Environmental Interventions

To evaluate the significance of a protective environment (PE) on febrile neutropenia and mortality in patients with cancer with chemotherapy-induced neutropenia

The intervention was comprised of engineering and design interventions, incorporating high-efficiency particulate filters, positive air pressure, well-sealed rooms, and infection control routines according to international recommendations for a PE. Outcomes were compared to those of patients admitted prior to the implementation of standard environmental practices.

• N = 371
• MALES: 47%, FEMALES: 53%
• KEY DISEASE CHARACTERISTICS: Acute myeloid leukemia, chronic myeloid leukemia, acute lymphoid leukemia, chronic lymphoid leukemia, multiple myeloma, Hodgkin disease, non-Hodgkin lymphoma, myelodysplastic syndrome, other hematologic malignancies, aplastic anemia, solid tumors
• OTHER KEY SAMPLE CHARACTERISTICS: Risk categories of autologous hematopoietic stem cell transplantation (HSCT), allogeneic HSCT, acute myeloid leukemia, and other diseases

• SITE: Single site 
• SETTING TYPE: Inpatient hospital  
• LOCATION: Brazil

• PHASE OF CARE: Active treatment

• Descriptive cohort

• Cumulative incidence of febrile neutropenia and death were determined by the Kaplan-Meier method.
• The adjusted hazard ratios were computed in a Cox regression model.

Fever occurred in 74.7% of episodes of neutropenia in the PE group and in 86.7% in the control group (p = 0.003). Adjusting for length of neutropenia, risk, category, antibacterial prophylaxis, and central venous catheter use, the PE reduced febrile neutropenia (p = 0.009). The PE also decreased overall mortality (p = 0.001) and 30-day mortality (p = 0.002). Gram-negative bacterial infections were more frequent after the intervention (p = 0.18), while gram-positive bacterial infections were similar (p = 0.85). Fungal infections were more frequent in the control group (p = 0.04).

This study shows the advantages of the PE on reducing febrile neutropenia and mortality among patients with cancer and indicates that multiple infection control interventions significantly can diminish hospital-acquired infections.

• Risk of bias (no control group)
• Risk of bias (no blinding)
• Risk of bias (no random assignment)

Although the study does not delineate what they are, an important part of the intervention is infection control routines. These routines include hand hygiene and the routine use of personal protective equipment. Infection control is essential not only to protect nurses, but also to prevent the transmission of infection from one patient to another, particularly when those patients are at higher risk because of chemotherapy-induced neutropenia, and their importance cannot be overstated.

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.