Daptomycin for the treatment of osteomyelitis and orthopaedic device infections: real-world clinical experience from a European registry.

Osteomyelitis is a serious infection predominantly caused by Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA). Orthopaedic device-related infections are complex and require a careful combination of surgical intervention and antimicrobial therapy. Daptomycin, a cyclic lipopeptide, effectively penetrates soft tissue and bone and demonstrates rapid concentration-dependent bactericidal activity against Gram-positive pathogens. This retrospective, non-interventional study evaluated clinical outcomes in patients with osteomyelitis or orthopaedic device infections treated with daptomycin from the European Cubicin® Outcomes Registry and Experience (EU-CORE(SM)) study. Patients were treated between January 2006 and April 2012, with follow-up to 2014. Clinical outcomes were assessed as success (cured or improved), failure or non-evaluable. Of 6,075 patients enrolled, 638 (median age, 63.5 years) had primary infections of osteomyelitis or orthopaedic device infections, 224 had non-prosthetic osteomyelitis, 208 had osteomyelitis related to a permanent or temporary prosthetic device, and 206 had orthopaedic device infections. The most commonly isolated pathogen was S. aureus (214 [49.1 %]; 24.8 % were MRSA). Overall, 455 (71.3 %) patients had received previous antibiotic therapy. Patients underwent surgical interventions, including tissue (225 [35.3 %]) and bone (196 [30.7 %]) debridement, as part of their treatment. Clinical success rates were 82.7 % and 81.7 % in S. aureus and coagulase-negative staphylococcal infections. Adverse events (AEs) and serious AEs assessed as possibly related to daptomycin were observed in 6.7 % and 1.9 % of patients, respectively. Daptomycin was discontinued by 5.5 % of patients due to AEs and 10 (1.6 %) deaths were reported. In conclusion, daptomycin was effective and safe in patients with osteomyelitis or orthopaedic device infections.

[Feedback on the evaluation of clinical pharmacy activities developed in surgery]. / Retour d'expérience sur l'évaluation des activités de pharmacie clinique développées en chirurgie.

INTRODUCTION: Our current development strategy integrates clinical pharmacy activities prioritized in surgical services. Patients in these services are typically risk patients: transfers, multiple prescribers, frequent medication change, pharmacotherapeutic risk classes. PATIENTS AND METHODS: Three clinical pharmacy activities (admission reconciliation, pharmaceutical analysis, participation doctors round) have been developed in orthopaedic surgery and neurosurgery. Pharmacists prospectively recorded data describing their activities: number of reconciliations and analyzed requirements and time required to achieve them. Data on pharmaceutical interventions were recorded on the basis ActIP®. The clinical significance of interventions was retrospectively rated by a team of two pharmacists and two physicians on the scale adapted Hatoum et al. RESULTS: Four thousand five hundred pharmaceutical analysis and 248 reconciliations were conducted. One hundred and fifty-six pharmaceutical interventions were issued. The average acceptance rate was 80%. A total of 5.8% of pharmaceutical interventions have been listed with a very significant clinical importance and 48.1% with at least significant clinical importance. The activities and documentation required pharmaceutical average daily time (senior pharmacist, resident and external pharmacist) about 6 hours. DISCUSSION AND CONCLUSION: Other studies, including comparative and medico-economic, must be conducted to support these results. Nevertheless, the indicators obtained attend a better readability of the clinical importance of the activities performed by clinical pharmacists and this particularly in surgical services, both by prescribers and authorities.

[Clinical pharmacy and surgery: Review]. / Pharmacie clinique et chirurgie : revue de la littérature.

Clinical pharmacy has been developed and evaluated in various medical hospital activities. Reviews conducted in this area reported a higher value of this discipline. In surgical services, evenly adverse drug events may occur, so clinical pharmacy activities must also help to optimize the management of drug's patient. The objectives of this literature review is to determine the profile of clinical pharmacy activities developed in surgical services and identify indicators. The research was conducted on Pubmed(®) database with the following keywords (2000-2013), "surgery", "pharmacy", "pharmacist", "pharmaceutical care", "impact" and limited to French or English papers. Studies dealing on simultaneously medical and surgical areas were excluded. Twenty-one papers were selected. The most frequently developed clinical pharmacy activities were history and therapeutic drug monitoring (antibiotics or anticoagulants). Two types of indicators were identified: activity indicators with the number of pharmaceutical interventions, their description and clinical signification, the acceptance rate and workload. Impact indicators were mostly clinical and economic impacts. The development of clinical pharmacy related to surgical patients is documented and appears to have, as for medical patients, a clinical and economical value.

Subcutaneous teicoplanin in staphylococcal bone and joint infections.

OBJECTIVE: We aimed to describe the use of subcutaneous teicoplanin as an alternative for the treatment of staphylococcal bone and joint infections. METHODS: A retrospective multicentric cohort (2002-2015) was conducted with patients receiving subcutaneous teicoplanin for a staphylococcal bone and joint infection. RESULTS: Forty patients were assessed. A median loading dose of 9.4 mg/kg/12h (IQR, 6.1-13.1) was administered to 35 patients, subcutaneously for 18 of them. Thirteen of these patients received three injections per week. No excess risk of failure was identified. The trough level was not significantly different between the various routes (p=0.462), and was significantly higher if the loading dose was≥9 mg/kg/injection (p<10-3). CONCLUSION: The use of subcutaneous teicoplanin seems to be acceptable as an alternative to other routes of administration for antibiotics.

Agreement between pre-operative and intra-operative bacteriological samples in 85 chronic peri-prosthetic infections.

BACKGROUND: Whether pre-operative microbiological sampling contributes to the management of chronic peri-prosthetic infection remains controversial. We assessed agreement between the results of pre-operative and intra-operative samples in patients undergoing single-stage prosthesis exchange to treat chronic peri-prosthetic infection. HYPOTHESIS: Agreement between pre-operative and intra-operative samples exceeds 75% in patients undergoing single-stage exchange of a hip or knee prosthesis to treat chronic peri-prosthetic infection. MATERIAL AND METHODS: This single-centre retrospective study included 85 single-stage prosthesis exchange procedures in 82 patients with chronic peri-prosthetic infection at the hip or knee. Agreement between pre-operative and intra-operative sample results was evaluated. Changes to the initial antibiotic regimen made based on the intra-operative sample results were recorded. RESULTS: Of 149 pre-operative samples, 109 yielded positive cultures, in 75/85 cases. Of 452 intra-operative samples, 354 yielded positive cultures, in 85/85 cases. Agreement was complete in 54 (63%) cases and partial in 9 (11%) cases; there was no agreement in the remaining 22 (26%) cases. The complete agreement rate was significantly lower than 75% (P=0.01). The initial antibiotic regimen was inadequate in a single case. DISCUSSION: Pre-operative sampling may contribute to the diagnosis of peri-prosthetic infection but is neither necessary nor sufficient to confirm the diagnosis and identify the causative agent. The spectrum of the initial antibiotic regimen cannot be safely narrowed based on the pre-operative sample results. We suggest the routine prescription of a probabilistic broad-spectrum antibiotic regimen immediately after the prosthesis exchange, even when a pathogen was identified before surgery. LEVEL OF EVIDENCE: IV, retrospective study.

[Knee septic arthritis]. / L'arthrite septique du genou.

The development of antibiotics and arthroscopic treatment have been two major turning points in the management of septic arthritis of the knee joint. We report a retrospective review of 78 patients managed in three surgery units and one rheumatology unit. Management practices varied between the units. Joint aspiration was proposed for all patients seen by rheumatologists. Certain surgeons proposed arthroscopy systematically at admission while others preferred a more selective approach. Arthroscopic wash-out was proposed as the first-line procedure for only 33 patients. All were given systemic antibiotics using a variety of protocols. The course under antibiotic treatment confirmed the potential gravity of septic arthritis of the knee joint since two patients died and 34 required surgery, half of which had more than one operation. The functional outcome at mean 19 months was rather poor. Only 65 knees were free of any implant and only 40 (62%) were pain free. Mean flexion was 116 degrees and 11 patients (17%) had significant flexion contracture. Factors of poor prognosis were initially high sedimentation rate, advanced stage according to Gächter, presence of specific germs (meti-R S. aureus, Gram-negative bacilli), and failure of first-line treatment. A management algorithm was proposed: initial aspiration for evacuation, medical treatment alone if there is no synovitis, and reduction synovectomy otherwise. The key to success is early well adapted treatment.

May one-stage exchange for Candida albicans peri-prosthetic infection be successful?

UNLABELLED: Fungal infection of a total joint arthroplasty has a low incidence but is generally considered as more difficult to cure than bacterial infection. As for bacterial infection, two-stage exchange is considered as the gold standard of treatment. We report two cases of one-stage total joint exchange for fungal peri-prosthetic infection with Candida albicans, where the responsible pathogens was only identified on intraoperative samples. This situation can be considered as a one-stage exchange for fungal peri-prosthetic infection without preoperative identification of the responsible organism, which is considered as having a poor prognosis. Both cases were free of infection after two years. One-stage revision has several potential advantages over two-stage revision, including shorter hospital stay and rehabilitation, no interim period with significant functional impairment, shorter antibiotic treatment, better functional outcome and probably lower costs. We suggest that one-stage revision for C. albicans peri-prosthetic infection may be successful even without preoperative fungal identification. LEVEL OF EVIDENCE: Level IV-Historical cases.

Incomplete or absent acute phase response in some postoperative patients.

In a prospective study, 74 patients were admitted for an open fracture of the lower limb and treated by osteosynthesis. None of them presented infectious complication during the postoperative period. Among them, 67 exhibited a classical acute phase response. In 5 patients, the response was apparently incomplete since no serum C-reactive protein (CRP) rise was observed after the injury; i.e. CRP concentrations remained inferior to the detection limit of the assay used; in contrast, serum alpha-1 acid glycoprotein (AAG) concentrations were temporarily increased, a variation associated with a concomitant decrease of transthyretin (TTR) concentration. In 2 other patients, CRP and AAG levels were not significantly modified. The 7 patients did not suffer hepatic insufficiency or protein malnutrition. In our series, incomplete or absent acute phase response was not rare (prevalence 9%) and was not related to an increased risk of postoperative infection. In contrast to CRP, the TTR response, i.e. a transitory decrease, was observed in all the 7 patients.

Diagnostic value of C-reactive protein and transthyretin in bone infections of the lower limb.

In a prospective study, white and red blood cell counts, hematocrit, erythrocyte sedimentation rate (ESR), albumin, alpha-1 acid glycoprotein, C-reactive protein (CRP), and transthyretin (TTR) values were determined by serial measurements during 23 days in 80 patients with an open fracture of the lower limb. Postoperative reference profiles were defined in 74 patients without septic complications. In the six remaining patients, serum CRP and TTR concentrations were found efficient for the early diagnosis of postoperative infections: a CRP/TTR mass concentration ratio higher than 0.6 from the 8th day after surgery was sensitive (100%) and specific (93%). Variations of CRP and TTR concentrations often preceded the clinical diagnosis in patients with early infection. ESR was found unreliable with regard to postoperative infection because of its high dependence with respect to red blood cell count.

[Cardiac arrest caused by pericardial heart dislocation]. / Arrêt circulatoire par luxation extrapéricardique du coeur.

A case is reported of a 33-year-old multiple injured patient with closed chest trauma and an unknown rupture of left pericardium and hemidiaphragm. A peroperative cardiac arrest, one year later, was related to dislocation of the heart. Thoracotomy for internal cardiac massage was responsible for a successful outcome.

[Risk of infection in centro-medullary locking nailing of open fractures of the femur and tibia]. / Le risque infectieux de l'enclouage centro-médullaire verrouillé des fractures ouvertes du fémur et du tibia.

Intramedullary reamed locking nail of open fractures remains controversial because of the risk of infection. 1,474 closed reamed locked nailings were performed between 1974 and 1989 for femoral (744 cases) or tibial (730 cases) fractures. 349 fractures were open: 100 femoral fractures (51 Gustilo and Anderson Grade I and 49 Grade II) and 249 tibial fractures (140 Grade I, 99 Grade II et 10 Grade III). 24 femoral (3.2%) and 46 tibial (6.3%) nails were followed by infection. This difference is significant (p < 0.01). Reoperations for infection occur more frequently for femoral than tibial fractures (p < 0.05). There is no difference between the results of infection treatment between femoral or tibial fractures. Traumatic opening of the femoral fracture site does not affect the occurrence of an infection, its severity or the results of its treatment. Traumatic opening of the tibial fracture site significantly increases the infection rate (p < 0.001), and the incidence of infection increases with the severity of the soft tissue lesions; but the severity of the infection and the results of its treatment are not modified. Acute closed reamed intramedullary locking nail is the best treatment for open femoral or tibial fractures with respect to the bone healing and infection rate for Grade I and II fractures. For Grade III fractures, nailing must be followed by a coverage flap.

Utility of measurement of gentamicin release from PMMA beads in wound drainage fluid after in-vivo implantation.

Acute or chronic osteomyelitis in 188 patients was treated by surgical debridement and filling of the cavity with gentamicin-PMMA beads. The gentamicin concentration was measured in the total drainage fluid of the first postoperative day. There was no correlation between this concentration and the amount of implanted beads. It is impossible to predict preoperatively the gentamicin concentration which will be obtained in situ. The measurement of gentamicin concentration in the total drainage fluid of the first postoperative day and its comparison to the minimal bactericidal concentration of responsible pathogens, allow very early assessment of the effectiveness of the local antibiotherapy and if necessary, adaptation, of systemic antibiotherapy.

[Total hip replacement prosthesis infected by Mycobacterium tuberculous]. / Prothèse totale de hanche infectée à Mycobacterium tuberculosis.

We examined the diagnostic and therapeutic approaches used for two patients with loosened total hip prostheses who developed Mycobacterium tuberculosis infection. Revision total hip arthroplasty (THA) was performed in one patient. The prosthesis was left in situ in the second patient due to lack of sufficient bone stock. Medical treatment was given. The diagnosis was established on direct examination of bacteriological samples and culture on specific media. Polymerase chain reaction identified the Mycobacterium tuberculosis complex. Non-specific granulomas were observed on the histology sections. For us, management of overt tuberculosis involving a THA depends on the quality of the fixation. If the prosthesis remains stable, medical treatment can be sufficient. If the prosthesis loosens, definitive ablation must be considered with possible revision THA later. Exceptionally, a loosened implant may be left in situ if the remaining bone stock is insufficient. Minimal duration of anti-tuberulosis treatment is six months.

[C-reactive protein and transthyretin in early diagnosis of infection after open fractures of the lower limbs (a preliminary study)]. / La protéine C-réactive et la transthyrétine dans le diagnostic précoce de l'infection après fracture ouverte des membres inférieurs (étude préliminaire).

PURPOSE OF THE STUDY: The authors investigated the value of C-reactive protein (CRP) and transthyretin (TTR) in the early diagnosis of infection after open fractures of the lower limb in an open, prospective study. MATERIAL AND METHODS: Eighty patients were treated with acute debridement and bone fixation. Follow-up included clinical, radiological, bacteriological and biological assessment: white cell blood count (WBC), erythrocyte sedimentation rate (ESR), CRP and TTR. Diagnosis of infection was based on macroscopic presence of pus. RESULTS: Post-operative reference biological profiles were defined in 74 cases without infection. Reference profiles of WBC and ESR showed unreliable interindividual variations and could not be considered for the diagnosis of infection. Reference profiles of CRP and TTR showed a respective increase (for CRP) and decrease (for TTR) in the early post-operative course, with return to normal values after 12 days. In 6 infected patients, CRP concentrations were suddenly increased and TTR concentrations decreased at the time (3 cases) or even before (3 cases) clinical diagnosis of infection. These variations were mostly simultaneous. No unusual profile was found. The ratio of CRP/TTR concentrations experienced also a sudden increase in infected cases. DISCUSSION: Because of not specifical and unreliable variations in the post-operative outcome of non infected patients, WBC and ESR cannot be considered for the early diagnosis of infection. CRP and TTR concentrations with a respective cut-off value of 100 mg/L and 120 mg/L were found efficient for the early diagnosis of infection, and preceded clinical diagnosis in three of them. A CRP/TTR ratio over 60 p. 100, 8 days or more after initial surgery was found to be very specific (93 p. 100) and sensitive (100 p. 100) for the diagnosis of infection. CONCLUSION: Serial quantifications of CRP and TTR should be performed every four days during the follow-up of open fractures in order to early diagnose a post-operative infection. Comparison of both CRP and TTR could allow a higher accuracy, because of the possible lack of variation of one the two markers.

[Secondary infection of joint implants: diagnostic criteria, treatment and prevention]. / Infection secondaire de prothèse articulaire: critères du diagnostic, traitement et prévention.

Peroperative contamination is the most frequent cause of infection after arthroplasty. For other cases of infection subsequent to bacteremia or a neighboring focus, it would be more appropriate to use the term "secondary" infections rather than hematogeneous infections. Arguments favoring secondary infection include long symptom-free interval between prosthesis implantation and the infectious episode, a causal germ not generally responsible for peroperative infection, presence of a distant infectious focus, positive blood culture, and a positive bacteriological sample from the prosthesis level showing the same strain as grown from the distant focus or blood samples. Both acute and chronic infections are observed, leading to prosthesis dysfunction. History taking generally identifies a neglected acute but transient episode. Search for a bacteriological diagnosis must be completed before initiating an antibiotic regimen. If detected very early, washing with open synovectomy and resection of suspicious tissue should be attempted in order to maintain the implant if possible. Local antibiotics have proven efficacy. Beyond a certain delay, treatment for chronic infection usually requires removing the prosthesis, cleaning the bone interface, and new arthroplasty delayed or not. Search for the portal must be undertaken early in order to initiate appropriate local treatment. The causal event may be any invasive procedure, with or without material implantation. The risk-benefit ratio for antibiotic prophylaxis remains to be determined.

Diagnostic accuracy of intra-articular C-reactive protein assay in periprosthetic knee joint infection--a preliminary study.

BACKGROUND: Periprosthetic joint infection often raises diagnostic challenges, as the published criteria are heterogeneous. New markers for predicting periprosthetic infection have been evaluated. Here, we assessed one of these markers, C-reactive protein (CRP), in joint fluid. HYPOTHESIS: We hypothesised that intra-articular CRP levels would perform better than serum CRP concentrations in diagnosing knee prosthesis infection. PATIENTS AND METHODS: We prospectively included 30 patients including 10 with native-knee effusions, 11 with prosthetic-knee aseptic effusions, and 11 with prosthetic-knee infection defined using 2011 Musculoskeletal Society criteria. Serum CRP was assayed using turbidimetry or nephelometry and intra-articular CRP using nephelometry. Appropriate statistical tests were performed to compare the three groups; P values < 0.05 were considered significant. RESULTS: Serum and intra-articular CRP levels were 5- to 16-fold higher in the group with periprosthetic infection than in the other two groups. Although the areas under the ROC curves were not significantly different, the likelihood ratios associated with the selected cut-offs suggested superiority of intra-articular CRP: a value > 2.78 mg/L suggested possible infection (100% sensitivity and 82% specificity) and a value > 5.37 mg/L probable infection (90% sensitivity and 91% specificity). DISCUSSION: Our findings suggest a possible role for intra-articular CRP assay in diagnosing knee prosthesis infection and perhaps periprosthetic infection at any site. LEVEL OF EVIDENCE: Level III, diagnostic study, development of a diagnostic criterion in consecutive patients comparatively to a reference standard.

Comparison of microbiological results of needle puncture vs. superficial swab in infected diabetic foot ulcer with osteomyelitis.

AIM: To study prospectively two methods for the bacteriological diagnosis of osteomyelitis related to diabetic foot ulcer: needle puncture performed across normal skin surrounding the foot ulcer and superficial swabbing of the ulcer. PATIENTS AND METHODS: Diabetic patients with a foot ulcer complicated by bone or joint infection, as detected by X-ray imaging, were included in the study. Ulcer swabbing and needle puncture were performed in each patient. To reach the tissue nearest the bone surface, needle puncture was guided by X-ray imaging and the drop of fluid obtained by aspiration was used for both aerobic and anaerobic bacterial culture. RESULTS: Twenty-one diabetic patients were included. The mean number of microorganisms isolated by needle puncture was significantly lower compared with that obtained by superficial swabbing: 1.09 vs. 2.04 (P < 0.02). Three bacterial species were isolated by needle puncture only in one patient while three or more bacterial isolates were obtained by superficial swabbing in six patients. No bacterial isolate was detected in five patients by needle puncture and in two patients by superficial swabbing. Staphylococcus aureus accounted for 70% of cases (seven patients) when a single bacterial species was obtained by needle puncture. After needle puncture, no wound complication or infection was observed. CONCLUSION: Culture of samples obtained by needle puncture revealed one or two bacterial isolates in two-thirds of diabetic patients with osteomyelitis following foot ulcer. Given the lack of complications, this invasive diagnostic technique should be considered for deep direct sampling in diabetic patients with osteomyelitis related to foot ulcer when surgical debridement is contraindicated or delayed.

[Venous lesions in relation to injections and the use of catheters]. / Lésions veineuses en relation avec les injections et l'utilisation de cathéters.

The point of this study is to draw attention to the many complications which are likely to arise when the venous network is injected or cathetered. The main complications affecting the peripheral veins are lesions at the puncture point, cutaneous necroses in the case of paravenous injections, accidental intra-arterial injection, and chemical and bacterial thrombophlebites. The catheterism of intrathoracic veins can cause lesions at the puncture point (pneumothorax, lesion of the carotid), wrong positioning of the catheter and of the vascular or cardiac perforations, and central venous thromboses responsible for septicemic conditions and/or pulmonary embolism.

The risk of post-operative infection after reamed intramedullary locked nailing of tibial fractures. A review of 730 cases.

730 consecutive acute reamed intramedullary locked nailing of tibial fractures were studied, according to Gustilo's classification of soft tissue lesions for the open fractures. There is a significant increase of post-operative infection rate if the tibial fracture is open, and the relative risk increases with the severity of soft tissue lesions. The comparison of these figures with those of other methods of treatment and the mechanical and clinical advantages of nailing leads us to propose this method for treatment of grade I, II and IIIa open fractures, while external the fixator seems better adapted for IIIb and c open fractures.