Immediate Treatment of Neutropenic Sepsis
Administer broad-spectrum intravenous antibiotics within the first hour of recognition—each hour of delay decreases survival by 7.6%. 1
Initial Antibiotic Selection
Start with antipseudomonal beta-lactam monotherapy using one of the following: [1, 2
- Meropenem (preferred for ESBL coverage)
- Imipenem/cilastatin (preferred for ESBL coverage)
- Ceftazidime
- Cefepime 2g IV every 8 hours 3
- Piperacillin-tazobactam 4.5g IV every 6 hours 2
The carbapenems (meropenem/imipenem) provide superior coverage for extended-spectrum beta-lactamase (ESBL)-producing organisms, which are increasingly common. 1, 2 Selection should be guided by local antibiogram data and the patient's recent antibiotic exposure. 2
When to Add Aminoglycoside Combination Therapy
Add aminoglycoside (gentamicin or amikacin) ONLY if: 4, 1, 2
- Severe sepsis with hemodynamic instability is present
- Suspected or documented multidrug-resistant gram-negative infection (particularly Pseudomonas aeruginosa or Acinetobacter)
Critical caveat: Routine aminoglycoside combination therapy in standard febrile neutropenia significantly increases renal toxicity without improving efficacy and should be avoided. 1, 2 The combination should not be continued beyond 3-5 days. 4, 5
Pre-Antibiotic Workup (Do Not Delay Antibiotics)
Obtain blood cultures before antibiotics but never delay administration: 4, 1
- At least 2 sets of blood cultures (aerobic and anaerobic bottles) 4
- One drawn percutaneously and one through each vascular access device (if present >48 hours) 4
- Site-specific cultures based on clinical presentation (urine, stool, respiratory) 1
Blood cultures detect bacteremia in only 30% of febrile neutropenia cases, so negative cultures should never delay or alter initial empirical therapy. 1, 2
Hemodynamic Resuscitation
Initiate aggressive fluid resuscitation targeting: 1, 2
- Mean arterial pressure ≥65 mmHg
- Central venous pressure 8-12 mmHg
- Urine output ≥0.5 mL/kg/hour
- Central venous oxygen saturation ≥70%
Use crystalloids preferentially over colloids—meta-analyses show colloids are associated with increased renal failure and mortality. 1 Avoid human albumin as it provides no favorable outcomes. 1
If hypotension persists despite fluids, start norepinephrine 0.1-1.3 mcg/kg/min IV infusion targeting mean arterial pressure ≥65 mmHg. 1, 2
Escalation for Persistent Fever
If fever persists beyond 72 hours, add vancomycin for gram-positive coverage, particularly if: 2
- Catheter-related infection suspected
- Severe mucositis present
- Hemodynamic instability present
If fever persists beyond 96-120 hours, add empirical antifungal therapy with an echinocandin (caspofungin or micafungin). 2
De-escalation Strategy
De-escalate to narrower spectrum antibiotics when ALL criteria are met: 1, 2
- Afebrile for 72 hours
- No clinical evidence of ongoing infection
- Culture results available showing specific pathogen susceptibility
- Neutrophil recovery beginning
Daily reassessment of antimicrobial therapy is mandatory to optimize efficacy, prevent resistance, avoid toxicity, and minimize costs. 4, 6
Duration of Therapy
Total duration is typically 7-10 days. 4, 1, 5
Extend beyond 10 days if: 2, 5
- Slow clinical response
- Documented fungal infection
- Persistent profound neutropenia
- Inadequate surgical source control
- Immunologic deficiencies
In patients whose fever resolves but who remain neutropenic beyond 7 days, the need for continued antimicrobial therapy should be re-evaluated frequently. 3
Critical Pitfalls to Avoid
- Never delay antibiotics for culture results—mortality increases 7.6% per hour of delay 1, 2
- Avoid routine aminoglycoside combinations in standard febrile neutropenia due to nephrotoxicity without benefit 1, 2
- Do not use sustained antimicrobial prophylaxis in severe inflammatory states of noninfectious origin 4
- Do not routinely use G-CSF or GM-CSF as adjunctive therapy—they do not reduce overall mortality and may cause respiratory deterioration with ARDS 2