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.

Perioperative cefazolin prescribing rates following suppression of alerts for non-IgE-mediated penicillin allergies.

BACKGROUND: Cefazolin is the preferred antimicrobial for the prevention of surgical site infections (SSIs) in many procedures. The presence of penicillin allergies can influence prescribing of alternative agents like vancomycin. In April 2022, Nebraska Medicine implemented a suppression of alerts for non-IgE-mediated and nonsevere penicillin allergies in the electronic medical record (EMR) upon cephalosporin prescribing. The objective of this study was to evaluate changes in perioperative cefazolin for SSI prophylaxis. METHODS: This was a quasi-experimental study of patients undergoing procedures for which cefazolin was the preferred agent per institutional guidance. Education on the change was distributed via e-mail to surgical staff and pharmacists. Pre- and post-intervention data were collected from April 2021 through March 2022 and April 11, 2022, through October 2022, respectively. Chart review was performed on patients with reported penicillin allergies for the top surgical procedures with <50% cefazolin utilization pre-intervention. The primary outcome was the administration of perioperative cefazolin in patients with penicillin allergies, including unknown reactions. RESULTS: A total of 6,676 patients underwent surgical procedures (pre-intervention n = 4,147, post-intervention n = 2,529). Documented penicillin allergies were similar between the pre- and post-intervention group (12.3% vs. 12.6%). In individuals with documented penicillin allergies, cefazolin prescribing increased from 49.6% to 74.3% (p < 0.01). Chart review for safety outcomes identified no difference in new severe reactions, rescue medication, SSIs, acute kidney injury, postoperative Clostridioides difficile infection, or methicillin-resistant Staphylococcus aureus infections. CONCLUSION: Following the suppression of EMR alerts for non-IgE-mediated and nonsevere penicillin allergies, cefazolin prescribing rates for SSI prophylaxis significantly improved.

In Outpatients Receiving Parenteral Vancomycin, Dosing Adjustments Produced by Area Under the Curve-Based and Trough-Based Monitoring Differ Only at the Extremes of the Therapeutic Trough Range.

Area under the curve (AUC)-based vancomycin dosing reduces nephrotoxicity but is burdensome. Reviewing 115 adults receiving ≥2 weeks of outpatient vancomycin, we found AUC-based and trough-based dose adjustments discordant only for troughs <12 or >16 mg/L. Selective versus universal outpatient AUC calculation would likely offer similar benefit with reduced workload.

Rise of the (possible) resistance: a review of susceptibility patterns for nontyphoidal Salmonella enterica in Nebraska.

Our institution sought to evaluate our antimicrobial stewardship empiric treatment recommendations for Salmonella. Results from 36 isolates demonstrated reduced susceptibilities to fluoroquinolones with 1 isolate susceptible only to ceftriaxone. Analysis supports the current recommendation of empiric ceftriaxone therapy for severe infection and updated recommendation for sulfamethoxazole-trimethoprim in non-severe infections.

Impact of specialty on the self-reported practice of using oral antibiotic therapy for definitive treatment of bloodstream infections.

Background: No established guidelines exist regarding the role of oral antibiotic therapy (OAT) to treat bloodstream infections (BSIs), and practices may vary depending on clinician specialty and experience. Objective: To assess practice patterns regarding oral antibiotic use for treatment of bacteremia in infectious diseases clinicians (IDCs, including physicians and pharmacists and trainees in these groups) and non-infectious diseases clinicians (NIDCs). Design: Open-access survey. Participants: Clinicians caring for hospitalized patients receiving antibiotics. Methods: An open-access, web-based survey was distributed to clinicians at a Midwestern academic medical center using e-mail and to clinicians outside the medical center using social media. Respondents answered questions regarding confidence prescribing OAT for BSI in different scenarios. We used χ2 analysis for categorical data evaluated association between responses and demographic groups. Results: Of 282 survey responses, 82.6% of respondents were physicians, 17.4% pharmacists, and IDCs represented 69.2% of all respondents. IDCs were more likely to select routine use of OAT for BSI due to gram-negative anaerobes (84.6% vs 59.8%; P < .0001), Klebsiella spp (84.5% vs 69.0%; P < .009), Proteus spp (83.6% vs 71.3%; P < .027), and other Enterobacterales (79.5% vs 60.9%; P < .004). Our survey results revealed significant differences in selected treatment of Staphylococcus aureus syndromes. Fewer IDCs than NIDCs selected OAT to complete treatment for methicillin-resistant S. aureus (MRSA) BSI due to gluteal abscess (11.9% vs 25.6%; P = .012) and methicillin-susceptible S. aureus (MSSA) BSI due to septic arthritis (13.9% vs 20.9%; P = .219). Conclusions: Practice variation and discordance with evidence for the use of OAT for BSIs exists among IDCs versus NIDCs, highlighting opportunities for education in both clinician groups.

Serious Adverse Events and Laboratory Monitoring Regimens for Outpatient Parenteral Antimicrobial Therapy With Cefazolin and Ceftriaxone.

The optimal laboratory monitoring frequency for outpatient parenteral antimicrobial therapy-related adverse events (OPAT-AEs) during cefazolin and ceftriaxone therapy is not well defined. We identified 2.7 OPAT-AEs per 1000 sets of weekly laboratory tests in this population, suggesting that less intensive laboratory monitoring may be safe and reasonable.

Use of a beta-lactam graded challenge process for inpatients with self-reported penicillin allergies at an academic medical center.

Background: The Antimicrobial Stewardship Program (ASP) at Nebraska Medicine collaborated with a board-certified allergist to develop a penicillin allergy guidance document for treating inpatients with self-reported allergy. This guidance contains an algorithm for evaluating and safely challenging penicillin-allergic patients with beta-lactams without inpatient allergy consults being available. Methods: Following multi-disciplinary review, an order set for beta-lactam graded challenges (GC) was implemented in 2018. This contains recommended monitoring and detailed medication orders to challenge patients with various beta-lactam agents. Inpatient orders for GC from 3/2018-6/2022 were retrospectively reviewed to evaluate ordering characteristics, outcomes of the challenge, and whether documentation of the allergy history was updated. All beta-lactam challenges administered to inpatients were included, and descriptive statistics were performed. Results: Overall, 157 GC were administered; 13 with oral amoxicillin and 144 with intravenous (IV) beta-lactams. Ceftriaxone accounted for the most challenges (43%). All oral challenges were recommended by an Infectious Diseases consult service, as were a majority of IV challenges (60%). Less than one in five were administered in an ICU (19%). Almost all (n = 150, 96%) were tolerated without any adverse event. There was one reaction (1%) of hives and six (4%) involving a rash, none of which had persistent effects. Allergy information was updated in the electronic health record after 92% of the challenges. Conclusion: Both intravenous and oral beta-lactam graded challenges were implemented successfully in a hospital without a regular inpatient allergy consult service. They were well-tolerated, administered primarily in non-ICU settings, and were often ordered by non-specialist services. In patients with a self-reported penicillin allergy, these results demonstrate the utility and safety of a broadly adopted beta-lactam GC process.

Implementation of a Rapid Multiplex Polymerase Chain Reaction Pneumonia Panel and Subsequent Antibiotic De-escalation.

Background: Net effects of implementation of a multiplex polymerase chain reaction (PCR) pneumonia panel (PNP) on antimicrobial stewardship are thus far unknown. This retrospective study evaluated the real-world impact of the PNP on time to antibiotic de-escalation in critically ill patients treated for pneumonia at an academic medical center. Methods: This retrospective, quasi-experimental study included adult intensive care unit (ICU) patients with respiratory culture results from 1 May to 15 August 2019 (pre-PNP group) and adult ICU patients with PNP results from 1 May to 15 August 2020 (PNP group) at Nebraska Medical Center. Patients were excluded for the following reasons: any preceding positive coronavirus disease 2019 PCR test, lack of antibiotic receipt, or non-respiratory tract infection indications for antibiotics. The primary outcome was time to discontinuation of anti-methicillin-resistant Staphylococcus aureus (MRSA) therapy. Secondary outcomes included time to discontinuation of antipseudomonal therapy, frequency of early discontinuation for atypical coverage, and overall duration (in days) of antibiotic therapy for pneumonia. Results: Sixty-six patients in the pre-PNP group and 58 in the PNP group were included. There were significant differences in patient characteristics between groups. The median time to anti-MRSA agent discontinuation was 49.1 hours in the pre-PNP and 41.8 hours in the PNP group (P = .28). The median time to discontinuation of antipseudomonal agents was 134.4 hours in the pre-PNP versus 98.1 hours in the PNP group (P = .47). Other outcomes were numerically but not significantly improved in our sample. Conclusions: This early look at implementation of a multiplex PNP did not demonstrate a statistically significant difference in antibiotic use but lays the groundwork to further evaluate a significant real-world impact on antibiotic de-escalation in ICU patients treated for pneumonia.

Treatment of Asymptomatic Bacteriuria after Implementation of an Inpatient Urine Culture Algorithm in the Electronic Medical Record.

Ordering urine cultures in patients without pyuria is associated with the inappropriate treatment of asymptomatic bacteriuria (ASB). In 2015, our institution implemented recommendations based on practice guidelines for the management of ASB and revised the urine culture ordering process to limit cultures in immunocompetent patients without pyuria. The purpose of this study was to determine how the treatment of ASB has changed over time since altering the urine culture ordering process to reduce unnecessary cultures at an academic medical center. A quasi-experimental study was conducted for inpatients with urine cultures from January to March of 2014, 2015, 2016 and 2020. The primary outcome was the antibiotic treatment of asymptomatic bacteriuria for over 24 h. The secondary outcomes were the total days of antibiotic therapy, type of antibiotic prescribed and overall urine culture rates at the hospital. A total of 200 inpatients with ASB were included, 50 at random from each year. In both 2014 and 2015, 70% of the patients with ASB received antibiotic treatment. Antibiotics were prescribed to 68% and 54% of patients with ASB in 2016 and 2020, respectively. The average duration of therapy decreased from 5.12 days in 2014 to 3.46 days in 2020. Although the urine cultures were reduced, there was no immediate impact in the prescribing rates for patients with ASB after implementing this institutional guidance and an altered urine culture ordering process. Over time, there was an observed improvement in prescribing and the total days of antibiotic therapy. This could be attributed to increased familiarity with the guidelines, culture ordering practices or improved documentation. Based on these findings, additional provider education is needed to reinforce the guideline recommendations on the management of ASB.

Use of a Novel Clinical Decision Support Tool for Pharmacist-Led Antimicrobial Stewardship in Patients with Normal Procalcitonin.

In 2018, a clinical decision support (CDS) tool was implemented as part of a "daily checklist" for frontline pharmacists to review patients on antibiotics with procalcitonin (PCT) <0.25 mcg/L. This study used a retrospective cohort design to assess change in antibiotic use from pharmacist interventions after this PCT alert in patients on antibiotics for lower respiratory tract infections (LRTI). The secondary outcome was antibiotic days of therapy (DOT), with a subgroup analysis examining antibiotic use and the length of stay (LOS) in patients with a pharmacist intervention. From 1/2019 to 11/2019, there were 165 alerts in 116 unique patients on antibiotics for LRTI. Pharmacists attempted interventions after 34 (20.6%) of these alerts, with narrowing spectrum or converting to oral being the most common interventions. Pharmacist interventions prevented 125 DOT in the hospital. Vancomycin was the most commonly discontinued antibiotic with an 85.3% use reduction in patients with interventions compared to a 27.4% discontinuation in patients without documented intervention (p = 0.0156). The LOS was similar in both groups (median 6.4 days vs. 7 days, p = 0.81). In conclusion, interventions driven by a CDS tool for pharmacist-driven antimicrobial stewardship in patients with a normal PCT resulted in fewer DOT and significantly higher rates of vancomycin discontinuation.

Antibacterial use in the age of SARS-CoV-2.

BACKGROUND: Balancing the use of antibacterial therapy against selection for resistance in this pandemic era has introduced both questions and guidelines. In this project, we explored how prescription of empirical antibacterial therapy differs between those with and without SARS-CoV-2 infection. METHODS: Multivariable logistic regression was used to determine whether COVID-19 status and other factors play a role in the prescription of antibacterial therapy in an inpatient setting at a large referral academic medical centre. Further analysis was conducted to determine whether these factors differ between those testing positive and negative for SARS-CoV-2. RESULTS: Of 405 patients in the cohort, 175 received antibacterial therapy and 296 tested positive for SARS-CoV-2. A positive SARS-CoV-2 test carried an OR of 0.3 (95% CI: 0.19, 0.49) for receiving antibacterial treatment in the first 48 h after admission (P < 0.0001) adjusting for age and procalcitonin results. Patients were 1% and 3% less likely to receive antibacterials for every year increase in age in the overall group and among those testing negative for SARS-CoV-2, respectively. Younger age was found to impact use of antibacterial therapy in both the overall analysis as well as the SARS-CoV-2 negative subgroup (P = 0.03 and P = 0.01). High procalcitonin values were found to be associated with increased antibacterial therapy use in both the overall and stratified analyses. CONCLUSIONS: Antibacterial therapy prescription differs by COVID-19 disease status, and procalcitonin results are most highly associated with antibacterial use across strata.

Use of a best practice alert linking Clostridioides difficile infection test results to a severity-based treatment order set.

We evaluated provider adherence to practice guidelines for inpatients diagnosed with Clostridoides difficile infection (CDI) before and after implementation of a best practice alert (BPA) linking a positive test result to guideline-based orders. After implementation of the BPA, guideline-based prescribing increased from 39.4% in 2013 to 67.7% in 2016 (P = .014).

Pharmacokinetic and pharmacodynamic aspects of antibiotic use in high-risk populations.

The study of pharmacokinetics includes the absorption, distribution, metabolism, and elimination of drugs. The pharmacologic effect that a medication has on the body is known as pharmacodynamics. With antimicrobials, pharmacokinetic and pharmacodynamic parameters become especially important because of the association between host drug concentrations, microorganism eradication, and resistance. This article focuses on the pharmacokinetic changes that can occur with antimicrobials when they are used in patients at high risk of infections and how they influence pharmacodynamic effects. The populations described here include patients with obesity and diabetes mellitus, renal or hepatic failure, chronic lung disease, severe burns, and long-term prosthetic devices and the elderly.

Outcomes of an extended-infusion piperacillin-tazobactam protocol implementation in a community teaching hospital adult intensive care unit.

OBJECTIVE: The purpose of this study is to evaluate the outcome differences between patients receiving piperacillin-tazobactam pre- and post-implementation of an extended infusion dosing protocol in a community teaching hospital adult intensive care unit. METHODS: On December 19th, 2011, extended infusion dosing of piperacillin-tazobactam was implemented at St. John's Hospital's intensive and cardiac care units (ICU/CCU) following IRB-approval. This is a historical case-control cohort study involving review of electronic medical charts of patients who received traditional or extended infusion therapy. Data was collected for patients that received piperacillin-tazobactam in the ICU/CCU from December 19th, 2010 through March 19th, 2011 for traditional infusion and from December 19th, 2011 through March 19th, 2012 for extended infusion. Primary endpoints were ICU/CCU mortality at discharge and length of stay. RESULTS: The study included 113 patients with 52 in the traditional-infusion group and 61 extended-infusion group. There was no statistically significant difference in the primary end-point of ICU/CCU mortality between the two groups (14.8% vs. 21.1%; p = 0.374). In the extended infusion group, there was a shorter length of ICU and CCU stay (8.32 vs. 12.06 days; p = 0.025) and shorter length of hospital stay (11.32 vs. 19.7 days; p = 0.006). The extended-infusion group showed a decrease in cost of therapy that was statistically significant ($120.21 vs. $155.17; p = 0.035). Adverse drug effects did not differ between the two study groups. CONCLUSION: This study showed that treatment with extended-infusion piperacillin-tazobactam therapy improved patient outcomes while maintaining patient safety and decreasing costs.

Monitoring of Outpatient Parenteral Antimicrobial Therapy and Implementation of Clinical Pharmacy Services at a Community Hospital Infusion Unit.

BACKGROUND: In 2004, the Infectious Diseases Society of America (IDSA) published monitoring guidelines for outpatient parenteral antimicrobial therapy (OPAT), but no assessment of their utilization has been reported. We evaluated adherence to these recommendations by physicians at infusion centers and then piloted a program of supervision of monitoring by pharmacists. METHODS: Phase I: We performed a retrospective case-control study of patients who received OPAT over 1 year at 2 hospital infusion centers. Controls were patients treated by an infectious diseases (ID) physician, and cases were those without an ID physician. Patients were excluded if they received fewer than 3 days of OPAT. Clinical pharmacy monitoring services were then implemented for patients on OPAT prescribed by non-ID physicians at 1 hospital's infusion unit. Two outcomes were measured: adherence to guidelines on monitoring and attainment of goal vancomycin and aminoglycoside serum concentrations when appropriate. The results for non-ID physicians were compared to both ID physicians and subsequently a pharmacist. RESULTS: Ninety-nine patients were included in the retrospective study. Compared with patients who had ID physician supervision, the non-ID physicians who prescribed OPAT for 39 patients had lower adherence to monitoring recommendations (35.9% vs 68.3%, P = .003). No difference could be detected in achievement of goal vancomycin and aminoglycoside serum concentrations for the 14 cases and 19 controls requiring therapeutic drug monitoring (57.1% vs 68.4%, respectively, P = .765). Seven patients were enrolled in the study after pharmacy monitoring was implemented. Adherence to monitoring recommendations for these patients was significantly improved compared to the prior patients who lacked ID physician supervision (35.9% vs 100%, P = .0065). CONCLUSION: Non-ID physicians are less likely to monitor OPAT according to the IDSA guidelines than ID physicians; however, pharmacist oversight improves adherence to recommendations. Further studies of monitoring of OPAT by pharmacists should investigate the impact of pharmacist involvement on prevention of adverse events and hospital readmissions.

Interferons as therapeutic agents for infectious diseases.

This article explains the rationale for development of interferons as therapeutic agents, and describes commercial products available today. It also provides a summary of studies that have been performed with interferons for use as exogenous biological response modifiers in viral infections. Overall, the best data exist for treatment of viral hepatitis B and C, for which interferons are a cornerstone of therapy. Although infections with human papillomavirus and common cold viruses sometimes respond favorably to interferons, their outcomes are far from ideal. Finally, the role of interferons as vaccine adjuvants is still being explored but could be promising.