continuation of FN Flashcards
Treatment of FN
Treatment Overview
1. The goal of initial antibiotic therapy is to prevent morbidity and mortality due to bacterial infections until more data is available to guide subsequent treatment decisions
a. The first dose of empiric antibiotic therapy should be administered within 1 hour after triage
b. Cultures are usually negative, but broad-spectrum antibacterial therapy is still warranted to cover possible occult infection
2. Most common source of infection is a patient’s own flora (gram-negative or gram-positive; fungal pathogens play more of a role in prolonged neutropenia)
a. Incidence of gram-positive and gram-negative infections are similar when antibacterial prophylaxis is NOT administered6
b. Incidence of gram-positive infections (especially Streptococcus viridans, coagulase-negative staphylococci, and vancomycin-resistant enterococci) increases in the setting of fluoroquinolone prophylaxis
3. Choice of Empiric Agent
a. No single agent or regimen has clearly emerged as superior
1) Effective regimens are bactericidal, cost-effective, and well-tolerated
b. Choice of empiric antibiotic should be based on:
1) Patient’s risk assessment (see section below)
2) Potential infecting organism (history of resistant pathogens, local susceptibility patterns)
3) Potential sites of infection
4) Need for antipseudomonal coverage
5) Clinical instability (hypotension, organ dysfunction)
6) Drug allergies
7) Recent antibiotic use (including prophylaxis
Common Site-Specific Pathogens2
Definition of Low-Risk FN
ASCO/IDSA and NCCN define low-risk patients as anyone who has a MASCC score ≥ 21 or CISNE score < 3, Talcott’s group 4, or if the patient has none of the high-risk factors listed below and most of the
following (note, this is a summation of the two guidelines combined):
1) Patient is ambulatory/outpatient at time of fever onset
2) No associated acute comorbid illness requiring inpatient therapy or close observation
3) Short duration of severe neutropenia defined as ANC ≤ 0.1 x 109 cells/L for < 7 days
4) ECOG performance status of 0 or 1
5) No hepatic or renal insufficiency
Definition of High-Risk FN
ASCO/IDSA and NCCN define high-risk patients as anyone who has a MASCC score < 21 or CISNE score ≥ 3, Talcott’s groups 1-3,
or if the patient has any of the high-risk factors listed below (note, this is a
summation of the two guidelines combined):
1) Patient is hospitalized at time of fever onset
2) Clinically unstable or significant comorbid conditions including hypotension, pneumonia, newonset abdominal pain, or neurologic changes
3) Prolonged duration of severe neutropenia defined as ANC ≤ 0.1 x 109 cells/L for ≥ 7 days
4) Hepatic or renal insufficiency (liver function tests > 5 x ULN or CrCl < 30 mL/min)
5) Progressive or uncontrolled cancer (leukemia patient not in complete remission or non-leukemia patient with disease progression after ≥ 2 cycles of chemotherapy)
6) Patient received alemtuzumab or allogeneic HCT; use of immune and/or targeted treatments
7) Grade 3-4 mucositis
Treatment of Low-Risk FN
a. ASCO/IDSA recommends the first dose of empiric antibiotics should be administered in the clinic,
emergency department or hospital and observed for ≥ 4 hours before discharge
b. NCCN recommends to consider an observation period (2-12 hours) to administer first dose of
antibiotics and monitor for reaction, as well as to confirm low-risk status and clinical stability
Treatment Options for Low-Risk FN Eligible for Outpatient Management
Treatment of High-Risk FN
- High-risk patients should be hospitalized to receive empiric IV antibiotic therapy
- Treatment typically consists of monotherapy with an antipseudomonal beta lactam
a. Other antimicrobials (aminoglycosides, fluoroquinolones, and/or vancomycin) may be added to initial therapy for complicated infections or suspected/proven antimicrobial resistance - Double coverage of gram-negatives with an aminoglycoside is not routinely recommended based on data from a meta-analysis demonstrating similar survival outcomes with less adverse events in patients receiving beta-lactam monotherapy as compared to double coverage8
a. Double coverage with a beta-lactam and aminoglycosides should be reserved for patients who are seriously ill/hemodynamically unstable or those with a history or risk factors for resistant gramnegative infections - Empiric vancomycin is not a routine component of initial therapy
a. Fever is not an indication for vancomycin
b. Randomized studies comparing empiric regimens with and without vancomycin have not demonstrated a reduction in duration of fever or mortality
c. Linezolid, tedizolid, quinupristin-dalfopristin, tigecycline, televancin, dalbavancin, oritavancin, ceftaroline, and daptomycin also have no proven role in routine empirical coverage
d. If empiric vancomycin is initiated, it should be discontinued within 48-72 hours if susceptible bacteria are not identified
e. Indications for addition of antibiotics active against resistant gram-positive organisms to the initial regimen are listed in the table below - Consider addition of atypical coverage (e.g., azithromycin, doxycycline, or fluoroquinolone) if concerned for community-acquired source
- Insufficient experience with ceftazidime/avibactam and
ceftolozane /tazobactam in treatment of FN
Empiric Treatment option for high risk FN
Antibacterial Agent Spectrum
Follow-up of FN
A. Modifications to empiric regimen should be guided by clinical/microbiological data (see table below)
1. Patients who become/remain hemodynamically unstable after receiving initial doses of standard agents should have their regimen broadened to include coverage for resistant gram-negative, gram-positive and anaerobic bacteria, as well as fungi
B. Patients with unexplained, persistent fever who are clinically stable rarely require a change to the initial antibiotic regimen
1. Time to defervescence typically 2-7 days (median = 5 days) in patients who have received appropriate empiric antibiotic therapy
2. No proven advantage to adding vancomycin for persistent or recurrent fever
3. If an infection is identified, modify antibiotics to target appropriate coverage for the site and the susceptibilities of any isolated organisms
a. If vancomycin or other coverage for gram-positive organisms was part of the initial regimen, it can be discontinued after 48-72 hours if no evidence of gram-positive infection
Recommendations for Modification to Initial Empiric Regimen in FN
Empirical Approach
High-risk patients with persistent fever after 4-7 days despite appropriate coverage (and no other source of infection identified) should be considered for anti-mold coverage (two clinical approaches)
Empirical Approach
&
Preemptive Approach:
Empirical
A Initiation of an antifungal agent at the first possible clinical evidence of fungal infection (persistent
fever ≥ 4 days of empirical antibiotic therapy)
Preemptive
B More-targeted, less broad treatment of only those patients with additional findings suggestive of IFI
(e.g., serologic tests or chest CT findings)
Advantage of Preemptive vrs Empirical
Preemptive therapy was associated with increased incidence of invasive fungal disease (without increasing mortality) compared to empirical antifungal therapy, but less exposure to antifungals and
decreased costs of antifungals
No data to guide empirical/preemptive antifungal in patients receiving anti-mold prophylaxis
