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Antibacterial Prophylaxis Reduces Infections During Induction Chemotherapy for ALL

TOP - February 2016, Vol 9, No 1

Orlando, FL–Bacterial infections during induction chemotherapy in pediatric patients with acute lymphoblastic leukemia (ALL) can largely be prevented with fluoroquinolone prophylaxis, according to a prospective, multicenter study from the Dana-Farber Cancer Institute (DFCI) ALL Consortium.

Pediatric patients who are newly diagnosed with ALL have a high risk for bacterial infections, primarily during treatment induction, according to Maria Luisa Sulis, MD, Assistant Professor, Pediatrics, Columbia University Medical Center, New York, who presented the study at the 57th American Society of Hematology Annual Meeting & Exposition. The main cause of treatment-related mortality during the treatment induction phase is infections; it also prolongs hospitalization and causes dose reductions and delays in chemotherapy.

"[In] the DFCI ALL Consortium Protocol 05-001, 24.7% of children experienced ≥1 documented bacterial infection," explained Dr Sulis. "Levofloxacin prophylaxis has been shown to reduce infections in adults with chemotherapy-induced neutropenia, but the role of antibacterial prophylaxis in children undergoing induction chemotherapy for ALL is unknown."

The aim of the study was to evaluate the protective effect of prophylactic fluoroquinolones in DFCI Protocol 11-001, and to compare the rate of infection to that documented in the earlier DFCI Protocol 05-001. The key findings of the study were that:

  • 87 patients received fluoroquinolone prophylaxis
  • 45% developed a new fever while on prophylaxis
  • 9.2% developed a documented bacterial infection
  • 4.5% developed Clostridium difficile enterocolitis.

"The results of our prospective, multi-institutional, nonrandomized study indicate that treating newly diagnosed pediatric ALL patients with antibiotics throughout the induction phase (including the use of antibiotic prophylaxis for afebrile patients) is effective at reducing the incidence of bacterial infections, and does not result in an increase in fungal infections or a high incidence of C difficile colitis," Dr Sulis and colleagues reported.

Study Methods

Between 2012 and 2015, researchers from 9 sites enrolled 229 patients (median age, 5.1 years) in Protocol 11-001. The patients received induction therapy with vincristine, methylprednisolone, doxorubicin, low-dose methotrexate, and pegylated L-asparaginase. Afebrile patients were started on fluoroquinolone prophylaxis at therapy initiation, and continued until recovery of white blood cell count at the end of induction.

Patients who developed fever or documented infection were switched to broad-spectrum antibiotics (eg, cefepime). Those with fever at presentation were started on broad-spectrum antibiotics rather than fluoroquinolone, and stayed on those or were switched to fluoroquinolone prophylaxis until count recovery, per the treating clinician. Antifungal prophylaxis was not required.

Researchers recorded all episodes of microbiologically documented bacterial infection, fungal infection, and C difficile enterocolitis. The rates of infection during Protocol 11-001 were compared with the rates among the 794 patients in the predecessor study, DFCI Protocol 05-001; this earlier study included nearly identical induction chemotherapy, but did not mandate antibiotic prophylaxis.

Of the 229 patients in Protocol 11-001, 87 (38%) afebrile persons were given upfront antibiotic prophylaxis, and 141 (61.6%) had fever at diagnosis and received broad-spectrum antibiotics; 2 afebrile patients did not receive antibiotic prophylaxis.

Of the patients who began prophylaxis, 45% subsequently developed fever. The number of patients experiencing an infection in Protocol 11-001 (13.5%) was significantly lower than in Protocol 05-001 (26.6%; P < .0001). The observed reduction was caused by a decrease in bacterial infection incidence (10.5% vs 24.7%; P < .0001), the authors of the study said.

"Fluoroquinolone prophylaxis decreased the rate of both gram-negative and gram-positive infections," Dr Sulis added. Significantly lower rates of Staphylococcus aureus (P = .0006) and Streptococcus viridans (P = .02) were recorded in Protocol 11-001 compared with Protocol 05-001.

Antibacterial prophylaxis was not associated with high rates of fungal infections (approximately 4% per arm) or C difficile colitis during induction, which was seen in 8.3% and mostly grade 2. Deaths during induction also did not differ, with rates of 0.9% in Protocol 11-001, and 2.0% in Protocol 05-001 (P = .34).

Age, presenting white blood cell count, and immunophenotype were not associated with infection development.

"The use of antibiotics during induction chemotherapy is safe, and does not lead to increased fungal infections," Dr Sulis concluded.

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