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

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

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

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

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

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.

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