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Diabetic foot osteomyelitis (DFO) is a severe, difficult to treat infection. Local antibiotic delivery has been studied as a potential therapeutic adjunct following surgery for DFO. This review aims to summarize the evidence on local antibiotic delivery systems in DFO. PubMed database was searched up to March 2020. Overall, 16 studies were identified and included: 3 randomized controlled trials (RCTs), 3 retrospective studies (RSs), and 10 case series. In the RCTs, gentamicin-impregnated collagen sponges significantly improved clinical healing rates and slightly improved duration of hospitalization. In the RSs, antibiotic-impregnated calcium sulfate beads non-significantly improved all healing parameters, but did not reduce post-operative amputation rates or time of healing. The majority of case series used calcium sulfate beads, achieving adequate rates of healing and eradication of infection. In conclusion, evidence for add-on local antibiotic delivery in DFO is still limited; more data are needed to assess this therapeutic measure.

Infection in orthopaedic and trauma surgery remains a destructive complication with particularly challenging diagnosis and treatment due to bacterial antibiotic resistance and biofilm formation. Along with surgical debridement and systemic antibiotics, an important type of adjuvant therapy is local antibiotic delivery, with the purpose of eliminating bacterial colonization and biofilm development. Calcium sulphate, as a synthetic absorbable biomaterial used for local antibiotic delivery, has experienced an increasing popularity during the last decade, with multiple promoted advantages such as predictable antibiotic elution kinetics, complete and quick biodegradation, good biocompatibility, and limited associated complications. A series of commercially available antibiotic-delivery systems based on calcium sulphate are under investigation and in clinical use, with different presentations, compositions, and application techniques. The current article presents the main available calcium-sulphate-based products and the existing data about the clinical and preclinical research results, stemming from their implementation as local antibiotic carriers for surgical site and implant-associated infections treatment and prevention. Cite this article: EFORT Open Rev 2021;6:297-304. DOI: 10.1302/2058-5241.6.200083

Objectives Rapid delivery of antibiotics is a cornerstone of sepsis therapy, although time targets for specific components of antibiotic delivery are unknown. We quantified time intervals comprising the task of antibiotic delivery and evaluated the association between interval delays and hospital mortality among patients treated in the emergency department for suspected sepsis. Design Retrospective cohort. Setting Twelve hospitals in Southeastern United States from 2014 to 2017. Patients Twenty-four thousand ninety-three encounters among 20,026 adults with suspected sepsis in 12 emergency departments. Measurements and main results We divided antibiotic administration into two intervals: time from emergency department triage to antibiotic order (recognition delay) and time from antibiotic order to infusion (administration delay). We used generalized linear mixed models to evaluate associations between these intervals and hospital mortality. Median time from emergency department triage to antibiotic administration was 3.4 hours (interquartile range, 2.0-6.0 hr), separated into a median recognition delay (time from emergency department triage to antibiotic order) of 2.7 hours(interquartile range, 1.5-4.7 hr) and median administration delay (time from antibiotic order to infusion) of 0.6 hours (0.3-1.2 hr). Adjusting for other risk factors, both recognition delay and administration delay were associated with mortality, but pairwise comparison with a no-delay reference group was not significant for up to 6 hours of recognition delay or up to 1.5 hours of administration delay. Conclusions Both recognition delays and administration delays were associated with increased hospital mortality, but only for longer delays. These results suggest that both metrics may be important to measure and improve for patients with suspected sepsis but do not support targets less than 1 hour.

Background:Effective management of prosthetic joint infection (PJI) requires prolonged, sustained delivery of antibiotics to the effective joint space. Calcium sulphate antibiotic delivery systems have been used in this setting, however, potentially serious complications including symptomatic hypercalcaemia have been described. There is relatively little prospective data on the results with the use of these compounds.Methods:A prospective study was performed between October 2016 and June 2018. 29 patients who underwent revision total hip arthroplasty (THA) for confirmed PJI were treated with Stimulan calcium sulphate antibiotic delivery system. Laboratory blood tests including serum calcium levels, C-reactive protein (CRP) and white cell count (WBC) were monitored for 6 weeks post-surgery. Wounds were assessed for discharge and radiographs for dissolution and for signs of heterotopic ossification.Results:The mean age was 67 years and mean ASA score III. There was no significant increase between the preoperative serum calcium and those at 2 and 6 weeks. The CRP and white cell count were significantly reduced at 6 weeks. Full dissolution occurred by 6 weeks post-op. 1 patient (3.4%) had a prolonged wound discharge.Conclusions:Stimulan is a valid option for management of patients with PJI following total hip arthroplasty. Complication rates are low following its use.

Yesil kimya, kolay, ucuz ve cevre dostu yontemlerle demir oksit nanopartikullerin uretimini mumkun kilar. Amoksisilin cesitli bakteri enfeksiyonlarinin tedavisinde kullanilmakla birlikte antibiyotik direnci tedavi icin buyuk bir problemdir. Demir oksit nanopartikulleri gerek bu problemlerin ustesinden gelinmesi icin gerekse antibiyotiklerin manyetik hedeflendirilmesi icin onde gelen alternatiflerden biridir. Bu calismada ihlamur ekstrakti kullanilarak yesil kimya temelli demir oksit nanopartikullerinin sentezlenmesi ve hedefli antibiyotik tasinim sisteminin olusturulmasi icin bu nanopartikullere amoksisilin yuklenmesi amaclanmistir. Demir oksit nanopartikulleri sulu ihlamur ekstrakti ve FeCl3 cozeltisi kullanilarak hazirlandi. Bu yapilar FTIR, SEM ve zetasizer ile karakterize edildi. Ilac adsropsiyonu icin degisen konsantrasyonlarda amoksisilin cozeltisi manyetik nanopartikuller ile inkube edildi ve pH 7,4 ortaminda ilac salim calismasi yapildi. Nanopartikullerin kuresel morfolojiye (70-88 nm) ve demir oksit yapisina sahip oldugu ayrica polifenoller ile sarili halde oldugu belirlendi. Nanopartikullere yuklenen optimum amoksisilin miktari 100.17 μg ilac/ mg nanopartikul olarak tespit edildi. Ilac saliminin ilk saatlerde daha hizli ardindan kontrollu bir sekilde devam ettigi gozlendi. Dusuk maliyet ve cevre dostu uretimle elde edilen amoksisilin yuklu demir oksit nanopartikullerin bakteriyel enfeksiyon hastaliklarinin manyetik hedefli tedavisinde potansiyel tasidigi dusunulmektedir.

Projections indicate an increase in primary and revision total joint arthroplasties (TJAs). Periprosthetic joint infections (PJIs) are one of the most common and devastating causes of failure after TJA. Perioperative administration of systemic and/or local antibiotics is used for both prophylaxis and treatment of PJI. Antibiotic stewardship is a term that has been met with clinical acceptance and success in other specialties of medicine. Identifying antibiotic best practice use in the fight against PJI is limited by studies that are extremely heterogeneous in their design. Variations in studies include antibiotic selection and duration, surgical débridement steps, type of antibiotic delivery (intra-articular, local, intravenous, and prolonged oral), mix of primary and revision surgery cohorts, both hip and knee cohorts, infecting organisms, and definitions of treatment success/failure. This review highlights the current challenges of antibiotic stewardship in TJA.

With the passage of time and more advanced societies, there is a greater emergence and incidence of disease and necessity for improved treatments. In this respect, nowadays, aptamers, with their better efficiency at diagnosing and treating diseases than antibodies, are at the center of attention. Here, in this review, we first investigate aptamer function in various fields (such as the detection and remedy of pathogens, modification of nanoparticles, antibiotic delivery and gene delivery). Then, we present aptamer-conjugated nanocomplexes as the main and efficient factor in gene delivery. Finally, we focus on the targeted co-delivery of genes and drugs by nanocomplexes, as a new exciting approach for cancer treatment in the decades ahead to meet our growing societal needs.

Polymethylmethacrylate (PMMA) represents the current gold standard as an antibiotic delivery carrier in orthopaedic surgery. Despite the accepted use of local antibiotic carriers, there aren't any conclusive data comparing PMMA to Bone Graft Substitutes. The aim of this in vitro study was to compare the elution profile of gentamicin from various preparations of PMMA cements and Herafill beads. All cements had high initial elution during the first hour which then slowly decreased, Herafill beads on the other hand showed its higher elution around the eighth hour. Herafill, in general, presented the highest elution of gentamicin regardless of its input amount.

Antibiotics are commonly added to poly(methyl methacrylate) (PMMA) by surgeons to locally treat infections such as in bone cement for joint replacement surgeries, as well as implantable antimicrobial "beads". However, this strategy is of limited value in high-risk patients where infections can be recurrent or chronic and otherwise hard to treat. Also, when only one drug is incorporated and applied toward polymicrobial infections (multiple bacterial species), there is a high risk that bacteria can develop antibiotic resistance. To combat these limitations, we developed a combination antibiotic PMMA composite system composed of rifampicin-filled β-cyclodextrin (β-CD) microparticles added into PMMA filled with a second drug. Different formulations were evaluated through zone of inhibition, drug activity, antibiotic release, and refilling, as well as mechanical studies. Our combination antibiotic PMMA composite system achieved up to an 8-fold increase in the duration of antimicrobial activity in comparison to clinically used antibiotic-filled PMMA. Inclusion of CD microparticles also allowed for refilling of additional antibiotics after simulated implantation, resulting in additional windows of therapeutic efficacy. Mechanical testing showed that our tested formulations did have a small, but significant decrease in mechanical properties when compared to unmodified controls. While further studies are needed to determine whether the tested formulations are still suitable for load-bearing applications (e.g., bone cement), our composites are certainly amenable for a variety of nonload-bearing applications (e.g., antimicrobial "beads" and temporary spacer in two-stage arthroscopic revisions).

Since its first use as a bone void filler at the end of the 19th century, calcium sulphate products have been adapted in different ways to aid orthopaedic surgeons. Calcium sulphate local antibiotic delivery systems offer a promising solution in the delivery of high antibiotic concentrations locally for an extended period of time. Over the years, multiple centres have reported side effects such as wound drainage, heterotrophic ossification and hypercalcaemia. This study was carried out to assess the risk of wound drainage in prosthetic joints after implantation of antibiotic-impregnated calcium sulphate beads. Two reviewers searched the literature in three online databases using the Cochrane methodology for systematic reviews. The search of databases yielded 182 articles. The studies without reported post-operative complications, mainly drainage outcomes, were excluded. After screening, seven articles were deemed suitable and selected. Out of the 1,112 cases identified, 43 joints developed wound drainage after calcium sulphate bead placement. This complication was resolved in all these cases by either conservative or operative approaches. The factors implicated in the development of wound drainage include the volume of the product used, procedural placement and host factors. The result of this systematic review shows that calcium sulphate products can be used for treatment and prophylaxis in prosthetic joints with a risk of post-procedural wound drainage. This risk, however, is lesser with the use of synthetic calcium sulphate products as compared with conventional calcium sulphate products.

Background: Plasma concentrate products have Rapidly developed during the last few years, and it had significantly improved regenerative medicine because of its specific features which enhance healing and reduce pain after surgeries. this research aims to improve the antibacterial effectiveness of PRF by adding different forms of antibiotics and evaluate the physical and antibacterial properties of the new PRF. Methods: In-Vitro experimental study was conducted; modified protocol was used which use two stages of centrifuging was used prepare PRF. Bacterial colonies and Miller-Hinton medium was prepared. Two types of bacteria were used for the culturing and incubation (Staphylococcus aureus, Enterococcus faecalis). Different forms and volumes of antibacterial agents (Lincomycin) were incorporated with the PRF. Physical and antibacterial properties were evaluated.Results: ampoule and solution forms had the highest levels of bacterial growth inhibiting, and best physical properties, bacterial inhibiting lasted for 10 days in culture. Significant difference was noticed between the modified PRF and the control group (pConclusion: The protocol proposed in this study succeeded to improve the antibacterial activity of the PRF with preserving the physical properties. No significant difference in physical properties were noticed between control group and PRF with antibiotic. Significance and impact of the study: PRF can be used as a local antibiotic delivering biomaterial adjacent to minor surgery, the results of this study can be used to reduce the post-operative infection that is frequent after oral surgeries.

Background: Many studies have investigated drug stability in extended home infusion pumps, but little is known of other factors that may affect the total daily dose the patient receives. It has been noted that up to 40% of these infusions are incomplete after the designated run out time. Aim: This study investigated whether concentration can affect the flow rate of home infusion pumps, and thus the total dose the patient receives in outpatient parenteral antimicrobial therapy (OPAT). Method: The flow rates of 10 different drug and dose formulations (4–18 g in 0.9% sodium chloride) in Baxter LV10 (Old Toongabbie, Australia) infusion pumps were investigated. The pumps were run out at 31°C and weighed at intervals, with flow rate and total volume infused calculated over the 24-h period. Results: Piperacillin/tazobactam 18 g was the only formulation not to meet the minimum standard of 90% of the volume being infused over the 24-h period. This indicates a failure of intended therapy. Across all infusions, the expected dose delivered (DD) can be calculated as %DD = −1.9x + 122.85, where x is the total drug and excipient weight within the infusor. Conclusion: Dose is inversely related to flow rate in the LV10 Baxter infusion pump. Under nominal conditions, any amount greater than 12.02 g in the 240-mL infusion pump will result in an incomplete run out over the 24-h period. Clinicians should be aware that prescribing daily doses higher than 17.28 g may result in

At present, some bacteria have developed significant resistance to almost all available antibiotics. One of the reasons that cannot be ignored is long-term exposure of bacteria to the sub-minimum inhibitory concentration (MIC) of antibiotics. Therefore, it is necessary to develop a targeted antibiotic delivery system to improve drug delivery behavior, in order to delay the generation of bacterial drug resistance. In recent years, with the continuous development of nanotechnology, various types of nanocarriers that respond to the infection microenvironment, targeting specific bacterial targets, and targeting infected cells, and so on, are gradually being used in the delivery of antibacterial agents to increase the concentration of drugs at the site of infection and reduce the side effects of drugs in normal tissues. Here, this article describes in detail the latest research progress on nanocarriers for antimicrobial, and commonly used targeted antimicrobial strategies. The advantages of the combination of nanotechnology and targeting strategies in combating bacterial infections are highlighted in this review, and the upcoming opportunities and remaining challenges in this field are rationally prospected.

Implantable orthopedic devices have had an enormously positive impact on human health; however, despite best practice, patients are prone to developing orthopedic device-related infections (ODRI) that have high treatment failure rates. One barrier to the development of improved treatment options is the lack of an animal model that may serve as a robust preclinical assessment of efficacy. We present a clinically relevant large animal model of chronic methicillin-resistant Staphylococcus aureus (MRSA) ODRI that persists despite current clinical practice in medical and surgical treatment at rates equivalent to clinical observations. Furthermore, we showed that an injectable, thermoresponsive, hyaluronic acid-based hydrogel loaded with gentamicin and vancomycin outperforms current clinical practice treatment in this model, eliminating bacteria from all animals. These results confirm that local antibiotic delivery with an injectable hydrogel can dramatically increase treatment success rates beyond current clinical practice, with efficacy proven in a robust animal model.

This retrospective study aimed to compare the outcomes and healing parameters of 3 groups of surgical treatment combined with and without local antibiotic administration in diabetic foot osteomyelitis (DFO). Overall, 25 patients with DFO who met the criteria were included in the study. Surgical debridement was used with systemic antibiotic administration alone (group A; n = 8) or combined with local application of antibiotic-loaded polymethylmethacrylate beads (group B; n = 9) or antibiotic-loaded hydroxyapatite and calcium sulfate beads (group C; n = 8). In total, 87.5% patients in group A, 100% in group B, and 87.5% in group C healed ( P = .543). Median time to healing was 17 weeks in group A, 18 weeks in group B, and 19 weeks in group C ( P = .094). One patient (12.5%) in group A was amputated. DFO recurrence rate was 12.5% in group A and 12.5% in group C ( P = .543). Median hospitalization was 9 days in group A, 8 days in group B, and 9 days in group C ( P = .081). In conclusion, adjunctive local antibiotic therapy was not shown to improve outcomes in surgically treated DFO.

Sutures are applied almost universally at the site of trauma or surgery, making them an ideal platform to modulate the local, postoperative biological response, and improve surgical outcomes. To date, the only globally marketed drug‐eluting sutures are coated with triclosan for antibacterial application in general surgery. Loading drug directly into the suture rather than coating the surface offers the potential to provide drug delivery functionality to microsurgical sutures and achieve sustained drug delivery without increasing suture thickness. However, conventional methods for drug incorporation directly into the suture adversely affect breaking strength. Thus, there are no market offerings for drug‐eluting sutures, drug‐coated, or otherwise, in ophthalmology, where very thin sutures are required. Sutures themselves help facilitate bacterial infection, and antibiotic eye drops are commonly prescribed to prevent infection after ocular surgeries. An antibiotic‐eluting suture may prevent bacterial colonization of sutures and preclude patient compliance issues with eye drops. We report twisting of hundreds of individual drug‐loaded, electrospun nanofibers into a single, ultra‐thin, multifilament suture capable of meeting both size and strength requirements for microsurgical ocular procedures. Nanofiber‐based polycaprolactone sutures demonstrated no loss in strength with loading of 8% levofloxacin, unlike monofilament sutures which lost more than 50% strength. Moreover, nanofiber‐based sutures retained strength with loading of a broad range of drugs, provided antibiotic delivery for 30 days in rat eyes, and prevented ocular infection in a rat model of bacterial keratitis.

Background As part of a session on the infected knee replacement at the British Orthopaedic Association congress in Liverpool, 2019, this topic was delivered as a lecture. The content and ideas of the lecture have been expanded to produce this article. Methods One-stage revision total knee replacement is not a new concept but remains controversial. This article is not written to persuade any surgeon to undertake the procedure but to simply give a working framework for how one surgeon performs the operation. We will cover the philosophy underpinning the rationale for single-stage revision (not 2-in-1 revision) including extensile exposure, a defined debridement protocol, reconstruction and fixation, antibiotic delivery and exclusion criteria. Results None. Conclusion The techniques outlined in this article should give confidence that one-stage revision knee replacement is a viable option when working within a multi-disciplinary team structure.

The epidermal skin barrier protects the body from a host of daily challenges, providing protection against mechanical insults and the absorption of chemicals and xenobiotics. In addition to the physical barrier, the epidermis also presents an innate defense against microbial overgrowth. This is achieved through the presence of a diverse collection of microorganisms on the skin (the “microbiota”) that maintain a delicate balance with the host and play a significant role in overall human health. When the skin is wounded, the local tissue with a compromised barrier can become colonized and ultimately infected if bacterial growth overcomes the host response. Wound infections present an immense burden in healthcare costs and decreased quality of life for patients, and treatment becomes increasingly important because of the negative impact that infection has on slowing the rate of wound healing. In this review, we discuss specific challenges of treating wound infections and the advances in drug delivery platforms and formulations that are under development to improve topical delivery of antimicrobial treatments.

Local antibiotic delivery is preferred for treating periodontitis due to the benefits of high local drug concentration and minimal side effects. However, commercial polymeric drug delivery systems lack bioactivity and need additional bone grafting to treat the periodontal bone loss. In the present work, calcium deficient hydroxyapatite (CDHA) nanoparticles incorporated gelatin-alginate (GA) films were developed as antibiotic releasing bone substitutes for treating infrabony periodontal defects. CDHA nanoparticles (

The review gives the characteristics of the general status of the problem of infection in the zone of surgical intervention including the field of traumatology and orthopaedics. The shortcomings of antibiotic use and methods of their local delivery for surgical and orthopaedic needs are considered. The conception of local use of antibacterial agents and the requirements for the current “ideal” antibacterial agent are given. Classification of the local antibiotic delivery systems on the basis of their physicochemical properties is presented as well as the number of prospective methods for the prevention of microorganisms’ adhesion on the surface of the implanted devices and systems that could be used in traumatology and orthopaedics are examined.

Background:A percutaneous antibiotic delivery technique (PAD-T) used for the adjunctive management of osteomyelitis is presented.Methods:This surgical technique incorporates a calcium sulfate and hydroxyapatite (calcium phosphate) bone void filler acting as a carrier vehicle with either an antibiotic or an antifungal medicine, delivering this combination directly into the area of osteomyelitis.Results:The benefit of the PAD-T is reviewed with a case presentation of a successfully treated calcaneal osteomyelitis.Conclusions:No previously reported PAD-T using a simple bone cortex incision in the adjunctive treatment of osteomyelitis has been reported. The PAD-T safely and effectively uses a calcium sulfate and hydroxyapatite bone void filler carrier vehicle to deliver either an antibiotic or an antifungal medicine directly into the area of osteomyelitis.

Antibiotic therapy is the routine method for treating bacterial infections and has saved hundreds of millions of lives over the last century. However, low bioavailability, side effects, and emergence of antibiotic-resistant bacteria are usually associated with the systemic administration of antibiotics. Polymer-based antibiotic delivery system (PADS), as a solution to the limitations of conventional antibiotic therapy, has received significant attention, for it is able to protect antibiotics from premature metabolism and optimize the pharmacokinetics. Moreover, PADS can be elaborately modified to target the infection sites through the specific ligand-receptor interactions in an active manner, or through the responses to endogenous and exogenous stimuli in a passive manner. Multiple polymeric nano-constructions have been used thus far to fabricate PADS, such as polymeric liposomes, polymeric micelles, highly branched polymers and dendrimers, and polymeric nanogels, exhibiting enhanced therapeutic effects compared with the corresponding free antibiotics. In addition, hybrid nanoplatforms integrating the inorganic or biological components have also been developed for PADS, which have the potential to achieve complementary and synergistic effects with antibiotic therapy. In this paper, we reviewed the advances that have been made in PADS for the treatment of bacterial infections in the past five years, highlighting the design principles and targeting capability, in an attempt to provide new insights for further researches.

Reconstruction of large bone defects can be complicated by the presence of both infection and local antibiotic administration. This can be addressed through a two-stage reconstructive approach, called the Masquelet technique, that involves the generation of an induced osteogenic membrane over a temporary poly(methyl methacrylate) (PMMA) space maintainer, followed by definitive reconstruction after the induced membrane is formed. Given that infection and antibiotic delivery each have independent effects on local tissue response, the objective of this study is to evaluate the interaction between local clindamycin release and bacterial contamination with regards to infection prevention and the restoration of pro-osteogenic gene expression in the induced membrane. Porous PMMA space maintainers with or without clindamycin were implanted in an 8 mm rat femoral defect model with or without Staphylococcus aureus inoculation for 28 days in a full-factorial study design (four groups, n = 8/group). Culture results demonstrated that 8/8 animals in the inoculated/no antibiotic group were infected at 4 weeks, which was significantly reduced to 1/8 animals in the inoculated/antibiotic group. Quantitative polymerase chain reaction analysis demonstrated that clindamycin treatment restores inflammatory cytokine and growth factor expression to the same levels as the no inoculation/no antibiotic group, demonstrating that clindamycin can ameliorate the negative effects of bacterial inoculation and does not itself negatively impact the expression of important cytokines. Main effect analysis shows that bacterial inoculation and clindamycin treatment have independent and interacting effects on the gene expression profile of the induced membrane, further highlighting that antibiotics play an important role in the regeneration of infected defects apart from their antimicrobial properties.

Antibiotic-impregnated calcium sulfate (AICS) beads have been used for prevention and treatment of periprosthetic joint infections. We evaluated post-operative complications following the use of AICS beads. 56 patients undergoing complex primary or revision hip or knee arthroplasty received antibiotic calcium sulfate beads. Primary outcomes were wound complication rates. Secondary outcomes included reoperation and reinfection rates. One case (1.7%) of persistent wound drainage occurred requiring surgical irrigation and a poly-exchange. No post-operative infections were seen. Use of 100% pure calcium sulfate AICS beads may help reduce post-operative wound complications. AICS appears to be a safe adjunct tool in local antibiotic delivery.

Supplemental Digital Content is available in the text., Introduction: Recommended time to start administration of first dose antibiotics for sepsis patients is 60 minutes from time 0. Institution-specific data revealed that only one-quarter of severe sepsis patients were meeting this goal when measured from the time of provider order entry. Reliance on a pneumatic tube system for first-dose antibiotic delivery was deemed largely responsible for this finding. This project aimed to increase the percentage of pediatric intensive care unit patients with severe sepsis receiving first dose antibiotics within 60 minutes of provider order entry to ≥50%. Methods: Baseline data were collected from May to June 2018 and resulted in the development of a new “antibiotic champion” process, which we piloted for 1 week in early August 2018. The primary outcome measure was the cumulative percentage of patients meeting the 60-minute goal as measured from provider order entry to start of antibiotic administration. A key secondary endpoint was the median time in minutes from provider order entry to antibiotic administration. Results: We included 14 patients in baseline data analysis and 16 patients in the pilot. The overall percentage of patients receiving antibiotics within 60 minutes of order entry increased from 29% to 75% (P-value: 0.026). The median time from provider order entry to antibiotic administration decreased by 36.5 minutes [baseline: 84.5 (range 58.8–117) versus pilot 48 (range 32–65), P-value: 0.0017]. Conclusion: The antibiotic champion process significantly increased the total percentage of severe sepsis patients meeting the 60-minute goal and decreased the median time to first-dose antibiotic administration for pediatric intensive care unit patients.

Introduction: Bone implant related infection is still one of the biggest challenges in bone and joint surgery. Antibiotic impregnated bone grafts seem to be promising in both treatment and prevention of these infections. However, great variance in methodology predominates this field of research. This paper gives an overview of the published literature.Methods: The PRISMA-flowchart was used as protocol for article selection. Medline was searched and articles were selected in accordance with predetermined exclusion criteria.Results: Forty-eight articles were included in the synthesis. Topics including bone graft type, manipulations of the graft, elution profile, bacterial inhibition, osteotoxicity, incorporation, special impregnation methods, clinical use and storage were investigated.Therapeutically, high initial levels seem appropriate for biofilm eradication. A single stage procedure in the treatment of bone implant related infection seems feasible. Prophylactically, the literature indicates a reduction of postoperative infections when using antibiotic impregnated bone grafts.Conclusion: Bone grafts are a suitable carrier for local antibiotic application both therapeutically and prophylactically.

The authors present a case of bilateral femoral emphysematous osteomyelitis caused by Escherichia coli in a 60-year-old woman with rheumatoid arthritis who was receiving long-term prednisone therapy. The infection in both femoral shafts was eradicated with surgical debridement, followed by insertion of intramedullary rods composed of culture-specific antibiotic cement into the femoral canals in conjunction with 6 weeks of intravenous antibiotics. The rods were subsequently removed, and no signs of further osteomyelitis were recognized at follow-up. To the authors' knowledge, this is the first case of its kind reported in the orthopedic literature. Emphysematous osteomyelitis, a rare and dangerous entity, can be successfully managed by intramedullary antibiotic delivery in the subacute setting. [ Orthopedics . 2019; 42(1):e128–e130.]

Multidrug-resistant (MDR) bacteria have increased at an alarming rate over recent decades and cause serious problems. The emergence of resistant infections caused by these bacteria has led to mortality and morbidity; consequently there is an urgent need to find solution for combating bacterial resistance. In the present paper, first, some mechanisms of antibiotic resistance such as changing the antibacterial agent's uptake and biofilm formation are discussed. Following, for removing the antibacterial resistance, a wide range of approaches like developing new generations of antibiotics, combination therapy, natural antibacterial substances and applying nanoparticulate systems have been explained. Among them, antibiotic delivery via nanoparticles, has been attracted more attention recently, so discussed in present review, separately.

Treating chronic bone infection is challenging, requiring complete excision of the affected areas and antimicrobial therapy. Acquiring active concentrations of antibiotics is difficult, as well as filling up bone defects resulting from sequestrectomy, and very few methods of treatment address both issues simultaneously. The authors describe the clinical results after using Collatamp G, a collagen-based, antibiotic filled sponge with two actions: local delivery of high antibiotic doses without systemic side effects and enhancement of healing due to collagen, thus covering the bone defect without any further osteoplastic surgery. This paper thus identifies Collatamp G as a biomaterial able to solve the above mentioned problems in treating bone infections.Keywords: bone infections, collagen matrix, gentamicine, antibiotic delivery

Acrylic bone cement has a variety of applications in orthopedic surgery. Primary uses in total arthroplasties are limited to prostheses fixation and antibiotic delivery. With the large number of total joint arthroplasties expected to continue to rise, understanding the role bone cement plays in the success of total joint arthroplasty can have a significant impact on daily practice. The literature is inconclusive on whether cemented or cementless fixation technique is superior, and choice of fixation type is mainly determined by surgeon preference and experience. Surgeons should understand that if poor techniques exist, short-term outcomes of the replaced joint may be at risk. Statement of clinical significance: This article attempts to clarify some points of bone cement use through a review of the mechanical properties related to bone cement, a comparison to alternative materials, influence of additives, and the effects on surgical outcomes. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:737-744, 2016.

Background Management of large infected bone defects is a major clinical and socioeconomic problem. The induced membrane technique has been widely used as a solution. However, it has apparent disadvantages such as limited autologous bone graft supply and lack of continuous infection control. Meanwhile, calcium sulfate/calcium phosphate composites have efficacious osteogenesis and antibiotic delivery capacity. For the first time, we analyzed the efficiency of calcium sulfate/calcium phosphate composites as a bone graft expander in the induced membrane technique to treat large infected bone defects. Methods We retrospectively analyzed the clinical data of 12 patients with large infected bone defects of 6.1-17.2 cm treated with the induced membrane technique from November 2016 to July 2019. In the second reconstruction stage, the bone defect was filled with a mixture of the autogenous iliac bone and vancomycin-impregnated calcium sulfate/calcium phosphate composites at a ratio of 3:1. We assessed the bony union by Samantha X-ray score and recorded infection recurrence and complications. Paley scale and SF-36 score were used to evaluate the function of adjacent joint and quality of life pre and postoperatively. Pearson's correlation coefficients were calculated for union time and other clinical scores. Results The mean follow-up was 69 weeks (ranging from 30 to 142) after the second stage of the operation. The mean Samantha X-ray score was 5.1 [3-6], preoperative and postoperative SF-36 scores showed that there were statistical differences in all the nine aspects, and the excellent rate of adjacent joint function was 75% (Paley). All cases were radiologically healed, and none of the 12 patients had infection recurrence or failure of fixation at the last follow-up. Two cases had delayed wound healing and were cured after dress changing. There was a significant correlation between union time and Samantha X-ray score (r =‒0.887; P=0.000), while there was no correlation between filling dose, size of the defect, and other outcomes. Conclusions This study provided evidence supporting calcium sulfate/calcium phosphate composites as an effective and safe bone graft expander in the induced membrane technique to treat large infected bone defect. This technique may help decrease the use of autologous bone graft and enhance the anti-infection effect of the induced membrane technique.

Infection in the setting of total joint arthroplasty, referred to as periprosthetic joint infection (PJI), is a devastating complication requiring prolonged and costly treatment. The unique environment around an artificial joint and ability of surrounding tissues to sequester bacteria collectively make prevention, diagnosis, and treatment of this condition challenging. In light of the unique pathogenesis of PJI, this review explores the limitations of contemporary treatments and discusses novel treatment options. Recent advancements in local antibiotic delivery platforms for preventing and treating PJI include titanium nanotube arrays, synthetic polymers, resorbable hydrogels, and cyclodextrin-based drug delivery options. In particular, cyclodextrins have facilitated great advancements in other clinical disorders and have demonstrated early promise as a future option in the arena of PJI. Novel treatment modalities for PJI optimize the implant surfaces to prevent bacterial biofilm formation or provide prolonged intra-articular antibiotic dosing to eradicate bacteria.

To describe the improvements of an early warning system for the identification of septic patients on the time to diagnosis, antibiotic delivery, and mortality.This was an observational cohort study that describes the successive improvements made over a period of 10 years using an early warning system to detect sepsis, including systematic active manual surveillance, electronic alerts via a telephonist, and alerts sent directly to the mobile devices of nurses. For all periods, after an alert was triggered, early treatment was instituted according to the institutional sepsis guidelines.In total, 637 patients with sepsis were detected over the study period. The median triage-to-diagnosis time was reduced from 19:20 (9:10 - 38:15) hours to 12:40 (2:50 - 23:45) hours when the manual surveillance method was used (p = 0.14), to 2:10 (1:25 - 2:20) hours when the alert was sent automatically to the hospital telephone service (p = 0.014), and to 1:00 (0:30 - 1:10) hour when the alert was sent directly to the nurse's mobile phone (p = 0.016). The diagnosis-to-antibiotic time was reduced to 1:00 (0:55 - 1:30) hours when the alert was sent to the telephonist and to 0:45 (0:30 - 1:00) minutes when the alert was sent directly to the nurse's mobile phone (p = 0.02), with the maintenance of similar values over the following years. There was no difference in the time of treatment between survivors and non-survivors.Electronic systems help reduce the triage-to-diagnosis time and diagnosis-to-antibiotic time in patients with sepsis.Descrever os efeitos de melhorias sucessivas nos sistemas de alerta precoce para identificação de pacientes com sepse, no que se refere ao tempo até o diagnóstico, à administração de antibióticos e à mortalidade.Trata-se de um estudo observacional de coorte, que descreve as sucessivas melhorias implantadas em um período de 10 anos no sistema de alerta precoce para detecção de sepse, incluindo vigilância ativa manual sistemática, alertas eletrônicos via telefonista, e alertas enviados diretamente a dispositivos móveis da enfermagem. Para todos os períodos, após o desencadeamento do alerta, o tratamento foi realizado segundo as diretrizes institucionais para sepse.Durante estes anos, detectaram-se 637 pacientes com sepse. O tempo mediano entre a triagem e o diagnóstico foi reduzido de 19:20 (9:10 - 38:15) horas para 12:40 (2:50 - 23:45) horas quando se utilizou o método manual de vigilância (p = 0,14), para 2:10 (1:25 - 2:20) horas quando o alerta foi enviado automaticamente ao serviço telefônico do hospital (p = 0,014) e para 1:00 (0:30 - 1:10) horas quando o alerta foi enviado diretamente ao telefone celular da enfermagem (p = 0,02), com manutenção de valores similares nos anos que se seguiram. Não houve diferença no tempo até o tratamento em relação aos pacientes sobreviventes e não sobreviventes.Sistemas eletrônicos auxiliam na redução do tempo entre a triagem e o diagnóstico e entre o diagnóstico e o início da antibioticoterapia em pacientes com sepse.

International audience; The last fifty years, ophthalmic drug delivery research has made much progress, challenging scientists about the advantages and limitations of this drug delivery approach. Topical eye drops are the most commonly used formulation in ocular drug delivery. Despite the good tolerance for patients, this topical administration is only focus on the anterior ocular diseases and had a high precorneal loss of drugs due to the tears production and ocular barriers. Antibiotics are popularly used in solution or in ointment for the ophthalmic route. However, their local bioavailability needs to be improved in order to decrease the frequency of administrations and the side effects and to increase their therapeutic efficiency. For this purpose, sustained release forms for ophthalmic delivery of antibiotics were developed. This review briefly describes the ocular administration with the ocular barriers and the currently topical forms. It focuses on experimental results to bypass the limitations of ocular antibiotic delivery with new ocular technology as colloidal and in situ gelling systems or with the improvement of existing forms as implants and contact lenses. Nanotechnology is presently a promising drug delivery way to provide protection of antibiotics and improve pathway through ocular barriers and deliver drugs to specific target sites.

Osteomyelitis is truly an infection of bone, and osteomyelitis of the jaws is defined as an inflammatory process of the medullary portion of the affected bone and eventually extends to include the haversian systems and the periosteum. Osteomyelitis of the jaws is caused primarily by contiguous spread of odontogenic infections originating from pulpal or periodontal tissues, and infections derived from trauma, especially compound fractures, are the second leading cause, and from the periostitis after gingival ulceration, infected lymph nodes or hematogenous origin account for an additional causes of jaw infections. Despite all recent advances in diagnosis and treatment modalities, such as surgical intervention, antibiotic, and hyperbaric oxygen treatment, for osteomyelitis of the jaws are well established, osteomyelitis of the jaws is still a very unique and difficult disease leading to uncertain outcomes with many complications involving facial disfigurement, loss of jaw functions by loss of affected bone, teeth, and nerve. Understanding of the pathophysiology and microbiology of the osteomyelitis is important to selection of adequate treatment, it is thought that the recent rapid progress in the research fields of tissue-engineered bone and antibiotic delivery systems should be adjusted and modified to the biological nature will be applicated to solve the minimal invasive treatment of osteomyelitis of the jaws. Therefore, the present study authors reviewed about pathophysiology and microbiology of osteomyelitis of the jaws, and recent trends of tissue engineering approaches, so intended to inform to clinicians and researchers about whole entities of this disease.

Chronic infections are one of the major challenges in orthopaedic surgery, both for surgeons and patients. They are characterised by obstinate persistency of the causing microorganisms and resulting long-term disablement of the patients, associated with remarkable costs for the health care system. Difficulties derive from the biofilm-mode of living of pathogens with resistances against immunological defence and antimicrobial substances, and osseous defects resulting from the disease itself and surgical interventions. Established techniques usually require multiple costly operations with extended periods of disablement and impairment of the patients, sometimes making the therapy worse than the disease. Better understanding of the backgrounds of the conditions has led to new surgical techniques and differentiated application of antibiotics, aiming in improved quality of life for our patients. Cite this article: EFORT Open Rev 2017;2. DOI: 10.1302/2058-5241.2.160063. Originally published online at www.efortopenreviews.org

Orthopaedic and trauma device-related infection (ODRI) remains one of the major complications in modern trauma and orthopaedic surgery.Despite best practice in medical and surgical management, neither prophylaxis nor treatment of ODRI is effective in all cases, leading to infections that negatively impact clinical outcome and significantly increase healthcare expenditure.The following review summarises the microbiological profile of modern ODRI, the impact antibiotic resistance has on treatment outcomes, and some of the principles and weaknesses of the current systemic and local antibiotic delivery strategies.The emerging novel strategies aimed at preventing or treating ODRI will be reviewed. Particular attention will be paid to the potential for clinical impact in the coming decades, when such interventions are likely to be critically important.The review focuses on this problem from an interdisciplinary perspective, including basic science innovations and best practice in infectious disease. Cite this article: Moriarty TF, Kuehl R, Coenye T, et al. Orthopaedic device related infection: current and future interventions for improved prevention and treatment. EFORT Open Rev 2016;1:89-99. DOI: 10.1302/2058-5241.1.000037. ispartof: EFORT open reviews vol:1 issue:4 pages:89-99 ispartof: location:England status: published

Bacterial or fungal infections can be a devastating complication acquired after environmental exposure to microorganisms, especially after injury, surgery, hospitalization, or implantation of biomaterials. The development of antibiotic-resistant strains of microorganisms provides further complications to treatment, as well as the formation of biofilm in tissue or on implanted biomaterials. Delivery of antibiotics systemically or locally can treat or prevent infection, but improved delivery systems are required for optimal release profile and efficacy. The natural biopolymer chitosan has been used in many forms, including films, coatings, beads, and hydrogels to deliver antibiotics and antimicrobials. This chapter reviews current research on chitosan for antibiotic delivery and provides general methods for assessing antibiotic release from chitosan biomaterials.

In case of implant associated infection, implant preservation is associated with high failure rates. Therefore, a removal or exchange of the implant is most often mandatory for treatment success. Alternatively, under certain conditions, local antibiotic delivery can be applied - preserving the implant, using for example calcium sulphate as a resorbable carrier. In this work, third-body wear on total hip prostheses caused by calcium sulphate particles was tested in a hip simulator. Inlays made of ultra-high-molecular-weight polyethylene (UHMWPE) and cross-linked polyethylene (XLPE) against 28 mm CoCrMo heads and 36 mm alumina pairings were tested in triplicate, both with and without calcium sulphate particles in the test liquid. Neither the alumina articulations nor the CoCrMo heads were affected by the calcium sulphate particles since calcium sulphate is a relatively soft material. The polyethylene inlays showed 39-89 % higher wear during exposure compared to references, but wear returned to normal when no more particles were added. Thus, calcium sulphate might be used as antibiotic carrier even in the presence of total hip prostheses without fearing excessive third-body wear.

Despite the wide success of antibiotics, the treatment of bacterial infections still faces significant challenges, particularly the emergence of antibiotic resistance. As a result, nanoparticle drug delivery platforms including liposomes, polymeric nanoparticles, dendrimers, and various inorganic nanoparticles have been increasingly exploited to enhance the therapeutic effectiveness of existing antibiotics. This review focuses on areas where nanoparticle approaches hold significant potential to advance the treatment of bacterial infections. These areas include targeted antibiotic delivery, environmentally responsive antibiotic delivery, combinatorial antibiotic delivery, nanoparticle-enabled antibacterial vaccination, and nanoparticle-based bacterial detection. In each area we highlight the innovative antimicrobial nanoparticle platforms and review their progress made against bacterial infections.

Objectives Severe extremity injuries are the most significant injury sustained in combat wounds. Despite optimal clinical management, non-union and infection remain common complications. In a concerted effort to dovetail research efforts, there has been a collaboration between the UK and USA, with British military surgeons conducting translational studies under the auspices of the US Institute of Surgical Research. This paper describes 3 years of work. Methods A variety of studies were conducted using, and developing, a previously validated rat femur critical-sized defect model. Timing of surgical debridement and irrigation, different types of irrigants and different means of delivery of antibiotic and growth factors for infection control and to promote bone healing were investigated. Results Early debridement and irrigation were independently shown to reduce infection. Normal saline was the most optimal irrigant, superior to disinfectant solutions. A biodegradable gel demonstrated superior antibiotic delivery capabilities than standard polymethylmethacrylate beads. A polyurethane scaffold was shown to have the ability to deliver both antibiotics and growth factors. Discussion The importance of early transit times to Role 3 capabilities for definitive surgical care has been underlined. Novel and superior methods of antibiotic and growth factor delivery, compared with current clinical standards of care, have been shown. There is the potential for translation to clinical studies to promote infection control and bone healing in these devastating injuries.

Although most bacterial infectious diseases can be treated successfully with the remarkable array of antibiotics, the microbial pathogens continue to be one of the most critical health challenges worldwide. One of the common efforts in addressing this issue lies in improving the existing antibacterial delivery systems since inefficient delivery can lead to poor therapeutic outcome of the administered drug. Recently, nanoliposomal systems have been widely used as promising strategies to overcome these challenges due to their unique set of properties. This article tries to briefly summarize the current studies that have taken advantage of liposomal nanoparticles as carriers to deliver antibacterial agents. The reviewed investigations demonstrate the immense potential of liposomal nanoparticles as carriers for antibiotic delivery and highlight the latent promise in this class of vehicles for treatment of bacterial infections. The future of these promising approaches lies in the development of more efficient techniques for preparing liposomal nanoparticles with great potential in effective and selective targeting of antibiotics to bacterial cells for eradication as well as the highest safety for human host.

Objective: The usage of antibiotic-impregnated polymethylmethacrylate (PMMA) beads is regarded as the gold standard for local antibiotic delivery. However, the relatively new antibiotic-impregnated collagen sponge has multiple advantages over it. The objective of this study is to compare the measurable effects between gentamicin-impregnated collagen sponge and gentamicin-impregnated (PMMA) beads in patients with osteomyelitis.Methods: This is a case–control study which involved 60 patients who were diagnosed with osteomyelitis between January 2014 and June 2015, and underwent first surgical debridement with application of either gentamicin-impregnated collagen sponge (n=28) or gentamicin-impregnated PMMA beads (n=32). The numbers of debridement, trend of blood parameters, duration of hospitalization, and total duration of systemic antibiotic therapy needed to be completed were reviewed from the patients’ file.Results: A total of 53 patients of 60 were diagnosed with osteomyelitis of the lower limbs, while the remaining seven were involving the upper limbs. The gentamicin-impregnated collagen sponge group has significant lower reoperative rate (p

Introduction: Chronic osteomyelitis, or bone infection, is a major worldwide cause of morbidity and mortality, as it is exceptionally hard to treat due to patient and pathogen-associated factors. Successful treatment requires surgical debridement together with long-term, high antibiotic concentrations that are best achieved by local delivery devices, either made of degradable or non-degradable materials. Areas covered: Non-degradable delivery devices are frequently constituted by polymethylmethacrylate-based carriers. Drawbacks are the need to remove the carrier (as the carrier itself may provide a substratum for bacterial colonization), inefficient release kinetics and incompatibility with certain antibiotics. These drawbacks have led to the quest for degradable alternatives, but also devices made of biodegradable calcium sulphate, collagen sponges, calcium phosphate or polylactic acids have their specific disadvantages. Expert opinion: Antibiotic treatment of osteomyelitis with the current degradable and non-degradable delivery devices is effective in the majority of cases. Degradable carriers have an advantage over non-degradable carriers that they do not require surgical removal. Synthetic poly(trimethylene carbonate) may be preferred in the future over currently approved lactic/glycolic acids, because it does not yield acidic degradation products. Moreover, degradable poly(trimethylene carbonate) yields a zero-order release kinetics that may not stimulate development of antibiotic-resistant bacterial strains due to the absence of long-term, low-concentration tail-release.