Live attenuated vaccines contain a form of the living organism that has been weakened so it should not cause disease. There is the possibility that the living microbe in the vaccine could become virulent and cause disease. Examples of live attenuated vaccines are intransal influenza vaccine, varicella vaccine, oral polio vaccine, and the measles, mumps, and rubella vaccine. The potential of attenuated microbes to become virulent is of concern related to prevention of infection among patients with cancer, particularly those who are significantly immunocompromised.
Freifeld, A.G., Bow, E.J., Sepkowitz, K.A., Boeckh, M.J., Ito, J.I., Mullen, C.A., . . . Wingard, J.R. (2011). Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the Infectious Diseases Society of America. Clinical Infectious Diseases, 52, e56-e93.
To provide a guide for the use of antimicrobial agents for chemotherapy-induced fever and neutropenia in patients with cancer. The patient population targeted included adult and pediatric patients with neutropenia.
For this guideline document, the IDSA Standards and Practice Guidelines Committee reconvened many members of their original guideline panel, together with additional experts, in the management of patients with fever and neutropenia. The committee included experts in infectious diseases, oncology, and hematopoietic stem cell transplantation (HSCT) in both adult and pediatric patients. The literature was reviewed and graded according to a systematic weighting of the level and grade of the evidence for making a recommendation.
Patients were undergoing the active treatment phase of care.
Antibiotic Prophylaxis
Fluoroquinolone prophylaxis should be considered for high-risk neutropenic patients (patients expected to have absolute neutrophil counts (ANCs) of 100 cells/mm3 or lower for more than seven days. Levofloxacin and ciprofloxacin are the agents that have been evaluated the most and are generally equivalent, although levofloxacin is preferred for patients at risk for oral mucositis-related invasive viridans group streptococcal infection (B-1). The addition of a gram-positive active agent to fluoroquinolone prophylaxis is not recommended (A-1). Antibacterial prophylaxis is not indicated for low-risk patients anticipated to be neutropenic for less than seven days (A-III).
Antifungal Prophylaxis
Patients at high risk for candida infection, such as recipients of allogeneic HSCT and patients with acute leukemia undergoing intensive chemotherapy, should be treated with antifungal prophylaxis with fluconazole, itraconazole, voriconazole, posaconazole, micafungin, or caspofungin (A-I). Patients aged 13 years or older who are undergoing intensive chemotherapy for acute leukemia or myelodysplastic syndrome who are at high risk for aspergillus infection may be treated with posaconazole for antifungal prophylaxis (B-I). Prophylaxis against aspergillus infection is not effective in recipients of pre-engraftment HSCTs, but it is recommended for patients with a prior history of invasive aspergillosis (A-III), anticipated neutropenia of at least two weeks (C-III), or a prolonged period of neutropenia prior to transplantation (C-III). Antifungal prophylaxis is not recommended for patients with an anticipated duration of neutropenia of less than seven days (A-III).
Antiviral Prophylaxis
Herpes simplex virus–positive patients undergoing allogeneic HSCT or leukemia induction therapy should receive acyclovir antiviral prophylaxis (A-I). Annual influenza vaccination is recommended for all patients being treated for cancer (A-II). The optimal timing has not been established, but serologic responses may be best between chemotherapy cycles (more than seven days after the last treatment) or more than two weeks prior to the start of therapy (B-III).
Colony-Stimulating Factors
Colony-stimulating factors are recommended for prophylaxis against neutropenia when the anticipated risk of fever and neutropenia is 20% or greater.
Prevention of Catheter-Related Bloodstream Infections
Hand hygiene, maximal sterile barrier precautions, and cutaneous antisepsis with chlorhexidine are recommended for all central venous catheter insertions (A-I).
Hand Hygiene
Hand hygiene is the most effective means of preventing infection in the hospital (A-II).
Environment
HSCT recipients should be in private rooms (B-III). Patients with neutropenia do not need to be placed in single-patient rooms. Allogeneic HSCT recipients should be in rooms with more than 12 air exchanges, high-efficiency particulate absorption filtration, and positive pressure (A-III). Plants and dried or fresh flowers should not be allowed in the rooms of hospitalized neutropenic patients (B-III).
Isolation and Barrier Precautions
No specific protective gear (gowns, gloves, or masks) are necessary during the routine care of neutropenic patients. Standard barrier precautions should be used for all patients when contact with body fluids is anticipated.
Food
In general, food should be well cooked. Well-cleaned uncooked fruits and vegetables are acceptable.
Skin and Oral Care
Daily showers are recommended to maintain skin integrity (expert opinion). Patients should brush their teeth two times per day or more with a regular toothbrush, and flossing can be performed if it can be performed without trauma (expert opinion). Patients with mucositis should rinse their mouths with sterile water, saline, or sodium bicarbonate rinses four to six times per day (expert opinion). Menstruating immunocompromised women should avoid tampons (expert opinion). Rectal thermometers, enemas, suppositories, and rectal examinations are contraindicated for patients with neutropenia (expert opinion).
This was a comprehensive guideline developed by the Infectious Diseases Society of America (IDSA) to guide clinicians in the care of patients with chemotherapy-induced neutropenia and in the management of febrile neutropenia. The full guide can be located at http://cid.oxfordjournals.org/content/52/4/e56.full.
Krüger, W.H., Bohlius, J., Cornely, O.A., Einsele, H., Hebart, H., Massenkeil, G., . . . Wolf, H.H. (2005). Antimicrobial prophylaxis in allogeneic bone marrow transplantation. Guidelines of the infectious diseases working party (AGIHO) of the German Society of Haematology and Oncology. Annals of Oncology, 16, 1381–1390.
To provide a guideline for the use of antimicrobial prophylaxis for patients in an allogeneic bone marrow transplantation setting.
This was classified as a guideline of evidence-based medicine criteria. The author used a table to rate available evidence-based articles about antimicrobial prophylaxis in allogeneic bone marrow transplant recipients.
Evidence was rated using this table.
Category, Grade Definition
Strength of Recommendation
A Good evidence to support a recommendation for use (strongly recommended)
B Moderate evidence to support a recommendation for use (generally recommended)
C Poor evidence to support a recommendation (optional)
D Moderate evidence to support a recommendation against use (generally not recommended)
E Good evidence to support a recommendation against use (never recommended)
Quality of Evidence
I Evidence from at least one well-executed randomized, controlled trial
II Evidence from at least one well-designed clinical trial without randomization; cohort or
case-controlled analytic studies (preferable from more than one center); multiple time-series
studies; or dramatic results from uncontrolled experiments
III Evidence from opinions of respected authorities based on clinical experience, descriptive
studies, or reports of expert committees.
Bacterial
Al: Fluoroquinolones should be used for antibacterial prophylaxis.
BII: Pneumococcus prophylaxis should be used for any patient with active chronic graft-versus-host disease and for the remainder of the patient's life following splenectomy.
BIII: Patients already receiving Pneumocystis carinii pneumonia (PCP)-prophylaxis with trimethoprim/sulfamethoxazole (TMP-SMZ) should have additional prophylaxis based on the epidemiology for the area and patterns of resistance.
DI: Anti-infectious prophylaxis with intravenous immunoglobulins should be used.
Cytomegalovirus
Preventing Exposure
AIII: All patients being considered for allogeneic stem cell transplant should have anti-cytomegalovirus (CMV) IgG-antibody testing. This is recommended to establish the risk for reactivation (de novo infection).
BIII: CMV-negative transplant candidates and patients should not share drinking cups or eating utensils that have been used by others. If a patient who is CMV-negative is in a monogamous relationship, his/her partner is advised to be CMV-serotested. If his/her partner is positive or the patient is not in a monogamous relationship, condom use during sexual contact is recommended.
Al: Transplant recipients who are CMV-seronegative should receive blood products from donors who have also tested negative. When blood banks lack CMV-negative donors, only leukocyte-depleted red cells and thrombocytes should be issued to this group.
DI: CMV prophylaxis should use preparations of human immunoglobulin for CMV-negative matched related donors.
Preventing Disease and Reactivation
BIII: For a CMV-positive recipient, most transplant physicians recommend a CMV-positive donor.
Al: Any patient at risk for CMV disease should be screened for pp65 antigenemia or nucleic acid using real-time polymerase chain reaction (PCR) at least weekly after transplant from days 10 to 100.
Al: Patients should begin pre-emptive therapy following one positive pp65 or two consecutive PCR results. Pre-emptive therapy is advised for two weeks, followed by another two weeks of maintenance therapy.
AI: In a pre-emptive setting, if the patient has resistance to ganciclovir, switching to foscarnet is recommended.
AI: The recommendation for herpes simplex virus (HSV) reactivation in IgG-positive patients is acyclovir. Acyclovir therapy should begin between the start of conditioning therapy and day 1 after the transplant and should continue until day 30 after stem cell transplantation.
Al: The recommendation of drugs for prophylaxis or therapy of CMV are ganciclovir and foscarnet. (Cidofovir has a BII recommendation.)
EI: High-dose acyclovir and valacyclovir should be used to prevent CMV.
El: Human immunoglobulins should be used for prophylaxis or therapy of CMV.
Herpes Simplex Virus
Preventing Exposure
AIII: Serum tests for anti-HSV serostatus are mandatory.
Preventing Reactivation
AI: Acyclovir should be used for standard reactivation prophylaxis, beginning between the start of conditioning therapy and day 1 posttransplant and continuing to day 30 following stem cell transplant.
CI: Evidence is lacking for the use of acyclovir prophylaxis increased to 100 days or more.
BIII: If repeated reactivation is present after 30 days of prophylaxis, continued therapy is recommended.
EIII: Acyclovir is not recommended for continued HSV prophylaxis at times when gancyclovir or foscarnet is used for CMV therapy or prophylaxis because gancyclovir and foscarnet are effective against HSV in vitro.
CIII: The effectiveness of valacyclovir and famciclovir in preventing HSV reactivation lacks the support of trials, but they are presumed effective.
Varicella-Zoster Virus
AIII: All patients being considered for stem cell transplant should avoid contact with those suspected of active varicella-zoster virus (VZV) infection or reactivation.
BIII: Those living with or in close contact with a transplant patient should be vaccinated before transplant.
AIII: To prevent nosocomial spread, transplant patients with overt VZV disease are to be isolated until all lesions are crusted.
CIII: Long-term acyclovir prophylaxis is not effective for prevention.
Epstein-Barr Virus
AIII: Seronegative transplant candidates and patients with Epstein-Barr virus (EBV) should not share drinking cups or eating utensils that have been used by others. If a patient negative for EBV is in a monogamous relationship, his/her partner is advised to be EBV-serotested. If his/her partner is positive or the patient is not in a monogamous relationship, condom use during sexual contact is recommended.
Community Respiratory Virus
AIII: Exposure prophylaxis is critical in avoiding respiratory syncytial virus, influenza, parainfluenza, and adenovirus.
BII: Those living with or working on units with transplant patients should be vaccinated for influenza.
BIII: Patients should receive a two-week course of amantadine or rimantadine for chemoprophylaxis if vaccination occurred during an influenza outbreak.
Yeasts
CIII: Foods at risk for allowing fungi to colonize in the gastrointestinal (GI) tract should be restricted.
AIII: Hand washing and disinfecting by personnel should be performed to prevent GI-colonizing fungi from reaching patients at risk.
Al: It is recommended to take fluconazole 400 mg/day IV or orally to prevent yeast infections in allogeneic stem cell recipients while they are neutropenic.
BI: One study found itraconazole superior to fluconazole but noted that GI side effects can limit oral use.
EII: Itraconazole is not recommended for yeast prophylaxis because of interactions with metabolism of busulfan.
EI: Itraconazole is not recommended for yeast prophylaxis because of interactions with metabolism of cyclophosphamide.
Molds
AII: Stem cell transplant candidates and patients must avoid construction, renovation, or other areas with dust exposure.
AII: Use of air conditioning with high-efficiency particulate absorption filtration or laminar air flow in transplant units reduces mold spore presence in the air and mortality related to fungal invasion.
BIII: Transplant patients should wear appropriate fitting masks when traveling through or to areas off the transplant unit.
BII: No drug demonstrates effectiveness for the primary prophylaxis of aspergillosis following bone marrow transplant.
DII: Itraconazole capsules are limited based on low bioavailability.
AI: For patients with acute leukemia, itraconazole solution reduced the incidence of invasive aspergillosis if plasma levels were greater than 500 ng/mL.
AIII: Secondary prophylaxis with a drug having systemic effectiveness was recommended despite a lack of trial evidence.
Pneumocystis jiroveci (formerly Pneumocystis carinii)
BIII: Stem cell recipients are not to have contact with patients with known PCP.
AII: TMP-SMZ prophylaxis should be used for all allogeneic transplant patients beginning at engraftment until the completion of immunosuppressive therapy or when chronic graft-versus-host disease is resolved.
AII: Dapsone or aerosolized pentacarinate should be used when TMP-SMZ is contraindicated or when the patient does not tolerate it. Higher breakthrough rates are noted with these alternate drugs.
Toxoplasmosis
AIII: Allograft recipient candidates should be tested for Toxoplasma gondii antibodies to identify risk for reactivation. Education should include ways to avoid exposure.
CIII: Toxoplasma prophylaxis at the time of acute graft-versus-host disease or secondary prophylaxis following history of toxoplasmosis should be performed.
Food
BIII: Foods with a risk of fungi, bacteria, or other contamination should be eliminated during and following stem cell transplant, and safer alternatives should be used (e.g., pasteurized cheese instead of unpasteurized cheese).
Vaccination After Stem Cell Transplant
AIII: Immunity against specific pathogens should be analyzed one year after allogeneic transplant with reimmunization with inactivated vaccine or toxoids.
The article also states that stem cell transplant recipients are not to receive live-attenuated virus vaccination during the two years after transplant. No rating was provided for this “strictly contraindicated” recommendation.
Specific recommendations with strong evidence, AI and EI, should be included in nursing practice guidelines with recommendations for and against practice, respectively. Other recommendations should not be included until higher evidence from trials can be demonstrated or included in the “Evidence Not Established” category.
Ljungman, P., Engelhard, D., de la Cámara, R., Einsele, H., Locasciulli, A., Martino, R., . . . Infectious Diseases Working Party of the European Group for Blood and Marrow Transplantation. (2005). Vaccination of stem cell transplant recipients: recommendations of the Infectious Diseases Working Party of the EBMT. Bone Marrow Transplantation, 35, 737–746.
To update previous recommendations (released in 1995 and last updated in 1999) for vaccinations in pediatric and adult hematopoietic stem cell transplantation (HSCT) recipients.
This resource was classified as a guideline.
Recommendations for 18 vaccinations were drawn from published data, most of which were specific to stem cell transplantation recipients. The strength of each recommendation and the quality of evidence supporting it are noted in a summary table, using grading standards endorsed by the Centers for Disease Control and Prevention (CDC).
Patients undergoing HSCT are advised to be vaccinated against bacterial and viral infections beginning six to 12 months after transplantation, with the exception of meningococcal vaccine. Because polysaccharide pneumococcal vaccines are ineffective in patients with chronic graft-versus-host disease (GVHD), antibiotic prophylaxis should be given to patients with GVHD in addition to the pneumococcal vaccine. Three doses of Haemophilus influenzae type B (Hib) conjugate vaccine, tetanus toxoid vaccine, and diphtheria toxoid vaccine should be given beginning six months posttransplantation and spaced one to three months apart. Routine vaccination against pertussis was not recommended. Bacillus Calmette-Guerin vaccine was specifically contraindicated in this population.
Inactivated influenza vaccine was recommended for all patients undergoing HSCT, beginning no earlier than four to six months posttransplantation. For patients undergoing allogeneic HSCT, influenza vaccination should be given annually (prior to influenza season) and continue at least as long as the patient remains immunocompromised. For patients undergoing autologous HSCT, the duration of yearly influenza vaccination should be assessed individually. Patients undergoing HSCT and those in close contact with them (e.g., family members and hospital staff who care for these patients) should be vaccinated against polio using the inactivated poliovirus vaccine only.
Patients undergoing HSCT should receive three doses of the inactivated vaccine, beginning six to 12 months following transplantation, with subsequent doses one to three months apart. Hepatitis B vaccination (HBV) is recommended for patients undergoing HSCT living in countries where HBV is recommended for the general public and should be given six to 12 months following HSCT. Vaccination with two doses of hepatitis A may be considered for patients who live or plan to travel to areas where the disease is endemic. The measles, mumps, and rubella (MMR) vaccine is generally recommended to begin no sooner that 24 months after HSCT but may be considered earlier if there is a high risk of measles. MMR is contraindicated in patients with chronic GVHD or ongoing immunosuppression. To prevent varicella, seronegative family members should be immunized with the varicella-zoster virus (VZV) vaccine. Seronegative patients undergoing HSCT may be considered for the VZV vaccine two years following transplantation, provided they are free of GVHD or ongoing immunosuppression. Vaccination of seropositive patients undergoing HSCT is not recommended.
Vaccination against yellow fever should only be considered in patients undergoing HSCT who must travel to areas of the world where yellow fever is endemic. Guidelines for serological testing of immune status are also included, again following the CDC grading standards. Immunity testing before vaccination is not necessary for tetanus toxoid, diphtheria toxoid, polio, influenza, pneumococcal, and Hib but is recommended for HBV, measles, mumps, and rubella (MMR), and varicella-zoster virus (VZV). Postvaccination testing to assess immune response is not recommended for tetanus toxoid, diphtheria toxoid, polio, Hib, or influenza. It is recommended for hepatitis B, MMR, and VZV and also may be considered for pneumococcal vaccine for patients at increased risk of poor response.
This article provided a concise summary for providers to use when considering the vaccination needs of HSCT recipients. It rated the strength of each recommendation using CDC guidelines. The article was extensively referenced to aid readers who wish to delve more deeply into the studies supporting each recommendation.
National Comprehensive Cancer Network. (2011). NCCN Clinical Practice Guidelines in Oncology: Prevention and treatment of cancer-related infections [v.2.2011]. Retrieved from https://www.nccn.org/professionals/physician_gls/pdf/infections.pdf
To provide guidance for clinical practices for the prevention and treatment of infection in patients with cancer.
This resource is a consensus-based guideline.
Patients were undergoing the active antitumor treatment phase of care.
The guideline
The National Comprehensive Cancer Network (NCCN) does not currently endorse the use of a vancomycin lock solution for long-term vascular access devices due to concerns about the emergence of bacterial resistance if widely used. Influenza vaccination with a vaccine that does not use live attenuated organisms can be safely given, and the guideline recommends administration at least two weeks before receiving cytotoxic therapy.
This study lacked high-quality evidence, with most recommendations being based on consensus.
This guideline provided comprehensive references to assess patient risk of infection and expert recommendations regarding interventions aimed at the prevention and treatment of infection in patients with cancer. The guideline does not discuss long-term survivorship issues in this area.
Tomblyn, M., Chiller, T., Einsele, H., Gress, R., Sepkowitz, K., Storek, J., . . . Centers for Disease Control and Prevention. (2009). Guidelines for preventing infectious complications among hematopoietic cell transplantation recipients: a global perspective. Biology of Blood and Marrow Transplantation, 15, 1143–1238.
To update previously published guidelines from 2000 for the prevention of infection in patients receiving any type of hematopoietic stem cell transplantation (HSCT). Patients analyzed were adults and pediatric populations receiving allogeneic or autologous HSCT.
The resource was presented as an evidence-based guideline. An international group of experts from identified professional organizations reviewed and graded evidence and developed recommendations.
The volume and highly specific process were not discussed.
Recommendations were made, and possible opportunistic infections at pre-engraftment, post-engraftment, and late phases of HSCT were identified. Recommendations included
Timing and appropriate individuals for various immunizations are important considerations, and it is recommended that users of this information refer to the full report. Overall, use of live vaccines is contraindicated for these patients; vaccination is contraindicated in those with chronic graft-versus-host disease or when patients are still immunosuppressed.
Some recommendations were based on expert opinion due to lack of research evidence in the area.
Specific interventions for prevention of infection among HSCT recipients is a complex field, and healthcare providers who work with these patients need to be aware of current knowledge. Evidence in this area continues to evolve as HSCT techniques change and further evidence is gained regarding the immediate and long-term effects of HSCT.