SUPPORTIVE CARE OF CHILDREN WITH CANCER: MANAGEMENT OF FEVER WITH SEVERE NEUTROPENIA
A. At onset with unknown pathogen
After diagnostic evaluation, promptly commence empiric broad-spectrum antibiotic coverage (see Section IV antibiotics). If a central venous catheter is in place, rotate antibiotic infusions to include all ports and lumens. Modifications of a "standard" selected regimen should be considered as follows:
If the patient has a history of allergy to penicillin, avoid semisynthetic penicillins and use an aminoglycoside, ceftazadime, or imipenem.
If a central venous catheter is suspected as the cause of fever, use vancomycin, not nafcillin, but discontinue its use after 72 hours if cultures are negative for Staphylococcus epidermidis.
If perianal tenderness is present, this suggests anaerobes. Add antianaerobic therapy.
If oral mucositis is severe, this suggests lower intestinal infection with anaerobes. Add anaerobic therapy and, if Streptococcus viridans is found, add vancomycin.
If peritonitis is possible, add vancomycin to cover Clostridia sp.
If pulmonary infiltrate is present and persists after 48 hours with continued fever, consider the merits of empiric therapy versus bronchial brushings or bronchoalveolar lavage; if this is not diagnostic, then consider needle or open lung biopsy.
a. Begin empiric therapy for Pneumocystis with trimethoprim-sulfamethoxazole and for Legionella with erythromycin.
b. If there is disease progression after 2 days of empiric
therapy, then brushings, bronchoalveolar lavage, needle, or open lung biopsy is strongly indicated. If this is
not possible, add antifungal therapy.
B. When a specific pathogen is not identified on culture
Continue antibiotic coverage until the patient is afebrile for 24 hours, and there is evidence of marrow recovery (increases in absolute phagocyte or neutrophil count for 1 or more days).
If fever and granulocytopenia persist for about 3 or more days, and all diagnostic procedures remain negative
a. Continue broad-spectrum antibiotics and add antifungal therapy if not already included.
b. Continue daily blood cultures, thorough physical
examinations, and repeated histories for clues.
c. Consider brain, perirenal, perianal, pelvic abscess,
pseudomembranous colitis, viral etiology, and recur-
d. Stop antibiotics after 14 days and repeat cultures daily
and monitor the patient several times daily.
3. Recurrence of fever demands prompt rehospitalization, complete diagnostic evaluation, and aggressive antibiotic therapy.
C. When a specific pathogen is identified on culture
Coagulase-negative and positive staphylococci and streptococci, including 5. viridans, are the most frequent pathogens.
Organisms seen less frequently in immune-compromised patients are: Pseudomonas aeruginosa, Escherichia coli, Klebsiella species, Enterobacter species, Proteus species, Salmonella species, Haemophilus influenzae, Neisseria species, Enterococcus faecalis, Cornebacterium species, Bacillus species, Listeria monocytogenes, and anaerobic cocci and bacilli as well. Fungal isolates include Candida, Aspergillus, Cryptococcus, Histoplasma, and Mucor species, among others.
Make certain that the optimal agent or agents are being used for the isolated organism when cultures and sensitivity are known, but continue empiric broad-spectrum coverage until the patient is afebrile and there is evidence of marrow recovery (increases in absolute monocyte, absolute neutrophil, and platelet counts for 2 consecutive days). Then antibiotics may be tailored to the specific agent.
Continue antibiotic therapy for a minimum of 10 days total (14 days if an indwelling catheter is present).
When a fungal infection is suspected or documented
Presume fungal infection when fever and neutropenia persist after 3-7 days of empiric broad-spectrum antibiotics.
Predisposing factors leading to fungal infections include prolonged hospitalization, prolonged granulocytopenia, prolonged use of broad-spectrum antibiotics, use of indwelling catheters, damaged mucosal barriers, and hyperalimentation.
The most common pathogens are Candida albicans, Candida tropicalis, Aspergillus fumigatus, and Aspergillus flavus. Less frequently seen are Cryptococcus neoformans, Histoplasma capsulatum, and mucormycosis.
E. When a viral infection is suspected or documented
For documented infection with herpes simplex treat with acyclovir 1500 mg/m2/day divided q8h (IV).
For documented infection with varicella zoster treat with acyclovir 750 mg/m2/day divided q8h IV until no new lesions appear. Ensure adequate hydration.
For documented infection with cytomegalovirus (CMV) treat with ganciclovir 10 mg/kg/day divided ql2h IV plus CMV immune globulin.
F. For documented or suspected infection with Pneumocystis
Treat with trimethoprim-sulfamethoxazole (TMP/SMX): TMP 15-20 mg/kg/day and SMX 75-100 mg/kg/day divided q8-12h for at least 14 days PO or IV.
If TMP/SMX is not tolerated, treat with pentamidine 3-4 mg/kg/day IV or TMP 5 mg/kg PO q6h plus dapsone 100 mg/day PO for 21 days.
G. For documented toxoplasmosis
Treat with Pyrimethamine loading dose 1 mg/kg/twice daily PO for 1-3 days, then 1 mg/kg/day for 4 weeks plus either sulfadiazine or trisulfapyrimidines 100 mg/kg/day PO in three to four divided doses for 4 weeks.