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Given the increasing threat of antimicrobial resistance, scientists are urgently seeking adjunct antimicrobial strategies, such as phage therapy (PT). However, despite promising results for the treatment of musculoskeletal infections in our center, crucial knowledge gaps remain. Therefore, a prospective observational study (PHAGEFORCE) and a multidisciplinary approach was set up to achieve and optimize standardized treatment guidelines. At our center, PT is strictly controlled and monitored by a multidisciplinary taskforce. Each phage treatment follows the same pathway to ensure standardization and data quality. Within the PHAGEFORCE framework, we established a testing platform to gain insight in the safety and efficacy of PT, biodistribution, phage kinetics and the molecular interaction between phages and bacteria. The draining fluid is collected to determine the phage titer and bacterial load. In addition, all bacterial isolates are fully characterized by genome sequencing to monitor the emergence of phage resistance. We hereby present a standardized bench-to-bedside protocol to gain more insight in the kinetics and dynamics of PT for musculoskeletal infections. [ABSTRACT FROM AUTHOR]

A judicious, well-planned bone and soft tissue debridement remains one of the cornerstones of state-of-the-art treatment of fracture-related infection (FRI). Meticulous surgical excision of all non-viable tissue can, however, lead to the creation of large soft tissue defects. The management of these defects is complex and numerous factors need to be considered when selecting the most appropriate approach. This narrative review summarizes the current evidence with respect to soft tissue management in patients diagnosed with FRI. Specifically we discuss the optimal timing for tissue closure following debridement in cases of FRI, the need for negative microbiological culture results from the surgical site as a prerequisite for definitive wound closure, the optimal type of flap in case of large soft tissue defects caused by FRI and the role of negative pressure wound therapy (NPWT) in FRI. Finally, recommendations are made with regard to soft tissue management in FRI that should be useful for clinicians in daily clinical practice. Level of evidence Level V. [ABSTRACT FROM AUTHOR]

The Belgian Society for Viruses of Microbes (BSVoM) was founded on 9 June 2022 to capture and enhance the collaborative spirit among the expanding community of microbial virus researchers in Belgium. The sixteen founders are affiliated to fourteen different research entities across academia, industry and government. Its inaugural symposium was held on 23 September 2022 in the Thermotechnical Institute at KU Leuven. The meeting program covered three thematic sessions launched by international keynote speakers: (1) virus–host interactions, (2) viral ecology, evolution and diversity and (3) present and future applications. During the one-day symposium, four invited keynote lectures, ten selected talks and eight student pitches were given along with 41 presented posters. The meeting hosted 155 participants from twelve countries. [ABSTRACT FROM AUTHOR]

Bacteroides fragilis is a commensal gut bacterium that is associated with a number of blood and tissue infections. It has not yet been recognized as one of the drug-resistant human pathogens, but cases of the refractory infections, caused by strains that are not susceptible to the common antibiotic regimes established for B. fragilis, have been more frequently reported. Bacteriophages (phages) were found to be a successful antibacterial alternative to antibiotic therapy in many cases of multidrug-resistant (MDR) bacterial infections. We have characterized the bacteriophage GEC_vB_Bfr_UZM3 (UZM3), which was used for the treatment of a patient with a chronic osteomyelitis caused by a B. fragilis mixed infection. Studied biological and morphological properties of UZM3 showed that it seems to represent a strictly lytic phage belonging to a siphovirus morphotype. It is characterized by high stability at body temperature and in pH environments for about 6 h. Whole genome sequencing analysis of the phage UZM3 showed that it does not harbor any known virulence genes and can be considered as a potential therapeutic phage to be used against B. fragilis infections. [ABSTRACT FROM AUTHOR]

Purpose: Fracture-related infection (FRI) is an important complication related to orthopaedic trauma. Although the scientific interest with respect to the diagnosis and treatment of FRI is increasing, data on the microbiological epidemiology remains limited. Therefore, the primary aim of this study was to evaluate the microbiological epidemiology related to FRI, including the association with clinical symptoms and antimicrobial susceptibility data. The secondary aim was to analyze whether there was a relationship between the time to onset of infection and the microbiological etiology of FRI. Methods: FRI patients treated at the University Hospitals of Leuven, Belgium, between January 1st 2015 and November 24th 2019 were evaluated retrospectively. The microbiological etiology and antimicrobial susceptibility data were analyzed. Patients were classified as having an early (<2 weeks after implantation), delayed (2-10 weeks) or late-onset (> 10 weeks) FRI. Results: One hundred ninety-one patients with 194 FRIs, most frequently involving the tibia (23.7%) and femur (18.6%), were included. Staphylococcus aureus was the most frequently isolated pathogen, regardless of time to onset (n=61; 31.4%), followed by S. epidermidis (n=50; 25.8%) and non-epidermidis coagulase-negative staphylococci (n=35; 18.0%). Polymicrobial infections (n=49; 25.3%), mainly involving Gram negative bacilli (GNB) (n=32; 65.3%), were less common than monomicrobial infections (n=138; 71.1%). Virulent pathogens in monomicrobial FRIs were more likely to cause pus or purulent discharge (n=45;54.9%; p=0.002) and fistulas (n=21;25.6%; p=0.030). Susceptibility to piperacillin/tazobactam for GNB was 75.9%. Vancomycin covered 100% of Gram positive cocci. Conclusion: This study revealed that in early FRIs, polymicrobial infections and infections including Enterobacterales and enterococcal species were more frequent. A time-based FRI classification is not meaningful to estimate the microbiological epidemiology and cannot be used to guide empiric antibiotic therapy. Large multicenter prospective studies are necessary to gain more insight into the added value of (broad) empirical antibiotic therapy. [ABSTRACT FROM AUTHOR]

Orthopedic device-related infections remain a serious challenge to treat. Central to these infections are bacterial biofilms that form on the orthopedic implant itself. These biofilms shield the bacteria from the host immune system and most common antibiotic drugs, which renders them essentially antibiotic-tolerant. There is an urgent clinical need for novel strategies to prevent these serious infections that do not involve conventional antibiotics. Recently, a novel antibiofilm coating for titanium surfaces was developed based on 5-(4-bromophenyl)- N -cyclopentyl-1-octyl-1 H -imidazol-2-amine as an active biofilm inhibitor. In the current study we present an optimized coating protocol that allowed for a 5-fold higher load of this active compound, whilst shortening the manufacturing process. When applied to titanium disks, the newly optimized coating was resilient to the most common sterilization procedures and it induced a 1 log reduction in biofilm cells of a clinical Staphylococcus aureus isolate (JAR060131) in vitro , without affecting the planktonic phase. Moreover, the antibiofilm effect of the coating in combination with the antibiotic cefuroxime was higher than cefuroxime treatment alone. Furthermore, the coating was successfully applied to a human-scale fracture fixation device resulting in a loading that was comparable to the titanium disk model. Finally, an in vivo biocompatibility and healing study in a rabbit osteotomy model indicated that these coated implants did not negatively affect fracture healing or osteointegration. These findings put our technology one step closer to clinical trials, confirming its potential in fighting orthopedic infections without compromising healing. [ABSTRACT FROM AUTHOR]

Fracture‐related infection (FRI) is a serious complication following musculoskeletal trauma. Accurate diagnosis and appropriate treatment depend on retrieving adequate deep tissue biopsies for bacterial culture. The aim of this cohort study was to compare intraoperative tissue cultures obtained by the Reamer‐Irrigator‐Aspirator system (RIA)‐system against standard tissue cultures obtained during the same surgical procedure. All patients had long bone fractures of the lower limbs and were assigned to the FRI or Control group based on the FRI consensus definition. The FRI group consisted of 24 patients with confirmed FRI and the Control group consisted of 21 patients with aseptic nonunion or chronic pain (in the absence of other suggestive/confirmatory criteria). Standard tissue cultures and cultures harvested by the RIA‐system showed similar results. In the FRI group, standard tissue cultures and RIA cultures revealed relevant pathogens in 67% and 71% of patients, respectively. Furthermore, in four FRI patients, cultures obtained by the RIA‐system revealed additional relevant pathogens that were not found by standard tissue culturing, which contributed to the optimization of the treatment plan. In the Control group, there were no false‐positive RIA culture results. As a proof‐of‐concept, this cohort study showed that the RIA‐system could have a role in the diagnosis of FRI as an adjunct to standard tissue cultures. Since scientific evidence on the added value of the RIA‐system in the management of FRI is currently limited, further research on this topic is required before its routine application in clinical practice. [ABSTRACT FROM AUTHOR]

Fracture-related infection (FRI) remains a challenging complication that creates a heavy burden for orthopaedic trauma patients, their families and treating physicians, as well as for healthcare systems. Standardization of the diagnosis of FRI has been poor, which made the undertaking and comparison of studies difficult. Recently, a consensus definition based on diagnostic criteria for FRI was published. As a well-established diagnosis is the first step in the treatment process of FRI, such a definition should not only improve the quality of published reports but also daily clinical practice. The FRI consensus group recently developed guidelines to standardize treatment pathways and outcome measures. At the center of these recommendations was the implementation of a multidisciplinary team (MDT) approach. If such a team is not available, it is recommended to refer complex cases to specialized centers where a MDT is available and physicians are experienced with the treatment of FRI. This should lead to appropriate use of antimicrobials and standardization of surgical strategies. Furthermore, an MDT could play an important role in host optimization. Overall two main surgical concepts are considered, based on the fact that fracture fixation devices primarily target fracture consolidation and can be removed after healing, in contrast to periprosthetic joint infection were the implant is permanent. The first concept consists of implant retention and the second consists of implant removal (healed fracture) or implant exchange (unhealed fracture). In both cases, deep tissue sampling for microbiological examination is mandatory. Key aspects of the surgical management of FRI are a thorough debridement, irrigation with normal saline, fracture stability, dead space management and adequate soft tissue coverage. The use of local antimicrobials needs to be strongly considered. In case of FRI, empiric broad-spectrum antibiotic therapy should be started after tissue sampling. Thereafter, this needs to be adapted according to culture results as soon as possible. Finally, a minimum follow-up of 12 months after cessation of therapy is recommended. Standardized patient outcome measures purely focusing on FRI are currently not available but the patient-reported outcomes measurement information system (PROMIS) seems to be the preferred tool to assess the patients' short and long-term outcome. This review summarizes the current general principles which should be considered during the whole treatment process of patients with FRI based on recommendations from the FRI Consensus Group.Level of evidence: Level V. [ABSTRACT FROM AUTHOR]

Background/aims: "Gentle" or "natural" cesarean sections are implemented to improve parental satisfaction. The objective of this study was to investigate whether there is a need for adopting such a gentle approach.Methods: We recruited those with low-risk pregnancies scheduled for elective cesarean delivery at term. Three questionnaires were administered to both partners: prior to delivery, 2-5 days after delivery, and 6 weeks postpartum. Questionnaires assessed the couple's expectations, fears, and satisfaction prior to and after cesarean section. Additionally, participants attended 2 structured interviews: one prior to delivery and one 6 weeks after delivery.Results: Fifteen couples underwent a "standard" cesarean section (group 1) and 6 underwent a "gentle" section (group 2). Overall, parental satisfaction with cesarean section was high. However, women in the standard group felt less involved in childbirth and both groups still preferred vaginal delivery in light of eventual future pregnancies. Participants in group 2 showed less fear of childbirth after delivery than prior to delivery. There were no differences in total questionnaire scores between groups or between mothers and partners.Conclusion: This study shows that there is room for improvement in satisfaction levels around cesarean section, even though satisfaction is generally high. A "gentle" cesarean section may help to achieve this. [ABSTRACT FROM AUTHOR]

Fracture-related infection (FRI) remains a challenging complication. It may result in permanent functional loss or even amputation in otherwise healthy patients. For these reasons, it is important to focus attention on prevention. In treatment algorithms for FRI, antibiotic stewardship programmes have already proved their use by means of a multidisciplinary collaboration between microbiologists, surgeons, pharmacists, infectious disease physicians and nursing staff. A similar approach, however, has not been described for infection prevention. As a first step towards achieving a multidisciplinary care package for infection prevention, this review summarises the most recent guidelines published by the World Health Organization (WHO) and US National Institutes of Health Centers for Disease Control and Prevention (CDC), primarily focusing on the musculoskeletal trauma patient. The implementation of these guidelines, together with close collaboration between infection control physicians, surgeons, anaesthesiologists and nursing staff, can potentially have a beneficial effect on the rate of FRI after musculoskeletal trauma surgery. It must be stated that most evidence presented here in support of these guidelines was not obtained from musculoskeletal trauma research. Although most preventive measures described in these studies can be generalised to the musculoskeletal trauma patient, there are still important differences with nontrauma patients that require further attention. Future research should therefore focus more on this very defined patient population and more specifically on FRI prevention. [ABSTRACT FROM AUTHOR]

In times where only a few novel antibiotics are to be expected, antimicrobial resistance remains an expanding global health threat. In case of chronic infections caused by therapy-resistant pathogens, physicians have limited therapeutic options, which are often associated with detrimental consequences for the patient. This has resulted in a renewed interest in alternative strategies, such as bacteriophage (phage) therapy. However, there are still important hurdles that currently impede the more widespread implementation of phage therapy in clinical practice. First, the limited number of good-quality case series and clinical trials have failed to show the optimal application protocol in terms of route of administration, frequency of administration, treatment duration and phage titer. Second, there is limited information on the systemic effects of phage therapy. Finally, in the past, phage therapy has been applied intuitively in terms of the selection of phages and their combination as parts of phage cocktails. This has led to an enormous heterogeneity in previously published studies, resulting in a lack of reliable safety and efficacy data for phage therapy. We hereby present a study protocol that addresses these scientific hurdles using a multidisciplinary approach, bringing together the experience of clinical, pharmaceutical and molecular microbiology experts. [ABSTRACT FROM AUTHOR]

Chronic rhinosinusitis is a common condition affecting 5–12% of the general population worldwide. In a limited number of cases, the disease is recalcitrant to medical and surgical interventions, causing a major impact on physical, social and emotional well-being and increasing pressure on healthcare systems. Biofilm formation and dysbiosis caused by Staphylococcus aureus and Pseudomonas aeruginosa play a role in the pathogenesis of recalcitrant chronic rhinosinusitis. In these cases, a promising treatment alternative is the application of bacteriophages, which are viruses that infect and lyse bacteria. In this review, we appraise the evidence for the use of bacteriophages in the treatment of recalcitrant chronic rhinosinusitis. Additionally, (dis)advantages of bacteriophages and considerations for implementation of phage therapy in otorhinolaryngology practice will be discussed. [ABSTRACT FROM AUTHOR]

Bacteriophage therapy has recently attracted increased interest, particularly in difficult-to-treat infections. Although it is not a novel concept, standardized treatment guidelines are currently lacking. We present the first steps towards the establishment of a "multidisciplinary phage task force" (MPTF) and a standardized treatment pathway, based on our experience of four patients with severe musculoskeletal infections. After review of their medical history and current clinical status, a multidisciplinary team found four patients with musculoskeletal infections eligible for bacteriophage therapy within the scope of Article 37 of the Declaration of Helsinki. Treatment protocols were set up in collaboration with phage scientists and specialists. Based on the isolated pathogens, phage cocktails were selected and applied intraoperatively. A draining system allowed postoperative administration for a maximum of 10 days, 3 times per day. All patients received concomitant antibiotics and their clinical status was followed daily during phage therapy. No severe side-effects related to the phage application protocol were noted. After a single course of phage therapy with concomitant antibiotics, no recurrence of infection with the causative strains occurred, with follow-up periods ranging from 8 to 16 months. This study presents the successful outcome of bacteriophage therapy using a standardized treatment pathway for patients with severe musculoskeletal infection. A multidisciplinary team approach in the form of an MPTF is paramount in this process. [ABSTRACT FROM AUTHOR]