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Treatment for infection in children


Medical editor Tore G. Abrahamsen MD
Pediatrician
Oslo University Hospital

General

Children undergoing chemotherapy are susceptible to infections due to reduced function of the immune system (neutropenia). Infections in children with cancer are potentially life-threatening, especially before the child has started antibiotics. 

Fever is often the only symptom. Symptoms such as lethargia, vomiting, and diarrhea may also be signs. Inflammation with redness, pain, swelling, and reduced organ function are often very mild or absent with neutropenia. 

Children with a fever should be immediately admitted to the hospital.

When broad spectrum antibiotics are given, the fever should be monitored.

When taking high-dose cytarabin, most children will develop a fever and raised CRP. This is drug-induced and should not be treated with antibiotics, however, the child's clinical status must be assessed. 

Indication

  • Fever and neutropenia

Goal

  • Prevention of sepsis
  • The child is able to complete treatment

Definitions

Neutropenia

Neutropenia is graded as: 

  • moderate - neutrophile < 1.0 x 109/l but > 0.5 x 109/l 
  • serious - neutrophile < 0.5 x 109/l but > 0.2 x 109/l 
  • very serious - neutrophile < 0.2 x 109/l 

Fever

Fever is defined as:

  • a single temperature measurement ≥ 38.5 °C, or
  • multiple measurements ≥ 38 °C with 1 hour interval

Preparation

The child is examined for sign of infection.

Tests taken from:

  • mouth/throat/nose
  • urine
  • CVC (central venous catheter) puncture point

Blood tests:

  • Hb, white with differential count, thrombocytes, CRP, urea/creatinin, ASAT, ALAT
  • Blood culture

A blood culture and other microbiology testing should be taken before antimicrobial treatment starts.

A pulmonary X-ray is then taken.

If there is secretion/puss around the point of puncture, with rubor/swelling along the tunnel ring, there may be a CVC infection. If there is suspicion, a blood culture should be taken from the CVC and peripheral vein.


Implementation

Treatment for sepsis from fever starts if neutropenia is expected, regardless of the granulocyte value.

All patients with fever and leukocytes < 1.0 x 109/l  and/or neutrophile < 0.5 x 109/l should have broad spectrum antibiotics.

Treatment should start as soon as possible. Treatment may be postponed maximally 30 minutes to take necessary tests if circulatory justifiable.

Bacterial infection

The standard combination regimen is amicillin and gentamicin.

The level of the drug concentration in the blood is measured when the child recieves gentamicin.  

If the child has recently taken neurotoxic drugs (cisplatin/carboplatin/ifosfamid), gentamicin should be avoided. An alternative regimen is cefotaxime or ceftazidim alone.

If there is no clinical improvement observed and CRP does not fall within 3 days, a new blood culture should be taken and alternative antibiotic started.

Alternative new regimens are:

  • vancomycin and ceftazidime 
  • meronem 

The level of the drug concentration in the blood should be monitored when the child takes vancomycin.

If therapy is still unsuccessfull, treatment should be reassessed for possible focus of infection and/or positive bacteriology. If there are symptoms in the mouth or intestines, metronidazole should be added.

Fungal infection  

Empirical fungal treatment should be considered if antiobiotic therapy is not effective after 5-7 days, or increase in fever/CRP after initial improvement. Be aware that steroid treatment increases the risk for fungal infection. 

Empirical fungal treatment

For a fungal infection the following are used:

  • fluconazol - is not effective against aspergillus and Candida krusei, and some Candida glabrata.
  • amphotericin B in one of two forms:
    • conventional amphotericin
    • liposomal amphotericin B  
  • voriconazole – against aspergillus
  • caspofungin – other choice against fungus

Pneumocystic jirovecii infections

Immunosupressed patients are susceptible to pneumocystic jirovecii infections. Clinically, this infection rapidly causes tachypnea, cyanosis/low 02-saturation. It is not always easy to identify on thoracic X-ray. This is a very serious disease and must often be treated on suspicion because it can progress in a matter of hours to respiratory failure. The condition usually requires treatment with a respirator and trimetoprim-sulfa. 

Other serious pneumonias in severely immune-supressed patients with long term illnesses may be caused by another fungus or cytomegalovirus (CMV).  

CVK infection

Initially, the catheter is inserted and antibiotic therapy is started with ampicillin/gentamicin or vancomycin/ceftazidime. The catheter should not be removed until conferring with the oncologist.

Diarrhea

Diarrhea may be induced by a virus, chemotherapy, antibiotic, or clostridium difficile toxin. For serious diarrhea in immunosuppressed patients, the clostridium toxin should be tested for in fresh stool. If this is positive, metronidazole should be given. 

Viral infections

Varicella, herpes zoster and herpes simplex infection

For varicella, herpes zoster, and herpes simplex infection, aciclovir is used. Treatment last at least 5 days or until all blisters have dried up.

For positive varicella exposure, varicella zoster immunoglobulin should be given.

Immune-supressed children should always be protected from varicella. Immunoglobulin is given for every new exposure to varicella when more than 8 weeks have gone since the last injection. There is controversy whether children who have had chicken pox should be given this prophylaxis, but most agree that it should be given regardless of this.

Systemic CMV infection

For a systemic CMV infection, ganiclovir is used.


Follow-up Care

Observe symptoms of new infection. The child should be especially monitored with regard to a fungal infection when there is a new rise in temperature after temporary improvement, and broad spectrum antibiotics have been given for > 7 days.


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