Experts Recommend Strategies for Antibiotic Use in Pediatric Patients With Hematologic Malignancies

By Cameron Kelsall, /alert Contributor

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An expert panel convened by 8th European Congress on Infections in Leukemia has issued guidelines for the use of antibiotic therapy in pediatric patients with leukemia and lymphoma, as well as those undergoing hematopoietic stem cell transplantation (HSCT).

The recommendations, which were published in The Lancet Oncology, cover antibacterial prophylaxis for bacterial infections, as well as initial empirical antibacterial therapy and appropriate de-escalation or discontinuation.

The risk for bacterial infections is elevated in pediatric patients with hematologic malignancies, and research suggests a growing resistance to antibacterial therapy, which can lead to increased morbidity and mortality rates.

Evidence-based guidelines for the optimal use of antibiotics have been developed for adult patients with cancer, but these recommendations are not necessarily transferable to pediatric patients. 

“[C]hildren have a different spectrum of cancer diagnoses compared with adults, and are consequently treated with different treatment protocols, which mostly have higher dose intensity,” wrote members of the expert panel. “Moreover, children usually have fewer comorbidities than adults, and the hematopoietic and immunological recovery also differs between children and adults. Finally, safety and pharmacokinetic data for pediatric patients is not always available for many antibiotics.”

The 16-member working group — comprised of pediatric hematologists and oncologists, transplant physicians and infectious disease experts — met during the 8th European Congress on Infections in Leukemia to formulate recommendations. 

The experts used the European Society of Clinical Microbiology and Infectious Diseases and European Confederation of Medical Mycology grading system to categorize recommendations as “strong” or “weak.” Proposed recommendations were presented to all members in attendance and adopted by a simple majority vote.

The panel recommended against the use of routine antibacterial prophylaxis for patients with leukemia or lymphoma, as well as those with neutropenia during pre-engraftment prior to HSCT. The recommendation was based on clinical trial and meta-analysis data that failed to show a significant reduction in bloodstream infections with antibiotic prophylaxis and provided inconclusive data on potential antibiotic resistance.

Recommendations for initial empirical antibiotic therapy for patients with febrile neutropenia were divided based on patient stability. The panel recommended that clinically stable patients receive monotherapy with an antipseudomonal non-carbapenem β-lactam plus β-lactamase inhibitor combination or fourth-generation cephalosporin. This category includes patients at low risk for resistant infections, without previous colonization or infections with resistant bacteria, and those treated at institutions with low rates of resistant pathogens.

For clinically unstable patients, defined as those with clear signs of severe sepsis or septic shock, the panel recommended carbapenem with or without a second anti–Gram-negative agent, and with or without a glycopeptide. This recommendation was made regardless of the patient’s risk for resistant infection.

“For patients who are colonized or were previously infected with resistant Gram-negative bacteria, or are in centers with a high rate of resistant pathogens, empirical treatment should be adjusted on the basis of the results of resistance testing,” the panel wrote.

Treatment centers should determine risk groups and surveillance strategies as a framework for de-escalation and discontinuation, according to the panel. “This strategy requires an analysis of the local epidemiology and a definition of patients at low risk of invasive infection and adverse outcome during febrile neutropenia, and depends on local infrastructure, ability to follow-up and patient return to hospital,” they wrote.

Patients with neutropenia and an identified causative pathogen should be treated with narrower-spectrum antibiotics as a part of the de-escalation process. The appropriate therapy should be determined by in-vitro susceptibility tests.

For patients with neutropenia and fever of unknown origin, de-escalation strategies should be determined by clinical factors. The panel recommended shifting clinically stable patients without colonization or previous infections to oral antibiotics from intravenous therapy after 72 hours, and endorsed discontinuation of all empirical antibiotics in appropriately selected patients.

Clinically unstable patients who stabilize after treatment with empirical antibiotics should not undergo therapeutic changes to initial therapy. De-escalation after 72 hours should be considered in clinically stable patients with previous colonization or infection.

“This includes discontinuation of any aminoglycoside, fluoroquinolone, colistin or any antibiotic directed against resistant Gram-positive pathogens, if given in combination, or a change to a narrower-spectrum antibiotic (eg, an antipseudomonal non-carbapenem β-lactam plus β-lactamase inhibitor combination),” the panel wrote.

In addition to the recommendations, the panel identified areas of future research, including the need for clinical trials to identify pediatric patients who may benefit from antibacterial prophylaxis. New antibiotic treatments are also needed to combat growing bacterial pathogen resistance, and further study should focus on safe de-escalation strategies for patients who remain at high risk for infection.

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