Treatment Of Orthopedic Infections Research Articles

Synergistic use of anti-inflammatory ketorolac and gentamicin to target staphylococcal biofilms

BackgroundWhile antibiotics remain our primary tools against microbial infection, increasing antibiotic resistance (inherent and acquired) is a major detriment to their efficacy. A practical approach to maintaining or reversing the efficacy of antibiotics is the use of other commonly used therapeutics, which show synergistic antibacterial action with antibiotics. Here, we investigated the extent of antibacterial synergy between the antibiotic gentamicin and the anti-inflammatory ketorolac regarding the dynamics of biofilm growth, the rate of acquired resistance, and the possible mechanism of synergy.MethodsControl (ATCC 12600, ATCC 35984) and clinical strains (L1101, L1116) of Staphylococcus aureus and Staphylococcus epidermidis with varying antibiotic susceptibility profiles were used in this study to simulate implant-material associated low-risk and high-risk biofilms in vitro. The synergistic action of gentamicin sulfate (GS) and ketorolac tromethamine (KT), against planktonic staphylococcal strains were determined using the fractional inhibitory concentration measurement assay. Nascent (6 h) and established (24 h) biofilms were grown on 316L stainless steel plates and the synergistic biofilm eradication activity was determined and characterized using adherent bacteria count, minimum biofilm eradication concentration (MBEC) measurement for GS, visualization by live/dead imaging, scanning electron microscopy, gene expression of biofilm-associated genes, and bacterial membrane fluidity assessment.ResultsGentamicin-ketorolac (GS-KT) combination demonstrated synergistic antibacterial action against planktonic Staphylococci. Control and clinical strains showed distinct biofilm growth dynamics and an increase in biofilm maturity was shown to confer further resistance to gentamicin for both ‘low-risk’ and ‘high-risk’ biofilms. The addition of ketorolac enhanced the antibiofilm activity of gentamicin against acquired resistance in staphylococcal biofilms. Mechanistic studies revealed that the synergistic action of gentamicin–ketorolac interferes with biofilm morphology and subverts bacterial stress response altering bacterial physiology, membrane dynamics, and biofilm properties.ConclusionThe results of this study have a significant impact on the local administration of antibiotics and other therapeutic agents commonly used in the prevention and treatment of orthopaedic infections. Further, these results warrant the study of synergy for the concurrent or sequential administration of non-antibiotic drugs for antimicrobial effect.

Switching from intravenous vancomycin to oral antibiotics reduces adverse events in a retrospective cohort of outpatients with orthopedic infections.

Vancomycin is frequently used for prolonged courses in treating osteoarticular infections despite a high rate of adverse drug events (ADE). The objective of this study was to evaluate the safety and effectiveness of transitioning to oral therapy compared to continuing parenteral vancomycin in patients with orthopedic infections. We conducted a single-center, retrospective cohort study of patients with orthopedic infections discharged on parenteral vancomycin with a planned duration of at least four weeks. We compared rates of ADE while on vancomycin to rates of ADE after switching to an oral regimen. As a secondary analysis, we compared unplanned hospital readmission within 60 days and treatment failure at one year between patients who were transitioned to oral antibiotics within four weeks of vancomycin initiation and those that were not. Two hundred twenty-eight patients met inclusion criteria. Vancomycin was associated with significantly greater toxicity compared to oral regimens. Fifty-one patients had an adverse event while on vancomycin (5.87 ADE per 1000 patient-days) while 9 patients had an adverse event on oral therapy (1.49 ADE per 1000 patient-days) (Rate difference 4.39 per 1000 patient days, 95% CI: 2.52 to 6.26 events per 1000 patient-days). In proportional hazards analysis, transition to an oral antibiotic regimen was independently associated with a lower rate of ADE (aHR 0.12, 95% CI: 0.02-0.86). Forty-one patients (18%) were transitioned to oral therapy within four weeks; these patients did not have an increased rate of unplanned readmission (12.2% vs 17.1%) or treatment failure (17.1% vs 21.9%). Patients transitioned to oral therapy within 4 weeks of discharge had significantly fewer adverse events and similar incidences of one-year treatment failure compared to patients maintained on parenteral vancomycin. Substituting oral antibiotics for parenteral vancomycin is a potential strategy to minimize vancomycin toxicity during the treatment of orthopedic infections.

In vitro cytocompatibility of antibacterial silver and copper-doped bioactive glasses

Fighting the formation of bacterial biofilm and simultaneously providing a bioactive environment for bone regeneration during the treatment of orthopedic infections is one of the greatest challenges in surgery. Moreover, the major global threat of rapidly increasing antimicrobial resistance calls for non-antibiotic alternatives. Bioactive glasses doped with antibacterial metal ions silver (Ag), or copper (Cu), offer a potential solution. However, an added challenge is the cytocompatibility of these antimicrobial biomaterials, which could be compromised due to the possible cytotoxic effect of the dopants.This work evaluates the cytocompatibility of two bioactive glasses, SBA2 and SBA3, either doped with Ag- (Ag-SBA2) or Cu-ions (Cu-SBA3) via ion-exchange process. The viability, proliferation, and morphology of human adipose stem cells (hASCs) were evaluated using different culture conditions: i) direct culture on glass discs, with and without pre-incubation, and ii) in medium containing glass dissolution byproducts. The release kinetics of the doped ions was evaluated in α-MEM and during cell culture. Moreover, the effect of protein adsorption on the cell response was studied by introducing a layer of fibronectin on the glass discs before direct culture with hASCs.Ag-SBA2 and Cu-SBA3 both initially inhibited the hASC viability in direct cell culture. However, cells remain viable with healthy morphology when cultured directly on pre-treated discs, or indirectly with the glass dissolution byproducts. This suggests that the cytotoxicity effect seems to arise from the contact toxicity between the cells and the material surface. Fibronectin adsorption significantly improved the cytocompatibility of Ag-SBA2, while Cu-SBA3 requires further optimization. To conclude, Ag-SBA2, through its contact toxicity, has the potential for treating early infection, without compromising long-term cytocompatibility and bioactivity. However, further optimization of the Cu-SBA3 glass is needed due to its cytotoxicity towards hASCs.

Comparison of three methods for assessment of drug elution: In vitro elution of gentamicin from a collagen-based scaffold

In vitro drug elution experiments are commonly performed when evaluating the fitness of drug delivery devices for in vivo use. Evaluation of drug elution characteristics spans many drug delivery applications including local delivery of antimicrobials and chemotherapeutics, and is of particular interest for prevention and treatment of orthopedic infections. Despite widespread utility, there is little agreement on methodology to perform such studies, and there are recognized limitations in published works. We evaluated three of the most commonly reported in vitro drug elution methods. We utilized a commercially available collagen matrix (Fibro-Gide®, Geistlich) and an antibiotic that is widely used for local antimicrobial therapy (gentamicin). The protocols used are: 1. complete replacement of media and washing of device, 2. complete replacement of media without washing, or 3. partial replacement of media. The results show statistically significant differences in elution characteristics among the three methods utilizing this delivery vehicle and drug. These results may provide the framework for moving toward more consistent methodology for in vitro elution experiments and address certain acknowledged limitations in the literature.

Influence of Antibiotic-Loaded Acrylic Bone Cement Composition on Drug Release Behavior and Mechanism.

Periprosthetic joint infection (PJI) is a devastating complication after total joint replacement with considerable morbidity and large economic burdens. Antibiotic-Loaded Bone Cement (ALBC) has been developed as a valuable tool for local administration and is becoming one of the most effective methods for the prevention and treatment of orthopedic infections. Controlling antibiotic release from ALBC is critical to achieve effective infection control, however, the antibiotic elution rates are generally low, and the mechanisms are poorly understood. Thus, the present study aims to investigate the effects of the basic acrylic bone cement components, including liquid/powder (monomer-to-polymer) ratios, radiopacifier, initiator, and doses of antibiotics on the porosity, antibiotic elution rates and mechanical properties of polymethylmethacrylate (PMMA) based ALBC. The obtained results from the in vitro studies suggested that a reduction in the liquid/powder ratio and an increase in the radiopacifier ratio and gentamicin doses led to increased porosity and release of antibiotic, while the initiator ratio exerted no effect on elution rates. In conclusion, we hope that by varying the composition of ALBC, we could considerably enhance the antibiotic elution rates by increasing porosity, while maintaining an adequate mechanical strength of the bone cements. This finding might provide insights into controlling antibiotic release from ALBC to achieve effective infection control after total joint replacement surgery.

Donepezil hydrochloride as a novel inducer for osteogenic differentiation of mesenchymal stem cells on PLLA scaffolds in vitro.

Over the past decades, bone defects caused by illness or trauma have been the most common traumatic injuries in humans and treatment of orthopedic infections has always been a serious challenge to experts in the world. In this project, poly L-lactic acid (PLLA) nanofibrous scaffolds were synthesized as a nontoxic, eco-friendly, and cost-effective scaffold by the electrospinning technique. Then, the impact of PLLA on the cell proliferation and osteogenic differentiation of human mesenchymal stem cells (hMSCs) was assayed in the presence and absence of donepezil hydrochloride (DH) which was prescribed in patients with Alzheimer's disease. Also, hMSCs were seeded on PLLA scaffold in the presence (PLLA-DH) and absence of 1μg mL-1 of DH under osteogenic induction media. Osteogenic differentiation of hMSCs was assessed by specific bone-related tests including alkaline phosphatase (ALP) activity, Alizarin red and von Kossa staining, calcium content assay. Also, Osteocalcin and osteopontin were evaluated as osteogenic proteins as well as ALP, osteonectin, osteocalcin, collagen type I (Col-I) and Runx2 as osteogenic genes via immunocytochemistry (ICC) and Real-time PCR analyses. The obtained data showed the higher ALP enzyme activity and biomineralization, more intensity during von Kossa staining as well as the increase in the expression rate of osteogenic related gene and protein markers in differentiated hMSCs on PLLA-DH. In conclusion, the present study revealed that the combination of PLLA scaffold with DH provides a scope to develop a suitable matrix in bone tissue engineering applications.

Irrigation Fluids Used for the Prevention and Treatment of Orthopaedic Infections.

➤ Intrawound irrigation is a mainstay in the prevention and treatment of surgical site infections.➤ There are 3 components of irrigation: delivery method, volume, and type of solution (with and without additives).➤ A low-pressure delivery system for a 1 to 9-L volume of solution should be used to irrigate wounds, with a greater volume indicated in the setting of contaminated or infected wounds.➤ Operative irrigation solutions are frequently supplemented with the addition of surfactants, antibiotics, or antiseptics.➤ There is limited evidence with regard to the optimal antiseptic or whether antiseptics confer any advantage. Current literature suggests that surfactants and antibiotics should be avoided.➤ To date, most studies on irrigation solutions in orthopaedics are retrospective, necessitating the organization of prospective randomized controlled trials to guide future evidence-based decisions.

Antibiotic-Loaded Polymethylmethacrylate Beads and Spacers in Treatment of Orthopedic Infections and the Role of Biofilm Formation.

Polymethylmethacrylate (PMMA) also referred as (acrylic) bone cement is a non-degradable biomaterial that has been used in clinical orthopedic practice for several decades. PMMA can be used in a plain formulation, but is often used in an antibiotic-loaded formulation in (primary and revision) arthroplasty and in treatment of orthopedic infections as prosthetic joint infections (PJI) and chronic osteomyelitis. In treatment of PJIs antibiotic-loaded PMMA is often used as a carrier material for local antibiotic delivery in addition to treatment with systemic antibiotics. In this case, the antibiotic-loaded PMMA is often used as a spacer or as a bead chain. Since the introduction of PMMA as an antibiotic carrier there is a tremendous amount of scientific and clinical papers published, which studied numerous different aspects of antibiotic-loaded PMMA. This paper will review the research regarding basic principles of antibiotic-loaded PMMA as mechanism of action, antibiotic-release capacities, choice of antibiotics and influences on mechanical properties of PMMA. Subsequently, concerns regarding the application of antibiotic-loaded PMMA, biofilm formation, antibiotic resistance and local or systemic toxicity will be discussed. In addition to these subjects, the role of antibiotic loaded PMMA in clinical treatment of PJIs and chronic osteomyelitis is discussed in the final part of this paper.

Biodegradable Electrosprayed NPs as Drug Carriers for Optimal Treatment of Orthopaedic Infections

Abstract The possibility of replacing the damaged joint by an artificial (hip replacement) is one of the most important achievements of the orthopaedic science because it enables the person suffering from osteoarthritis to regain a normal life. However, infections that can be created after an implantation are one of the major complications that can lead to implant failure. Therefore, a preliminary study of vancomycin drug loaded Polycaprolactone (PCL) nanoparticles were created via Electrospraying Process, making it a promising nanovehicle to prevent and treat orthopedic implant-associated infections. Scanning Electron Microscopy (SEM) measurements confirmed the successful fabrication of these structures. Finally, drug release kinetics was established to observe the sustained release of the drug and degradation studies were performed in order to evaluate the mass loss of polymers.

Antibiotic stability over six weeks in aqueous solution at body temperature with and without heat treatment that mimics the curing of bone cement

ObjectivesThermal stability is a key property in determining the suitability of an antibiotic agent for local application in the treatment of orthopaedic infections. Despite the fact that long-term therapy is a stated goal of novel local delivery carriers, data describing thermal stability over a long period are scarce, and studies that avoid interference from specific carrier materials are absent from the orthopaedic literature.MethodsIn this study, a total of 38 frequently used antibiotic agents were maintained at 37°C in saline solution, and degradation and antibacterial activity assessed over six weeks. The impact of an initial supplementary heat exposure mimicking exothermically curing bone cement was also tested as this material is commonly used as a local delivery vehicle. Antibiotic degradation was assessed by liquid chromatography coupled to mass spectrometry, or by immunoassays, as appropriate. Antibacterial activity over time was determined by the Kirby-Bauer disk diffusion assay.ResultsThe heat exposure mimicking curing bone cement had minimal effect on stability for most antibiotics, except for gentamicin which experienced approximately 25% degradation as measured by immunoassay. Beta-lactam antibiotics were found to degrade quite rapidly at 37°C regardless of whether there was an initial heat exposure. Excellent long-term stability was observed for aminoglycosides, glycopeptides, tetracyclines and quinolones under both conditions.ConclusionsThis study provides a valuable dataset for orthopaedic surgeons considering local application of antibiotics, and for material scientists looking to develop next-generation controlled or extended-release antibiotic carriers.Cite this article: E. Samara, T. F. Moriarty, L. A. Decosterd, R. G. Richards, E. Gautier, P. Wahl. Antibiotic stability over six weeks in aqueous solution at body temperature with and without heat treatment that mimics the curing of bone cement. Bone Joint J 2017;6:296–306. DOI: 10.1302/2046-3758.65.BJR-2017-0276.R1.

Deactivation of Palacos R Bone Cement with the Addition of Rifampin Antibiotic Powder An In-Vivo Experience -Case Report

Use of antimicrobial impregnated polymethylmethacrylate (PMMA) bone cement in the treatment of orthopaedic infections is widely accepted.1 Antibiotic powder is routinely added to PMMA, and formed into beads or spacers when treating infected bone or periprosthetic infections. Antibiotics placed into the PMMA elute via a water diffusion process.2 This results in high local doses of the antimicrobial agent with reduced systemic toxicity.3 Two stage reimplantation protocols utilizing antibiotic loaded PMMA cement generally provide the highest rates of successful treatment.4,5 With the increasing number of resistant organisms, success of this treatment protocol requires antimicrobial therapy targeted at the specific organism found. There exists a great deal of data on the use of certain antimicrobial agents in PMMA cement.1,6,7 However, there are few published reports of the addition of rifampin. This is the first clinical report on the failure of Palacos® R cement (Heraeus Kulzer GmbH, Wehrheim, Germany) to set when rifampin is added.

‘To bead or not to bead?’ Treatment of osteomyelitis and prosthetic joint-associated infections with gentamicin bead chains

Gentamicin-containing polymethylmethacrylate (PMMA) beads are frequently used to prevent and treat orthopaedic infections. The beads are typically inserted to fill anatomical defects secondary to surgical debridement. Local gentamicin use results in low serum levels whilst achieving high concentrations at the site of infection. However, a systematic review of the available literature showed that, despite these theoretical advantages, no prospective study has thus far proven gentamicin-containing PMMA beads to be effective in treating orthopaedic infections. Available studies are based on small patient numbers and do not show significantly better results when local and parenteral antibiotics are combined compared with systemic therapy alone. These poor results may be explained partially by reduced aminoglycoside efficacy when biofilms or gentamicin-resistant bacteria are present. Moreover, little is known regarding the potential side effects of gentamicin-containing beads. In this paper, the pros and cons regarding the use of gentamicin-containing PMMA beads are discussed. It is concluded that more well-executed, prospective studies are needed to settle the discussion on the use of gentamicin-containing beads in the treatment of orthopaedic infections.

Oral Agents for the Treatment of Orthopedic Infections Caused by Methicillin-resistant Staphylococci

Oral Agents for the Treatment of Orthopedic Infections Caused by Methicillin-resistant Staphylococci

Enhancement of antibiotic elution from acrylic bone cement

Antibiotic-loaded acrylic bone cement is a well-established tool in the prophylaxis and treatment of orthopedic infections. Numerous studies about its pharmacokinetic properties have demonstrated that only a small part of the incorporated antibiotic amounts can be released, mostly over the first 8-10 weeks. Therefore, in the past 10 years, several attempts have been made for enhancement of the drug elution from bone cement. This article reviews this experience and pays special attention on biantibiotic combinations, additives other than antimicrobial agents, as well as the effect of ultrasound on the antibiotic elution characteristics.

Does Antibiotic Elution From PMMA Beads Deteriorate after 1-year Shelf Storage?

Antibiotic-impregnated polymethylmethacrylate beads are widely used as an adjunct in the treatment of orthopaedic infections. Because there is no commercially available bead in the United States, surgeons must manufacture bead sets at the time of implantation. This can be time consuming and wasteful. We hypothesized antibiotic-impregnated beads would maintain consistent elution for up to 1 year after manufacturing and storage. Tobramycin-impregnated antibiotic beads were manufactured using a bead mold. The antibiotic was either hand-mixed into the polymethylmethacrylate powder (1.2 g/40 g) or came premixed from the factory (1 g/40 g). Packages of beads were gas-sterilized and stored at room temperature. Beads were tested at 0, 1, 2, 3, 6, and 12 months. Antibiotic levels in the eluent from each day of the month were measured. We were unable to detect any difference in the amount of antibiotic elution between beads tested immediately after manufacture and beads manufactured and stored for 6 or 12 months. Beads with hand-mixed antibiotics eluted higher levels of antibiotics than the beads prepared with factory-mixed antibiotics. We conclude antibiotic beads can be made, sterilized, and used after 1 year of storage with no deleterious effect on antibiotic elution characteristics.

Treatment of orthopedic infections caused by resistant staphylococci

During 1999-2005 we treated 15 patients with linezolid for relevant infections of locomotion apparatus (7 cases with endoprosthesis infection, 5x osteomyelitis and 3x another infection). With the exception of one case the antibiotic therapy was always combined with appropriate surgical intervention. Average period of linezolid administration was 26 d; linezolid was applied from the beginning intravenously on average for 10 d, and then orally for 16 d (average). There were no undesirable effects in the file. Success rate reached 86.6%. MRSA strains were proved by standard methods: growth on Mueller-Hinton agar with increased concentration of NaCl and 2 mg/L of oxacilline, and measuring inhibitory zones around cephoxitine disk. The sensitivity to other antibiotics was specified by disk-diffusion test; that to linezolid was verified by E-test. Linezolid represents a medical reserve for the treatment of multiresistant Gram-positive infections or for emergencies, when allergy onset, high toxicity risk, intolerance, etc. do not allow to use other, in vitro effective, antibiotics.

Antibiotic‐containing hyaluronic acid gel as an antibacterial carrier: Usefulness of sponge and film‐formed HA gel in deep infection

We have developed a novel bioabsorbable antibacterial carrier using hyaluronic acid (HA) gel for prevention and treatment of orthopedic infections. In this study, we investigated the in vivo antibacterial effects of two forms of this new material, an HA gel sponge and an HA gel film. A titanium cylinder was inserted into the intramedullary cavity of each rabbit femur, along with an HA gel sponge or HA gel film containing antibiotics. The HA gel sponge contained gentamycin, vancomycin, tobramycin, or minomycin. The HA gel film contained gentamycin or vancomycin. After 0, 7, and 14 days, the rabbit bone marrow was collected, and the antibacterial activity of the HA gel was determined by agar diffusion test. As a control, we used Septocoll, a commercially available antibacterial carrier. Both the HA gel sponge and HA gel film exhibited antibacterial activity. The present results indicate that HA gel containing antibiotics is a clinically useful bioabsorbable antibacterial carrier.

Role of linezolid in the treatment of orthopedic infections

Gram-positive organisms, particularly staphylococci and streptococci, are responsible for the majority of bone and joint infections. The rising incidence of antimicrobial resistance among Staphylococcus aureus, coagulase-negative staphylococci and enterococci means that novel antibiotics with unique mechanisms of antimicrobial activity are needed, especially in orthopedic infections. Linezolid is the first of the oxazolidinones, a new class of antibacterial agents particularly effective against Gram-positive infections including methicillin- and vancomycin-resistant strains. With an excellent oral bioavailability and acceptable safety profile, linezolid offers a valuable alternative to more traditional therapies, such as glycopeptides. No large randomized trials have been published on its use in patients with orthopedic infections, but early results are encouraging. Reported adverse events, especially bone marrow suppression and optic neuropathy seen with prolonged administration, mean that treatment of such patients must be undertaken with careful follow-up of laboratory tests. Until now, little resistance has been reported.

Treatment of Gram-positive bone and joint infection: authors' response

Sir, We have noted with interest the points made by Frippiat et al. and make the following comments. We have not stated that the newer quinolones should not be considered for treatment of Gram-positive bone and joint infections. We agree that this group of antibiotics offers an attractive alternative to standard parenteral therapy because of their potency against Gram-positive pathogens and good bioavailability, but caution that the safety of the newer quinolones in long-term use is not yet established. There is a lack of clinical experience and data regarding long-term outcome with these agents treating chronic infections in man, compared with older fluoroquinolones. Quinolone resistance is increasing; the development of resistance to the new fluoroquinolones in Gram-positive organisms has been reported in a pharmacodynamic study, and Frippiat et al. also refer to a clinical case where resistance developed in one of seven of their patients treated for Grampositive prosthetic joint infection. In agreement with Frippiat et al., our advice to clinicians is that until there are more clinical data available, the addition of a second antibiotic (often rifampicin) should be considered when using a quinolone to treat deep infection, over a prolonged duration. The optimum dose of rifampicin for use as a second agent in treatment of orthopaedic infection has not been identified, although bone penetration studies have suggested that 600 mg twice daily will give optimal bone concentrations when compared with 300 mg twice daily or 600 mg daily. We usually recommend a dose between 300–600 mg twice daily, depending on the size of the patient and the causal pathogen. This dose is comparable to the dose of 10–20 mg/kg/day suggested by Frippiat et al. Finally, we agree that whereas linezolid is an attractive option for oral treatment of MRSA and other multi-resistant Gram-positive infection, it is not recommended for use in chronic infection, such as osteomyelitis, due to the lack of safety data when used for >28 days. We have not yet encountered optic neuropathy in association with prolonged linezolid treatment, but have observed thrombocytopenia in some patients, a recognized side effect, and advise clinicians to monitor full blood count weekly when prescribing linezolid for both inpatients and outpatients. References

Antimicrobial efficacy of a new antibiotic-loaded poly(hydroxybutyric-co-hydroxyvaleric acid) controlled release system

Failure of orthopaedic devices, mainly femoral hip replacements, due to infection is of increasing medical importance. There is a need for improved antibiotic delivery systems in the treatment of orthopaedic infections and here we have evaluated polyhydroxyalkanoate formulations for their suitability as a constant delivery system for gentamicin. Gentamicin was incorporated in poly(hydroxybutyric-co-hydroxyvalerate) (PHBV) with 8% or 12% hydroxyvalerate (HV) content at 2:1 or 5:1 (weight to weight) ratio. In conjunction with an elution study, a scanning electron microscopy and a porosity study were carried out to explore physical characteristics of the complexes before and after the leaching effect. The antibacterial effectiveness of the complexes was analysed in a bacterial adhesion assay using clinical isolates of Staphylococcus haemolyticus and Staphylococcus aureus. In addition, the polymers were exposed to pooled human blood to test their biocompatibility in both static and dynamic environments. We have shown that increasing the HV content from 8% to 12% leads to a faster release of the integrated antibiotic. An increase in antibiotic content enhanced the homogeneity while decreasing the permeability of the complexes and reducing the release rate. A significant reduction in the number of the adherent S. aureus and gentamicin-resistant S. haemolyticus within a 48 h exposure to our formulations confirmed the effectiveness of the PHBV/gentamicin complexes. Finally, these formulations did not alter the haemodynamics of the pooled blood samples after an extended period of time. Taken together, the PHBV/gentamicin formulations may prove to be effective preventive therapeutic modalities in implant-related Staphylococcus infections.