Background Patients with reported beta lactam antibiotic allergies (BLA) 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 1/1/2013-12/31/2017 to characterize reported antibiotic allergies at time of transplant. Inpatient antibiotic use was examined for 100 days post-transplant. Incidence rate ratios (IRR) comparing antibiotic use in BLA and non-BLA groups were calculated using multivariable negative binomial models for two metrics: days of therapy (DOT)/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 BLA. Inpatient antibiotics were administered to 2020 (94%) patients during the first 100 days post-transplant; average antibiotic exposure was 41% of inpatient days (Interquartile range (IQR) 16.7%, 62.5%). BLA patients had significantly higher DOT for vancomycin (IRR 1.4; 95% confidence interval (CI) [1.2, 1.7]; p<0.001), clindamycin (IRR 7.6; 95% CI [2.2, 32.4]; p=0.001), aztreonam in HCT (IRR 9.7; 95% CI [3.3, 35.0]; p<0.001), and fluoroquinolones in SOT (IRR 2.9; 95% CI [2.1, 4.0]; p<0.001); 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 beta lactam antibiotic alternatives. Pre-transplant antibiotic allergy evaluation may optimize antibiotic use in this population.

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.

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 deescalation 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.

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 (BSI) in U.S. cancer patients, it is unclear if current guidelines remain relevant. Methods In a cross-sectional study, fourteen U.S. cancer centers prospectively identified BSIs in high-risk FN patients, including those receiving chemotherapy for hematologic malignancies or hematopoietic stem cell transplantation. Results Among 389 organsims 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 &gt; 2, predicted for critical illness within 30 days. Mortality was 4% by day 7 and 10% overall. Conclusion In accordance with U.S. 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.

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.

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.

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