Noninvasively Imaging pH at the Surface of Implanted Orthopedic Devices with X-ray Excited Luminescence Chemical Imaging.

Implanted medical device-associated infections are a leading cause of fixation failure, and early diagnosis is the key to successful treatment. During infection, acidosis near the implant plays a role in antibiotic resistance and low pH is a potential infection indicator. Herein, we describe a pH sensor which attaches to the implants to noninvasively image local pH with high spatial resolution. The sensor has two layers: a scintillator layer which emits 620 and 700 nm light upon X-ray irradiation and a pH indicator layer containing bromocresol green dye that absorbs 620 nm luminescence in neutral/basic pH and passes 700 nm light at all pHs. We also developed a dedicated imaging system capable of scanning relatively large specimens through thick tissues. A focused X-ray beam irradiates one spot on the sensor, and the 620 to 700 nm peak ratio is measured to determine the local pH; images are acquired by scanning the X-ray beam across the surface and measuring the pH point-by-point. The sensor was covered with varying thickness slices of chicken breast tissue (0-19 mm) to evaluate how the tissue affects the peak intensity and ratio. Thick tissues attenuated both 620 and 700 nm light, with more attenuation at 620 nm than 700 nm. Although this spectral distortion shifted the pH calibration curve, the effect could be corrected for using a scintillator film region with no pH indicator layer as a spectral reference. The sensor was attached to an orthopedic plate affixed to a human cadaveric tibia and imaged through tissue. This approach provides both high spatial resolution from focused X-ray excitation and surface chemical specificity from the indicator dye, providing a tool for imaging local pH through tissue.

Revision spine surgery in patients without clinical signs of infection: How often are there occult infections in removed hardware?

PURPOSE: To examine the incidence of occult infection in revision spine surgeries and its correlation with preoperative inflammatory markers. METHODS: We retrospectively reviewed all patients who underwent revision spine surgery and hardware removal between 2010 and 2016. Patients who had preoperative clinical signs of infection were excluded. The hardware and surrounding tissue culture results were obtained. The patients' diagnosis and preoperative inflammatory marker (ESR, CRP, and procalcitonin) levels were recorded. RESULTS: A total of 162 consecutive patients were included in this study. The patients' mean age was 61 years (range 14-88). One hundred and three patients (63.6%) were female. Seventy-two patients (44.4%) had loose hardware and 88 patients (54.3%) had pseudarthrosis. Postoperatively, the hardware and/or surrounding tissue culture was positive in 15 patients (9.3%). The most commonly identified organisms were Propionibacterium acnes (7/15, 46.7%) and Staphylococcus (6/15, 40.0%). The other identified organisms were Pseudomonas aeruginosa (1/15, 6.7%) and Serratia marcescens (1/15, 6.7%). Only four patients with positive cultures had elevated preoperative ESR and CRP levels. Only two patients with positive cultures had elevated preoperative procalcitonin levels. There is no correlation between the patients' preoperative ESR, CRP, procalcitonin levels, and positive culture results (p > 0.05). CONCLUSIONS: Our study shows that occult infections are present in 9.3% of patients who underwent revision spine surgery and hardware removal although they did not have clinical signs of infection. Those commonly used preoperative inflammatory markers such as ESR, CRP, and procalcitonin may not be sensitive enough to detect occult infections in these patients. These slides can be retrieved under Electronic Supplementary Material.

Novel Antibacterial Coating on Orthopedic Wires To Eliminate Pin Tract Infections.

Novel approaches to the prevention of microbial infections after the insertion of orthopedic external fixators are in great demand because of the extremely high incidence rates of such infections, which can reach up to 100% with longer implant residence times. Monolaurin is an antimicrobial agent with a known safety record that is broadly used in the food and cosmetic industries; however, its use in antimicrobial coatings of medical devices has not been studied in much detail. Here, we report the use of monolaurin as an antibacterial coating on external fixators for the first time. Monolaurin-coated Kirschner wires (K-wires) showed excellent antibacterial properties against three different bacterial strains, i.e., methicillin-sensitive Staphylococcus aureus (MSSA), methicillin-resistant Staphylococcus aureus (MRSA), and Staphylococcus epidermidis Approximately 6.0-log reductions of both planktonic and adherent bacteria were achieved using monolaurin-coated K-wires, but monolaurin-coated K-wires did not show any observable cytotoxicity with mouse osteoblast cell cultures. Overall, monolaurin-coated K-wires could be promising as potent antimicrobial materials for orthopedic surgery.

Extended-Spectrum Beta-Lactamase Infections in Orthopedic-Related Devices and Prosthetic Joints.

Extended-spectrum beta-lactamase-producing Enterobacteriaceae have increasingly become a public health issue in a variety of infections, including urinary tract infections and postoperative infections. The complications that occur due to these organisms in bone, joint, and prosthetic joints have not been well defined. This study reviewed the clinical characteristics, risk factors, and outcomes of patients with extended-spectrum beta-lactamase-producing Enterobacteriaceae infections of prosthetic joints or orthopedic-related hardware. Six infections met the inclusion criteria that resulted in a 100% failure rate when the hardware or prosthetic joint was not replaced initially. However, when the hardware or prosthetic joint was replaced, all of the patients did well. The use of carbapenems remains effective in these cases. [Orthopedics. 2016; 39(4):e668-e673.].

Prosthetic Joint and Orthopedic Device Related Infections. The Role of Biofilm in the Pathogenesis and Treatment.

Prosthetic joint infections (PJI) in orthopedic related devices (ORD) are major issues following replacement of joints. It results in serious morbidity and mortality and is expensive to treat and manage. The pathogenesis of these infections is related to the presence of biofilm on the metallic and plastic surfaces of the devices. This biofilm results in poor penetration of antibiotics resulting in persistence and difficulty in eradication of the infection despite appropriate antibiotics. This paper summarizes the present data of biofilm as it relates to PJI/ORD.

Factors associated with treatment failure in vertebral osteomyelitis requiring spinal instrumentation.

Patients with vertebral osteomyelitis may require instrumentation for spinal stabilization. Determining the optimal duration and type of antimicrobial therapy for these patients is challenging. The aim of this study was to examine risk factors for treatment failure, in particular antimicrobial duration, in a cohort of patients requiring spinal instrumentation for vertebral osteomyelitis. We conducted a retrospective cohort study of all patients with vertebral osteomyelitis who had spinal instrumentation between January 2002 and January 2012 at the University of Maryland Medical Center. The primary outcome measure was treatment failure >4 weeks postoperatively. We identified 131 patients with vertebral osteomyelitis requiring spinal instrumentation, 94 of whom had >4 weeks of follow-up and were included in the primary analysis. Treatment failure occurred in 22 of the 94 patients (23%) at a median of 4 months after surgery. Among patients who failed therapy, 20 of 22 failed within 1 year of surgery. Cervical and thoracic infection sites and the presence of negative cultures were associated with fewer treatment failures. Addition of rifampin and the use of chronic suppressive antimicrobials did not affect treatment failure rate. Twenty-three percent of patients with spinal instrumentation for vertebral osteomyelitis experienced treatment failure. Treatment failure almost always occurred within the first year of spinal instrumentation.

Prevention of orthopedic device-associated osteomyelitis using oxacillin-containing biomineral-binding liposomes.

PURPOSE: To develop novel biomineral-binding liposomes (BBL) for the prevention of orthopedic implant associated osteomyelitis. METHODS: A biomineral-binding lipid, alendronate-tri(ethyleneglycol)-cholesterol conjugate (ALN-TEG-Chol), was synthesized through Cu(I)-catalyzed Huisgen 1,3-dipolar cycloaddition (a versatile click reaction). Mixing with other excipients, the new lipid was used to develop BBL. Thermodynamic behavior was studied by differential scanning calorimetry (DSC). In vitro biomineral-binding potential and kinetics were evaluated on hydroxyapatite (HA, a widely used material for orthopedic implant devices) particles. Oxacillin was encapsulated into BBL and used for in vitro evaluation in preventing Staphylococcus aureus biofilm formation. RESULTS: DSC analysis showed that ALN-TEG-Chol could inhibit the phase transition of liposomes by reducing its cooperativity, yielding liposomes with thermodynamic stability similar to liposomes containing regular cholesterol. BBL showed fast and strong binding ability to HA. Oxacillin-loading BBL demonstrated significantly better preventive efficacy against bacteria colonization when challenged with S. aureus isolate, implying its potential in preventing orthopedic implant associated osteomyelitis. CONCLUSIONS: In this proof of concept study, novel BBL has been successfully developed and validated for reducing the frequency of implantable device-related infections.

Staphylococcus simulans as an authentic pathogenic agent of osteoarticular infections.

OBJECTIVES: To evaluate the role of Staphylococcus simulans in bone and joint infections (BJI) and determine their main characteristics. METHODS: A search of the database of the microbiology laboratories of Lille hospital and Tourcoing hospital was performed. Only results from blood, bone, and orthopedic device cultures were taken into account for hospitalized patients between January 2004 and January 2009. We considered cases in which S. simulans was the only bacteria isolated in all of the patients' biological samples with clinical and laboratory signs of infection. For patients with complete medical records, we recorded the clinical and epidemiological data. RESULTS: Six cases of BJI due to S. simulans were recorded, with five cases related to orthopedic devices infections. Three patients lived in rural areas. In four out of six patients, S. simulans was isolated in intraoperative biopsy material. In one patient, S. simulans grew in synovial fluid and in another in blood cultures only. The latter patient had a spondylodiscitis, and chronic foot ulcers due to gout disease were suspected to be the origin of the infection. All patients were healed after a mean follow up of 9 ± 3 months. Orthopedic devices were removed in four of the five patients concerned. The combination of rifampicin plus levofloxacin was used in four patients. CONCLUSION: The present data suggest that, even though S. simulans remains rarely observed in clinical pathology, its role in osteoarticular infections, especially in the case of infected orthopedic devices, is not exceptional. As for the antibiotic treatment, the combination of rifampicin and levofloxacin seems to be an effective strategy according to our clinical results.

New methods for the detection of orthopedic and other biofilm infections.

The detection and identification of bacteria present in natural and industrial ecosystems is now entirely based on molecular systems that detect microbial RNA or DNA. Culture methods were abandoned, in the 1980s, because direct observations showed that <1% of the bacteria in these systems grew on laboratory media. Culture methods comprise the backbone of the Food and Drug Administration-approved diagnostic systems used in hospital laboratories, with some molecular methods being approved for the detection of specific pathogens that are difficult to grow in vitro. In several medical specialties, the reaction to negative cultures in cases in which overt signs of infection clearly exist has produced a spreading skepticism concerning the sensitivity and accuracy of traditional culture methods. We summarize evidence from the field of orthopedic surgery, and from other medical specialties, that support the contention that culture techniques are especially insensitive and inaccurate in the detection of chronic biofilm infections. We examine the plethora of molecular techniques that could replace cultures in the diagnosis of bacterial diseases, and we identify the new Ibis technique that is based on base ratios (not base sequences), as the molecular system most likely to fulfill the requirements of routine diagnosis in orthopedic surgery.

Comparison of vancomycin and teicoplanin trough serum levels in patients with infected orthopedic devices: new data for old therapies.

We compared retrospectively vancomycin and teicoplanin trough serum levels after loading doses and, subsequently, after high daily doses, in 52 patients (26 in each group) who had developed infections after implantation of an orthopedic device. The target trough serum level was > 25 mg/l. Trough levels were significantly higher at 2 days (±1) and 5 days (±1) in patients who received teicoplanin compared with patients who received a continuous perfusion of vancomycin (26.1 vs. 16 mg/l at day 2 ± 1, P = 0.01; 27.8 vs. 19.9 mg/l at day 5 ± 1, P = 0.01). One of the 26 patients taking vancomycin reached the target trough serum level by day 2 (±1), whereas 10 of the 26 patients taking teicoplanin reached the target by that time (P = 0.002). At day 5 (±1), 6/26 patients taking vancomycin reached the target, versus 13/26 patients taking teicoplanin (P = 0.04). However, physicians should remain cautious when administering teicoplanin empirically because of the higher MIC90 values observed for coagulase-negative staphylococci compared with vancomycin.

Antibiotic-loaded allograft decreases the rate of acute deep wound infection after spinal fusion in cerebral palsy.

STUDY DESIGN: A retrospective matched cohort study with control group. OBJECTIVE: To compare the infection rate after posterior spinal fusion with unit rod instrumentation with or without gentamicin-impregnated allograft bone in children with cerebral palsy (CP). SUMMARY OF BACKGROUND DATA: Previous studies evaluating wound infection rates after spinal fusion surgery in children with CP report an 8.7% to 10% wound infection rate. The concept of using antibiotic-loaded bone graft (AbBGF) to provide local antibiotics has been explored in high risk patients, such as those with osteomyelitis or infected joint arthroplasty. There have been no reports of using AbBGF prophylactically in spine surgery. METHODS: After IRB approval, the medical records of 220 children with CP who underwent spinal fusion with unit rod instrumentation for a primary spinal deformity between January 2000 through December 2006 at a single institution were retrospectively reviewed. We evaluated the incidence of postoperative wound infection in patients with AbBGF and those without bone graft (BGF). RESULTS: One hundred fifty-four patients received AbBGF during spinal fusion surgery and 6 patients (3.9%) developed a deep wound infection. Ten (15.2%) of the 66 patients without AbBGF developed a deep wound infection. The difference between groups was statistically different (P = 0.003). The mean age at surgery, preoperative Cobb angle, correction rate, operative time, and estimated blood loss were not statistically different between the 2 groups (P > 0.05). The length of hospital stay was decreased in the AbBGF group (P < 0.05). CONCLUSION: The incidence of deep wound infection after spinal fusion in 220 children with CP scoliosis decreased from 15% to 4% with the use of prophylactic antibiotics in the corticocancellous allograft bone.

Temporary antibiotic cement-covered gamma nail spacer for an infected nonunion of the proximal femur.

We report the case of an infected nonunion of the proximal femoral in an elderly patient. There was extensive involvement of the entire proximal femur precluding salvage. An impromptu use of a cephalomedullary nail coated with antibiotic-laden bone cement is described, followed by reimplantation with a revision-type proximal femoral prosthesis. The patient had resection of the proximal femur, placement of a temporary functional spacer, and reimplantation after a course of antibiotics, with good success. The method we describe is a reasonable alternative when standard off-the-shelf systems or other methods of temporary spacer creation are not available.

Infections associated with orthopedic implants.

PURPOSE OF REVIEW: We review recent advances in the prevention, diagnosis and treatment of infections associated with joint prostheses and internal fixation devices. RECENT FINDINGS: The perioperative antimicrobial prophylaxis should be administered 60-30 min before incision or before inflation of the tourniquet. New diagnostic approaches include sonication of removed implants to dislodge adherent microorganisms growing in biofilms and the use of molecular techniques to improve diagnostic yield. Treatment of implant-associated infections without removal of the device is an established option for selected patients. Treatment with rifampin combinations in staphylococcal infections is crucial for success. As demonstrated in vitro, in animal studies and in clinical trials, quinolones are suitable combination agents with rifampin against susceptible staphylococci, but increasing antimicrobial resistance requires evaluation of alternative combination agents, such as quinpristin-dalfopristin, linezolid, and daptomycin, although clinical experience is limited. New antimicrobial agents, such as dalbavancin, tigecycline, iclaprim, and novel rifamycin derivatives are studied. SUMMARY: Better understanding of the interaction between microorganisms, the implant and the host may improve our current approach to the diagnosis and treatment of implant-associated infections. The treatment modality depends on duration of infection, stability of the implant, antimicrobial susceptibility of the pathogen and condition of the surrounding soft tissue.

Late implant infections caused by Propionibacterium acnes in scoliosis surgery.

One hundred and one consecutive adolescent scoliosis patients instrumented from the posterior between 1995 and 2002, with a minimum follow-up of 24 months (maximum 106 months), were reviewed for incidence of infection. Stainless steel implants with pedicle screws were used in the thoracic and lumbar spine of all patients. All were operated on by a single surgeon. There were no early infections. Incidence of late infection was 6.9% (seven patients). Clinical indicators for infection were the sudden onset of local pain and swelling without fever after an initial pain-free interval. There were no reliable laboratory parameters. Normal CRP and ESR did not rule out a late infection. Extended cultures were done from intraoperative swabs. Propionibacterium acnes was found in six patients. There were no other organisms identified. No causative organism could be identified in one patient, despite extended cultures. All patients were successfully treated with implant removal and antibiotic therapy for 4-9 weeks. No pseudarthrosis was seen on implant removal. Despite bony fusion, loss of correction between 10 degrees and 26 degrees was observed in three patients after implant removal.

Use of structural allografts in spinal osteomyelitis: a review of 47 cases.

OBJECT: The use of structural allografts in spinal osteomyelitis remains controversial because of the perceived risk of persistent infection related to a devitalized graft and spinal hardware. The authors have identified 47 patients over the last 3.5 years who underwent a surgical decompression and stabilization procedure in which fresh-frozen allografts were used after aggressive removal of infected and devitalized tissue. The patients subsequently underwent 6 weeks of postoperative antibiotic therapy (12 months for those with tuberculosis [TB]). METHODS: Follow-up data included results of serial clinical examinations, radiography, laboratory analysis (erythrocyte sedimentation rate and white blood cell count), and clinical outcome questionnaires. Of the original 47 patients (14 women and 33 men, aged 14-83 years), 39 were available for follow up. The average follow-up period at the time this article was submitted was 17 +/- 9 months (median 14 months, range 6-45 months). In the majority of cases (57%), a Staphylococcus species was the infectious organism. Predisposing risk factors included intravenous drug abuse (IVDA), previous surgery, diabetes, TB, and concurrent infections. During the follow-up period only two patients suffered recurrent infection at a contiguous level; both had a history of IVDA and one also had a chronic excoriating skin condition. No other recurrent infections have been identified, and no patient has required reoperation for persistent infection or allograft/hardware failure. CONCLUSIONS: It is the authors' opinion that the use of structural allografts in combination with aggressive tissue debridement and adjuvant antibiotic therapy provide a safe and effective therapy in cases of spinal osteomyelitis requiring surgery.

Late-developing infection in instrumented idiopathic scoliosis.

STUDY DESIGN: This is a retrospective review of all patients requiring either Cotrel-Dubousset or Moss Miami rod removal. All initial spinal instrumentations were for adolescent idiopathic scoliosis from 1985 through 1994. Twenty-two patients who underwent rod removal for late-developing infection constitute the study group. OBJECTIVES: To determine the bacteriology and treatment of patients with late-developing infection after posterior spinal instrumentation for scoliosis. SUMMARY OF BACKGROUND DATA: There have been conflicting reports regarding this entity, some reporting a high percentage of positive cultures and others a low yield. The latter have attributed the entity to fretting corrosion. Much literature describes late appearance of infection with large foreign bodies (implants). Glycocalyx, a membrane that surrounds bacteria adjacent to surgical implants, results in poor antibiotic penetration, poor macrophage action, and difficulty in culturing bacteria. METHODS: One thousand two hundred forty-seven patients who underwent posterior instrumentation from 1985 through 1994 were reviewed. Those requiring implant removal were further studied. Those with late-developing infection (more than 1 year after the initial procedure) were further reviewed. Culture reports, presence of pseudarthrosis, and antibiotic regimen after implant removal were the primary parameters studied. RESULTS: Twenty-two patients (1.7%) experienced development of late infection a mean of 3.1 years after the initial procedure. In specimens from these patients cultured only 72 hours, only 1 of 10 was positive. Of those cultured for 7-10 days (the last 12) 11 were positive, usually for low-virulence skin organisms. After surgery, patients received antibiotics parenterally for 48 hours and orally for 7 days. All wounds were closed primarily. Four patients had pseudarthroses, two underwent revised procedures with titanium implants without signs of infection at more than 2 years' follow-up. CONCLUSIONS: Late-appearing infection with spinal instrumentation can be treated with device removal, primary skin closure, and short-term oral antibiotics. The infections affect soft tissue, not the bone.

Local plate infections in a rabbit model.

We used 30 New Zealand white rabbits to compare the susceptibility to bacterial challenge of two different orthopaedic implants: a standard-design stainless steel plate, or a PC-FIX titanium plate applied on the right tibia were compared with sham operated animals. Directly after surgery Staphylococcus aureus (10(8)-10(9) colony forming units) were inoculated close to the plate. The infection rate in the group of plated animals was 11/20 (stainless steel plates 6/10, PC-FIX titanium plates 5/10) and in sham operated animals only 1/10. Thus, a foreign body increased the risk for infection (p = 0.02). However, the implant type did not appear to be of major importance when the bacteria were inoculated locally. In experimental haematogenous infections, by contrast, implant design and material are considered to be important. This may either indicate different pathogenic mechanisms in locally and haematogenously induced infections, or simply that the large number of microorganisms in local inoculation 'overload' the normal defence systems.