Treatment of infections

Author:  Dipl.-Biol. Maria Yiallouros, Gesche Tallen, MD, PhD, Editor:  PD Dr. med. Gesche Tallen, English Translation:  Hannah McRae, Last modification: 2015/01/13 https://kinderkrebsinfo.de/doi/e121693

If a child or adolescent with cancer shows signs of infection (see section, “What are the signs of infection?"), in particular fever during neutropenia, rapid intervention is required. If the patient is at home during this time, she or he must be admitted to the treatment centre for diagnostics and prompt initiation of treatment (see below).

If signs of infection are observed in a child or teenager with cancer, a so-called empirical antibacterial treatment is usually started promptly. These regimens are designed to cover the most commonly encountered pathogens.

The subsequent treatment approach, for example continuing with the initial antibacterial regimen versus changing it to different substances or including additional agents such as antiviral and/or antifungal drugs, respectively, depends on various factors. These include:

• whether or not a pathogen has been identified, and if so, whether or not the identified bacteria is sensitive to the antibiotics given while awaiting the results of the pathogen search (this sensitivity will be determined in the laboratory by a so-called antibiogram)
• the course of the fever
• if additional symptoms such as pain, tenderness, redness are resolving upon treatment and if follow-up diagnostic tests show improving results (for example reduced signs of pneumonia in a chest x-ray)

The following section provides information on the different diagnostic tests that are performed to identify the type of infection as well as further details regarding the corresponding treatment.

Evaluation of patients with signs of infection

When suspicious of an infection in a child or adolescent with cancer, the doctors:

• take the patient’s medical history
• do a physical exam
• take blood samples (to determine the patient's blood cell count and other parameters in the blood, altered levels of which may be indicative of a certain type of infection, and to obtain blood cultures for identification of the pathogen and its sensitivity to various antibiotics)
• collect urine and stool samples for pathogen search and analysis

Depending on the organ system that is obviously affected most, some of the following additional tests may be performed to identify the cause of infection: mouth swabs, swabs of central line exit site or from a surgical wound, lumbar puncture for analysis of the cerebrospinal fluid, diagnostic imaging (such as a chest x-ray or an ultrasound of the abdominal cavity).

Treatment begins after these tests are completed.

Care of febrile patients with neutropenia

Children and adolescents with cancer who present with fever and neutropenia are always considered an emergency. Therefore, the treatment team should be notified promptly in this situation in order to get the necessary diagnostics (see above) initiated.

Even while still awaiting the test results, the patients are generally given antibiotics that are effective against multiple types of bacteria and/or fungi (known as broad-spectrum antibiotics or empirical therapy). These antibiotics are usually given intravenously (IV) (systemic antibiotic treatment). Hence, the patient might have to be admitted to the hospital or at least come to the outpatient clinic for daily treatment.

Depending on the test results, the antibiotic treatment may have to be adjusted accordingly later. For example, if a lung infection (pneumonia) is diagnosed, the subsequent antibiotic treatment might be continued with different agents that are more specific to the bacteria causing the disease. Or, if the patient has been diagnosed with chickenpox (infection with the varicella zoster virus), any anticancer treatment must be paused until the patient has completed antiviral therapy. The length of antibiotic therapy may vary -- usually, antibiotics are given until the patient is not neutropenic any more [BEU2005‎] [GRO2005‎] [LAW2005b‎] [SCH2005‎] [SIM2005‎].

In some febrile patients with neutropenia however, the source of infection remains unidentified despite thorough diagnostic testing. Nevertheless, a setting like this does not at all rule out a potentially underlying serious infection. In order to avoid the risk of spreading bacteria throughout the whole body (sepsis), a broad-spectrum antibiotic treatment is given in this situation as well.

Care of afebrile neutropenic patients with localizing signs of infection

In some neutropenic patients suffering from an infection, fever may be absent, particularly, when the neutropenia is profound and the patient is on corticosteroids (which have immunosuppressing effects). In this situation, the presence of an infection may only be detected by being attentive to seemingly minor complaints from the child or to subtle physical signs. For example, headaches or abdominal pain as well as redness or tenderness along a central line's tunnel track may be indicative of a ventricular shunt-, an intraabdominal-, or a deep soft tissue infection, respectively, even if the patient is afebrile.

The absence of fever in such a setting should never imply that an underlying infection is under control or not serious. Instead, it requires to be pursued by the doctors thoroughly. Therefore, blood samples and swabs, for example from suspicious sites, need to be taken from the patient. After that, broad spectrum antibiotic therapy should begin promptly in order to prevent unchecked progression of infection in the neutropenic patient.

Care of febrile non-neutropenic patients

Even if the patient is not neutropenic when having a fever, the caregiver team should be notified to give advice on how to appropriately deal with this situation.

If localized signs of infection are present (such as redness, tenderness and swelling), the patient should be tested to find the origin of the fever (for example blood tests for pathogen search, especially if the patient has a central line, stool tests in case of diarrhea, or swabs of suspicious sites). Patients with localized findings should always receive appropriate antibiotic treatment based on the site involved. These antibiotics can often be taken orally so that the patient does not have to stay in the hospital.

Sometimes, the antibiotics given while awaiting the test results have to be changed or supplemented by additional substances later, if a pathogen has been identified that is not covered by the initial regimen. If the test results come back negative (not indicative of any pathogen), antibiotic treatment may be discontinued in patients who are otherwise in good clinical condition. Children and adolescents who are non-neutropenic, feeling well and do not show any focus of infection may not receive any treatment at all. Instead, a non-neutropenic, febrile child with a central line should always get antibiotics that cover a wide variety of bacteria.

Care of patients with infections of the central nervous system (shunt- and reservoir infections)

The treatment of patients with an infection associated with a ventriculoperitoneal shunt or a ventricular catheter, such as a Rickham reservoir, is carried out in close collaboration with a neurosurgeon. The neurosurgeon decides, based on the patient’s condition and the results of the pathogen search, which actions should take place in addition to the initial broad-spectrum antibiotic treatment.

Usually, a shunt removal and subsequent temporary replacement by an external ventricular drainage (see above) is required during antibiotic treatment. Also, infections originating from a Rickham reservoirs require removal of the device until the infection is successfully treated.

Shunt and Rickham reservoir infections carry a high risk of fatal complications if not treated accordingly, because pathogens can spread via the cerebrospinal fluid (CSF), thereby causing meningitis or even infection of the brain tissue (encephalitis).

The removal of the shunt or Rickham reservoir is a minor routine procedure for a neurosurgeon. It is usually performed under general anesthesia.

Care of patients with central line infections

Patients with an infection of their indwelling vascular catheter usually receive a broad spectrum antibiotic treatment, which includes coverage of Staphylococcus, a bacterium that is frequently causing this type of infection.

If the infection does not subside with the medication, or if the infection is caused by more persistent bacteria or fungi, the catheter might have to be removed temporarily. This decision is carefully made, based on the patient’s condition, the appearance of the catheter exit site, and the type of pathogens that have been identified. Removing a central line does not take long and is not painful.