Aims

To investigate the efficacy of ethylenediaminetetraacetic acid-normal saline (EDTA-NS) in dispersing biofilms and reducing bacterial infections.

Aim. Antibiotic concentration at the infected site is a relevant information to gain knowledge about deep-seated infections. The combination of antibiotic therapy and debridement is often indicated to treat these infections. At University Hospital Basel the most frequently administered antibiotic before debridement is amoxicillin in combination with clavulanic acid. Amoxicillin is a fragile beta-lactam antibiotic that brings multiple challenges for its quantification. As for many sample materials only little material is available, the aim of this work was to establish a sensitive and reliable quantification method for amoxicillin that only requires a small sample mass. We did not quantify clavulanic acid as we focused on the drug with antibiotic action. Method. Usually discarded sample material during debridement was collected and directly frozen. The thawed tissues were prepared using simple protein precipitation and manual homogenization with micro pestles followed by a matrix cleanup with online solid-phase extraction. Separation was performed by HPLC followed by heated electrospray ionization and tandem mass spectrometry. Results. During method development, amoxicillin showed partial formation of a covalent methanol adduct when performing protein precipitation. Furthermore, multiple in-source products of amoxicillin during ionization could be observed. Adding an aqueous buffer to the samples before protein precipitation and summing up the signals of amoxicillin and its in-source acetonitrile-sodium-adduct led to successful method validation for a calibration range of 1–51 mg/kg using 10 mg of each tissue sample. The imprecision was < 8% over the entire concentration range and the bias was ≤ 10 %. The quantitative matrix effect was < 6 % in six different tissue samples. Until now we measured amoxicillin in samples from nine patients with prosthetic joint infection, bursitis, or an abscess who obtained amoxicillin between 5 hours and 15 minutes before sampling and found concentrations between 1.4 and 35 mg/kg. Conclusions. With this method, we developed a fast, simple, and sensitive quantification assay for amoxicillin in tissue samples with little material that can now be applied to different study samples

Aim. In this study we investigated the effects of non-steroidal anti-inflammatory drugs (NSAIDs) with different cyclooxygenase (COX) selectivity on orthopaedic device-related infections (ODRIs) in a rat model. Specifically, we aimed to measure the impact of NSAID therapy on bone changes, bacterial load, and cytokine levels after treatment with antibiotics. In addition, we compared the effects of long vs short-term celecoxib (a COX-2 inhibitor) treatment on the same outcomes. Method. Skeletally mature female Wistar rats were implanted with Staphylococcus epidermidis-contaminated polyetheretherketone (PEEK) screws (1.5 × 10. 6. CFU per screw) in the proximal right tibia and monitored for 7 days. All animals received subcutaneous antibiotics (rifampicin plus cefazolin) for two weeks from day 7 to 21. In phase I of the study, rats were randomly assigned to receive 28 days of oral treatment with acetylsalicylic acid, ibuprofen, celecoxib, or vehicle control. In phase II, an additional group received seven days of celecoxib treatment from day 0 to 7. After implantation, bone changes were monitored using in vivo micro-CT and histology. Quantitative bacteriology was performed at euthanasia. Plasma samples were collected to measure cytokine levels at four time points (day 0, 6, 20, and 28). Results. The combination of antibiotic therapy resulted in treatment success in 85.71% of cases, while the addition of long-term celecoxib treatment reduced it to 45.45%. Long-term celecoxib treatment significantly reduced bone loss (33.85% mean difference [95% CI 14.12–53.58], p=0.0004 on day 6 bone fraction) and periosteal reaction (0.2760 μm mean difference [95% CI 0.2073–0.3448], p<0.0001 on day 14 periosteal thickness) during the early post-infection period compared to the control group. Short-term celecoxib treatment showed similar radiological results, however, there was no significant reduction in treatment success in the celecoxib group (88.9%). No differences in the selected inflammatory markers were observed. Conclusion. Our findings highlight the potential benefits of short-term use of celecoxib in improving bone fraction during the early post-infection period without impairing the efficacy of antibiotic therapy. This study suggests that celecoxib may be a useful addition to the multimodal approach to pain management in orthopaedic device-related infections

We investigated the effects of non-steroidal anti-inflammatory drugs (NSAIDs) with different cyclooxygenase (COX) selectivity on orthopaedic device-related infections (ODRIs) in a rat model. We aimed to measure the impact of NSAID therapy on bone changes, bacterial load, and cytokine levels after treatment with antibiotics. We also compared the effects of long vs short-term celecoxib (a COX-2 inhibitor) treatment on the same outcomes. Skeletally mature female Wistar rats were implanted with Staphylococcus epidermidis- contaminated polyetheretherketone (PEEK) screws in the proximal right tibia and monitored for 7 days. All animals received subcutaneous antibiotics (rifampicin plus cefazolin) for two weeks from day 7 to 21. In phase I of the study, rats were randomly assigned to receive 28 days of oral treatment with acetylsalicylic acid, ibuprofen, celecoxib, or vehicle control. In phase II, an additional group received seven days of celecoxib treatment from day 0 to 7. Bone changes were monitored using in vivo micro-CT and histology. Quantitative bacteriology was performed at euthanasia. Plasma samples were collected to measure cytokine levels on days 0, 6, 20, and 28. Combination antibiotic therapy resulted in treatment success in 85.71% of cases, while the addition of long-term celecoxib treatment reduced it to 45.45%. Long-term celecoxib treatment significantly reduced bone loss (33.85% mean difference [95% CI 14.12–53.58], p=0.0004 on day 6 bone fraction) and periosteal reaction (0.2760 μm mean difference [95% CI 0.2073–0.3448], p<0.0001 on day 14 periosteal thickness) during early infection compared to the control group. Short- term celecoxib treatment showed similar radiological results without a reduction in treatment success (88.9%). No differences in the inflammatory markers were observed. Our findings highlight the potential benefits of short-term use of celecoxib in improving bone fraction during the early post-infection period without impairing the efficacy of antibiotic therapy

Aims. Periprosthetic joint infections (PJIs) are rare, but represent a great burden for the patient. In addition, the incidence of methicillin-resistant Staphylococcus aureus (MRSA) is increasing. The aim of this rat experiment was therefore to compare the antibiotics commonly used in the treatment of PJIs caused by MRSA. Methods. For this purpose, sterilized steel implants were implanted into the femur of 77 rats. The metal devices were inoculated with suspensions of two different MRSA strains. The animals were divided into groups and treated with vancomycin, linezolid, cotrimoxazole, or rifampin as monotherapy, or with combination of antibiotics over a period of 14 days. After a two-day antibiotic-free interval, the implant was explanted, and bone, muscle, and periarticular tissue were microbiologically analyzed. Results. Vancomycin and linezolid were able to significantly (p < 0.05) reduce the MRSA bacterial count at implants. No significant effect was found at the bone. Rifampin was the only monotherapy that significantly reduced the bacterial count on implant and bone. The combination with vancomycin or linezolid showed significant efficacy. Treatment with cotrimoxazole alone did not achieve a significant bacterial count reduction. The combination of linezolid plus rifampin was significantly more effective on implant and bone than the control group in both trials. Conclusion. Although rifampicin is effective as a monotherapy, it should not be used because of the high rate of resistance development. Our animal experiments showed the great importance of combination antibiotic therapies. In the future, investigations with higher case numbers, varied bacterial concentrations, and changes in individual drug dosages will be necessary to be able to draw an exact comparison, possibly within a clinical trial. Cite this article: Bone Joint Res 2022;11(3):143–151

Aims

Removal of infected components and culture-directed antibiotics are important for the successful treatment of chronic periprosthetic joint infection (PJI). However, as many as 27% of chronic PJI patients yield negative culture results. Although culture negativity has been thought of as a contraindication to one-stage revision, data supporting this assertion are limited. The aim of our study was to report on the clinical outcomes for one-stage and two-stage exchange arthroplasty performed in patients with chronic culture-negative PJI.

Aim. Treatment of chronic prosthetic joint infection (PJI) combines exchange arthroplasty and effective antibiotic therapy. Staphylococci are the most frequent microorganism isolated in PJIs, with resistance to methicillin found in 15–50% of the cases. Data from randomized trials on treatment of methicillin-resistant staphylococci are lacking and the choice of antibiotic(s) and recommendations vary according to authors. To date, combination therapy including vancomycin is the treatment of choice. Minocycline, a cyclin antibiotic, is naturally effective against methicillin-resistant staphylococci. We use this antibiotic since many years in combination with vancomycin for the treatment of multi-drug resistant staphylococcal bone and joint infections. The aim of this study is to analyze the outcome of patients treated with combination antibiotic therapy including minocycline for the treatment of chronic methicillin-resistant staphylococcal PJI. Method. We conducted a cohort study between 2004 and 2014 in our referral center for bone and joint infections. Data were extracted from the prospective database. All the patients receiving an initial combination therapy including at least 4 weeks of minocycline, given orally, and another IV antibiotic, usually high-dose continuous IV vancomycin, for chronic MR staphylococcal PJI and who underwent one or two stage exchange arthroplasty, were included. They were followed prospectively for at least 2 years. Results. We included 42 patients: 26 patients (62%) had one-stage, 16 patients (38%) had two stage exchange arthroplasty. Median duration of IV and total antibiotic therapy was 42 [40–44] days and 84 [84–88] days, respectively. 41 patients (98%) received vancomycin as associated initial therapy. Thirty-six patients received 100mgx3 per day of minocycline. Six received >300mg per day because of low serum concentrations. Median follow-up was 48 months (IQR 27–58). Survival rate without infection was 84,5% at 2 years, 70.2% at 6 years. Four patients reported adverse events due to minocycline: one had grade 4 thrombopenia leading to minocycline withdrawal, two had grade 2 liver toxicity. One patient had grade 1 nauseas. Two patients with MR Staphylococcus epidermidis knee arthroplasty experienced relapse. Three patients with hip arthroplasty infection developed a new infection within 2 year due to MSSA, Pseudomonas aeruginosa, and plurimicrobial for the last one. Three further patients developed a new infection 3 (n=2) and 4 years later. They were all acute haematogenous infections. Conclusions. Our data support the use of minocycline combination therapy with high-dose IV vancomycin for the treatment of chronic PJI due to methicillin-resistant Staphylococci

This longitudinal microCT study revealed the osteolytic response to a Staphylococcus epidermidis-infected implant in vivoand also demonstrates how antibiotics and/or a low bone mass state influence the morphological changes in bone and the course of the infection. Colonisation of orthopaedic implants with Staphylococcus aureusor S. epidermidisis a major clinical concern, since infection-induced osteolysis can drastically impair implant fixation or integration within bone. High fracture incidence in post-menopausal osteoporosis patients means that this patient group are at risk of implant infection. The low bone mass in these patients may exacerbate infection-induced osteolysis, or alter antibiotic efficacy. Therefore, the aims of this study were to examine the bone changes resulting from a S. epidermidisimplant infection in vivousing microCT imaging, and to determine if a low bone mass stateinfluences the course of the infection and the efficacy of antibiotic therapy. An in vivomodel system using microCT scanning [1], involving the implantation of either a sterile or a S. epidermidis-colonised PEEK screw into the proximal tibia of 24 week-old female Wistar rats, was used to investigate the morphological changes in bone following infection over a 28 day period. In addition, the efficacy of a combination antibiotic therapy (rifampin and cefazolin: administered twice daily from days 7–21 post-screw implantation) for affecting osteolysis was also assessed. A subgroup of animals was subjected to ovariectomy (OVX) at 12 weeks of age, allowing for a 12 week period for bone loss prior to screw implantation at 24 weeks. Bone resorption and formation rates, bone-implant contact and peri-implant bone volume in the proximity of the screw were assessed by microCT scanning at days 0, 3, 6, 9, 14, 20 and 28 days post-surgery. Following euthanasia at day 28, the implanted screw, bone and soft tissues were subjected to quantitative bacteriology as a measure of the efficacy of the antibiotic regimen. In non-OVX animals S. epidermidisinfection induced marked osteolysis, which peaked between 9 and 14 days post-screw implantation. Peak bone resorption was detected at day 6, before recovering to baseline levels at day 14. Infection also resulted in extensive deposition of mineralised tissue, initially within the periosteal region (day 9–14), then subsequently in the osteolytic region at day 20–28. Quantitative bacteriology indicated all non-OVX animals remained infected. Rifampin and cefazolin successfully cleared the infection in 5/6 non-OVX animals group although there was no difference observed in CT-derived bone parameters. OVX resulted in extensive loss of trabecular bone but this did not alter the temporal pattern of infection-induced osteolysis, or mineralised tissue deposition, which was similar to that observed in the non-OVX animals. Similarly, there was no difference in bacterial counts between non-OVX and OVX animals (39,005 colony-forming units (CFU) [range: 3,675–156,800] vs 37,665 CFU [range 3,250–84,000], respectively). Interestingly, antibiotic treatment was less effective in the OVX animals (3/5 remained infected), suggesting that antibiotics have reduced efficacy in OVX animals. This study demonstrates S. epidermidis-induced osteolysis displays a similar temporal pattern in both normal and low bone mass states, with comparable bacterial loads present within the localised infection site

We retrospectively reviewed the records of 16 children treated for spondylodiscitis at our hospital between 2000 and 2007. The mean follow-up was 24 months (12 to 38). There was a mean delay in diagnosis in hospital of 25 days in the ten children aged less than 24 months. At presentation only five of the 16 children presented with localising signs and symptoms. Common presenting symptoms were a refusal to walk or sit in nine children, unexplained fever in six, irritability in five, and limping in four. Plain radiography showed changes in only seven children. The ESR was the most useful investigation when following the clinical course of the disease. Positive blood cultures were obtained in seven children with Staphylococcus aureus being isolated in five. Antibiotics were used in 14 children and spinal bracing in six. Children with spondylodiscitis often present with a confusing clinical picture leading to late diagnosis.

The early use of MRI in the investigation of children with an atypical picture may avoid unnecessary delay in starting treatment and possibly prevent long-term problems. All except one of our children had made a complete clinical recovery at final follow-up. However, all six children in the > 24-month age group showed radiological evidence of degenerative changes which might cause problems in the future.

Biofilm-associated infections in wounds or on implants are difficult to treat. Eradication of the bacteria is nearly always impossible, despite the use of specific antibiotics. The bactericidal effects of high-energy extracorporeal shock waves on Staphylococcus aureus have been reported, but the effect of low-energy shock waves on staphylococci and staphylococcal biofilms has not been investigated. In this study, biofilms grown on stainless steel washers were examined by electron microscopy. We tested ten experimental groups with Staph. aureus-coated washers and eight groups with Staph. epidermidis. The biofilm-cultured washers were exposed to low-energy shock waves at 0.16 mJ/mm. 2. for 500 impulses. The washers were then treated with cefuroxime, rifampicin and fosfomycin, both alone and in combination. All tests were carried out in triplicate. Viable cells were counted to determine the bactericidal effect. The control groups of Staph. aureus and Staph. epidermidis revealed a cell count of 6 × 10. 8. colony-forming units/ml. Complete eradication was achieved using the combination of antibiotic therapy (single antibiotic in Staph. aureus, a combination in Staph. epidermidis) and shock wave application (p < 0.01). We conclude that shock waves combined with antibiotics could be tested in an in vitro model of infection

Infection following hip arthroplasty although uncommon can have devastating outcomes. Obesity, defined as a BMI of ≥ 30, is a risk factor for infection in this population. Coagulase negative staphylococcus aureus (CNS) is the commonest causative organism isolated from infected arthroplasties. This study was performed to determine if there has been a change in the causative organisms isolated from infected hip arthroplasties and to see if there is a difference in obese patients. Data on all deep infection following primary and revision hips was obtained from the surgical site infection register from April 1998 to Nov 2007. Case notes were reviewed retrospectively. There were 49 patients with 51 infected arthroplasties; 25 infected Primary THAs and 26 infected Revision THAs. We found a female preponderance in the infected primary and revision THAs (n=30). 63.2% of all patients had a BMI of ≥ 30, compared to only 34.7% of the non infected population (p< 0.0001). Over the period studied, CNS was the most common organism isolated (56.8%) followed by mixed organisms (37.2%) and staphylococcus aureus (25.4%). Multiple organisms were found exclusively in obese patients. In more than half of cases the causative organisms were resistant to more than two antibiotics. This study shows that over the last 10 years, CNS continues to be the most frequently isolated organism in infected hip arthroplasties. Multiple organisms with multiple antibiotic resistances are common in obese patients. On this basis we recommend that combination antibiotic therapy should be considered in obese patients

Introduction: Infection following hip arthroplasty although uncommon can have devastating outcomes. Obesity, defined as a BMI of ≥ 30, is a known risk factor for infection in this population. Coagulase negative Staph Aureus (CNS) is the commonest causative organism isolated from infected arthroplasties. This study was performed to determine if there has been a change in the causative organisms isolated from infected hip arthroplasties and to see if there is a difference in obese patients. Methods: Data on all deep infection following primary and revision hips was obtained from the surgical site infection register from April 1998 to November 2007. All case notes were reviewed retrospectively. Results: There were 49 patients with 51 infected arthroplasties; 25 infected Primary THAs and 26 infected Revision THAs. We found a female preponderance in the infected primary and revision THAs (n=30). 65.3% of all patients had a BMI of ≥ 30. Over the period studied, Coagulase negative Staph was the most common organism isolated (56.8%) followed by mixed organisms (37.2%) and Staph Aureus (25.4%). Multiple organisms were found exclusively in obese patients. In more than half of cases the causative organisms were resistant to ≥ 2 antibiotics. Discussion: This study shows that over the last 10 years, CNS continues to be the most frequently isolated organism in infected hip arthroplasties. Multiple organisms with multiple antibiotic resistances are common in obese patients. On this basis we recommend that combination antibiotic therapy should be considered in obese patients

Aim: To present the features and management of Pyogenic myositis in children. Method: Two boys of four and six years old presented to our hospital within 6 months. The initial presentation suggested septic arthritis of the hip with pain, pyrexia and limited hip movements. Serum inflammatory markers were significantly raised. Hip rotation, however, was not severely reduced when examined carefully. Neither case demonstrated an effusion on ultrasound of the hip joint. The diagnosis was made on magnetic resonance imaging which produced striking images. Staphylococcus aureus was isolated from blood cultures in each case. Results: Both children settled with antibiotic treatment alone. The bacterial strain in the second case was of a type requiring combination antibiotic therapy for effective treatment. Conclusions: Pyogenic myositis is not a common diagnosis in previously healthy children presenting with hip pain. It is a condition that has been reported more frequently recently and which should have a higher profile since it is probably under-diagnosed. Urgent magnetic resonance imaging is recommended for atypical cases of musculoskeletal infection in children. Care must be taken to prescribe antibiotic therapy appropriate to the particular bacterial strain