Constantinos Ketonis

Periprosthetic infection: where do we stand with regard to Gram stain?

Background and purpose One of the routinely used intraoperative tests for diagnosis of periprosthetic infection (PPI) is the Gram stain. It is not known if the result of this test can vary according to the type of joint affected or the number of specimen samples collected. We examined the role of this diagnostic test in a large cohort of patients from a single institution. Materials and methods A positive gram stain was defined as the visualization of bacterial cells or “many neutrophils” (> 5 per high-power field) in the smear. The sensitivity, specificity, and predictive values of each individual diagnostic arm of Gram stain were determined. Combinations were performed in series, which required both tests to be positive to confirm infection, and also in parallel, which necessitated both tests to be negative to rule out infection. Results The presence of organisms and “many” neutrophils on a Gram smear had high specificity (98–100%) and positive predictive value (89–100%) in both THA and TKA. The sensitivities (30–50%) and negative predictive values (70–79%) of the 2 tests were low for both joint types. When the 2 tests were combined in series, the specificity and positive predictive value were absolute (100%). The sensitivity and the negative predictive value improved for both THA and TKA (43–64% and 82%, respectively). Interpretation Although the 2 diagnostic arms of Gram staining can be combined to achieve improved negative predictive value (82%), Gram stain continues to have little value in ruling out PPI. With the advances in the field of molecular biology, novel diagnostic modalities need to be designed that can replace these traditional and poor tests.

Bacterial Colonization of Bone Allografts: Establishment and Effects of Antibiotics

BackgroundBone grafts are frequently used to supplement bone stock and to establish structural stability. However, graft-associated infection represents a challenging complication leading to increased patient morbidity and healthcare costs.Questions/purposesWe therefore designed this study to (1) determine if increasing initial S. aureus inoculation of bone allograft results in a proportionate increase in colonization; (2) assess if antibiotics decrease colonization and if antibiotic tethering to allograft alters its ability to prevent bacterial colonization; and (3) determine if covalent modification alters the allograft topography or its biological properties.MethodsAllograft bone and vancomycin-modified bone (VAN-bone) was challenged with different doses of S. aureus for times out to 24 hours in the presence or absence of solution vancomycin. Bacterial colonization was assessed by fluorescence, scanning electron microscopy (SEM), and by direct colony counting. Cell density and distribution of osteoblast-like cells on control and modified allograft were then compared.ResultsBacterial attachment was apparent within 6 hours with colonization and biofilm formation increasing with time and dose. Solution vancomycin failed to prevent bacterial attachment whereas VAN-bone successfully resisted colonization. The allograft modification did not affect the attachment and distribution of osteoblast-like cells.ConclusionsAllograft bone was readily colonized by S. aureus and covered by a biofilm with especially florid growth in natural topographic niches. Using a novel covalent modification, allograft bone was able to resist colonization by organisms while retaining the ability to allow adhesion of osteoblastic cells.Clinical RelevanceGeneration of allograft bone that can resist infection in vivo would be important in addressing one of the most challenging problems associated with the use of allograft, namely infection.

Vancomycin Bonded to Bone Grafts Prevents Bacterial Colonization

ABSTRACT Infection is an important medical problem associated with the use of bone allografts. To retard bacterial colonization, we have recently reported on the modification of bone allografts with the antibiotic vancomycin (VAN). In this report, we examine the ability of this antibiotic-modified allograft to resist bacterial colonization and biofilm formation. When antibiotic was coupled to the allograft, a uniform distribution of the antibiotic was apparent. Following challenges with Staphylococcus aureus for 6 h, the covalently bonded VAN decreased colonization as a function of inoculum, ranging from 0.8 to 2.0 log10 CFU. Furthermore, the VAN-modified surface resisted biofilm formation, even in topographical niches that provide a protected environment for bacterial adhesion. Attachment of the antibiotic to the allograft surface was robust, and the bonded VAN was stable whether incubated in aqueous media or in air, maintaining levels of 75 to 100% of initial levels over 60 days. While the VAN-modified allograft inhibited the Gram-positive S. aureus colonization, in keeping with VAN′s spectrum of activity, the VAN-modified allograft was readily colonized by the Gram-negative Escherichia coli. Finally, initial toxicity measures indicated that the VAN-modified allograft did not influence osteoblast colonization or viability. Since the covalently tethered antibiotic is stable, is active, retains its specificity, and does not exhibit toxicity, it is concluded that this modified allograft holds great promise for decreasing bone graft-associated infections.

Antibacterial activity of bone allografts: comparison of a new vancomycin-tethered allograft with allograft loaded with adsorbed vancomycin.

Bacterial contamination of bone allograft is a significant complication of orthopedic surgery. To address this issue, we have engineered a method for covalently modifying bone allograft tissue with the antibiotic vancomycin. The goal of this investigation was to compare the biocidal properties of this new allograft material with those of vancomycin physisorbed onto graft material. The duration of antibiotic release from the vancomycin-modified allograft matrix was determined, and no elution was observed. In contrast, the adsorbed antibiotic showed a peak elution at 24h that then decreased over several days. We next used an Staphylococcus aureus disk diffusion assay to measure the activity of the eluted vancomycin. Again we found that no active antibiotic was eluted from the covalently modified allograft. Similarly, when the vancomycin-modified allograft morsel was used in the assay, no measurable elution was observed; amounts of antibiotic released from the adsorbed samples inhibited S. aureus growth for 4-7 days. Probably the most telling property of the allograft was that after 2 weeks, the tethered allograft was able to resist bacterial colonization. Unlike the elution system in which vancomycin was depleted over the course of days-weeks, the antibiotic on the allograft was stably bound even after 300 days, while its biocidal activity remained undiminished for 60 days. This finding was in stark contrast to the antibiotic impregnated allograft, which was readily colonized by bacteria. Finally we chose to evaluate three indicators of cell function: expression of a key transcription factor, expression of selected transcripts, and assessment of cell morphology. Since the tethered antibiotic appeared to have little or no effect on any of these activities, it was concluded that the stable, tethered antibiotic prevented bacterial infection while not modifying bone cell function.

Staphylococcal Persistence Due to Biofilm Formation in Synovial Fluid Containing Prophylactic Cefazolin

ABSTRACT Antibiotic prophylaxis is standard for patients undergoing surgical procedures, yet despite the wide use of antibiotics, breakthrough infections still occur. In the setting of total joint arthroplasty, such infections can be devastating. Recent findings have shown that synovial fluid causes marked staphylococcal aggregation, which can confer antibiotic insensitivity. We therefore asked in this study whether clinical samples of synovial fluid that contain preoperative prophylactic antibiotics can successfully eradicate a bacterial challenge by pertinent bacterial species. This study demonstrates that preoperative prophylaxis with cefazolin results in high antibiotic levels. Furthermore, we show that even with antibiotic concentrations that far exceed the expected bactericidal levels, Staphylococcus aureus bacteria added to the synovial fluid samples are not eradicated and are able to colonize model implant surfaces, i.e., titanium pins. Based on these studies, we suggest that current prophylactic antibiotic choices, despite high penetration into the synovial fluid, may need to be reexamined.

Evolving Strategies To Prevent Implant-associated Infections

The consequences of implantassociated infection are significant and usually require revision surgery, with removal of the implant and prolonged antibiotic treatment. Various approaches to reduce the rate of infection have been investigated. Two recent strategies are (1) coating implants with antibiotics and (2) covalently attaching antimicrobial molecules onto the implant surface. The purpose of these bioactive surfaces is to disrupt the metabolic machinery of the microbes or to prevent bacterial adhesion to the implant and, consequently, the development of biofilm.

Optimal Positioning for Volar Plate Fixation of a Distal Radius Fracture: Determining the Distal Dorsal Cortical Distance

Distal radius fractures are currently among the most common fractures of the musculoskeletal system. With a population that is living longer, being more active, and the increasing incidence of osteoporosis, these injuries will continue to become increasingly prevalent. When operative fixation is indicated, the volar locking plate has recently become the treatment of choice. However, despite its success, suboptimal position of the volar locking plate can still result in radiographic loss of reduction. The distal dorsal cortical distance is being introduced as an intraoperative radiographic tool to help optimize plate position and minimize late loss of fracture reduction.

Timing of Debridement and Infection Rates in Open Fractures of the Hand A Systematic Review

Background: Literature on open fracture infections has focused primarily on long bones, with limited guidelines available for open hand fractures. In this study, we systematically review the available hand surgery literature to determine infection rates and the effect of debridement timing and antibiotic administration. Methods: Searches of the MEDLINE, EMBASE, and Cochrane computerized literature databases and manual bibliography searches were performed. Descriptive/quantitative data were extracted, and a meta-analysis of different patient cohorts and treatment modalities was performed to compare infection rates. Results: The initial search yielded 61 references. Twelve articles (4 prospective, 8 retrospective) on open hand fractures were included (1669 open fractures). There were 77 total infections (4.6%): 61 (4.4%) of 1391 patients received preoperative antibiotics and 16 (9.4%) of 171 patients did not receive antibiotics. In 7 studies (1106 open fractures), superficial infections (requiring oral antibiotics only) accounted for 86%, whereas deep infections (requiring operative debridement) accounted for 14%. Debridement within 6 hours of injury (2 studies, 188 fractures) resulted in a 4.2% infection rate, whereas debridement within 12 hours of injury (1 study, 193 fractures) resulted in a 3.6% infection rate. Two studies found no correlation of infection and timing to debridement. Conclusions: Overall, the infection rate after open hand fracture remains relatively low. Correlation does exist between the administration of antibiotics and infection, but the majority of infections can be treated with antibiotics alone. Timing of debridement, has not been shown to alter infection rates.

Wide Awake Trigger Finger Release Surgery: Prospective Comparison of Lidocaine, Marcaine, and Exparel.

Background: Local anesthetics are routinely used in hand surgery for procedures such as trigger finger releases (TFRs). However, little is known as to the difference in efficacy and patient experience with various local anesthetics. We prospectively evaluated the efficacy of Lidocaine (L), Marcaine (M), and Exparel (E) to elucidate differences in pain scores and opioid consumption between these groups. Methods: All consecutive TFR performed over a 6-month period in 2014 at our institution were divided to receive Lidocaine, Marcaine, or Marcaine with postoperative Exparel. Pain levels, daily opioid consumption, and adverse reactions were recorded and analyzed for postoperative day (POD) 0-3. Results: A total of 154 patients were enrolled (L:53, M:50, E:51). The Lidocaine group reported the highest pain levels for POD 0-1. Marcaine pain levels were similar to Exparel on POD 0 but higher on POD 1. Opioid consumption on POD 0-1 was significantly different with E:27%, M:58% and L:59% as was the number of pills consumed (E:0.70, M: 1.08 and L:1.62). In addition, 50% of Exparel patients required no pain medications and experienced significantly less adverse reactions (E:4%, M:10%, L:13%). By POD 2-3, there were no statistical differences between the 3 groups. Conclusions: Patients treated with Marcaine attain better pain control than Lidocaine on POD 0-1but only patients who received Exparel maintained the lowest pain levels through POD 0-3 while using little-to-no opioid medications and with less adverse reactions than Lidocaine or Marcaine alone.

Neurolysis with Amniotic Membrane Nerve Wrapping for Treatment of Secondary Wartenberg Syndrome: A Preliminary Report

BACKGROUND Entrapment of the superficial sensory branch of the radial nerve (SRN) commonly results in debilitating pain of the dorsoradial wrist. Symptom relief following SRN neurolysis is often incomplete or temporary due to recurrent perineural scarring. METHODS We performed a retrospective review with prospective follow-up of all patients with SRN neuropathy who were treated with neurolysis and nerve wrapping using an amnion-based allograft adhesion barrier over a one-year interval. Measured outcomes included pain rated by Visual Analog Scale (VAS) and Quick Disabilities of the Arm, Shoulder and Hand (QuickDASH) functional outcome scores. RESULTS Three females satisfied inclusion. At mean follow-up of 28.9 months, all three patients exhibited improved pain (mean VAS change -4.7 ± 0.6), function (mean QuickDASH change -40 ± 5), and subjective satisfaction. No adverse events or reactions to the implanted tissue occurred. CONCLUSIONS SRN entrapment neuropathy was safely and effectively treated with neurolysis and amnion nerve wrapping in this small series. Use of this technique for perineural scar prevention warrants additional study in larger groups of patients and in other upper extremity entrapment neuropathies.