Principles of management of infection in the immunocompromised patient

Susceptibility to infection

Immunocompromised patients have alterations in phagocytic, cellular or humoral immunity that increase both the risk of infection and the ability to combat infection. Patient immunity may be impaired temporarily or permanently as a result of either an immunodeficiency disease state (congenital or acquired) or induced immunosuppression due to a disease state or its management using cytotoxic, immunosuppressive or radiation therapy (organ transplantation or malignant diseases).

The cause and duration of immunodeficiency affects the degree of risk towards infection. There is an inverse relationship between infection risk and absolute neutrophil count. Risk is highest for severe neutropenia (absolute neutrophils <500 cells per mm³).

High-risk:
- Haematological malignancies
- AIDS patients with low CD4+ counts
- Bone marrow transplantation
- Splenectomy
- Genetic disorders such as severe combined immunodeficiency.
Intermediate-risk:
- Solid tumours (particularly after cytotoxic chemotherapy)
- HIV/AIDS
- Solid organ transplant.
Low-risk:
- Long-term corticosteroid use (such as patients with rheumatoid arthritis)
- Patients with areas of locally reduced immune function
- Diabetics.

Patients who are profoundly neutropenic (absolute neutrophil count <500 mm³), asplenic or have a dysfunctional spleen (regardless of neutrophil count) are at special risk and infections in these patients should be treated as a medical emergency.

Aetiology of infection in the immunocompromised patient

The predominant pathogens

in immunocompromised patients vary by type of immunosuppression and often by degree and duration of the immunodeficiency. The source of the infection may be exogenous or endogenous, although this is very difficult to determine as skin and mucous membrane flora often alter in hospitalised patient

A very wide range of organisms can cause infection in immunocompromised patients. Opportunistic pathogens must not be overlooked.
A profoundly immunocompromised patient who has been immunosuppressed for a long time may be vulnerable to more than one infection and different organisms may emerge during a single febrile episode.
Commensals such as Candida and other fungi, and viruses such as cytomegalovirus, can lead to serious infection.
Broad-spectrum antibiotic use increases the risk of secondary fungal infections.
As these patients are often in-patients, nosocomial infections are a particular risk.
Neutropenic patients are at particular risk from Gram-positive organisms. This reflects a change over the past 20 years from predominantly Gram-negative infection.
Diabetic patients are susceptible to infection due to the short-term influence of hyperglycaemia on host defence mechanisms, particularly on neutrophil function and the arterial system. Diabetic patients with poor glycemic control may have abnormalities in lymphocyte number and function.

Detection and diagnosis

Detecting infection in the immunocompromised patient

Immunocompromised patients are vulnerable to a broad-range of infectious agents and, due to the state of immunosuppression, presentation will be atypical and the course fulminant.

Fever is often the only symptom of infection in the immunocompromised patient and always requires further investigation. No pathognomonic pattern or degree of fever can be associated with specific infection and, rarely, fever may be absent during infection in the profoundly immunocompromised. However, if fever of >38°C persists for 2 h or more, broad-spectrum antibiotic therapy should be administered intravenously.

Fever is the cardinal sign of infection in neutropenic patients. It may be the only manifestation, but may not be always be present. Fever always requires further investigation.

Skin and mucous membrane infections can be very widespread and highly visible. In contrast, it is often difficult to identify the site of infection. Signs of inflammation other than fever are often mild or absent and, in patients undergoing cytotoxic chemotherapy, the side-effects of the treatment may mimic infection, eg. pain or mucositis.

Diagnosis of infection

The wide-range of potential pathogens means that standard culture media may not cover all the possibilities and the microbiology department should be alerted to the patient’s clinical history and extent of immunosuppression. Initiation of treatment should not be delayed pending laboratory results, but treatment should be tailored once the results are obtained.

Laboratory evaluation

Specimens should be selected based on the signs and symptoms presented and should reflect the disease process. Blood samples should always be taken and both bacterial and fungal cultures should be assessed. Blood counts may also be useful to assess the degree of neutropenia. Cultures may also be obtained from:

Cerebrospinal fluid
Urine and stool samples, which may indicate a UTI or gastrointestinal infection
Nose and throat swabs or a sputum sample if the signs present in the oropharynx
If a viral infection is suspected, a cytomegalovirus antigen test may be performed, particularly in transplant and HIV/AIDS patients.

Principles for management

Generally, the treatment should target the pathogen most likely to be involved, depending upon the host condition and duration of immunosuppression

. Resistant or opportunistic organisms should always be considered. The core regimen should include:

A combination of broad-spectrum antibiotics at high-doses to combat Gram-positive and Gram-negative aerobes, plus antifungal therapy from the outset of treatment to prevent secondary fungal infection
Administration via IV for rapid onset of action
Consideration of local factors ie. underlying disease state, presence of an intravascular device, local bacterial ecology and known resistance patterns.

Once results of the culture and sensitivities are known, consult the hospital microbiologist and tailor antibiotic treatment accordingly.

Empirical therapy

Consult your microbiologist or local treatment guidelines for initial empirical therapy.

If fever persists and no pathogen is isolated it is possible that a viral or fungal infection is present. Alternatively, non-infective conditions such as graft-versus-host disease or thrombosis should be considered.

The immunocompromised patient with fever should be examined every day while fever persists.

Treatment regimens

Patients with HIV or AIDS should be managed by a specialist team. The possibility of TB or other diseases common in AIDS, such as Pneumocystis carinii pneumonia should be considered.
Neutropenic patients
Transplant patients
Asplenic patients
Rheumatoid arthritis
Diabetic patients

Principles for prophylaxis

Immunisation
Chemoprophylaxis