Comparison of subsequent infusion hypersensitivity reactions to paclitaxel using two different infusion strategies.

PURPOSE: The purpose of this study was to compare the incidence of rescue medication utilization with up to 3 subsequent doses of paclitaxel in patients who underwent an infusion rate escalation versus those who continued on the standard infusion rate after experiencing an initial paclitaxel infusion hypersensitivity reaction (HSR) requiring rescue medications. METHODS: A retrospective, single-center review was conducted on patients who experienced a paclitaxel infusion HSR requiring rescue medications to their first or second lifetime dose of paclitaxel. RESULTS: A total of 99 patients were included for analysis, and from this group, 22 patients were continued on the standard infusion rate, while 77 patients were changed to an infusion rate escalation. The rate of subsequent rescue medication utilization was 5% in patients who were continued at the standard infusion rate versus 23% in patients who were changed to an infusion rate escalation (p = 0.064). The incidence of subsequent rescue medication utilization was unrelated to disease stage (p = 0.39), the paclitaxel dosing regimen (p = 0.99), or a diagnosis of asthma (p = 0.99). CONCLUSION: This single-center, retrospective study suggests that while not statistically significant, there was a potentially clinically meaningful increase in the rate of subsequent rescue medication utilization in patients who were changed to an infusion rate escalation compared to those who continued on the same standard infusion rate after experiencing an initial HSR to paclitaxel.

Clinical Outcomes Associated With Linezolid Resistance in Leukemia Patients With Linezolid-Resistant Staphylococcus epidermidis Bacteremia.

BACKGROUND: Coagulase-negative staphylococci, including Staphylococcus epidermidis, are the most common cause of bloodstream infection in cancer patients. Linezolid resistance is increasingly identified in S. epidermidis, but whether such resistance alters the clinical course of S. epidermidis infections is unknown. The purpose of this study was to assess the clinical impact of linezolid resistance in leukemia patients with S. epidermidis bloodstream infection. METHODS: This was a retrospective, single-center cohort study of all adult leukemia patients with S. epidermidis bacteremia treated with empiric linezolid between 2012 and 2015. The primary end point was adverse clinical outcome on day 3, defined as a composite of persistent bacteremia, fever, intensive care unit admission, or death. Fourteen- and 30-day mortality were also assessed. RESULTS: Eighty-two unique leukemia patients with S. epidermidis were identified. Linezolid resistance was identified in 33/82 (40%). Patients with linezolid-resistant S. epidermidis were significantly more likely to have persistent bacteremia (41% vs 7%; adjusted relative risk [aRR], 5.15; 95% confidence interval [CI], 1.63-16.30; P = .005); however, adverse short-term clinical outcomes overall were not more common among patients with linezolid-resistant S. epidermidis (61% vs 33%; aRR, 1.46; 95% CI, 0.92-2.32; P = .108). No differences were observed in 14- or 30-day mortality. CONCLUSIONS: Leukemia patients with linezolid-resistant S. epidermidis bacteremia who were treated with linezolid were significantly more likely to have persistent bacteremia compared with those with linezolid-sensitive isolates. Interventions to limit the clinical impact of linezolid-resistant S. epidermidis are warranted.

Clonal Emergence of Invasive Multidrug-Resistant Staphylococcus epidermidis Deconvoluted via a Combination of Whole-Genome Sequencing and Microbiome Analyses.

Background: Pathobionts, bacteria that are typically human commensals but can cause disease, contribute significantly to antimicrobial resistance. Staphylococcus epidermidis is a prototypical pathobiont as it is a ubiquitous human commensal but also a leading cause of healthcare-associated bacteremia. We sought to determine the etiology of a recent increase in invasive S. epidermidis isolates resistant to linezolid. Methods: Whole-genome sequencing (WGS) was performed on 176 S. epidermidis bloodstream isolates collected at the MD Anderson Cancer Center in Houston, Texas, between 2013 and 2016. Molecular relationships were assessed via complementary phylogenomic approaches. Abundance of the linezolid resistance determinant cfr was determined in stool samples via reverse-transcription quantitative polymerase chain reaction. Results: Thirty-nine of the 176 strains were linezolid resistant (22%). Thirty-one of the 39 linezolid-resistant S. epidermidis infections were caused by a particular clone resistant to multiple antimicrobials that spread among leukemia patients and carried cfr on a 49-kb plasmid (herein called pMB151a). The 6 kb of pMB151a surrounding the cfr gene was nearly 100% identical to a cfr-containing plasmid isolated from livestock-associated staphylococci in China. Analysis of serial stool samples from leukemia patients revealed progressive staphylococcal domination of the intestinal microflora and an increase in cfr abundance following linezolid use. Conclusions: The combination of linezolid use plus transmission of a multidrug-resistant clone drove expansion of invasive, linezolid-resistant S. epidermidis. Our results lend support to the notion that a combination of antibiotic stewardship plus infection control measures may help to control the spread of a multidrug-resistant pathobiont.

Blinatumomab: Bridging the Gap in Adult Relapsed/Refractory B-Cell Acute Lymphoblastic Leukemia.

Adult patients with acute lymphoblastic leukemia who relapse after frontline therapy have extremely poor outcomes despite advances in chemotherapy and hematopoietic stem cell transplantation. Blinatumomab is a first-in-class bispecific T-cell engager that links T cells to tumor cells leading to T-cell activation and tumor cell lysis. In December 2014, the Food and Drug Administration approved blinatumomab for treatment of relapsed or refractory Philadelphia chromosome-negative precursor B-cell acute lymphoblastic leukemia. In a phase II trial, blinatumomab produced response rates of 43%, and 40% of patients achieving a complete remission proceeded to hematopoietic stem cell transplantation. Early use of blinatumomab was complicated with adverse effects, including cytokine release syndrome and neurotoxicity. Management strategies, including dexamethasone premedication and 2-step dose escalation during the first cycle of blinatumomab, have decreased the incidence and severity of these adverse effects. Blinatumomab currently is being studied for other B-cell malignancies and has the potential to benefit many patients with CD19+ malignancies in the future.