Phenolphthalein used to assess permeability of antibiotic-laden polymethylmethacrylate: a pilot study.

Elution of antibiotics from polymethylmethacrylate laden with antibiotics is dependent on the permeability of the polymethylmethacrylate. Increasing polymethylmethacrylate permeability by adding fillers has been suggested to increase antibiotic elution but the resulting increase in permeability has not been assessed directly. A simple method to assess polymethylmethacrylate permeability is proposed. Phenolphthalein was added to the polymethylmethacrylate to indicate the level of penetration of fluid with pH of 10.3. Glycine in three different amounts (0.45 g, 7 g, and 28 g) or a combination of antibiotics (13.6 g) was added as a filler to increase the permeability. Beads of each mixture were made and soaked in fluid with a pH of 10.3. An immediate intense magenta coloration occurred on contact of the beads with the fluid. A zone of magenta was seen to penetrate into the depths of polymethylmethacrylate beads. That penetration increased with the amount of the filler and with time in the fluid bath. The type of filler material also affected the rate of fluid penetration. Permeability of various antibiotic polymethylmethacrylate mixtures can be determined qualitatively using this method. The observations may be useful to determine which mixtures warrant more expensive antibiotic elution studies.

Is aseptic loosening truly aseptic?

Surgeons who treat osteomyelitis or infected implants think that microorganisms can live on and around implanted biomaterials and necrotic bone without clinical manifestations of infection. Gristina and Costerton, in their seminal work, suggested that such bacteria persist within biofilms and that they are often overlooked when diagnosis is based on standard microbiologic culture techniques. Subsequent studies using specialized techniques including sonication to remove adherent bacteria and direct detection using various forms of microscopy have confirmed that bacteria are present in many culture-negative cases. This led to the suggestion that at least some cases of failed orthopaedic implants that were considered aseptic loosening based on the absence of clinical signs of infection and the failure to isolate bacteria may actually have an infectious etiology. In addition to biofilms, potentially important concepts that also may contribute to false-negative culture results include the failure to recognize small colony variants induced during growth in vivo and the presence of bacteria inside host cells including osteoblasts. Importantly, bacteria persisting as small colony variants within biofilms and/or inside osteoblasts also may be an explanation for the recurrent nature of musculoskeletal infection.

A guide to reduce allogeneic transfusions in elective orthopaedic surgery.

The principles and techniques used to reduce or eliminate blood transfusions can be applied to the standard practice of orthopaedic surgery. The overall goal is to enable orthopaedic surgeons who are interested in reducing allogeneic transfusions to find a method that fits their practice.

Early detection of bone infection and differentiation from post-surgical inflammation using 2-deoxy-2-[18F]-fluoro-D-glucose positron emission tomography (FDG-PET) in an animal model.

Diagnosing bone infection in the context of post-surgical inflammation is problematic since many of the early signs of infection are similar to normal post-surgical changes. We used a rabbit osteomyelitis model to evaluate the use of 2-deoxy-2-[(18)F]-fluoro-d-glucose positron emission tomography (FDG-PET) as a means of detecting post-operative infection in the context of post-surgical inflammation. Comparisons were made between infected and non-infected rabbits in which infection with Staphylococcus aureus was initiated at the time of surgery. Weekly PET scans were obtained 30 and 60 min after the introduction of FDG and analyzed based on standardized uptake values (SUV) at the surgical site and visual assessment of the presence or absence of infection. Concurrent X-rays were taken immediately prior to scanning. At 4weeks post-operatively, animals were sacrificed for histologic and bacteriologic confirmation of infection. Uptake of FDG was evident in the bone of all rabbits on day 1 post-surgery, however, SUV comparisons from the surgical site could not be used to distinguish between the infected and uninfected groups until day 15. Visual analysis of FDG-PET scans revealed a significant difference (p<0.01) between the infected and uninfected groups as early as day 8. This was due in part to the ability to visualize regional lymph nodes by FDG-PET.

The effect of glycine filler on the elution rate of gentamicin from acrylic bone cement: a pilot study.

Elution of antibiotics from acrylic bone cement (polymethylmethacrylate [PMMA]) is dependent on the access of fluid to the depths of the cement that contains the antibiotic. Commercially prepared antibiotic beads that are porous have higher elution rates than hand-mixed, nonporous antibiotic PMMA mixtures. To increase the elution of gentamicin from hand-mixed PMMA, glycine was added as a filler to produce porosity. Elution of gentamicin from the antibiotic PMMA-glycine mixture increased with increasing amounts of glycine. With 3.6 g gentamicin powder and 14 g of crystalline glycine per batch of Palacos PMMA, the elution of gentamicin from the PMMA at 2 days was, similar to the previously documented elution of gentamicin from commercially prepared porous Septopal PMMA beads. With further investigation it may be possible to identify a specific filler and a volume of filler that can be hand mixed in antibiotic PMMA to produce the elution behavior that is needed for specific clinical requirements.

The current status of material used for depot delivery of drugs.

The ideal local antibiotic delivery system has not been created. Antibiotic-laden bone cement has become the gold standard in the treatment of infected orthopaedic implants and there are confirmatory laboratory and clinical data that support the use of these materials. Heat-stable antibiotics elute from antibiotic-laden bone cement and do not have a notable influence on the compressive strengths of bone cement if the antibiotics are used in appropriate amounts. If the proper antibiotic is chosen, placed in the appropriately porous materials in sufficient amounts, and implanted in bone, antibiotic levels in the surrounding bone are many times greater than can be achieved by safe systemic antibiotic doses. Although the materials that have been manufactured commercially have been used for over 30 years in Europe, until recently, they have not been available in the United States. Currently, there are five antibiotic-laden bone cement composites that have been approved by the FDA and that are available for clinical use. Studies are being done to search for biodegradable implants preferable to antibiotic-laden bone cement; however, these studies and the materials are still in early stages and development. Currently, there are no FDA-approved biodegradable materials available for use to treat infected orthopaedic implants. As new materials become available and their elution characteristics are recorded, it is important for surgeons to understand how the data were collected so they can have a clear understanding of the elution characteristics of the material used and how the material acts in different environments. Even with extensive historic, clinical, and research data that prove the effectiveness of antibiotic-laden cement, the ideal drug delivery system is neither agreed on nor available.

A consensus statement on empiric therapy for suspected gram-positive infections in surgical patients.

BACKGROUND: Multidrug resistance among gram-positive pathogens in tertiary and other care centers is common. A systematic decision pathway to help select empiric antibiotic therapy for suspected gram-positive postsurgical infections is presented. DATA SOURCES: A Medline search with regard to empiric antibiotic therapy was performed and assessed by the 15-member expert panel. Two separate panel meetings were convened and followed by a writing, editorial, and review process. CONCLUSIONS: The main goal of empiric treatment in postsurgical patients with suspected gram-positive infections is to improve clinical status. Empiric therapy should be initiated at the earliest sign of infection in all critically ill patients. The choice of therapy should flow from beta-lactams to vancomycin to parenteral linezolid or quinupristin-dalfopristin. In patients likely to be discharged, oral linezolid is an option. Antibiotic resistance is an important issue, and in developing treatment algorithms for reduction of resistance, the utility of these new antibiotics may be extended and reduce morbidity and mortality.

Nightly enteral nutrition support of elderly hip fracture patients: a pilot study.

OBJECTIVES: Assess whether postoperative nightly enteral nutrition support improves outcomes of elderly patients with an acute hip fracture DESIGN: Randomized controlled trial. SETTING: A University and a Department of Veteran's Affairs Hospital SUBJECTS: Adults >64 years of age who underwent surgical repair of an acute hip fracture. INTERVENTIONS: Subjects randomized to the control (Ctrl) group received standard care while the treatment (Tx) group received standard care plus up to 1,375 Kcal [5,755 kJ/d] of nasoenteral tube feedings each night. When tube feedings had to be discontinued, Tx subjects were asked to drink an equivalent amount of the nutritional supplement each night. MEASURES OF OUTCOME: Rate of postoperative complications and 6-month postoperative survival. RESULTS: Fifty-seven patients were randomized to the Tx (n = 27, mean age 75.9 +/- 7.4 yrs) or Ctrl groups (age 81.7 +/- 7.7 yrs). All subjects had reduced volitional nutrient intakes after surgery. During the first week subsequent to surgery, there was no difference between the treatment and control groups in the amount of nutrients that they volitionally consumed during the day. However, the treatment subjects had a greater total daily nutrient intake (Median 5,866 (IQR 5,024 to 7,335) kJ/d vs. 3,965 (IQR 2,968 to 4,664) kJ/d, p < 0.001). However, by the second postoperative week this difference was no longer statistically significant. Intolerance to the tube feedings developed commonly. There was no difference between the groups in the rate of postoperative life-threatening complications or mortality within six months subsequent to surgery. CONCLUSIONS: This study failed to confirm findings from a prior study of improved postoperative survival with nutrition support. However, it was conducted on multiple hospital wards which may have contributed to the higher rate of tube-related problems and less nutrient delivery signifying the need for further study.

Allograft reconstruction for extensor mechanism rupture after total knee arthroplasty: 4.8-year follow-up.

Three patients who experienced extensor mechanism rupture after total knee arthroplasty underwent reconstruction using an allograft consisting of quadriceps tendon, patella, patellar tendon, and tibial tubercle. All patients who failed initial attempts to repair the extensor mechanism disruption achieved pain relief at average 4.8-year follow-up. Patients were able to extend their knee actively against resistance. Ambulation with full weight bearing was possible in all patients; however, one patient required a cane. Few reports have been published on allograft reconstruction of the extensor mechanism. The current study supports its use for patients who have failed to achieve knee extension with reconstruction by other means.

Surgical hand scrub practices in orthopaedic surgery.

The purpose of this study was to determine whether the practice of surgical hand scrubbing among orthopaedic surgeons, faculty, residents, and nurses met the institution's recommended 5-minute scrub policy and how often a 2-minute surgical hand scrub was used. Forty-eight subjects' hand scrub times were recorded discreetly for a total of 125 observations. All individuals scrubbed for a mean of 2.54 minutes and all scrubbed less than the 5-minute institutionally recommended policy. We found that 35.2% scrubbed less than 2 minutes and 64.8% scrubbed greater than 2 minutes. The subjects studied were polled to determine whether they knew the scrub policy, the minimum effective scrub time, and their perception of how long they scrub. Three of the 16 respondents correctly answered the question regarding the hospital's recommended policy regarding scrub time of 5 minutes. All stated they thought they scrubbed at least 2 minutes and all agreed that at least a 2-minute scrub should be done.

Detecting bacterial colonization of implanted orthopaedic devices by ultrasonication.

Glycocalyx-producing bacteria have been observed on orthopaedic devices that were removed for reasons other than infection. It has been suggested that the bacteria adhere to foreign surfaces within a biofilm and elude standard culture techniques. The authors adapted previously used ultrasonication protocols that disrupt the surface biofilm before culturing removed orthopaedic devices from patients without clinical evidence of infection. Patients having revision total joint arthroplasty of the hip or knee who lacked current or prior clinical evidence of infection were studied prospectively. During surgery, the femoral component and a corresponding control femoral implant were placed in separate sterile bags of saline. The implant and saline combination was placed in an ultrasonication bath for 30 minutes at 60 Hz. The saline solution was passed through a 0.45-microm pore filter, and the filter residue was cultured on sheep blood agar. None of the 21 implants yielded positive culture on routine microbiologic testing. However, using the ultrasonication protocol, a coagulase-negative Staphylococcus grew from one of the removed implants. Numerous total joint implant failures that are attributed to aseptic loosening may be a result of subclinical infection from bacteria within a biofilm. The current study supports the concept that biofilm-protected bacterial colonization of implants may occur without overt signs of infection and ultrasonication can be used to enhance identification of these bacteria.

The effect of sampling method on the elution of tobramycin from calcium sulfate.

Release rate is a critical property of all drug delivery vehicles, including antibiotic-laden bioerodibles. In vitro elution studies, used to evaluate release rates, use different sampling methods, including changing the entire amount of buffer and partial exchanges each day. Two groups of 10% calcium sulfate-tobramycin pellets were eluted in 20 mL of buffer for 30 days. Group I had 5 mL of buffer withdrawn and replaced daily whereas Group II had the entire 20 mL of buffer changed daily. The results show that the complete exchange method caused a significantly faster release of antibiotic than the partial exchange method. In the complete exchange group, greater than 50% of the tobramycin was released by 24 hours, whereas in the partial exchange group, 50% of the antibiotic was not released until Day 6. The two methods of sampling used to evaluate this bioerodible material provide data that allow the user to anticipate how the material will function in relatively inert and volatile environments. The method used to sample the elution of antibiotics from bioerodible materials affects the amount of antibiotic eluted. It therefore is important to know the method of sampling when making a decision to use a bioerodible material to deliver antibiotics locally.

The treatment of experimental osteomyelitis by surgical debridement and the implantation of calcium sulfate tobramycin pellets.

Calcium sulfate was used as a biodegradable delivery system for the administration of antibiotics in musculoskeletal infection. New Zealand white rabbits were infected with Staplylococcus aureus, debrided, and randomized to one of four treatment groups: calcium sulfate pellets with 10% tobramycin sulfate, placebo calcium sulfate pellets and IM tobramycin, placebo calcium sulfate pellets, or debridement. Serum and wound exudate tobramycin concentrations and serum calcium levels were measured. Radiographs, cultures, and histology were analyzed for efficacy and treatment. Rabbits treated with 10% tobramycin sulfate pellets showed a significantly higher eradication of infection (11/13) than rabbits treated with debridement only (5/12), placebo pellets and IM tobramycin (5/14). or placebo pellets (3/13). In the group receiving 10% tobramycin sulfate pellets, serum tobramycin concentrations peaked 3 h post-operatively at 5.87 microg/ml and were non-detectable after day 1. In the group receiving placebo pellets and IM tobramycin, serum concentrations peaked at 7.82 microg/ml 1 h post-operatively, fell to 6.12 microg/ml on day 2, and averaged 4.18 microg/ ml for the remainder of the treatment period. The wound exudate tobramycin concentrations in the animals treated with tobramycin sulfate pellets peaked at 11.9 mg/ml on day 1 and dropped to 2.5 microg/ml on day 7. There was no significant difference in the serum calcium levels in any of the treatment groups. Calcium sulfate containing tobramycin sulfate has potential utility as a biodegradable local antibiotic delivery system in the treatment of musculoskeletal infections.