Urine polymerase chain reaction tests: stewardship helper or hinderance?

Urine polymerase chain reaction is a laboratory test promoted to healthcare professionals working in long-term care facilities as a rapid diagnostic platform for urinary tract infection. Little is known about the place of this testing and its potential impact on antimicrobial stewardship programs. In this commentary, we review the currently available literature and provide recommendations for long-term care stewardship programs to consider.

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.

Outcomes and factors associated with cryptococcal disease among cirrhotics: A study of the national inpatient sample 2005 to 2014.

BACKGROUND: Cryptococcal disease (CD) confers a higher mortality in cirrhotic patients compared to non-cirrhotic patients. Factor association for CD in cirrhotic patients is poorly understood. Our aim was to determine the incidence, demographic, and comorbidities associated with CD among cirrhotic patients in the United States (US). METHOD: Retrospective analysis of admissions of cirrhotic patients, with or without CD, using the National Inpatient Sample (NIS) database from 2005 to 2014. The number of admissions were reported in raw and weighted frequencies. The trends of CD among cirrhotic patients and overall CD were evaluated. Rao-Scott chi-square, t-tests, and multivariate logistic regressions were performed to evaluate variables and CD among cirrhotic patients. RESULTS: There were 886,962 admissions for cirrhosis, and 164 of these with CD. By adjusted odds ratio (AOR), CD was more often associated with cirrhosis in Southern (2.95; 95 % CI 1.24, 7.02) and Western regions (4.45; 95 % CI 1.91, 10.37), Hispanic patients (1.80; 95 % CI 1.01, 3.20), and patients with chronic kidney disease (CKD) (3.13; 95 % CI 2.09, 4.69). Of note, CD in cirrhotic patients was associated with higher inpatient mortality (AOR of 3.89, 95 % CI 2.53, 5.99), longer length of stay (9.87 vs. 4.88 days), and a higher total charge ($76,880 vs. $ 37,227) when compared to cirrhotic patients without CD. DISCUSSION: Patients with cirrhosis admitted with CD have a high inpatient mortality. The geographical location and CKD were important factors associated with CD among cirrhotic patients. Autoimmune liver diseases and immunosuppression did not appear to increase the risk of CD.

Approach to febrile neutropenia in patients undergoing treatments for hematologic malignancies.

Febrile neutropenia (FN) is common among hematologic malignancy patients, including recipients of hematopoietic cell transplantation (HCT) and cellular therapies such as chimeric antigen receptor (CAR)-T-cell therapy. Prompt empiric antibiotic use has been the mainstay for decades but a "one-size-fits-all" approach is no longer broadly accepted, as treatment-related infectious risk are more understood. Growing antimicrobial resistance is an increasing clinical challenge. Evolving strategies on de-escalation of broad-spectrum antibiotics in FN without identified infection are areas of particular interest.

Identifying Effective Durations of Antibiotic Therapy for the Treatment of Carbapenem-resistant Enterobacterales Bloodstream Infections: A Multicenter Observational Study.

In a propensity-score-weighted cohort of 183 adults with carbapenem-resistant Enterobacterales bacteremia at 24 US hospitals, patients receiving short courses of active therapy (7-10 days, median 9 days) experienced similar odds of recurrent bacteremia or death within 30 days as those receiving prolonged courses of active therapy (14-21 days, median 14 days).

Donor call simulation: A novel medical education tool to evaluate trainees' clinical decision-making in transplant infectious disease.

BACKGROUND: Evaluating organ suitability for transplantation based on infection risk is a core competency in transplant infectious disease (TID). It is unclear if trainees have opportunities to practice during training. We created a simulation curriculum to develop and evaluate this skill among infectious disease (ID) trainees. METHODS: We created six simulation questions about organ suitability for transplant based on infection risk. During trainees' TID rotations, faculty texted or paged the simulation cases posing as the transplant coordinator. Trainees had 15 min to ask questions before deciding the suitability of the organ and explained their clinical reasoning in a survey. Trainees completed a post-simulation survey to evaluate its effectiveness. RESULTS: ID trainees, including residents and fellows on rotation, from seven centers participated. Eighty-seven percent (13/15) of trainees felt the simulation was effective in teaching them this concept, and 80% (12/15) felt prepared for clinical practice. The proportion of correct responses was generally high among the six different cases (43%-100%); correct responses increased for some cases in the post-activity survey. Of the 100 clinical reasoning decisions made during the activity, 19% were discordant, where the trainee correctly identified suitable organs for incorrect reasons. CONCLUSION: Our simulation was effective in teaching when to accept or reject an organ for transplant and was a valuable educational tool. By evaluating clinical reasoning for decisions our simulation provides educators with nuanced insight and allows for targeted coaching. This study demonstrates a critical need for further educational tools in TID.

Infectious complications among CD19 CAR-T cell therapy recipients: A single-center experience.

BACKGROUND: CD19 chimeric antigen receptor (CAR)-T cell therapy has emerged as an effective treatment in those with refractory or relapsed lymphoma. CD19 CAR-T cell therapy can cause direct and indirect toxic adverse effects and increased risk for infection. Infectious complications and optimal antimicrobial prophylaxis strategies are an ongoing area of investigation. METHODS: A single-center retrospective cohort study was conducted to review recipients of CD19 CAR-T cell therapy between April 2018 and December 2020. Patient characteristics and clinical outcomes were extracted from the electronic health records. RESULTS: Infectious complications were identified in 18/50 (36%) recipients with 31 episodes of infection. The median time to infection was 225 days (range 0-614). Bacterial infections were most common with bloodstream infection followed by sinusitis and skin and soft tissue infection. Eight viral infections were identified, most being respiratory viral illnesses. Two fungal infections were identified: Pneumocystis jirovecii pneumonia (PJP) and disseminated fusariosis. Seventeen infections (54.8%) were classified as severe: leading to death, requiring hospitalization, need for empiric intravenous antibiotics, or significant alteration in hospital course. No characteristics were found to be statistically significant risks for infection, although a trend toward significance was seen in prior autologous stem cell transplant recipients (p = .12) and those with recurrent neutropenia (p = .14). Three patients (6%) died from infection. CONCLUSION: Infections were common after CD19 CAR-T cell therapy and occurred beyond the first year. Further multicenter studies are needed to define infectious risks and optimize antimicrobial prophylaxis recommendations in recipients of CD19 CAR-T cell therapy.

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.

Opportunities for Antimicrobial Stewardship Interventions Among Solid Organ Transplant Recipients.

Although antimicrobial stewardship programs have excelled over the past decade, uptake and application of these programs to special populations such as solid organ transplant recipients have lagged. Here, we review the value of antimicrobial stewardship for transplant centers and highlight data supporting interventions that are ripe for adoption. In addition, we review the design of antimicrobial stewardship initiatives, targets for both syndromic and system-based interventions.

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.

The interplay of infectious diseases consultation and antimicrobial stewardship in candidemia outcomes: A retrospective cohort study from 2016 to 2019.

OBJECTIVE: To evaluate the need for mandatory infectious diseases consultation (IDC) for candidemia in the setting of antimicrobial stewardship guidance. DESIGN: Retrospective cohort study from January 2016 to December 2019. SETTING: Academic quaternary-care referral center. PATIENTS: All episodes of candidemia in adults (n = 92), excluding concurrent bacterial infection or death or hospice care within 48 hours. METHODS: Primary outcome was all-cause 30-day mortality. Secondary outcomes included guideline-adherence and treatment choice. Guideline-adherence was assessed with the EQUAL Candida score. RESULTS: Of 186 episodes of candidemia, 92 episodes in 88 patients were included. Central venous catheters (CVCs) were present in 66 episodes (71.7%) and were the most common infection source (N = 38, 41.3%). The most frequently isolated species was Candida glabrata (40 of 94, 42.6%). IDC was performed in 84 (91.3%) of 92 candidemia episodes. Mortality rates were 20.8% (16 of 77) in the IDC group versus 25% (2 of 8) in the no-IDC group (P = .67). Other comparisons were numerically different but not significant: repeat blood culture (98.8% vs 87.5%; P = .17), echocardiography (70.2% vs 50%; P = .26), CVC removal (91.7% vs 83.3%; P = .45), and initial echinocandin treatment (67.9% vs 50%; P = .44). IDC resulted in more ophthalmology examinations (67.9% vs 12.5%; P = .0035). All patients received antifungal therapy. Antimicrobial stewardship recommendations were performed in 19 episodes (20.7%). The median EQUAL Candida score with CVC was higher with IDC (16 vs 11; P = .001) but not in episodes without CVC (12 vs 11.5; P = .81). CONCLUSIONS: In the setting of an active antimicrobial stewardship program and high consultation rates, mandatory IDC may not be warranted for candidemia.

Beta-lactam allergies, surgical site infections, and prophylaxis in solid organ transplant recipients at a single center: A retrospective cohort study.

BACKGROUND: Beta-lactam allergies (BLAs) are common in hospitalized patients, including transplant recipients. BLA is associated with decreased use of preferred surgical site infection (SSI) prophylaxis and increased SSIs, but this has not been studied in the transplant population. METHODS: We reviewed adult heart, kidney, and liver transplant recipients between January 1, 2016 and December 31, 2019 to characterize reported BLA and collect SSI prophylaxis regimens at time of transplant. We compared the use of preferred SSI prophylaxis and SSI incidence based on reported BLA status. Post hoc we collected antibiotic days of therapy (DOT) (excluding pneumocystis prophylaxis) in the 30-day period posttransplant for patients without SSI. We utilized descriptive statistics for comparisons. RESULTS: Of 691 patients included (116 heart, 400 kidney, and 175 liver transplant recipients), 118 (17%) reported BLA. Rash and hives were the two most reported BLA reactions (36% and 24%), categorized as potential T-cell mediated and IgE mediated, respectively. Preferred SSI prophylaxis was prescribed in 13 (11%) patients with BLA and 573 (92%) without BLA (p < .001). No difference could be detected in SSI incidence between BLA and non-BLA patients (4.2 vs. 4.3%, p = 1.0). Of 659 without SSI, 169 (25.6%) received antibiotics within 30 days of transplant; mean antibiotic DOT for BLA and non-BLA patients were 3.5 ± 8.0 versus 2.3 ± 5.8, p = .12. CONCLUSION: BLA transplant recipients received nonpreferred SSI prophylaxis more frequently than non-BLA recipients, but there was no difference in 30-day SSIs between the groups. One-fourth of solid organ transplant recipients received systemic antibiotics within 30 days of transplant.

Bloodstream Infections in Hematologic Malignancy Patients With Fever and Neutropenia: Are Empirical Antibiotic Therapies in the United States Still Effective?

Background: Rising antimicrobial resistance rates may impact the efficacy of empirical antibiotic treatment for febrile neutropenia in high-risk cancer patients. Lacking contemporary data about the epidemiology, antibiotic resistance patterns, and clinical outcomes from bloodstream infections (BSIs) in US cancer patients, it is unclear if current guidelines remain relevant. Methods: In a cross-sectional study, 14 US cancer centers prospectively identified BSIs in high-risk febrile neutropenic (FN) patients, including those receiving chemotherapy for hematologic malignancies or hematopoietic stem cell transplantation. Results: Among 389 organisms causing BSI in 343 patients, there was an equal distribution of gram-negative (GN) and gram-positive (GP) bacteria, with variability across centers. Cefepime and piperacillin-tazobactam were the most commonly prescribed empirical antibiotics for FN, at 62% and 23%, respectively; a GP-directed agent was empirically included in nearly half of all FN episodes within the first 24 hours. Susceptibility to fluoroquinolones, cefepime, piperacillin-tazobactam, and carbapenems was 49%, 84%, 88%, and 96%, respectively, among GN isolates. Critical illness (CrI), defined as a new requirement for mechanical ventilation, vasopressor, or death within 30 days, occurred in 15% and did not correlate with fluoroquinolone prophylaxis, organism type, initial antibiotics, or adequacy of coverage. Only severity of illness at presentation, signified by a Pitt bacteremia score ≥2, predicted for critical illness within 30 days. Mortality was 4% by day 7 and 10% overall. Conclusions: In accordance with US guidelines, cefepime or piperacillin-tazobactam remain effective agents or empirical treatment for high-risk cancer patients with FN who are stable at presentation, maintaining high GN pathogen susceptibility and yielding excellent outcomes.

The limits of refusal: An ethical review of solid organ transplantation and vaccine hesitancy.

Patients pursuing solid organ transplantation are encouraged to receive many vaccines on an accelerated timeline. Vaccination prior to transplantation offers the best chance of developing immunity and may expand the pool of donor organs that candidates can accept without needing posttransplant therapy. Furthermore, transplant recipients are at greater risk for acquiring vaccine-preventable illnesses or succumbing to severe sequelae of such illnesses. However, a rising rate of vaccine refusal has challenged transplant centers to address the phenomenon of vaccine hesitancy. Transplant centers may need to consider adopting a policy of denial of solid organ transplantation on the basis of vaccine refusal for non-medical reasons (i.e., philosophical or religious objections or personal beliefs that vaccines are unnecessary or unsafe). Arguments supporting such a policy are motivated by utility, stewardship, and beneficence. Arguments opposing such a policy emphasize justice and respect for persons, and seek to avoid worsening inequities or medical coercion. This paper examines these arguments and situates them within the special cases of pediatric transplantation, emergent transplantation, and living donation. Ultimately, a uniform national policy addressing vaccine refusal among transplant candidates is needed to resolve this ethical dilemma and establish a consistent, fair, and standard approach to vaccine refusal in transplantation.

De-escalation of empiric broad spectrum antibiotics in hematopoietic stem cell transplant recipients with febrile neutropenia.

Febrile neutropenia (FN) is a common serious complication in patients undergoing hematopoietic stem cell transplantation (HSCT) requiring urgent evaluation and initiation of empiric broad spectrum antibiotics (BSA). The appropriate duration of BSA for FN in patients with negative cultures and no identifiable infection remains undefined. We retrospectively analyzed allogenic and autologous HSCT patients with FN and negative infectious work-up at our facility from 2012 to 2018. The early de-escalation group (EDG) included those who had BSA de-escalation to fluoroquinolone prophylaxis at least 24 h prior to absolute neutrophil count (ANC) recovery after the patient was fever-free for at least 48 h. Among 297 patients undergoing their first HSCT who experienced FN with negative infectious work-up, 83 patients were de-escalated early with the remaining 214 in the standard of care group (SCG) whose BSA were continued until ANC was > 500. Duration of broad-spectrum antibiotics was shorter in EDG compared to SCG (3.86 days vs. 4.62 days, p = 0.03). Rates of mortality, new infections, and clinical decompensation requiring intensive care unit transfer and/or pressor use within 30 days were all similar between the two groups (0% vs. 0.4% p = 1.00, 0% vs. 1.4% p = 0.56, 13.2% vs. 8.4% p = 0.27). This indicates that it is safe to de-escalate antibiotics prior to ANC recovery, leading to less BSA exposure.

Antibiotic Prescribing and Respiratory Viral Testing for Acute Upper Respiratory Infections Among Adult Patients at an Ambulatory Cancer Center.

BACKGROUND: Outpatient antibiotic prescribing for acute upper respiratory infections (URIs) is a high-priority target for antimicrobial stewardship that has not been described for cancer patients. METHODS: We conducted a retrospective cohort study of adult patients at an ambulatory cancer center with URI diagnoses from 1 October 2015 to 30 September 2016. We obtained antimicrobial prescribing, respiratory viral testing, and other clinical data at first encounter for the URI through day 14. We used generalized estimating equations to test associations of baseline factors with antibiotic prescribing. RESULTS: Of 341 charts reviewed, 251 (74%) patients were eligible for analysis. Nearly one-third (32%) of patients were prescribed antibiotics for URIs. Respiratory viruses were detected among 85 (75%) of 113 patients tested. Antibiotic prescribing (P = .001) and viral testing (P < .001) varied by clinical service. Sputum production or chest congestion was associated with higher risk of antibiotic prescribing (relative risk [RR], 2.3; 95% confidence interval [CI], 1.4-3.8; P < .001). Viral testing on day 0 was associated with lower risk of antibiotic prescribing (RR, 0.4; 95% CI 0.2-0.8; P = .01), though collinearity between viral testing and clinical service limited our ability to separate these effects on prescribing. CONCLUSIONS: Nearly one-third of hematology-oncology outpatients were prescribed antibiotics for URIs, despite viral etiologies identified among 75% of those tested. Antibiotic prescribing was significantly lower among patients who received an initial respiratory viral test. The role of viral testing in antibiotic prescribing for URIs in outpatient oncology settings merits further study.