Over the last decade, the therapeutic landscape for hematological malignancies (HMs) has witnessed a remarkable surge in the development of novel biological and small‐molecule‐targeted ...immunomodulatory agents. These therapies have drastically improved survival, but some come at the cost of increased risk of bacterial, viral, and/or fungal infections and on‐target off‐tumor immunological side effects. To mitigate such risks, physicians must be well informed about infectious complications and necessary preventive measures, such as screening, vaccinations, and antimicrobial prophylaxis. Furthermore, physicians should be vigilant about the noninfectious side effects of these agents that can mimic infections and understand their potential drug–drug interactions with antimicrobials. Strengthening and harmonizing the current surveillance and reporting system for drug‐associated infections in real‐world settings is essential to better ascertain the potential infections associated with these agents. In this review, we aimed to summarize the infection risks associated with novel agents used for specific HMs and outline recommended strategies for monitoring and prophylaxis.
•COVID-19 prevention via vaccination or pre-exposure monoclonal antibodies remain the cornerstone for prevention of severe illness, hospitalization, and death from SARS-CoV-2 in hematopoietic stem ...cell transplantation and cellular therapy recipients•Optimal timing for transplantation and cellular therapy has to be individualized taking into consideration the urgency of treatment, as well as clinical and other considerations such as severity of illness, therapeutics and circulating variants.•Optimal duration of therapy, sequential therapy or combination therapy have not been studied in HCT/cell therapy recipients. Treatment related mutations are a concern in immunocompromised patients with persistent high-level viral replication.•The long-term outcomes of COVID-19-recovered HCT recipients are yet to be determined.
This document is intended as a guide for diagnosis and management of Coronavirus Disease 2019 (COVID-19), caused by the virus SARS-CoV-2, in adult and pediatric HCT and cellular therapy patients. This document was prepared using available data and with expert opinion provided by members of the (ASTCT) Infectious Diseases Special Interest Group (ID-SIG) and is an update of pervious publication. Since our original publication in 2020, the NIH and IDSA have published extensive guidelines for management of COVID-19 which are readily accessible ( NIH Guidelines , IDSA Guidelines ). This update focuses primarily on issues pertaining specifically to HCT/cellular therapy recipients. Information provided in this manuscript may change as new information becomes available.
Background: Various strategies aimed at limiting inappropriate antimicrobial use including antibiotic time out (ATO) have been proposed to combat the development of antimicrobial resistance, yet ...there are limited studies that have assessed the impact of ATO on clinical outcomes. Methods: This single-center retrospective study reviewed the effect of a passive ATO strategy by comparing 100 adult patients with an ATO matched by infection type to 100 antibiotic-treated adult patients lacking an ATO note. Results: No difference in clinical outcomes was observed, however, ATO did result in improved optimization of antibiotic selection and duration, and reduction of piperacillin/tazobactam and vancomycin use. Conclusion: Further studies are warranted to evaluate the impact of ATO on clinical outcomes of a larger homogenous population with specified infectious diagnoses and clinical characteristics.
Purpose of Review
The development of new antibody-based therapies has changed the landscape of the treatment of malignancies and improved post-transplant outcomes for transplant recipients. Use of ...these new therapies has led to recognition of unintended, potentially serious infectious complications. This review seeks to provide an overview of the infectious risks of these agents and assist clinicians in how to address them.
Recent Findings
Due to its profound depletion of B- and T-lymphocytes, alemtuzumab increases the risk of viral reactivation and other intracellular pathogens. Anti-CD20 agents increase the risk of hepatitis B virus reactivation and carry the risk of progressive multifocal leukoencephalopathy. Immune checkpoint inhibitors can cause immune-related adverse events that can masquerade as infections. Eculizumab increases the risk of
Neisseria
infections. Brentuximab vedotin appears to increase the overall risk of infection, though no specific prophylaxis strategies are recommended. Belatacept increases the risk of post-transplant lymphoproliferative disorders and
Pneumocystis jirovecii
pneumonia.
Summary
While improving outcomes and survival, novel therapies may have off-target effects, increasing the risk of bacterial, viral, and fungal infections. Clinicians must be aware of potential infectious complications and take measures to screen for latent infections, provide immunizations, and provide chemoprophylaxis (as indicated). Clinicians also need to be aware of potential non-infectious, inflammatory autoimmune complications of these agents that could present similarly to infection. Multi-disciplinary and multi-institutional research is needed to better define the association between these therapies and infection, and develop protocols to reduce infectious risk.
Purpose
Bloodstream infections (BSI) are significant causes of morbidity and mortality in cancer patients. These patients often receive 10 to 14 days of intravenous (IV) antibiotics. The objective of ...this study was to compare the outcomes of cancer patients transitioned from IV to oral (PO) therapy compared to continuation of IV treatment.
Methods
This was a single-center, retrospective cohort study of hospitalized adult cancer patients with gram-negative bacteremia. Patients transitioned to a PO fluoroquinolone (FQ) within 5 days were allocated to the IV-to-PO group, while the remaining patients comprised the IV group. The primary outcome was the composite of treatment failure, defined as infection-related readmission, infection recurrence, or inpatient mortality. A multivariable logistic regression model was constructed to account for confounding variables. Secondary outcomes assessed included infection-related length of stay (LOS), hospital LOS, and adverse events, such as
Clostridioides difficile
infection and catheter-related complications.
Results
The IV-to-PO group included 78 patients, while the remaining 133 patients were allocated to the IV group. Differences at baseline included more hematologic malignancy, neutropenia, ICU admissions, and higher Pitt bacteremia scores in the IV group. The rate of treatment failure was significantly higher in the IV group (24% vs 9%;
p
< 0.01), which persisted in the logistic regression (aOR 3.5, 95% CI 1.3–9.1). The IV-to-PO group had decreased infection-related and hospital length of stay, as well as fewer catheter-related complications.
Conclusions
The use of PO FQ may be considered for the definitive treatment of uncomplicated Enterobacterales BSI in cancer patients.
Abstract
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.
Abstract
There is currently a critical need to determine the efficacy of SARS-CoV-2 vaccination for immunocompromised patients. In this study, we determined the neutralizing antibody response in 160 ...cancer patients diagnosed with chronic lymphocytic leukemia (CLL), lung cancer, breast cancer, and various non-Hodgkin’s lymphomas (NHL), after they received two doses of mRNA vaccines. Serum from 46 mRNA vaccinated health care workers (HCWs) served as healthy controls. We discovered that (1) cancer patients exhibited reduced neutralizing antibody titer (NT
50
) compared to HCWs; (2) CLL and NHL patients exhibited the lowest NT
50
levels, with 50-60% of them below the detection limit; (3) mean NT
50
levels in patients with CLL and NHL was ~2.6 fold lower than those with solid tumors; and (4) cancer patients who received anti-B cell therapy exhibited significantly reduced NT
50
levels. Our results demonstrate an urgent need for novel immunization strategies for cancer patients against SARS-CoV-2, particularly those with hematological cancers and those on anti-B cell therapies.
Lung transplant recipients are at increased risk for infection in the early postoperative phase, thus perioperative antibiotics are employed. This retrospective study evaluated the efficacy of short‐ ...vs long‐course perioperative antibiotics in lung transplant patients. Lung transplant patients with donor positive cultures between August 2013 and September 2019 were evaluated, excluding those with cystic fibrosis, death within 14 days and re‐transplants. The primary outcome was 30‐day freedom from donor‐derived respiratory infection. A total of 147 patients were included (57 short vs 90 long‐course). Median perioperative antibiotic duration was 6 days in the short‐course vs 14 days in the long‐course group (P < .0001). Thirty‐day freedom from donor‐derived respiratory infection was present in 56 (98%) patients in the short‐course vs 85 (94%) patients in the long‐course group (P = .41). There was no difference in development of Clostridioides difficile infections (P = .41), while cumulative ventilator time and time to post‐op extubation were longer in the long‐course group (P = .001 and .004, respectively). Among lung transplant recipients with positive donor respiratory cultures, short‐course perioperative antibiotics were as effective as long‐course antibiotics in preventing donor‐derived bacterial respiratory infections.
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