PAEDIATRIC
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INFECTIONS IN IMMUNOCOMPROMISED PATIENTS
In this topic:
1. FEBRILE NEUTROPENIA
1. FEBRILE NEUTROPENIA
1.1 First line
Fever >38°C, neutrophil<500mm³
Common organisms:
Enterobacteriaceae (Klebsiella sp., E. coli etc.)
Pseudomonas Aerobic Gram-positive (Staphylococci, Streptococci)
Preferred
Cefepime 50mg/kg/dose IV in q8h (max. 6g/day)
Alternative
Piperacillin/tazobactam 300 - 400 mg/kg/day IV in 4 divided doses (max. 16g/day of piperacillin component)
Comments
Use monotherapy with an anti-pseudomonal β–lactam agents.
Meta-analysis has shown that there is no clinical advantage with β-lactam and aminoglycoside combination therapy.
Also need to look at local epidemiological data.
1.2 Second line:
Persistent fever > 72 hours*
Common organisms:
Enterobacteriaceae (Klebsiella sp, E. coli etc.)
Pseudomonas Aerobic Gram-positive (Staphylococci, Streptococci)
Enterococci
Other resistant organisms
*DO NOT MODIFY INITIAL COVERAGE BASED SOLELY ON PERSISTENCE OF FEVER.
Preferred
Meropenem 60-120mg/kg/day IV in 3 divided doses (max. 6g/day)
MAY ADD
Vancomycin 60 mg/kg/day in 3-4 divided doses (max. 2g/day)
Alternative
--
Comments
Escalate to second line if patient is unstable, to cover resistant gram negative, gram positive and anaerobes.
Consider adding vancomycin in suspected catheter-related infections, positive blood culture for gram positive cocci, hypotensive patients and patients who are known to be colonised with MRSA.
In patients responding to initial empiric antibiotic therapy, discontinue double coverage (empirical vancomycin, if initiated) or double gram negative after 24-72 hours if there is no specific microbiologic indication to continue combination therapy.
1.3 Third line
Fever > 4-7 days with no identified source of fever
Bacterial:
Candida sp.
Aspergillus sp.,
Fusarium sp.
Viral: Respiratory viruses are the most common, HSV, VZV
Preferred
Imipenem/cilastatin 60-100 mg/kg/day IV in 4 divided doses (max. 4g/day)
PLUS
Amphotericin B 0.5mg/kg/dose IV q24h & gradually escalate by (0.25- 1mg/kg/dose) q24h
(max. 1.5mg/kg/day)
OR
Lipid formulation of amphotericin B 3-5mg/kg/day
Alternative
Imipenem/cilastatin 60-100 mg/kg/day IV in 4 divided doses (max. 4g/day)
PLUS
Caspofungin 70mg/m2/dose IV q24h at Day 1, then 50mg/m2/dose IV q24h (max. 70mg/dose for loading and maintenance dose)
Comments
1/3 of febrile neutropenic patients with persistent fever >1 week have systemic fungal infections.
Initiate antifungal in patients at high risk of invasive fungal disease with prolonged (≥ 96 hours) febrile neutropenia unresponsive to broad spectrum antibacterial agents.
Amphotericin based antifungal is considered broader spectrum than echinocandin (E.g.: caspofungin).
References:
β lactam monotherapy versus β lactam-aminoglycoside combination therapy for fever with neutropenia: systematic review and meta-analysis. BMJ 2003; 326:1111
Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the Infectious Diseases Society of America. Freifeld AG, Bow EJ, Sepkowitz KA, Boeckh MJ, Ito JI, Mullen CA, Raad II, Rolston KV, Young JA, Wingard JR, Clin Infect Dis. 2011;52(4):e56
Empiric treatment against invasive fungal diseases in febrile neutropenic patients: a systematic review and network meta-analysis. Ken Chen, Qi Wang, Roy A. Pleasants, Long Ge. Wei Liu, Kanging Peng and Suodi Zhai. BMC Infectious Diseases. 2017; 17;159
A Randomized, Double-Blind, Multicenter Study of Caspofungin versus Liposmal Amphotericin B for Empirical Antifungal Therapy in Pediatric Patients with Persistent Fever and Neutropenia. Maertens JA, Maedro L, Reilly AF, Lehrnbecher T, Groll AH, Jafri HS, Green M, Nania JJ, Kartsonis NA, Chow JW, Arndt CAS, DePauw BE, Walsh T. Pediatr Infect Dis J. 2010; 29:415-420
Lehmecher T. et al. Guideline for the Management of Fever and Neutropenia in Pediatric Patients With Cancer and Hematopoietic Cell Transplantation Recipients: 2023 Update. J Clin Oncology 2023;41:1774-85.
Sanford Antimicrobial Guideline 2023
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