Single-stage treatment of chronic osteomyelitis with a new absorbable, gentamicin-loaded, calcium sulphate/hydroxyapatite biocomposite: a prospective series of 100 cases.

AIMS: Chronic osteomyelitis may recur if dead space management, after excision of infected bone, is inadequate. This study describes the results of a strategy for the management of deep bone infection and evaluates a new antibiotic-loaded biocomposite in the eradication of infection from bone defects. PATIENTS AND METHODS: We report a prospective study of 100 patients with chronic osteomyelitis, in 105 bones. Osteomyelitis followed injury or surgery in 81 patients. Nine had concomitant septic arthritis. 80 patients had comorbidities (Cierny-Mader (C-M) Class B hosts). Ten had infected nonunions. All patients were treated by a multidisciplinary team with a single-stage protocol including debridement, multiple sampling, culture-specific systemic antibiotics, stabilisation, dead space filling with the biocomposite and primary skin closure. RESULTS: Patients were followed up for a mean of 19.5 months (12 to 34). Infection was eradicated in 96 patients with a single procedure and all four recurrences were successfully managed with repeat surgery. Adverse events were uncommon, with three fractures, six wound leaks and three unrelated deaths. Outcome was not dependant on C-M host class, microbial culture, wound leakage or presence of nonunion. CONCLUSION: This single-stage protocol, facilitated by the absorbable local antibiotic, is effective in the treatment of chronic osteomyelitis. It offers a more patient-friendly treatment compared with other published treatment options. Cite this article: Bone Joint J 2016;98-B:1289-96.

Gentamicin coating of plasma chemical oxidized titanium alloy prevents implant-related osteomyelitis in rats.

Implant related infection is one of the most feared and devastating complication associated with the use of orthopaedic implant devices. Development of anti-infective surfaces is the main strategy to prevent implant contamination, biofilm formation and implant related osteomyelitis. A second concern in orthopaedics is insufficient osseointegration of uncemented implant devices. Recently, we reported on a macroporous titanium-oxide surface (bioactive TiOB) which increases osseointegration and implant fixation. To combine enhanced osseointegration and antibacterial function, the TiOB surfaces were, in addition, modified with a gentamicin coating. A rat osteomyelitis model with bilateral placement of titanium alloy implants was employed to analyse the prophylactic effect of gentamicin-sodiumdodecylsulfate (SDS) and gentamicin-tannic acid coatings in vivo. 20 rats were randomly assigned to four groups: (A) titanium alloy; PBS inoculum (negative control), (B) titanium alloy, Staphylococcus aureus inoculum (positive control), (C) bioactive TiOB with gentamicin-SDS and (D) bioactive TiOB plus gentamicin-tannic acid coating. Contamination of implants, bacterial load of bone powder and radiographic as well as histological signs of implant-related osteomyelitis were evaluated after four weeks. Gentamicin-SDS coating prevented implant contamination in 10 of 10 tibiae and gentamicin-tannic acid coating in 9 of 10 tibiae (infection prophylaxis rate 100% and 90% of cases, respectively). In Group (D) one implant showed colonisation of bacteria (swab of entry point and roll-out test positive for S. aureus). The interobserver reliability showed no difference in the histologic and radiographic osteomyelitis scores. In both gentamicin coated groups, a significant reduction of the histological osteomyelitis score (geometric mean values: C = 0.111 ± 0.023; D = 0.056 ± 0.006) compared to the positive control group (B: 0.244 ± 0.015; p < 0.05) was observed. The radiographic osteomyelitis scores confirmed these histological findings.

[Classification of haematogenous and post-traumatic osteomyelitis]. / Klassifikation der Osteomyelitis und Osteitis.

A classification of osteomyelitis must reflect the complexity of the disease and, moreover, provide conclusions for the treatment. The classification is based on the following eight parameters: source of infection (OM [osteomyelitis]/OT [post-traumatic OM]), anatomic region, stability of affected bone (continuity of bone), foreign material (internal fixation, prosthesis), range of infection (involved structures), activity of infection (acute, chronic, quiescent), causative microbes (unspecific and specific bacteria, fungi) and comorbidity (immunosuppressive diseases, general and local). In the long version of the classification, which was designed for scientific studies, the parameters are named by capital letters and specified by Arabic numbers, e.g., an acute, haematogenous osteomyelitis of a femur in an adolescent with diabetes mellitus, caused by Staphylococcus aureus, multi-sensible is coded as: OM2 Lo33 S1a M1 In1d Aa1 Ba2a K2a. The letters and numbers can be found in clearly arranged tables or calculated by a freely available grouper on the internet (www.osteomyelitis.exquit.net). An equally composed compact version of the classification for clinical use includes all eight parameters, but without further specification. The above-mentioned example in the compact version is: OM 3 S a Ba2 K2. The short version of the classification uses only the first six parameters and excludes causative microbes and comorbidity. The above mentioned example in the short version is: OM 3 S a. The long version of the classification describes an osteomyelitis in every detail. The complexity of the patient's disease is clearly reproducible and can be used for scientific comparisons. The for clinical use suggested compact and short versions of the classification include all important characteristics of an osteomyelitis, can be composed quickly and distinctly with the help of tables and provide conclusions for the individual treatment. The freely available grouper (www.osteomyelitis.exquit.net) creates all three versions of the classification in one step.

[Joint infections. Known facts and new trends]. / Die Gelenkinfektion. Bekanntes und neue Trends.

Acute septic arthritis is a surgical emergency because rapid septic destruction of articular cartilage can lead to impairment or even loss of joint function. Diagnosis consists of patient history, clinical examination, laboratory results, (sonography- guided) joint aspiration and radiography. Emergency therapy is based on arthroscopic or open joint debridement and lavage combined with systemic antibiotic therapy. No data are available for the recommendation of local antibiotics but antiseptic solutions are not recommended because of cartilage damage. New trends in diagnostics are positron emission tomography/computed tomography (PET/CT), urine sticks for analysis of joint fluid and molecular pathology. Chronic joint empyema is more diagnostically demanding and is difficult to treat. In cases of necrotic and infected articular cartilage, joint resection has to be performed for quiescence of infection. Options following successful treatment of empyema are arthroplasty, arthrodesis or permanent resection.

[Definition of the Diagnosis Osteomyelitis-Osteomyelitis Diagnosis Score (ODS)]. / Zur Definition der Diagnose Osteomyelitis - Osteomyelitis-Diagnose-Score (ODS).

AIM: The disease "osteomyelitis" is characterised by different symptoms and parameters. Decisive roles in the development of the disease are played by the causative bacteria, the route of infection and the individual defense mechanisms of the host. The diagnosis is based on different symptoms and findings from the clinical history, clinical symptoms, laboratory results, diagnostic imaging, microbiological and histopathological analyses. While different osteomyelitis classifications have been published, there is to the best of our knowledge no score that gives information how sure the diagnosis "osteomyelitis" is in general. METHOD: For any scientific study of a disease a valid definition is essential. We have developed a special osteomyelitis diagnosis score for the reliable classification of clinical, laboratory and technical findings. The score is based on five diagnostic procedures: 1) clinical history and risk factors, 2) clinical examination and laboratory results, 3) diagnostic imaging (ultrasound, radiology, CT, MRI, nuclear medicine and hybrid methods), 4) microbiology, and 5) histopathology. RESULTS: Each diagnostic procedure is related to many individual findings, which are weighted by a score system, in order to achieve a relevant value for each assessment. If the sum of the five diagnostic criteria is 18 or more points, the diagnosis of osteomyelitis can be viewed as "safe" (diagnosis class A). Between 8-17 points the diagnosis is "probable" (diagnosis class B). Less than 8 points means that the diagnosis is "possible, but unlikely" (class C diagnosis). Since each parameter can score six points at a maximum, a reliable diagnosis can only be achieved if at least 3 parameters are scored with 6 points. CONCLUSION: The osteomyelitis diagnosis score should help to avoid the false description of a clinical presentation as "osteomyelitis". A safe diagnosis is essential for the aetiology, treatment and outcome studies of osteomyelitis.

[Vacuum-assisted closure therapy for the treatment of acute postoperative osteomyelitis]. / Vakuumtherapie bei akuter postoperativer Osteitis.

AIM: Vacuum-assisted closure is used frequently for the treatment of posttraumatic osteomyelitis of the extremities. After debridement and repeated VAC dressing changes, the wounds are closed by secondary suture, split-thickness skin grafts or local flaps. However, no objective parameters describe the time point for secondary wound closure. Our thesis was that negative microbiological results from bone specimens can indicate the time for secondary wound closure. Moreover, treatment course and clinical outcome after 3.4 years should be compared to those of other surgical approaches for acute postoperative osteomyelitis from the literature. PATIENTS AND METHODS: 43 patients with acute postoperative osteomyelitis of the extremities and the pelvis were treated by serial bone and soft tissue debridements and VAC therapy and analysed prospectively. Debridements were repeated until the wounds were macroscopically free from signs of infection (good granulation/no necrosis). During each revision a bone specimen was taken for microbiological analysis. Number of revisions, bacterial cultures, type of wound closure and recurrence of infection after 3 years and 5 months on average after the last surgery was analysed. RESULTS: 9.8 debridements on average were performed until eradication of infection and secondary wound closure. Despite the absence of macroscopic infection, bacteria were still found in bone samples from 15 of 43 patients. Three biopsies were free of bacteria for the first time right before wound closure, 25 samples had become negative during the treatment. Six recurrences (19.3 %) were noted after 3.4 years on average. Four patients from the group of negative bone biopsies (19 %) and two patients from the group of persisting bacteria before secondary closure (20 %) had a recurrence of infection. CONCLUSION: In about one third of the bone biopsies bacteria persisted. This bacterial load had no correlation to wound healing and rate of recurrence after over 3 years. In conclusion, microbiological bone samples are not suitable as an indicator for the time point of secondary wound closure. Compared to other treatment options in acute postoperative osteomyelitis from the literature (especially implantation of local antibiotics), no advantage of vacuum-assisted closure could be shown concerning number of debridements and rate of recurrences.

[Vacuum-assisted closure therapy for the treatment of skin and soft-tissue infections. Are wound specimens of use in planning secondary wound closure?]. / Vakuumtherapie bei Haut- und Weichgewebsinfektionen der Extremitäten. Nutzen des Wundabstrichs bei der Planung des sekundären Wundverschlusses?

AIM: Vacuum-assisted closure is used frequently for the treatment of skin and soft-tissue infections (SSTI) of the extremities. After debridement and repeated VAC dressing changes, the wounds are closed by secondary suture, split-thickness skin grafts or local flaps. However, no objective parameters describe the time point for secondary wound closure. Our thesis was that negative microbiological results from wound specimens can indicate the time for secondary wound closure. PATIENTS AND METHODS: 24 patients with SSTI of the extremities were treated by serial debridements and VAC therapy and analysed prospectively. Debridements were repeated until the wounds were macroscopically free from signs of infection (good granulation/no necrosis). During each revision specimens were taken for microbiological analysis. Moreover, number of revisions, bacterial cultures, type of wound closure and wound status after 3 years and 5 months on average after the last surgery were analysed. RESULTS: 6.3 revisions on average were performed until secondary wound closure was possible. In spite of the absence of macroscopic infection, bacteria were still found in tissue samples from 14 of 24 wounds. 6 wounds were free of bacteria for the first time right before wound closure, 3 wounds had become negative during the treatment. After 3.4 years on average, the wounds of all 18 patients available for examination had healed well and were free from signs of infection. CONCLUSION: Vacuum-assisted closure resulted in clean, good granulating wounds without necrosis. However, in more than half of the wounds bacteria persisted. This bacterial load had no correlation to wound healing and outcome after over 3 years. In conclusion, microbiological tissue samples are not suitable as indicator for the time point of secondary wound closure in SSTI.

[Preservation of hip prosthesis with local surgical revision and creation of a fistula persistens : an option for palliative treatment of periprosthetic infection in old, polymorbid patients?]. / Hüftprothesenerhalt mit lokaler chirurgischer Revision und Anlage einer Fistula persistens : Ausnahmeoption zur palliativen Therapie des periprothetischen Infekts bei alten polymorbiden Patienten?

BACKGROUND: The number of implanted hip prostheses is increasing constantly. At the same time the patients are becoming older and older. Thus, also patients with periprosthetic infections are older and therefore sicker. Uniform guidelines for the treatment of infected arthroplasties are controversial. Empirical studies show that the explantation of the original prosthesis and implantation of a revision may be the option with the greatest chance of success. These very aggressive procedures may overburden the old, polymorbid patient. The aim of this study was to ascertain whether or not keeping the hip prosthesis in combination with local debridement, formation of a permanent fistula and long-term administration of antibiotics is a possible option for the treatment of infected hip prostheses in old and polymorbid patients. PATIENTS: Between 01.01.2004 and 28.01.2007, 12 patients with periprosthetic infection after hip arthroplasty (PIH) were treated. Their average age was 79.8 years. Eleven patients were rated ASA III preoperatively. The prostheses were on average 23.8 weeks old when the first signs of infection occurred. In 10 cases the infection was caused by Staphylococcus (MRSA 3x). The main comorbidities were hypertension, diabetes, coronary heart disease and thyroid malfunction. RESULTS: After a mean 8.83 months, six patients were deceased (average age 85.50 years). In five of the remaining six patients the fistula worked without any problem. In one case the fistula was occluded. None of the patients showed any sign of acute infection. All were able to walk with full weight-bearing on the affected hip. CONCLUSION: Restricting the indication to old, polymorbid patients, preservation of the arthroplasty in combination with local surgical debridement, permanent fistula and long-term systemic administration of antibiotics seems to be an alternative to explantation of the prosthesis with consecutive revision arthroplasty or resection arthroplasty.

[Treatment of MRSA infection in orthopedic surgery]. / Behandlung der MRSA-Infektion in der septischen Extremitätenchirurgie.

INTRODUCTION: Infection with methicillin-resistant Staphylococcus aureus (MRSA) remains a major challenge both therapeutically and hygienically. METHODS: Between January 2000 and January 2002, 27 patients with MRSA infections were treated and evaluated in a prospective clinical study. For effective wound management, operative revisions were performed every 3rd day. Following debridement, the wounds were vacuum sealed and specific i.v. antibiotics were administered. Wound closure was performed if three consecutive wound samples submitted for bacterial culture remained negative. RESULTS: All patients with MRSA infections were treated successfully until signs of infection disappeared and bacterial cultures were negative. An average of 7.3 operations per patient was required to eradicate MRSA infection. Follow-up of patients revealed recurrence of infection in four patients. CONCLUSION: Prevention of further spreading and successful treatment of MRSA infections in reconstructive orthopedic surgery is possible with appropriate surgical and hygienic concepts. In almost every second patient complex revision procedures were required.

Xenogeneic rejection mechanisms shown by intravital microscopy.

The importance of this model is that it showed exactly where in the organ the xenogeneic damage occurred. The liver received the blood mainly via portal veins, which merge with the pulsatile arterioles in the Disse spaces. This periportal area is followed by the sinusoids and ends in the central or postsinusoidal vein. IVM enables us to differentiate between perfused and unperfused sinusoids and to calculate the ratio. Not all sinusoids are perfused at any time. It appears that 5% to 10% are unperfused. During xenoperfusion, only 65% of sinusoids show blood flow after a perfusion of 12 minutes. This is less than in hemorrhagic shock. Only the combined platelet inhibitors and apheresis resulted in remarkable improvement. The calculation of an index indicates the improvement of acinar perfusion. Thrombocytes and leukocytes remain, however, in the liver. In conclusion, the model used to analyze the dynamics of microvascular liver perfusion and sinusoidal perfusion is suitable for such investigations in a xenogeneic model. It has no major side effects, either on the perfusing blood or on the liver, as proved in the isogeneic control group. The important finding in our eyes is that the perfusion failure begins in the periportal fields, where the blood enters the foreign microvasculature and where the leukocytes first come in contact with the foreign endothelium. All previous manipulations had only a minor impact on this contact of cells with the foreign endothelium. The study indicates that the early events of xenogeneic hyperacute rejection are of unspecific character and involve leukocytes and thrombocytes to a major degree, thus being responsible for the dramatic decrease in the microcirculation in xenogeneic livers.

Monitoring of microhemodynamic changes during ex vivo xenogeneic liver perfusion using intravital microscopy.

The main targets of xenogeneic rejection mechanisms are the endothelial cells of the graft. Their activation and the consequent alteration of the organ's microcirculation lead to the destruction of the xenograft. Microhemodynamic changes occurring during this process are still poorly characterized. The aim of this study was to analyze the microcirculation during xenogeneic ex vivo hemoperfusion of rat livers and to monitor the impact of treatment strategies using intravital fluorescence microscopy. In contrast to the isogeneic control group, blood flow almost completely stopped within the first minutes of xenoperfusion. Simultaneously, perfusion pressure increased and bile production was reduced. Acetylsalicylate (Aspisol) and the platelet-activating factor antagonist WEB 2170 improved the microcirculation and function of the xenoperfused liver. The combination showed a synergistic effect. After apheresis of preformed xenogeneic antibodies, the parameters measured were comparable with those seen in isogeneic experiments. Complement degradation with cobra venom factor revealed a minor improvement in perfusion. A rapid, extensive, and irreversible leukocyte accumulation in terminal portal vessels was observed in all xenogeneic experiments. Blood counts of the perfusate confirmed the early trapping of leukocytes and platelets in the xenoperfused liver, indicating nonimmunological, cellular involvement in this rejection process.

Organs from animals for man.

In the following review some of the problems of xenotransplantation shall be discussed, based on the few experimental data available so far and on reports in the literature describing investigations which may be of importance for xenotransplantation. The impact of gravity on the upright posture of man versus almost all other mammals, the dysfunction between enzymes and hormones in different species and the lack of interactions between interleukins, cytokines and vasoactive substances will be taken into consideration. The question must be asked whether different levels of carrier molecules or serum proteins play a role in the physiological network. Even though the development of transgenic animals or other imaginative manipulations may lead to the acceptance of any type of xenografted organ, it has to be established for how long the products of the xenografts are able to act in the multifactorial orchestra. We are far from understanding xenogeneic molecular mechanisms involved in toxicity, necrosis and apoptosis or even reperfusion injury and ischemia in addition to the immediate mechanisms of the hyperacute xenogeneic rejection. Here, cell adhesion, blood clotting and vasomotion collide and bring micro- and macrocirculation to a standstill. All types of xenogeneic immunological mechanisms studied so far were found to have a more serious impact than those seen in allogeneic transplantation. In addition we are now only beginning to understand that so-called immunological parameters in allogeneic mechanisms act also in a true physiological manner in the xenogeneic situation. These molecular mechanisms occur behind the curtain of hyperacute, accelerated, acute or chronic xenograft rejection of which only some folds have been lifted to allow glimpses of part of the total scene. Other obstacles are likely to arise when long-term survival is achieved. These obstacles include retroviral infections, transfer of prions and severe side effects of the massive immunosuppression which will be needed. Moral, ethical and religious concerns are under debate and the species-specific production of proteins of the foreign donor species developed for clinical use suddenly appears to be a greater problem than anticipated.

Intravital microscopic investigation of xenogeneic microcirculation and impact of complement depletion by cobra venom factor.

Discordant xenografts are hyperacutely rejected within minutes. Disturbances in the microcirculation are considered to be the central mechanisms of hyperacute xenogeneic rejection (HXR). In this study intravital fluorescence microscopy was applied to investigate the dynamics of microcirculatory alterations in a setting in which HXR was inhibited by complement (C) depletion. Blood flow was measured as rat livers were perfused with isogeneic rat or xenogeneic human blood to assess the pattern of either physiological isogeneic hemoperfusion or in the course of HXR. Next, the complement system of the perfusate was inactivated by cobra venom factor (CVF) in order to inhibit HXR. Liver sinusoids of the isogeneic group were homogeneously perfused (sinusoidal perfusion rate 93.6+/-0.3%), whereas in the xenogeneic group the sinusoidal perfusion rate dropped to 67.1+/-3%. The perfusion in the periportal zone of an acinus was significantly lower ( 59.0+/-3.3%) than in the pericentral zone (76.2+/-3.1%). Treatment with CVF improved the sinusoidal perfusion to a value of 85.6+/-2.3%, physiological perfusion, however could not be reached. In contrast to the isogeneic group, massive white blood cell (WBC) and platelet accumulation was found in the xenogeneic group, especially in the terminal portal vessels and in the periportal zone of liver acini. WBC and platelet counts show that the adherence of these cells appears rapidly in the first 5 min after reperfusion as firm adherence. CVF was not able to inhibit WBC and platelet accumulation, indicating that WBC endothelial interactions do not require an intact complement system. Bile flow, a parameter of liver function, decreased only slightly during isogeneic perfusion. The addition of CVF to the rat blood reduced the bile flow to one half of the untreated isogeneic flow, indicating a hepatotoxic side-effect of CVF. In xenogeneic perfusion the bile flow dropped to 62.6% and with the addition of CVF to 37.5% in the first 15 min after reperfusion. The bile flow of the CVF treated groups recovered during the perfusion but could not reach isogeneic values.