Efficacy of different bioactive glass S53P4 formulations in biofilm eradication and the impact of pH and osmotic pressure.

AIM: The challenging properties of biofilm-associated infections and the rise of multidrug-resistant bacteria are prompting the exploration of alternative treatment options. This study investigates the efficacy of different bioactive glass (BAG) formulations - alone or combined with vancomycin - to eradicate biofilm. Further, we study the influence of BAG on pH and osmotic pressure as important factors limiting bacterial growth. METHOD: Different BAG S53P4 formulations were used for this study, including (a) powder (<45 µm), (b) granules (500-800 µm), (c) a cone-shaped scaffold and (d) two putty formulations containing granules with no powder (putty A) or with additional powder (putty B) bound together by a synthetic binder. Inert glass beads (1.0-1.3 mm) were included as control. All formulations were tested in a concentration of 1750 mg/ml in Müller-Hinton-Broth against methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant Staphylococcus epidermidis (MRSE). Vancomycin was tested at the minimum-inhibitory concentration for each strain. Changes in pH and osmolality over time were assessed at 0 h, 24 h, 72 h and 168 h. RESULTS: All tested BAG formulations showed antibiofilm activity against MRSA and MRSE. Powder and putty B were the most effective formulations suppressing biofilm leading to its complete eradication after up to 168 h of co-incubation, followed by granules, scaffold and putty A. In general, MRSE appeared to be more susceptible to bioactive glass compared to MRSA. The addition of vancomycin had no substantial impact on biofilm eradication. We observed a positive correlation between a higher pH and higher antibiofilm activity. CONCLUSIONS: BAG S53P4 has demonstrated efficient biofilm antibiofilm activity against MRSA and MRSE, especially in powder-containing formulations, resulting in complete eradication of biofilm. Our data indicate neither remarkable increase nor decrease in antimicrobial efficacy with addition of vancomycin. Moreover, high pH appears to have a direct antimicrobial impact; the role of high osmolality needs further investigation.

SUCCESS RATE AFTER 2-STAGE SPACER-FREE TOTAL HIP ARTHROPLASTY EXCHANGE AND RISK FACTORS FOR REINFECTION: A PROSPECTIVE COHORT STUDY OF 187 PATIENTS.

BACKGROUND: Two-stage prosthesis exchange is the treatment of choice for chronic periprosthetic joint infection (PJI) of a total hip arthroplasty (THA), especially when the bone and surrounding soft tissues are compromised or difficult-to-treat pathogens are implicated. THE AIMS OF OUR STUDY WERE: (1) to determine the outcome of two-stage prosthesis exchange for the treatment of PJI after THA; and (2) to determine risk factors for reinfection leading to subsequent revision surgeries after reimplantation. METHODS: We prospectively enrolled 187 consecutive patients who underwent a two-stage THA exchange with resection arthroplasty for PJI from 2013 to 2019. The mean (± SD [standard deviation]) duration of follow-up was 54.2 ± 24.9 months (range, 36 to 96), and the mean interval until reimplantation was 9.8 ± 8.9 weeks (range, 2 to 38). All patients remained in a spacer-free girdlestone situation between the two stages of treatment. Patients who remained infection-free after their two-stage treatment were considered to have achieved treatment success. RESULTS: The overall success rate was 85.6%. The cumulative probability of reinfection was 11.5% after one year and 14% after two years after reimplantation. High virulence or DTT (difficult-to-treat) pathogens were significant and independent risk factors for reinfection (HR [hazard ratio] = 3.71, 95% CI [confidence interval]: 1.47 to 9.36, P = 0.006 and HR = 3.85, 95% CI: 1.73 to 8.57, respectively, P = 0.001), as was previous two-stage hip prosthesis exchange (HR = 3.58, 95% CI: 1.33 to 9.62, P = 0.01). Overall reoperation and revision rates were 26.2 and 16.6%, respectively. Re-infected patients had an 80% higher probability of reoperation than non-infected ones (P < 0.001, log-rank = 102.6), and they were 55% more likely to undergo revision surgery during their follow-up (P < 0.001, log-rank = 55.4). CONCLUSION: Reinfection rates after two-stage spacer-free THA revision for PJI still remain high, but are comparable to those including cement spacers. Patients who have had prior failed two-stage implant exchanges or are infected by high-grade or difficult-to-treat pathogens are at high risk for treatment failure.

The Safety and Efficacy of Microporous Polysaccharide Hemospheres in Terms of the Complication Rates in Total Hip Arthroplasty for Femoral Neck Fractures: A Control-Matched Retrospective Cohort.

AIMS: This study aimed to assess the safety and efficacy of microporous polysaccharide hemospheres (MPSHs) in managing blood loss and reducing the risk of postoperative haematoma and early periprosthetic joint infection (PJI) following total hip arthroplasty (THA) for femoral neck fracture (FNF), in the context of the existing treatment challenges. METHODS: A control-matched retrospective analysis of 163 patients undergoing unilateral primary THA for displaced FNF between 2020 and 2023 was performed. The study group consisted of 74 patients who received MPSH administered intraoperatively. The control group consisted of 89 patients who received no topical haemostatics. One-to-one case-control matching between groups was performed. The primary outcome was a perioperative change in the haematologic values (haemoglobin, red blood cell count, haematocrit, platelet concentration) and transfusion rate. The secondary outcomes were the incidence of postoperative local haematoma formation, prolonged wound secretion, surgical site infection (SSI), and PJI within 3 months of surgery. RESULTS: Our analysis found no statistically significant differences in the haematologic parameters between the control and study cohorts. The changes in the haemoglobin concentration were not significant between the control group (3.18 ± 1.0 g/dL) and the treatment group (2.87 ± 1.15 g/dL) (p = 0.3). There were no significant differences (p = 0.24) in the haematocrit and red blood cell concentration (p = 0.15). The platelet levels did not significantly differ (p = 0.12) between the groups. Additionally, we found no significant discrepancy in the incidence of early PJI or blood transfusion rates between the groups. No adverse effects following MPSH use were recorded in the study group. CONCLUSIONS: Routine use of MPSH in THA for FNF management appears to be safe, with no observed adverse events related to Arista® use. Although there was a tendency towards reduced blood loss in the Arista® AH group, MPSH did not significantly impact bleeding complications, local haematoma formation, or subsequent PJI.

Adverse Events Associated with Prolonged Antibiotic Therapy for Periprosthetic Joint Infections-A Prospective Study with a Special Focus on Rifampin.

Periprosthetic Joint Infection (PJI) is a significant contributor to patient morbidity and mortality, and it can be addressed through a range of surgical interventions coupled with antibiotic therapies. Following surgical intervention(s), prolonged administration of oral antibiotics is recommended to cure PJI. There is a lack of reports on the adverse events (AEs) associated with oral antibiotics, particularly rifampin. This investigation sought to elucidate the occurrence of antibiotic-related AEs after an initial regimen of intravenous antibiotic administration, supplemented by an extended course of oral antibiotics. A prospective study of patients diagnosed with PJI of the hip, knee, or shoulder who underwent single-stage exchange arthroplasty (SSE) (10%), two-stage exchange arthroplasty (TSE) (81%), or debridement, antibiotics, and implant retention (DAIR) (6%) was performed. The primary outcome of interest was the detection of AEs, the secondary outcome the detection of a correlation between rifampin use and the incidence of AEs, and the tertiary outcome was whether oral antibiotic treatment needed to be adjusted or discontinued due to AEs. In addition, subjective tolerability was monitored throughout the study. A total of 336 events were identified for 73 out of 80 patients. The most frequently used antibiotics were rifampin and co-trimoxazole. Most AEs occurred in the gastrointestinal tract (46%). The most frequent AEs were nausea, inappetence, diarrhea, and skin rash. In 6% of cases, the AEs led to antibiotic discontinuation, and in 29% of cases, a dose adjustment of the oral therapy occurred, mainly with amoxicillin or co-trimoxazole. The majority of patients (55%) rated the subjective tolerability as good. In conclusion, AEs during antibiotic treatment for PJI are common. They mainly affect the gastrointestinal tract. Rifampin use might be a reason for the higher incidence of AEs compared to non-rifampin antibiotic treatment.

Alginate microbeads and hydrogels delivering meropenem and bacteriophages to treat Pseudomonas aeruginosa fracture-related infections.

Bacteriophage (phage) therapy has shown promise in treating fracture-related infection (FRI); however, questions remain regarding phage efficacy against biofilms, phage-antibiotic interaction, administration routes and dosing, and the development of phage resistance. The goal of this study was to develop a dual antibiotic-phage delivery system containing hydrogel and alginate microbeads loaded with a phage cocktail plus meropenem and evaluate efficacy against muti-drug resistant Pseudomonas aeruginosa. Two phages (FJK.R9-30 and MK.R3-15) displayed enhanced antibiotic activity against P. aeruginosa biofilms when tested in combination with meropenem. The antimicrobial activity of both antibiotic and phage was retained for eight days at 37 °C in dual phage and antibiotic loaded hydrogel with microbeads (PA-HM). In a mouse FRI model, phages were recovered from all tissues within all treatment groups receiving dual PA-HM. Moreover, animals that received the dual PA-HM either with or without systemic antibiotics had less incidence of phage resistance and less serum neutralization compared to phages in saline. The dual PA-HM could reduce bacterial load in soft tissue when combined with systemic antibiotics, although the infection was not eradicated. The use of alginate microbeads and injectable hydrogel for controlled release of phages and antibiotics, leads to the reduced development of phage resistance and lower exposure to the adaptive immune system, which highlights the translational potential of the dual PA-HM. However, further optimization of phage therapy and its delivery system is necessary to achieve higher bacterial killing activity in vivo in the future.

Are Hamstring Grafts a Predisposing Factor to Infection in R-ACL Surgery? A Comparative In Vitro Study.

BACKGROUND: The objective of the present study was to evaluate the formation of biofilms in bone patellar tendon bone grafts (BPTB grafts), and to compare it to the formation of biofilm formation in quadrupled hamstring anterior cruciate ligament grafts (4×Ht graft). METHODS: A descriptive in vitro study was conducted. One 4×Ht graft and one BPTB graft were prepared. They were then contaminated with a strain of S. epidermidis. Later, a quantitative analysis was conducted by means of microcalorimetry and sonication with plating. Additionally, a qualitative analysis was conducted by means of electron microscopy. RESULTS: No significant differences were found between the bacterial growth profiles of the 4×Ht graft and the BPTB graft in microcalorimetry and colony counting. In the samples analyzed with electron microscopy, no specific biofilm growth pattern was identified upon comparing the BPTB graft to the 4×Ht graft. CONCLUSIONS: There were no significant differences found at either the quantitative or qualitative level when comparing bacterial growth in the BPTB graft to that in the 4×Ht graft. Therefore, the presence of sutures in the 4×Ht graft cannot be established as a predisposing factor for increased biofilm growth in this in vitro study.

Voriconazole Admixed with PMMA-Impact on Mechanical Properties and Efficacy.

BACKGROUND: There are currently no recommendations to direct the optimal diagnosis and treatment of fungal osteoarticular infections, including prosthetic joint infections and osteomyelitis. Active agents (fluconazole; amphotericin B) are regularly applied per os or intravenously. Other drugs such as voriconazole are used less frequently, especially locally. Voriconazole is less toxic and has promising results. Local antifungal medication during primary surgical treatment has been investigated by implanting an impregnated PMMA cement spacer using intra-articular powder or by daily intra-articular lavage. The admixed dosages are rarely based on characteristic values and microbiological and mechanical data. The purpose of this in vitro study is to investigate the mechanical stability and efficacy of antifungal-admixed PMMA with admixed voriconazole at low and high concentrations. METHODS: Mechanical properties (ISO 5833 and DIN 53435) as well as efficacy with inhibition zone tests with two Candida spp. were investigated. We tested three separate cement bodies at each measuring time (n = 3) Results: Mixing high dosages of voriconazole causes white specks on inhomogeneous cement surfaces. ISO compression, ISO bending, and DIN impact were significantly reduced, and ISO bending modulus increased. There was a high efficacy against C. albicans with low and high voriconazole concentrations. Against C. glabrata, a high concentration of voriconazole was significantly more efficient than a dose at a low concentration. CONCLUSIONS: Mixing voriconazole powder with PMMA (Polymethylmethacrylate) powder homogeneously is not easy because of the high amount of dry voriconazole in the powder formulation. Adding voriconazole (a powder for infusion solutions) has a high impact on its mechanical properties. Efficacy is already good at low concentrations.

Interdisciplinary Infection Prevention and Control Bundle in Neurosurgical Patients: Results of a Prospective Cohort Study.

BACKGROUND: Surgical site infections (SSIs) account for one of the most common causes of nosocomial infections. Bundle approaches for infection prevention and control do not capture the full complexity of neurosurgical interventions. OBJECTIVE: To study the efficacy of an interdisciplinary infection prevention and control bundle (IPCB) in neurosurgery. METHODS: This was a prospective, single-center, observational study, analyzing 3 periods: before (2014), during (2017), and after (2019) full implementation of IPCB. IPCB included the following infection prevention measures: preoperative decolonization, patient engagement, operating room (OR) hygiene protocol, and pre-, peri-, and postoperative standard operating procedures (SOPs) while infection control measures included intraoperative sonication, blood culture inoculation, and interdisciplinary SSI management. All neurosurgical patients being readmitted to the hospital for SSIs within 90 days after receiving index surgery were included in the trial (403/9305). RESULTS: Implementation of IPCB resulted in more frequently succeeded pathogen isolation in patients with SSI (2014: 138 isolates in 105 (83%) patients with SSI, 2017: 169 isolates in 124 (91%) patients with SSI, and 2019: 199 isolates in 136 (97%) patients with SSI; P < .001). Proportion of gram-positive SSI and virulence was declining ( P = .041, P = .007). The number of repeated revision surgeries decreased from 26 (20%) in 2014 and 31 (23%) in 2017 to 18 (13%) in 2019 ( P = .085). Significantly, fewer patients experienced sepsis in response to SSI (2014: 12%, 2017: 10%, and 2019: 3.6%, P = .035). In-hospital mortality rate was declining from 12 (9.4%) in 2014 to 9 (6.6%) in 2017 to 5 (3.6%) in 2019 ( P = .148). CONCLUSION: Introducing an interdisciplinary IPCB in neurosurgery leads to a significant reduction of sepsis and decreased in-hospital mortality while a pathogen switch toward gram-negative bacteria was observed. Minimizing diagnostic gap of pathogen detection toward a more efficient anti-infective treatment may be the main reason for the substantial decrease in morbidity and mortality.

Local Antibiotic Delivery Options in Prosthetic Joint Infection.

Prosthetic Joint Infection (PJI) causes significant morbidity and mortality for patients globally. Delivery of antibiotics to the site of infection has potential to improve the treatment outcomes and enhance biofilm eradication. These antibiotics can be delivered using an intra-articular catheter or combined with a carrier substance to enhance pharmacokinetic properties. Carrier options include non-resorbable polymethylmethacrylate (PMMA) bone cement and resorbable calcium sulphate, hydroxyapatite, bioactive glass, and hydrogels. PMMA allows for creation of structural spacers used in multi-stage revision procedures, however it requires subsequent removal and antibiotic compatibility and the levels delivered are variable. Calcium sulphate is the most researched resorbable carrier in PJI, but is associated with wound leakage and hypercalcaemia, and clinical evidence for its effectiveness remains at the early stage. Hydrogels provide a versatile combability with antibiotics and adjustable elution profiles, but clinical usage is currently limited. Novel anti-biofilm therapies include bacteriophages which have been used successfully in small case series.

Global research characteristics and trends of infection after spinal implant surgery: a bibliometric analysis.

Background: With the growing awareness of postoperative infection, increasing focus has been placed on infection after spinal implant surgery (IASIS). This study aimed to explore the development and trends of research regarding IASIS using bibliometric analysis. Methods: Scientific articles on IASIS research published between February 1, 2000, and December 31, 2020 were retrieved from the Web of Science database. Results: A total of 820 publications were included in the bibliometric analysis, with studies originating from 46 countries and 6 languages. Researchers from the United States published the highest number of articles and collaborated closely with researchers in Canada, Germany, and Japan. The author with the most publications was Alexander R. Vaccaro. The journal with the most articles and citations was Spine. Most of the research was performed on risk factors and the incidence of IASIS. Co-occurrence analysis revealed that the most recent research trend was likely related to the management of IASIS and the international consensus meeting. Three clusters of research were identified through a thematic map: diagnosis and treatment of IASIS, scoliosis-related infection, and risk factors and prevention of IASIS. Conclusions: Research on IASIS increasingly grew between 2000 and 2020. Spinal surgeons and institutes from the United States had the highest number of publications and academic impact in this field. Diagnosis-related problems and multidisciplinary work on IASIS require further attention in the future. Current trends in IASIS are likely associated with IASIS management and the international consensus meeting.

Prevention of Surgical Site Infections in Spine Surgery: An International Survey of Clinical Practices Among Expert Spine Surgeons.

STUDY DESIGN: Questionnaire-based survey. OBJECTIVES: Surgical site infection (SSI) is a common complication in spine surgery but universal guidelines for SSI prevention are lacking. The objectives of this study are to depict a global status quo on implemented prevention strategies in spine surgery, common themes of practice and determine key areas for future research. METHODS: An 80-item survey was distributed among spine surgeons worldwide via email. The questionnaire was designed and approved by an International Consensus Group on spine SSI. Consensus was defined as more than 60% of participants agreeing to a specific prevention strategy. RESULTS: Four hundred seventy-two surgeons participated in the survey. Screening for Staphylococcus aureus (SA) is not common, whereas preoperative decolonization is performed in almost half of all hospitals. Body mass index (BMI) was not important for surgery planning. In contrast, elevated HbA1c level and hypoalbuminemia were often considered as reasons to postpone surgery. Cefazoline is the common drug for antimicrobial prophylaxis. Alcohol-based chlorhexidine is mainly used for skin disinfection. Double-gloving, wound irrigation, and tissue-conserving surgical techniques are routine in the operating room (OR). Local antibiotic administration is not common. Wound closure techniques and postoperative wound dressing routines vary greatly between the participating institutions. CONCLUSIONS: With this study we provide an international overview on the heterogeneity of SSI prevention strategies in spine surgery. We demonstrated a large heterogeneity for pre-, peri- and postoperative measures to prevent SSI. Our data illustrated the need for developing universal guidelines and for testing areas of controversy in prospective clinical trials.

The role of biopsy in diagnosing infection after hip and knee arthroplasty: a meta-analysis.

INTRODUCTION: Early diagnosis of periprosthetic hip and knee infection still represents a major challenge, as no single test can achieve ideal results. Currently, multiple preoperative indicators were performed to diagnose periprosthetic joint infection (PJI) to confirm or exclude infection in the early stage. However, the diagnostic value of biopsy-related tests in diagnosing periprosthetic hip and knee infection remains unclear. MATERIALS AND METHODS: Publications in PubMed, Embase, and the Web of Science databases were searched systematically until October 2020. Inclusion and exclusion criteria were used for screening biopsy-related studies of the diagnosis of periprosthetic hip and knee infection. RESULTS: Three biopsy-related tests were identified in 14 articles and further analyzed in the present meta-analysis. The combined method had the highest value for the area under the curve (0.9805), followed by histology (0.9425) and microbiological tests (0.9292). In the subgroup, statistical differences were identified in sensitivity and specificity for PJI diagnosis between the synovial fluid culture and biopsy culture group, as well as in the biopsy-related combined method and serum C-reactive protein. CONCLUSIONS: Biopsy culture does not appear to be advantageous compared to synovial fluid culture in the preoperative diagnosis of periprosthetic hip and knee infection. In contrast, combined biopsy microbial culture with histology analysis shows great potential in improving the preoperative diagnosis of PJI. The standard procedure of biopsy needs to be further explored. Further research is required to verify our results.

Surgical Site Infections Associated With Implanted Pulse Generators for Deep Brain Stimulation: Meta-Analysis and Systematic Review.

OBJECTIVES: The aim of this study was to identify and systematically analyze relevant literature on surgical site infections (SSIs) associated with implantable pulse generator (IPG) procedures for deep brain stimulation (DBS). MATERIALS AND METHODS: In compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we conducted a systematic review and meta-analyses of 58 studies that reported SSI rates of 11,289 patients and 15,956 IPG procedures. A meta-analysis of proportions was performed to estimate the pooled proportion of SSIs across DBS procedures in general and to estimate the proportion of SSIs that occur at the IPG pocket. Moreover, a meta-analysis of odds ratio (OR) was conducted on those studies that reported their results of applying topical vancomycin powder during closure of the IPG wound. Results are presented as rates and OR with 95% CIs. RESULTS: The pooled proportion of SSIs was 4.9% (95% CI, 4.1%-6.1%) among all DBS procedures. The dominant SSI localization was the IPG pocket in 61.2% (95% CI, 53.4%-68.5%). A trend toward a beneficial effect of vancomycin powder over standard wound closure was found with an OR of 0.46 (95% CI, 0.21-1.02). Most studies (79.1%) that reported their treatment strategy in case of SSI had a strict protocol of removal of the IPG, followed by antimicrobial treatment and reimplantation of the IPG once the SSI had been eradicated. CONCLUSIONS: The IPG pocket was identified as the main site of SSI after DBS procedures. Most studies recommend complete IPG removal, antimicrobial treatment, and reimplantation of an IPG once the SSI has been eradicated. Future studies are needed to clarify the role of alternative approaches (eg, topical vancomycin powder) in the prevention of SSI associated with IPG.

Phage-Based Control of Methicillin Resistant Staphylococcus aureus in a Galleria mellonella Model of Implant-Associated Infection.

Staphylococcus aureus implant-associated infections are difficult to treat because of the ability of bacteria to form biofilm on medical devices. Here, the efficacy of Sb-1 to control or prevent S. aureus colonization on medical foreign bodies was investigated in a Galleria mellonella larval infection model. For colonization control assays, sterile K-wires were implanted into larva prolegs. After 2 days, larvae were infected with methicillin-resistant S. aureus ATCC 43300 and incubated at 37 °C for a further 2 days, when treatments with either daptomycin (4 mg/kg), Sb-1 (107 PFUs) or a combination of them (3 x/day) were started. For biofilm prevention assays, larvae were pre-treated with either vancomycin (10 mg/kg) or Sb-1 (107 PFUs) before the S. aureus infection. In both experimental settings, K-wires were explanted for colony counting two days after treatment. In comparison to the untreated control, more than a 4 log10 CFU and 1 log10 CFU reduction was observed on K-wires recovered from larvae treated with the Sb-1/daptomycin combination and with their singular administration, respectively. Moreover, pre-infection treatment with Sb-1 was found to prevent K-wire colonization, similarly to vancomycin. Taken together, the obtained results demonstrated the strong potential of the Sb-1 antibiotic combinatory administration or the Sb-1 pretreatment to control or prevent S. aureus-associated implant infections.

Novel Stenotrophomonas maltophilia Bacteriophage as Potential Therapeutic Agent.

A novel bacteriophage CUB19 specific to the bacterial species Stenotrophomonas maltophilia was isolated from hospital sewage and characterized as a new species belonging to a proposed new phage genus 'Cubvirus' (Caudoviricetes). Its genome contains a total of 48,301 bp and 79 predicted genes, among which some have been associated with packaging and lysis-associated proteins, structural proteins, or DNA- and metabolism-associated proteins. No lysogeny-associated proteins or known virulence proteins were identified on the phage genome. CUB19 showed stability over a wide range of temperatures (-20 °C-60 °C) and pH values (pH 3-pH 13). Despite its narrow host range, this phage has potent observed antimicrobial and antibiofilm activity. A time-killing curve assay showed significant biofilm reduction after 24 h exposure to CUP19. Isothermal microcalorimetry assays investigating phage-antibiotic combinations revealed the effectiveness of CUB19 during co-administration with increasing antibiotic doses, regardless of the administration approach (simultaneous or staggered). These are encouraging indications for its application as a targeted therapeutic agent against resilient biofilm-associated Stenotrophomonas infections.

In Vitro Evaluation of Five Newly Isolated Bacteriophages against E. faecalis Biofilm for Their Potential Use against Post-Treatment Apical Periodontitis.

State-of-the-art treatment of root canal infection includes the use of mechanical debridement and chemical agents. This disinfection method is limited, and microorganisms can remain in the canal system. Enterococcus faecalis appears with a high prevalence in secondary and persistent root canal infections and can be linked to endodontic treatment failure due to its various resistance mechanisms. Here, we evaluated the activity of newly isolated bacteriophages against clinical isolates of E. faecalis (including one vancomycin- and gentamicin-resistant strain) as a single treatment or in combination with gentamicin and vancomycin. For the resistant strain, daptomycin and fosfomycin were tested. Sixteen E. faecalis strains were used to screen for the presence of bacteriophages in sewage. Five different bacteriophages were characterized in terms of virion morphology, host range and killing-kinetics against each E. faecalis host strain. To investigate the antibiofilm effect of antibiotic and phages, E. faecalis biofilm was grown on porous glass beads and treated with different antibiotic concentrations and with isolated bacteriophages alone or in staggered combinations. A strong biofilm reduction was observed when phages were combined with antibiotic, where combinations with gentamicin showed a better outcome compared to vancomycin. Regarding the resistant strain, daptomycin had a superior antibiofilm effect than fosfomycin.

Novel Bacteriophage Specific against Staphylococcus epidermidis and with Antibiofilm Activity.

Staphylococcus epidermidis has emerged as the most important pathogen in infections related to indwelling medical devices, and although these infections are not life-threatening, their frequency and the fact that they are extremely difficult to treat represent a serious burden on the public health system. Treatment is complicated by specific antibiotic resistance genes and the formation of biofilms. Hence, novel therapeutic strategies are needed to fight these infections. A novel bacteriophage CUB-EPI_14 specific to the bacterial species S. epidermidis was isolated from sewage and characterized genomically and phenotypically. Its genome contains a total of 46,098 bp and 63 predicted genes, among which some have been associated with packaging and lysis-associated proteins, structural proteins, or DNA- and metabolism-associated proteins. No lysogeny-associated proteins or known virulence proteins were identified in the phage genome. CUB-EPI_14 showed stability over a wide range of temperatures (from -20 °C to 50 °C) and pH values (pH 3-pH 12) and a narrow host range against S. epidermidis. Potent antimicrobial and antibiofilm activities were observed when the phage was tested against a highly susceptible bacterial isolate. These encouraging results open the door to new therapeutic opportunities in the fight against resilient biofilm-associated infections caused by S. epidermidis.

Microbiological Advantages of Open Incisional Biopsies for the Diagnosis of Suspected Periprosthetic Joint Infections.

BACKGROUND: Periprosthetic joint infection (PJI) represents a serious complication following total hip (THA) and knee arthroplasty (TKA). When preoperative synovial fluid cultures remain inconclusive, open incisional joint biopsy (OIB) can support causative microorganism identification. OBJECTIVE: This study investigates the potential benefit of OIB in THA and TKA patients with suspected PJI and ambigious diagnostic results following synovial fluid aspiration. METHODS: We retrospectively assessed all patients treated from 2016 to 2020 with suspected PJI. Comparing the microbiology of OIB and the following revision surgery, we calculated sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and the number needed to treat (NNT). RESULTS: We examined the diagnostic validity of OIB in 38 patients (20 female) with a median age of 66.5 years. In THA patients (n = 10), sensitivity was 75%, specificity was 66.67%, PPV was 60%, NPV was 80%, and NNT was 2.5. In TKA patients (n = 28), sensitivity was 62.5%, specificity was 95.24%, PPV was 83.33%, NPV was 86.96%, and NNT was 1.42. CONCLUSIONS: Our results indicate that OIB represents an adequate diagnostic tool when previously assessed microbiological results remain inconclusive. Particularly in TKA patients, OIB showed an exceptionally high specificity, PPV, and NPV, whereas the predictive validity of the diagnosis of PJI in THA patients remained low.

Outcome Analysis of the Use of Cerament® in Patients with Chronic Osteomyelitis and Corticomedullary Defects.

BACKGROUND: Chronic osteomyelitis (OM) is a progressive but mostly low-grade infection of the bones. The management of this disease is highly challenging for physicians. Despite systematic treatment approaches, recurrence rates are high. Further, functional and patient-reported outcome data are lacking, especially after osseous defects are filled with bioresorbable antibiotic carriers. OBJECTIVE: To assess functional and patient-reported outcome measures (PROM) following the administration of Cerament® G or V due to corticomedullary defects in chronic OM. METHODS: We conducted a retrospective study from 2015 to 2020, including all patients who received Cerament® for the aforementioned reason. Patients were diagnosed and treated in accordance with globally valid recommendations, and corticomedullary defects were filled with Cerament® G or V, depending on the expected germ spectrum. Patients were systematically followed up, and outcome measures were collected during outpatient clinic visits. RESULTS: Twenty patients with Cierny and Mader type III OM were included in this study and followed up for 20.2 ± 17.2 months (95%CI 12.1-28.3). Ten of these patients needed at least one revision (2.0 ± 1.3 revisions per patient (95%CI 1.1-2.9) during the study period due to OM persistence or local wound complications. There were no statistically significant differences in functional scores or PROMs between groups. CONCLUSION: The use of Cerament® G and V in chronic OM patients with corticomedullary defects appears to have good functional outcomes and satisfactory PROMs. However, the observed rate of local wound complications and the OM persistence rate may be higher when compared to previously published data.

Photocatalytic Quantum Dot-Armed Bacteriophage for Combating Drug-Resistant Bacterial Infection.

Multidrug-resistant (MDR) bacterial infection is one of the greatest challenges to public health, a crisis demanding the next generation of highly effective antibacterial agents to specifically target MDR bacteria. Herein, a novel photocatalytic quantum dot (QD)-armed bacteriophage (QD@Phage) is reported for combating green fluorescent protein-expressing Pseudomonas aeruginosa (GFP-P. aeruginosa) infection. The proposed QD@Phage nanosystem not only specifically binds to the host GFP-P. aeruginosa while preserving the infectivity of the phage itself, but also shows a superior capacity for synergistic bacterial killing by phage and by the photocatalytic localized reactive oxygen species (ROS) generated from anchored QD components. Notably, this highly targeted QD@Phage nanosystem achieves robust in vitro antibacterial elimination for both planktonic (over 99.9%) and biofilm (over 99%) modes of growth. In a mouse wound infection model, this system also shows remarkable activity in eliminating the wound infection and promoting its recovery. These results demonstrate that the novel QD@Phage nanosystem can diversify the existing pool of antibacterial agents and inspire the development of promising therapeutic strategies against MDR bacterial infection.