All patients presenting with fever following anticancer therapy should be managed as neutropenic, and receive empiric antibiotics until proven otherwise. Management may be subsequently modified if neutrophil count and function are found to be adequate.
Time to first dose:
- patients with features of systemic compromise (such as hypotension, hypoxia, confusion, major organ dysfunction) should receive antibiotics within 30 minutes of presentation. Where possible, blood culture samples should be taken before administering antibiotics (grade C)*
- clinically stable patients should receive antibiotics within 1 hour of presentation after appropriate cultures have been taken (grade C)*
- administration of antibiotics should not be delayed by the conduct of laboratory or radiological investigations (grade C)*
* Refers to the levels of evidence and grades of recommendations used in the published guidelines.
Refer to Patient evaluation, risk assessment and initial management of febrile neutropenia for more information.
Step 1: Perform septic workup
- 1 set blood cultures (aerobic and anaerobic bottles) from each lumen of central venous access device (CVAD) (if in situ)
- 1 set blood cultures from peripheral blood
- blood tests: FBC (with differentials), EUC, CMP, LFTs, serum lactate
- mid-stream urine/catheter specimen urine
- sputum sample (if clinically indicated)
- respiratory swabs (if clinically indicated)
- stool sample (if clinically indicated)
- swab of CVAD exit site (only if clinically indicated)
- swab of any other wounds/focal lesions
- arterial blood gas (if clinically indicated).
Chest x-ray (if unavailable still proceed to step 2 and ensure arrangements for CXR have been made).
DO NOT WAIT FOR RESULTS
Step 2: Commence empiric antibiotic therapy (doses are for normal kidney function)
The following regimens are intended for initial therapy only. Treatment should be reassessed as soon as expert advice or additional information is available. Appropriateness of antimicrobial therapy needs to be evaluated daily (at a minimum).
Immediate management of neutropenic feverrr
| Patient group |
Recommendation (grading and level of evidence) |
Patients without features of systemic compromise
(Beta-lactam monotherapy is recommended unless allergy to the recommended agent/s) |
No penicillin allergy:
Piperacillin-tazobactam 4.5 g IV 6 hourly (grade A) OR
Cefepime 2 g IV 8 hourly
Other reasonable choice for monotherapy is ceftazidime 2 g IV 8 hourly (grade A)
|
|
Non-life threatening penicillin allergy (rash):
Cefepime 2 g IV 8 hourly (grade C)
Other reasonable choices for monotherapy are ceftazidime 2 g IV 8 hourly or meropenem 1 g IV 8 hourly (grade C)
|
|
Life-threatening (immediate) penicillin allergy or beta-lactam allergy:
Aztreonam 1-2 g IV 8 hourly OR ciprofloxacin 400 mg IV 12 hourly (expert opinion)
+ vancomycin 25 to 30mg/kg IV as initial loading dose then individualise dose based on trough levels*. Seek expert advice.
|
Patients with systemic compromise
(The combination of a beta-lactam antibiotic with an aminoglycoside is the regimen of choice) |
As for patients without features of systemic compromise (see above):
+ gentamicin 4 to 7 mg/kg IV once daily, adjusted to level**
+/– vancomycin 25 to 30mg/kg IV as initial loading dose then individualise dose based on trough levels*
|
| Patients with cellulitis, obviously infected vascular devices, or MRSA carriers with extensive skin breaks/desquamation |
As for patients without features of systemic compromise (see above):
+ vancomycin 25 to 30mg/kg IV as initial loading dose then individualise dose based on trough levels*
|
| Patients with features of abdominal or perineal infection |
As for patients without features of systemic compromise (see above):
+ metronidazole 500 mg IV/PO 12 hourly if receiving cefepime, ceftazidime or ciprofloxacin first-line (grade D)
Alternatively, piperacillin-tazobactam or meropenem will provide adequate anaerobic cover, if required (grade B), other than for suspected or proven Clostridium difficile-associated diarrhoea or colitis
|
| Patients recently colonised with multidrug-resistant Gram-negative bacteria and requiring broader-spectrum therapy |
Isolates susceptible to carbapenems:
Meropenem 1g IV 8 hourly***
+ vancomycin 25 - 30mg/kg IV as initial loading dose then individualise dose based on trough levels* for patients with systemic compromise
OR
+/– vancomycin if patient has MRSA or has vascular device (see above).
For isolates not susceptible to carbapenems, seek expert advice.
|
© Adapted from Internal Medicine Journal 2011
* Clinicians caring for a patient with immediate hypersensitivity to one beta-lactam who have subsequently tolerated an alternative suitable antipseudomonal beta-lactam agent may elect to administer this second agent under careful supervision. Empirical vancomycin is recommended for 48-72 hrs.r Refer to the Therapeutic Guidelines: Antibiotics for dosing guidance for subsequent doses. Review vancomycin use after 72 hrs. If culture results are not available by 72 hours and empirical intravenous therapy is still required, it is not necessary to continue treatment with vancomycin empirically provided that the patient is clinically improving. Concurrent use with piperacillin-tazobactam has been shown to result in an increased rate of nephrotoxicity, monitor kidney function and assess treatment duration.
** Consider kidney function when determining dose and frequency. In adults, if the patient is obese (body mass index [BMI] 30kg/m2 or more), use adjusted body weight to calculate the dose. If actual body weight (for patients who are not obese) or adjusted body weight (for patients who are obese) is greater than 100kg, use a weight of 100kg to calculate the dose. For obese patients with a BMI of 35 kg/m2 or more, seek expert advice. In non-critical sepsis or septic shock patients, use dose at lower end of the range (4 to 5mg/kg).r Refer to the Therapeutic Guidelines: Antibiotics for dosing guidance. Seek expert advice for patients with impaired kidney function, central nervous system or other deep-seated infection; or infection caused by a pathogen with a vancomycin minimum inhibitory concentration (MIC) more than 1.5 mg/L.
*** For patients with a history of severe cutaneous adverse drug reactions, consider meropenem only in critical situations with limited options.
Note: Recommendations for individual antibiotics may not align directly with the Therapeutic Goods Administration (TGA) approved indications. Therefore, following these recommendations may lead to off-label use of some agents.
Summary
- Beta-lactam monotherapy, such as piperacillin-tazobactam (Tazocin®) or cefepime, is the empiric therapy of choice for all clinically stable patients with neutropenic fever. Ceftazidime is an acceptable alternative, although if infection with a Gram-positive bacterium is suspected (e.g. patients with mucositis), piperacillin-tazobactam or cefepime are preferred as they have superior activity against Gram-positive bacteria compared to ceftazidime.
- An antipseudomonal beta-lactam antibiotic plus gentamicin is recommended for patients with systemic compromise.
- All patients should receive antibiotics as soon as possible; within 30 minutes of presentation for patients in septic shock, and within 1 hour for all other patients.
- Vancomycin is not recommended as routine initial empiric therapy, and should be reserved for patients with specific indication as outlined above.
| This is initial immediate therapy only and subsequent treatment should be based on clinical findings and at the discretion of the treating clinician. |