Treatment Of Bone Infections Research Articles

519 Outcomes of Management with Ilizarov Frames in Bone Infection: An Observational Study

Abstract Aim The successful treatment and eradication of bone infection requires a multifaceted approach and may recur even after excision if resultant bone void is not managed effectively. This paper aims to review the clinical effectiveness of antibiotic-impregnated bone void filler and current empirical antibiotic guidelines. Method We report a retrospective study of 18 patients with chronic osteomyelitis following injury or surgery managed via Ilizarov Ring Fixator (IRF). All patients were managed by IRF stabilisation procedures with debridement, microbiological sampling, and bone void filling with antibiotic-impregnated biocomposite material, in addition to culture-specific systemic antimicrobial therapy. Results Patients were followed up for a mean of 15.9 months. Infection was eradicated in 94.1% of patients in a grossly comorbid demographic. Comorbidities associated with increased risk of osteomyelitis were noted in 72.2% of patients. Anaerobic bacteria were identified in culture for four (22.2%) of the 18 patients. Conclusions We detected a higher than suspected growth of anaerobes in our samples, suggesting the need for metronidazole in empirical antibiotic treatment. This study would suggest that the use of STIMULAN® may be preferable in this National Health Service from a cost-effect perspective, as our results are comparable to those using other bone void fillers.

Investigations on the effect of swift heavy silicon ion irradiation on hydroxyapatite

The effect of swift heavy silicon ion irradiation on hydroxyapatite prepared by hydrothermal technique was analyzed. The physical and biological properties were studied using G1XRD, Micro-Raman, photoluminescence, AFM, SEM, EDX, in vitro bioactivity, antimicrobial activity and drug release. When compared with pristine the crystallinity increases with an increase in fluence. Slight reduction in crystallinity was noted for irradiated samples at higher fluence (1×1013 and 1×1014 ions/cm2) than lower fluence (1×1012 ions/cm2). After irradiation the υ4 O-P-O asymmetric bending mode peak at 583 cm−1 disappeared. The PL intensity increases with an increase in fluence and it had become narrow and showed red shift. This suggests the material could find application as phosphors. The enhancement in band gap was attained for irradiated samples than Hpris (5.38–5.5 eV). AFM studies revealed the enhancement of roughness, particle size and pores on irradiation. SEM exposed the creation of pores along with an increase in porosity (2 µm to 30 µm). Formation of platy crystals was noted for 1×1013 ions/cm2 sample. In vitro bioactivity results with the formation of spherical (2 µm) apatite deposition along with the presence of interconnected pores (2–10 µm) which could enhance osteointegration and osteoconduction. In addition, Ca/P ratio was found to increase after soaking in SBF. Initial burst release followed by sustained release was obtained upto 45 h. Therefore it could assist in the treatment of bone and joint infection. Hence, SHI had improved the material to be used in biomedical field as an implant due to its enhanced properties such as crystallinity, pore size, surface roughness, PL intensity, antimicrobial activity, drug release and bioactivity.

Correction to: Hydroxyapatite-based antibacterial bio-nanomaterials: an insight into the synthesis using mussel shell as a calcium source, physicochemical properties, and nanoindentation characteristics

We report the synthesis of hydroxyapatite (HAp)-based antibacterial biomaterials using a mussel shell as a calcium source and by the integration of silver ions via a wet precipitation method. The silver doping at 2 mol% can provide silver-doped carbonated HAp while at 10 mol% can offer silver-doped carbonated HAp/silver oxide nanocomposite. The synthesized Ag-integrated samples exhibit the H (263–903Mpa) and E (0.96–3.31GPa) almost similar to cancellous bone with good antibacterial inhibition on S. aureus (15 ± 02 mm) and E. coli (26 ± 02 mm) growth. Hence, they can be a potential precursor to make bone fillers for the treatment of bone infections.

Treatment of bone and periprosthetic infections with bacteriophages : Asystematic review

HintergrundDie Behandlung von Knochen- und Protheseninfektionen bleibt trotz moderner Behandlungskonzepte mit interdisziplinärem Therapieansatz schwierig und weitere Maßnahmen zur Verbesserung des Behandlungsergebnisses sind wünschenswert. Präklinischen Studien liefern ein vielversprechendes Bild der Wirksamkeit von Bakteriophagen zur Behandlung von Knochen- und Protheseninfektionen.Ziel der ArbeitDie vorliegende Arbeit gibt eine systematische Übersicht über die klinische Anwendung von Bakteriophagen zur Behandlung von Knochen- und Protheseninfektionen.Material und MethodenEine systematische Suche wurde in PubMed zur Identifikation von primären klinischen Daten zur Anwendung der Phagentherapie bei Patienten mit Knochen- und Protheseninfektion durchgeführt.ErgebnisseElf Studien wurden eingeschlossen, bestehend aus 8 Fallberichten und 3 Fallserien. Indikationen der Phagentherapie waren periprothetische Infektionen (n = 12, 52,2 %), frakturassoziierte Infektionen (n = 9, 39,1 %), Osteomyelitis (n = 1, 4,4 %) und eine Iliosakralgelenkinfektion nach Zementaugmentation einer Metastase (n = 1, 4,4 %). Die Interventionen waren heterogen, Phagen wurden intravenös verabreicht, intraoperativ ins Gelenk injiziert, intraoperativ lokal angewendet oder über Drainagen appliziert. In Kombination mit Antibiotikatherapie konnte eine vollständige Infekteradikation bei 18 Patienten (78,3 %) erreicht werden. Bei 91,3 % der Patienten wurden keine Nebenwirkungen berichtet.SchlussfolgerungBakteriophagen sind eine vielversprechende Behandlungsmethode von Knochen- und Protheseninfektionen in Kombination mit einer Antibiotikatherapie. Zukünftige klinische Studien mit höherem Evidenzgrad werden benötigt, um eine erfolgreiche Translation der Bakteriophagentherapie in die klinische Praxis weiter zu etablieren.

Antibacterial and osteogenic activities of clindamycin-releasing mesoporous silica/carboxymethyl chitosan composite hydrogels.

Conventional treatment of jaw bone infection is often ineffective at controlling bacterial infection and enhancing bone regeneration. Biodegradable composite hydrogels comprised of carboxymethyl chitosan (CMCS) and clindamycin (CDM)-loaded mesoporous silica nanoparticles (MCM-41), possessing dual antibacterial activity and osteogenic potency, were developed in the present study. CDM was successfully loaded into both untreated and plasma-treated MCM-41 nanoparticles, denoted as (p)-MCM-41, followed by the incorporation of each of CDM-loaded (p)-MCM-41 into CMCS. The resulting CDM-loaded composite hydrogels, (p)-MCM-41-CDM-CMCS, demonstrated slow degradation rates (about 70% remaining weight after 14-day immersion), while the CDM-free composite hydrogel entirely disintegrated after 4-day immersion. The plasma treatment was found to improve drug loading capacity and slow down initial drug burst effect. The prolonged releases of CDM from both (p)-MCM-41-CDM-CMCS retained their antibacterial effect against Streptococcus sanguinis for at least 14 days in vitro. In vitro assessment of osteogenic activity showed that the CDM-incorporated composite hydrogel was cytocompatible to human mesenchymal stem cells (hMSCs) and induced hMSC mineralization via p38-dependent upregulated alkaline phosphatase activity. In conclusion, novel (p)-MCM-41-CDM-CMCS hydrogels with combined controlled release of CDM and osteogenic potency were successfully developed for the first time, suggesting their potential clinical benefit for treatment of intraoral bone infection.

Intravenous fosfomycin for the treatment of patients with bone and joint infections: a review

ABSTRACT Introduction Fosfomycin is a wide spectrum bactericidal antibiotic with a unique mode of action, low toxicity, and good penetration in tissues with deep-seated infections, including bone and joint infections. Areas covered Data were extracted from 19 published articles. Three hundred and sixty-five patients, with broad age range, received intravenous fosfomycin for the treatment of bone and joint infections (including arthritis, acute and chronic osteomyelitis, discitis, periprosthetic joint infection). Fosfomycin was given as part of a combination antimicrobial therapy in the majority of patients (93.7%). The dosage of fosfomycin ranged from 4 g/day (in one case) to 24 g/day. The dosage of fosfomycin, in some cases, mostly pediatric, was calculated based on body weight, ranging from 50 mg/kg/day to 250 mg/kg/day. The duration of fosfomycin treatment ranged from a couple of days up to 3 months. The most common isolated pathogen was Staphylococcus aureus (38.9%). Three hundred patients (82.2%) were successfully treated. Fosfomycin was well tolerated, as few patients developed mild adverse events, mostly gastrointestinal discomfort, hypernatremia, skin rash, and neutropenia. Expert opinion The available data suggests that intravenous fosfomycin may be beneficial for the treatment of patients with bone and joint infections, especially when used as part of a combination antibiotic regimen.

Construction of Antimicrobial Material-Loaded Porous Tricalcium Phosphate Beads for Treatment of Bone Infections.

Due to low success rates of antibiotic therapy in most osteomyelitis diseases, continuous efforts have been made to fabricate local delivery systems with high antimicrobial effects. Here, we reported a kind of ε-polylysine(PL)/Ag-loaded porous tricalcium phosphate (TCP) bead instead of antibiotics as local delivery systems for the treatment of Staphylococcus aureus-caused osteomyelitis. Such local delivery systems were prepared by the fabrication of porous TCP beads at first and then the loading of Ag and PL in turn into porous TCP beads via in situ Ag-doping and layer-by-layer methods. In vitro experiments demonstrated that the release of PL and Ag was controllable. Especially, the release dosage of Ag could be controlled to be less than 0.05 ppm 28 days later. The surface coating of PL improved the cytocompatibility and antibacterial activity of local delivery systems. In vivo experiments demonstrated that the Ag/PL-loaded porous TCP beads displayed strong antibacterial activity and good osteoconductivity, and the combination of Ag and PL was better than the use of single antibacterial materials to treat S. aureus-caused osteomyelitis. The implantation of Ag into the infected marrow had low toxicity because Ag has been integrated into the TCP grains, which could be absorbed in marrow. Therefore, the Ag/PL-loaded porous TCP beads presented potential for treating osteomyelitis, especially sequestrum-debrided osteomyelitis.

Antibacterial and antioxidant activity of cinnamon essential oil-laden 45S5 bioactive glass/soy protein composite scaffolds for the treatment of bone infections and oxidative stress

This study aimed to fabricate cinnamon essential oil (CO)-laden 45S5 bioactive glass (BG)/soy protein (SP) scaffolds exhibiting antioxidant and antibacterial activity. In this regard, 45S5 BG-based scaffolds were produced by the foam replica method, and subsequently the scaffolds were coated with various concentrations of CO (2.5, 5 and 7 (v/v) %) incorporated SP solution. Scanning electron microscopy images revealed that the CO-laden SP effectively attached to the 45S5 BG scaffold struts. The presence of 45S5 BG, SP and CO was confirmed using Fourier transform infrared spectroscopy. Compressive strength results indicated that SP based coatings improved the scaffolds' mechanical properties compared to uncoated BG scaffolds. The loading efficiency and releasing behaviour of the different CO concentrations were tested by gas chromatography-mass spectroscopy and UV–Vis spectroscopy. The results showed that CO incorporated scaffolds have controlled releasing behaviour over seven days. Furthermore, the coating on the scaffold surfaces slightly retarded, but it did not inhibit, the in vitro bioactivity of the scaffolds. Moreover, the antioxidant and antibacterial activity of CO was studied. The free radical scavenging activity measured by DPPH was 5 ± 1, 41 ± 3, 44 ± 1 and 43 ± 1 % for BGSP, CO2.5, CO5 and CO7, respectively. The antioxidant activity was thus enhanced by incorporating CO. Agar diffusion and colony counting results indicated that the incorporation of CO increased the antibacterial activity of scaffolds against S. aureus and E. coli. In addition, cytotoxicity of the scaffolds was investigated using MG-63 osteoblast-like cells. The results showed that the BG-SP scaffold was non-toxic under the investigated conditions, whereas dose-dependent toxicity was observed in CO-laden scaffolds. Considered together, the developed phytotherapeutic agent laden 45S5 BG-based scaffolds are promising for bone tissue engineering exhibiting capability to combat bone infections and to protect against oxidative stress damage.

Novel calcium phosphate cement with biofilm-inhibition and platelet lysate delivery to enhance osteogenesis of encapsulated human periodontal ligament stem cells

Osteomyelitis is caused by Staphylococcus aureus (S. aureus), with associated progressive bone loss. This study developed for the first time a calcium phosphate cement (CPC) for delivery of doxycycline (DOX) and human platelet lysate (hPL) to fight against S. aureus infection and enhance the osteogenesis of human periodontal ligament stem cells (hPDLSCs). Chitosan-containing CPC scaffolds were fabricated in the absence (CPCC) or presence of DOX (CPCC+DOX). In addition, hPL was encapsulated in alginate microbeads and incorporated into CPCC+DOX (CPCC+DOX+ hPL). Flexural strength of CPCC+DOX + hPL was (5.56 ± 0.55) MPa, lower than (8.26 ± 1.6) MPa of CPCC+DOX (p < 0.05), but exceeding the reported strength of cancellous bone. CPCC+DOX and CPCC+DOX + hPL exhibited strong antibacterial activity against S. aureus, reducing biofilm CFU by 4 orders of magnitude. The hPDLSCs encapsulated in microbeads were co-cultured with the CPCs. The hPDLSCs were able to be released from the microbeads and showed a high proliferation rate, increasing by about 8 folds at 14 days for all groups. The hPL was released from the scaffold and promoted the osteogenic differentiation of hPDLSCs. ALP activity was 28.07 ± 5.15 mU/mg for CPCC+DOX + hPL, higher than 17.36 ± 2.37 mU/mg and 1.34 ± 0.37 mU/mg of CPCC+DOX and CPCC, respectively (p < 0.05). At 7 days, osteogenic genes (ALP, RUNX2, COL-1, and OPN) in CPCC+DOX + hPL were 3–10 folds those of control. The amount of hPDLSC-synthesized bone mineral with CPCC+DOX + hPL was 3.8 folds that of CPCC (p < 0.05). In summary, the novel CPC + DOX + hPL-hPDLSCs scaffold exhibited strong antibacterial activity, excellent cytocompatibility and hPDLSC osteogenic differentiation, showing a promising approach for treatment and prevention of bone infection and enhancement of bone regeneration.

Development of Bisphosphonate-Conjugated Antibiotics to Overcome Pharmacodynamic Limitations of Local Therapy: Initial Results with Carbamate Linked Sitafloxacin and Tedizolid.

The use of local antibiotics to treat bone infections has been questioned due to a lack of clinical efficacy and emerging information about Staphylococcus aureus colonization of the osteocyte-lacuno canalicular network (OLCN). Here we propose bisphosphonate-conjugated antibiotics (BCA) using a “target and release” approach to deliver antibiotics to bone infection sites. A fluorescent bisphosphonate probe was used to demonstrate bone surface labeling adjacent to bacteria in a S. aureus infected mouse tibiae model. Bisphosphonate and hydroxybisphosphonate conjugates of sitafloxacin and tedizolid (BCA) were synthesized using hydroxyphenyl and aminophenyl carbamate linkers, respectively. The conjugates were adequately stable in serum. Their cytolytic activity versus parent drug on MSSA and MRSA static biofilms grown on hydroxyapatite discs was established by scanning electron microscopy. Sitafloxacin O-phenyl carbamate BCA was effective in eradicating static biofilm: no colony formation units (CFU) were recovered following treatment with 800 mg/L of either the bisphosphonate or α-hydroxybisphosphonate conjugated drug (p < 0.001). In contrast, the less labile tedizolid N-phenyl carbamate linked BCA had limited efficacy against MSSA, and MRSA. CFU were recovered from all tedizolid BCA treatments. These results demonstrate the feasibility of BCA eradication of S. aureus biofilm on OLCN bone surfaces and support in vivo drug development of a sitafloxacin BCA.

In-vitro assessment of β-tricalcium phosphate/bredigite-ciprofloxacin (CPFX) scaffolds for bone treatment applications

In the present study, β-tricalcium phosphate (β-TCP) scaffolds with various amounts of bredigite (Bre) were fabricated by the space holder method. The effect of bredigite content on the structure, mechanical properties, in vitro bioactivity, and cell viability was investigated. The structural assessment of the composite scaffolds presented interconnected pores with diameter of 300–500 μm with around 78%–82% porosity. The results indicated that the compressive strength of the scaffolds with 20% bredigite (1.91 MPa) was improved in comparison with scaffolds with 10% bredigite (0.52 MPa), due to the reduction of the average pore and grain sizes. Also, the results showed that the bioactivity and biodegradability of β-TCP/20Bre were better than that of β-TCP/10Bre. Besides, in this study, the release kinetics of ciprofloxacin (CPFX) loaded β-TCP/Bre composites as well as the ability of scaffolds to function as a sustained release drug carrier was investigated. Drug release pattern of β-TCP/bredigite-5CPFX scaffolds exhibited the rapid burst release of 43% for 3 h along with sustained release (82%) for 32 h which is favorable for bone infection treatment. Antibacterial tests revealed that the antibacterial properties of β-TCP/bredigite scaffolds are strongly related to the CPFX concentration, wherein the scaffold containing 5% CPFX showed the most significant zone of inhibition (33 ± 0.5 mm) against Staphylococcus aureus. The higher specific surface areas of nanostructure β-TCP/bredigite scaffolds containing CPFX lead to an initial rapid release followed by constant drug delivery. MTT assay showed that the cell viability of β-TCP/bredigite scaffold loading with up to 1%–3% CPFX (95 ± 2%), is greater than for scaffolds containing 5% CPFX (84 ± 2%). In Overall, it may suggested that β-TCP/bredigite containing 1%–3% CPFX possesses great cell viability and antibacterial activity and be employed as bactericidal biomaterials and bone infection treatment.

Financial Impact of the Surgical Treatment of Infection on the Practice of Orthopedic Trauma

Objectives: The treatment of bone, muscle, and joint infections has been under the purview of orthopedic surgeons for years. As care has become more specialized, orthopedic surgeons are offloading infection cases to services such as general surgery or podiatry. Orthopedics as a field has already yielded portions of spine to neurosurgery, recovery to physiatrists, and foot and ankle to podiatry. The purpose of this study was to report the financial impact of infection treatment on our group practice at a busy community Level II trauma center.&#x0D; Design: Retrospective Economic Review&#x0D; Setting: Level II Trauma Center&#x0D; Patients/Participants: All patients receiving orthopedic surgical intervention at our facility from January 1, 2018 to December 31, 2018.&#x0D; Intervention: Surgical treatment of bone, muscle and joint infections.&#x0D; Main Outcome Measurements: Surgical Volume, Relative Value Units, Physician Charges, Physician Collections and Payer Mix&#x0D; Results: The surgical treatment of infections including irrigation and debridement, wound closure and amputations amounted to 908 out of 3700 total cases. This included 11,405 total RVUs, 5,771 work RVUs, $2,056,677 in charges and $407,479 in collections over the 2018 calendar year. This was 16.8% of total RVUs, 19% of all charges, and 15% of collections for the orthopedic trauma service. The payer mix for these patients was less favorable with a collection rate of 20% compared to a 25% average for all surgical cases.&#x0D; Conclusions: The treatment of orthopedic infections represents a large proportion of surgical volume for orthopedic surgeons covering hospital call. Relinquishing control of these patients will result in significant financial loss as well as a decrease in our ability to control the episode of care and patient access in the changing healthcare environment.&#x0D; Level of Evidence: Therapeutic Level III

Real-World Clinical Use and Outcomes of Telavancin for the Treatment of Bone and Joint Infections: Results from the Telavancin Observational Use Registry (TOUR™).

BackgroundAdditional antibiotic options are needed to treat bone and joint infections caused by penicillin-resistant Gram-positive pathogens.ObjectiveThis subanalysis of the Telavancin Observational Use Registry (TOUR™) aimed to record real-world telavancin usage patterns in patients with bone and joint infections treated with telavancin.MethodsTOUR was a multicenter observational-use registry study conducted at 45 US sites between January 2015 and March 2017. Patient characteristics, infection type, infecting pathogen(s), previous treatment, telavancin dosing and duration, clinical response, and adverse event data were collected by retrospective medical chart reviews. As such, inclusion/exclusion criteria were limited, and any patient receiving at least one dose of telavancin at the discretion of the treating physician was eligible. Patients were assessed as either positive clinical response, failed treatment, or indeterminate outcome.ResultsOf the 1063 patients enrolled in TOUR, 27.4% (291/1063) were patients with bone and joint infections including osteomyelitis (with or without prosthetic material), acute septic arthritis, and prosthetic joint infections. Most of these patients had osteomyelitis without prosthetic material (191/291; 66.0%). Among patients assessed at the end of treatment, 211/268 (78.7%) achieved a positive clinical response, 26/268 (9.7%) failed treatment, and 31/268 (11.6%) had an indeterminate outcome. The most frequent pathogen was methicillin-resistant Staphylococcus aureus (110/291; 37.8%). The median (interquartile range [IQR as Q1, Q3]) telavancin dose was 750.0 mg (IQR, 750, 750 mg) or 8.2 mg/kg (IQR, 6.8, 9.7 mg/kg) administered for a median of 26 days (IQR, 12, 42 days). These assessments were recorded in the registry ≥ 30 days after the last dose of telavancin was administered.ConclusionsReal-world data from the TOUR study show that clinicians are using once-daily telavancin with positive clinical outcomes for the treatment of bone and joint infections caused by Gram-positive pathogens.Clinical Trial RegistrationThis trial was registered with ClinicalTrials.gov (NCT02288234) on 11 November, 2014.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40801-021-00255-6.

Treatment of bone and joint infections by ceftazidime/avibactam and ceftolozane/tazobactam: a cohort study

Ceftazidime/avibactam (C/A) and ceftolozane/tazobactam (C/T) are two novel antibacterials with known efficacy against Gram-negative bacteria (GNB). We aimed to describe the efficacy and safety of surgical management combined with C/A or C/T treatment for bone and joint infections (BJIs). We conducted an observational, bicentric study of patients treated with C/A or C/T for a BJI between May 2016 and June 2019. Failure was defined as the need for unplanned additional antibiotic treatment or orthopaedic surgery, or death due to the BJI up to the patient's latest visit. Overall, 15 patients were included. Nine patients were treated with C/A, mainly for polymicrobial BJI due to multidrug-resistant (MDR) bacteria (Enterobacteriaceae, n=7). Six patients were male, the median age was 66 years and the median Charlson comorbidity index (CCI) was 5. It was the first septic episode at the site in 3/9 patients. The cure rate was 7/9 (median follow-up, 272 days). Two patients showed C/A-related confusion. Five patients were treated with C/T for BJI involving MDR Pseudomonas aeruginosa. Four patients were male, the median age was 53 years and the median CCI was 2. All patients had previous septic episodes at the infection site. The cure rate was 3/5 (median follow-up, 350 days). One patient was successfully treated by C/T then C/A for multistage spondylodiscitis. In our experience, C/A and C/T are two effective and safe options, even as salvage treatment for BJI due to MDR-GNB despite the absence of label, however more data are warranted.

Anti-biofilm activity of dalbavancin against methicillin-resistant Staphylococcus aureus (MRSA) isolated from human bone infection

The presence of methicillin-resistant Staphylococcus aureus (MRSA) in bone infections difficults its treatment and is a sign of concern. The aim of this study was to evaluate in vitro activity of dalbavancin on pre-established adhered cells and 24 h old biofilms of MRSA strains isolated from a human bone infection. Thirty-three MRSA were isolated from osteomyelitis episodes. The antimicrobial susceptibility of these strains was assessed by the Kirby-Bauer disc diffusion method and the presence of resistance genes was screened by PCR. MRSA planktonic minimum inhibitory concentration and minimum bactericidal concentration were assessed. Minimum biofilm eradication concentration (MBEC) was performed by the microtiter biofilm formation assay. All 33 MRSA strains were classified as multidrug-resistant strains and susceptible to dalbavancin. Dalbavancin inhibited the growth of 54.6% and 52% of strains at the concentrations of 0.05 µg/mL and 1 µg/mL, respectively. The MBEC values up to 0.4 µg/mL demonstrated that dalbavancin was active against most strains in pre-established adhered cells and 24 h old biofilms. The current results show that dalbavancin is active against adhered cells and biofilms in vitro, suggesting that this antimicrobial agent may be an option for the treatment of bone infections caused by MRSA.

Does local implantation of gentamicin impair renal function in patients undergoing surgery for chronic bone infection?

&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;The treatment of chronic bone infection often involves excision of dead bone and implantation of biomaterials which elute antibiotics. Gentamicin is a preferred drug for local delivery, but its systemic use carries a well-established risk of nephrotoxicity. We aim to establish the risk of acute kidney injury (AKI) with local delivery in a ceramic carrier.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;163 patients with Cierny-Mader type 3 or 4 chronic osteomyelitis had a single-stage operation including filling of the osseous defect with a calcium sulphate-hydroxyapatite carrier containing gentamicin. Mean gentamicin dosing was 191.3 mg (maximum 525 mg). Glomerular filtration rate (GFR) was calculated pre-operatively and during the first seven days post-operatively. Renal impairment was graded using the chronic kidney disease (CKD) staging system, and AKI was assessed using the RIFLE criteria.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;155 cases had adequate data to allow calculation of pre- and post-operative GFR. 7 had pre-existing renal disease. 70 patients (45.2%) had a temporary GFR drop post-operatively, with the greatest decrease occurring at a mean of 3.06 days following surgery. Twenty cases had a &amp;gt;10% decline in GFR, but 12 resolved within 7 days. 7 patients transiently fell into the “Risk” category according to RIFLE criteria, but no patient had a change consistent with “Injury”, “Failure” or “Loss” of renal function and none had clinical signs of new acute renal impairment post-operatively. &lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;Renal function is not significantly affected by local implantation of gentamicin up to 525 mg. The presence of pre-existing renal disease is not a contraindication to local gentamicin therapy.&lt;/p&gt;&lt;p&gt;&lt;strong&gt; &lt;/strong&gt;&lt;/p&gt;

In vitro bioactivity and antibacterial capacity of 45S5 Bioglass®-based compositions containing alumina and strontium

Abstract A modified 45S5 Bioglass® containing 2 mol% alumina and 2 mol% strontium oxide was prepared. In vitro bioactivity in powder and monolithic samples was conducted. Fourier transform infrared analysis and pH change in simulated body fluid were investigated for powder samples after 480 min of immersion. Additionally, X-ray diffraction and scanning electron microscopy after 7 and 14 days of immersion in simulated body fluid were investigated for monolithic samples. The formation of phosphate and carbonate phase precursors of hydroxycarbonate apatite was observed after 480 min for powder samples, and the hydroxycarbonate apatite pattern and morphology were confirmed after 7 days of immersion for monolithic samples. It seems that changes in composition did not affect reactivity but caused a decrease in the maxima of pH. Cytotoxicity and cell viability obtained by using the NCTC clone 929 cell line did not show any significant loss of cell viability or cytotoxicity. Moreover, after overnight incubation, the samples demonstrated safe disinfection for Escherichia coli. For these reasons, the use of these new bioactive glasses can be considered a promising alternative for the reconstruction of bone defects and even for the treatment and suppression of bone infections.

Gastrocnemius pedicled muscle flap for knee and upper tibia soft tissue reconstruction. A useful tool for the orthopaedic surgeon

Soft tissue defect coverage has always been a challenge for the orthopaedic surgeon. Over the last decades the surgery of flaps has completely changed the prognosis for large defects. The purpose of this study is to retrospectively review our experience with the gastrocnemius muscle as pedicled local flaps for reconstruction of knee and upper third of the tibia soft tissue defects.Twenty-seven patients underwent reconstruction of soft tissue defects around the knee using pedicled gastrocnemius muscle flaps. There were eighteen men and nine women ranged in with a mean age of 50.3 years. Medial gastrocnemius was used in 21 cases, and lateral gastrocnemius in 5 cases. In one patient, soleus and medial gastrocnemius were transferred simultaneously. All but one had at the same time split thickness skin graft for coverage of the muscle.All muscle flaps transferred were successful. There were no complications and all flaps survived completely without vascular compromise, satisfactory coverage of the defect, and good primary wound healing. There has been no recurrence of osteomyelitis. The donor sites healed perfectly with no remarkable resultant functional disability. A mean follow-up of 4.4 years revealed acceptable cosmetic results with high patient satisfaction.Our results indicate that the gastrocnemius muscle transfer is a useful technique for coverage of soft tissue defects in the upper tibia and around the knee in our orthopaedic practice. It is a reliable option for the coverage of exposed bone, the filling up of deep cavities and the treatment of bone infection. The principal advantage of a muscle flap is to bring a real blood supply to the recipient site and to improve the trophicity of the surrounding tissues. The pedicled muscle flap is our preference for the management of soft tissue defects around the knee, when no other procedure, apart from free flap is suitable. The pedicle flap is easier, quicker and with less complications than a free flap. Orthopaedic surgery has gained much from the use of island flap, however, it requires knowledge of the vascular anatomy and its variations promoted through cadaveric dissections and flap dissection courses.

Long-Acting Lipoglycopeptides for the Treatment of Bone and Joint Infections.

Background: The long-acting lipoglycopeptides dalbavancin and oritavancin possess excellent microbiologic activity against gram-positive bacteria and provide prolonged tissue exposure at sites of infection. Moreover, these antibiotics are well tolerated and do not require therapeutic drug monitoring. Methods: Pharmacokinetic/pharmacodynamic experiments ascertained that one to two doses of these long-acting agents can provide an extended period (≥6 weeks) of antimicrobial therapy. Results: Clinical studies subsequently found that microbiologic and clinical response rates with these agents were comparable to standard antibiotic agents used in the treatment of bone and joint infections. In addition, pharmacoeconomic analyses have discovered cost savings with the use of these antimicrobial agents in the treatment of serious deep-seated bacterial infections. Conclusions: Thus, these long-acting lipoglycopeptides offer potential for cost-effective outpatient parenteral antibiotic therapy of difficult to treat infections, such as osteomyelitis.

Formulation and characterization of hydroxyapatite-based composite with enhanced compressive strength and controlled antibiotic release.

A composite based on hydroxyapatite (HA) and chitosan (CS) combined with ciprofloxacin (CIP) was formulated by the solid-liquid mixing method. The optimization of the solid to the liquid ratio and the use of chitosan in a small amount (≤5wt%) promoted the preparation of stable and rigid monoliths. A synergistic effect of CS and CIP contents on the compressive strength of the CIP-loaded composite was evidenced. The compressive strength of the fabricated biocomposite ranged in values from 1 to 6MPa, comparable to those reported for cancellous bone. The improvement of the mechanical properties with the increase of the rate of organic components was correlated with the diminution of the surface area and the reduction in the pore volume of the specimens. On the other hand, the in vitro release experiments of the antibiotic indicated a sustained and controlled release of CIP over 10 days. Moreover, in vitro antibacterial tests performed on the biocomposite HA-CS5-CIP showed significant inhibition of Staphylococcus aureus and Escherichia coli pathogens. According to the showed results, the formulated composite with three-phase components could be a promising material for bone repair and local antibiotic release for the treatment of bone infections.