Objectives. Meropenem may be an important drug in the treatment of open tibial fractures and chronic osteomyelitis. Therefore, the objective of this study was to describe meropenem pharmacokinetics in plasma, subcutaneous adipose tissue (SCT), and cancellous bone using microdialysis in a porcine model. Methods. Six female pigs were assigned to receive 1000 mg of meropenem intravenously over five minutes. Measurements of meropenem were obtained from plasma, SCT, and cancellous bone for eight hours thereafter. Microdialysis was applied for sampling in solid tissues. The meropenem concentrations were determined using ultra-high-performance liquid chromatography. Results. The penetration of meropenem into cancellous bone, expressed as the ratio of plasma to cancellous bone area under the concentration-curve from zero to the last measured value, was incomplete and delayed. The time with concentration above the minimal inhibitory concentration (T. >MIC. ), for an MIC of 0.5 μg/ml, was shorter for cancellous bone in comparison with both plasma and SCT. For MICs above 0.5 μg/ml, T. >MIC. in cancellous bone was only shorter than SCT. Considering an MIC of 4 μg/ml, no animals achieved the target of 40% T. >MIC. in plasma and cancellous bone, while less than 20% achieved it in SCT. Conclusion. The main finding of this study was short T. >MIC. in cancellous bone after intravenous administration of 1000 mg meropenem. Consequently, in order to achieve sufficient tissue concentration in the cases of open tibial fractures and chronic osteomyelitis, supplemental application of meropenem may be necessary. Cite this article: P. Hanberg, A. Lund, K. Søballe, M. Bue. Single-dose pharmacokinetics of meropenem in porcine cancellous bone determined by microdialysis: An animal study. Bone Joint Res 2019;8:342–348. DOI: 10.1302/2046-3758.87.BJR-2018-0308.R1

Aims. Prompt and sufficient broad-spectrum empirical antibiotic treatment is key to preventing infection following open tibial fractures. Succeeding co-administration, we dynamically assessed the time for which vancomycin and meropenem concentrations were above relevant epidemiological cut-off (ECOFF) minimal inhibitory concentrations (T > MIC) in tibial compartments for the bacteria most frequently encountered in open fractures. Low and high MIC targets were applied: 1 and 4 µg/ml for vancomycin, and 0.125 and 2 µg/ml for meropenem. Methods. Eight pigs received a single dose of 1,000 mg vancomycin and 1,000 mg meropenem simultaneously over 100 minutes and 10 minutes, respectively. Microdialysis catheters were placed for sampling over eight hours in tibial cancellous bone, cortical bone, and adjacent subcutaneous adipose tissue. Venous blood samples were collected as references. Results. Across the targeted ECOFF values, vancomycin displayed longer T > MIC in all the investigated compartments in comparison to meropenem. For both drugs, cortical bone exhibited the shortest T > MIC. For the low MIC targets and across compartments, mean T > MIC ranged between 208 and 449 minutes (46% to 100%) for vancomycin and between 189 and 406 minutes (42% to 90%) for meropenem. For the high MIC targets, mean T > MIC ranged between 30 and 446 minutes (7% to 99%) for vancomycin and between 45 and 181 minutes (10% to 40%) for meropenem. Conclusion. The differences in the T > MIC between the low and high targets illustrate how the interpretation of these results is highly susceptible to the defined MIC target. To encompass any trauma, contamination, or individual tissue differences, a more aggressive dosing approach may be considered to achieve longer T > MIC in all the exposed tissues, and thereby lower the risk of acquiring an infection after open tibial fractures. Cite this article: Bone Joint Res 2022;11(2):112–120

Fracture related infection remains a major challenge in musculoskeletal trauma surgery. Despite best practice, treatment strategies suffer from high failure rates due to antibiotic resistance and tolerance. Bacteriophages represent a promising alternative as they retain activity against such bacteria. However, optimal phage administration protocols remain unknown, although injectable hydrogels, loaded with phage and conventional antibiotics, may support conventional therapy. In this study we tested the activity of meropenem, and two newly isolated bacteriophages (ϕ9 and ϕ3) embedded within alginate-chitosan microbeads and a hydrogel. Antibiotic and phage stability and activity were monitored in vitro, over a period of 10 days. In vivo, the same material was tested in treatment of a 5-day old Pseudomonas aeruginosa infection of a tibial plate osteotomy in mice. Treatment involved debridement and 5 days of systemic antibiotic therapy plus: i- saline, ii-phages in saline, iii-phages and antibiotics loaded into a hydrogel (n=7 mice/group). To assess the efficacy of the treatments, the infection load was monitored during revision surgery with debridement of the infected tissue after 5,10 and 13 days (euthanasia) by CFU and PFU quantification. In vitro testing confirmed that the stability of meropenem and activity of ϕ9 and ϕ3, was not affected within the alginate beads or hydrogel over 10 days. The in vivo study showed that all mice receiving phages and antibiotics loaded into a hydrogel survived the infection with a reduction of the bacterial load in the soft tissue. Active phages could be recovered from the infected site at euthanasia (10. 4. PFU/g). The hydrogel loaded with bacteriophages and meropenem showed a positive result in locally reducing the infection load indicating a synergistic effect of the selected antimicrobials. Overall, our new strategy shows encouraging results for improving the treatment of antibiotic-resistant biofilm infections that are related to medical implants

Aim. Prompt and sufficient broad spectrum empirical antibiotic treatment is key to prevent infection following open tibial fractures. Succeeding co-administration, we dynamically assessed the time for which vancomycin and meropenem concentrations were above relevant epidemiological cut-off minimal inhibitory concentrations (T>MIC) in tibial compartments for the bacteria most frequently encountered in open fractures. Low and high MIC-targets were applied: 1 and 4 µg/mL for vancomycin and 0.125 and 2 µg/mL for meropenem. Materials and methods. 8 pigs received a single dose of 1000 mg vancomycin and 1000 mg meropenem simultaneously over 100 min and 10 min, respectively. Microdialysis catheters were placed for sampling over 8 h in tibial cancellous bone, cortical bone, and adjacent subcutaneous adipose tissue. Venous blood samples were collected as references. Results. Across the targeted epidemiological cut-off values, vancomycin displayed longer T>MIC in all the investigated compartments in comparison to meropenem. For both drugs, cortical bone exhibited the shortest T>MIC. For the low MIC targets and across compartments, T>MIC ranged between 208–499 min (46–100%) for vancomycin and 189–406 min (42–90%) for meropenem. For the high MIC targets, T>MIC ranged between 30–446 min (7–99%) for vancomycin and 45–181 min (10–40%) for meropenem. Conclusion. The differences in the T>MIC between the low and high targets illustrates how the interpretation of these results is highly susceptible to the defined MIC target. To encompass any trauma, contaminating or individual tissue differences, a more aggressive dosing approach may be considered to achieve longer T>MIC in all the exposed tissues and thereby lowering the risk of acquiring an infection after open tibial fractures

Aims. This study investigated vancomycin-microbubbles (Vm-MBs) and meropenem (Mp)-MBs with ultrasound-targeted microbubble destruction (UTMD) to disrupt biofilms and improve bactericidal efficiency, providing a new and promising strategy for the treatment of device-related infections (DRIs). Methods. A film hydration method was used to prepare Vm-MBs and Mp-MBs and examine their characterization. Biofilms of methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli were treated with different groups. Biofilm biomass differences were determined by staining. Thickness and bacterial viability were observed with confocal laser scanning microscope (CLSM). Colony counts were determined by plate-counting. Scanning electron microscopy (SEM) observed bacterial morphology. Results. The Vm-MBs and Mp-MBs met the experimental requirements. The biofilm biomass in the Vm, Vm-MBs, UTMD, and Vm-MBs + UTMD groups was significantly lower than in the control group. MRSA and E. coli biofilms were most notably damaged in the Vm-MBs + UTMD group and Mp-MBs + UTMD group, respectively, with mean 21.55% (SD 0.08) and 19.73% (SD 1.25) remaining in the biofilm biomass. Vm-MBs + UTMD significantly reduced biofilm thickness and bacterial viability (p = 0.005 and p < 0.0001, respectively). Mp-MBs + UTMD could significantly decrease biofilm thickness and bacterial viability (allp < 0.001). Plate-counting method showed that the numbers of MRSA and E. coli bacterial colonies were significantly lower in the Vm-MBs + UTMD group and the Mp, Mp-MBs, UTMD, Mp-MBs + UTMD groups compared to the control group (p = 0.031). SEM showed that the morphology and structure of MRSA and E. coli were significantly damaged in the Vm-MBs + UTMD and Mp-MBs + UTMD groups. Conclusion. Vm-MBs or Mp-MBs combined with UTMD can effectively disrupt biofilms and protectively release antibiotics under ultrasound mediation, significantly reducing bacterial viability and improving the bactericidal effect of antibiotics. Cite this article: Bone Joint Res 2024;13(9):441–451

The aim of the study is to evaluate the effect of acrylic cement CMW1 (DePuy) containing 2,5% of gentamicin and addition of 5 % and 10 % of respective vancomycin, meropeneme and ceftriaxone on growth inhibition of reference strains of MRSA, E. faecalis, S. aureus, P. aeruginosa and E. coli.

From every portion of investigated acrylic cement CMW1 discs were cut with a diameter of 15mm and a thickness of 5mm, average weight 1.365 g (+/− 0,257g). Inoculum was prepared with the reference strains: MR3 S. aureus methicillin-resistant (MRSA), ATCC 29219 E. faecalis, ATCC 25923 S. ureus, ATCC 27853 P. aeruginosa and ATCC 25922 E. coli. A colonies of bacteria taken from a 18-hour culture on solid medium were addend to tubes with sterile physiological saline solution to obtain a density of 0.5 McFarland (5 × 105 CFU / ml). The suspension was distributed evenly over the Mueller-Hinton (MH) medium (Biomerieux, France). Prepared discs of CMW1 cement were put with a sterile forceps on the plate with a dry medium. The plates were incubated aerobically at 24 hr and the temp. 37°C.

After 24 hours the diameter of zone of inhibition of bacterial growth on a plate was measured (in mm) and average size of the inhibition zone was calculated. The CMW1 cement inhibited to a comparable degree growth of reference strains with the exception of E. faecalis. The addition of vancomycin increased by 1/5 inhibitory potential of CMW1 cement on growth of MRSA, S. aureus, P. aeruginosa and E. coli. and significantly for E. faecalis. Changing the concentration of vancomycin, meropeneme and ceftriaxone from 5% to 10% do not increased the inhibitory potential of CMW1 cement on the growth of MRSA, S. aureus, P. aeruginosa, E. coli and E. faecalis. Addition of meropeneme increased inhibitory potential of CMW1 cement against MRSA by 1/3, P. aeruginosa and E. coli by ½, E. faecalis by 3/4 and against S. aureus by 100%. Addition of ceftriaxone to CMW1 cement increased the inhibiting of the growth of MRSA similiarly to 5% and 10% of vancomycin, E. faecalis as meropeneme 5% and 10 %, while the growth of S. aureus and P. aeruginosa, less than meropeneme.

Addition of antibiotics to acrylic cement increased its antibacterial properties. Increase if vancomycine concentrations from 5 to 10% had no stronger antibacterial effect.

Aim. Fracture-related infection (FRI) is a challenging complication. This study aims to investigate (1) microbial patterns in fracture-related infection (FRI), (2) the comparison of isolated pathogens in FRI patients with early, delayed, and late onset of infection and (3) antibiotic susceptibility profiles to identify effective empiric antibiotic therapy for FRI. Method. Patients treated for FRI from 2013 to 2020 were grouped into early (< 2 weeks), delayed (2– 10 weeks) and late (> 10 weeks) onset of infection. Pathogens detected during treatment were evaluated for pathogens. Antibiotic susceptibility profiles were examined with respect to broadly used antibiotics and antibiotic combinations. Results. In total 117 patients (early n=19, delated n=60, late n=38) were included in the study. Infection was polymicrobial in 10 cases (8.6%) and culture-negative in 11 cases (9.4%). Staphylococcus aureus was the most frequently detected pathogen (40.5%), followed by Staphylococcus epidermidis (17.2%) and gram-negative bacteria (16.4%). Pathogen distribution did not differ statistically significant between the groups. Highest effectiveness could be achieved by the combination of meropenem + vancomycin (95.7%) and gentamycin + vancomycin (94.0%). More than 90% of all patients would have also been covered by co-amoxiclav + glycopeptide (93.2%), ciprofloxacin + glycopeptide and piperacillin/tazobactam + glycopeptide (92.3% each) as well as ceftriaxone + glycopeptide (91.5%). Comparing the predicted efficacy of empiric antimicrobial regimens between the subgroups only revealed a statistically significant difference regarding the combination ciprofloxacin with a glycopeptide (F= 3.304, p=.04), for which more patients with an early onset of infection would have been susceptible. Conclusions. Microbiological pattern for the causative microorganism between early, delayed, and late FRI are comparable. Empiric therapy combinations such as meropenem + vancomycin, gentamycin +vancomycin or co-amoxiclav + glycopeptide are effective antibiotic strategies. To bypass unwanted side effects of systemic antibiotics and reduce the risk of antimicrobial resistance, the administration of local antibiotic carriers should be implemented in clinical practice

Antibiotic-laden bone cement is an important strategy of treatment for an established bone infection. It was aimed to find the safe antibiotic dose intervals of the antibiotic cements soaked in Phosphate Buffered Saline solution and to determine whether there was a difference in terms of mechanical strength between the prepared samples. This study was done in our institute Microbiology and Metallurgy laboratories. All samples were prepared using manual mixing technique using 40 g radiopaque Biomet® Bone cement (Zimmer Biomet, Indiana, USA) under sterile conditions at 19 ± 2 ºC. In this study, vancomycin (4 groups − 0.5, 2, 4, 6 g), teicoplanin (4 groups − 0.8, 1.2, 2, 2.4 g), daptomycin (4 groups − 1, 2, 2.5, 3 g), piperacillin-tazobactam (4 groups − 0.125, 0.5, 1, 2 g) and meropenem (4 groups − 0.5, 2, 4, 6 g) were measured in a assay balance and added to the cement powder. Antibiotic levels ranged from the lowest 0.625% to the highest 15%. 80×10×4 mm rectangle prism-shaped sample for mechanical measurements in accordance to ISO 5833 standart and 12×6×1 mm disc-shaped samples for microbiological assesments were used. Four sample for each antibiotic dose and control group was made. Prepared samples were evaluated macroscopically and faulty samples were excluded from the study. Prepared samples were kept in Phosphate Buffered Saline solution renewed every 24 hours at 37 ºC. At the end of 6 weeks, all samples were tested with Instron ® 3369 (Norwood Massachusetts, USA) four point bending test. Staphylococcus aureus (ATCC 29213) strain was used for samples of antibiotics containing vancomycin, teicoplanin and daptomycin after the samples prepared for antibiotic release were maintained under sterile conditions and kept in Phosphate Buffered Saline solution as appropriate. For samples containing meropenem and piperacillin - tazobactam antibiotics, Pseudomonas aeruginosa (ATCC 27853) strain was used. The addition of more than 5% antibiotics to the cement powder was significantly reduced mechanical strength in all groups(p <0.05) however the power of significance was changed depending on the type of antibiotic. In general, adding antibiotics with 2.5% and less for cement amount was not cause significant changes in mechanical measurements. There was a negative correlation between the increase in the amount of antibiotics mixed with cement and the durability of the cement (p: <0.001, r: −0.883 to 0.914). In this study, especially the antibacterial effects of piperacillin-tazobactam, containing 0.25 gr and 0.5 gr antibiotic doses, were found to be low. There was no bacterial growth in all other groups for 21 days. Considering the mechanical properties of groups containing meropenem, vancomycin, daptomycin and teicoplanin, it was observed that all antibiotic cements remained above the limit value of 50 MPa in the bending test at concentrations containing 2.5% and less antibiotics. This was not achieved for the piperacillin-tazobactam group. The findings of the study showed that each antibiotic has different MPa values at different doses. Therefore, it could be concluded that not only the antibiotic dose but also the type oould change the mechanical properties. In the light of these findings, mixing more than 2.5% antibiotics in cement for the antibiotic types included in the study was ineffective in terms of antibacterial effect and mechanically reduces the durability of cement below the standard value of 50 MPa

Objectives. The optimal protocol for antibiotic loading in the articulating cement spacers for the treatment of prosthetic joint infection (PJI) remains controversial. The objective of the present study was to investigate the effectiveness of articulating cement spacers loaded with a new combination of antibiotics. Methods. A retrospective cohort study involving 114 PJI cases treated with implantation of an articulating cement spacer between 2005 and 2016 was performed. The treatment outcomes of the conventional protocol (i.e. gentamicin and vancomycin (GV protocol)) were compared with those reported using the sophisticated antibiotic-loading protocol (i.e. vancomycin, meropenem, and amphotericin (VMA protocol)). Results. There were 62 and 52 PJI cases treated with the GV and VMA protocols, respectively. Antimicrobial susceptibility testing revealed that 22/78 of all isolates (28.2%) in this series were resistant to gentamicin, whereas there were no vancomycin-, meropenem-, or amphotericin-resistant strains. The overall infection recurrence rates were 17.7% (11/62) and 1.9% (1/52), respectively (p = 0.006). In patients with a negative preoperative culture, there was no infection recurrence reported in the VMA cohort (0/45 (0%) vs 10/54 (18.5%) in the GV cohort; p = 0.002). Multivariate analysis indicated that the VMA protocol correlated with a decreased risk of infection recurrence compared with the GV protocol (p = 0.025). Conclusion. The sophisticated VMA protocol for the loading of antibiotics in articulating cement spacers, as part of a two-stage exchange, was associated with a reduced rate of infection recurrence. This proposed protocol appears to be safe and effective, especially in patients with negative culture results prior to the first-stage operation. Cite this article: Bone Joint Res 2019;8:526–534

Objectives. The optimal protocol for antibiotic loading in the articulating cement spacers for the treatment of prosthetic joint infection (PJI) remains controversial. The objective of the present study was to investigate the effectiveness of articulating cement spacers loaded with a new combination of antibiotics. Methods. A retrospective cohort study involving 114 PJI cases treated with implantation of an articulating cement spacer between 2005 and 2016 was performed. The treatment outcomes of the conventional protocol (i.e. gentamicin and vancomycin (GV protocol)) were compared with those reported using the sophisticated antibiotic-loading protocol (i.e. vancomycin, meropenem, and amphotericin (VMA protocol)). Results. There were 62 and 52 PJI cases treated with the GV and VMA protocols, respectively. Antimicrobial susceptibility testing revealed that 22/78 of all isolates (28.2%) in this series were resistant to gentamicin, whereas there were no vancomycin-, meropenem-, or amphotericin-resistant strains. The overall infection recurrence rates were 17.7% (11/62) and 1.9% (1/52), respectively (p = 0.006). In patients with a negative preoperative culture, there was no infection recurrence reported in the VMA cohort (0/45 (0%) vs 10/54 (18.5%) in the GV cohort; p = 0.002). Multivariate analysis indicated that the VMA protocol correlated with a decreased risk of infection recurrence compared with the GV protocol (p = 0.025). Conclusion. The sophisticated VMA protocol for the loading of antibiotics in articulating cement spacers, as part of a two-stage exchange, was associated with a reduced rate of infection recurrence. This proposed protocol appears to be safe and effective, especially in patients with negative culture results prior to the first-stage operation. Cite this article: Bone Joint Res 2019;8:526–534

Aim. Currently, gram-negative bacteria (GNB), including multidrug-resistant (MDR-GNB) pathogens, are gaining importance in the aetiology of prosthetic joint infection (PJI). To characterize the antimicrobial resistance patterns of Gram-negative bacteria (GNB) causing hip prosthetic joint infections in elderly patients treated at a Brazilian tertiary academic hospital. Method. This is a retrospective, cross-sectional study of patients over 60 years of age undergoing hip arthroplasty from 2018 to 2023 at a tertiary academic trauma, which were diagnosed with hip prosthetic joint infection. PJI diagnosed was based on EBJIS criteria, in which intraoperative tissue cultures identified the pathogens. Demographics, reason for arthroplasty, type of implant and susceptibility patterns using disk diffusion method were analysed. Results. Overall, among 17 elderly patients diagnosed with hip infected arthroplasty, 45 bacterial isolated were identified. Debridement, irrigation, antibiotic and implant retention (DAIR) procedures due to uncontrolled infection occurred in 47.0% (n=8/17), and five patients underwent more than two DAIR surgeries. Tissue cultures yielded eleven different bacterial species, with GNB accounted for 64.4% (n=29/45) of pathogens. Klebsiella pneumoniae, Acinetobacter baumannii, Escherichia coli, and Pseudomonas aeruginosa were identified in 34.5% (n=10/29), 17.25% (n=5/29), 13.8% (n=4/29), and 13.8% (n=4/29), respectively. In the resistance profile analysis, E. coli was most sensitive to antibiotics, whereas K. pneumoniae showed resistance rates higher than 70% for cephalosporins, carbapenems, and quinolones. All A. baumannii isolates were resistant to meropenem, and 80% of these isolates were resistant to amikacin. Conclusions. This study emphasizes the role of GNB in the microbiological profile of PJI among elderly patients at a tertiary hospital in a Brazilian centre. The present study portrays a worryingly higher rates of MDR-GNB, mainly to quinolones and cephalosporins resistance which have been the cornerstone of PJI antibiotic treatment. In addition, higher rates carbapenems and aminoglycosides resistance shows a threat to antibiotic treatment of PJI. More global studies need to be carried out to show a likely change in the microbial epidemiology of PJI

Aim. Empiric antibiotic therapy for suspected pyogenic spondylodiscitis (SD) should be initiated immediately with severely ill patients and may also be necessary for culture-negative SD. The aim of this study was to infer an appropriate empiric antibiotic regimen by analyzing the antimicrobial susceptibility of isolated pathogens from microbiologically proven pyogenic spondylodiscitis. Method. We performed a retrospective review of adult patients with clinically proven SD treated at our level 1 trauma center between 2013 and 2020. Demographic data, radiologic findings, and treatment modalities were evaluated. The appropriateness of empiric antibiotic regimens was assessed based on the antibiograms of the isolated pathogens. Anamneses were used to distinguish between community-acquired (CA) and healthcare-associated (HA) pathogens, which included cases that had a hospital stay or invasive intervention in the past 6 months. Results. A total of 155 patients (male: N=88; female: N=67; mean age 66.1 ± 12.4 years) with SD were identified. In n= 74 (47.7%) cases, the infections were associated with the healthcare system (HA). N=34 (21.9%) patients suffered from sepsis. The lumbar spine was involved in 47.1% of the cases, the thoracic spine in 37.3%, and the cervical spine in 7.8%. In 7.8% of the cases, SD occurred in multiple spinal segments. N=96 (62.0%) patients were treated surgically. The mean hospital stay was 36.4 ± 36.3 days. Antibiograms of n=45 patients (HA: N=22; CA: N=23) could be retrospectively evaluated: The most frequently identified pathogens were Staphylococcus aureus (46.7%), Coagulase-negative Staphylococci (17.8%), Enterobacteriaceae (15.6%) and Streptococcus species (15.6%). Overall, 82.2% (HA: 68.2%; CA: 95.5%) of the isolated pathogens were sensitive to piperacillin/tazobactam, 77.8% (HA: 81.8%; CA: 72.2%) to vancomycin, 64.4% (HA: 68.2%; CA: 59.1%) to clindamycin, and 55.6% (HA: 36.4%; CA: 72.7%) to ceftriaxone. To a combination of vancomycin plus meropenem 97.8% of pathogens were sensitive (HA: 95.5%; CA: 100.0%), to vancomycin plus ciprofloxacin 91.1% (HA: 86.4%; CA: 95.7%), and to vancomycin plus cefotaxime 93.3% (HA: 90.9%; CA: 95.7%). In 14 cases, empiric antibiosis was adjusted based on the results of the antibiogram. Conclusions. Antibiotic resistance of CA SD pathogens differed significantly from HA SD. The identification of the pathogen and the analysis of its susceptibility guides the antibiotic therapy. Vancomycin in combination with a carbapenem, broad-spectrum cephalosporin, or fluoroquinolone may be appropriate for empiric treatment of HA SD

Infection remains among the first reasons for failure of joint prosthesis. Currently, the golden standard for treating prosthetic joint infections (PJIs) is two-stage revision. However, two-stage procedures have been reported to be associated with higher costs and possible higher morbidity and mortality, compared to one-stage. Furthermore, recent studies showed the ability of a fast-resorbable, antibacterial-loaded hydrogel coating to reduce surgical site infections after joint replacement, by preventing bacterial colonization of implants. Aim of this study was then to compare the infection recurrence rate after a one-stage, cemenless exchange, performed with an antibacterial coated implant versus a standardized two-stage revision procedure. In this two-center prospective study, 22 patients, candidate to revision surgery for PJI, were enrolled to undergo a one-stage revision surgery with cementless implants, coated intra-operatively with a fast-resorbable, antibiotic-loaded hyaluronan and poly-D,L-lactide based hydrogel coating (“Defensive Antibacterial Coating”, DAC, Novagenit, Italy). DAC was reconstructed according to manufacturer indications and loaded with Vancomycin or Vancomycin + Meropenem, according to cultural examinations, and directly spread onto the implant before insertion. This prospective cohort was compared with a retrospective series of 22 consecutive patients, matched for age, sex, host type, site of surgery, that underwent a two stage procedure, using a preformed, antibiotic-loaded spacer (Tecres, Italy) and a cementless implant. The second surgery, for definitive implant placing, was performed only after CRP normalization and no clinical sign of infection. Clinical, laboratory and radiographic evaluation were performed at 3, 6 and 12 months, and every 6 months thereafter. Infection recurrence was defined by the presence of a sinus tract communicating with the joint, or at least two among the following criteria: clinical signs of infections; elevated CRP and ESR; elevated synovial fluid WBC count; elevated synovial fluid leukocyte esterase; a positive cultural examination from synovial fluid; radiographic signs of stem loosening. The two groups did not differ significantly for age, sex, host type and site of surgery (18 knees and 4 hips, respectively). The DAC hydrogel was loaded intra-operatively, according to cultural examination, with vancomycin (14 patients) or vancomycin and meropenem (8 cases). At a mean follow-up of 20.2 ± 6.3 months, 2 patients (9.1%) in the DAC group showed an infection recurrence, compared to 3 patients (13.6%) in the two-stage group. No adverse events associated with the use of DAC or radiographic loosening of the stem were observed at the latest follow-up months. This is the first report on one-stage cementless revision surgery for PJI, performed with a fast-resorbable antibacterial hydrogel coating. Our data, although in a limited series of patients and at a relatively short follow-up, show similar infection recurrence rate after one-stage exchange with cementless, coated implants, compared to two-stage revision. These findings warrant further studies in the possible applications of antibacterial coating technologies to treat implant-related infections

Treatment of open fractures is complex and controversial. The purpose of the present study is to add evidence to the management of open tibial fractures, where tissue loss necessitates cover with a free flap. We identified factors that increase the risk of complications. We questioned whether early flap coverage improved the clinical outcome and whether we could improve our antibiotic treatment of open fractures. From 2002 to 2013 we treated 56 patients with an open tibial fracture covered with a free flap. We reviewed patient records and databases for type of trauma, smoking, time to tissue cover, infection, amputations, flap loss and union of fracture. We identified factors thatincrease the risk of complications. We analyzed the organisms cultured from open fractures to propose the optimal antibiotic prophylaxis. Follow-up was minimum one year. Primary outcome was infection, bacterial sensitivity pattern, amputation, flap failure and union of the fracture. When soft tissue cover was delayed beyond 7 days, infection rate increased from 27% to 60% (p<0.04). High-energy trauma patients had a higher risk of amputation, infection, flap failure and non-union. Smokers had a higher risk of non-union and flap failure. The bacteria found were often resistant to Cefuroxime, aminoglycosides or amoxicillin, but sensitive to Vancomycin or Meropenem. Flap cover within one week is essential to avoid infection. High-energy trauma and smoking are important predictors of complications. We suggest antibiotic prophylaxis with Vancomycin and Meropenem until the wound is covered in these complex injuries. The authors wish to thank Christian E Forrestal for secretarial assistance, spreadsheets and figures, MD Maria Petersen for academic feedback and typography. Table: Culture results. Depicts the organisms isolated from the wounds, their number N and the number of bacteria that were fully susceptible to antibiotics according to the culture results in falling order on day 2–30 from the trauma. Most organisms were resistant to Cefuroxime. A blank space denotes that the organism was not tested against this antibiotic. A “0” denotes that the organism was not fully sensitive to the antibiotic

The purpose of the study was to retrospectively assess the patients treated to date with the vac ulta system using a technique of antibiotic instillation. The vac ulta system is licensed for use with anti-septic instillation fluid but we have now treated a number of patients with antibiotic instillation under the guidance of the microbiology department. All patients being treated with the vac ulta system were included in the study. There were no exclusions. Pathology treated, infecting organism, antibiotic used and length of treatment were all recorded. Any antibiotic related complications were noted. Treatment was judged successful with resolution of presenting symptoms, normalization of inflammatory markers and three negative foam cultures. There were 21 patients included in the study. There were 13 male and 8 female patients. Length of treatment ranged from 1 week to 10 weeks with a mean of 4.2 weeks. Follow up ranged from 1 month to 42 months with a mean follow up of 17.9 months. The most common pathogen was Staph. Aureus(11 cases). Enterobacter, ESBL, Strep. Milleri, MRSA and Citrobacter were also treated. Antibiotics instilled included flucloxacillin, meropenem, gentamicin, vancomycin, meropenem and teicoplanin. There were no antibiotic reactions/allergies. Pathologies treated included osteomyelitis, two stage amputations for infection, infected non-union and infected metalwork. Infection recurred in 2 of 21 patients (10%), with one recurring at 18 months and one at 2 years. The 90% treatment success rate is highly encouraging in this notoriously difficult group of patients to treat. In this series vac instill was an effective treatment of infection and allows antibiotic treatment to be targeted to the infected tissues. There were no adverse reactions seen. Larger series with longer follow up are no needed but we believe this technique is safe, successful and easily administered can be cautiously adopted on a wider basis

Introduction. Infection following traumatic injury of the tibia is challenging, with surgical debridement and prolonged systemic antibiotic therapy well established. Local delivery via cement beads has shown improved outcome, but these often require further surgery to remove. Osteoset-T is a bone-graft substitute composed of calcium sulphate and 4%-Tobramycin, available in pellets that are packed easily into bone defects. Concerns remain regarding the sterile effluent produced as it resorbs, along with the risk of acute kidney injury following systemic absorption. Purpose. We present outcomes of 22 patients treated with Osteoset-T. Methods. Medical notes were reviewed of every case of osteomyelitis of the tibia over a 30-month period, in which Osteoset-T had been used. Excision of infected soft tissue and tibial debridement was performed. Metalwork whenever present removed, before Osteoset-T pellets were packed into any cortical defects or the intra-medullary canal. Further stabilisation (n=9) and soft tissue reconstruction (n=7) was undertaken as required. Intravenous vancomycin and meropenem was administered after sampling. Meropenem discontinued after 3 days if no gram negatives cultured, and vancomycin continued for 1 week. Thereafter targeted antibiotic therapy given for 6 weeks, or ciprofloxacin and rifampicin orally if no growth. Results. Average follow-up was 16 months, with wound complications encountered in 50%. A wound discharge in the early post-operative period was noted in 8 patients (36%) independent of site of Osteoset-T placement, with 6 demonstrating wound healing complications. Whereas only 5 of 14 patients without wound leak developed wound complications, but the difference did not reach significance (p=0.18, Fisher exact test). Union rate and infection eradication was 100%, with only one patient developing a transient acute kidney injury. Conclusion. Despite a high incidence of wound discharge that may promote healing complications, Osteoset-T is an effective adjunct in treatment of chronic tibial osteomyelitis following trauma, with nephrotoxicity concerns not warranted

Summary Statement. An Implant Disposable Antibacterial Coating (i-DAC®) is described, consisting of a fully resorbable, biocompatible hydrogel, able to release antibacterial and antibiofilm agents. Direct application of the hydrogel on implants prevented infection occurrence in an in vitro model of peri-prosthetic infection. Introduction. Biofilm-related infections are among the main reasons for failure of joint prosthesis with high associated social and economical costs. Bacterial adhesion and subsequent biofilm formation have been shown to develop early after biomaterials implant into the human body, when a “race to the surface” takes place between the host's cells and the colonizing bacteria eventually present at the surgical site. Providing an antibacterial/antibiofilm coating of the implant may then play a strategic role in preventing biofilm related infections. Here we report the results of a series of in vitro and in vivo studies, partially performed under the European 7th Framework Programme (Implant Disposable Antibiotic Coating, IDAC, collaborative research project # 277988), concerning a fully resorbable, biocompatible antibacterial hydrogel coating (DAC®, Novagenit, Italy). The patented hydrogel, a co-polimer comprising of hyaluronic acid and a polylactic acid, has been designed to be mixed with various antibacterial agents and applied directly on the implant at the time of surgery, being fully resorbed within few days. Patients & Methods. The tested hydrogel (DAC®, Novagenit, Italy) is a derivative of a low molecular weight hyaluronan, grafted with poly-D, L-lactic acid and provided in powder form. At the point of care, the powder is hydrated with the antibiotic or antibiofilm solution, thus generating the final compound to be applied onto the implant surface. In vitro studies were conducted using DAC® coating on different biomaterials, including titanium, chrome-cobalt and polyethylene discs. The release of different antibacterial agents, including vancomycin, ciprofloxacin, meropenem, gentamycin, amikacin, tobramycin, clindamycin, doxycyclin, linezolid, NAsalycilate and N-acetylcisteine, adequately mixed with the hydrogel, has been tested by means of gas chromatography and microbiological methods. In vivo studies were then performed on 35 rabbits divided in 7 groups. Animals were implanted with an intramedullary titanium rod in their femur, with a known inoculum of methicillin-resistant Staph. aureus and vancomycin-loaded DAC® at different concentrations (2% and 5%) and compared with controls. Results. Regardless of the tested material, in vitro studies showed the ability of the hydrogel to be loaded and to sustain the release of the following antibacterial/antibiofilm compounds for up to 96 hours: vancomycin, ciprofloxacin, meropenem, gentamycin, amikacin, tobramycin, clindamycin, doxycyclin, linezolid, NAsalycilate, N-acetylcisteine. In vivo studies showed a bacterial load reduction ranging from 94% to 99.9% using vancomycin-loaded DAC®, compared to controls. Discussion/Conclusion. DAC®, a fast-resorbable antibacterial coating, showed the ability to be loaded with various antibacterial compounds and the ability to provide a highly significant reduction of bacterial colonization of implanted biomaterials in an animal model, opening a new pathway to local prevention and treatment of biofilm-/implant-related infections

Aim. Antibiotic loaded spacers are often used during a two-stage exchange for periprosthetic joint infections (PJI) both for its mechanical properties and as a means for local antibiotic delivery. The main goal of this study is to compare the rate of positive cultures during reimplantation with the use of different antibiotic loaded spacers: aminoglycoside only vs. combined glycopeptide/aminoglycoside vs. combined glycopeptide/carbapenem/aminoglycoside. Method. We retrospectively evaluated every two-stage exchange procedures for infected hip/knee arthroplasty between 2012–2018. Microbiological findings in the first and second stage were registered as well as the type of spacer and antibiotic(s) used. Cases in whom no cultures were obtained during reimplantation and cases without sufficient data on antibiotic(s) used in cement spacers were excluded. Results. Fifty-four cases were included (20THA and 34TKA), with an overall rate of positive cultures during reimplantation of 18.5% (10/54). The rate of positive cultures was statistically significant higher among spacers with monotherapy with aminoglycoside compared to spacers with combined antibiotic therapy- 35.7% (5/14) vs. 12.5% (5/40) respectively(p<0.05). Comparing those with combined glycopeptide/aminoglycoside (2/19) with triple glycopeptide/carbapenem/aminoglycoside therapy (3/21) there was no significant difference. Microorganisms present during the second stage were mostly staphylococci (coagulase-negative in four cases, S.aureus in three), Corynebacterium striatum, Enterococcus faecalis, C.albicans in one case each. In most cases (8/10), the isolated microorganism was the same as the first stage and was resistant to the antibiotic(s) used in the spacer in seven cases. Failure rate with the need for subsequent surgery was significantly higher at 60% (6/10) in cases with positive cultures at reimplantation compared to 4.5% (2/44) for those with negative cultures during reimplantation(p=0.0005). Conclusions. It has recently been suggested that adding a glycopeptide to the spacer may be advantageous when compared to spacers with aminoglycoside monotherapy, as it will produce significantly lower rates of positive cultures during reimplantation which have been shown to increase the risk of subsequent failure as is the case in our study. Local unavailability of obtaining powder aminoglycosides has driven us to manually add high doses of vancomycin and meropenem to commercially available low-dose gentamicin cement in many of our spacers and they seem to to perform just as well as commercially available vancomycin/gentamicin combination. Although many other variables not considered in this study may influence the rate of positive cultures during the second stage (quality of initial debridement, systemic antibiotic therapy, etc.), we believe these results portrait a sufficiently accurate picture of clinical results with the use of different spacers

The management of post-traumatic bone infections relies on antibiotic therapy and surgical debridement. Antibiotic concentration in infected bone is a major determinant of response to medical treatment. The aim is to assess glycopeptides, fluoroquinolones and carbapenems diffusion in infected human bone, since they are widely used for treating bone infections. Twenty-four patients with septic pseudoarthrosis undergoing surgical debridement and treated with glycopeptides/fluoroquinolones/carbapenems iv for > 1 week were studied. Plasma and bone specimens were collected intraoperatively at a mean of 4.8h after antibiotic administration. Antibiotic concentrations were measured by the HPLC-UV method. Five patients received vancomycin: mean bone concentrations were 2.4mg/L in cortical and 7.1mg/L in cancellous bone, with a bone/plasma extraction of 12% and 36%, respectively. Nine patients were treated with teicoplanin: bone concentrations were 2.5mg/L for cortical and 8.3mg/L for cancellous bone (14% and 46% of plasma levels). Five patients received a fluoroquinolone. Ciprofloxacin concentrations were 1.8mg/L in cortical bone and 30.2mg/L in cancellous and newly formed bone (respective bone/plasma ratios 1.06 and 8.4). Levofloxacin concentrations were 0.3 and 2.69mg/L in cortical and cancellous bone, with diffusion rates of 12% and 108%, respectively. Five patients received a carbapenem. Imipenem diffusion rates were respectively 7.5% and 58.3% for cortical and cancellous bone (bone concentrations 0.09 mg/L and 0.7 mg/L). Meropenem levels were 1.2 mg/L and 5.2 mg/L in cortical and cancellous bone, with respective diffusion rates of 3.6% and 15%. Both glycopeptides provided concentrations exceeding the MIC of infecting agents, with satisfactory bone diffusion. Fluoroquinolones, especially ciprofloxacin, displayed excellent diffusion. Ciprofloxacin concentrations in cancellous and new bone were far higher than in plasma, suggesting accumulation into highly vascularized tissue. Imipenem had better diffusion than meropenem, but bone levels were under the MIC of susceptible agents. Glicopeptides and fluoroquinolones appear excellent options for bone infections, while carbapenems should be a second choice treatment

Aims

Gram-negative periprosthetic joint infection (PJI) has been poorly studied despite its rapidly increasing incidence. Treatment with one-stage revision using intra-articular (IA) infusion of antibiotics may offer a reasonable alternative with a distinct advantage of providing a means of delivering the drug in high concentrations. Carbapenems are regarded as the last line of defense against severe Gram-negative or polymicrobial infection. This study presents the results of one-stage revision using intra-articular carbapenem infusion for treating Gram-negative PJI, and analyzes the characteristics of bacteria distribution and drug sensitivity.

Aims

This aim of this study was to analyze the detection rate of rare pathogens in bone and joint infections (BJIs) using metagenomic next-generation sequencing (mNGS), and the impact of mNGS on clinical diagnosis and treatment.

Previous studies showed that a fast-resorbable antibacterial hydrogel coating (DAC®, Novagenit Srl, Mezzolombardo, TN, Italy) composed of covalently linked hyaluronan and poly-D, L-lactide, is able to reduce early post-surgical infection both after joint replacement and osteosynthesis. Aim of the present report is to investigate medium-term safety and efficacy of the coating in patients undergoing primary and revision cementless total hip replacement (THR). We designed a two-phases study. In both phases, DAC was prepared according to manufacturer's instructions. In brief, the syringe prefilled with 300 mg of sterile DAC powder was mixed, at the time of surgery, with a solution of 5 mL of sterile water and with the tailored antibiotics, at a concentration ranging from 25 mg/mL to 50 mg/mL. The resulting antibacterial hydrogel was then spread on the outer surface of the prosthesis just before implantation. In the first phase, safety was assessed. Forty-six patients (13 primary and 33 revision THR) were treated with DAC between 2013 and 2015 and evaluated at a 2.8 ± 0.7 years follow up (FU). Antibiotics used for DAC reconstruction were Vancomycin in 33 cases, Vancomycin + Meropenem in 10, Vancomycin + Rifampicin, Teicoplanin or Ceftazidime in 1 case, respectively. Patients were evaluated at 3, 6, 12 months and yearly after with a clinical and radiographic FU. No evidence of infection and no failure/loosening of the prosthesis were observed. No adverse events were reported. The second phase was designed to evaluate efficacy of DAC in preventing infection recurrences after a two stage revision for infected THR. Twenty-seven patients, treated with DAC coating, were compared with a control group of 32, treated in the same time period, without the coating. Demographics, host type and and identified bacteria were similar in the two groups (18.6% of MRSA in DAC group vs 18.5% MRSA in no-DAC group). Patients were evaluated clinically and radiographically at 3, 6, 12 months and yearly thereafter. At a minimum 2 years FU (mean 2.7), we observed 1 dislocation in each group and 2 cases of loosening in the no-DAC group. 4 cases (11%) of recurrence of infection in the no-DAC group (1 MRSA and 3 St. Epidermidis) and no infection recurrences in the DAC group. Due to the small cohort of patients this difference is not statistically significant (Fisher's exact test, p=0.18). This is, to our knowledge, the longest observation concerning the safety and efficacy of the DAC antibacterial coating, applied to hip replacement. The results are in line with those previously reported and point out the absence of side effects of the antibacterial coating in this application and the tendency to reduce re-infection in second stage. This finding needs to be confirmed by a larger dataset

Aims

To explore the clinical efficacy of using two different types of articulating spacers in two-stage revision for chronic knee periprosthetic joint infection (kPJI).

Aims

Dead-space management, following dead bone resection, is an important element of successful chronic osteomyelitis treatment. This study compared two different biodegradable antibiotic carriers used for dead-space management, and reviewed clinical and radiological outcomes. All cases underwent single-stage surgery and had a minimum one-year follow-up.

Aims

Periprosthetic joint infections (PJIs) with prior multiple failed surgery for reinfection represent a huge challenge for surgeons because of poor vascular supply and biofilm formation. This study aims to determine the results of single-stage revision using intra-articular antibiotic infusion in treating this condition.

Aims

Musculoskeletal infection is a devastating complication in both trauma and elective orthopaedic surgeries that can result in significant morbidity. Aim of this study was to assess the effectiveness and complications of local antibiotic impregnated dissolvable synthetic calcium sulphate beads (Stimulan Rapid Cure) in the hands of different surgeons from multiple centres in surgically managed bone and joint infections.

Aims

Gram-negative infections are associated with comorbid patients, but outcomes are less well understood. This study reviewed diagnosis, management, and treatment for a cohort treated in a tertiary spinal centre.

Aims

To explore the effect of different durations of antibiotics after stage II reimplantation on the prognosis of two-stage revision for chronic periprosthetic joint infection (PJI).

Aims

One-stage revision hip arthroplasty for periprosthetic joint infection (PJI) has several advantages; however, resection of the proximal femur might be necessary to achieve higher success rates. We investigated the risk factors for resection and re-revisions, and assessed complications and subsequent re-revisions.

Aims

It can be extremely challenging to determine whether to perform reimplantation in patients who have contradictory serum inflammatory markers and frozen section results. We investigated whether patients with a positive frozen section at reimplantation were at a higher risk of reinfection despite normal ESR and CRP.

Aims

We aimed to report the mid- to long-term rates of septic and aseptic failure after two-stage revision surgery for periprosthetic joint infection (PJI) following total hip arthroplasty (THA).

Antibiotic resistance represents a threat to human health. It has been suggested that by 2050, antibiotic-resistant infections could cause ten million deaths each year. In orthopaedics, many patients undergoing surgery suffer from complications resulting from implant-associated infection. In these circumstances secondary surgery is usually required and chronic and/or relapsing disease may ensue. The development of effective treatments for antibiotic-resistant infections is needed. Recent evidence shows that bacteriophage (phages; viruses that infect bacteria) therapy may represent a viable and successful solution. In this review, a brief description of bone and joint infection and the nature of bacteriophages is presented, as well as a summary of our current knowledge on the use of bacteriophages in the treatment of bacterial infections. We present contemporary published in vitro and in vivo data as well as data from clinical trials, as they relate to bone and joint infections. We discuss the potential use of bacteriophage therapy in orthopaedic infections. This area of research is beginning to reveal successful results, but mostly in nonorthopaedic fields. We believe that bacteriophage therapy has potential therapeutic value for implant-associated infections in orthopaedics.

Cite this article: Bone Joint J 2021;103-B(2):234–244.

Aims

Flucloxacillin is commonly administered intravenously for perioperative antimicrobial prophylaxis, while oral administration is typical for prophylaxis following smaller traumatic wounds. We assessed the time, for which the free flucloxacillin concentration was maintained above the minimum inhibitory concentration (fT > MIC) for methicillin-susceptible Staphylococcus aureus in soft and bone tissue, after intravenous and oral administration, using microdialysis in a porcine model.

Aims

To explore the effect of different types of articulating antibiotic-loaded cement spacers in two-stage revision for chronic hip prosthetic joint infection (PJI).

Objectives

Thermal 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.

Aims

The aims of this study were to report the efficacy of revision surgery for patients with co-infective bacterial and fungal prosthetic joint infections (PJIs) presenting to a single institution, and to identify prognostic factors that would guide management.

Aims

Leucocyte esterase (LE) has been shown to be an accurate marker of prosthetic joint infection (PJI), and has been proposed as an alternative to frozen section (FS) histology for intraoperative diagnosis. In this study, the intraoperative assessment of LE was compared with FS histology for the diagnosis of prosthetic hip infection.

Aims

Single-stage revision is not widely pursued due to restrictive inclusion criteria. In this study, we evaluated the results of single-stage revision of chronically infected total hip arthroplasty (THA) using broad inclusion criteria and cementless implants.

Aims

Advocates of debridement, antibiotics and implant retention (DAIR) in hip periprosthetic joint infection (PJI) argue that a procedure not disturbing a sound prosthesis-bone interface is likely to lead to better survival and functional outcome compared with revision. This case-control study aims were to compare outcome of DAIRs for infected primary total hip arthroplasty (THA) with outcomes following primary THA and two-stage revision of infected primary THAs.

Little information is available about several important aspects of the treatment of melioidosis osteomyelitis and septic arthritis.

We undertook a retrospective review of 50 patients with these conditions in an attempt to determine the effect of location of the disease, type of surgical intervention and duration of antibiotic treatment on outcome, particularly complications and relapse.

We found that there was a 27.5% risk of osteomyelitis of the adjacent bone in patients with septic arthritis in the lower limb. Patients with septic arthritis and osteomyelitis of an adjacent bone were in hospital significantly longer (p = 0.001), needed more operations (p = 0.031) and had a significantly higher rate of complications and re-presentation (p = 0.048).

More than half the patients (61%), most particularly those with multifocal bone and joint involvement, and those with septic arthritis and osteomyelitis of an adjacent bone who were treated operatively, needed more visits to theatre.

Cite this article: Bone Joint J 2015;97-B:277–82.

The treatment of chronic osteomyelitis often includes surgical debridement and filling the resultant void with antibiotic-loaded polymethylmethacrylate cement, bone grafts or bone substitutes. Recently, the use of bioactive glass to treat bone defects in infections has been reported in a limited series of patients. However, no direct comparison between this biomaterial and antibiotic-loaded bone substitute has been performed.

In this retrospective study, we compared the safety and efficacy of surgical debridement and local application of the bioactive glass S53P4 in a series of 27 patients affected by chronic osteomyelitis of the long bones (Group A) with two other series, treated respectively with an antibiotic-loaded hydroxyapatite and calcium sulphate compound (Group B; n = 27) or a mixture of tricalcium phosphate and an antibiotic-loaded demineralised bone matrix (Group C; n = 22). Systemic antibiotics were also used in all groups.

After comparable periods of follow-up, the control of infection was similar in the three groups. In particular, 25 out of 27 (92.6%) patients of Group A, 24 out of 27 (88.9%) in Group B and 19 out of 22 (86.3%) in Group C showed no infection recurrence at means of 21.8 (12 to 36), 22.1 (12 to 36) and 21.5 (12 to 36) months follow-up, respectively, while Group A showed a reduced wound complication rate.

Our results show that patients treated with a bioactive glass without local antibiotics achieved similar eradication of infection and less drainage than those treated with two different antibiotic-loaded calcium-based bone substitutes.

Cite this article: Bone Joint J 2014; 96-B:845–50.

Prophylactic antibiotics can decrease the risk of wound infection and have been routinely employed in orthopaedic surgery for decades. Despite their widespread use, questions still surround the selection of antibiotics for prophylaxis, timing and duration of administration. The health economic costs associated with wound infections are significant, and the judicious but appropriate use of antibiotics can reduce this risk.

This review examines the evidence behind commonly debated topics in antibiotic prophylaxis and highlights the uses and advantages of some commonly used antibiotics.

Cite this article: Bone Joint J 2016;98-B:1014–19.

Drug therapy forms an integral part of the management of many orthopaedic conditions. However, many medicines can produce serious adverse reactions if prescribed inappropriately, either alone or in combination with other drugs. Often these hazards are not appreciated. In response to this, the European Union recently issued legislation regarding safety measures which member states must adopt to minimise the risk of errors of medication.

In March 2014 the Medicines and Healthcare products Regulatory Agency and NHS England released a Patient Safety Alert initiative focussed on errors of medication. There have been similar initiatives in the United States under the auspices of The National Coordinating Council for Medication Error and The Joint Commission on the Accreditation of Healthcare Organizations. These initiatives have highlighted the importance of informing and educating clinicians.

Here, we discuss common drug interactions and contra-indications in orthopaedic practice. This is germane to safe and effective clinical care.

Cite this article: Bone Joint J 2015;97-B:434–41.

We report our experience using a biodegradable calcium sulphate antibiotic carrier containing tobramycin in the surgical management of patients with chronic osteomyelitis. The patients were reviewed to determine the rate of recurrent infection, the filling of bony defects, and any problems with wound healing. A total of 193 patients (195 cases) with a mean age of 46.1 years (16.1 to 82.0) underwent surgery. According to the Cierny–Mader classification of osteomyelitis there were 12 type I, 1 type II, 144 type III and 38 type IV cases. The mean follow-up was 3.7 years (1.3 to 7.1) with recurrent infection occurring in 18 cases (9.2%) at a mean of 10.3 months post-operatively (1 to 25.0). After further treatment the infection resolved in 191 cases (97.9%). Prolonged wound ooze (longer than two weeks post-operatively) occurred in 30 cases (15.4%) in which there were no recurrent infection. Radiographic assessment at final follow-up showed no filling of the defect with bone in 67 (36.6%), partial filling in 108 (59.0%) and complete filling in eight (4.4%). A fracture occurred in nine (4.6%) of the treated osteomyelitic segments at a mean of 1.9 years (0.4 to 4.9) after operation.

We conclude that Osteoset T is helpful in the management of patients with chronic osteomyelitis, but the filling of the defect in bone is variable. Prolonged wound ooze is usually self-limiting and not associated with recurrent infection.

Cite this article: Bone Joint J 2014; 96-B:829–36

Blast and ballistic weapons used on the battlefield cause devastating injuries rarely seen outside armed conflict. These extremely high-energy injuries predominantly affect the limbs and are usually heavily contaminated with soil, foliage, clothing and even tissue from other casualties. Once life-threatening haemorrhage has been addressed, the military surgeon’s priority is to control infection.

Combining historical knowledge from previous conflicts with more recent experience has resulted in a systematic approach to these injuries. Urgent debridement of necrotic and severely contaminated tissue, irrigation and local and systemic antibiotics are the basis of management. These principles have resulted in successful healing of previously unsurvivable wounds. Healthy tissue must be retained for future reconstruction, vulnerable but viable tissue protected to allow survival and avascular tissue removed with all contamination.

While recent technological and scientific advances have offered some advantages, they must be judged in the context of a hard-won historical knowledge of these wounds. This approach is applicable to comparable civilian injury patterns. One of the few potential benefits of war is the associated improvement in our understanding of treating the severely injured; for this positive effect to be realised these experiences must be shared.

Haematogenous osteomyelitis in newborns and infants usually occurs in the long bones and is rare in the short or flat bones. We present two neonates with osteomyelitis of the upper cervical spine affecting the second to fourth cervical vertebrae and the first and second cervical vertebrae, respectively. Despite some delay in diagnosis, both responded successfully to conservative treatment with antibiotics, a cervical collar and needle puncture. The latest follow-up at six and seven years, respectively, showed no persistent neurological deficit and a normal diameter of the cervical spinal canal on MRI.

Deep prosthetic joint infection remains an uncommon but serious complication of total hip replacement. We reviewed 24 patients with recalcitrant hip wounds following infected total hip replacement treated with either pedicled rectus femoris or vastus lateralis muscle flaps between 1998 and 2009. The mean age of the patients was 67.4 years (42 to 86) with ten men and 14 women.

There had been a mean of four (1 to 8) previous attempts to close the wound. A total of 20 rectus femoris and five vastus lateralis flaps were used, with one of each type of flap failing and requiring further reconstruction. All patients had positive microbiology. At a mean follow-up of 47 months (9 to 128), 22 patients had a healed wound and two had a persistent sinus. The prosthesis had been retained in five patients. In the remainder it had been removed, and subsequently re-implanted in nine patients. Six patients continued to take antibiotics at final follow-up.

This series demonstrates the effectiveness of pedicled muscle flaps in healing these infected wounds. The high number of previous debridements suggests that these flaps could have been used earlier.

We report a case of Lemierre’s syndrome complicated by an epidural abscess. This manifestation of Lemierre’s syndrome has not been described previously.

We describe a technique of ‘cross-hip distraction’ to reduce a dislocated hip with subsequent reconstruction of the joint for septic arthritis with extensive femoral osteomyelitis. A 27-year-old woman presented with a dislocated, collapsed femoral head and chronic osteomyelitis of the femur. Examination revealed a leg-length discrepancy of 7 cm and an irritable hip. A staged technique was used with primary clearance of osteomyelitis and secondary reconstruction of the hip. A cross-hip monolateral external fixator was used to establish normal anatomy followed by an arthroplasty. A good functional outcome was achieved. The use of cross-hip distraction avoids soft-tissue and nerve damage and achieved improved abductor function before arthroplasty.

Revision arthroplasty after infection can often be complicated by both extensive bone loss and a relatively high rate of re-infection. Using allograft to address the bone loss in such patients is controversial because of the perceived risk of bacterial infection from the use of avascular graft material. We describe 12 two-stage revisions for infection in which segmental allografts were loaded with antibiotics using iontophoresis, a technique using an electrical potential to drive ionised antibiotics into cortical bone.

Iontophoresis produced high levels of antibiotic in the allograft, which eluted into the surrounding tissues. We postulate that this offers protection from infection in the high-risk peri-operative period. None of the 12 patients who had two-stage revision with iontophoresed allografts had further infection after a mean period of 47 months (14 to 78).