Credit: CDC/Kimberly Smith
and Christine Ford
NEW YORK—Hand washing is still the single most effective method to prevent the transmission of infection, but additional measures can reduce the risk of cancer-related infections, according to a speaker at the NCCN 9th Annual Congress: Hematologic Malignancies.
In her presentation, Laura Zitella, RN, of the Stanford Cancer Institute in California, discussed current recommendations for pharmacologic and non-pharmacologic infection prophylaxis.
She noted that NCCN Guidelines on the Prevention and Treatment of Cancer-Related Infections state that the highest risk of infection is in patients undergoing allogeneic hematopoietic stem cell transplant (HSCT), acute leukemia patients undergoing induction or consolidation therapy, patients receiving alemtuzumab therapy, patients with graft-vs-host disease (GVHD) treated with high-dose steroids, and patients with neutropenia anticipated to last greater than 10 days.
Antibiotic prophylaxis
Prior to 2005, Zitella said, no survival benefit was observed for antibiotic prophylaxis. All of this changed with the results of a meta-analysis. The analysis included 95 randomized, controlled trials and 9283 patients, the majority having acute leukemia or undergoing HSCT.
For the first time, antibiotic prophylaxis was shown to confer a survival benefit. In neutropenic patients, prophylaxis reduced overall mortality by 33% and infection-related mortality by 42%, compared with placebo or no treatment.
Prophylaxis is not recommended for low-risk neutropenic patients, Zitella said, because it is not proven to decrease morality.
And the drugs of choice are levofloxacin (500-750 mg PO daily) or ciprofloxacin (500-750 mg PO twice daily).
Colony-stimulating factors
Consensus guidelines for the use of colony-stimulating factors (CSFs) are a compilation of ASCO, EORTC, ESMO, and NCCN guidelines.
CSFs may be used prophylactically to prevent chemotherapy-induced neutropenia, febrile neutropenia, and infection. They reduce the duration of hospitalization, the duration of parenteral antibiotics, and have shown a survival benefit.
CSFs are recommended if the risk of febrile neutropenia is 20% or greater. CSFs are not routinely recommended for patients undergoing radiation treatment, acute myeloid leukemia induction, or patients with Hodgkin lymphoma.
Antifungal prophylaxis
Zitella noted that fluconazole is the best-studied antifungal prophylaxis and is recommended as the primary prophylaxis for HSCT patients.
In double-blind, placebo-controlled trials, fluconazole reduced mucosal candidiasis and invasive Candida infections in patients undergoing HSCT. And it improved survival at day 110 after transplant.
Posaconazole prophylaxis has proven effective in patients with acute myeloid leukemia or myelodysplastic syndromes undergoing intensive chemotherapy. The drug reduced invasive fungal infections, including aspergillosis, and improved survival.
For patients with GVHD on immunosuppressive therapy, posaconazole and fluconazole prophylaxis were equivalent in preventing invasive fungal infections. However, posaconazole reduced the incidence of invasive aspergillosis and fungal-related mortality.
The NCCN guidelines, Zitella said, spell out which antifungal agents should be used for each disease or therapeutic intervention.
Antiviral prophylaxis
HSV and VZV
Patients requiring antiviral prophylaxis for herpes simplex virus (HSV) and varicella zoster virus (VZV) should be seropositive and have acute leukemia, GVHD treated with steroids, prior HSV reactivation under treatment, or have undergone HSCT.
Zitella pointed out that patients treated with proteasome inhibitors, such as bortezomib, alemtuzumab, or purine analaogs, such as fludarabine, are more at risk and should also receive antiviral prophylaxis.
Recommended drugs include valacyclovir, acyclovir, or famciclovir.
CMV
Cytomegalovirus-positive (CMV+) patients at high risk include those who have received an allogeneic HSCT or treatment with alemtuzumab.
Zitella explained that for these patients, prophylaxis is uncommon, and a pre-emptive strategy should be used, including testing 3 to 6 months after transplant or in the setting of GVHD and 2 months after alemtuzumab therapy.
CMV viremia should be treated with valganciclovir, ganciclovir, foscarnet, or cidofovir.
HBV
Zitella noted that 30% of the world population has been infected with hepatitis B virus (HBV), and reactivation during cancer treatment can lead to fulminant hepatitis and death.
NCCN recommends that patients undergoing immunosuppressive therapy, allogeneic HSCT candidates, patients receiving anti-CD20 monoclonal antibodies, those treated with alemtuzumab, and patients receiving systemic therapy who have an obvious risk factor for HBV infection should be tested.
Entecavir, tenofovir, adefovir, telbivudine, or lamivudine may be used to prevent HBV reactivation.
Pneumocystis pneumonia prophylaxis
Patients undergoing allogeneic HSCT, patients with acute lymphoblastic leukemia, those treated with alemtuzumab, and those with a CD4 count below 200 cells/mcL should receive pneumocystis pneumonia prophylaxis.
Trimethorpim/sulfamethoxazole is the drug of choice. Atovaquone, dapsone, and inhaled or IV pentamidine are alternatives.
Vaccines
Zitella pointed out that recommended vaccines include influenza, pneumococcal, and tetanus, diphtheria, and acellular pertussis.
She cautioned that live attenuated vaccines should not be given to cancer patients. Other vaccines to avoid include smallpox; measles, mumps, and rubella; varicella zoster; rotavirus; yellow fever; oral typhoid; BCG; and oral polio vaccine.
Neutropenic precautions
Low microbial diets are a hot topic among patients undergoing cancer treatment, Zitella said. Fresh fruits and vegetables used to be restricted, but no studies show that dietary restrictions decrease the risk of infection.
Zitella stressed, however, that standard food safety recommendations of the USDA/FDA should be followed.
She also noted that HEPA filtration is protective against molds in high-risk patients, antiseptic bathing has contradictory evidence, the benefit of laminar airflow is unclear, and protective isolation has not been proven to reduce the risk of infection.
