Protective Isolation

To review prospective comparative studies that address infection prevention for high-risk patients undergoing chemotherapy and stem cell transplant recipients to evaluate the evidence for best practice and assess for mortality.

Databases searched were CENTRAL (the Cochrane Library issue 4, 2006), PubMed (1966–2008), and LILACS (1982–2006). Unpublished trials that were presented at the following conferences were also queried: American Society of Hematology (2001–2006), American Society of Clinical Oncology (1995–2006), and European Society for Medical Oncology (2002–2006). The references lists from all included studies were reviewed to identify additional studies. 

Keywords searched were not provided by the authors.

Studies were included if they 

• Were prospective comparative studies that included patients with cancer in the hospital or outpatients who were receiving chemotherapy for solid tumors.
• Reported hematological malignancies.
• Reported stem cell transplant recipients.  
• Compared an intervention to placebo, no treatment, or another intervention, as well as all environmental measures, barrier precautions, and other nonpharmacological measures used for the prevention of infectious diseases.

Studies were excluded if they were nonrandomized studies that compared patients with different types of cancer or compared different treatment protocols (i.e. stem cell transplant versus chemotherapy) or if they assessed pharmacological interventions, such as antimicrobial prophylaxis and mouth rinse preparations, unless these interventions were applied together or as a control for the infection-control interventions.

Forty studies were included.

Method of Study Evaluation

Prevention of infection measures used in the studies were identified and grouped together: control of air quality (air filtration), protective isolation, and suppression of the endogenous flora (antibiotics). Subgroup analyses were performed for two major outcomes: all-cause mortality at 100 days and documented infections.

• The total sample size was 40 studies; the sample range across studies was 45 to 3900.
• Twenty-six studies in the analysis studied protective isolation, 11 assessed outpatient versus inpatient care, and three evaluated other random interventions.  
• Twenty-nine studies assessed patients with acute leukemia, six included patients with other hematologic malignancies, and 22 included hematopoietic stem cell transplant (HSCT) recipients exclusively.
• No study included patients with solid tumors at low risk for infection.

The primary outcome, all-cause mortality, was assessed at 30 days, 100 days, and at the longest follow-up reported in each study. Secondary outcomes included the rate and types of infections (including bacteremia), the need for hospitalization and length of hospital stay, the length of the febrile period, infection-related mortality, bacterial and fungal colonization, and antibiotic and antifungal treatment.

• Protective isolation, including control of air quality, barrier isolation, and endogenous suppression due to antibiotics, were shown to significantly reduce mortality (relative risk [RR] = 0.79; 95% confidence interval [CI] [0.72, 0.87]).
• Antibiotic prophylaxis was the main component mediating the beneficial effect of isolation interventions. Improved survival was only shown when antibiotic and antifungal prophylaxis was used with air quality control or barrier isolation (RR = 0.66; 95% CI [0.55, 0.79] in studies with prophylaxis compared with RR = 0.93; 95% CI [0.75, 1.15] in studies without prophylaxis).
• Protective isolation with prophylactic antibiotics also significantly reduced infection, whereas control of air quality or barrier isolation alone did not.
• Control of air quality did not significantly reduce mold infections.  Outpatient mortality was also significantly lower than inpatient mortality (RR = 0.72; 95% CI [0.55, 0.95]).

A combination of air quality control, barrier isolation, and prophylactic antibiotics is estimated to reduce 30-day all-cause mortality by 40% in high-risk cancer patients, including allogeneic or autologous HSCT recipients and patients with acute leukemia. Prophylactic antibiotic use is the most significant preventive strategy; air quality control and barrier isolation did not show an independent contribution, and their use should be reserved for patients at highest risk of infection. Survival significantly improved with outpatient management, which included the use of prophylactic antibiotics without environmental controls.

The reduced mortality seen in outpatient management may be due to

• Selection bias (healthier patients are able to remain outpatient)
• Decreased risk of infection from hospital pathogens
• Use of antibiotic prophylaxis.

There is no evidence that any of these preventive strategies (air quality control, barrier isolation, or prophylactic antibiotics) are necessary or appropriate for low-risk cancer patients with solid tumors.

To evaluate protective isolation versus no isolation.

The authors evaluated single protective isolation (single-bed room and clean gowns, gloves, and masks for people entering room) versus standard care (two-bed room and reminder sign to wash hands).

Forty-three episodes of neutropenia occurred in adult patients.

• Inpatient
• Hematology-oncology unit

This was a randomized study.

No significant difference was found between isolated and nonisolated patients regarding the incidence of infection, time of onset of first infection, and days with fever.

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.