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Basic science. Investigate the ability of local applicaiton of vancomycin, either in powder form or suspended within poly(lactic-co-glycolic acid) microspheres (MS), to treat infection using a rat spinal model. Surgical site infections (SSIs) are a serious complication after spine surgery and are associated with high morbidity and mortality and often caused my coagulase negative staphylococci. A comprehensive approach to reduce SSIs has been recommended including the use of topical vancomycin. Animal and human studies have shown improved control of infection with local compared to systemic antibiotics. K-wires seeded with methicillin-resistant Staphylococcus epidermidis RP62A (MRSE) were treated with vancomycin powder, carboxymethylcellulose sodium salt (CMC) (microsphere carrier), vancomycin powder, blank MS or vancomycin-loaded MS for 24 or 48 h in vitro after which bacteria were enumerated. In addition, a spinal instrumentation model was developed in rats with a bacterial seeded K-wire implanted into the right side of L4 and L5. Rats underwent no treatment or were treated locally with either vancomycin powder, blank MS or vancomycin-loaded MS. After 8 weeks, the K-wire, bone, soft tissue and wire fastener were cultured and results analyzed. Vancomycin powder and vancomycin-loaded MS resulted in significantly fewer bacteria remaining in vitro than did CMC. Vancomycin powder- treated animals’ cultures were significantly lower than all other groups (P

Omadacycline, vancomycin, and rifampin, as well as rifampin combination therapies, were evaluated in an experimental rat model of methicillin-resistant Staphylococcus aureus (MRSA) osteomyelitis. All treatment groups had less MRSA recovered than saline-treated animals. The emergence of rifampin resistance was observed in 3 of 16 animals with rifampin monotherapy and none with rifampin combination therapy. After treatment, the median tibial bacterial loads were 6.04, 0.1, 4.81, and 5.24 log10 CFU/g for saline-, rifampin-, vancomycin-, and omadacycline-treated animals, respectively. Omadacycline or vancomycin administered with rifampin yielded no detectable MRSA. Omadacycline administered with rifampin deserves evaluation in humans as a potential treatment for osteomyelitis.

After staphylococci, streptococci and enterococci are the most frequent causes of periprosthetic joint infection (PJI). MICs and minimum biofilm bactericidal concentrations of rifampin, rifabutin, and rifapentine were determined for 67 enterococcal and 59 streptococcal PJI isolates. Eighty-eight isolates had rifampin MICs of ≤1 μg/ml, among which rifabutin and rifapentine MICs were ≤ 8 and ≤4 μg/ml, respectively. There was low rifamycin in vitro antibiofilm activity except for a subset of Streptococcus mitis group isolates. IMPORTANCE Rifampin is an antibiotic with antistaphylococcal biofilm activity used in the management of staphylococcal periprosthetic joint infection with irrigation and debridement with component retention; some patients are unable to receive rifampin due to drug interactions or intolerance. We recently showed rifabutin and rifapentine to have in vitro activity against planktonic and biofilm states of rifampin-susceptible periprosthetic joint infection-associated staphylococci. After staphylococci, streptococci and enterococci combined are the most common causes of periprosthetic joint infection. Here, we investigated the in vitro antibiofilm activity of rifampin, rifabutin, and rifapentine against 126 Streptococcus and Enterococcus periprosthetic joint infection isolates. In contrast to our prior findings with staphylococcal biofilms, there was low antibiofilm activity of rifampin, rifabutin, and rifapentine against PJI-associated streptococci and enterococci, apart from some Streptococcus mitis group isolates.

The most common organism-type causing orthopedic foreign body infection is the staphylococci, of which Staphylococcus aureus and Staphylococcus epidermidis are especially common. These organisms form biofilms on orthopedic foreign body surfaces, rendering such infections challenging and time consuming to treat. Our group evaluates novel therapeutics for orthopedic foreign body infection in animal models. A current limitation of most animal models is that that they only allow for the removal of one sample per animal, at the time of sacrifice. Herein, we describe a novel rat model of foreign body osteomyelitis that allows removal of foreign bodies at different time points, from the same infected animal. We demonstrate that this model can be used for both S. aureus and S. epidermidis orthopedic foreign body infection, with 3.56, 3.60 and 5.51 log10 cfu/cm2 S. aureus recovered at four, five and six weeks, respectively, after infection, and 2.08, 2.17 and 2.62 log10 cfu/cm2 S. epidermidis recovered at four, five and six weeks, respectively, after infection. We evaluated the model with S. aureus infection treated with rifampin 25 mg/kg twice daily for 21 days. Using quantitative cultures, we were no longer able to detect bacteria as of the 14th day of treatment with bacteria becoming detectable again 7 days following the discontinuation of rifampin a period. This novel model allows monitoring of evolution of infection at the infection site in the same animal.

MRSA periprosthetic 1 joint infection (PJI) can be challenging to treat due to biofilm formation, alongside sometimes limited vancomycin activity (1-3).

Introduction: Antibiotic envelopes are being developed for cardiac implantable electronic device (CIED) wrapping to reduce the risk of infections. Methods: Fifteen CIED infection-associated bacterial isolates of Staphylococcus aureus, Staphylococcus epidermidis and Cutibacterium acnes were used to assess in vitro biofilm formation on Hylomate® compared to titanium, silicone and polyurethane coupons pre-treated with vancomycin (400 µg/ml), bacitracin (1000 U/ml) or a combination of rifampin (80 µg/ml) plus minocycline (50 µg/ml). Scanning electron microscopy (SEM) was performed to visualize bacteria on Hylomate®. Results: There was significantly less (p

Background Owing to patient intolerance or drug interactions, alternative agents to rifampin are needed for management of staphylococcal periprosthetic joint infection. In the current study, we evaluated rifabutin, rifapentine and rifampin, with and without vancomycin, in a rat model of foreign body osteomyelitis. Methods Proximal tibiae were inoculated with methicillin-resistant Staphylococcus aureus (MRSA) and a Kirschner wire (K-wire) implanted in each. After 4 weeks of infection, rifampin, rifabutin, or rifapentine were administered, alone or with vancomycin. Tibiae and K-wires were cultured, and medians were reported as log10 colony-forming units (CFUs) per gram of bone or log10 CFUs per K-wire, respectively. Results Rifampin, rifabutin or rifapentine administered with vancomycin yielded less MRSA from bones (0.10, 3.02, and 0.10 log10 CFUs/g, respectively) than did no treatment (4.36 log10 CFUs/g) or vancomycin alone (4.64 log10 CFUs/g) (both P ≤ .02). The K-wires of animals receiving no treatment or vancomycin monotherapy recovered medians of 1.76 and 2.91 log10 CFUs/g per K-wire, respectively. In contrast, rifampin, rifabutin and rifapentine administered with vancomycin yielded medians of 0.1 log10 CFUs per K-wire, respectively. Rifampin resistance was detected in a single animal in the rifampin monotherapy group. Conclusions Rifabutin or rifapentine with vancomycin were as active as rifampin with vancomycin against MRSA in rat foreign body osteomyelitis, suggesting that rifabutin and/or rifapentine may be alternatives to rifampin in the clinical management of staphylococcal periprosthetic joint infections.

This study evaluated the in vitro activity of oritavancin in combination with rifampin or gentamicin against methicillin-resistant Staphylococcus epidermidis (MRSE) biofilms. Oritavancin, rifampin, and gentamicin were tested against 20 MRSE isolates recovered from prosthetic joint infection (PJI). Time-kill studies were used to evaluate the activities of the three antimicrobial agents individually vs. combinations of oritavancin with rifampin or gentamicin against MRSE biofilms formed on Teflon coupons. At 24 h, the combination of oritavancin and rifampin resulted in a significant (P≤0.001) reduction in biofilm density compared with either antimicrobial alone for 85% (17/20) of isolates. Oritavancin combined with gentamicin showed a significant (P≤0.001) reduction in biofilm density compared with either antimicrobial alone against 55% (11/20) of isolates at 24 h. Synergy (defined as a ≥2 log10 cfu/cm2 decrease at 24 h for the antimicrobial combination compared with the most active single antimicrobial) was observed against 65% (13/20) of the isolates for oritavancin in combination with rifampin and 35% (7/20) of the isolates for oritavancin in combination with gentamicin. Oritavancin in combination with rifampin or gentamicin demonstrated bactericidal activity (defined as a ≥3 log10 cfu/cm2 reduction at 24 h from the starting biofilm bacterial density) for 85% (17/20) and 80% (16/20) isolates, respectively. Our study suggests that oritavancin and rifampin combination therapy may be an option for antimicrobial management of PJIs caused by MRSE.

Background Disclosing agents are dyes used in dentistry to colorize plaque (biofilm) and may offer a means for intraoperative detection of biofilms on orthopedic implants. Methylene blue (MB) stains biofilm and is safely used in orthopedic applications. Injection of MB into acutely infected prosthetic knees before debridement may enable visualization of biofilm, which could influence treatment decisions. The aims of this study were to determine if MB could be used to visualize biofilm on total knee arthroplasty (TKA) implants and to determine if MB staining has an antimicrobial effect that might interfere with subsequent culture. Methods Staphylococcus epidermidis biofilms were formed on TKA polyethylene liners and polymethylmethacrylate (PMMA) and Teflon discs. After staining biofilms on these implants, the bacterial densities were determined through sonication and quantitative culture. The antimicrobial activity of MB staining was determined by measuring the bacterial density of S. epidermidis biofilms on PMMA discs incubated in 0.05% MB for 24 hours vs 30 seconds and comparing it with controls unexposed to MB. Results MB stained S. epidermidis biofilms grown on TKA implants and Teflon and PMMA discs in vitro. Sonication and quantitative culture of the stained implants showed that bacterial densities were at supraphysiological levels. Staining did not affect the ability to culture the organism. Conclusion MB is a possible cost-effective and novel method to expeditiously identify intraoperative biofilm. To further evaluate MB staining and its potential clinical usefulness, future studies are needed to assess the ability of MB to stain physiological levels of biofilm.

Periprosthetic infections are devastating for patients and more efficacious preventive strategies are needed. Surface-modified implants using antibacterial coatings represent an option to cope with this problem; however, manufacturing limitations and cytotoxicity have curbed clinical translation. Among metals with antibacterial properties, copper has shown superior in vitro antibacterial performance while maintaining an acceptable cytotoxicity profile. A thin film containing copper could prevent early biofilm formation to limit periprosthetic infections. This pilot study presents the in vitro antibacterial effect, cytotoxicity, and copper ion elution pattern of a thin film of titanium-copper oxide (TiCuO). (1) Do titanium alloy (Ti6Al4V) discs coated with a thin film of TiCuO reduce Staphylococcus epidermidis biofilm and planktonic cell density compared with uncoated discs? (2) Do Ti6Al4V discs coated with a thin film of TiCuO affect normal human osteoblast viability compared with untreated cells? (3) Is copper ion concentration generated by coated discs lower than previously published copper ion concentrations that cause 50% toxicity in similar human cell lines in vitro (TC50)? Ninety Ti6Al4V discs (12.5 mm diameter; 1.25 mm thick) were used in this study. Seventy-two Ti6Al4V discs were coated with a thin film of either titanium oxide (TiO) or TiCuO containing 20%, 40%, or 80% copper using high-power impulse magnetron sputtering (HiPIMS). Eighteen Ti6Al4V discs remained uncoated for control purposes. We tested antibacterial properties of S epidermidis grown on discs in wells containing growth medium. After 24 hours, planktonic bacteria as well as biofilms removed by sonication were quantitatively cultured. Annexin/Pi staining was used to quantify in vitro normal human osteoblast cell viability at 24 hours and Day 7, respectively. Copper elution was measured at Days 1, 2, 3, 7, 14, and 28 using an inductively coupled plasma mass spectrometer to analyze aliquots of culture medium. Copper ion concentration achieved at 24 hours was compared with previously published TC50 for gingival fibroblast, a phenotypically similar cell line with available data regarding copper ion exposure. Discs coated with TiCuO 80% copper showed greater biofilm and planktonic cell density reduction when compared with other tested compositions (analysis of variance [ANOVA]; p < 0.001). Discs coated with TiCuO 80% copper showed mean biofilm and planktonic cell density of 4.0 log10 (SD = 0.4) and 5.7 log10 (SD = 0.2). Discs coated with TiCuO 80% showed a mean difference in biofilm and planktonic cell density of 2.5 log10 (95% confidence interval [CI], 1.9–3.1 log10; p < 0.001) and 1.2 (95% CI, 0.6–1.8; p < 0.001), respectively, when compared with uncoated discs. Normal human osteoblast viability did not differ among all groups at 24 hours (ANOVA; p = 0.2) and Day 7 (ANOVA; p = 0.7). Discs coated with TiCuO 80% copper showed a mean difference (95% CI) in relative cell viability (%) at 24 hours and Day 7 of 31.1 (95% CI, −19.4 to 81.7; p = 0.4) and −5.0 (95% CI, −7.8 to 17.9; p = 0.9), respectively, when compared with untreated cells. For all TiCuO-coated discs, copper ion elution peaked at 24 hours and slowly decreased in a curvilinear fashion to nearly undetectable levels by Day 28. Discs coated with TiCuO 80% copper showed mean copper ion concentration at 24 hours of 269.4 µmol/L (SD = 25.2 µmol/L) and this concentration was lower than previously published TC50 for similar human cell lines at 24 hours (344 µmol/L, SEM = 44 µmol/L). This pilot study demonstrates a proof of concept that a thin-film implant coating with TiCuO can provide a potent local antibacterial environment while remaining relatively nontoxic to a human osteoblast cell line. Further research in an animal model will be necessary to establish efficacy and safety of this technique and whether it might be useful in the design of implants. A thin film coating with TiCuO demonstrates high antibacterial activity and low cellular cytotoxicity to human osteoblasts in vitro. Taken together, these properties represent a potential strategy for preventing periprosthetic infection if further work in animal models can confirm these results in vivo.

Bacteriophage-derived lysins are being developed as anti-infective agents. In an acute osteomyelitis methicillin-resistant Staphylococcus aureus (MRSA) model, rats receiving no treatment or treatment with daptomycin, exebacase (CF-301), or daptomycin plus exebacase had means of 5.13, 4.09, 4.65, and 3.57 log(10) CFU/gram of bone, respectively. All treated animals had fewer bacteria than did untreated animals (P ≤ 0.0001), with daptomycin plus exebacase being more active than daptomycin (P = 0.0042) or exebacase (P < 0.001) alone.

Background The vancapticins are modified vancomycin derivatives developed by adding membrane targeting motifs to the C-terminus of vancomycin. We determined the in vitro activity of a lead vancapticin candidate against periprosthetic joint infection-associated methicillin-resistant Staphylococcus aureus (MRSA) in the planktonic and biofilm states, and the effect of adding 0.002% polysorbate 80 (P-80; Sigma-Aldrich) on vancapticin susceptibility testing. Methods Thirty-seven clinical isolates of MRSA collected at Mayo Clinic (Rochester, Minnesota) were studied. Vancapticin minimum inhibitory concentrations (MICs) were determined using Clinical and Laboratory Standards Institutes guidelines. Minimum biofilm bactericidal concentrations (MBBCs) were determined using a pegged lid microtiter plate assay. Vancapticin MIC and MBBC values were assessed with and without P-80. Vancapticin, vancomycin, and dalbavancin biofilm time-kill assays were performed using biofilms formed by 10 MRSA isolates on Teflon coupons. Results Vancapticin MICs with and without P-80 ranged from 0.015 to 0.12 μg/mL and 0.25 to 1 μg/mL, respectively. Vancapticin MBBCs with and without P-80 ranged from 0.25 to 4 μg/mL and 1 to 8 μg/mL, respectively. Reductions of biofilm bacterial densities on Teflon coupons after 8 and 24 hours of incubation with vancapticin, vancapticin with P-80, vancomycin, or dalbavancin with P-80 were less than 3-log10 cfu/cm2 for all isolates tested. Conclusion Vancapticin has promising in vitro activity against planktonic MRSA and MRSA in a pegged lid biofilm assay, but was not bactericidal against biofilms on Teflon coupons. P-80 decreased vancapticin MICs and MBBCs. Disclosures Mark A. Blaskovich, PhD, MAB Consulting (Consultant)The University of Queensland (Employee, Grant/Research Support, Other Financial or Material Support, Inventor on patent) Robin Patel, MD, Accelerate Diagnostics (Grant/Research Support)CD Diagnostics (Grant/Research Support)Contrafect (Grant/Research Support)Curetis (Consultant)GenMark Diagnostics (Consultant)Heraeus Medical (Consultant)Hutchison Biofilm Medical Solutions (Grant/Research Support)Merck (Grant/Research Support)Next Gen Diagnostics (Consultant)PathoQuest (Consultant)Qvella (Consultant)Samsung (Other Financial or Material Support, Dr. Patel has a patent on Bordetella pertussis/parapertussis PCR issued, a patent on a device/method for sonication with royalties paid by Samsung to Mayo Clinic, and a patent on an anti-biofilm substance issued.)Selux Dx (Consultant)Shionogi (Grant/Research Support)Specific Technologies (Consultant)

Diagnosis of persistent infection at the time of reimplantation for staged revision of infected arthroplasties is challenging. Implant sonication culture for the diagnosis of prosthetic joint infection (PJI) has improved sensitivity compared to standard periprosthetic tissue culture. We report our experience with periprosthetic tissue culture and sonication culture of antimicrobial agent-containing cement spacers (ACSs) collected during second stages of staged revisions for arthroplasty infection. We studied 87 ACSs from 66 patients undergoing two-stage revision arthroplasty for PJI submitted for sonication culture, along with conventional periprosthetic tissue cultures. Two or more positive periprosthetic tissue cultures with the same organism were considered a positive tissue culture. For sonication culture, ≥20 CFU of bacteria per 10 ml of sonicate fluid was considered positive. The sensitivity and specificity of periprosthetic tissue and ACS sonication culture in detecting persistent infection, as well as their association with outcome, were assessed. Persistent infection occurred in 26% of cases. Periprosthetic tissue and sonicate fluid culture had specificities of 96.3 and 100% (P = 0.50), respectively, and sensitivities of 31.6 and 26.3% (P = 1.00), respectively, for the diagnosis of persistent infection. Thirteen subjects deemed not to have persistent infection at time of reimplantation and who had negative periprosthetic tissue and sonicate fluid cultures subsequently developed overt infection. Sonication culture of cement spacers identifies a similar proportion of patients with persistent infection during staged revisions, as detected by periprosthetic tissue cultures; both have low sensitivities to detect persistent infection.

We have previously demonstrated that culturing periprosthetic tissue in blood culture bottles (BCBs) improves sensitivity compared to conventional agar and broth culture methods for diagnosis of prosthetic joint infection (PJI). We have also shown that prosthesis sonication culture improves sensitivity compared to periprosthetic tissue culture using conventional agar and broth methods. The purpose of this study was to compare the diagnostic accuracy of tissue culture in BCBs (subsequently referred to as tissue culture) to prosthesis sonication culture (subsequently referred to as sonicate fluid culture). We studied 229 subjects who underwent arthroplasty revision or resection surgery between March 2016 and October 2017 at Mayo Clinic in Rochester, Minnesota. Using the Infectious Diseases Society of America (IDSA) PJI diagnostic criteria (omitting culture criteria) as the gold standard, the sensitivity of tissue culture was similar to that of the sonicate fluid culture (66.4% versus 73.1%, P = 0.07) but was significantly lower than that of the two tests combined (66.4% versus 76.9%, P < 0.001). Using Bayesian latent class modeling, which assumes no gold standard for PJI diagnosis, the sensitivity of tissue culture was slightly lower than that of sonicate fluid culture (86.3% versus 88.7%) and much lower than that of the two tests combined (86.3% versus 99.1%). In conclusion, tissue culture in BCBs reached sensitivity similar to that of prosthesis sonicate fluid culture for diagnosis of PJI, but the two tests combined had the highest sensitivity without compromising specificity. The combination of tissue culture in BCBs and sonicate fluid culture is recommended to achieve the highest level of microbiological diagnosis of PJI.

The antibiofilm activity of oritavancin in combination with rifampin, gentamicin, or linezolid was evaluated against 10 prosthetic joint infection (PJI)-related methicillin-resistant Staphylococcus aureus (MRSA) isolates by time-kill assays. Oritavancin combined with rifampin demonstrated statistically significant bacterial reductions compared with those of either antimicrobial alone for all 10 isolates ( P ≤ 0.001), with synergy being observed for 80% of the isolates.

Background Orthopedic foreign body-associated infection can be difficult to treat due to the formation of biofilms protecting microorganisms from both antimicrobials and the immune system. Exebacase (EXE) is a phage-derived lysin which acts as a direct lytic agent by hydrolyzing the peptidoglycan cell wall of Staphylococcus aureus. In this study, the activity of EXE was evaluated in comparison to daptomycin against MRSA biofilms on orthopedic Kirschner wires (K-wires). Methods MRSA strain IDRL-6169 was studied; it has a MIC of 0.5 µg/mL for both daptomycin (DAP) and EXE. Biofilms were formed in 1 mL of 106 cfu/mL tryptic soy broth on 0.5x0.1 mm threaded stainless steel K-wires for 10 hours, after which the wires were removed from the media and placed into 0.04 mL of either DAP or EXE at 0 (vehicle only), 0.098, 0.98, or 9.8 mg/mL. DAP+EXE was also tested, each at 0.098 mg/mL. Bacteria were quantified after 0, 2, 4, 8, and 12 hours of incubation at 37ºC. Testing was performed in triplicate. Results were reported as log10 cfu/K-wire reduction relative to vehicle alone. A 3-log10 cfu/K-wire reduction was considered bactericidal. P-values were calculated using Kruskal–Wallis. Results The bacterial burden of vehicle alone ranged from 5.49- to 6.33-log10 cfu/K-wire at all time points. Bacterial reductions for each treatment compared with carrier solution are shown in the table. DAP showed no bactericidal activity. EXE showed bactericidal activity at all concentrations at all time points studied except 0.098 mg/mL at 8 hours. There was no significant difference between EXE at 0.098 and 0.98 mg/mL at any time point but EXE at 9.8 mg/mL did show superiority over the lower concentrations. DAP+EXE 0.098 mg/mL was bactericidal at all time points. Conclusion EXE showed a rapid effect against MRSA biofilms on orthopedic K-wires apparent within the first 2 hours of exposure and was more active than daptomycin alone at the same concentrations. Disclosures All authors: No reported disclosures.

We previously showed that culture of samples obtained by prosthesis vortexing and sonication was more sensitive than tissue culture for prosthetic joint infection (PJI) diagnosis. Despite improved sensitivity, culture-negative cases remained; furthermore, culture has a long turnaround time. We designed a genus-/group-specific rapid PCR assay panel targeting PJI bacteria and applied it to samples obtained by vortexing and sonicating explanted hip and knee prostheses, and we compared the results to those with sonicate fluid and periprosthetic tissue culture obtained at revision or resection arthroplasty. We studied 434 subjects with knee ( n = 272) or hip ( n = 162) prostheses; using a standardized definition, 144 had PJI. Sensitivities of tissue culture, of sonicate fluid culture, and of PCR were 70.1, 72.9, and 77.1%, respectively. Specificities were 97.9, 98.3, and 97.9%, respectively. Sonicate fluid PCR was more sensitive than tissue culture ( P = 0.04). PCR of prosthesis sonication samples is more sensitive than tissue culture for the microbiologic diagnosis of prosthetic hip and knee infection and provides same-day PJI diagnosis with definition of microbiology. The high assay specificity suggests that typical PJI bacteria may not cause aseptic implant failure.

Foreign-body-associated infections are often difficult to treat, given that the associated microorganisms are in a biofilm state. Previously, we showed that a low-amperage direct electrical current (DC) reduces Propionibacterium acnes biofilms formed on implant-associated materials in vitro . In this study, low-amperage DC was compared to ceftriaxone treatment or no treatment in a novel rat femur model of foreign-body osteomyelitis. A platinum implant seeded with a P. acnes biofilm (10 7 CFU/cm 2 ) and 10 9 CFU of planktonic P. acnes was placed in the femoral medullary cavity. One week later, rats were assigned to one of three treatment groups: no treatment, ceftriaxone treatment, or 200-μA-DC treatment. After 2 weeks of treatment, there were fewer bacteria in the bones of the ceftriaxone group (3.06 log 10 CFU/g of bone [ P = 0.0209]) and the 200-μA-DC group (0.5 log 10 CFU/g [ P = 0.0015]) than in those of the control group (6.58 log 10 CFU/g). The DC-exposed animals exhibited fewer bacteria than the ceftriaxone-treated animals ( P = 0.0330). There were fewer bacteria on the implanted wires in the groups treated with ceftriaxone (0.1 log 10 CFU/cm 2 ) or a 200-μA DC (0.1 log 10 CFU/cm 2 ) than in the control group (2.53 log 10 CFU/cm 2 [ P , 0.0003 for both comparisons]). Low-amperage DC may be useful for treating, or aiding in the treatment of, foreign-body infections caused by P. acnes .

Beards in the operating room are controversial because of their potential to retain and transmit pathogenic organisms. Many bearded orthopedic surgeons choose to wear nonsterile hoods in addition to surgical masks to decrease contamination of the operative field. The goal of this study was to determine whether nonsterile surgical hoods reduce the risk of bacterial shed ding posed by beards. Bearded (n=10) and clean-shaven (n=10) subjects completed 3 sets of standardized fa cial motions, each lasting 90 seconds and performed over blood agar plates, while unmasked, masked, and masked and hooded. The plates were cultured for 48 hours under aerobic and anaerobic conditions. Colony-forming units (CFUs) were quantified, expanded, and identified. Overall, the addition of surgical hoods did not decrease the total number of anaerobic and aerobic CFUs isolated per subject, with a mean of 1.1 CFUs while hooded compared with 1.4 CFUs with the mask alone ( P =.5). Unmasked subjects shed a mean of 6.5 CFUs, which was significantly higher than the number of CFUs shed while masked ( P =.02) or hooded ( P =.01). The bearded group did not shed more than the clean-shaven group while unmasked (9.5 vs 3.3 CFUs, P =.1), masked (1.6 vs 1.2 CFUs, P =.9), or hooded (0.9 vs 1.3 CFUs, P =.6). Bearded surgeons did not appear to have an increased likelihood of bacterial shedding compared with their nonbearded counter parts while wearing surgical masks, and the addition of nonsterile surgical hoods did not decrease the amount of bacterial shedding observed. [ Orthopedics. 2016; 39(2):e290–e294.]

Background Periprosthetic infection is a potentially devastating complication of elbow arthroplasty, associated with formation of microbial biofilm on the implant surface. The definitive microbiologic diagnosis of periprosthetic infection after elbow arthroplasty may be difficult to establish. Our study aim was to compare the diagnostic accuracy of conventional periprosthetic tissue culture and culture of fluid derived from vortexing and bath sonication of the explanted hardware (a biofilm-sampling strategy). Materials and methods Patients undergoing revision elbow arthroplasty at our institution between July 2007 and July 2010, from each of whom 2 or more periprosthetic tissue cultures and 1 implant sonicate culture were obtained, were studied. A standardized definition of orthopedic implant–associated infection was applied. Results We identified 27 subjects with aseptic failure and 9 with prosthetic elbow infection. Rheumatoid arthritis was the most common underlying disorder. The Coonrad-Morrey prosthesis was the most common type of implant used. The sensitivities of implant sonicate and periprosthetic tissue culture were 89% and 55%, respectively ( P = .18), and the specificities were 100% and 93%, respectively ( P = .16). Coagulase-negative staphylococci (n = 7) and Staphylococcus aureus (n = 2) were isolated in cases of infection. Conclusion Culture of the implant by sonication is at least as sensitive as periprosthetic tissue culture to detect prosthetic elbow infection.

We are developing electrical approaches to treat biofilm-associated orthopedic foreign-body infection. Although we have previously shown that such approaches have antibiofilm activity, the effects on bone have not been assessed. Herein, low-amperage 200 μA fixed direct current (DC) was compared with no current, in a rat femoral foreign-body infection model. In the infected group, a platinum implant seeded with S. epidermidis biofilm (105 CFU/cm2), plus 50 μL of a 109 CFU suspension of bacteria, were placed in the femoral medullary cavity of 71 rats. One week later, rats were assigned to one of four groups: infected with no current or DC, or uninfected with no current or DC. After 2 weeks, bones were removed and subjected to histopathology, micro-computed tomography (μCT), and strength testing. Histopathology showed no inflammation or bony changes/remodeling in the uninfected no current group, and some osteoid formation in the DC group; bones from the infected no current group had evidence of inflammation without bony changes/remodeling; along with inflammation, there was moderate osteoid present in the DC group. μCT showed more cortical bone volume and density, trabecular thickness, and cancellous bone volume in the DC group compared with the no current group, for both uninfected and infected bones (p 0.05). © 2018 The Authors. JBMR Plus Published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research.

We determined the MIC and minimum biofilm bactericidal concentration (MBBC) of tedizolid and vancomycin against 97 isolates of Staphylococcus aureus and 74 isolates of Staphylococcus epidermidis associated with prosthetic joint infection. All isolates were vancomycin susceptible in the planktonic state; all staphylococci studied had a tedizolid MIC ≤0.5 μg/mL. The MBBC90 was >32 and >128 μg/mL for tedizolid and vancomycin, respectively.

Introduction Methicillin-resistant S. aureus (MRSA) is a common cause of bone and joint infection. BT2-peg2-vancomycin is an investigational bone-targeted formulation of vancomycin which we hypothesized would have increased antimicrobial activity compared to conventional vancomycin in a chronic experimental MRSA osteomyelitis model. Methods We tested bone affinity using an hydroxyapatite (HA) binding assay, assessed the in vitro antimicrobial susceptibility of 30 MRSA isolates, and compared vancomycin and BT2-peg2-vancomycin in a rat experimental osteomyelitis model. Results Vancomycin did not bind to hydroxyapatite (HA binding index = 0), whereas BT2-peg2-vancomycin showed appreciable binding (HA binding index = 57). The MIC50 was 1 μg/ml and the MIC90 was 2 μg/ml for both vancomycin and BT2-peg2-vancomycin. The MBC90 was 16 and 4 μg/ml for vancomycin and BT2-peg2-vancomycin, respectively. Treatment with 50 mg/kg of vancomycin every 12 hours (median, 4.73 log10 cfu/g), 63.85 mg/kg (equivalent to 50 mg/kg vancomycin) of BT2-peg2-vancomycin every 12 hours (median, 3.93 log10 cfu/g) or 63.85 mg/kg of BT2-peg2-vancomycin once per week (median, 5.00 log10 cfu/g) was more active than no treatment (median, 5.22 log10 cfu/g) (P =0.0481). Treatment with 63.85 mg/kg of BT2-peg2-vancomycin every 12 hours was more active than all other treatment regimens evaluated (P≤0.0150), but was associated with high plasma BT2-peg2-vancomycin levels, decreased animal weight, increased kidney size, creatinine and BUN, and leukocytosis with tubulointerstitial nephritis. Conclusion With optimization of pharmacokinetic parameters to prevent toxicity, BT2-peg2-vancomycin may be useful in the treatment of MRSA osteomyelitis.

Rifampin monotherapy was compared to the combination of linezolid or vancomycin with rifampin in an experimental rat model of methicillin-resistant Staphylococcus aureus (MRSA) chronic foreign body osteomyelitis. MRSA was inoculated into the proximal tibia, and a titanium wire was implanted. Four weeks after infection, rats were treated intraperitoneally for 21 days with rifampin alone ( n = 16), linezolid plus rifampin ( n = 14), or vancomycin plus rifampin ( n = 13). Thirteen animals received no treatment. At completion of treatment, qualitative cultures of the wire and quantitative cultures of the bone (reported as median values) were performed. Quantitative cultures from the control, rifampin monotherapy, linezolid-plus-rifampin, and vancomycin-plus-rifampin groups revealed 4.54, 0.71, 0.10, and 0.50 log 10 CFU/gram of bone, respectively. The bacterial load was significantly reduced in all treatment groups compared to that in the control group. Rifampin resistance was detected in isolates from 10, 2, and 1 animal in the rifampin, linezolid-plus-rifampin, and vancomycin-plus-rifampin groups, respectively. Cultures of the removed wire revealed bacterial growth in 1 and 2 animals in the rifampin and linezolid-plus-rifampin groups, respectively, with no growth in the vancomycin-plus-rifampin group and growth from all wires in the untreated group. In conclusion, we demonstrated that combination treatment with linezolid plus rifampin or vancomycin plus rifampin is effective in an animal model of MRSA foreign body osteomyelitis in the context of retention of the infected foreign body.

Objective The purpose of this study was to determine whether the Qoustic Wound Therapy System (Arobella Medical, LLC, Minnetonka, Minnesota) kills planktonic bacterial cells and/or removes bacterial biofilms. Design The Qoustic Wound Therapy System was evaluated against Pseudomonas aeruginosa, Staphylococcus epidermidis, and Staphylococcus aureus planktonic cells and biofilms in vitro. Main results P aeruginosa, S epidermidis, and S aureus planktonic cells decreased by a mean of 5.10, 4.99, and 5.22 log10 colony-forming units/mL, respectively, with 4 Qoustic Wound Therapy System treatment minutes. After 10 minutes of treatment, P aeruginosa, S epidermidis, and S aureus biofilms decreased by a mean of 1.34, 1.46, and 1.02 log10 colony-forming units/cm, respectively. Conclusion The Qoustic Wound Therapy System, using the Qoustic Qurette, kills planktonic bacteria and reduces bacterial biofilms in vitro.

STUDY DESIGN: This is a prospective study comparing the diagnosis of spinal implant infection by conventional peri-implant tissue culture with a technique which uses a combination of vortexing and bath sonication to dislodge bacteria growing as a biofilm on the surface of retrieved spinal implants.OBJECTIVE: We hypothesized that the biofilm-sampling technique would be more sensitive than peri-implant tissue culture.SUMMARY OF BACKGROUND DATA: Culture of peri-implant tissue is inaccurate for the diagnosis of orthopedic device-related infection; cultures taken from the implant may be more sensitive. We have developed a technique which uses vortexing-bath sonication to sample bacterial biofilms on the surface of retrieved hip and knee implants, and shown that it is more sensitive than peri-prosthetic tissue culture for the microbiologic diagnosis of prosthetic knee, hip, and shoulder infection.METHODS: We compared peri-implant tissue culture to the vortexing-bath sonication technique which samples bacterial biofilm on the surface of retrieved spinal implants, for the diagnosis of spinal implant infection. In addition, we compared detection of Staphylococcus and Propionibacterium acnes by rapid cycle real-time polymerase chain reaction with culture of sonicate fluid.RESULTS: A total of 112 subjects were studied; 22 had spinal implant infection. The sensitivities of peri-implant tissue and sonicate fluid culture were 73% and 91% (P = 0.046), and the specificities were 93% and 97%, respectively. P. acnes and coagulase-negative staphylococci were the most frequent microorganisms detected among subjects with spinal implant infection, with P. acnes detected in 56 and 45%, and coagulase-negative staphylococci detected in 31 and 40% of peri-implant tissue and sonicate fluid cultures, respectively. Compared with the culture of sonicate fluid, polymerase chain reaction was 100 and 67% sensitive for the detection of culture-positive Staphylococcus and P. acnes spinal implant infection, respectively.CONCLUSION: Implant sonication followed by culture is more sensitive than peri-implant tissue culture for the microbiologic diagnosis of spinal implant infection.