Recent Advancements in Bone Tissue Engineering: Integrating Smart Scaffold Technologies and Bio-Responsive Systems for Enhanced Regeneration.

In exploring the challenges of bone repair and regeneration, this review evaluates the potential of bone tissue engineering (BTE) as a viable alternative to traditional methods, such as autografts and allografts. Key developments in biomaterials and scaffold fabrication techniques, such as additive manufacturing and cell and bioactive molecule-laden scaffolds, are discussed, along with the integration of bio-responsive scaffolds, which can respond to physical and chemical stimuli. These advancements collectively aim to mimic the natural microenvironment of bone, thereby enhancing osteogenesis and facilitating the formation of new tissue. Through a comprehensive combination of in vitro and in vivo studies, we scrutinize the biocompatibility, osteoinductivity, and osteoconductivity of these engineered scaffolds, as well as their interactions with critical cellular players in bone healing processes. Findings from scaffold fabrication techniques and bio-responsive scaffolds indicate that incorporating nanostructured materials and bioactive compounds is particularly effective in promoting the recruitment and differentiation of osteoprogenitor cells. The therapeutic potential of these advanced biomaterials in clinical settings is widely recognized and the paper advocates continued research into multi-responsive scaffold systems.

Defining the Optimal Duration of Therapy for Hospitalized Patients With Complicated Urinary Tract Infections and Associated Bacteremia.

BACKGROUND: Limited data are available to guide effective antibiotic durations for hospitalized patients with complicated urinary tract infections (cUTIs). METHODS: We conducted an observational study of patients ≥18 years at 24 US hospitals to identify the optimal treatment duration for patients with cUTI. To increase the likelihood patients experienced true infection, eligibility was limited to those with associated bacteremia. Propensity scores were generated for an inverse probability of treatment weighted analysis. The primary outcome was recurrent infection with the same species ≤30 days of completing therapy. RESULTS: 1099 patients met eligibility criteria and received 7 (n = 265), 10 (n = 382), or 14 (n = 452) days of therapy. There was no difference in the odds of recurrent infection for patients receiving 10 days and those receiving 14 days of therapy (aOR: .99; 95% CI: .52-1.87). Increased odds of recurrence was observed in patients receiving 7 days versus 14 days of treatment (aOR: 2.54; 95% CI: 1.40-4.60). When limiting the 7-day versus 14-day analysis to the 627 patients who remained on intravenous beta-lactam therapy or were transitioned to highly bioavailable oral agents, differences in outcomes no longer persisted (aOR: .76; 95% CI: .38-1.52). Of 76 patients with recurrent infections, 2 (11%), 2 (10%), and 10 (36%) in the 7-, 10-, and 14-day groups, respectively, had drug-resistant infections (P = .10). CONCLUSIONS: Seven days of antibiotics appears effective for hospitalized patients with cUTI when antibiotics with comparable intravenous and oral bioavailability are administered; 10 days may be needed for all other patients.

Real-World Impact of the Accelerate PhenoTest BC Kit on Patients With Bloodstream Infections in the Improving Outcomes and Antimicrobial Stewardship Study: A Quasiexperimental Multicenter Study.

BACKGROUND: Bloodstream infections (BSIs) are a leading cause of morbidity and mortality. The Improving Outcomes and Antimicrobial Stewardship study seeks to evaluate the impact of the Accelerate PhenoTest BC Kit (AXDX) on antimicrobial use and clinical outcomes in BSIs. METHODS: This multicenter, quasiexperimental study compared clinical and antimicrobial stewardship metrics, prior to and after implementation of AXDX, to evaluate the impact this technology has on patients with BSIs. Laboratory and clinical data from hospitalized patients with BSIs (excluding contaminants) were compared between 2 arms, 1 that underwent testing on AXDX (post-AXDX) and 1 that underwent alternative organism identification and susceptibility testing (pre-AXDX). The primary outcomes were time to optimal therapy (TTOT) and 30-day mortality. RESULTS: A total of 854 patients with BSIs (435 pre-AXDX, 419 post-AXDX) were included. Median TTOT was 17.2 hours shorter in the post-AXDX arm (23.7 hours) compared with the pre-AXDX arm (40.9 hours; P<.0001). Compared with pre-AXDX, median time to first antimicrobial modification (24.2 vs 13.9 hours; P<.0001) and first antimicrobial deescalation (36.0 vs 27.2 hours; P=.0004) were shorter in the post-AXDX arm. Mortality (8.7% pre-AXDX vs 6.0% post-AXDX), length of stay (7.0 pre-AXDX vs 6.5 days post-AXDX), and adverse drug events were not significantly different between arms. Length of stay was shorter in the post-AXDX arm (5.4 vs 6.4 days; P=.03) among patients with gram-negative bacteremia. CONCLUSIONS: For BSIs, use of AXDX was associated with significant decreases in TTOT, first antimicrobial modification, and time to antimicrobial deescalation.

Improving outcomes and antibiotic stewardship (IOAS) for patients with Gram-positive bloodstream infections through use of rapid testing: a quasi-experimental multicentre study of the Accelerate PhenoTest™ BC Kit.

BACKGROUND: Data from the Improving Outcomes and Antibiotic Stewardship for Patients with Bloodstream Infections: Accelerate PhenoTest™ BC Kit (AXDX) Registry Study were analysed to determine the impact of rapid organism identification and antimicrobial susceptibility testing (AST) for Gram-positive bacteraemia. PATIENTS AND METHODS: This multicentre, quasi-experimental study evaluated clinical and antimicrobial stewardship metrics following the implementation of AXDX. Data from hospitalized patients with bacteraemia were compared between groups, one that underwent testing on AXDX (post-AXDX) and one that underwent traditional identification and AST (pre-AXDX). An analysis of patients with Gram-positive bacteraemia was performed. The primary outcome was time to optimal therapy (TTOT). Secondary outcomes included time to first antibiotic modification (overall and Gram-positive), duration of unnecessary MRSA coverage, incidence of adverse events, length of stay and mortality. RESULTS: A total of 219 (109 pre-AXDX, 110 post-AXDX) patients with Gram-positive bacteraemia were included. Median TTOT was 36.3 h (IQR, 16.9-56.7) in the pre-AXDX group and 20.4 h (IQR, 7.5-36.7) in the post-AXDX group (P = 0.01). Compared with pre-AXDX, median time to first antibiotic modification (29.1 versus 15.9 h; P = 0.002), time to first Gram-positive antibiotic modification (33.2 versus 17.2 h; P = 0.003) and median duration of unnecessary MRSA coverage (58.4 versus 29.7 h; P = 0.04) were reduced post-AXDX. A trend towards decreased acute kidney injury (24% versus 13%; P = 0.06) was observed in the post-AXDX group. Groups did not differ in other secondary outcomes. CONCLUSIONS: Implementation of AXDX testing for patients with Gram-positive bacteraemia shortened the TTOT and reduced unnecessary antibiotic exposure due to faster antibiotic modifications.

Potential for Pharmacy-Public Health Collaborations Using Pharmacy-Based Point-of-Care Testing Services for Infectious Diseases.

CONTEXT: Health care professionals must continually identify collaborative ways to combat antibiotic resistance while improving community health and health care delivery. Clinical Laboratory Improvement Amendments of 1988 (CLIA)-waived point-of-care (POC) testing (POCT) services for infectious disease conducted in community pharmacies provide a means for pharmacists to collaborate with prescribers and/or public health officials combating antibiotic resistance while improving community health and health care delivery. OBJECTIVE: To provide a comprehensive literature review that explores the potential for pharmacists to collaborate with public health professionals and prescribers using pharmacy-based CLIA-waived POCT services for infectious diseases. DESIGN: Comprehensive literature review. SETTING: PubMed and Google Scholar were searched for manuscripts and meeting abstracts for the following key words: infectious disease, community pharmacy, rapid diagnostic tests, rapid assay, and POC tests. INTERVENTION: All relevant manuscripts and meeting abstracts utilizing POCT in community pharmacies for infectious disease were reviewed. OUTCOME MEASURE: Information regarding the most contemporary evidence regarding CLIA-waived POC infectious diseases tests for infectious diseases and their use in community pharmacies was synthesized to highlight and identify opportunities to develop future collaborations using community pharmacy-based models for such services. RESULTS: Evidence demonstrates that pharmacists in collaboration with other health care professionals can leverage their knowledge and accessibility to provide CLIA-waived POCT services for infectious diseases. Testing for influenza may augment health departments' surveillance efforts, help promote rationale antiviral use, and avoid unnecessary antimicrobial therapy. Services for human immunodeficiency virus infection raise infection status awareness, increase access to health care, and facilitate linkage to appropriate care. Testing for group A streptococcal pharyngitis may curb inappropriate outpatient antibiotic prescribing. However, variance in pharmacy practice statues and the application of CLIA across states stifle collaboration. CONCLUSION: CLIA-waived POCT services for infectious diseases are a means for pharmacists, public health professionals, and prescribers to collaboratively combat antibiotic resistance and improve community health.

Impact of an antimicrobial stewardship intervention on urinary tract infection treatment in the ED.

STUDY OBJECTIVE: The study objective is to assess changes in treatment of uncomplicated urinary tract infections (UTIs) after implementation of recommendations based on national guidelines and local resistance rates. METHODS: This preintervention and postintervention study included patients discharged home from the emergency department (ED) with an uncomplicated UTI at a 439-bed teaching hospital. Emergency department prescribers were educated on how local antimicrobial resistance rates impact UTI practice guidelines. Empiric treatment according to recommendations was assessed as the primary outcome. Agreement between chosen therapy and isolated pathogen susceptibility was compared before and after education. Reevaluation in the ED or hospital admission within 30 days for a UTI was also evaluated. RESULTS: A total of 350 patients were studied (174 before and 176 after education). Of those, 255 had cystitis, and 95 had pyelonephritis. After education, choice of therapy consistent with recommendations increased from 44.8% to 83% (difference, 38.2%; 95% confidence interval [CI], 33%-43%; P < .001). The change was predominately driven by an increase in nitrofurantoin use for cystitis from 12% to 80% (difference, 68%; 95% CI, 62%-73%; P < .001). Agreement between empiric treatment and the isolated pathogen susceptibility improved for cystitis 74% to 89% (P = .05), and no change occurred in 30-day repeat ED visits for a UTI. CONCLUSIONS: After implementation of treatment recommendations for uncomplicated UTIs based on local resistance, empiric antibiotic selection improved in the ED. To further meet goals of antimicrobial stewardship, additional interventions are needed.

Epidemiology of Gram-Negative Bloodstream Infections in the United States: Results From a Cohort of 24 Hospitals.

Background: To address knowledge gaps in management of Gram-negative bloodstream infection, the Antibiotic Stewardship Implementation Collaborative was established consisting of programs from 24 academic and community hospitals across the United States. Methods: A retrospective cohort study was conducted of unique adult patients with Gram-negative bloodstream infection hospitalized at participating hospitals from January to December 2019. Patient level and microbiologic data were collected via electronic medical record review with a standardized data collection form and data dictionary. Data analysis was largely descriptive. The Pearson χ2 test to compare categorical variables and the Wilcoxon rank sum test for continuous variables were used. Results: In total, 4851 bacterial isolates from 3710 eligible unique patients were included in the cohort. Most common source of infection was the urinary tract (47.9%). Source control was achieved in 84% of cases. Escherichia coli (2471, 51.0%) was the most common Gram-negative organism recovered. Antibiogram combining isolates from all participating centers with species-level susceptibilities and source specific antibiograms for isolates from urinary, respiratory, and intraabdominal source were created. Northeast sites contributed the most extended spectrum beta-lactamase (ESBL) producing organisms (73%), but West sites had the highest percentage of ESBL producers of total isolates (16%). A statistically significant difference in percentage of ESBL-producing organisms in Whites vs. non-Whites (14.6 % and 9.5 %, respectively, P<0.01) was observed. Conclusions: While the present study was conducted pre-pandemic, it highlights the need for stewardship data collaboratives to enhance our understanding of the antimicrobial resistance patterns.

Impact on time to active antimicrobial therapy with 24-hour pharmacist review of Accelerate Pheno BC Kit results.

The Accelerate Pheno platform provides rapid identification and susceptibility data. We demonstrate successful incorporation of 24-hour pharmacist review of Accelerate Pheno results that reduced the number of patients going >3 hours from result without an order for active antimicrobial therapy from 29 (2.8%) of 1,043 to 9 (0.85%) of 1,053 (P < .001).

Revisiting Oral Fluoroquinolone and Multivalent Cation Drug-Drug Interactions: Are They Still Relevant?

Fluoroquinolones are a widely-prescribed, broad-spectrum class of antibiotics with several oral formulations notable for their high bioavailability. For certain infections, fluoroquinolones are the first line or only treatment choice. When administered orally, fluoroquinolones require proper administration to ensure adequate systemic absorption and, thereby, protect patients from treatment failure. Oral drug preparations that contain multivalent cations are well known to chelate with fluoroquinolones in the gastrointestinal tract; co-administration may lead to clinically significant decreases in oral fluoroquinolone bioavailability and an overall increase in fluoroquinolone-resistant bacteria. Based on a search and evaluation of the literature, this focused review describes oral fluoroquinolone-multivalent cation drug-drug interactions and their magnitude and offers several clinical management strategies for these potentially clinically significant interactions.

Antibiotic Classification and Indication Review for the Infusion Nurse.

Outpatient parenteral antimicrobial therapy (OPAT) has become an increasingly common practice for the treatment of infections. The infusion nurse plays a vital role in administering, monitoring, and educating patients about parenteral antibiotics, while bridging communication between the patient and OPAT team. It is important for the infusion nurse to know common indications, adverse effects, monitoring parameters, and the mechanism of action for antibiotics used in OPAT to provide optimal patient care. This review includes those antibiotics, which are frequently administered or recently approved with a high likelihood of being used in OPAT.