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Bacterial infection treatment for chronic wounds has posed a major medical threat and challenge. Bacteria at the wounded sites can compete with the immune system and subsequently invade live tissues, leading to more severe tissue damage. Therefore, there is an urgent demand for wound dressings with antibacterial and anti-inflammatory properties. Considering the concept of moist healing, hydrogels with a three-dimensional (3D) network structure are widely used as wound dressings due to their excellent hydrophilicity, water retention properties, and biocompatibility. Developing antibacterial hydrogels for the treatment of infected wounds has been receiving extensive attention recently. This article categorizes antibacterial hydrogels according to their materials and antibacterial modes, and introduces the recent findings and progress regarding their status. More importantly, with the development of emerging technologies, new therapies are utilized to prepare antibacterial hydrogels such as nanoenzymes, photothermal therapy (PTT), photodynamic therapy (PDT), metal–organic frameworks (MOFs), and other external stimuli-responsive methods. Therefore, this review also examines their progress, challenges, and future trends as wound dressings. In the following studies, there will still be a focus on antibacterial hydrogels that have a high performance, multi-functions, and intelligence, especially biocompatibility, a high and long-lasting antibacterial property, responsiveness, and on-demand therapeutic ability. [ABSTRACT FROM AUTHOR]

Bacterial infection treatment for chronic wounds has posed a major medical threat and challenge. Bacteria at the wounded sites can compete with the immune system and subsequently invade live tissues, leading to more severe tissue damage. Therefore, there is an urgent demand for wound dressings with antibacterial and anti-inflammatory properties. Considering the concept of moist healing, hydrogels with a three-dimensional (3D) network structure are widely used as wound dressings due to their excellent hydrophilicity, water retention properties, and biocompatibility. Developing antibacterial hydrogels for the treatment of infected wounds has been receiving extensive attention recently. This article categorizes antibacterial hydrogels according to their materials and antibacterial modes, and introduces the recent findings and progress regarding their status. More importantly, with the development of emerging technologies, new therapies are utilized to prepare antibacterial hydrogels such as nanoenzymes, photothermal therapy (PTT), photodynamic therapy (PDT), metal–organic frameworks (MOFs), and other external stimuli-responsive methods. Therefore, this review also examines their progress, challenges, and future trends as wound dressings. In the following studies, there will still be a focus on antibacterial hydrogels that have a high performance, multi-functions, and intelligence, especially biocompatibility, a high and long-lasting antibacterial property, responsiveness, and on-demand therapeutic ability.

Bacterial infections, especially those caused by drug-resistant bacteria, have seriously threatened human life and health. There is urgent to develop new antibacterial agents to reduce the problem of antibiotics. Biomedical materials with good antimicrobial properties have been widely used in antibacterial applications. Among them, hydrogels have become the focus of research in the field of biomedical materials due to their unique three-dimensional network structure, high hydrophilicity, and good biocompatibility. In this review, the latest research progresses about hydrogels in recent years were summarized, mainly including the preparation methods of hydrogels and their antibacterial applications. According to their different antibacterial mechanisms, several representative antibacterial hydrogels were introduced, such as antibiotics loaded hydrogels, antibiotic-free hydrogels including metal-based hydrogels, antibacterial peptide and antibacterial polymers, stimuli-responsive smart hydrogels, and light-mediated hydrogels. In addition, we also discussed the applications and challenges of antibacterial hydrogels in biomedicine, which are expected to provide new directions and ideas for the application of hydrogels in clinical antibacterial therapy. [ABSTRACT FROM AUTHOR]

Nowadays, mesoporous bioactive glasses (MBGs) are envisaged as promising candidates in the field of bioceramics for bone tissue regeneration. This is ascribed to their singular chemical composition, structural and textural properties and easy-to-functionalize surface, giving rise to accelerated bioactive responses and capacity for local drug delivery. Since their discovery at the beginning of the 21st century, pioneering research efforts focused on the design and fabrication of MBGs with optimal compositional, textural and structural properties to elicit superior bioactive behavior. The current trends conceive MBGs as multitherapy systems for the treatment of bone-related pathologies, emphasizing the need of fine-tuning surface functionalization. Herein, we focus on the recent developments in MBGs for biomedical applications. First, the role of MBGs in the design and fabrication of three-dimensional scaffolds that fulfil the highly demanding requirements for bone tissue engineering is outlined. The different approaches for developing multifunctional MBGs are overviewed, including the incorporation of therapeutic ions in the glass composition and the surface functionalization with zwitterionic moieties to prevent bacterial adhesion. The bourgeoning scientific literature on MBGs as local delivery systems of diverse therapeutic cargoes (osteogenic/antiosteoporotic, angiogenic, antibacterial, anti-inflammatory and antitumor agents) is addressed. Finally, the current challenges and future directions for the clinical translation of MBGs are discussed. [ABSTRACT FROM AUTHOR]

Objective: Biofilm infections in chronic wounds are common and pose a significant clinical challenge. This challenge was addressed by developing the SoftOx Biofilm Eradicator (SBE) composed of hypochlorous acid (HOCl) and acetic acid with strong broad-spectrum antimicrobial activity. Approach: First-in-human study investigating the safety and tolerability as primary endpoints and wound size effect and antimicrobial efficacy as secondary endpoints of SBE treatment in chronic leg wound patients. The study was divided into two as follows: a randomized, double-blinded, Single Ascending Dose (SAD) phase ( n = 16 SBE; n = 4 placebo), where patients were treated with SBE or saline (placebo) only once, followed by an open-label, Multiple Ascending Dose (MAD) phase ( n = 8), where patients were treated with SBE once daily or twice daily over five days. Reporting is according to CONSORT guidelines. Results: SBE was safe and well-tolerated in chronic leg wound patients. There were no significant differences in pain during and after treatment with SBE or the placebo. The SBE treatment reduced bioburden in wounds compared to baseline, with 98% and 49% median reduction after SBE or placebo treatment, respectively. A dose-dependent trend in absolute wound size reduction was observed in the MAD groups with a median (min, max) change of -2.99 (-14.25, -1.5) cm 2 in the once-daily and -10.48 (-17.95, -0.38) cm 2 in the twice-daily group, respectively. Innovation and Conclusion: This study demonstrated the safe use of HOCl-based SBE in chronic leg wounds with promising trends of immediate antimicrobial action and beneficial effect on wound healing.

Aims: Fungal periprosthetic joint infections (fPJIs) are rare complications, constituting only 1% of all PJIs. Neither a uniform definition for fPJI has been established, nor a standardized treatment regimen. Compared to bacterial PJI, there is little evidence for fPJI in the literature with divergent results. Hence, we implemented a novel treatment algorithm based on three-stage revision arthroplasty, with local and systemic antifungal therapy to optimize treatment for fPJI. Methods: From 2015 to 2018, a total of 18 patients with fPJI were included in a prospective, single-centre study (DKRS-ID 00020409). The diagnosis of PJI is based on the European Bone and Joint Infection Society definition of periprosthetic joint infections. The baseline parameters (age, sex, and BMI) and additional data (previous surgeries, pathogen spectrum, and Charlson Comorbidity Index) were recorded. A therapy protocol with three-stage revision, including a scheduled spacer exchange, was implemented. Systemic antifungal medication was administered throughout the entire treatment period and continued for six months after reimplantation. A minimum follow-up of 24 months was defined. Results: Eradication of infection was achieved in 16 out of 18 patients (88.8%), with a mean follow-up of 35 months (25 to 54). Mixed bacterial and fungal infections were present in seven cases (39%). The interval period, defined as the period of time from explantation to reimplantation, was 119 days (55 to 202). In five patients, a salvage procedure was performed (three cementless modular knee arthrodesis, and two Girdlestone procedures). Conclusion: Therapy for fPJI is complex, with low cure rates according to the literature. No uniform treatment recommendations presently exist for fPJI. Three-stage revision arthroplasty with prolonged systemic antifungal therapy showed promising results. Cite this article: Bone Jt Open 2021;2(8):671–678.

Over the past decade, much attention has been paid to chitosan as a potential drug carrier because of its non-toxicity, biocompatibility, biodegradability and antibacterial properties. The effect of various chitosan characteristics on its ability to carry different antibiotics is discussed in the literature. In this work, we evaluated the influence of the different molecular weights of this polymer on its potential as an antibacterial membrane after adding gentamicin (1% w/w). Three types of chitosan membranes without and with antibiotic were prepared using a solvent casting process. Their microstructures were analyzed with a 4K digital microscope, and their chemical bonds were studied using FTIR spectroscopy. Furthermore, cytocompatibility on human osteoblasts and fibroblasts as well as antibacterial activity against Staphylococcus aureus (S. aureus.) and Escherichia coli (E. coli) were assessed. We observed that the membrane prepared from medium-molecular-weight chitosan exhibited the highest contact angle (≈85°) and roughness (10.96 ± 0.21 µm) values, and its antibacterial activity was unfavorable. The maximum tensile strength and Young’s modulus of membranes improved and elongation decreased with an increase in the molecular weight of chitosan. Membranes prepared with high-molecular-weight chitosan possessed the best antibacterial activity, but mainly against S. aureus. For E. coli, is not advisable to add gentamicin to the chitosan membrane, or it is suggested to deplete its content. None of the fabricated membranes exhibited a full cytotoxic effect on osteoblastic and fibroblast cells. Based on our results, the most favorable membrane as a gentamicin carrier was obtained from high-molecular-weight chitosan.

Nanozymes have shown promise for antibacterial applications, but their effectiveness is often hindered by low catalytic performances in physiological conditions and uncontrolled production of hydroxyl radicals (·OH). To address these limitations, a comprehensive approach is presented through the development of an adenosine triphosphate (ATP)-activated cascade reactor (GGPcs). The GGPcs reactor synergistically combines the distinct properties of zeolitic imidazolate framework-8 (ZIF-8) and chitosan-integrated hydrogel microsphere. The ZIF-8 allows for the encapsulation of G-quadruplex/hemin DNAzyme to achieve ATP-responsive ·OH generation at neutral pH, while the hydrogel microsphere creates a confinement environment that facilitates glucose oxidation and provides a sufficient supply of H 2 O 2 . Importantly, the integrated chitosan in the hydrogel microsphere shields ZIF-8 from undesired disruption caused by gluconic acid, ensuring the responsive specificity of ZIF-8 toward ATP. By activating GGPcs with ATP secreted by bacteria, its effectiveness as an antibacterial agent is demonstrated for the on-demand treatment of bacterial infection with minimal side effects. This comprehensive approach has the potential to facilitate the design of advanced nanozyme systems and broaden their biological applications., (© 2023 Wiley‐VCH GmbH.)

Endodontic implant pathology (EIP) refers to cases in which endodontic infections cause infections in adjacent implants, and vice versa. This case report demonstrates the successful resolution of two types of EIPs, implant endodontitis and endodontic implantitis, by endodontic intervention with surgical treatment. In case 1, the patient complained of tooth discomfort after implant placement in the adjacent tooth. The tooth was sensitive to percussion and showed slight mobility with a negative reaction to an electric pulp test. The symptoms persisted despite conventional root canal treatment, and surgical treatment of the symptomatic tooth and implant lesion was performed. In case 2, the patient suffered from repeated infection around a newly installed implant. The adjacent devitalized tooth exhibited a periapical lesion that was contiguous with the implant. Conventional root canal treatment and retreatment did not successfully resolve the symptoms. Surgical root canal therapy was then performed with regenerative biomaterials as needed. Neither case showed radiographic or clinical evidence of failure after 4 and 5 years of follow-up, respectively, after the surgery and the adjacent implants were successfully osseointegrated. Endodontic intervention combined with surgical treatment resolved both types of EIPs and led to tooth preservation and successful osseointegration of adjacent implants. [ABSTRACT FROM AUTHOR]

Background: The prevention and treatment of periprosthetic joint infection is of utmost importance to orthopedic surgeons. Irrigation solutions have become a popular additive to the prevention and treatment armamentarium.Methods: This symposium summarizes the mechanism of action, basic science, and clinical research to date on the use of irrigation solutions. The four most commonly used irrigation solutions, povidone iodine, chlorhexidine, hydrogen peroxide, and acetic acid, are discussed. In addition, the role of antibiotic powers is reviewed.Results: Each solution has its risks and benefits that must be weighed by the surgeon. There is no clear irrigation solution that is superior. The role of additive antibiotic powder (vancomycin) remains controversial.Conclusion: More rigorous prospective clinical trials are needed to determine the optimal irrigation solution for the prevention and treatment of periprosthetic joint infection. [ABSTRACT FROM AUTHOR]

On 31 January 2020, World announced COVID-19 as an Emergency Public Health of International Concern. The number of patients in Indonesia continues to grow. Anti-viral in the COVID-19 Drug Information Laboratory in Indonesia are Lopinavir/Ritonavir, Favipiravir, Remdemsivir, Oseltamivir, Chloroquine Phosphate and Hydroxychloroquine Phosphate. Therefore, it is necessary to know the basis and management of its use. An online systematic search was performed on articles published until 30 March 2020. We use search keywords that are tailored to the purpose of writing. All six antivirals were used for the treatment of RNA virus. Chloroquine, Hydroxychloroquine and Remdesivir effectively control the SARS-CoV2 virus invitro. Lopinavir/Ritonavir, Hydroxychloroquine and Oseltamivir have been used clinically for the treatment of SARS-CoV2 virus. In 2020, there are 42 clinical trials of six antivirals. Guidance of the antivirus are from China, Belgium and Indonesia. Its differences are based on the patient's condition. There is a lack of evidence of six antiviral effectiveness against the SARS-CoV2 virus. It has been used for other RNA viruses. It is supported by a safety profile. In a pandemic situation and the absence of a specific antivirus, the use of the six antiviruses can be done and be useful. [ABSTRACT FROM AUTHOR]

Due to the variability in the etiology and clinical manifestation of infectious diseases, immunological analysis techniques play an increasingly important role in their diagnosis. These can be subdivided into nonspecific techniques, which reveal general changes indirectly associated with the pathology, and specific techniques, which reveal the precise immune mechanism of the pathology. Some modern principles of disease treatment are discussed as well. [ABSTRACT FROM AUTHOR]

Purpose: Odontogenic infection sources represent a predisposing risk factor for patients with cardiac valvular disease (CVD) awaiting cardiac valve replacement procedures.Study Design: The incidence and quality of odontogenic infection sources (foci) were evaluated on 152 consecutive patients (study group, SG) undergoing cardiac valve replacement and were compared to 150 age-, gender- and residence-matched non-cardiac patients (control group, CG). Clinical and radiographic examinations were used to evaluate the incidence of odontogenic infection sources, grouped into potential (high risk) and facultative foci (possible risk), and the presence/severity of periodontal disease (PD). Foci and PD were compared among the overall SG and the CG and also among a sophisticated subdivision of the study group, especially with respect to aortic valve (AVR) and mitral valve replacement (MVR).Results: Overall, 218 potential and 116 facultative odontogenic foci were found in 87 (58.3%) and in 79 (51.9%) patients of the SG respectively. The overall incidence of odontogenic infection sources and the incidence and severity of PD did not differ between the SG and the CG. However, in comparison with the CG (48%), the incidence of potential odontogenic infection foci was significantly higher in patients scheduled for AVR than in those scheduled to undergo MVR (70.4% vs. 25.0%, p < 0.01). Additionally, in patients scheduled for AVR, a significantly higher number (p < 0.01) of individual potential dentogenic infection foci (1.7 vs. 0.8 foci/valve) and a higher prevalence of PD (60.2%) was seen than for patients scheduled for MVR (31.8%) or for patients without CVD (1.0 foci/valve; 39.3%; p < 0.05).Discussion: Although the overall incidence of odontogenic infection sources did not differ between the patients with and without CVD, a sophisticated subdivison of CVD may be crucial, demonstrating that patients with AVR differ significantly from those with MVR and with the healthy CG. Cardiologists and cardiac surgeons play an important role in organising oral rehabilitation of patients scheduled for valve replacement. [ABSTRACT FROM AUTHOR]

This review focuses on the design of mesoporous silica nanoparticles for infection treatment. Written within a general context of contributions in the field, this manuscript highlights the major scientific achievements accomplished by professor Vallet-Regí’s research group in the field of silica-based mesoporous materials for drug delivery. The aim is to bring out her pivotal role on the envisage of a new era of nanoantibiotics by using a deep knowledge on mesoporous materials as drug delivery systems and by applying cutting-edge technologies to design and engineer advanced nanoweapons to fight infection. This review has been divided in two main sections: the first part overviews the influence of the textural and chemical properties of silica-based mesoporous materials on the loading and release of antibiotic molecules, depending on the host–guest interactions. Furthermore, this section also remarks on the potential of molecular modelling in the design and comprehension of the performance of these release systems. The second part describes the more recent advances in the use of mesoporous silica nanoparticles as versatile nanoplatforms for the development of novel targeted and stimuli-responsive antimicrobial nanoformulations for future application in personalized infection therapies.

Objective: This study aimed to classify the pre-auricular sinus before performing radical dissection, so as to achieve optimal aesthetic results. Methods: The recent five-year clinical data of 53 patients with a congenital pre-auricular sinus and infection treated in the hospital were reviewed. According to the sinus course, pre-auricular and post-auricular types were defined, and regional dissection was performed using the modified supra-auricular or post-auricular approach. Results: All patients achieved primary intention healing of the incision, and were followed up for six months to five years. No recurrence was found, and the incision scar was completely concealed. Conclusion: Surgical approaches for regional dissection might be adopted based on the different types of pre-auricular sinuses, and further radical dissection might be performed to achieve optimal aesthetic results. [ABSTRACT FROM AUTHOR]

The article describes the case of a 63-year-old female patient with total hip arthroplasty with a massive swelling of the right hip joint. Topics include an open synovial biopsy performed to search for abrasive wear particles, the microbiological culturing of tissue samples and synovial fluid over two weeks, and an improvement in the clinical condition of the patient under high-dose cortisone therapy.

Immune checkpoint inhibitors (ICIs) have been widely used in management of malignant tumor. Programmed death ligand 1 (PD-1)/programmed death ligand 1 (PD-L1) inhibitors have been introduced to treat non-small cell lung cancer (NSCLC) in recent years. Currently, PD-1/PD-L1 inhibitors are considered to have minor side effects and do not independently increase the risk of infection. However, they may cause immune-related adverse events (irAEs) that can require immunosuppressive therapy with corticosteroids and/or immunosuppressants, leading to opportunistic infections. Furthermore, there were reports about reactivation of chronic/latent infections without irAEs. Thus, immune checkpoint inhibitor related infections have drawn more and more attention in the world. In this paper, we described the potential mechanism, available clinical data and recommendation of diagnosis and management for PD-1/PD-L1 inhibitor related infections. [ABSTRACT FROM AUTHOR]

Background: Acute Respiratory Infections (ARIs) are among the leading causes of morbidity and mortality in children under the age of five in Pakistan. Gauging the knowledge and practices of mothers related to ARIs may hold a key role in reducing the incidence and complications. Our study assessed the knowledge of mothers regarding ARIs among children under five years in accordance with WHO guidelines, and its association with education and socioeconomic status of mothers. In addition, we studied the association between education of mothers and socioeconomic status with vaccination status of child. Methods: This cross-sectional study was conducted from May to December 2016 at Civil Hospital, Ziauddin Hospital and Gulshan-e-Sikanderabad PHC Karachi and involved mothers with at least one child under the age of five years. Four hundred mothers were interviewed using a questionnaire. Results were analysed using SPSS 20.0. Results: 51% of mothers were found to have an above average understanding about ARIs with a mean score of 13.35±3.03 out of a possible 20. There is no association between knowledge of mothers and their level of education. Education level of the mother was found to have a significant association with the vaccination status of youngest child. Mothers having no education or just religious education had the highest percentages of incomplete vaccinations. Conclusion: Most mothers had above average knowledge of what classified as an ARI and could identify the danger signs. Uneducated mothers had incomplete vaccinations of their youngest child. The majority of mothers had satisfactory breastfeeding habits. [ABSTRACT FROM AUTHOR]

To estimate the prevalence and incidence of needlestick injuries associated with insulin injection among nurses working in hospitals in China and to quantify the direct healthcare costs associated with insulin injection-related needlestick injuries. We conducted a large online survey among hospital nurses from 31 provinces, municipal cities, and autonomous regions in China from October 2016 to February 2017. The survey covered a wide range of questions, including geographical location, years of experience, insulin injection practice, number of insulin injection-related needlestick injuries in the past 12 months, interventions for needlestick injuries, and treatment costs. We developed a cost estimate model and categorized costs into two major components: infection prevention and treatment of infections. We received a total of 10,447 questionnaires, of which 9873 were complete and validated. 39.1% of the nurses reported at least one needlestick injury while administering diabetic injections at some point in the past. The incidence of needlestick injuries involving injection pens was 139.5 per 1000 nurses per year and, with adjustment for exposure, 10.2 needlestick injuries per 100,000 injections. Among the respondents, 3.2% reported of having hepatitis B virus infection and 0.9% having hepatitis C virus infection as a result of needlestick injuries. The total costs of one insulin injection-related needlestick injury was estimated to range from ¥1,884 - ¥2,389. Insulin injection-related needlestick injuries were common in nurses working in hospitals in China and imposed a significant economic burden. More resources should be allocated for preventive efforts for needlestick injuries, including adoption of injection devices with advanced safety features. [ABSTRACT FROM AUTHOR]

Background The bacillus Calmette-Guérin (BCG) vaccine against tuberculosis might reduce the non–tuberculosis-related child mortality rate in low-income settings. We tested the hypothesis that BCG vaccination at birth would reduce early childhood hospitalization for infection in Denmark, a high-income setting. Hospitalization for infection was a secondary outcome in a randomized trial with the primary aim to estimate the potential non-specific effects of BCG vaccination at birth on all-cause hospitalization. Methods A total of 4262 children included in the Danish Calmette Study were assigned randomly to either receive the BCG vaccine or not and were followed through the Danish National Patient Register. The outcome was number of hospitalizations for infection until the age of 15 months. Data were analyzed by Cox regression in intention-to-treat (ITT) and per-protocol (PP) analyses. Results In the ITT analysis, we observed 588 hospitalizations for infection (mean, 0.28 hospitalization per child) among the 2129 children allocated to receive the BCG vaccine and 595 hospitalizations for infection (mean, 0.28 hospitalization per child) among the 2133 children allocated to the control group (hazard ratio [HR], 0.99 [95% confidence interval (CI), 0.85–1.15]). The PP analysis yielded an HR of 1.00 (95% CI, 0.86–1.16). Predefined interaction ITT analyses showed that among 740 children with a BCG-vaccinated mother, the HR for BCG-vaccinated children was 0.65 (95% CI, 0.45–0.94); the HR for children who had a non–BCG-vaccinated mother was 1.10 (95% CI, 0.93–1.29) (P =.01, test of no interaction). Cesarean delivery modified the effect of BCG vaccination (HRs, 0.73 [95% CI, 0.54–0.99] in children born by cesarean section vs 1.10 [95% CI, 0.92–1.30] in other children; P =.02). When the outcome was defined as time to first hospitalization, the HR for premature children after BCG vaccination was 1.81 (95% CI, 0.95–3.43), whereas the HR was 0.94 (95% CI, 0.82–1.08) for children born at term (P =.05). Conclusion BCG vaccination did not affect the rate of hospitalization for infection up to the age of 15 months in Danish children. In future studies, the role of maternal BCG-vaccination, premature birth, and cesarean delivery needs further exploration. [ABSTRACT FROM AUTHOR]

In 2016, the American Academy of Pediatrics published a clinical practice guideline that more specifically defined apparent life-threatening events as brief resolved unexplained events (BRUEs) and provided evidence-based recommendations for the evaluation of infants who meet lower-risk criteria for a subsequent event or serious underlying disorder. The clinical practice guideline did not provide recommendations for infants meeting higher-risk criteria, an important and common population of patients. Therefore, we propose a tiered approach for clinical evaluation and management of higher-risk infants who have experienced a BRUE. Because of a vast array of potential causes, the initial evaluation prioritizes the diagnosis of time-sensitive conditions for which delayed diagnosis or treatment could impact outcomes, such as child maltreatment, feeding problems, cardiac arrhythmias, infections, and congenital abnormalities. The secondary evaluation addresses problems that are less sensitive to delayed diagnosis or treatment, such as dysphagia, intermittent partial airway obstruction, and epilepsy. The authors recommend a tailored, family-centered, multidisciplinary approach to evaluation and management of all higher-risk infants with a BRUE, whether accomplished during hospital admission or through coordinated outpatient care. The proposed framework was developed by using available evidence and expert consensus. [ABSTRACT FROM AUTHOR]

Background and purpose — The evidence-based algorithms for treatment of periprosthetic joint infection (PJI) recommend surgical intervention in combination with the use of systemic antibiotics. However, still it is not unusual to treat total knee arthroplasty (TKA) patients with suspected infection using only antibiotics. We investigated treatment pathways for TKA patients with suspected infection in Lithuania. Patients and methods — Of the 4,069 TKA patients (4,269 knees) registered in the Lithuanian Arthroplasty Register (2013–2015) 2,769 patients (2,825 knees) were interviewed 2 years after the surgery. The patients were asked if they had been subject to antibiotic treatment after the TKA surgery and/or if any additional surgical interventions on the operated knee had been performed. The number of patients treated with antibiotics due to problems in the operated knee was identified and cumulative revision rates (CRR) were calculated. Results — 180 (7%) patients of the total 2,769 reported that they had been prescribed antibiotics after the primary TKA; 132 of these patients (70%) said they had received antibiotics due to problems with the operated knee. The 2-year CRR after TKA in patients not treated with antibiotics was 0.7% (95% CI 0.4–1), as compared with 24% (95% CI 17–32) in those who had used antibiotics due to the problems in the operated knee for more than 1 week. Interpretation — In Lithuania there seems to be a lack of adherence to evidence-based treatment guidelines when infection is suspected after primary TKA. [ABSTRACT FROM AUTHOR]

Background: Preliminary studies have reported promising results for the utility of gallium‐68 (Ga‐68) citrate positron emission tomography‐computed tomography (PET–CT) for infection imaging. This technique offers reduced radiation dose to patients, shorter time between injection and imaging and reduced time for image acquisition compared to the 'gold standard' nuclear imaging technique: gallium‐67 (Ga‐67) citrate scintigraphy. Aims: To compare the two imaging modalities to ascertain whether Ga‐68 citrate PET–CT is of equivalent diagnostic efficacy for bone and joint infection or pyrexia of unknown origin (PUO) and to assess image quality and reporter confidence. Methods: Patients with PUO and suspected bone or joint infection underwent Ga‐67 citrate scintigraphy and Ga‐68 citrate PET–CT. Participants were followed up for 3 months to record subsequent treatment, investigations and outcome. Results: 60 patients were recruited to this multicentre prospective study: 32 for bone and joint infection, 28 for PUO. The results show a sensitivity of 81% for Ga‐67 citrate scintigraphy and 69% for Ga‐68 citrate PET–CT, a specificity of 79% for Ga‐67 citrate and 67% for Ga‐68 citrate and were concordant for 76% of the participants. The reporting physician confidence was significantly lower for Ga‐68 citrate (P < 0.05), frequently due to prominent physiologic blood pool activity adjacent to the site of infection. Conclusion: The sensitivity and specificity of Ga‐68 citrate PET–CT were found to be consistently lower than Ga‐67 citrate scintigraphy. Additionally, due to the insufficient level of confidence of the reporting physicians for the Ga‐68 citrate PET–CT, this modality could not currently be recommended to replace Ga‐67 citrate scintigraphy for routine clinical use. [ABSTRACT FROM AUTHOR]

Background: Longitudinal studies of dental prescribing in Australia show that dentists make some inappropriate prescribing choices; literature has shown that dentists tend to overprescribe antibiotics and prescribe for incorrect indications. The unnecessary use of antibiotics is a contributing factor towards the development of antibiotic resistance. The aims of the study were to obtain a greater understanding of the perceptions, attitudes and factors that influence dental prescribing for all major relevant drug classes.Method: Semi-structured interviews of 15 purposively sampled dentists practising in Victoria, Australia were conducted from June-September 2018. Two dentists practised in rural areas and the remainder in urban locations. The range of clinical experience varied from 2.5 to 37 years, with a mean of 13 years. The transcripts were analysed thematically.Results: Dentists generally preferred amoxicillin as first-line therapy for odontogenic infections, with some confusion about the spectrum and uses of antibiotics. Overprescribing was evident, mostly due to basing judgement for use of antibiotics on symptoms rather than clinical signs. Other factors, such as time pressure, patient expectations, pressure from assistant staff, concern about online criticism and medico-legal considerations, influenced prescribing. Of the dentists who prescribed anxiolytics, most did not have a care protocol for their sedated patients.Conclusion: A variety of prescribing practices were described, and future interventions should target misconceptions around the appropriate use and choice of antibiotics, resources to address the shortfall in knowledge of therapeutics, patient education and staff training, as well as appropriate care and monitoring of sedated patients. [ABSTRACT FROM AUTHOR]

• Malaria, a protozoal infection caused by Plasmodium parasites leading to more than one million deaths each year. • The malaria parasites turn to acquire resistance against most of the existing drugs. • The intracellular nature and scattered location of the parasites produce a great challenge for developing a new molecule. • Nanotechnology based malaria therapy could be one of the approaches to target a drug directly into the infected host cells. Malaria, one of the major infectious disease-causing sizeable morbidity, mortality and economic loss worldwide. The main drawback for the failure to eradicate malaria is the spread of multiple drug resistance to the majority of currently available chemotherapy. At present nanotechnology offers an advanced opportunity in the delivery of drugs and vaccines to the desired targeted site in the body following oral and systemic administration. It confers the major advantages like improving drug pharmacokinetic profiles, reduce dose frequency and reduction in drug toxicity. Hence, Nano-based drug delivery system can provide a promising prospect in the way of malaria treatment. This paper is a review of recent researches highlighting includes nanocarriers loaded antimalarial drugs for better therapeutic efficacy and future perspective in the treatment of malaria. [ABSTRACT FROM AUTHOR]

In a Perspective for the Tuberculosis Special Issue, Kevin Schwartzman and colleagues discuss the choices and implications for personal versus public health benefits when pursuing tuberculosis elimination in low-incidence countries. [ABSTRACT FROM AUTHOR]

Despite the developments in controlling infectious disease around the world, they are still the second biggest cause of morbidity and mortality due in part to the increase in drug resistance among large numbers of the bacterial strains. This means that new strategies are needed to prevent and treat infectious disease. As a result, several ancient methods have been re-evaluated and the substances/procedures employed historically to cure diseases are now attracting renewed scientific attention. Honey is one such product that used to be widely used to combat bacteria. This review covers the antibacterial activity of honey, its use in the treatment of infection and diseases, and the features that are relevant to its activity. [ABSTRACT FROM AUTHOR]

• The rate of infection after conversion of external fixation to intramedullary nailing (IMN) is not well known. • The time interval of 2 step regimen for conversion of external fixation to intramedullary nailing is uncertain. Some authors have recommended about 9 days. • Registries capturing important parameters to the development of infection should be established. Pin tract infection in external fixation (ExFix) is a frequent finding which can eventually lead to loosening, osteomyelitis and loss of fixation. Its diagnosis is based on high empiricism and low validity, although it is possible to distinguish between minor and major infection. The first is limited to soft tissues, whereas the latter includes bone involvement. The rate of infection after conversion of external fixation to intramedullary nailing (IMN) is not well known. Unfortunately, papers referring to infection after the conversion of ExFix to intramedullary nailing (IMN) are of evidence level IV or V. It is suggested that conversion of ExFix to IMN should be carried out in a 2 step regimen. The time interval of 2 step regimen is uncertain although some authors have recommended to occur within 9 days. There is no consensus as to which prophylaxis protocol should be applied prior to conversion. In order to throw more light into this important issue, registries capturing important related parameters to the development of infection should be established. [ABSTRACT FROM AUTHOR]

This review article covers the most important steps of the pioneering work of Patrick Couvreur and tries to shed light on his outstanding career that has been a source of inspiration for many decades. His discovery of biodegradable poly(alkyl cyanoacrylate) (PACA) nanoparticles (NPs) has opened large perspectives in nanomedicine. Indeed, NPs made from various types of alkyl cyanoacrylate monomers have been used in different applications, such as the treatment of intracellular infections or the treatment of multidrug resistant hepatocarcinoma. This latest application led to the Phase III clinical trial of Livatag®, a PACA nanoparticulate formulation of doxorubicin. Despite the success of PACA NPs, the development of a novel type of NP with higher drug loadings and lower burst release was tackled by the discovery of squalene-based nanomedicines where the drug is covalently linked to the lipid derivative and the resulting conjugate is self-assembled into NPs. This pioneering work was accompanied by a wide range of novel applications which mainly dealt with the management of unmet medical needs (e.g. pancreatic cancer, brain ischaemia and spinal cord injury). [ABSTRACT FROM AUTHOR]

Although solid organ transplant (SOT) recipients with pretransplant serology for cytomegalovirus (CMV-R+) are considered at intermediate risk for CMV infection post transplantation, CMV infection remains a major cause of morbidity in this population. We prospectively characterized whether having pretransplant CMV-specific cellular immunity is independently associated with controlling infection after transplantation in R + SOT recipients. A prospective cohort of consecutive R + SOT recipients that received pre-emptive treatment for CMV infection was monitored after transplantation and variables were recorded during the follow-up. The cytomegalovirus-specific T-cell immune response was characterized by intracellular cytokine staining and viral loads determined using real-time PCR. One hundred and thirty-five R + SOT recipients were included (67 kidney, 64 liver, four liver–kidney). Only one-third of the patients (42; 31.85%) had CMV-specific T-cell immunity (CD8+CD69+INF-γ+ T cells >0.25%) before transplantation. Patients with negative pretransplant immunity had more CMV infection (49, 52.7% vs. 15, 35.7%; p 0.07) and received more antiviral therapy than those with immunity (32, 34.4% vs. 6, 14.3%, p 0.016). Having CMV specific immunity was an independent factor for protection from developing viraemia ≥2000 IU/mL (OR 0.276, 95% CI 0.105–0.725, p < 0.01) and lower administration of treatment (OR 0.398, 95% CI 0.175–0.905, p 0.028). Only patients with no pretransplant CMV-specific T-cell response were diagnosed with CMV-disease (8, 8.6% vs. 0, 0%, p 0.05). Our results show that having a pretransplant CMV specific T-cell response may be associated with a lower rate of CMV viraemia and less antiviral treatment after transplantation; however, more prospective studies are needed to confirm these findings. [ABSTRACT FROM AUTHOR]

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Bacteriophages (BPs) are viruses that can infect and kill bacteria without any negative effect on human or animal cells. For this reason, it is supposed that they can be used, alone or in combination with antibiotics, to treat bacterial infections. In this narrative review, the advantages and limitations of BPs for use in humans will be discussed. PubMed was used to search for all of the studies published from January 2008 to December 2018 using the key words: "BPs" or "phages" and "bacterial infection" or "antibiotic" or "infectious diseases." More than 100 articles were found, but only those published in English or providing evidence-based data were included in the evaluation. Literature review showed that the rapid rise of multi-drug-resistant bacteria worldwide coupled with a decline in the development and production of novel antibacterial agents have led scientists to consider BPs for treatment of bacterial infection. Use of BPs to overcome the problem of increasing bacterial resistance to antibiotics is attractive, and some research data seem to indicate that it might be a rational measure. However, present knowledge seems insufficient to allow the use of BPs for this purpose. To date, the problem of how to prepare the formulations for clinical use and how to avoid or limit the risk of emergence of bacterial resistance through the transmission of genetic material are not completely solved problems. Further studies specifically devoted to solve these problems are needed before BPs can be used in humans. [ABSTRACT FROM AUTHOR]

Introduction: Extremity war-wounds present an elevated risk of infection and compromise reconstructive procedures. In a French military hospital, a multi-disciplinary meeting (MDM) was created to standardize the care given to soldiers with osteoarticular infection. The aim of this study was to evaluate the usefulness of MDM decisions.Methods: An observational case study was performed including the French wounded at war treated for an osteoarticular infection between 2004 and 2016. They were separated into two groups according to their time of management: before (group A) or after (group B) the MDM creation in September 2010. Various operative and bacteriological parameters were analyzed retrospectively. A questionnaire was created to evaluate healthcare professionals' satisfaction toward the usefulness of the MDM on their practice.Results: During the study period, 38 patients were included: 19 in group A and 19 in group B. Initial tests found an infection with one pathogen in 15 patients, an infection with 2 pathogens in 11 patients, and an infection with 3 or more pathogens in 12 patients. Enterobacter cloacae was the most common pathogen. Pseudomonas aeruginosa and Escherichia coli were also frequent. The mean number of samples taken to conduct the bacteriological tests per operating session was significantly higher for group B than for group A. Twelve of the 14 questioned healthcare professionals believed the MDM was very useful in their patient management.Conclusion: The MDM seems to have had a beneficial impact on orthopedic surgeon practices. A significant increase of the number of samples taken was the most obvious sign that the French recommended practices for osteoarticular infections were followed since the creation of MDM. [ABSTRACT FROM AUTHOR]

The study aims to determine whether 8 weeks of antibiotics is non-inferior to 12 weeks in patients with acute deep spinal implant infection (SII). In the retrospective study of all SII cases (2009–2016), patients aged ≥ 15 years with microbiologically confirmed SII treated with debridement and implant retention were included. Whenever possible, tailored antibiotic treatment was used: rifampin/linezolid in gram-positive and quinolones in gram-negative infection. Patients were divided into short treatment course (8 weeks, ST group) and extended treatment (12 weeks, ET group). Primary outcome measure was percentage of cures at 1-year follow-up. One-hundred-twenty-four patients considered, 48 excluded based on the above criteria, leaving 76 patients, 28 ST and 48 ET. There were no differences in patient age, comorbidities, underlying pathologies, infection location, or surgery characteristics between groups. Surgery-to-debridement time was similar (18.5-day ST vs. 19-day ET; P = 0.96). Sixteen SII cases (21.1%) occurred with bloodstream infection. Pathogens found were Enterobacteriaceae (35, 46.1%), Staphylococcus aureus (29, 38.2%), coagulase-negative staphylococci (12, 15.8%), Pseudomonas aeruginosa (12, 15.8%), and Enterococcus faecalis (7, 9.2%). Twenty seven (35.5%) had polymicrobial infection. E. faecalis was more frequent in the ST group (7, 25% vs. 0; P < 0.001), and P. aeruginosa in ET (1, 3.6% vs. 11, 22.9%; P = 0.05). Five patients died of causes unrelated to SII. At 1-year follow-up, cure rates (21/26 ST, 80.8% vs. 39/45 ET, 86.7%; P = 0.52) and recurrences (2/26, 7.7% vs. 2/45, 4.4%; P = 0.62) were similar. Eight-week antimicrobial courses were not inferior to 12 weeks in patients with acute deep SII treated with prompt debridement, proper wound healing, and optimized antibiotics. [ABSTRACT FROM AUTHOR]

Background: The neonatal mortality rate in Uganda has been 24–27/1000 live births for the last 14 years. Aim: To determine the impact on neonatal mortality of the introduction of infection prevention and treatment guidelines in a resource-poor setting. Methods: A prospective study was undertaken in Kagando Hospital, a rural hospital in Western Uganda of infants live-born in hospital and those admitted from the community or other hospitals between 2013 and 2017. Guidelines were developed from a literature review and informed by local doctors and nurses and a visiting paediatrician. The guidelines highlighted that unwell infants should be admitted to the neonatal unit which was a section of the paediatric ward, emphasised hand hygiene, the separation of infants with and without sepsis and that unwell infants should be treated with evidence-based antibiotic regimens and enteral feeds withheld from unwell infants. Mortality within 28 days of birth was audited for 3 months before and after the intervention; the audit was repeated 3 and 5 years later. Results: Pre-intervention, there were 137 neonatal admissions and 79 neonatal deaths in 3 months (0.58 deaths per admission). Post-intervention there were 187 admissions and the death rate was lower (0.26 deaths per admission, p < 0.001). Three years after the intervention, there were 60 deaths among 233 admissions (0.26 deaths per admission, p < 0.001) and, at 5 years, 53 deaths among 315 admissions (0.17 deaths per admission, p < 0.001). Conclusion: These data suggest that the introduction of infection, prevention and treatment guidelines can reduce neonatal mortality in a resource-poor setting. [ABSTRACT FROM AUTHOR]

Osteomyelitis treatment is one of the most challenging issues in orthopedics, which is developed primarily by antibiotic resistant micro organisms. An efficient approach to overcome this issue is repurposing existing drug molecules to combine with the bioactive materials for making local drug delivery carriers. In the present study, we synthesized the repurposed sertraline drug loaded hydroxyapatite (HA) using eggshell biowaste as the calcium source via the in situ precipitation method. The physico-chemical analysis, antibacterial activity, biofilm formation, and bioactivity of the as prepared sample were studied. In situ sertraline loaded HA exhibited a controlled and prolonged release of sertraline that could efficiently prevent and inhibit the S. aureus biofilm formation, which was confirmed by CLSM and CFU. Moreover, it exhibited an excellent bioactivity; thus, it has great potential for the treatment of osteomyelitis infection. [ABSTRACT FROM AUTHOR]

The emerging antimicrobial resistance leading to gram-positive infections (GPIs) is one of the major public health threats worldwide. GPIs caused by multidrug resistant bacteria can result in increased morbidity and mortality rates along with escalated treatment cost and hospitalisation stay. In India, GPIs, particularly methicillin-resistant Staphylococcus aureus (MRSA) prevalence among invasive S. aureus isolates, have been reported to increase exponentially from 29% in 2009 to 47% in 2014. Apart from MRSA, rising prevalence of vancomycin-resistant enterococci (VRE), which ranges from 1 to 9% in India, has raised concerns. Moreover, the overall mortality rate among patients with multidrug resistant GPIs in India is reported to be 10.8% and in ICU settings, the mortality rate is as high as 16%. Another challenge is the spectrum of adverse effects related to the safety and tolerability profile of the currently available drugs used against GPIs which further makes the management and treatment of these multidrug resistant organisms a complex task. Judicious prescription of antimicrobial agents, implementation of antibiotic stewardship programmes, and antibiotic policies in hospitals are essential to reduce the problem of drug-resistant infections in India. The most important step is development of newer antimicrobial agents with novel mechanisms of action and favourable pharmacokinetic profile. This review provides a synopsis about the current burden, treatment options, and the challenges faced by the clinicians in the management of GPIs such as MRSA, Quinolone-resistant Staphylococcus, VRE, and drug-resistant pneumococcus in India. [ABSTRACT FROM AUTHOR]

Introduction: Establishing a systematic multidisciplinary approach in the treatment of prosthetic joint infections (PJI) of the hip and analyzing its effect on clinical decision-making.Patients and Methods: Forty-six patients diagnosed with PJI of the hip were included in the retrospective study. The treatment plan was either established by a single-discipline approach (n = 20) or by a weekly multidisciplinary infections conference (n = 26) consisting of at least an orthopedic surgeon, microbiologist and pathologist. Recorded data included the length of hospital stay, number and type of surgeries, medical complications, recovered organisms as well as the number of applied antibiotics.Results: Patients discussed in the multidisciplinary infections conference showed a significantly shorter in-hospital stay (29 vs 62 days; p < 0.05), a significant reduction in surgeries (1.8 vs 5.1; p < 0.05) and a smaller number of antibiotics required (2.8 vs 4.2; p < 0.05). No significant difference could be found comparing inpatient complications between the two groups. Staphylococcus aureus and coagulase-negative staphylococci were the most frequently recovered organisms in both patient groups.Conclusion: This study demonstrates the successful implementation of a weekly infections conference as an instrument to introduce a multidisciplinary approach to PJI of the hip. Implementation of these conferences significantly improves the treatment plan compared to a single-discipline approach, which we therefore highly recommend for other institutions. Multidiscipline may even affect clinical outcome which needs to be further investigated. [ABSTRACT FROM AUTHOR]

Purpose: The presence of Propionibacterium acnes in a substantial component of resected disc specimens obtained from patients undergoing discectomy or microdiscectomy has led to the suggestion that this prominent human skin and oral commensal may exacerbate the pathology of degenerative disc disease. This hypothesis, therefore, raises the exciting possibility that antibiotics could play an important role in treating this debilitating condition. To date, however, little information about antibiotic penetration into the intervertebral disc is available. Methods: Intervertebral disc tissue obtained from 54 microdiscectomy patients given prophylactic cefazolin (n = 25), clindamycin (n = 17) or vancomycin (n = 12) was assayed by high-performance liquid chromatography, with cefaclor as an internal standard, to determine the concentration of antibiotic penetrating into the disc tissue. Results: Intervertebral disc tissues from patients receiving the positively charged antibiotic clindamycin contained a significantly greater percentage of the antibacterial dose than the tissue from patients receiving negatively charged cefazolin (P < 0.0001) and vancomycin, which has a slight positive charge (P < 0.0001). Conclusion: Positively charged antibiotics appear more appropriate for future studies investigating potential options for the treatment of low-virulence disc infections. These slides can be retrieved under Electronic Supplementary Material. [ABSTRACT FROM AUTHOR]

Background: Several studies have implicated herpes simplex virus-type 1 (HSV-1) in the pathophysiology of schizophrenia. A recent trial demonstrated that the anti-viral medication valacylovir, which prevents replication of activated HSV-1, improved selected cognitive deficits in people with schizophrenia. In this study, we examined demographic and illness related differences between HSV-1 positive versus HSV-1 negative subjects with early phase schizophrenia and attempted to replicate the previous valacyclovir treatment results in this population.Methods: 170 subjects with schizophrenia (HSV-1 positive N = 70; HSV-1 negative N = 96) from 12 US sites participated in the HSV-1 positive versus negative comparisons, and were randomized 1:1 to valacyclovir (1.5 g BID) or placebo for a 16-week, double-blind efficacy trial. The primary endpoints were working and verbal memory.Results: The HSV-1 positive group, as compared to the HSV-1 negative group, were older (p < 0.001) with fewer males (p = 0.003), and had a longer duration of illness (p = 0.008), more positive symptoms (p = 0.013), poorer quality of life (p = 0.034) and more impairment on the letter-number sequencing test, which is a measure of working memory (p = 0.045). Valacyclovir failed to significantly improve any of the cognitive indices, symptom or functioning measures.Conclusions: HSV-1 sero-positivity appears to be a marker of a subgroup with a more severe form of schizophrenia. Valacyclovir was not efficacious in the study, perhaps because the herpes virus was in the dormant, non-activated state and therefore non-responsive to valacyclovir effects. ClinicalTrials.gov Identifier: NCT02008773. [ABSTRACT FROM AUTHOR]

Background Injection drug use (IDU) and IDU-related infections have increased dramatically. However, the incidence of IDU-related infections may be underreported because drug use is not recorded in diagnostic records where associated infections are identified. Our goal was to estimate a more accurate incidence of IDU-related infections by including IDU-related infections not recorded at the time infections are diagnosed. Methods We performed a retrospective cohort study using inpatient and emergency department visits from the Healthcare Cost and Utilization Project for California, Florida, and New York. We identified all patients diagnosed with bacteremia or sepsis, endocarditis, osteomyelitis or septic arthritis, and skin or soft tissue infection. We estimated the incidence of IDU-related infections by identifying cases where drug use was recorded at the time of an infection and cases where drug use was not recorded at the time of infection but within 6 months before or after the infection diagnosis. We also analyzed factors associated with unrecorded IDU. Results There has been an increasing trend in the number of IDU-related infections. The annual number of IDU-related infections increased between 105% and 218% after incorporating infections in which drug use was unrecorded. Factors associated with drug use being unrecorded included emergency department diagnosis, the level of hospital experience treating drug use, age <18 years, and having Medicare as the primary payer. Conclusions More than half of all IDU-related infections may be unrecorded in existing surveillance estimates. There may be many missed opportunities to record, diagnose, or treat underlying drug abuse among patients presenting with IDU-related infections. [ABSTRACT FROM AUTHOR]

Abstract Background Ceftazidime-avibactam has in vitro activity against Gram-negative bacilli that produce Class A, C and some D β-lactamases, and has been successfully used in the treatment of infections caused by cephalosporin and carbapenem-resistant Enterobacteriaceae. However, actual experience in the treatment of OXA-48 carbapenemase-producing Enterobacteriaceae (CPE) is limited. Objective To review the characteristics and prognosis of OXA-48 CPE infections treated with ceftazidime-avibactam since introduction of the drug to the current centre during the period October 2014 to December 2016. Methods Retrospective assessment of episodes of infection caused by OXA-48 CPE treated with ceftazidime-avibactam, analysing data collected from infection diagnosis until 90 days after the end of treatment. Results Twenty-four episodes were analysed. Ceftazidime-avibactam was given as the initial definitive treatment in 15 (62.5%) and as salvage therapy in nine (37.5%). Intraabdominal (seven, 29%), urinary (six, 25%) and respiratory (five, 21%) were the most common sources. The 30-day and 90-day mortality rates were 8.3% and 20.8%, respectively. Clinical cure at 30 days was achieved in 62.5% of episodes. Four (16.7%) patients had adverse events, two of them were related to impaired renal function. Among patients who finished the treatment with ceftazidime-avibactam, seven (35%) were diagnosed with infection recurrence within 90 days of the end of treatment. Conclusions From experience, ceftazidime-avibactam is an effective drug for treating infections due to OXA-48 CPE. From these results a better safety profile than the current best available therapy could be expected. [ABSTRACT FROM AUTHOR]

Background: Perioperative infection and sepsis are of fundamental concern to perioperative clinicians. However, standardised endpoints are either poorly defined or not routinely implemented. The Standardised Endpoints in Perioperative Medicine (StEP) initiative was established to derive a set of standardised endpoints for use in perioperative clinical trials.Methods: We undertook a systematic review to identify measures of infection and sepsis used in the perioperative literature. A multi-round Delphi consensus process that included more than 60 clinician researchers was then used to refine a recommended list of outcome measures.Results: A literature search yielded 1857 titles of which 255 met inclusion criteria for endpoint extraction. A long list of endpoints, with definitions and timescales, was generated and those potentially relevant to infection and sepsis circulated to the theme subgroup and then the wider StEP-COMPAC working group, undergoing a three-stage Delphi process. The response rates for Delphi rounds 1, 3, and 3 were 89% (n=8), 67% (n=62), and 80% (n=8), respectively. A set of 13 endpoints including fever, surgical site, and organ-specific infections as defined by the US Centres for Disease Control and Sepsis-3 are proposed for future use.Conclusions: We defined a consensus list of standardised endpoints related to infection and sepsis for perioperative trials using an established and rigorous approach. Each endpoint was evaluated with respect to validity, reliability, feasibility, and patient centredness. One or more of these should be considered for inclusion in future perioperative clinical trials assessing infection, sepsis, or both, thereby permitting synthesis and comparison of future results. [ABSTRACT FROM AUTHOR]

Patients often affirm the goal to pursue comfort at the end of life, although clinicians may struggle with how best to provide comfort and face the ethical dilemma of treating or allowing a suspected infection to unfold. Treating an infection at the end of life does not allow for uniform improvement in symptoms and more time with family and friends. Additionally, there is potential for burden to the patient or health care system and treatment may occur to the exclusion of other comfort measures. Currently, the practice of providing or forgoing antibiotics at the end of life is variable, and literature supporting best practices can be contradictory. Data to support the use or withholding of treatment have been scant and vary across settings and patient populations. We review common obstacles providers face, prognostication tools that may assist in clinical decision making, the ethical support for withholding therapy, and how to factor in potential burdens of treatment. We propose that nurses, whether at the bedside in an acute care or nursing facility or in the home setting as a member of the interdisciplinary home hospice team, are uniquely qualified to help patients and families navigate this challenging clinical decision. [ABSTRACT FROM AUTHOR]

Graphical abstract Abstract Local drug delivery into oral cavity offers many advantages over systemic administration in treatment of the oral infections. In this study, monolayer and bilayered mucoadhesive film and wafer formulations were developed as local drug delivery platforms using chitosan and hydroxypropyl methylcellulose (HPMC). Cefuroxime axetil (CA) was used as the model drug. Surface morphology, mechanical strength, water uptake, in vitro adhesion, disintegration and in vitro release properties of the formulations were investigated. Furthermore, antimicrobial activity of the formulations was evaluated against E. coli and S. aureus. HPMC based formulations were found to disintegrate within <30 min whereas chitosan based formulations remained intact up to 6 h. Significantly higher drug release was obtained with wafer formulations. Antimicrobial activity was found to increase in presence of chitosan, and HPMC was also observed to contribute to this action. Bilayered wafer formulation, with adhesive chitosan backing layer and HPMC based drug loaded layer, providing prolonged drug release and suitable adhesive properties, with suitable mechanical strength, would be suggested as a promising local delivery system for treatment of the infections in the oral cavity. [ABSTRACT FROM AUTHOR]