Implementation of a pharmacy-driven rapid bacteremia response program.

PURPOSE: This report describes a comprehensive pharmacy-driven rapid bacteremia response program. SUMMARY: This novel program positioned the pharmacy department at a large, community health system to receive and respond to critical microbiologic diagnostic testing results, 24/7/365. The program empowered pharmacists to provide centralized, comprehensive care including assessing blood culture Gram stain results, adjusting antibiotic therapy per protocol, ordering repeat blood cultures, analyzing and interpreting rapid molecular diagnostic test results, placing orders for contact isolation, and communicating antibiotic recommendations to the treatment team. In the first year after program implementation, 2,282 blood culture Gram stains and 2,046 rapid diagnostic test results were called in to the pharmacy department. The program reduced the median time to effective therapy in patients who did not already have active antimicrobial orders from over 10 hours to less than 1 hour. Based on the Gram stain results, antibiotics were started per protocol in 34.2% of patients. Based on the rapid molecular diagnostic test results, adjustments were made to antibiotic regimens in 55.7% of cases after discussion with a provider. Of these adjustments, 39.9% were for escalation of antibiotics and 37.7% were for de-escalation of antibiotics. CONCLUSION: By expanding the scope of pharmacy practice, barriers to optimizing clinical care were overcome.

The Norton Healthcare electronic antimicrobial stewardship program: An opt-out approach to antimicrobial stewardship.

PURPOSE: To describe the Norton Healthcare electronic antimicrobial stewardship program (E-ASP), a novel prospective audit and feedback approach that leverages the electronic medical record to overcome efficiency barriers. Additionally, to describe an accompanying opt-out antimicrobial stewardship approach that addresses provider nonresponsiveness. SUMMARY: Prospective audit and feedback is recommended by antimicrobial stewardship guidelines; however, execution can be difficult due to labor requirements, delays in communication, and provider nonparticipation. The Norton E-ASP was developed to address these issues by reliably identifying target patients, documenting assessments, streamlining recommendation delivery, promoting handoff, and providing automated tracking of recommendation responses. Opt-out stewardship allows recommendations to be implemented if not rejected after 24 hours. CONCLUSION: A 25% reduction in target antimicrobial use has been achieved and sustained with the program. Use of the Norton E-ASP, including opt-out antimicrobial stewardship, broadened the reach and furthered the impact of infectious diseases pharmacists. Successes of this program justified addition of 3 full-time infectious diseases pharmacist positions at a large community health system. This strategy may serve as a model for tele-antimicrobial stewardship or other pharmacy recommendations.

Limited impact of a nudge comment in promoting de-escalation to first-generation cephalosporins in urinary tract infections.

In this study, we evaluated the impact of a microbiology nudge on de-escalation to first-generation cephalosporins in hospitalized patients with urinary tract infections secondary to Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis isolates with minimum inhibitory concentrations (MICs) ≤ 16 µg/mL. De-escalation to first generation-cephalosporins was uncommon at MICs = 4-16 µg/mL.

Fluoroquinolone stewardship at a community health system: A decade in review.

Objective: To describe inpatient fluoroquinolone use and susceptibility data over a 10-year period after the implementation of an antimicrobial stewardship program (ASP) led by an infectious diseases pharmacist starting in 2011. Design: Retrospective surveillance study. Setting: Large community health system. Methods: Fluoroquinolone use was quantified by days of therapy (DOT) per 1,000 patient days (PD) and reported quarterly. Use data are reported for inpatients from 2016 to 2020. Levofloxacin susceptibility is reported for Pseudomonas aeruginosa and Escherichia coli for inpatients from 2011 to 2020 at a 4 adult-hospital health system. Results: Inpatient fluoroquinolone use decreased by 74% over a 5-year period, with an average decrease of 3.45 DOT per 1,000 PD per quarter (P < .001). Over a 10-year period, inpatient levofloxacin susceptibility increased by 57% for P. aeruginosa and by 15% for E. coli. P. aeruginosa susceptibility to levofloxacin increased by an average of 2.73% per year (P < .001) and had a strong negative correlation with fluoroquinolone use, r = -0.99 (P = .002). E. coli susceptibility to levofloxacin increased by an average of 1.33% per year (P < .001) and had a strong negative correlation with fluoroquinolone use, r = -0.95 (P = .015). Conclusions: A substantial decrease in fluoroquinolone use and increase in P. aeruginosa and E. coli levofloxacin susceptibility was observed after implementation of an antimicrobial stewardship program. These results demonstrate the value of stewardship services and highlight the effectiveness of an infectious diseases pharmacist led antimicrobial stewardship program.

Antimicrobial stewardship in patients with confirmed coronavirus disease 2019 (COVID-19).

Hospitalized coronavirus disease 2019 (COVID-19) patients receiving antibiotics (n = 173) were retrospectively assigned to the early or late discontinuation groups. The length of therapy was shorter in the early discontinuation group (3 vs 7 days; P < .0001). Mortality rates (14.3% vs 20.7%; P = .316) and length of stay (7 vs 9 days; P = .063) were similar.

Results of a local combination therapy antibiogram for Pseudomonas aeruginosa isolates: is double worth the trouble?

PURPOSE: To determine the frequency at which fluoroquinolones and aminoglycosides demonstrate in vitro activity against non-urinary, non-skin/skin structure Pseudomonas aeruginosa isolates exhibiting decreased susceptibilities to one or more ß-lactam agents. METHODS: ß-lactam-non-susceptible P. aeruginosa isolates recovered from blood, bone, lower respiratory tract, pleural fluid, cerebrospinal fluid, or peritoneal fluid cultures between October 2010 and October 2014 were reviewed from four community hospitals within a single health-system. Only the first isolate per patient was included for analysis. The likelihood that each isolate was susceptible to a non-ß-lactam antimicrobial was then determined and summarized within a combination antibiogram. RESULTS: In total, 179 P. aeruginosa isolates with decreased susceptibilities to one or more ß-lactam agents were assessed. Because no appreciable differences in antimicrobial susceptibility profile were observed between hospitals, the isolates were evaluated in aggregate. Susceptibility rates for ß-lactam monotherapy ranged from 34% to 75%. Aminoglycosides possessed increased antibacterial activity compared to fluoroquinolones. Tobramycin was the non-ß-lactam most likely to expand antimicrobial coverage against ß-lactam-non-susceptible P. aeruginosa with activity against 64%, 66%, and 65% of cefepime-, piperacillin-tazobactam-, and meropenem-non-susceptible isolates, respectively (p < 0.001 for all). CONCLUSIONS: The results of this study support the use of aminoglycosides over fluoroquinolones for achieving optimal, empiric antimicrobial combination therapy for P. aeruginosa when dual antimicrobial therapy is clinically necessary. Future efforts aimed at optimizing combination therapy for P. aeruginosa should focus on systemic interventions that limit the selection of fluoroquinolones in combination with ß-lactams to expand coverage based on local susceptibility rates.

Sleep Duration and Academic Performance Among Student Pharmacists.

OBJECTIVE: To identify sleep patterns and frequency of daytime sleepiness and to assess the association between sleep duration and academic performance among student pharmacists. METHODS: A cross-sectional design was used. An anonymous self-administered paper questionnaire was administered to first-year through third-year students at a pharmacy school. RESULTS: Questionnaires were completed by 364 student pharmacists (79.4% response rate and 93.8% cooperation rate). More than half of student pharmacists obtained less than 7 hours of sleep at night during a typical school week (54.7%) and a large majority on the night prior to an examination (81.7%). Almost half (47.8%) felt daytime sleepiness almost every day. Longer sleep duration the night prior to an examination was associated with higher course grades and semester grade point averages (GPAs). CONCLUSION: A majority of student pharmacists had suboptimal durations of sleep, defined as fewer than 7 hours. Adequate sleep the night prior to an examination was positively associated with student course grades and semester GPAs.

Mapping structurally defined guanine oxidation products along DNA duplexes: influence of local sequence context and endogenous cytosine methylation.

DNA oxidation by reactive oxygen species is nonrandom, potentially leading to accumulation of nucleobase damage and mutations at specific sites within the genome. We now present the first quantitative data for sequence-dependent formation of structurally defined oxidative nucleobase adducts along p53 gene-derived DNA duplexes using a novel isotope labeling-based approach. Our results reveal that local nucleobase sequence context differentially alters the yields of 2,2,4-triamino-2H-oxal-5-one (Z) and 8-oxo-7,8-dihydro-2'-deoxyguanosine (OG) in double stranded DNA. While both lesions are overproduced within endogenously methylated (Me)CG dinucleotides and at 5' Gs in runs of several guanines, the formation of Z (but not OG) is strongly preferred at solvent-exposed guanine nucleobases at duplex ends. Targeted oxidation of (Me)CG sequences may be caused by a lowered ionization potential of guanine bases paired with (Me)C and the preferential intercalation of riboflavin photosensitizer adjacent to (Me)C:G base pairs. Importantly, some of the most frequently oxidized positions coincide with the known p53 lung cancer mutational "hotspots" at codons 245 (GGC), 248 (CGG), and 158 (CGC) respectively, supporting a possible role of oxidative degradation of DNA in the initiation of lung cancer.

Novel route to a finite center-of-mass momentum pairing state for superconductors: A current-driven Fulde-Ferrell-Larkin-Ovchinnikov state.

The previously studied Fulde-Ferrell-Larkin-Ovchinnikov (FFLO) state is stabilized by a magnetic field via the Zeeman coupling in spin-singlet superconductors. Here we suggest a novel route to achieve nonzero center-of-mass momentum pairing states in superconductors with Fermi surface nesting. We investigate two-dimensional superconductors under a uniform external current, proportional to a finite pair momentum of q(e). We find that an FFLO state with a spontaneous pair momentum of q(s) is stabilized above a certain critical current that depends on the direction of the external current. A finite q(s) arises in order to make the total pair-momentum of q(t)(=q(s) + q(e)) perpendicular to the nesting vector, which is independent of spin states of Cooper pairs. We also discuss experimental signatures of the FFLO state.