17.1 Febrile neutropenia syndrome

Type of Infection	First Line (with Dosage and Duration)	Alternative First Line (with dosage and Duration)	Comments
Hemodynamically stable	Piperacillin- tazobactam 4.5g IV q6h Or Cefoperazone- sulbactam 3g IV q12h	Meropenem 1g IV q8h Or Imipenem 500mg IV q6h	If blood cultures are negative, patient is haemodynamically stable but still febrile, blood culture should be repeated & alternate cause of fever should be looked for (fungal/viral). Continue broad-spectrum antibiotics until the patient is afebrile for at least 3 days.
Hemodynamically unstable	Meropenem 1g IV q8h + Vancomycin 25 mg/kg loading and 15 mg/kg q8h/12h + Inj Polymyxin B (15-20 lakhs units IV stat, followed by 7.5-10 lakhs IV q12h	Imipenem 500mg IV q6h	Consider adding Caspofungin if fungal infection is a consideration (persistent fever with negative cultures) Ceftazidime-avibactam +/- aztreonam is a reserve drug to be used as targeted therapy after susceptibility reporting for CR Klebsiella. Resistance among E coli and Pseudomonas is common and it is inactive against Acinetobacter, so it is not recommended for empiric use.

For common etiological agents of Febrile neutropenia syndrome, see Annexure B.17.1

Additional Information

For patients with Febrile neutropenia syndrome following points should be considered:

When to add glycopeptides?
- Haemodynamic instability or other evidence of severe sepsis, septic shock or pneumonia.
- Colonisation with MRSA or penicillin-resistant S.pneumoniae.
- Suspicion of serious catheter-related infection e.g. chills or rigours with infusion through catheter and cellulitis around the catheter exit site.
- Skin or soft-tissue infection at any site.
- Positive blood culture for gram-positive bacteria, before final identification and susceptibility testing is available.
When should empirical colistin or polymyxin B be added in febrile neutropenic patients?
- Haemodynamic instability.
- Colonisation with carbapenem-resistant gram-negative bacteria.
- Previous infection with carbapenem-resistant gram-negative bacteria.
- GNB in blood, sensitivity pending, persistent fever with haemodynamic instability.
When to start Empirical Antifungal Therapy:
- Empirical antifungal therapy is not advised unless patient is unstable, use of CT chest and fungal biomarkers like serum Galactomannan and serum beta D glucan is encouraged.
- Febrile after 72 hrs of antibiotic therapy.

More Information

Unexplained persistent fever in the otherwise stable patient doesn't require a change in empirical antibiotic regimen. Continue the regimen till ANC is >500 cells/mm3.
If glycopeptide has been started as a part of empirical regimen, STOP after 48 hrs, if no evidence of gram-positive infection.
Antibiotic therapy in febrile neutropenia can be stopped if patients are afebrile for 3 days, provision for close observation is present and culture negative irrespective of ANC recovery.
Shifting to oral antibiotics during neutropenia can be done if stable and susceptibility to the oral drug has been demonstrated.

References

1. When to add glycopeptides? Haemodynamic instability or other evidence of severe sepsis, septic shock or pneumonia. Colonisation with MRSA or penicillin-resistant S. pneumoniae. Suspicion of serious catheter-related infection e.g. chills or rigours with infusion through catheter and cellulitis around the catheter exit site. Skin or soft-tissue infection at any site. Positive blood culture for gram-positive bacteria, before final identification and susceptibility testing is available.

2. When should empirical colistin or polymyxin B be added in febrile neutropenic patients? Haemodynamic instability. Colonisation with carbapenem-resistant gram-negative bacteria. Previous infection with carbapenem-resistant gram-negative bacteria. GNB in blood, sensitivity pending, persistent fever with haemodynamic instability.

3. When to start Empirical Antifungal Therapy: Empirical antifungal therapy is not advised unless patient is unstable, use of CT chest and fungal biomarkers like serum Galactomannan and serum beta D glucan is encouraged. Febrile after 72 hrs of antibiotic therapy.