The addition of doxycycline to fluoroquinolones for bacterial prophylaxis in autologous stem cell transplantation for multiple myeloma.

BACKGROUND: Bacterial prophylaxis with a fluoroquinolone (FQ) during autologous stem cell transplant (ASCT) is common, although not standardized among transplant centers. The addition of doxycycline (doxy) to FQ prophylaxis was previously linked to reduced neutropenic fever and bacteremia in multiple myeloma (MM) patients undergoing ASCT although several confounders were present. We compared the incidence of neutropenic fever and bacteremia between MM patients variably receiving prophylaxis with FQ alone and FQ-doxy during ASCT. METHODS: Systematic retrospective chart review of MM patients who underwent ASCT between January 2016 and December 2021. The primary objective was to determine the effect of bacterial prophylaxis on neutropenic fever and bacteremia within 30 days of ASCT. Multivariable logistic regression for neutropenic fever and univariate logistic regression for bacteremia accounted for differences in subject characteristics between groups. RESULTS: Among 341 subjects, 121 received FQ and 220 received FQ-doxy for prophylaxis. Neutropenic fever developed in 67 (55.4%) and 87 (39.5%) subjects in the FQ and FQ-doxy groups, respectively (p = .005). Bacteremia was infrequent, with 5 (4.1%) and 5 (2.3%) cases developing in the FQ and FQ-doxy groups, respectively (p = .337). Among Gram-negative bacteremia events, 7/7 Escherichia coli strains were FQ-resistant, and 5/7 were ceftriaxone-resistant. CONCLUSION: The FQ-doxy prophylaxis group had fewer cases of neutropenic fever than the FQ group, however, there was no significant difference in bacteremia. High rates of antibiotic resistance were observed. An updated randomized controlled trial investigating appropriate prophylaxis for ASCT in the context of current oncology standards and changing antimicrobial resistance rates is warranted.

Diagnostic testing and antibiotic utilization among inpatients evaluated for coronavirus disease 2019 (COVID-19) pneumonia.

We evaluated diagnostic test and antibiotic utilization among 252 patients from 11 US hospitals who were evaluated for coronavirus disease 2019 (COVID-19) pneumonia during the severe acute respiratory coronavirus virus 2 (SARS-CoV-2) omicron variant pandemic wave. In our cohort, antibiotic use remained high (62%) among SARS-CoV-2-positive patients and even higher among those who underwent procalcitonin testing (68%).

Impact of a multipronged approach to reduce the incidence of Clostridioides difficile infections in hospitalized patients.

BACKGROUND: Effective approaches to reduce Clostridioides difficile infections (CDI) in hospitalized patients are needed. We report data from 3 years preceding and 3 years following interventions that proved successful, with detailed analysis of all cases the first year after implementation. METHODS: Interventions included a nursing protocol to identify cases present on admission by asking if the patient had 1 or more liquid stools in the last 24 hours, and a 2-step testing algorithm with samples positive by polymerase chain reaction (PCR) for the C. difficile toxin gene reflexing to an enzyme immunoassay (EIA) for the toxin antigen. RESULTS: Healthcare-associated infections due to CDI fell from ∼160 in each of the preceding 3 years to <65 in each of the subsequent 3 years (P < .001), while the ratio of observed-to-expected hospital-onset cases diminished to ∼0.50 (P < .02). In the first year, 395 samples were PCR(+), but only 118 (29.9%) of these were EIA(+). 55 (46.6%) of the PCR(+)/EIA(+) samples were from hospital day 1 or 2 and classified as present on admission. The mean time from stool collection to report of PCR results was ∼7.5 hours, and the EIA took on average only 68 additional minutes to be reported. CONCLUSIONS: The number of incident CDI cases can be dramatically decreased by implementing an admission screening question and a 2-step testing algorithm.

The impact of coronavirus disease 2019 (COVID-19) on the antimicrobial stewardship pharmacist workforce: A multicenter survey.

Objective: The coronavirus disease 2019 (COVID-19) pandemic has required healthcare systems and hospitals to rapidly modify standard practice, including antimicrobial stewardship services. Our study examines the impact of COVID-19 on the antimicrobial stewardship pharmacist. Design: A survey was distributed nationally to all healthcare improvement company members. Participants: Pharmacist participants were mostly leaders of antimicrobial stewardship programs distributed evenly across the United States and representing urban, suburban, and rural health-system practice sites. Results: Participants reported relative increases in time spent completing tasks related to medication access and preauthorization (300%; P = .018) and administrative meeting time (34%; P = .067) during the COVID-19 pandemic compared to before the pandemic. Time spent rounding, making interventions, performing pharmacokinetic services, and medication reconciliation decreased. Conclusion: A shift away from clinical activities may negatively affect the utilization of antimicrobials.

Real-World Application of a Procalcitonin Monitoring Protocol in a Pediatric Intensive Care Unit.

OBJECTIVE: Procalcitonin (PCT) is a biomarker used as an indicator for inflammation and bacterial infections. In October 2018, our PICU implemented a PCT monitoring protocol incorporating cutoffs established in previous studies to help guide antibiotic decision-making in patients undergoing sepsis evaluation. The study objective was to evaluate adherence to the protocol with regard to PCT monitoring and antibiotic use. METHODS: This retrospective review included PICU patients with systemic inflammatory response syndrome ages > 1 month to 18 years with at least 1 PCT level and blood culture obtained during the 9 months following protocol implementation. Patients were excluded if they received < 48 hours of antibiotic therapy, were neutropenic, or had antibiotics initiated at another hospital. Patients were evaluated for protocol adherence, defined as antibiotic continuation or discontinuation per protocol guidance without excess PCT monitoring. Descriptive statistics were employed. RESULTS: Out of 100 patients evaluated, 50 patients were included. Full adherence was observed in 17 patients (34%). Reasons for non-adherence were excess PCT monitoring (54.5%), antibiotic continuation (30.3%), or both (15.2%). Of patients who were non-adherent due to antibiotic continuation, 61.5% had a positive respiratory viral panel (RVP). A total of 49 excess PCT levels were drawn, resulting in an additional $2,000 in health care costs and $15,000 in patient charges. CONCLUSIONS: Overall, the impact of our PCT monitoring protocol was difficult to evaluate due to non-adherence, but it highlights potential areas of focus for improving PCT monitoring and antimicrobial stewardship, such as inclusion of RVP results.

Multicenter point prevalence evaluation of the utilization and safety of drug therapies for COVID-19 at the onset of the pandemic timeline in the United States.

KEY POINTS: In a multicenter point-prevalence study, we found that the rate of supportive care was high; among those receiving COVID-19 drug therapies, adverse reactions occurred in 12% of patients. PURPOSE: There are currently no FDA-approved medications for the treatment of coronavirus disease 2019 (COVID-19). At the onset of the pandemic, off-label medication use was supported by limited or no clinical data. We sought to characterize experimental COVID-19 therapies and identify safety signals during this period. METHODS: We conducted a noninterventional, multicenter, point prevalence study of patients hospitalized with suspected/confirmed COVID-19. Clinical and treatment characteristics within a 24-hour window were evaluated in a random sample of up to 30 patients per site. The primary objective was to describe COVID-19-targeted therapies. The secondary objective was to describe adverse drug reactions (ADRs). RESULTS: A total of 352 patients treated for COVID-19 at 15 US hospitals From April 18 to May 8, 2020, were included in the study. Most patients were treated at academic medical centers (53.4%) or community hospitals (42.6%). Sixty-seven patients (19%) were receiving drug therapy in addition to supportive care. Drug therapies used included hydroxychloroquine (69%), remdesivir (10%), and interleukin-6 antagonists (9%). Five patients (7.5%) were receiving combination therapy. The rate of use of COVID-19-directed drug therapy was higher in patients with vs patients without a history of asthma (14.9% vs 7%, P = 0.037) and in patients enrolled in clinical trials (26.9% vs 3.2%, P < 0.001). Among those receiving drug therapy, 8 patients (12%) experienced an ADR, and ADRs were recognized at a higher rate in patients enrolled in clinical trials (62.5% vs 22%; odds ratio, 5.9; P = 0.028). CONCLUSION: While we observed high rates of supportive care for patients with COVID-19, we also found that ADRs were common among patients receiving drug therapy, including those enrolled in clinical trials. Comprehensive systems are needed to identify and mitigate ADRs associated with experimental COVID-19 treatments.

A survey of US hospitals' criteria for the allocation of remdesivir to treat COVID-19.

PURPOSE: To determine how hospitals across the United States determined allocation criteria for remdesivir, approved in May 2020 for treatment of coronavirus disease 2019 (COVID-19) through an emergency use authorization, while maintaining fair and ethical distribution when patient needs exceeded supply. METHODS: A electronic survey inquiring as to how institutions determined remdesivir allocation was developed. On June 17, 2020, an invitation with a link to the survey was posted on the Vizient Pharmacy Network Community pages and via email to the American College of Clinical Pharmacy's Infectious Disease Practice and Research Network listserver. RESULTS: 66 institutions representing 28 states responded to the survey. The results showed that 98% of surveyed institutions used a multidisciplinary team to develop remdesivir allocation criteria. A majority of those teams included clinical pharmacists (indicated by 97% of respondents), adult infectious diseases physicians (94%), and/or adult intensivists (69%). Many teams included adult hospitalists (49.2%) and/or ethicists (35.4%). Of the surveyed institutions, 59% indicated that all patients with COVID-19 were evaluated for treatment, and 50% delegated initial patient identification for potential remdesivir use to treating physicians. Prioritization of remdesivir allocation was often determined on a "first come, first served" basis (47% of respondents), according to a patient's respiratory status (28.8%) and/or clinical course (24.2%), and/or by random lottery (22.7%). Laboratory parameters (10.6%), comorbidities (4.5%), and essential worker status (4.5%) were rarely included in allocation criteria; no respondents reported consideration of socioeconomic disadvantage or use of a validated scoring system. CONCLUSION: The COVID-19 pandemic has exposed the inconsistencies of US medical centers' methods for allocating a limited pharmacotherapy resource that required rapid, fair, ethical and equitable distribution. The medical community, with citizen participation, needs to develop systems to continuously reevaluate criteria for treatment allocation as additional guidance and data emerge.

Multicenter point-prevalence evaluation of the utilization and safety of drug therapies for COVID-19.

BACKGROUND: There are currently no FDA-approved medications for the treatment of COVID-19. At the onset of the pandemic, off-label medication use was supported by limited or no clinical data. We sought to characterize experimental COVID-19 therapies and identify safety signals during this period. METHODS: We conducted a non-interventional, multicenter, point prevalence study of patients hospitalized with suspected/confirmed COVID-19. Clinical and treatment characteristics within a 24-hour window were evaluated in a random sample of up to 30 patients per site. The primary objective was to describe COVID-19 targeted therapies. The secondary objective was to describe adverse drug reactions (ADRs). RESULTS: A total of 352 patients from 15 US hospitals were included. Most patients were treated at academic medical centers (53.4%) or community hospitals (42.6%). Sixty-seven patients (19%) were receiving drug therapy in addition to supportive care. Drug therapies included hydroxychloroquine (69%), remdesivir (10%), and interleukin-6 inhibitors (9%). Five patients (7.5%) were receiving combination therapy. Patients with a history of asthma (14.9% vs. 7%, p=0.037) and those enrolled in clinical trials (26.9% vs. 3.2%, p<0.001) were more likely to receive therapy. Among those receiving COVID-19 therapy, eight patients (12%) experienced an ADR, and ADRs were more commonly recognized in patients enrolled in clinical trials (62.5% vs 22%, OR=5.9, p=0.028). CONCLUSIONS: While we observed high rates of supportive care for patients with COVID-19, we also found that ADRs were common among patients receiving drug therapy including in clinical trials. Comprehensive systems are needed to identify and mitigate ADRs associated with experimental COVID-19 therapies.

Impact of removing ESBL designation from culture reports on the selection of antibiotics for the treatment of infections associated with ESBL-producing organisms.

We characterized the impact of removal of the ESBL designation from microbiology reports on inpatient antibiotic prescribing. Definitive prescribing of carbapenems decreased from 48.4% to 16.1% (P = .01) and ß-lactam-ß-lactamase inhibitor combination increased from 19.4% to 61.3% (P = .002). Our findings confirm the importance of collaboration between microbiology and antimicrobial stewardship programs.

Customizing an Electronic Medical Record to Automate the Workflow and Tracking of an Antimicrobial Stewardship Program.

BACKGROUND: Documenting the actions and effects of an antimicrobial stewardship program (ASP) is essential for quality improvement and support by hospital leadership. Thus, our ASP tallies the number of charts reviewed, types of recommendations, how and to whom they were communicated, whether they were followed, and any effects on antimicrobial days of therapy. Here we describe how we customized the electronic medical record at our institution to facilitate our workflow and data analysis, while highlighting principles that should be adaptable to other ASPs. METHODS: The documentation system involves creation of a novel and intuitive ASP form in each chart reviewed and 2 mutually exclusive tracking systems: 1 for active forms to facilitate the daily ASP workflow and 1 for finalized forms to generate cumulative reports. The ASP form is created by the ASP pharmacist, edited by the ASP physician, reopened by the pharmacist to assess whether the recommendation was followed and to quantify any antimicrobial days avoided or added, then reviewed and finalized by the ASP physician. Active forms are visible on a real-time "MPage," whereas all finalized forms are compiled nightly into 65 informative tables and associated graphs. RESULTS AND CONCLUSIONS: This system and its underlying principles have automated much of the documentation, facilitated follow-up of interventions, improved the completeness and validity of recorded data and analysis, enabled our ASP to expand its activities, and been associated with decreased antimicrobial usage, drug resistance, and C. difficile infections.

The Impact of AUC-Based Monitoring on Pharmacist-Directed Vancomycin Dose Adjustments in Complicated Methicillin-Resistant Staphylococcus aureus Infection.

OBJECTIVE: This study aimed to assess the impact of area under the curve (AUC)-based vancomycin monitoring on pharmacist-initiated dose adjustments after transitioning from a trough-only to an AUC-based monitoring method at our institution. METHODS: A retrospective cohort study of patients treated with vancomycin for complicated methicillin-resistant Staphylococcus aureus (MRSA) infection between November 2013 and December 2016 was conducted. The frequency of pharmacist-initiated dose adjustments was assessed for patients monitored via trough-only and AUC-based approaches for trough ranges: 10 to 14.9 mg/L and 15 to 20 mg/L. RESULTS: Fifty patients were included: 36 in the trough-based monitoring and 14 in the AUC-based-monitoring group. The vancomycin dose was increased in 71.4% of patients when troughs were 10 to 14.9 mg/L when a trough-only approach was used and in only 25% of patients when using AUC estimation (P = .048). In the AUC group, the dose was increased only when AUC/minimum inhibitory concentration (MIC) <400; unchanged regimens had an estimated AUC/MIC ≥400. The AUC-based monitoring did not significantly increase the frequency of dose reductions when trough concentrations were 15 to 20 mg/L (AUC: 33.3% vs trough: 4.6%; P = .107). CONCLUSIONS: The AUC-based monitoring resulted in fewer patients with dose adjustments when trough levels were 10 to 14.9 mg/L. The AUC-based monitoring has the potential to reduce unnecessary vancomycin exposure and warrants further investigation.

Characterization of Drug-Related Problems Occurring in Patients Receiving Outpatient Antimicrobial Therapy.

BACKGROUND: Despite the numerous benefits of outpatient parenteral antimicrobial therapy (OPAT), appreciable risks of drug-related problems (DRPs) exist. No studies to date comprehensively assess DRPs in this population. OBJECTIVES: Objectives of this study were to (1) characterize the frequency and types of DRPs experienced by patients discharged on OPAT and (2) determine the fraction of adverse drug reactions (ADRs) resulting in hospital readmission or emergency department (ED) presentation and changes in therapy. METHODS: This was a retrospective chart analysis evaluating consecutive adult patients discharged on OPAT between May 2015 and October 2015. Patients were assessed for the presence of DRPs until the cessation of antimicrobial treatment, including oral step-down therapy. The outcome of each ADR was recorded, including those resulting in hospital readmissions, presentation to the ED, or changes in antimicrobials. RESULTS: Among 144 patients discharged on OPAT, 199 DRPs occurred in 91 (63.2%) patients. Harm and potential impaired efficacy occurred in 76.9% and 23.1%, respectively. The ADRs comprised 59% of DRPs, occurring in 44.4% of patients. The second most common DRP type was drug interactions (DIs), accounting for 22.6% of DRPs. Rifampin, fluoroquinolones, and daptomycin had the highest frequencies of preventable DRPs in the form of DIs, whereas cephalosporins had the fewest DRPs. Approximately 26% of ADRs caused changes in therapy and 9% resulted in hospital readmission or ED utilization. CONCLUSION: DRPs with the potential to cause patient harm or impair treatment efficacy often occur with OPAT, most commonly ADRs and DIs. Enhanced monitoring and transitions of care management may reduce the incidence of these DRPs.

Are Vancomycin Trough Concentrations of 15 to 20 mg/L Associated With Increased Attainment of an AUC/MIC ≥ 400 in Patients With Presumed MRSA Infection?

PURPOSE: To determine whether there is an association between higher vancomycin trough concentrations and attainment of a calculated area under the concentration-time curve (AUC)/minimum inhibitory concentration (MIC) ≥400. METHODS: A retrospective analysis was conducted among vancomycin-treated adult patients with a positive methicillin-resistant Staphylococcus aureus (MRSA) culture. Attainment of a calculated AUC/MIC ≥400 was compared between patients with troughs in the reference range of 15 to 20 mg/L and those with troughs in the following ranges: <10, 10 to 14.9, and >20 mg/L. Nephrotoxicity was assessed as a secondary outcome based on corrected average vancomycin troughs over 10 days of treatment. RESULTS: Overall, 226 patients were reviewed and 100 included. Relative to troughs ≥10, patients with vancomycin troughs <10 mg/L were 73% less likely to attain an AUC/MIC ≥400 (odds ratio [OR] 0.27, 95% confidence interval [CI]: 0.01-0.75). No difference was found in the attainment of an AUC/MIC ≥400 in patients with troughs of 10 to 14.9 mg/L and >20 mg/L when compared to patients with troughs of 15 to 20 mg/L. The mean corrected average vancomycin trough was higher in patients developing nephrotoxicity compared to those who did not (19.5 vs 14.5 mg/L, P < .001). CONCLUSION: Achieving vancomycin serum trough concentrations of 15 to 20 mg/L did not result in an increased attainment of the AUC/MIC target relative to troughs of 10 to 14.9 mg/L but may increase nephrotoxicity risk.