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.

Bacteriophage therapy for periprosthetic joint infections: Current limitations and research needed to advance this therapeutic.

Bacteriophage therapy is a promising treatment for periprosthetic joint infections (PJIs), particularly given these agents have innate abilities to degrade the biofilm matrix and lyse bacteria within. However, many aspects of this therapy are poorly understood causing treatments to lack uniform effectiveness and reproducibility, which is in part a consequence of several inherent limitations to using bacteriophages to treat PJI. Herein, these limitations are discussed as are additional translational research that needs to be conducted to advance this therapeutic. These include determining if bacteria causing PJIs are polyclonal, consequences of bacteriophage attachment receptor phenotypic variations and ramifications of bacteriophage activity when bacteria interact with in vivo macromolecules. Only with the realization of the current limitations and subsequent knowledge gained from translational research will the potential of bacteriophages to reduce the morbidity and mortality in PJI be fully elucidated.

Impact of Bacterial Phenotypic Variation with Bacteriophage therapy: A Pilot Study with Prosthetic Joint Infection Isolates.

BACKGROUND: Given the specificity of bacteriophage attachment receptors, a single bacterial isolate is currently utilized to match to a bacteriophage therapeutic, thereby extrapolating activity to all bacteria in vivo. Consistently, the main bacteriophage attachment receptor for Staphylococcus aureus is teichoic acid, and it is known that this receptor has phenotypic variations in different in vivo environments. Consequently, the aim of this study was to determine whether bacteriophage activity is similar across all in vivo prosthetic joint infection environments. METHODS: Three patients with prosthetic joint infections who had S. aureus grow from arthrocentesis cultures and at least three deep tissue cultures were analyzed for growth inhibition with a library of 56 bacteriophages. RESULTS: Discordant bacteriophage activity was seen across the different in vivo environments. Furthermore, bacteriophages with the most robust lytic potential to the arthrocentesis isolates usually did not demonstrate activity corresponding to all the deep tissue clinical isolates. CONCLUSION: Variations of bacteriophage activity can occur between the different in vivo clinical environments, which is likely secondary to different glycosylation patterns of teichoic acid. Consequently, if discordant activity is present, retreating with bacteriophages that have activity is likely needed for effective, reproducible outcomes.

Photoacoustic discrimination of antibiotic-resistant and sensitive Staphylococcus aureus isolates.

OBJECTIVES: Bacteremia is a serious and potentially lethal condition. Staphylococcus aureus is a leading cause of bacteremia and methicillin-resistant S. aureus (MRSA) accounts for more than a third of the cases. Compared to methicillin-sensitive S. aureus, MRSA is more than twice as likely to be fatal. Furthermore, subpopulations of seemingly isogenic bacteria may exhibit a range of susceptibilities, often called heterogenous resistance. These heterogeneous antibiotic-resistant infections are often misdiagnosed as hospital-acquired secondary infections because there are no clinically used tests that can differentiate between homogeneous and heterogeneous antibiotic resistance. We describe the development and proof of concept of rapid bacterial identification using photoacoustic flow cytometry and labeled bacteriophages with the characterization and differentiation of heterogeneous antibiotic-resistant bacterial infections. METHODS: In photoacoustic flow cytometry, pulsed laser light is delivered to a sample flowing past a focused transducer and particles that absorb laser light create an acoustic response. Optically labeled bacteriophage are added to a bacterial mixture that flows through the photoacoustic chamber. The presence of target bacteria is determined by bound labeled phage which are detected photoacoustically. Incubation of bacterial samples in the presence and absence of the antibiotic daptomycin creates a difference in bacterial cell numbers that is quantified using photoacoustic flow cytometry. RESULTS: Four clinical isolates were tested in the presence and absence of daptomycin. Photoacoustic events for each isolate were recorded and compared to growth curves. Samples treated with daptomycin fell into three categories: resistant, susceptible, and heterogeneous resistant. CONCLUSIONS: Here we show a method to determine the presence of bacteria as a marker for bloodstream infection level and antibiotic sensitivity in less than 4 hours. Additionally, these results show an ability to identify heterogeneous resistant strains that are often misidentified.

[Biomechanical analysis of sitting-up movement of knee joint after robot-assisted unicompartmental knee arthroplasty].

OBJECTIVE: To investigate the effect of Navio robot-assisted unicompartmental knee arthroplasty (UKA) on the biomechanics of knee joint during sitting-up movement, and to determine whether UKA can maintain the biomechanical characteristics of knee joint. METHODS: The clinical data of 8 patients with medial compartment osteoarthritis treated with medial fixed platform of Navio robot-assisted UKA between January 2018 and January 2019 and had the complete follow-up data were retrospectively analyzed. There were 4 males and 4 females; the age ranged from 58 to 67 years, with an average of 62.3 years. The disease duration was 6-18 months, with an average of 13 months. The varus deformity ranged from 4° to 6°, with an average of 5°; the knee flexion range of motion was 0°-130°, with an average of 110°. All patients had no extension limitation. The imaging data of bilateral knees during sitting-up movement were collected by biplane C-arm X-ray machine at 3 weeks before operation and 7 months after operation. The three-dimensional models of femur and tibia were established by dual-energy CT scanning, and the three-dimensional models of femur and tibia were matched and synchronized with the femur and tibia in X-ray film by automatic matching tracer software. The biomechanical parameters of femur and tibia were measured, including internal rotation/external rotation, varus/valgus, forward/backward displacement of medial and lateral tibia contact center, and lateral compartment joint space. RESULTS: Eight patients were followed up 5-7 months, with an average of 6.4 months. In the comparison of the affected side before and after operation, except for the difference of varus/valgus which was significant ( t=4.959, P=0.002), the differences in other indicators was not significant ( P>0.05). There were significant differences in varus/valgus and internal rotation/external rotation between healthy and affected sides at 3 weeks before operation ( P<0.05), and the differences in other indicators was not significant ( P>0.05). At 7 months after operation, the difference in the forward and backward displacement of medial tibia contact center was significant ( t=3.798, P=0.007), and the differences in other indicators was not significant ( P>0.05). CONCLUSION: UKA can effectively correct the varus and valgus of the knee joint, and restore the rotational biomechanical characteristics of the affected knee joint. It does not affect the establishment of the lateral compartment joint space, but the medial and lateral tibia contact center still changes.

Engineered Cationic Antimicrobial Peptides (eCAPs) to Combat Multidrug-Resistant Bacteria.

The increasing rate of antibiotic resistance constitutes a global health crisis. Antimicrobial peptides (AMPs) have the property to selectively kill bacteria regardless of resistance to traditional antibiotics. However, several challenges (e.g., reduced activity in the presence of serum and lack of efficacy in vivo) to clinical development need to be overcome. In the last two decades, we have addressed many of those challenges by engineering cationic AMPs de novo for optimization under test conditions that typically inhibit the activities of natural AMPs, including systemic efficacy. We reviewed some of the most promising data of the last two decades in the context of the advancement of the field of helical AMPs toward clinical development.

Reframing Financial Incentives Around Reducing Readmission After Radical Cystectomy.

OBJECTIVE: To better understand the financial implications of readmission after radical cystectomy, an expensive surgery coupled with a high readmission rate. Currently, whether hospitals benefit financially from readmissions after radical cystectomy remains unclear, and potentially obscures incentives to invest in readmission reduction efforts. MATERIALS AND METHODS: Using a 20% sample of national Medicare beneficiaries, we identified 3544 patients undergoing radical cystectomy from January 2010 to November 2014. We compared price-standardized Medicare payments for index admissions and readmissions after surgery. We also examined the variable financial impact of length of stay and the proportion of Medicare payments coming from readmissions based on overall readmission rate. RESULTS: Medicare patients readmitted after cystectomy had higher index hospitalization payments ($19,164 readmitted vs $18,146 non-readmitted, P = .03) and an average readmission payment of $7356. Adjusted average Medicare readmission payments and length of stay varied significantly across hospitals, ranging from $2854 to $15,605, and 2.0 to 17.1 days, respectively (both P <.01), with longer length of stay associated with increased payments. After hospitals were divided into quartiles based on overall readmission rates, the percent of payments coming from readmissions ranged from 5% to 13%. CONCLUSION: Readmissions following radical cystectomy were associated with increased Medicare payments for the index hospitalization, and the readmission payment, potentially limiting incentives for readmission reduction programs. Our findings highlight opportunities to reframe efforts to support patients, caregivers, and providers through improving the discharge and readmission processes to create a patient-centered experience, rather than for fear of financial penalties.

Dynamic readmission prediction using routine postoperative laboratory results after radical cystectomy.

OBJECTIVE: To determine if the addition of electronic health record data enables better risk stratification and readmission prediction after radical cystectomy. Despite efforts to reduce their frequency and severity, complications and readmissions following radical cystectomy remain common. Leveraging readily available, dynamic information such as laboratory results may allow for improved prediction and targeted interventions for patients at risk of readmission. METHODS: We used an institutional electronic medical records database to obtain demographic, clinical, and laboratory data for patients undergoing radical cystectomy. We characterized the trajectory of common postoperative laboratory values during the index hospital stay using support vector machine learning techniques. We compared models with and without laboratory results to assess predictive ability for readmission. RESULTS: Among 996 patients who underwent radical cystectomy, 259 patients (26%) experienced a readmission within 30 days. During the first week after surgery, median daily values for white blood cell count, urea nitrogen, bicarbonate, and creatinine differentiated readmitted and nonreadmitted patients. Inclusion of laboratory results greatly increased the ability of models to predict 30-day readmissions after cystectomy. CONCLUSIONS: Common postoperative laboratory values may have discriminatory power to help identify patients at higher risk of readmission after radical cystectomy. Dynamic sources of physiological data such as laboratory values could enable more accurate identification and targeting of patients at greatest readmission risk after cystectomy. This is a proof of concept study that suggests further exploration of these techniques is warranted.

Characterising 'bounce-back' readmissions after radical cystectomy.

OBJECTIVE: To examine predictors of early readmissions after radical cystectomy (RC). Factors associated with preventable readmissions may be most evident in readmissions that occur within 3 days of discharge, commonly termed 'bounce-back' readmissions, and identifying such factors may inform efforts to reduce surgical readmissions. PATIENTS AND METHODS: We utilised the Healthcare Cost and Utilization Project's State Inpatient Databases to examine 1867 patients undergoing RC in 2009 and 2010, and identified all patients readmitted within 30 days of discharge. We assessed differences between patients experiencing bounce-back readmission compared to those readmitted 8-30 days after discharge using logistic regression models and also calculated abbreviated LACE scores to assess the utility of common readmissions risk stratification algorithms. RESULTS: The 30-day and bounce-back readmission rates were 28.4% and 5.6%, respectively. Although no patient or index hospitalisation characteristics were significantly associated with bounce-back readmissions in adjusted analyses, bounce-back patients did have higher rates of gastrointestinal (14.3% vs 6.7%, P = 0.02) and wound (9.5% vs 3.0%, P < 0.01) diagnoses, as well as increased index and readmission length of stay (5 vs 4 days, P = 0.01). Overall, the median abbreviated LACE score was 7, which fell into the moderate readmission risk category, and no difference was observed between readmitted and non-readmitted patients. CONCLUSION: One in five readmissions after RC occurs within 3 days of initial discharge, probably due to factors present at discharge. However, sociodemographic and clinical factors, as well as traditional readmission risk tools were not predictive of this bounce-back. Effective strategies to reduce bounce-back readmission must identify actionable clinical factors prior to discharge.