Aim. Implant-associated infection usually require prolonged treatment or even removal of the implant. Local application of antibiotics is used commonly in orthopaedic and trauma surgery, as it allows reaching higher concentration in the affected compartment, while at the same time reducing systematic side effects. Ceftriaxone release from calcium sulphate has a particularly interesting, near-constant release profile in vitro, making it an interesting drug for clinical application. Purpose of the present study was to investigate the potential cytotoxicity of different ceftriaxone concentrations and their influence on osteogenic differentiation of human pre-osteoblasts. Method. Human pre-osteoblasts were cultured up to 28 days in different ceftriaxone concentrations, ranging between 0 mg/L and 50’000 mg/L. Cytotoxicity was determined quantitatively by measuring lactate dehydrogenase release, metabolic activity, and cell proliferation. Gene expression analysis of bone-specific markers as well as mineralization and protein expression of collagen-I (Col-I) were investigated to assess osteogenic differentiation. Results. Cytotoxic effects on human pre-osteoblasts could be shown above 15’000 mg/L after 1 and 2 days, whereas subtoxic effects could be observed at concentrations at 500 mg/L after 10 days. Cell proliferation showed no clear alteration up to 1000 mg/L, though a notable decline at 1500 mg/L could be seen after 10 days. Gene and protein expression of Col-I showed a concentration-dependent decrease at day 10 and 14, but also mineralization levels of human pre-osteoblasts presented a similar trend at day 28. Interestingly, the degree of mineralization was already impaired at concentrations above 250 mg/L. Conclusions. These findings provided extensive insights into the influence of different ceftriaxone concentrations on viability, proliferation, gene, and protein expression but also mineralization of human bone pre-osteoblasts. While short-term cytotoxicity is observed only at very high concentrations, metabolism may be impaired at much lower concentrations when exposure is prolonged. Release of ceftriaxone expected from calcium sulphate however remains below thresholds of impaired bone mineralization, even after 4 weeks of exposure. This study demonstrates the importance of properly selecting and monitoring antibiotic concentrations during clinical application

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. Ceftobiprole, a broad-spectrum cephalosporin, could be used for post-operative treatment of bone implant-associated infections. The aim of the study is to evaluate the in vitro susceptibility of bacteria isolated from bone implant-associated infections to ceftobiprole. Method. We conducted an in vitro, retrospective and comparative study between July 2013 to April 2017 including patients with bone implant-associated infections (prosthesis joint infection (PJI) and osteosynthesis material (OM)). To evaluate MIC distribution of ceftobiprole against Gram positive and Gram negative strains and to compare activity of ceftobiprole to vancomycin for Gram positive and ceftriaxone or ceftazidime for Gram negative strains, we tested all strains (stored in Cryobank storage system) for minimal inhibitory concentrations (MIC) determination by E-test bandelet for ceftobiprole and comparator antibiotics. Results. We collected 63 Gram negative strains (57 Enterobateriaceae and 6 Pseudomonas aeruginosa), isolated from 25 patients with OM and 38 patients with PJI (23 hips and 15 knees), and 100 Gram positive strains (85 Staphylococcus sp, 8 E. faecalis, 7 Propionibacterium sp.) isolated from 38 patients with OM and 62 patients with PJI (33 hips, 28 knees, 1 shoulder). A total of 61.4% of Enterobacteriaceae were susceptible both with ceftobiprole and ceftriaxone, 100% of P. aeruginosa were susceptible with ceftazidime and 83,3% with ceftobiptrole and finally 100% of Gram positive were susceptible both with ceftobiprole and vancomycin (susceptibility interpretation was based on EUCAST breakpoints). Conclusions. Our results suggest that ceftobiprole has a good in vitro activity against strains isolated from bone implant-associated infections. It could be an effective alternative to vancomycin and ceftriaxone or ceftazidime in post-operative treatment but pharmacokinetics and pharmacodynamics studies must be performed in bone tissue

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

Spondylodiscitis rarely coexists with endocarditis (around 5% of patients with endocarditis). Furthermore, viridans streptococci are not common pathogens of spondylodiscitis and finally the combination of spondylodiscitis and right – sided endocarditis due to viridans streptococci is rare. We present a case of right-sided native valve endocarditis due to Streptococcus mutans presenting as cervical and lumbar spondylodiscitis in a patient with obstructive cardiomyopathy. A 52 year – old man with a history of hypertrophic obstructive cardiomyopathy was admitted with fever and back pain of ten days duration, followed by torticollis. He had undergone dental therapy some weeks before symptom appearance, due to bad oral hygiene, without receiving any chemoprophylaxis. Magnetic resonance imaging revealed L4-L5 and C4-C5 spondylodiscitides. Four blood cultures drawn were all positive for Streptococcus mutans, while fine needle aspiration of the lumbar lesion was unsuccessful. Transesophageal echocardiogram revealed tricuspid and possible pulmonary valve vegetations. The patient was treated with ceftriaxone plus gentamicin for 2 weeks and then ceftriaxone only, for a total of 3 months. He had an uneventful recovery and was referred for cardiosurgical consultation. Physicians managing cases of spondylodiscitides should bear in mind to rule out endocarditis, especially in cases with underlying cardiopathy. The possibility of coexistence is even greater when there is sustained bacteremia and the pathogen isolated from blood cultures is a common pathogen for endocarditis

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

To report a case and a review of the literature about TKA infection caused by P. multocida. We report the case of a 65 year old woman, with history of a left TKA for primary osteoarthritis. Six months after surgery, the patient presented with fever and a wound in her right leg, two days after being bitten by her cat. She was treated with flucloxacilin. One week later, she returned complaining about pain and stifness in her left knee. She presented fever, swelling, erythema, warmness and pain of the left knee. Complete blood count revealed leukocytosis with neutrophilia. Erythrocyte Sedimentation Rate and C-Reactive Protein were elevated. The knee joint was aspirated and a large amount of purulent fluid was obtained and sent to gram stain and culture. The X-ray of the knee was normal. Gram stain showed a large number of leucocytes and gram-negative coccobacilli. The patient began ceftriaxone, empirically. The culture grew Pasteurella multocida sensitive to ceftriaxone, therefore the treatment was maintained during hospitalization period. The patient showed a gradual improvement over the time and inflammatory markers remained negative since the first week of treatment. After three weeks of intravenous antibiotic treatment, the patient was discharged with oral ciprofloxacin. After a three year follow-up, she remained asymptomatic. ESR and CRP remained negative in every measure and no alterations on knee radiography were detected. P. multocida is a facultative anaerobic Gram-negative coccobacillus, commensal in the nasopharyngeal tract of domestic pets. Prosthetic joint infection caused by P. multocida is rare and we found reports of 22 TKA and 5 THA infections caused by this organism. Although all options of treatment contemplate intravenous antibiotherapy, it can be combined with different operative techniques. Of the 27 patients, only two were successfully treated without the need of a surgical intervention. We have chosen a conservative approach based on several factors: the patient had no risk factors; the prosthesis was not loose; the existence of one case described of a successfully treatment with antibiotherapy alone (the second case we refer above was only published recently); a good early and maintained response to antibiotic treatment. We advocate that in selected patients, with no risk factors, with a sensitive organism, we should try conservative treatment first. However, if infection signs are severe, we should proceed to surgical debridement and sinovectomy and if the radiography shows any signs of loosening of the implant, it should be removed

Aim. Infection rates after management of open fractures are still high. Existing guidelines regarding prevention of this complication are inhomogeneous. A survey directed to orthopaedic trauma surgeons worldwide aims to give an overview of current practices in the management of open fractures. Method. An international group of trauma surgeons and infection specialists with experience in the field of musculoskeletal infections developed a questionnaire that was distributed via email to all AOTrauma members worldwide. Descriptive statistical analysis was performed. Results. 1197 orthopaedic trauma surgeons answered the survey (response rate: 4,9% of all opened emails). Cephalosporins are the most commonly used antibiotics for systemic prophylaxis in open fractures (cefazolin: 51,46% cefuroxime: 23,6%, ceftriaxone: 14,54%). In Gustilo type III open fractures gentamicin (49,12%) and metronidazole (33,58%) are often added. 86% (n=1033) reported to give the first dosage of systemic antibiotics in the emergency department as soon as the patient arrives. Only 3% (n=34) reported pre-hospital administration at the scene of the accident or during transport to the hospital. While most respondents administer antibiotics over 24h in type I open fractures (34%, n=405), for type II open fractures the most often mentioned duration is 72h (26%, n=306). For type III a 7 days course was most often performed (38%, n=448). Overall, there is a tendency to longer durations with increasing severity. However, a vast majority agreed that the optimal duration is not well defined in the literature (71%, n=849). 20psi,”Jet-Lavage”). The amount of irrigation fluid has a bimodal distribution with two peaks at 4–6 liters (24%, n=286) and at 8–10 liters (24%, n=282). Conclusions. Results from our survey give an overview of current practices and identify certain aspects in the management of open fractures where treatment protocols are very heterogenous and guidelines not well accepted. These controversies demand for further research in this field to provide better evidence

Aims. This case series aims to describe the clinical consequences of juxta-physeal sub-acute osteomyelitis in children, specifically growth and limb deformity. Methods. All children diagnosed with osteomyelitis between 2014 and 2016 at a single University Teaching Hospital in the UK were included. Juxta-physeal sub-acute osteomyelitis was identified using magnetic resonance imaging obtained within 48-hours of presentation. These cases were followed up prospectively on a regular basis in the outpatient clinic. Any clinical evidence of limb or growth deformity was evaluated using long-leg standing radiographs. Results. During the study period, 63 paediatric osteomyelitis cases were identified and four of these (6%) had juxta-physeal sub-acute osteomyelitis. All bone infections were located either in the distal femur or proximal tibia. All cases were treated with six weeks of intravenous ceftriaxone and three children underwent surgical procedures. All four cases developed a growth deformity in the affected limb. Conclusions. A variety of growth disturbances can occur following sub-acute osteomyelitis which could be secondary to physeal stimulation and overgrowth. In this series, overgrowth occurred in the physis immediately adjacent to the Brodie's abscess. Subsequently, the presence of a medial abscess caused a valgus deformity and a lateral abscess caused a varus deformity. This phenomenon has not been well-described in the literature. The tibial and femoral physes are amongst the most active in the body, which may explain the reason for the observed overgrowth deformity in these cases. The age of the patient and the method of treatment did not appear to influence the emergence of the growth deformity. None of our patients had recurrence or development of chronic osteomyelitis within the measured time period. In view of these findings, we recommend regular follow-up including assessment for limb deformity for a minimum of 3-years following the treatment of sub-acute osteomyelitis

Prosthetic joint infections (PJI) are caused by a variety of microorganisms but most frequently by staphylococci. The results of treatment of PJI due to organisms other than staphylococci are less known. The aim of this study is to evaluate the outcomes after streptococcal PJI. The data of 26 streptococcal (13 hip and 13 knee PJI from 24 patients) were retrieved from hospital based PJI register, and analyzed. There were 15 female and 11 male patients (mean age 66 y). Most (13) PJI were hematogenous. 15 PJI had been treated with debridement and retention (D&R) of the infected joint, 1 with permanent resection arthroplasty, 9 had two stage revision and 1 patient had one stage partial replacement. After the microbiological diagnosis was established most patients received 2–3 weeks of penicillin G or ceftriaxone followed by 2–6 months of oral amoxicillin. All patients had regular follow-ups after the procedure at least at 1 month, three months and one year. The results were classified as: PJI cure (in absence of clinical signs and symptoms of infection and with negative CRP), probable failure (in absence of clinical signs and symptoms of infection but with elevated CRP), definite failure (if a new treatment was necessary), and mechanical failure (aseptic loosening, periprosthetic fracture, quadriceps rupture). One foreign patient was lost to follow up. The mean follow up time for the rest was 60 months (from 16 to 167) months. There was probable prosthesis failure in 1 case, definite prosthesis failure in 7 cases and mechanical failure in 3 cases. The mean survival time of the failed prostheses was 28 (range from 2 to 83) months. 6 failures (40 %) occurred in group of cases that had undergone D&R, and 1 (6 %) in the two stage revision group. Among the 7 definite failures in 4 patients antibiotic treatment was empirically started after the symptoms reappeared resulting in long remission periods. Comparing to the published results of staphylococcal PJI it seems that D&R of the prosthesis for streptococcal PJI is considerably less successful. Rifampicin as a proven treatment of choice for staphylococcal infections is probably the main reason for the difference. An unexpected feature of streptococcal PJI is that definite failures are easily suppressed for long time with a short course of oral antibiotics

External fixation is widely used in orthopaedic and trauma surgery. Infections around pin or wire sites, which are usually localised, non-invasive, and are easily managed, are common. Occasionally, more serious invasive complications such as necrotising fasciitis (NF) and toxic shock syndrome (TSS) may occur.

We retrospectively reviewed all patients who underwent external fixation between 1997 and 2012 in our limb lengthening and reconstruction programme. A total of eight patients (seven female and one male) with a mean age of 20 years (5 to 45) in which pin/wire track infections became limb- or life-threatening were identified. Of these, four were due to TSS and four to NF. Their management is described. A satisfactory outcome was obtained with early diagnosis and aggressive medical and surgical treatment.

Clinicians caring for patients who have external fixation and in whom infection has developed should be aware of the possibility of these more serious complications. Early diagnosis and aggressive treatment are required in order to obtain a satisfactory outcome.

Cite this article: Bone Joint J 2015;97-B:1296–1300.

The number of arthroplasties being undertaken is expected to grow year on year, and periprosthetic joint infections will be an increasing socioeconomic burden. The challenge to prevent and eradicate these infections has resulted in the emergence of several new strategies, which are discussed in this review.

Cite this article: Bone Joint J 2015;97-B:1162–9.

We have prospectively studied the outcome of infections associated with implants which were retained and treated using a standardised antimicrobial protocol. Over a period of four years, we studied 24 consecutive patients who had symptoms of infection for less than one year, a stable implant, no sinus tract and a known pathogen which was susceptible to recommended antimicrobial agents. The infections involved hip prostheses (14), knee prostheses (5), an internal fixation device (4), and an ankle prosthesis (1).

Twenty patients had a successful outcome at a median follow-up of 3.7 years (1.8 to 4.7); four had failure of the implant after a median follow-up of 1.2 years (0.3 to 2.5). The probability of survival without failure of treatment was 96% at one year (95% confidence interval (CI) 88 to 100), 92% at two years (95% CI 80 to 100) and 86% at three years (95% CI 72 to 100).

Patients with a short-term infection but with a stable implant, no sinus tract and a known pathogen may be successfully treated by retention of the implant and the use of a standardised regimen of antimicrobial treatment.

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.