Tosh, Pritish K.

Abstract Background Over 80% of patients with hematologic malignancies develop some form of infectious complication, most commonly febrile neutropenia. Patients with febrile neutropenia have 10% mortality, which increases if antibiotic administration is delayed past 30 minutes. Studies have suggested β-lactam allergy may delay administration of antibiotic while putting patients at greater risk for inappropriate antibiotic choice and adverse effects stemming from this. We sought to describe the risks associated with β-lactam allergy in the neutropenic population. Methods We conducted a retrospective, descriptive study from January 2016 to December 2017 identifying patients with febrile neutropenia and a reported history of β-lactam allergy. Baseline characteristics, allergy data, treatment data, and outcomes were collected and analyzed. Results We identified 31 patients with febrile neutropenia and β-lactam allergy during this time period. Etiologies of neutropenia were hematologic malignancy (61.2%), stem cell transplantation (12.9%), solid-organ malignancy (22.6%), and autoimmune (3.3%). Reported reactions to β-lactams were rash (41.9%), hives (9.7%), anaphylaxis (3.2%), other (9.7%), and unknown (35.5%). Average time to antibiotic administration was 142.5 minutes. Antibiotic choice was cefepime (61.3%), piperacillin–tazobactam (6.5%), carbapenem (22.6%), fluoroquinolone (6.5%), cefepime and fluoroquinolone (3.2%), and vancomycin (58.1%). 51.6% received initial antibiotics consistent with the 2010 IDSA guidelines. Six patients underwent penicillin skin testing, all negative. 1 patient developed C. difficile infection, 1 developed MRSA colonization, and 3 developed VRE colonization. Mortality was 3.2% at 30 days and 16.1% at 90 days. Conclusion Our study estimated the antibiotic usage patterns and outcomes in patients with febrile neutropenia and reported β-lactam allergy. This showed low adherence to an established guideline for antibiotic choice in these patients. With rising antimicrobial resistance, there is a need to develop strategies to reduce inappropriate antimicrobial use, especially in patients with febrile neutropenia. Preemptive β-lactam allergy evaluation warrants further evaluation in the neutropenic population. Disclosures All authors: No reported disclosures.

Abstract Background The epidemiology of fungal infections in hematologic malignancies has changed in the past decade. Triazole prophylaxis has decreased Candida spp infections while infections due to other molds such as Aspergillus and Fusarium species have increased. Fusariosis has very poor prognosis, and after aspergillosis, is the most common invasive fungal infection in this patient population. We sought to describe fusariosis in patients with hematologic malignancy at the Mayo Clinic. Methods We performed a retrospective review of patients with culture-positive Fusarium infection from January 2003 to October 2016 at the Mayo Clinic, Rochester, MN. The records of patients were reviewed for demographics, diagnosis, treatment, and outcomes including mortality. Patients without a diagnosis of hematologic malignancy were excluded. Patients were classified with proven or probable Fusariosis based on the Revised Definitions of Invasive Fungal Disease from the EORTC/MSG Consensus Group. Results We identified 14 patients with hematologic malignancies (age range 17–76 years; median 60 years) with a confirmed culture diagnosis of Fusarium infection classified as proven (9 patients) or probable (5 patients). Two cases were isolated pulmonary infections, 3 extra-pulmonary, and 9 disseminated cases. Two patients had previously undergone stem cell transplantation. Eight patients (57%) were receiving antifungal prophylaxis at the time of diagnosis: 2 on voriconazole, 1 on posaconazole, 1 on fluconazole, 3 on echinocandins, and 1 on Amphotericin B. Nine patients (64%) were neutropenic at the time of diagnosis. Amphotericin was the initial treatment in 7 (50%) patients, with voriconazole added for 4 patients for combination therapy the first week. Voriconazole monotherapy was given initially in 5 patients. Seven patients (50%) were deceased at 6 weeks after culture positivity, with an additional 2 patients deceased by 12 weeks. Conclusion Fusarium infection outcomes in patients with hematologic malignancies are poor. Neutropenia was common in those diagnosed, and infections were more likely to be disseminated, with high mortality rates. Amphotericin was commonly used as initial treatment, with many physicians recommending combination therapy with two agents, commonly voriconazole. Disclosures All authors: No reported disclosures.

Abstract Background: There is demonstrated benefit when administering fluoroquinolones as infection prophylaxis in neutropenic patients; however, side effects, drug interactions and increasing drug resistance necessitate investigation toward safe and effective alternative therapies. This study investigates the use of oral third generation cephalosporins as antibacterial prophylaxis during chemotherapy-induced neutropenia to establish knowledge on alternative treatment options. Methods: A retrospective chart review was performed to compare incidence of febrile neutropenia and documented infection rates in Acute Myeloid Leukemia (AML) and intermediate to high International prognostic scoring system (IPSS) risk myelodysplastic syndrome (MDS) patients receiving antibacterial chemoprophylaxis at Mayo Clinic between January 2006 and April 2016. Patients were included if they were 18 years or older, had a diagnosis confirmed on bone marrow biopsy, received induction or first relapse induction-remission chemotherapy regimens and then subsequently were prescribed fluoroquinolone or an oral third generation cephalosporin prophylaxis for anticipated profound and prolonged neutropenia. The main regimens prescribed were cytarabine + anthracycline (7+3), daunorubicin + cytarabine + nilotinib, mitoxantrone + etoposide + cytarabine, all-trans-retinoic acid (ATRA) + anthracycline, all-trans-retinoic acid (ATRA) + arsenic, clofarabine + cytarabine, or an investigational trial. After meeting inclusion criteria the treatment arms were matched via Charlson comorbidity index ( ± 3) and age ( ± 5). Patients with a documented infection 48 hours after switching from either broad spectrum antibiotics to antibacterial prophylaxis, or from levofloxacin prophylaxis to an oral third generation cephalosporin were excluded from the study. All patients provided consent for review of their medical records for research purposes. This study was approved by the Mayo Foundations institutional review board. Results: A total of 565 patients admitted to Mayo Clinic inpatient leukemia service for chemotherapy and concurrently prescribed antibacterial prophylaxis with either levofloxacin or an oral third generation cephalosporin were screened between January 1, 2006 and April 1, 2016. Of those screened 397 patients met the inclusion criteria, and subsequently 123 patients were matched via Charlson comorbidity index and age. Patient characteristics are presented in Table I. Of the 123 study patients, 80 (65%) were male, and the median age was 58.6 years (IQR: 53.3-68.5). The population was comprised of 115 (93.5%) patients with AML, and 8 (6.5%) patients with MDS. By 30 days after prophylaxis start 109 of the 123 patients developed febrile neutropenia (89.9%, 95% CI: (82.8-94.1)). There was no difference in the risk of febrile neutropenia between those on levofloxacin and those on an oral third generation cephalosporin (hazard ratio [HR] = 1.057, 95% CI: 0.64-1.75, p=0.83). The mean ANC value at the time of febrile neutropenia was 0.47 (SD: 1.4). Documented reasons that patients did not receive an oral fluoroquinolone were QTc prolongation (34.2%), rash (21.1%), tendonitis (2.6%), anaphylaxis (5.3%), drug interaction with a treatment study drug (23.7%), or other (13.1%). Three patients died 30 days or less after the last dose of chemoprophylaxis (40 day survival: 96.6%, 95% CI: 92.7-100); two of the reported deaths were due to infection. Of the 111 patients who had a documented febrile episode, 40 (36%) had a culture positive infection. Gram positive organisms caused 27 (71.1%) of the infections, 11 (28.9%) were gram negative organisms, and 1 (2.6%) infection was due to an anaerobic organism. There were 3 (7.5%) polymicrobial infections, and 36 (90%) monomicrobial infections. The majority of the patients had bloodstream as the documented site of infection. Of the documented culture positive infections 15 (39.5%) showed resistance to levofloxacin and 6 (15.8%) had resistance to third generation cephalosporins when susceptibility testing was reported. Conclusions: These findings demonstrate comparable safety and efficacy of oral third generation cephalosporins compared to fluoroquinolones and contribute to the growing body of literature surrounding antibacterial prophylaxis during chemotherapy-induced neutropenia. Further prospective, randomized investigation is warranted. Disclosures No relevant conflicts of interest to declare.

Patients with febrile neutropenia (FN) often are subject to antibiotic and diagnostic test overuse. We sought to improve appropriate use of antimicrobials and diagnostic tests for patients with FN. We used a blended quality approach with Lean Six Sigma tools and iterative improvement of a clinical decision aid to guide providers through empirical antimicrobial selection and diagnostic evaluation of patients with FN during a yearlong period. We evaluated the incidence of nonadherence to best practice before, during, and after rollout of a clinical decision aid in conjunction with an educational initiative. At baseline, 71% of patients with FN had at least one critical deviation from best practice. During the project, the percentage decreased to 27.3%; 4 months after the project was completed, the percentage was 33.3% ( P = .04). A clinical decision aid can improve adherence to best practices for the empirical management of FN.

Background: Corticosteroid therapy is a well-recognized risk factor for Pneumocystis pneumonia (PCP); however, it has also been proposed as an adjunct to decrease inflammation and respiratory failure. Objective: To determine the association between preadmission corticosteroid use and risk of moderate-to-severe respiratory failure at the time of PCP presentation. Methods: This retrospective cohort study evaluated HIV-negative immunosuppressed adults diagnosed with PCP at Mayo Clinic from 2006 to 2016. Multivariable regression models were used to evaluate the association between preadmission corticosteroid exposure and moderate-to-severe respiratory failure at presentation. Results: Of the 323 patients included, 174 (54%) used preadmission corticosteroids with a median daily dosage of 20 (interquartile range: 10-40) mg of prednisone or equivalent. After adjustment for baseline demographics, preadmission corticosteroid therapy did not decrease respiratory failure at the time of PCP presentation (odds ratio: 1.23, 95% confidence interval: 0.73-2.09, P = .38). Additionally, after adjusting for inpatient corticosteroid administration, preadmission corticosteroid use did not impact the need for intensive care unit admission ( P = .98), mechanical ventilation ( P = .92), or 30-day mortality ( P = .11). Conclusions: Corticosteroid exposure before PCP presentation in immunosuppressed HIV-negative adults was not associated with a reduced risk of moderate-to-severe respiratory failure.

Background. Acute kidney injury (AKI) is a common complication of treatment with liposomal amphotericin B (LAmB). The trajectory of renal recovery after LAmB-associated AKI has not been well described, nor has effect of LAmB dose on recovery of renal function been explored. Objective. Characterize the pattern of renal recovery after incident AKI during LAmB and determine potential influencing factors. Methods. This retrospective cohort study analyzed patients who developed a ≥50% increase in serum creatinine while on LAmB. Patients were followed up until complete renal recovery or death or for 30 days, whichever occurred first. The primary outcome was complete renal recovery, defined as serum creatinine convalescence to within 10% of the patient’s pretreatment baseline. Multivariable modeling was used to identify independent predictors of renal recovery. Results. Ninety-eight patients experienced nephrotoxicity during LAmB, 94% of which received doses <7 mg/kg/day. Fifty-one patients at least partially recovered renal function and, of these, 32 exhibited complete recovery after a mean 9.8 ± 7.8 days. No statistical relationship was found between LAmB dose at the time of AKI or cumulative exposure to LAmB and the likelihood of renal recovery. Concomitant nephrotoxins, age, and pretreatment renal function did not modify this effect in multivariable analysis. Conclusion and Relevance. Our data suggests that LAmB dose did not impact the likelihood of renal recovery. Additional investigation is needed to confirm these findings when aggressive dosing strategies are employe. Additional research is also warranted to further characterize the course of recovery after LAmB-associated nephrotoxicity and comprehensive spectrum of renal outcomes.

The clinical utility of ganciclovir therapeutic drug monitoring (TDM) is unknown. We retrospectively analyzed adult patients treated for cytomegalovirus (CMV) infection with ganciclovir with TDM between 2005 and 2015.