Dirk Jan F. Moojen

Identification of orthopaedic infections using broad-range polymerase chain reaction and reverse line blot hybridization.

BACKGROUND Culture remains the gold standard in the diagnosis of bacterial infection, but molecular biological techniques have yielded promising results. In this study, we validated a combined polymerase chain reaction and reverse line blot hybridization protocol for identifying musculoskeletal infections. METHODS Samples were obtained from seventy-six patients undergoing orthopaedic surgery for various aseptic and septic indications. The diagnosis of infection was based on a review of all available clinical and culture data. In addition to routine culture for aerobic and anaerobic growth, samples were analyzed with a broad-range 16S rRNA polymerase chain reaction and subsequent reverse line blot hybridization with use of twenty-eight group, genus, and species-specific oligonucleotide probes. RESULTS An infection was diagnosed on the basis of patient data in thirty-one patients. All but one of the patients with a clinical diagnosis of infection had a positive result of the polymerase chain reaction-reverse line blot hybridization. Five of the forty-five patients in whom an infection was not suspected on the basis of patient data had at least one positive result of the polymerase chain reaction-reverse line blot hybridization. Cultures demonstrated microorganisms in twenty-five patients with an infection and in two patients in whom an infection was not suspected on the basis of the patient data. Staphylococcus aureus was the most common organism grown on culture. The species identified by the polymerase chain reaction-reverse line blot hybridization was in full accordance with that grown on culture in all but one patient. CONCLUSIONS Polymerase chain reaction-reverse line blot hybridization performed well in detecting and identifying the various bacterial species and was more sensitive than routine culture. It identified Staphylococcus aureus as the most frequently found microorganism. Five patients in whom an infection was not suspected on the basis of the patient data had a positive result of the polymerase chain reaction, which may have been caused by contamination of the samples. However, three of these patients had aseptic loosening of a total hip prosthesis, suggesting the presence of a low-grade bacterial infection that remained undetected by the culture but was detected by the polymerase chain reaction-reverse line blot hybridization. LEVEL OF EVIDENCE Diagnostic Level III.

Perivascular and Diffuse Lymphocytic Inflammation are not Specific for Failed Metal-on-metal Hip Implants

BackgroundSeveral studies suggest that histologic findings from tissues obtained at revision arthroplasty for failed metal-on-metal (MOM) total hip implants may reflect an immune reaction to particles or ions in some patients. However, only a limited number of cases without MOM implants were reported as controls in those studies.Questions/purposesThe purpose of this study is to better define the extent and distribution of morphologic features attributed to an immune reaction in tissues sampled at revision surgery for failed nonMOM THA.Patients and MethodsAs part of a multicenter, prospective study, we reviewed 612 capsular and interface tissues obtained from 130 patients at revision THA. The samples were selected from periacetabular regions (154 samples from 103 patients), femoral implant/cement-bone interface (154 samples from 79 patients), and from areas of the joint capsule that had an intraoperative gross appearance suggesting the possibility of either infection or metallosis (256 samples from 129 patients). All patients had more than one sample obtained. The extent and distribution of lymphocytes and plasma cells, acute inflammation, and visible particles of debris were graded using criteria similar to those described to grade inflammation around failed MOM implants.ResultsWe identified perivascular lymphocytes in 111 biopsy samples taken from 65 (50%) of 130 patients, and in 87 specimens from 57 (53%) of 107 patients thought to have aseptic loosening. Diffusely distributed lymphocytes were identified in 86 (66%) of 130 patients, and in 66 (62%) of the 107 hips with aseptic loosening, although few had the highest grade of inflammation. Increasing extent of diffuse and perivascular lymphocytes correlated with increasing extent of metal particles.ConclusionsMild lymphocytic inflammation, diffuse and especially perivascular, is common in tissues around failed nonMOM implants. Although extensive inflammation in an inflammatory pseudotumor pattern is rare, it does occur in some cases of failed metal-polyethylene hip arthroplasties. The importance of inflammation is unknown, but the extent of diffuse inflammation shows a positive correlation with metal debris, so it could reflect a reaction to particles or ions in some patients.

In Vitro Release of Antibiotics from Commercial PMMA Beads and Articulating Hip Spacers

The efficacy and benefits of high-dose antibiotic cement spacers compared with beads in the treatment of an infected prosthesis have been shown. However, in clinical practice, commercial, low-dose antibiotic bone cement is often used. This study investigated the in vitro antibiotic release of hip spacers made from Refobacin-Palacos-R or Antibiotic-Simplex-P cement compared with Septopal beads. Antibiotic concentrations were measured during 6 weeks. All carriers showed a burst release, but spacers showed little additional release after the first week. Cumulative release was 27.5 +/- 2.3 mg for Palacos, 23.8 +/- 0.2 mg for Simplex, and 188.3 +/- 9.3 mg for Septopal (P < .001). Despite the efficacy of high-dose antibiotic bone cement spacers, we believe one should be cautious toward using low-dose antibiotic bone cement for spacers because this could result in an unsuccessful eradication of infection.

Incidence of low-grade infection in aseptic loosening of total hip arthroplasty

Purpose We investigated the hypothesis that many total hip arthroplasty revisions that are classified as aseptic are in fact low-grade infections missed with routine diagnostics. Methods In 7 Dutch hospitals, 176 consecutive patients with the preoperative diagnosis of aseptic loosening of their total hip arthroplasty were enrolled. During surgery, between 14 and 20 tissue samples were obtained for culture, pathology, and broad-range 16S rRNA PCR with reverse line blot hybridization. Patients were classified as either not being infected, suspected of having infection, or infected according to strict, predefined criteria. Each patient had a follow-up visit after 1 year. Results 7 patients were classified as infected, 4 of whom were not identified by routine culture. 15 additional patients were suspected of having infection. 20 of these 22 patients received a cemented prosthesis, fixated with antibiotic-loaded bone cement. All 22 patients received prophylactic systemic antibiotics. 7 of them reported complaints one year after surgery, but only one showed signs of early loosening. However, additional surgery was not performed in any of the patients. Interpretation Although the proportions were not as high as previously reported in the literature, between 4% and 13% of patients with the preoperative diagnosis of aseptic loosening were infected. However, as thorough debridement was performed during surgery and prophylactic antibiotics were used, the diagnosis of infection did not have any obvious clinical consequences, as most patients performed well at the 1-year follow-up. Whether this observation has implications for long-term implant survival remains to be seen.

Prophylaxis of infection and effects on osseointegration using a tobramycin-periapatite coating on titanium implants—An experimental study in the rabbit

No options are available for local antibiotic delivery from uncemented implants. By loading a porous titanium implant with a biomimetic HA‐coating (PeriApatite, PA) with antibiotics, we could obtain adequate local antibiotic concentrations and reduce infection susceptibility. This study investigated the efficacy of a tobramycin‐loaded PA‐coated titanium foam implant in preventing infection, as well as the effects on osseointegration. In 72 New Zealand White rabbits, an uncoated (Ti), PA‐coated (PA), or Tobramycin‐PA‐coated (PA‐tobra) titanium foam rod was implanted intramedullary in the left tibiae after contamination of the implant bed with none (control), 103, 104 or 105 CFU Staphylococcus aureus. PA‐tobra implants were loaded with 2.4 mg tobramycin. After 28 days analysis was done by bacteriology, histopathology and histomorphometry. Six percent of the contaminated PA‐tobra rabbits were infected, whereas this was 53 and 67% for PA and Ti, respectively (p < 0.001). Quantitative cultures were also significantly lower in the PA‐tobra group (p = 0.003). None of the control rabbits were infected. Histopathological and histomorphometrical scores were both better for the PA‐tobra group, although only significant compared to Ti. No significant differences were observed between PA and Ti rabbits. We conclude that the application of tobramycin to PA‐coated titanium foam implants appears to be an effective local antibiotic strategy for uncemented implants for infection prophylaxis and has a beneficial effect on implant fixation, which will result in improved long‐term implant survival.

No efficacy of silver bone cement in the prevention of methicillin-sensitive Staphylococcal infections in a rabbit contaminated implant bed model

Data from literature showed that a new type of metallic silver PMMA cement had good results in infection prophylaxis. This study investigated the in vivo efficacy of silver cement in the prevention of methicillin‐sensitive Staphylococcal infections, compared to plain and tobramycin‐containing cement. In 48 rabbits, 0.6% silver, 1% silver, plain, or tobramycin PMMA cement was injected into the femoral medullary canal after contamination with 105, 106, or 107 colony forming units (CFU) Staphylococcus aureus. After 14 days, bone was collected for bacteriology and histopathology. All plain and silver cement rabbits were infected, whereas only two tobra rabbits were infected (p < 0.001). The number of bacteria cultured (10logCFU) from bone adjacent to the cement, was 6.4 ± 0.3 and 6.1 ± 0.3 for the 0.6% and 1% silver rabbits. For the rabbits with plain and tobra cement, this was 6.2 ± 0.2 (p > 0.95) and 0.0 ± 0.0 (p < 0.001), respectively. Two tobra rabbits had a positive culture of a distal bone sample. Histological sections of plain, 0.6%, and 1% silver rabbits all showed signs of infection; these signs were absent in the tobra rabbits. Silver and plain cement were not effective in preventing infection, whereas tobra cement was effective. As silver cement predominantly exhibits an antimicrobial effect at the direct cement surface, this cement seems less useful in situations where there are bacteria present in surrounding tissues, like revision surgery. Whether silver cement has relevance in the prevention of bacterial colonization of cement remains to be determined.

Total Hip Arthroplasty After Acetabular Fracture Is Associated With Lower Survivorship and More Complications.

BackgroundDespite modern fracture management techniques allowing for near anatomic reduction of acetabular fractures, there continues to be a risk of posttraumatic arthritis and need for total hip arthroplasty (THA). Few well-controlled studies have compared THA after acetabular fractures with THAs performed for other indications in terms of survivorship or complications, and none, to our knowledge, present 10-year survivorship data in this setting.Questions/purposes(1) How does the 10-year survival of THA compare between those patients who underwent THA after an acetabular fracture and those who underwent THA for primary arthritis or avascular necrosis (AVN)? (2) Is there an increased risk of serious complications like infection, dislocation, and aseptic loosening as well as heterotopic ossification associated with a THA performed after a previous acetabular fracture?MethodsThis retrospective case-control study compared findings of patients who underwent THA after acetabular fracture versus a matched cohort of patients who had received a primary THA for primary osteoarthritis or AVN. Between 1987 and 2011, we performed 95 THAs after acetabular fracture; of those, 74 (78%) met inclusion criteria and had documented followup beyond 2 years in our institutional registry. We selected 74 matched patients based on an algorithm that matched patients based on preoperative diagnosis, date of operation, age, gender, and type of prosthesis. During this time, we performed approximately 8000 THAs that were potentially available for matching based on complete followup beyond 2 years. We compared cases and control subjects using the Kaplan-Meier survivorship estimator as well as a comparison of the proportions in each group that developed major complications (including infection, dislocation, loosening, and heterotopic ossification) based a retrospective chart review.ResultsThe 10-year survivorship after THA was lower in patients with a previous acetabular fracture than in the matched cohort (70%, 95% confidence interval [CI], 64%–78%, versus 90%, 95% CI, 86–95%; p < 0.001). There was no difference in the 10-year survival rate for those patients whose acetabular fracture was initially treated conservatively and those treated by open reduction and internal fixation. Patients with previous acetabular fracture had a higher likelihood of developing infection (7% [five of 74] versus 0% [zero of 74]; odds ratio [OR], 11.79; p = 0.028), dislocation (11% [eight of 74] versus 3% [two of 74]; OR, 4.36; p = 0.048), or heterotopic ossification (43% [32 of 74] versus 16% [12 of 74]; OR, 3.93; p < 0.001).ConclusionsIn this case-control study, patients with a prior acetabular fracture had markedly inferior 10-year survivorship and more frequent serious complications when compared with patients undergoing THA for primary osteoarthritis or AVN. Given these findings, management of these complex cases should be in highly specialized units where the expertise of arthroplasty and trauma reconstruction is available.Level of EvidenceLevel III, therapeutic study.

Similar success rates for single and multiple debridement surgery for acute hip arthroplasty infection.

Background — Treatment of an acute total hip arthroplasty (THA) infection aims at control of the infection with retention of the implant by surgical debridement and antibiotic treatment. There is no clear evidence whether a single surgical debridement is sufficient or whether multiple procedures are necessary for optimal treatment. Methods — From a prospective database of patients with acute THA infection, we retrospectively reviewed 68 patients treated in 2 large teaching hospitals. Hospital S used a protocol in which each patient received a single surgical debridement and only additional surgery if infectious symptoms persisted (group S; n = 33). In hospital M, patients always received multiple surgical debridements (group M; n = 35). Both groups received systemic antibiotic treatment. Removal of the implant or persistent infection at follow-up was considered failure of treatment. Mean follow-up of the patients was 5 (2–11) years. Results — Mean time between implantation and debridement was 19 days. 4 patients in group S were considered failure, as opposed to 10 patients in group M (p = 0.09). 9 patients in group S had additional surgery, which resulted in 3 of the 4 failures. At final follow-up, 30 patients in group S and 33 patients in group M had a good clinical result (p = 0.6). Interpretation — In patients with acute THA infection, a single debridement with only additional surgery on indication appears to be at least as successful for retention of the primary implant and control of infection as a strategy with multiple surgical debridements.

Missed low-grade infection in suspected aseptic loosening has no consequences for the survival of total hip arthroplasty

Background and purpose — Aseptic loosening and infection are 2 of the most common causes of revision of hip implants. Antibiotic prophylaxis reduces not only the rate of revision due to infection but also the rate of revision due to aseptic loosening. This suggests under-diagnosis of infections in patients with presumed aseptic loosening and indicates that current diagnostic tools are suboptimal. In a previous multicenter study on 176 patients undergoing revision of a total hip arthroplasty due to presumed aseptic loosening, optimized diagnostics revealed that 4–13% of the patients had a low-grade infection. These infections were not treated as such, and in the current follow-up study the effect on mid- to long-term implant survival was investigated. Patients and methods — Patients were sent a 2-part questionnaire. Part A requested information about possible re-revisions of their total hip arthroplasty. Part B consisted of 3 patient-related outcome measure questionnaires (EQ5D, Oxford hip score, and visual analog scale for pain). Additional information was retrieved from the medical records. The group of patients found to have a low-grade infection was compared to those with aseptic loosening. Results — 173 of 176 patients from the original study were included. In the follow-up time between the revision surgery and the current study (mean 7.5 years), 31 patients had died. No statistically significant difference in the number of re-revisions was found between the infection group (2 out of 21) and the aseptic loosening group (13 out of 152); nor was there any significant difference in the time to re-revision. Quality of life, function, and pain were similar between the groups, but only 99 (57%) of the patients returned part B. Interpretation — Under-diagnosis of low-grade infection in conjunction with presumed aseptic revision of total hip arthroplasty may not affect implant survival.

Antibiotic prophylaxis is not indicated prior to dental procedures for prevention of periprosthetic joint infections: A systematic review and new guidelines from the Dutch Orthopaedic and Dental Societies

Background and purpose — To minimize the risk of hematogenous periprosthetic joint infection (HPJI), international and Dutch guidelines recommended antibiotic prophylaxis prior to dental procedures. Unclear definitions and contradictory recommendations in these guidelines have led to unnecessary antibiotic prescriptions. To formulate new guidelines, a joint committee of the Dutch Orthopaedic and Dental Societies conducted a systematic literature review to answer the following question: can antibiotic prophylaxis be recommended for patients (with joint prostheses) undergoing dental procedures in order to prevent dental HPJI? Methods — The Medline, Embase, and Cochrane databases were searched for randomized controlled trials (RCTs), reviews, and observational studies up to July 2015. Studies were included if they involved patients with joint implants undergoing dental procedures, and either considered HPJI as an outcome measure or described a correlation between HPJI and prophylactic antibiotics. A guideline was formulated using the GRADE method and AGREE II guidelines. Results — 9 studies were included in this systematic review. All were rated “very low quality of evidence”. Additional literature was therefore consulted to address clinical questions that provide further insight into pathophysiology and risk factors. The 9 studies did not provide evidence that use of antibiotic prophylaxis reduces the incidence of dental HPJI, and the additional literature supported the conclusion that antibiotic prophylaxis should be discouraged in dental procedures. Interpretation — Prophylactic antibiotics in order to prevent dental HPJI should not be prescribed to patients with a normal or an impaired immune system function. Patients are recommended to maintain good oral hygiene and visit the dentist regularly.