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).

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.

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.

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.

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.

Reported ß-Lactam and Other Antibiotic Allergies in Solid Organ and Hematopoietic Cell Transplant Recipients.

BACKGROUND: Patients with reported ß-lactam antibiotic allergies (BLAs) are more likely to receive broad-spectrum antibiotics and experience adverse outcomes. Data describing antibiotic allergies among solid organ transplant (SOT) and hematopoietic cell transplant (HCT) recipients are limited. METHODS: We reviewed records of adult SOT or allogeneic HCT recipients from 1 January 2013 to 31 December 2017 to characterize reported antibiotic allergies at time of transplantation. Inpatient antibiotic use was examined for 100 days posttransplant. Incidence rate ratios (IRRs) comparing antibiotic use in BLA and non-BLA groups were calculated using multivariable negative binomial models for 2 metrics: days of therapy (DOT) per 1000 inpatient days and percentage of antibiotic exposure-days. RESULTS: Among 2153 SOT (65%) and HCT (35%) recipients, 634 (29%) reported any antibiotic allergy and 347 (16%) reported BLAs. Inpatient antibiotics were administered to 2020 (94%) patients during the first 100 days posttransplantation; average antibiotic exposure was 41% of inpatient-days (interquartile range, 16.7%-62.5%). BLA patients had significantly higher DOT for vancomycin (IRR, 1.4 [95% confidence interval {CI}, 1.2-1.7]; P < .001), clindamycin (IRR, 7.6 [95% CI, 2.2-32.4]; P = .001), and aztreonam in HCT (IRR, 9.7 [95% CI, 3.3-35.0]; P < .001), and fluoroquinolones in SOT (IRR, 2.9 [95% CI, 2.1-4.0]; P < .001); these findings were consistent when using percentage of antibiotic exposure-days. CONCLUSIONS: Transplant recipients are frequently exposed to antibiotics and have a high prevalence of reported antibiotic allergies. Reported BLA was associated with greater use of ß-lactam antibiotic alternatives. Pretransplant antibiotic allergy evaluation may optimize antibiotic use in this population.

Approach to infection and disease due to adenoviruses in solid organ transplantation.

PURPOSE OF REVIEW: Adenoviruses are an important cause of morbidity and mortality of solid organ transplant patients and remain a clinical challenge with regard to diagnosis and treatment. In this review, we provide an approach to identification and classification of adenovirus infection and disease, highlight risk factors, and outline management options for adenovirus disease in solid organ transplant patients. RECENT FINDINGS: Additional clinical data and pathologic findings of adenovirus disease in different organs and transplant recipients are known. Unlike hematopoietic cell transplant recipients, adenovirus blood PCR surveillance and preemptive therapy is not supported in solid organ transplantation. Strategies for management of adenovirus disease continue to evolve with newer antivirals, such as brincidofovir and adjunctive immunotherapies, but more studies are needed to support their use. SUMMARY: Distinguishing between adenovirus infection and disease is an important aspect in adenovirus management as treatment is warranted only in symptomatic solid organ transplant patients. Supportive care and decreasing immunosuppression remain the mainstays of management. Cidofovir remains the antiviral of choice for severe or disseminated disease. Given its significant nephrotoxic effect, administration of probenecid and isotonic saline precidofovir and postcidofovir infusion is recommended.

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.

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.

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.

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.

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.

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.

Unintended Consequences of Pretransplant Vancomycin-Resistant Enterococcus Screening on Antimicrobial Stewardship Among Allogeneic Hematopoietic Cell Transplant Recipients.

We examined vancomycin-resistant enterococci (VRE)-directed antimicrobial use and VRE bacteremia in a cohort of allogeneic hematopoietic cell transplantation patients from a center where VRE screening is standard prior to transplant. In this cohort, VRE bacteremia (VREB) was infrequent. In patients without VREB, colonized patients received VRE therapy more often than noncolonized patients.Infect Control Hosp Epidemiol 2018;39:730-733.