ACPHS Research Commons (Albany College of Pharmacy and Health Sciences)
Not a member yet
791 research outputs found
Sort by
Impact of a purified microbiome therapeutic on abundance of antimicrobial resistance genes in patients with recurrent Clostridioides difficile infection.
No full textClick on the Resource Link to access the article (may not be free).Background: The gastrointestinal microbiota is an important line of defense against colonization with antimicrobial resistant (AR) bacteria. In this post hoc analysis of the Phase 3 ECOSPOR III trial, we assessed impact of a microbiota-based oral therapeutic (fecal microbiota spores, live [VOWSTTM Oral Spores; VOS, formerly SER-109]) compared with placebo, on AR gene (ARG) abundance in patients with recurrent Clostridioides difficile infection (rCDI).
Methods: Adults with rCDI were randomized to receive VOS or placebo orally for 3 days following standard-of-care antibiotics. ARG and taxonomic profiles were generated using whole metagenomic sequencing of stool at baseline and Weeks 1, 2, 8, and 24 post-treatment.
Results: Baseline (n=151) and serial post-treatment stool samples collected through 24 weeks (total n=472) from 182 patients (59.9% female; mean age 65.5 years) in ECOSPOR III as well as 68 stool samples obtained at a single timepoint from a healthy cohort were analyzed. Baseline ARG abundance was similar between arms and significantly elevated vs. the healthy cohort. By Week 1, there was a greater decline in ARG abundance in VOS vs. placebo (p=0.003) in association with marked decline of Proteobacteria and repletion of spore-forming Firmicutes, as compared with baseline. We observed abundance of Proteobacteria and non-spore forming Firmicutes were associated with ARG abundance, while spore-forming Firmicutes abundance was negatively associated.
Conclusions: This proof-of-concept analysis suggests that microbiome remodeling with Firmicutes spores may be a potential novel approach to reduce ARG colonization in the gastrointestinal tract.https://doi.org/10.1093/cid/ciad63
Incidence of acute kidney injury (AKI) and its impact on patient outcomes among adult hospitalized patients with carbapenem-resistant Gram-negative infections who received targeted treatment with a newer β-lactam or β-lactam/β-lactamase inhibitor-, polymyxin- or aminoglycoside-containing regimen.
No full textBackground: Limited comparative data exist on acute kidney injury (AKI) risk and AKI-associated outcomes in hospitalized patients with carbapenem-resistant Gram-negative infections (CR-GNIs) treated with a newer β-lactam/β-lactam-β-lactamase inhibitor (BL/BL-BLI)-, polymyxin (PB)- or aminoglycoside (AG)-containing regimen. This study quantified the risk of AKI and AKI-related outcomes among patients with CR-GNIs treated with a newer BL/BL-BLI-, PB- or AG-containing regimen.
Methods: A multicentre, retrospective, observational study was performed (2016-20). The study included adult hospitalized patients with (i) baseline estimated glomerular filtration rates ≥30 mL/min/1.73 m2; (ii) CR-GN pneumonia, complicated urinary tract infection or bloodstream infection; and (iii) receipt of newer BL/BL-BLI, PG or AG within 7 days of index CR-GN culture for ≥3 days. Outcomes included AKI, in-hospital mortality and hospital costs.
Results: The study included 750 patients and most (48%) received a newer BL/BL-BLI. The median (IQR) treatment duration was 8 (5-11), 5 (4-8) and 7 (4-8) days in the newer BL/BL-BLI group, AG group and PB group, respectively. The PB group had the highest adjusted AKI incidence (95% CI) (PB: 25.1% (15.6%-34.6%) versus AG: 8.9% (5.7%-12.2%) versus newer BL/BL-BLI: 11.9% (8.1%-15.7%); P = 0.001). Patients with AKI had significantly higher in-hospital mortality (AKI: 18.5% versus 'No AKI': 5.6%; P = 0.001) and mean hospital costs (AKI: 38,763; P = 0.043).
Conclusions: The AKI incidence was highest among PB patients and patients with AKI had worse outcomes. Healthcare systems should consider minimizing the use of antibiotics that augment AKI risk as a measure to improve outcomes in patients with CR-GNIs.Grant FundedMerck Sharp & Dohme LLCMerck & Co., Inc.http://www.ncbi.nlm.nih.gov/pmc/articles/pmc10761276/https://doi.org/10.1093/jac/dkad35
HIV-Associated Neurocognitive Disorder: A Look into Cellular and Molecular Pathology.
No full textClick on the Resource Link to access the article (may not be free).Despite combined antiretroviral therapy (cART) limiting HIV replication to undetectable levels in the blood, people living with HIV continue to experience HIV-associated neurocognitive disorder (HAND). HAND is associated with neurocognitive impairment, including motor impairment, and memory loss. HIV has been detected in the brain within 8 days of estimated exposure and the mechanisms for this early entry are being actively studied. Once having entered into the central nervous system (CNS), HIV degrades the blood-brain barrier through the production of its gp120 and Tat proteins. These proteins are directly toxic to endothelial cells and neurons, and propagate inflammatory cytokines by the activation of immune cells and dysregulation of tight junction proteins. The BBB breakdown is associated with the progression of neurocognitive disease. One of the main hurdles for treatment for HAND is the latent pool of cells, which are insensitive to cART and prolong inflammation by harboring the provirus in long-lived cells that can reactivate, causing damage. Multiple strategies are being studied to combat the latent pool and HAND; however, clinically, these approaches have been insufficient and require further revisions. The goal of this paper is to aggregate the known mechanisms and challenges associated with HAND.Grant FundedAI165295/National Institute of Allergy and Infectious DiseasesHL160229/National Heart Lung and Blood InstituteAI162076/National Institute of Allergy and Infectious Diseaseshttp://www.ncbi.nlm.nih.gov/pmc/articles/pmc11083163/https://doi.org/10.3390/ijms2509469
2024 ACPHS Student Summer Research Award Recipients
No full textThe Student Summer Research Award Program is open to all Albany College of Pharmacy and Health Sciences students interested in pursuing laboratory, clinical, or other research projects and scholarly activities under the guidance of a faculty mentor. The research experience occurs over the course of the summer (May through August)
Comparative evaluation of early treatment with ceftolozane/tazobactam versus ceftazidime/avibactam for non-COVID-19 patients with pneumonia due to multidrug-resistant Pseudomonas aeruginosa
No full textMethods: The study included non-COVID-19 adult hospitalized patients with MDR-PSA PNA in the PINC AI Healthcare Database (2016-22) who received ceftolozane/tazobactam or ceftazidime/avibactam within 3 days of index culture for ≥2 days. Outcomes were mortality, recurrent MDR-PSA PNA, discharge destination, post-index culture day length of stay (LOS) and costs (in US dollars, USD), and hospital readmission.Results: The final sample included 197 patients (117 ceftolozane/tazobactam, 80 ceftazidime/avibactam). No significant differences were observed in mortality and post-index culture LOS and costs between groups. In the multivariable analyses, patients who received ceftolozane/tazobactam versus ceftazidime/avibactam had lower recurrent MDR-PSA PNA (7.9% versus 18.0%, P = 0.03) and 60 day PNA-related readmissions (11.1% versus 28.5%, P = 0.03) and were more likely to be discharged home (25.8% versus 9.8%, P = 0.03). Compared with ceftazidime/avibactam patients, ceftolozane/tazobactam patients had lower adjusted median total antibiotic costs (5052 USD versus 8099 USD, P = 0.003) and lower adjusted median comparator (ceftolozane/tazobactam or ceftazidime/avibactam) antibiotic costs (3938 USD versus 6441 USD, P = 0.005). In the desirability of outcome ranking (DOOR) analysis, a ceftolozane/tazobactam-treated patient was more likely to have a more favourable outcome than a ceftazidime/avibactam-treated patient [DOOR probability: 59.6% (95% CI: 52.5%-66.8%)].Conclusions: Early treatment with ceftolozane/tazobactam may offer some clinical and cost benefits over ceftazidime/avibactam in patients with MDR-PSA PNA. Further large-scale studies are necessary to comprehensively understand the outcomes associated with these treatments for MDR-PSA PNA.Grant FundedMerck Sharp & Dohme LLCMerck & Co., Inc.https://pmc.ncbi.nlm.nih.gov/articles/PMC11531822/https://doi.org/10.1093/jac/dkae31
Assessment of Student Pharmacists' Co-Curricular Professionalization Using an Impact Scale.
No full textCo-curricular participation is a required component of the pharmacy program. Assessment of co-curricular activities has proven challenging due to lack of manpower to address the workload of reviewing multiple critical reflections. This project documented the professionalization impact of co-curricular involvement and secondarily explored the utility of our assessment tool, the Co-curricular Impact Scale (CIS), developed to streamline the assessment process. First- through third-professional-year students (P1, P2, P3) participated in five co-curricular domains: (i) professional development/education; (ii) patient care service; (iii) legislative advocacy; (iv) leadership/service to the pharmacy profession; and (v) healthcare-related community service. For the CIS, 16 questions were developed and mapped to 11 educational outcomes and included assessing the impact of immersing in an authentic learning experience, collaborating with healthcare professionals, and preparing for the pharmacist role. A group of 296 students rated the impact of participation as low, moderate, or significant for five events annually. Based on 717 entries, the two attributes deemed most impactful were: "Activity immersed me in an authentic learning experience" (95% ≥ Moderate Impact) and "Activity improved my self-confidence" (93% ≥ Moderate Impact). P1 students found slightly less impact in co-curricular participation (83.5%) than P2 (88.4%) and P3 (86.8%) counterparts. The CIS proved to be an efficient method to collate impact of co-curricular involvement upon student professionalization.https://doi.org/10.3390/pharmacy12040117https://pmc.ncbi.nlm.nih.gov/articles/PMC11359949
Treatment of critically ill patients with cefiderocol for infections caused by multidrug-resistant pathogens: review of the evidence.
No full textClick on the Resource Link to access the article (may not be free).Appropriate antibiotic treatment for critically ill patients with serious Gram-negative infections in the intensive care unit is crucial to minimize morbidity and mortality. Several new antibiotics have shown in vitro activity against carbapenem-resistant Enterobacterales (CRE) and difficult-to-treat resistant Pseudomonas aeruginosa. Cefiderocol is the first approved siderophore beta-lactam antibiotic with potent activity against multidrug-resistant, carbapenem-resistant, difficult-to-treat or extensively drug-resistant Gram-negative pathogens, which have limited treatment options. The spectrum of activity of cefiderocol includes drug-resistant strains of Acinetobacter baumannii, P. aeruginosa, Stenotrophomonas maltophilia, Achromobacter spp. and Burkholderia spp. and CRE that produce serine- and/or metallo-carbapenemases. Phase 1 studies established that cefiderocol achieves adequate concentration in the epithelial lining fluid in the lung and requires dosing adjustment for renal function, including patients with augmented renal clearance and continuous renal-replacement therapy (CRRT); no clinically significant drug-drug interactions are expected. The non-inferiority of cefiderocol versus high-dose, extended-infusion meropenem in all-cause mortality (ACM) rates at day 14 was demonstrated in the randomized, double-blind APEKS-NP Phase 3 clinical study in patients with nosocomial pneumonia caused by suspected or confirmed Gram-negative bacteria. Furthermore, the efficacy of cefiderocol was investigated in the randomized, open-label, pathogen-focused, descriptive CREDIBLE-CR Phase 3 clinical study in its target patient population with serious carbapenem-resistant Gram-negative infections, including hospitalized patients with nosocomial pneumonia, bloodstream infection/sepsis, or complicated urinary tract infections. However, a numerically greater ACM rate with cefiderocol compared with BAT led to the inclusion of a warning in US and European prescribing information. Cefiderocol susceptibility results obtained with commercial tests should be carefully evaluated due to current issues regarding their accuracy and reliability. Since its approval, real-world evidence in patients with multidrug-resistant and carbapenem-resistant Gram-negative bacterial infections suggests that cefiderocol can be efficacious in certain critically ill patient groups, such as those requiring mechanical ventilation for COVID-19 pneumonia with subsequently acquired Gram-negative bacterial superinfection, and patients with CRRT and/or extracorporeal membrane oxygenation. In this article, we review the microbiological spectrum, pharmacokinetics/pharmacodynamics, efficacy and safety profiles and real-world evidence for cefiderocol, and look at future considerations for its role in the treatment of critically ill patients with challenging Gram-negative bacterial infections.https://doi.org/10.1186/s13613-023-01146-5http://www.ncbi.nlm.nih.gov/pmc/articles/pmc10272070
International consensus recommendations for the use of prolonged-infusion beta-lactam antibiotics: Endorsed by the American College of Clinical Pharmacy, British Society for Antimicrobial Chemotherapy, Cystic Fibrosis Foundation, European Society of Clinical Microbiology and Infectious Diseases, Infectious Diseases Society of America, Society of Critical Care Medicine, and Society of Infectious Diseases Pharmacists.
No full textClick on the Resource Link to access the article (may not be free).Intravenous β-lactam antibiotics remain a cornerstone in the management of bacterial infections due to their broad spectrum of activity and excellent tolerability. β-lactams are well established to display time-dependent bactericidal activity, where reductions in bacterial burden are directly associated with the time that free drug concentrations remain above the minimum inhibitory concentration (MIC) of the pathogen during the dosing interval. In an effort to take advantage of these bactericidal characteristics, prolonged (extended and continuous) infusions (PIs) can be applied during the administration of intravenous β-lactams to increase time above the MIC. PI dosing regimens have been implemented worldwide, but implementation is inconsistent. We report consensus therapeutic recommendations for the use of PI β-lactams developed by an expert international panel with representation from clinical pharmacy and medicine. This consensus guideline provides recommendations regarding pharmacokinetic and pharmacodynamic targets, therapeutic drug-monitoring considerations, and the use of PI β-lactam therapy in the following patient populations: severely ill and nonseverely ill adult patients, pediatric patients, and obese patients. These recommendations provide the first consensus guidance for the use of β-lactam therapy administered as PIs and have been reviewed and endorsed by the American College of Clinical Pharmacy (ACCP), the British Society for Antimicrobial Chemotherapy (BSAC), the Cystic Fibrosis Foundation (CFF), the European Society of Clinical Microbiology and Infectious Diseases (ESCMID), the Infectious Diseases Society of America (IDSA), the Society of Critical Care Medicine (SCCM), and the Society of Infectious Diseases Pharmacists (SIDP).https://doi.org/10.1002/phar.284