of F-AuNPs also attenuated the production of several important virulence factors and impaired bacterial swarming, swimming, and twitching motilities. Findings from the present study provide important insights into the potential of F-AuNPs as an effective new drug for controlling P. aeruginosa-biofilm-related infections.

Matrix metalloprotease-1 inhibits and disrupts Enterococcus faecalis biofilms.

Enterococcus faecalis is a major opportunistic pathogen that readily forms protective biofilms leading to chronic infections. Biofilms protect bacteria from detergent solutions, antimicrobial agents, environmental stress, and effectively make bacteria 10 to 1000-fold more resistant to antibiotic treatment. Extracellular proteins and polysaccharides are primary components of biofilms and play a key role in cell survival, microbial persistence, cellular interaction, and maturation of E. faecalis biofilms. Degradation of biofilm components by mammalian proteases is an effective antibiofilm strategy because proteases are known to degrade bacterial proteins leading to bacterial cell lysis and growth inhibition. Here, we show that human matrix metalloprotease-1 inhibits and disrupts E. faecalis biofilms. MMPs are cell-secreted zinc- and calcium-dependent proteases that degrade and regulate various structural components of the extracellular matrix. Human MMP1 is known to degrade type-1 collagen and can also cleave a wide range of substrates. We found that recombinant human MMP1 significantly inhibited and disrupted biofilms of vancomycin sensitive and vancomycin resistant E. faecalis strains. The mechanism of antibiofilm activity is speculated to be linked with bacterial growth inhibition and degradation of biofilm matrix proteins by MMP1. These findings suggest that human MMP1 can potentially be used as a potent antibiofilm agent against E. faecalis biofilms.

A new anti-biofilm strategy of enabling arbitrary surfaces of materials and devices with robust bacterial anti-adhesion via a spraying modified microsphere method

Despite adopting diverse strategies and fabrication methods to prevent biofilm formation, the existing sophisticated fabrication methods for sole wettable or smart surfaces and their unsatisfactory anti-adhesive durability need to be improved for their practical applications.

Evaluation of Antibiofilm Efficacy of Nanoparticle Agents Using Photodynamic Therapy; An In Vitro Study

Objective: This study evaluated the antibiofilm efficacy of nanoparticle agents using photodynamic therapy. Methods: A total of Ninety dentin section blocks were used in this study. Dentin section blocks were prepared to be (4×4×1 mm) (Length× Width × thickness) respectively. Each dentin section was placed in 1.5 mL polypropylene tube filled with brain heart infusion (BHI) broth then underwent sterilization using autoclave at 121°C for 20 minutes and the sterilization was confirmed using bacterial count test. Cultivation of Standard strains of E. Faecalis ATCC 29212 and Staph. Epidermidis ATCC 12228 were prepared then inoculated on dentin section blocks and incubated for 3 weeks at 37°C in incubator (The medium was changed every 3 days). The specimens were grouped into 4 groups according to Final irrigant rinse were used: G1: final rinse using chitosan nanoparticles (CSnps)., G2: final rinse using Rose Bengal dye (RB), G3: final rinse using chitosan nanoparticles conjugated with Rose Bengal dye (CSRBnps) and G4: control group. Each group was activated using a diode laser 635 nm for 5 minutes at energy fluence 30 J/cm2. Then, the effect of tested final rinsing on multispecies biofilm was assessed with Confocal Laser Scanning Electron Microscope (CLSM) and data were statistically analyzed. Results: With regard to the antimicrobial effectiveness of tested irrigants, the highest mean percentage of dead bacteria was found in {CSRBnp (Group 3)} (88.38 ± 5.45) followed by {Csnp (Group 1)} (75.73 ± 5.15) followed by Rose Bengal dye (Group 2) (59.43 ± 8.14). The least mean percentage of dead bacteria was found in Control group (Group 4)} (7.25 ± 1.12). With a statistically significant difference between groups where (p<0.001). Conclusion: Functionalization of chitosan nanoparticles with Rose Bengal dye is a potent antibiofilm strategy for disinfection of the root canal system.

Inhalable Levofloxacin Liposomes Complemented with Lysozyme for Treatment of Pulmonary Infection in Rats: Effective Antimicrobial and Antibiofilm Strategy.

Treatment of bacterial infections becomes increasingly complicated due to increasing bacterial resistance and difficulty in developing new antimicrobial agents. Emphasis should be laid on improvising the existing treatment modalities. We studied the improved antimicrobial and antibiofilm activity of levofloxacin (LFX) and lysozyme (LYS) in microbiological studies. LFX at sub-minimum inhibitory concentration with LYS eradicated > 85% of preformed biofilm. LFX was actively loaded into the liposomes using pH gradient method and was spray-dried with LYS solution. Percent entrapment of LFX in liposome was > 80% and prolonged cumulative release of 85% LFX at the end of 12h. In vitro lung deposition study and solid-state characterization for spray dried LFX liposome in combination with LYS (LFX liposome-LYS) was performed. Co-spray dried product had mass median aerodynamic diameter ranging < 5μm. In pharmacodynamic study, Staphylococcus aureus infected rats were treated with LFX liposome-LYS. Lungs, bronchoalveolar lavage fluid(BALF), and nasal fluid were evaluated for microbial burden. Expression of cytokine levels in BALF and serum were also studied by ELISA. In addition, mRNA expression for lung inflammatory mediators and lung myeloperoxidase activity were carried out. Further, lungs and histological changes were observed grossly. Untreated infected rat lungs demonstrated higher mRNA expression for inflammatory markers, cytokine levels, and microbial load compared to vehicle control. Conversely, LFX liposome-LYS significantly abated these adverse repercussions. Histology findings were also in agreement of above. Acute toxicity study revealed safeness of LFX liposome-LYS. Our findings confirm LFX liposome-LYS exhibited prolonged, improved antibiofilm and antimicrobial efficacy in treating S. aureus infection.

Restoring balance: biofilms and wound dressings.

Biofilms are responsible for stimulating and maintaining wound inflammation, increasing infection risk and delaying wound closure. Appropriate biofilm management is required to fight against local and systemic infection and to restore balance to the wound environment. The most effective way to remove biofilms involves the use of mechanical techniques, with the wound dressing representing an important component of this strategy. Wound dressing fibres, such as polyacrylate fibres, have been shown to be effective in affecting biofilm architecture by disrupting the biofilm matrix. This helps enhance the efficacy of antimicrobials, such as silver. Focusing an antibiofilm strategy on active agents alone does not constitute a sustainable approach to biofilm management. Furthermore, adding too many active chemicals into a wound can be highly detrimental to the wound bed, and potentially may have both short- and long-term biological concerns. Particular attention on the characteristics and key features of wound dressings is discussed in this paper. The aim of the paper is to review the ideal characteristics of wound dressings, in conjunction with antimicrobials, that are considered a fundamental part of an antibiofilm strategy and growing requirement for enhanced wound healing.

Antibiofilm activities of norharmane and its derivatives against Escherichia coli O157:H7 and other bacteria

BackgroundBacterial biofilms exhibit reduced sensitivity to conventional antibiotics and host defence systems and contribute to the persistence of chronic bacterial infections. HypothesisThe antibiofilm approach using plant alkaloids provides an alternative to antibiotic strategies. Study designIn this study, the antibiofilm activities of various plant alkaloids were investigated against enterohemorrhagic Escherichia coli O157:H7 and Pseudomonas aeruginosa. In the subsequent investigation, the effects of five norharmane derivatives were investigated. ResultHarmaline significantly inhibited biofilm formation by E. coli O157:H7, P. aeruginosa PAO1, P. aeruginosa PA14, and Klebsiella oxytoca, and norharmane (β-carboline) was found to have antibiofilm activity. It was also found that functional groups at the C-1 and C-7 positions of norharmane could play important roles in its antibiofilm activity. Confocal and electron microscopic observations confirmed biofilm inhibition by harmaline and norharmane, and both reduced fimbriae production and swarming and swimming motilities. Furthermore, harmaline and norharmane attenuated the virulence of E. coli O157:H7 in a Caenorhabditis elegans nematode model. ConclusionThese findings strongly suggest that harmaline and norharmane could have potential use in antibiofilm strategy against persistent bacterial infections.

Can Phage Therapy Solve the Problem of Recalcitrant Chronic Rhinosinusitis?

Chronic rhinosinusitis (CRS) affects 5-15% of the global population. In some patients, the infectious exacerbations of the disease are recalcitrant to medical treatment and surgery. These cases are probably associated with the presence of bacterial biofilms. Bacteriophage (phage) therapy seems to be a promising antibiofilm strategy. The efficacy of phage therapy in sinonasal infections has been demonstrated both in vitro and in animal models. In the past, phage preparations were also administered to humans with CRS with favorable outcomes and no significant side effects. Very recently, the safety and efficacy of phage therapy in otolaryngological infections has been demonstrated in pioneer Phase I/II clinical trials. This review addresses the potential of phage therapy to treat CRS. We also discuss issues that require further research.

Ephemeral biogels to control anti-biofilm agent delivery: From conception to the construction of an active dressing

Chronic wound colonization by bacterial biofilms is common and can cause various complications. An anti-biofilm strategy was developed around the co-entrapment of a commercially available antiseptic, PHMB (polyhexamethylene biguanide 4mgmL−1), with EDTA (Ethylen diamine tetra acetic acid, 20mM) in a gelatin gel. The two active compounds act synergistically against bacterial biofilms, but their efficiency is strongly reduced (16-fold) when entrapped inside the 5% gelatin gel, and they weaken the mechanical properties (50-fold) of the gel. Increasing the gelatin concentration to 7% allows for good mechanical properties but large diffusional constraints. An active ephemeral gel, a chemical gel with controlled hydrolysis, was conceived and developed. When the ephemeral gel was solubilized after 48h, PHMB delivery increased, leading to good anti-biofilm activity. The various gels were examined over 24 and 48h of contact with P. aeruginosa and S. aureus biofilms, two types of bacterial biofilms frequently encountered in chronic wounds. The ephemeral gel eradicated the dense biofilms (>6.107CFU·cm−2) produced by either single or mixed strains; a similar efficiency was measured for biofilms from strains of both laboratory and clinical origin. The formulation was then adapted to develop a dressing prototype that is active against biofilms and fulfils the requirements of an efficient wound care system.

Pulmonary delivery of synergistic combination of fluoroquinolone antibiotic complemented with proteolytic enzyme: A novel antimicrobial and antibiofilm strategy

Bacterial resistance remains a major hindrance in treatment with antimicrobial agents. Therefore, we assessed the improved antimicrobial and antibiofilm activity of Levofloxacin (LFX) and Serratiopeptidase (SRP) combinations in in vitro microbiological studies. Further, pharmacodynamic and pharmacokinetic studies of liposomal LFX in combination with SRP (LFX liposome-SRP) were performed in S. aureus infected rats. LFX at sub-MIC with SRP eradicated >90% of the preformed biofilm. The entrapment efficiency of LFX in liposome was >80% and the co-spray dried product had MMAD <5 μm. We observed high LFX concentration in the lung (3.39 μg/ml over 3 h) and AUC/MIC ≥100. In a pharmacodynamic study, untreated infected rat lungs demonstrated higher mRNA expression for inflammatory markers, cytokine levels and microbial load compared to control. Conversely, LFX liposome-SRP significantly abated these adverse repercussions. Histological findings were also in agreement with these observations. Furthermore, our findings corroborate exhibited improved antibiofilm and antimicrobial efficacy of LFX liposome-SRP in treating S. aureus infection.

Stimulated phase-shift acoustic nanodroplets enhance vancomycin efficacy against methicillin-resistant Staphylococcus aureus biofilms.

PurposeBacterial biofilms on the surface of prostheses are becoming a rising concern in managing prosthetic joint infections. The inherent resistant features of biofilms render traditional antimicrobial therapy unproductive and revision surgery outcomes uncertain. This situation has prompted the exploration of novel antimicrobial strategies. The synergy of ultrasound microbubbles and vancomycin has been proposed as an efficient alternative for biofilm eradication. The purpose of this study was to evaluate the anti-biofilm effect of stimulated phase-shift acoustic nanodroplets (NDs) combined with vancomycin.Materials and methodsWe fabricated lipid phase-shift NDs with a core of liquid perfluoropentane. A new phase change mode for NDs incorporating an initial unfocused low-intensity pulsed ultrasound for 5 minutes and a subsequent incubation at 37°C into a 24-hour duration was developed. Methicillin-resistant Staphylococcus aureus (MRSA) biofilms were incubated with vancomycin and NDs under the hybrid stimulation. Biofilm morphology following treatment was determined using confocal laser scanning microscopy and scanning electron microscopy. Resazurin assay was used to quantify bactericidal efficacy against MRSA biofilm bacteria.ResultsNDs treated sequentially with ultrasound and heating at 37°C achieved gradual and substantial ND vaporization and cavitation in a successive process. NDs after stimulation were capable of generating stronger destruction on biofilm structure which was best characterized by residual circular arc margins and more dead bacteria. Furthermore, NDs combined with vancomycin contributed to significantly decreasing the metabolic activity of bacteria in MRSA biofilms (P<0.05).ConclusionPhase-shift acoustic NDs could exert a significant bactericidal effect against MRSA biofilms through a new stimulation mode. Acoustic NDs present advantages over microbubbles for biofilm damage. This anti-biofilm strategy could be used either alone or as an enhancer of traditional antibiotics in the control of prosthetic joint infections.

A Topical Hydrogel with Deferiprone and Gallium-Protoporphyrin Targets Bacterial Iron Metabolism and Has Antibiofilm Activity.

Many infectious diseases are associated with multidrug-resistant (MDR) bacteria residing in biofilms that require high antibiotic concentrations. While oral drug delivery is frequently ineffective, topical treatments have the potential to deliver higher drug concentrations to the infection site while reducing systemic side effects. This study determined the antibiofilm activity of a surgical wound gel loaded with the iron chelator deferiprone (Def) and the heme analogue gallium-protoporphyrin (GaPP), alone and in combination with ciprofloxacin. Activity against MDR Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa, and Acinetobacter johnsonii biofilms was assessed in the colony biofilm and artificial wound model by enumeration of CFU and correlative light/electron microscopy. While Staphylococcus biofilms were equally susceptible to GaPP and Def-GaPP gels (log10 reduction of 3.8 and 3.7, respectively), the Def-GaPP combination was crucial for significant activity against P. aeruginosa biofilms (log10 reduction of 1.3 for GaPP and 3.3 for Def-GaPP). When Def-GaPP gel was combined with ciprofloxacin, the efficacy exceeded the activity of the individual compounds. Def-GaPP delivered in a surgical wound gel showed significant antibiofilm activity against different MDR strains and could enhance the gel's wound-healing properties. Moreover, Def-GaPP indicated a potentiation of ciprofloxacin. This antibiofilm strategy has potential for clinical utilization as a therapy for topical biofilm-related infections.

Prevention of Propionibacterium acnes biofilm formation in prosthetic infections in vitro

The role of Propionibacterium acnes in shoulder arthroplasty and broadly in orthopedic prosthetic infections has historically been underestimated, with biofilm formation identified as a key virulence factor attributed to invasive isolates. With an often indolent clinical course, P acnes infection can be difficult to detect and treat. This study investigates absorbable cements loaded with a broad-spectrum antibiotic combination as an effective preventive strategy to combat P acnes biofilms. P acnes biofilm formation on an unloaded synthetic calcium sulfate (CaSO4) bone void filler cement bead was evaluated by scanning electron microscopy over a period of 14 days. Beads loaded with tobramycin alone or vancomycin alone (as comparative controls) and beads loaded with a vancomycin-tobramycin dual treatment were assessed for their ability to eradicate planktonic P acnes, prevent biofilm formation, and eradicate preformed biofilms using a combination of viable-cell counts, confocal microscopy, and scanning electron microscopy. P acnes surface colonization and biofilm formation on unloaded CaSO4 beads was slow. Beads loaded with antibiotics were able to kill planktonic cultures of 106 colony-forming units/mL, prevent bacterial colonization, and significantly reduce biofilm formation over periods of weeks. Complete eradication of established biofilms was achieved with a contact time of 1 week. This study demonstrates that antibiotic-loaded CaSO4 beads may represent an effective antibacterial and antibiofilm strategy to combat prosthetic infections in which P acnes is involved.