Introduction
Methods
Category, grade | Definition |
---|---|
Strength of recommendation | |
A | Strongly supports a recommendation for use |
B | Moderate evidence to support a recommendation for use |
C | Marginally supports a recommendation for use |
D | Supports a recommendation against use |
Quality of evidence—level | |
I | Evidence from at least one properly designed randomized, controlled trial |
II | Evidence from at least one well-designed clinical trial, without randomization; from cohort or case-controlled analytic studies (preferably from > 1 center); from multiple time series; or from dramatic results of uncontrolled experiments |
III | Evidence from opinions of respected authorities; based on clinical experience; descriptive case studies; or reports of expert committees |
Quality of evidence—index (for level II) | |
r | Meta-analysis or systematic review of randomized controlled trials |
t | Transferred evidence, that is, results from different patient cohorts, or similar immune status situation |
h | Comparator group is a historical control |
u | Uncontrolled trial |
a | Published abstract (presented at an international symposium or meeting) |
Patients and risk factors
Clinical situation | Intention/recommendation | Intervention | SoR | QoE | References |
---|---|---|---|---|---|
Patients with prolonged neutropenia (> 7 days)a | Identify patients at risk for FN | Consider as high-risk patients | A | I | |
Patients with neutropenia > 0 and ≤ 7 daysa and significant additional risk factorsb | Consider as high-risk patients | B | II | ||
Patients with neutropenia ≤ 7 days without additional risk factors | Consider as low-risk patients | A | I |
Patient-related risk factorsa | |
Prolonged neutropenia (> 7 days) | |
Type and stage of underlying malignancy | |
Administered type and dosage of chemotherapy | |
First chemotherapy cycle | |
Cardiac insufficiency | |
Low baseline creatinine clearance | |
Low baseline leukocyte count | |
Elevated baseline levels of alkaline phosphatase and bilirubin |
New anti-cancer agents and antibacterial prophylaxis
Spectrum of pathogens in infections of neutropenic patients
Resistance development
Novel considerations regarding microbiome and resistome
Efficacy of prophylaxis
Clinical setting | Intention/recommendation | Intervention | SoR | QoE | References |
---|---|---|---|---|---|
High-risk patients receiving first chemotherapy cycle | Prevent fever and infections by using antibacterial prophylaxisa | Antibacterial prophylaxis | A | I | |
High-risk patients receiving subsequent chemotherapy cycles | B | I | |||
Low-risk patients receiving first chemotherapy cycle | B | I | |||
Low-risk patients receiving subsequent chemotherapy cycles | C | I | |||
High-risk patients | Reduce mortality by using antibacterial prophylaxis | B | II | ||
Low-risk patients | C | II | |||
Patients receiving eculizumab, ravulizumab, or splenectomy or patients with functional asplenia without effective meningococcal vaccination | Prevent meningococcal disease | Penicillin V 250 mg b.i.d. or ciprofloxacin 500 mg q.d. until 4 weeks after immunization or documented protective titers | A | IIu |
Duration of prophylaxis administration
Clinical setting | Intention/recommendation | Intervention | SoR | QoE | References |
---|---|---|---|---|---|
Patients with indication for antibacterial prophylaxis at high risk for infection | Prevention of fever or infection | Start antibacterial prophylaxis with start of cytostatic drugs | B | IIu | |
Patients with indication for antibacterial prophylaxis at low risk for infection | Start antibacterial prophylaxis 5–8 days after beginning chemotherapy | B | III | ||
Start of empirical broad-spectrum antibiotic treatment OR End of neutropenia | Reduce side effects, prevent resistance development | Termination of antibacterial prophylaxis | A | IIu | |
Patient with breakthrough infection receiving FQ prophylaxis | Treatment of infection | Use of FQ for empirical therapy | D | III |
Drugs for antibacterial prophylaxis
Clinical setting | Intention/recommendation | Intervention | SoR | QoE | References |
---|---|---|---|---|---|
Neutropenic patients with indication for antibacterial prophylaxisa | Prevent FN or death | Use fluoroquinolone prophylaxis, if indicated | A | I | |
Prevent FN or death | Use therapeutic dose TMP-SMX instead of FQs, if indicated | B | IIt | ||
Prevent FN or death | Prefer selective gut decontamination vs. systemically active antibacterials | * | |||
Reduce side effects of antibacterials | Prefer fluoroquinolone prophylaxis vs. TMP-SMX | A | II | ||
Prevent FN or death | Ciprofloxacin and levofloxacin as FQs of choice for prophylaxis | A | II | ||
Prevent FN and reduce incidence of gram-positive infections | Combine fluoroquinolone with an agent active against gram-positive bacteria | D | II | ||
Neutropenic patients with indication for antibacterial prophylaxis and known colonization with multiresistant bacteria | Prevent FN or death | FQ prophylaxis if known colonization by FQ-resistant gram-negative bacteria | D | IIt, u |
Recent warnings regarding fluoroquinolone safety
Selective digestive tract decontamination
Indication for Pneumocystis jirovecii prophylaxis
Significant risk | Intermediate risk | Special indications |
---|---|---|
• Acute lymphoblastic leukemia • Allogeneic stem cell transplantation • Long-term steroids with > 20 mg q.d. prednisone equivalent for > 4 weeks • Fludarabine + cyclophosphamide + rituximab | • R-CHOP14 or escalated BEACOPP • Nucleoside analogs • Brain irradiation with high-dose steroids • CD4 cell count < 200/μl | • Alemtuzumab • Idelalisib (drug label) • Brain irradiation + temozolomide |
Clinical setting | Intention/recommendation | Intervention | SoR | QoE | Reference |
---|---|---|---|---|---|
Patients at significant risk for developing PcP | Prevent PcP | Use chemoprophylaxis | A | I | |
Patients at intermediate risk | C | III | |||
Patients receiving idelalisib, alemtuzumab, or temozolomide (with radiation) treatment | A | IIu, t | |||
Patients at significant risk for developing PcP | Reduce mortality | Use chemoprophylaxis | A | IIr | [127] |
Patients at intermediate risk | C | III | [127] |
Choice of drugs and doses for PcP prophylaxis
Clinical setting | Intention/recommendation | Intervention | SoR | QoE | References |
---|---|---|---|---|---|
Patients with indication for PcP prophylaxis | Prevent PcP | Use TMP-SMX as first-choice agent | A | IIt, r | |
Use one single-strength (80/400 mg) tablet daily or one double-strength tablet (160/800 mg) either daily or thrice a week | B | IIt | |||
Patients with intolerance or severe adverse effects due to TMP-SMX | Use atovaquone as second-choice drug - 1500 mg/day | A | IIt | ||
Use dapsone as second-choice drug - 100 mg/day | A | IIt | |||
Use pentamidine (aerosolized) as second-choice drug - 300 mg once monthly | B | IIt |