Feasibility of using bacteriophage therapy to treat Staphylococcal aureus fracture-related infections.

OBJECTIVE: Staphylococcus aureus fracture-related infections (FRIs) are associated with significant morbidity in part because conventional antibiotic therapies have limited ability to eradicate S. aureus in sessile states. Therefore, the objective of this study was to assess the feasibility of using Staphylococcal bacteriophages for FRI by testing the activity of a library of Staphylococcal bacteriophage therapeutics against historically preserved S. aureus FRI clinical isolates. METHODS: Current Procedural Terminology codes were used to identify patients with FRI from January 1, 2021 to December 31, 2021. Preserved S. aureus FRI isolates from the cases were then tested against a library of 51 Staphylococcal bacteriophages from an American company. This was conducted by assessing the ability of bacteriophages to reduce bacterial growth over time. Growth inhibition greater than 16 h was considered adequate for this study. RESULTS: All of the S. aureus preserved clinical isolates had at least one bacteriophage with robust lytic activity and six bacteriophages (11.8 %) had robust lytic activity to seven or more of the clinical isolates. However, 41 of the bacteriophages (80.4 %) had activity to less than three of the clinical isolates and no bacteriophage had activity to all the clinical isolates. CONCLUSION: Our findings show that Staphylococcal bacteriophage therapeutics are readily available for S. aureus FRI clinical isolates. However, when correlated with the current barriers to using bacteriophages to treat FRI, designated Staphylococcal bacteriophage cocktails with broad spectrum activity should be created.

The Location of Biofilms on Chronic Prosthetic Joint Infections and the Ramifications for Clinical Practice.

Revision surgery is paramount to cure chronic prosthetic joint infections because these infections are associated with biofilms on prosthetics that conventional antibiotics cannot eradicate. However, there is a paucity of research on where in vivo biofilms are located on infected prosthetics. Consequently, the objective of this pilot study was to address this gap in knowledge by staining 5 chronically infected prosthetics, that were removed at the time of revision surgery, with methylene blue. Scanning electron microscopic images were then taken of the methylene blue-stained areas to visualize biofilms. The findings show that all chronically infected prosthetics had biofilms located on the bone-prosthetic interface, yet only 2 had biofilms also located on the prosthetic interface exposed to synovial fluid. Subsequently, this pilot study provides a pathophysiological understanding of why the current treatment paradigm for chronic periprosthetic joint infection requires a revision surgery and not debridement and an implant retention surgery.

Are Biodegradable Calcium Sulfate Antibiotic Beads Effective and Safe Adjuvants for Diabetic Foot Osteomyelitis?

INTRODUCTION:  Diabetic foot osteomyelitis (DFO) is a highly morbid condition that commonly affects diabetic patients. Biodegradable calcium-sulfate antibiotic beads (CaSO4) are theoretical adjuvant agents to reduce morbidity in DFO. However, there is a paucity of research on the safety and effectiveness of CaSO4 beads in DFO. Therefore, the purpose of this study was to assess the safety and effectiveness of CaSO4 beads in different DFO locations. METHODS: We conducted a retrospective cohort study between January 1, 2015 and January 1, 2022 of patients with DFO who underwent surgical intervention and adjuvant CaSO4 beads placement. The location of DFO was determined based on the forefoot, midfoot, or hindfoot locations. Outcomes measured were ulcer-free time points of three and six months as well as recurrence of DFO at 12 months. Safety was also evaluated with incidences of acute kidney injury, wound drainage, and hypercalcemia. RESULTS: Forty-five cases were included. Of these, only 9/45 (20%) and 13/45 (29%) were ulcer-free at three months and six months, respectively. DFO recurred in 19/45 (42%) patients. Safety outcomes were significant for wound drainage (62%) and acute kidney injury (9%). Stratifying according to the location of DFO showed no statistically significant difference in outcomes. CONCLUSION: In this cohort study, adjuvant CaSO4 beads showed high rates of ulcer persistence and DFO recurrence. Given the limited benefits seen here and the potential for high rates of wound drainage, the use of adjuvant CaSO4 beads should be used cautiously until a multicenter randomized clinical trial is conducted to definitely evaluate the safety and effectiveness of CaSO4 beads in DFO.

Risk Factors for Infection Recurrence After Surgical Resection of Advanced Stage Osteonecrosis of the Mandible.

BACKGROUND: Advanced stage osteoradionecrosis (ORN) and medication-related osteonecrosis of the jaw (MRONJ) are challenging disease entities requiring multimodal therapy including surgical resection. However, risk factors associated with infection recurrence are poorly understood. PURPOSE: The purpose of this study was to identify risk factors associated with infection recurrence following resection of advanced stage ORN or MRONJ of the mandible. STUDY DESIGN, SETTING, SAMPLE: This was a retrospective cohort study including patients who underwent segmental mandibulectomy for management of ORN or MRONJ between 2016 and 2021 at the authors' institution. Subjects who did not have margin viability data were excluded. PREDICTOR/EXPOSURE/INDEPENDENT VARIABLE: The primary predictor variable was viability of resection margins on histopathologic analysis (viable or nonviable). Secondarily, other risk factors categorized as demographic (age, sex, race), medical (comorbidities), and perioperative (reconstructive modality, antibiotic duration, microbiological growth) were evaluated. MAIN OUTCOME VARIABLE: The primary outcome variable was time to infection recurrence defined as time from surgical resection to clinical diagnosis of a fistula tract, abscess, or persistent inflammatory symptoms necessitating surgical intervention. COVARIATES: Not applicable. ANALYSES: Descriptive and bivariate statistics were used to identify associations between risk factors and time to infection recurrence. A significance level of P ≤ .05 was considered significant. RESULTS: The cohort consisted of 57 subjects with a mean age of 63.3 ± 10.0 years (71.9% Male, 75.4% White) treated for ORN (47.4%) or MRONJ (52.6%). A total of 19/57 (33%) subjects developed a recurrence of infection with 1 and 2 year survival of 75.8 and 66.2%, respectively. Nonviable resection margins were associated with earlier time to infection recurrence (P ≤ .001, hazard ratio (HR) = 11.9, 95% confidence interval (CI) = 3.84 to 36.7) as was younger age (P = .005, HR = 0.921, 95% CI = 0.869 to 0.976) and atypical pathogen growth on culture (P = .002, HR = 8.58, 95% CI = 2.24 to 32.8). CONCLUSIONS AND RELEVANCE: Histopathologic margin viability was associated with earlier time to infection recurrence following resection of advanced stage ORN or MRONJ of the mandible. Additional studies are needed to identify interventions that may improve outcomes in this demographic.

Adjuvant intra-articular vancomycin for recalcitrant Staphylococcal prosthetic joint infections of the knee.

OBJECTIVE: Chronic prosthetic joint infection patients who fail conventional two-stage revision surgery are an especially difficult to treat patient population. Consequently, the objective of this study was to investigate the safety and long-term effectiveness of adjuvant intra-articular vancomycin therapy in conjunction with two-stage revision knee arthroplasties for recalcitrant Staphylococcal prosthetic joint infections. METHODS: This was an observational cohort study of twelve patients with recalcitrant Staphylococcal prosthetic joint infections of the knee which had failed previous revision surgeries. Each patient subsequently underwent two-stage revision with placement of Hickman catheters to deliver intra-articular vancomycin therapy. In addition, systemic antibiotic therapy was administered for 6 weeks, and long-term follow-up was evaluated then for 5 years. RESULTS: Seventy-five percent of the cohort have had no recurrence of their infections at 5 years. Two patients formed fistulas requiring above the knee amputations, and three patients had acute kidney injury. All patients had maximum measurable serum vancomycin trough levels that ranged from 6.1 to 93.6 mcg/mL. CONCLUSION: The aggressive protocol used in this cohort with repeat two-stage revision surgery, intra-articular vancomycin and systemic antibiotics was able to prevent recurrence of infection in most patients, but higher than expected rates of acute kidney injury were observed in this study. Therefore, while intra-articular vancomycin therapy may have some effectiveness in treating recalcitrant prosthetic joint infections, its ability to eradicate all bacterial niduses is unproven, and clinicians should be cognizant of potential adverse events that can occur with this therapy.

The stability of Staphylococcal bacteriophage in presence of local vancomycin concentrations used in clinical practice.

PURPOSE: To evaluate the stability of a clinically used Staphylococcal bacteriophage with doses of vancomycin that are encountered with local administration of vancomycin for musculoskeletal infections. METHODS: A Staphylococcal bacteriophage was evaluated for stability in different pH ranges. Then that same bacteriophage was evaluated for stability with different concentrations of vancomycin and with vancomycin biodegradable antibiotic beads. RESULTS: The bacteriophage had stability within a pH range of 4-10. There was a statistically significant (P < 0.05) decrease in the amount of bacteriophage over 24 h for vancomycin concentrations of 10 mg/mL and 100 mg/mL compared to lower vancomycin concentrations (1 mg/mL, 0.1 mg/mL and normal saline). However, no statistically significant decrease in the amount of bacteriophage was seen with biodegradable vancomycin beads over 24 h. CONCLUSION: These findings have important clinical ramifications in that they show local administration of bacteriophages with concomitant local vancomycin powder therapy should be avoided. Moreover, these findings should spearhead further research into bacteriophage stability in in vivo environments.

Suppressive Antibiotic Therapy After Debridement, Antibiotics, and Implant Retention is Well-Tolerated Without Inducing Resistance: A Multicenter Study.

BACKGROUND: Suppressive antibiotic therapy (SAT) after total joint arthroplasty (TJA) debridement, antibiotics, and implant retention (DAIR) maximizes reoperation-free survival. We evaluated SAT after DAIR of acutely infected primary TJA regarding: 1) adverse drug reaction (ADR)/intolerance; 2) reoperation for infection; and 3) antibiotic resistance. METHODS: Patients who underwent total knee arthroplasty (TKA) or total hip arthroplasty (THA) DAIR for acute periprosthetic joint infection at two academic medical centers from 2015 to 2020 were identified (n = 115). Data were collected on patient demographics, infecting organisms, antibiotics, ADR/intolerances, reoperations, and antibiotic resistances. Median SAT duration was 11 months. Stepwise multivariate logistic regressions were used to identify covariates significantly associated with outcomes of interest. RESULTS: There were 11.1 and 16.3% of TKA and THA DAIR patients, respectively, who had ADR/intolerance to SAT. Patients prescribed trimethoprim/sulfamethoxazole (P = .0014) or combination antibiotic therapy (P = .0169) after TKA DAIR had increased risk of ADR/intolerance. There was no difference in reoperation-free survival between TKA (83.3%) and THA (65.1%) DAIR (P = .5900) at mean 2.8-year follow-up. Risk of reoperation for infection was higher among TKA Staphylococcus aureus infections (P = .0004) and lower with increased SAT duration (P < .0450). The optimal duration of SAT was nearly 2 years. No cases of antibiotic resistance developed due to SAT. CONCLUSIONS: Consider SAT after TJA DAIR due to improved reoperation-free survival and favorable safety profile. Prolonged SAT did not induce antibiotic resistance. Use trimethoprim/sulfamethoxazole with caution because of the increased likelihood of ADR/intolerance. LEVEL OF EVIDENCE: Therapeutic Level III.

Do bacteriophages have activity in synovial fluid and against synovial fluid induced bacterial aggregates?

Bacteriophage therapy is a promising adjuvant therapy for the treatment of periprosthetic joint infections. However, there is a paucity of knowledge about the activity of bacteriophages in synovial fluid. Therefore, this study evaluated the activity of a clinically used bacteriophage in synovial fluid as well as the ability of that bacteriophage to prevent the formation of and eradicate bacteria in synovial fluid induced aggregates. The results of this study reinforce that synovial fluid induced aggregates form rapidly in numerous synovial fluid concentrations. More importantly, there was a statistically significant reduction in bacteriophage activity in synovial fluid compared to tryptic soy broth (p < 0.05) and the bacteriophage could not prevent the formation synovial fluid induced aggregates. Also the bacteriophage could not significantly reduce the amount of bacteria in the synovial fluid induced aggregates when compared to controls, and this was not secondary to resistance. Rather the reduced activity seems to be caused by bacteriophages being hindered in the ability to attach to bacterial receptors. We hypothesize this occurred because the viscosity of synovial fluid slowed bacteriophage interactions with planktonic bacteria and the synovial fluid polymers obstructed the bacteriophage attachment receptors thereby preventing attachment to bacteria in the aggregates. These findings have clinical ramifications, supporting the use of bacteriophage therapy as an adjunct to surgical interventions and not in isolation, at the nascent stage. While these findings show a shortcoming of bacteriophage therapy in periprosthetic joint infections, the knowledge gained should spearhead further research to ultimately devise effective and reproducible bacteriophage therapeutics.

Do All Prosthetic Joint Infection Clinical Isolates Form Aggregates in Synovial Fluid That Are Resistant to Antibiotic Agents?

Background: Chronic prosthetic joint infections (PJI) are associated with substantial morbidity because conventional antibiotic agents lack activity to bacteria in biofilms that necessitates prosthetic removal to attempt definitive cure. However, these are complex infections that go beyond biofilms and bacteria can be present in various other different states such as synovial fluid aggregates. Consequently, the purpose of this study was to assess the propensity of historically preserved PJI clinical isolates to form synovial fluid aggregates and if aggregation occurred then what is proclivity to be tolerant to high doses of antibiotic agents. Patients and Methods: Historically preserved chronic PJI clinical isolates from 2021 were evaluated for their ability to form synovial fluid aggregates under static and dynamic conditions in 24-microwell plates. Tolerance to vancomycin, gentamicin, or amphotericin was conducted by adding high concentrations of these antibiotic agents to synovial fluid microbial aggregates. Results: All clinical isolates formed synovial fluid aggregates under dynamic conditions, which with the use of scanning electron microscopy showed dense collections of bacteria with synovial fluid polymers. However, under static conditions only Staphylococcus aureus formed aggregates. Importantly, all the microbes in these aggregates were tolerant to high concentrations of antibiotic agents. Conclusions: This study demonstrates that synovial fluid aggregation occurred with all bacterial and fungal species assessed. Therefore, the findings here have important clinical ramifications given the extent that this phenomenon occurs across microbial species and the propensity for the microbes in these aggregates to be tolerant to antibiotic agents.

Is Corynebacterium striatum an emerging prosthetic joint infection pathogen and how should it be treated?

Introduction: The aim of this study was to assess the incidence of Corynebacterium striatum prosthetic joint infections (PJI) to determine if an increase has occurred recently. Moreover, susceptibility testing was conducted on C. striatum preserved isolates to determine antibiotic options for these infections. Methods: Retrospective review of PJI cases was conducted from 1/2017 through 1/2021 compared to 1/2021 through 7/2022 to determine how many cases of C. striatum have occurred for each of these time points. From these cases, demographics, outcomes and risk factors for C. striatum PJI were recorded. The preserved clinical isolates from these cases were tested for susceptibility to different antibiotics. Results: A statistically significant increase in the proportion of C. striatum PJI cases (1.98 to 7.84, p=0.0489) has occurred over the past 16 months at a single institution. Chronic wounds and exposure to daptomycin were associated with the majority of these cases. Susceptibility testing of the clinical isolates showed uniform susceptibility to vancomycin, linezolid and dalbavancin. Uniform resistance was seen with ciprofloxacin, tetracycline and doxycycline as well. Interestingly, 85.7% of the isolates displayed inducible daptomycin resistance after overnight exposure to daptomycin. Conclusions: C. striatum is an emerging PJI pathogen. It is important for clinicians to be cognizant that this pathogen can have inducible high level daptomycin resistance and that daptomycin is likely not a reliable antibiotic for these infections. While vancomycin and linezolid are the traditional antibiotics to use in these infections, other antibiotics such as dalbavancin, may also have utility, but more research is needed to determine the effectiveness of this antibiotic in C. striatum infections.

A rare case of Sphingomonas paucimobilis ventriculitis.

Introduction: Nosocomial ventriculitis is a severe infection that habitually plagues neurological intensive care units. It is usually associated with external ventricular drains. Unfortunately, classic cerebral spinal fluid parameters are less specific and sensitive compared to community acquired meningitis. This is in part secondary to indolent bacteria commonly infecting external ventricular drains leading to ventriculitis. Case report: Herein, a rare case of Sphingomonas paucimobilis ventriculitis in an immunocompetent host is reported. The patient had classic symptoms of ventriculitis, but her cerebral spinal fluid parameters were benign and initial cultures were negative. Consequently, treatment was tailored to an assumed respiratory infection only to have recurrence of her symptoms. Repeat analysis of her cerebral spinal fluid was again benign, but her cerebral spinal fluid culture grew S. paucimobilis. Subsequently, the patient was treated with cefepime, which resolved her symptoms. She completed a two-week course and has had no recurrence of her infection. Conclusions: This case reinforces the need for clinicians to have heightened awareness of this emerging pathogen, its antibiotic resistance patterns, and the unique composition of this bacterium's cell wall which has ramifications on disease presentation.

The stability of Staphylococcal bacteriophages with commonly used prosthetic joint infection lavage solutions.

The aim of this study was to assess the viability of four Staphylococcal bacteriophages when exposed to different concentrations of commonly used lavage solutions in the surgical treatment of prosthetic joint infections (PJI). Four tailed Staphylococcal bacteriophages and six different lavage solutions (chlorhexidine 4%, hydrogen peroxide 3%, acetic acid 3%, povidone iodine 10%, sodium hypochlorite 0.5%, and Vashe solution) at 100%, 1%, and 0.01% concentrations were used in this experiment. In addition, the temporal impact of exposing bacteriophages to these lavage solutions was also evaluated at 5-min exposures and 24-h exposures. The results show that the titers of the four bacteriophages were statistically significantly decreased for all lavage solutions (100% and 1%) at 5-min exposures and 24-h exposures. However, with 0.01% concentrations of the lavage solutions, only acetic acid caused a statistically significant decrease in bacteriophage titers compared to normal saline control. Our findings suggest that tailed Staphylococcal bacteriophages do not remain stable in high concentrations of the most commonly used lavage solutions. However, at very dilute concentrations the bacteriophages do remain viable. This has important clinical ramifications in that it shows when using bacteriophage therapy for PJI it is critical to thoroughly wash out any lavage solutions before the introduction of therapeutic bacteriophages especially when acetic acid is used.

Salphage: Salvage bacteriophage therapy for a chronic Enterococcus faecalis prosthetic joint infection.

Chronic prosthetic joint infections are difficult to treat without conducting revision surgery because conventional antibiotics cannot eradicate bacteria that reside in biofilms. Consequently, novel therapeutics are needed to help treat prosthetic joint infections with one being bacteriophage therapy given its innate biofilm activity. Herein a sixty-nine-year-old man with a recalcitrant Enterococcus faecalis prosthetic joint infection is discussed. The patient was successfully treated with personalized bacteriophage therapy and after two years of follow up he has not had a clinical recurrence. Overall, this case report supports that bacteriophage therapy for prosthetic joint infections has promise to reduce the morbidity that is associated with current treatments. However, more research is needed to assess whether this therapeutic is helping eradicate infections or if it is making bacteria less pathogenic. This is an important point which will need to be evaluated as this therapeutic continues to be developed for all infections.

Feasibility of Using Bacteriophage Therapy to Reduce Morbidity and Mortality Associated with Spinal Epidural Abscesses.

BACKGROUND: The aim of this study was to determine the feasibility of using bacteriophage therapeutics in spinal epidural abscess (SEA) by reviewing the causes and outcomes of SEA at a single institution and testing a bacteriophage for activity against preserved SEA clinical isolates. MATERIALS AND METHODS: Medical records were reviewed of patients that received incision and drainage for SEA at a single medical center. Causative organisms, incidence of coinciding bacteremia and outcomes were recorded. A subset of SEA patients (N = 11), that had preserved clinical isolates, were assessed to evaluate if a bacteriophage therapeutic had ample activity to those isolates as seen with spot tests and growth inhibition assays. RESULTS: Staphylococcus aureus was the predominate bacterial cause (71%) and bacteremia was associated with 96% of S. aureus SEA. Over 50% of the patients either died within three months, had recurrence of their infection, required repeat debridement, or had long term sequalae. A single bacteriophage had positive spot tests for all the S. aureus clinical isolates and inhibited bacterial growth for more than 24 hours for 9 of the 11 (82%) clinical isolates. CONCLUSION: SEA is associated with significant mortality and morbidity making this a potential indication for adjuvant bacteriophage therapeutics. Since S. aureus is the predominate cause of SEA and most cases are associated bacteremia this creates a potential screening and treatment platform for Staphylococcal bacteriophages therapeutics, allowing for potential pilot studies to be devised.

Bacterial Burden, Not Local Immune Response, Differs Between Acute and Chronic Peri-Prosthetic Joint Infections.

Background: Conducting gram stains in peri-prosthetic joint infections (PJI) is known to have poor sensitivity. However, the aims of this study were to use gram stain results of acute and chronic PJI to determine differences with respect to bacterial burden and levels of local innate immunologic response. Patients and Methods: Patients with acute and chronic PJI from January 1, 2016 and December 31, 2020 were identified by use of Current Procedural Terminology codes. Manual review of medical records for infecting organisms and gram stain results for stained bacteria and for local tissue inflammation (amount of polymorphonuclear leukocytes seen on high powered microscopic fields) were recorded. Statistical comparisons between acute (n = 70) and chronic (n = 134) PJI were analyzed with respect to gram stain sensitivity and amount of local tissue inflammation. Results: The ability to identify stained bacteria was statistically significantly higher in the acute cohort (61.4%) than the chronic cohort (9.7%; p < 0.0001). Interestingly, the amount of local inflammation was similar for acute and chronic PJI except in the subgroup analysis with chronic polymicrobial (p = 0.0229) and chronic culture negative (p = 0.0001) PJI. Conclusions: This study shows that both acute and chronic PJI had similar levels of local inflammation seen on gram stains, despite higher bacterial burdens in acute infections. This suggests that innate immune responses, and thus likelihood of infection eradication, is not solely dependent on bacterial burden. These findings should spearhead further research evaluating the different immunologic responses that occur in acute and chronic PJI to improve diagnostics, therapeutics, and infection-free implant survival.

Effective use of a two-dose regimen of dalbavancin to treat prosthetic joint infections and spinal hardware infections.

PURPOSE: Dalbavancin is an attractive antibiotic for the treatment of Gram-positive musculoskeletal infections given its long half-life and prolonged duration in cortical bones. For certain patient populations compliance with antibiotic regimens can be problematic. Therefore, the purpose of this study was to assess the effectiveness, tolerance, and compliance of treating prosthetic joint and spinal hardware infections with a unique two-dose regimen of dalbavancin. METHODS: Identification of patients that had prosthetic joint infections and spinal hardware infections from January 1, 2017, through December 31, 2021, that had received a two-dose regimen of dalbavancin for these infections was conducted. Patient demographics, infection recurrence, compliance and adverse drug reactions to the two-dose regimen of dalbavancin were recorded. Furthermore, preserved clinical isolates from these infections were assessed for susceptibility to dalbavancin with microbroth dilutions. RESULTS: All patients were fully compliant with the two dose dalbavancin regimen and no patient had any adverse reactions to the two-dose dalbavancin regimen. Thirteen of fifteen patients (85.7%) have not had any recurrence of their infections and all preserved clinical isolates showed susceptibility to dalbavancin. DISCUSSION: The two-dose regimen of dalbavancin is an effective and attractive option in treating prosthetic joint and spinal hardware infections to forgo long term central venous access and ensure compliance. However, the use of rifampin and suppression antibiotics still needs to be considered when treating these infections. Nonetheless this study supports that a two-dose dalbavancin regimen is a viable alternative in certain clinical settings and consideration for a randomized controlled clinical trial should be entertained to prove its non-inferiority to conventional treatments.

A pilot study for evaluating the feasibility of using alpha-defensin to support the diagnosis of ventriculitis.

OBJECTIVES: Nosocomial ventriculitis is a difficult infectious condition to diagnose given that typical cerebral spinal fluid (CSF) parameters, commonly used in the diagnosis of meningitis, lack sensitivity and specificity in nosocomial ventriculitis. Consequently, novel diagnostics are needed to aid in diagnosing this condition. Herein a pilot study using alpha-defensins (α-defensins) to diagnose ventriculitis is discussed. METHODS: From May 01, 2022, to December 30, 2022, ten patients with culture-proven external ventricular drain (EVD)-associated ventriculitis and ten patients without EVD-associated ventriculitis had CSF preserved. Levels of α-defensins were compared between the two cohorts with enzyme-linked immunosorbent assay. RESULTS: There was a statistically significant (P ˂0.0001) higher level of CSF α-defensins in the ventriculitis cohort compared to the non-ventriculitis cohort. The levels of α-defensins were not affected by blood in CSF or bacterial virulence. Patients with other infectious conditions had increased levels of α-defensins but these levels were still statistically significantly (P ˂0.001) less than those seen in the ventriculitis cohort. CONCLUSION: This pilot study shows that α-defensins have promise as a biomarker to aid in the diagnosis of ventriculitis. If larger studies support the findings here, this biomarker can help improve diagnostic accuracy and decrease unwarranted empirical broad-spectrum antibiotic use in suspected EVD-associated ventriculitis.

Experience Using Adjuvant Bacteriophage Therapy for the Treatment of 10 Recalcitrant Periprosthetic Joint Infections: A Case Series.

Periprosthetic joint infections are a devastating complication of joint replacement surgery. One novel therapeutic that has potential to change the current treatment paradigm is bacteriophage therapy. Herein, we discuss our experiences with bacteriophage therapy for 10 recalcitrant periprosthetic joint infections and review the treatment protocols utilized to achieve successful outcomes.

A unique case of Rhizopus oryzae brain abscess treated with intracavitary amphotericin.

Here we present a case of a poorly controlled diabetic who developed extensive rhinocerebral mucormycosis. Systemic and intrathecal amphotericin were not able to improve his life threatening infection. Therefore, salvage therapy with intracavitary amphotericin B deoxycholate was used to instill antifungal therapy directly into the patient's brain abscess. For proper dosing of intracavitary amphotericin B deoxycholate, we devised a formula which can be theoretically applied for all intracavitary therapies. Unfortunately, the patient's family withdrew care 6 days after starting intracavitary amphotericin and efficacy of this therapy could not be evaluated.