Osseointegrated Titanium Implants for Limb Prostheses Attachments: Infectious Complications

Femoral amputation is a devastating event. Percutaneous, bone anchored prosthetic systems reduce problems associated with socket suspended prostheses, but the design is inherently vulnerable to infection. The aims of this thesis were to determine the risk of implant-associated infection, bacterial biofilm properties and the functional impact using this implant treatment regime. Definition of implant related osteomyelitis was based on clinical signs, radiography and positive tissue cultures. In 3-year prospective study 39 patients were evaluated twice for infectious frequency, clinical presentation, and its relation to bacterial flora at the skin-implant interface (Paper 1). The frequency of implant infection was 5% at inclusion and 18% at follow-up. The most common bacteria in superficial, and deep cultures were Staphylococcus aureus and coagulase-negative staphylococci. Despite frequent colonization by potentially virulent bacteria, limited disability, and only one implant removal was found. Phenotypical and genotypical biofilm formation was determined in 13 (7 staphylococcal, 6 enterococcal) osteomyelitis strains (Paper II). Antimicrobial resistance was tested with a novel combination of the Calgary biofilm MBEC device, and a custom-made susceptibility MIC plate. The majority of the strains produced biofilm with increased antimicrobial resistance, compared to their planktonic counterparts. Slime producing strains tolerated higher antimicrobial concentrations compared to non-producers. All staphylococcal strains carried ica genes. The long-term risk of implant-associated infection, and its relation to patient and method specific factors was determined in a 20-year retrospective analysis of the first 96 femoral implant patients (102 implants) (Paper III). A 10-year cumulative risk of 20% for developing osteomyelitis (16 patients), and a 10-year cumulative risk of 9 % for implant extraction due to osteomyelitis (10 patients) was found. Antibiotic treatment (median 3.5 months) and selective minor debridement, with retained implants, cured 7 out of 18 patients at the 24- month follow-up (Paper IV). Six patients were cured after implant extraction, and 5 had chronic low-grade infections with stable implants, but variable use of the external prosthetic leg. The most common pathogens were S. aureus and E. faecalis. C-reactive protein serum levels were significantly higher in patients with osteomyelitis caused by S. aureus than other pathogens. It is concluded that the finding of an increased risk of osteomyelitis with time using this implant system calls for; i) careful patient selection and information of long term risks, ii) further studies on infection control, iii) consideration of biofilm in treatment, and iv) improved diagnostics, and antibiotic delivery

Genomics of Staphylococcus aureus and Staphylococcus epidermidis from periprosthetic joint infections and correlation to clinical outcome

The approach of sequencing or genotyping to characterize the pathogenic potential of staphylococci from orthopedic device-related infection (ODRI) has been applied in recent studies. These studies described the genomic carriage of virulence in clinical strains and compared it with those in commensal strains. Only a few studies have directly correlated genomic profiles to patient outcome and phenotypic virulence properties in periprosthetic joint infections (PJIs). We investigated the association between genomic variations and virulence-associated phenotypes (biofilm-forming ability and antimicrobial resistance) in 111 staphylococcal strains isolated from patients with PJI and the infection outcome (resolved/unresolved). The presence of a strong biofilm phenotype in Staphylococcus aureus and an antibiotic-resistant phenotype in Staphylococcus epidermidis were both associated with treatment failure of PJI. In S. epidermidis, multidrug resistance (MDR) and resistance to rifampicin were associated with unresolved infection. Sequence type 45 (ST45) and ST2 were particularly enriched in S. aureus and S. epidermidis, respectively. S. epidermidis ST2 caused the majority of relapses and was associated with MDR and strong biofilm production, whereas ST215 correlated with MDR and non/weak biofilm production. S. aureus agr II correlated with resolved infection, while S. epidermidis agr I was associated with strong biofilm production and agr III with non/weak production. Collectively, our results highlight the importance of careful genomic and phenotypic characterization to anticipate the probability of the strain causing treatment failure in PJI. Due to the high rate of resistant S. epidermidis strains identified, this study provides evidence that the current recommended treatment of rifampicin and a fluoroquinolone should not be administered without knowledge of the resistance pattern

Osseointegrated titanium implants for limb prostheses attachments: infectious complications.

BackgroundThe concept of osseointegration involves direct contact between titanium implant and bone. This transcutaneous prosthetic system for amputees is intended to assure stable long-term fixation. Most metal transcutaneous implants have failed, primarily owing to infection.Questions/purposesWe determined the frequency and describe the presentation of infectious complications with this novel method. We also evaluated the bacterial flora at the skin-penetration area and its relation to the development of local and implant-related infection.Patients and methodsWe prospectively followed 39 patients with arm and leg amputations fitted with transcutaneous osseointegrated titanium implants a mean of 56 months earlier (range, 132-133 months). There were 33 femoral, one tibial, four ulnar, four radial, and three humeral implants. Patients were selected during a 6-month period in 2005 and identically reevaluated after 3 years. Implant infection was defined as definite, probable, or possible based on clinical, radiologic, and microbiologic evidence.ResultsThe frequency of implant infection was 5% at inclusion and 18% at followup. One patient with infection recovered owing to antibiotic treatment and another patient had the implant removed. Most implant infections had low infectious activity, and in five of the seven patients with infections, prosthetic use was not affected. The most common bacteria in superficial and deep cultures were Staphylococcus aureus and coagulase-negative staphylococci.ConclusionsDespite frequent colonization around the skin-implant interface by potentially virulent bacteria such as Staphylococcus aureus and bacteria associated with biomedical device infections such as coagulase-negative staphylococci, this titanium implant system for bone-anchored prostheses caused few infections leading to disability or implant removal.Level of evidenceLevel IV, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence

Osteomyelitis Risk in Patients With Transfemoral Amputations Treated With Osseointegration Prostheses.

BackgroundPercutaneous anchoring of femoral amputation prostheses using osseointegrating titanium implants has been in use for more than 25 years. The method offers considerable advantages in daily life compared with conventional socket prostheses, however long-term success might be jeopardized by implant-associated infection, especially osteomyelitis, but the long-term risk of this complication is unknown.Questions/purposes(1) To quantify the risk of osteomyelitis, (2) to characterize the clinical effect of osteomyelitis (including risk of implant extraction and impairments to function), and (3) to determine whether common patient factors (age, sex, body weight, diabetes, and implant component replacements) are associated with osteomyelitis in patients with transfemoral amputations treated with osseointegrated titanium implants.MethodsWe retrospectively analyzed our first 96 patients receiving femoral implants (102 implants; mean implant time, 95 months) treated at our center between 1990 and 2010 for osteomyelitis. Six patients were lost to followup. The reason for amputation was tumor, trauma, or ischemia in 97 limbs and infection in five. All patients were referred from other orthopaedic centers owing to difficulty with use or to be fitted with socket prostheses. If found ineligible for this implant procedure no other treatment was offered at our center. Osteomyelitis was diagnosed by medical chart review of clinical signs, tissue culture results, and plain radiographic findings. Proportion of daily prosthetic use when osteomyelitis was diagnosed was semiquantitatively graded as 1 to 3. Survivorship free from implant- associated osteomyelitis and extraction attributable to osteomyelitis respectively was calculated using the Kaplan-Meier estimator. Indication for extraction was infection not responsive to conservative treatment with or without minor débridement or loosening of implant.ResultsImplant-associated osteomyelitis was diagnosed in 16 patients corresponding to a 10-year cumulative risk of 20% (95% CI 0.12-0.33). Ten implants were extracted owing to osteomyelitis, with a 10-year cumulative risk of 9% (95% CI 0.04-0.20). Prosthetic use was temporarily impaired in four of the six patients with infection who did not undergo implant extraction. With the numbers available, we did not identify any association between age, BMI, or diabetes with osteomyelitis; however, this study was underpowered on this endpoint.ConclusionThe increased risk of infection with time calls for numerous measures. First, patients should be made aware of the long-term risks, and the surgical team should have a heightened suspicion in patients with method-specific presentation of possible infection. Second, several research questions have been raised. Will the surgical procedure, rehabilitation, and general care standardization since the start of the program result in lower infection rates? Will improved diagnostics and early treatment resolve infection and prevent subsequent extraction? Although not supported in this study, it is important to know if most infections arise as continuous bacterial invasion from the skin and implant interface and if so, how this can be prevented?Level of evidenceLevel IV, therapeutic study

Biofilm properties in relation to treatment outcome in patients with first-time periprosthetic hip or knee joint infection

Background: periprosthetic joint infections (PJI) are challenging complications following arthroplasty. Staphylococci are a frequent cause of PJI and known biofilm producers. Biofilm formation decreases antimicrobial susceptibility, thereby challenging favourable treatment outcomes. The aims of this study were to characterize the biofilm abilities and antimicrobial susceptibilities of staphylococci causing first-time PJI and correlate them to clinical outcome (infection resolution and recurrence). Methods: reoperations for PJI of the hip or knee between 1st January 2012 to 30th June 2015 performed at the Sahlgrenska University Hospital were identified in a local database. Medical records were reviewed and clinical parameters recorded for patients whose intraoperative bacterial isolates had been stored at the clinical laboratory. Staphylococcal strains isolated from reoperations due to first-time PJI were characterised by their ability to form biofilms using the microtiter plate test. Antimicrobial susceptibility of the strains was determined by minimum inhibitory concentration (MIC) when grown planktonically, and by minimum biofilm eradication concentration (MBEC) when grown as biofilms. MBEC determination was conducted using the Calgary biofilm device (CBD) and a custom-made antimicrobial susceptibility plate containing eight clinically relevant antimicrobial agents. Results: the study group included 49 patients (70 bacterial strains) from first-time PJI, whereof 24 (49%) patients had recurrent infection. Strong biofilm production was significantly associated with recurrent infection. Patients infected with strong biofilm producers had a five-fold increased risk for recurrent infection. Strains grown as biofilms were over 8000 times more resistant to antimicrobial agents compared to planktonic cultures. Biofilms were more susceptible to rifampicin compared to other antimicrobials in the assay. Increased biofilm susceptibility (MBEC ​> ​MIC) was observed for the majority of the bacterial strains and antimicrobial agents. Conclusions: Strong biofilm production was significantly associated with increased antimicrobial resistance and PJI recurrence. This underscores the importance of determining biofilm production and susceptibility as part of routine diagnostics in PJI. Strong staphylococcal biofilm production may have implications on therapeutic choices and suggest more extensive surgery. Furthermore, despite the increased biofilm resistance to rifampicin, results from this study support its use in staphylococcal PJI. The Translational Potential of this Article: Like for many biomaterial-associated infections, staphylococci are a common cause of PJI. Their ability to adhere to surfaces and produce biofilms on medical devices is proposed to play a role. However, clinical studies where biofilm properties are directly linked to patient outcome are scarce. This study demonstrates that the majority of staphylococci isolated from first-time PJI were biofilm producers with increased antimicrobial resistance. Patients suffering an infection caused by a staphylococcal strain with strong biofilm production ability had a five-fold greater risk of recurrent infection. This novel finding suggests the importance of evaluating biofilm production as a diagnostic procedure for the guidance of treatment decisions in PJI.This work was sponsored by the European Union's Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 754412 [MoRE2020 - Region Västra Götaland], CARe - Centre for Antibiotic Resistance Research at University of Gothenburg, Swedish Research Council [2018–02891], the Swedish state under the agreement between the Swedish government and the county councils, the ALF agreement [ALFGBG-725641 ; ALFGBG-719961], the Inga-Britt and Arne Lundberg Foundation, the Hjalmar Svensson Foundation, Doctor Felix Neuberghs Foundation, the Adlerbertska Foundation, the Sylvan Foundation, Göteborgs Läkarsällskap/The Gothenburg Medical Society research grants [for PhD-studies and Svea Bäcksins grant GLS-780551 ], and the Area of Advance Materials of Chalmers/GU Biomaterials within the Strategic Research Area initiative launched by the Swedish government

Reduction of early surgical site and other care related infections in 3553 hip fracture patients : lessons learned from the 5-year Safe Hands project

Background: Surgical site infection (SSI) after acute hip fracture surgery is a devastating complication associated with increased suffering and mortality. The aim of the study was to investigate early SSI, sepsis, pneumonia and urinary tract infections over five years, before and after the implementation of the Safe Hands project. Methods: This was a single-centre observational study with a 5-year longitudinal design, investigating the effects of an infection-prevention intervention targeting the clinical care pathway of individuals with acute hip fracture. Statistical analyses were based on routinely collected patient outcome data comprising 3553 patients. The study conforms to the criteria of the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE). Results: The incidence of early SSIs decreased from 2.5% in years 1–2 to 1.1% in years 4–5. Similar results were observed for sepsis (2.7% to 1.3%) and urinary tract infections (14.2% to 4.2%). The multivariable regression results suggest that, for every observed year, the odds of early SSIs decreased. Male gender, procedure time, sepsis and preoperative skin damage increased the odds significantly. Conclusions: Our preventive bundle, based on partnership between researchers, managers and clinicians and a strong commitment to change from the involved professions, appear to be effective in reducing the frequency of potentially devastating SSIs and other hospital acquired infections after hip fracture surgery. The use of external and internal facilitators was crucial to enable individual and organisational learning and overcoming barriers to improvements. Trial registration: Clinical Trials.gov ID: NCT02983136 Registered 6 December 2016—Retrospectively registered