Infection in the immunocompromised host

The term ‘immunocompromised host’ embraces a group of overlapping conditions in which the ability to respond normally to an infective challenge is in some way impaired. This includes patients with underlying conditions such as protein–calorie malnutrition and diabetes, as well as organ transplant recipients, those with haematological malignancies and others receiving therapeutic immunosuppression, and patients with HIV infection. Many patients have multiple risk factors that increase the risk of opportunistic infection.

General clinical approach

A high level of awareness is essential to the management of patients who are immunocompromised; infections can progress with frightening rapidity, the early physical signs are often muted, and the microbiology can be confusing. Aside from a full history and detailed physical examination, assessment should take account of risk factors such as the depth and duration of neutropenia, or the dose and duration of immunosuppressive therapies. It is particularly helpful to try to form a judgement of how quickly the condition is progressing. Patients must be reviewed frequently and will often require empirical antimicrobial therapy, but when possible it is better to try to establish the cause of the infection before starting treatment. This is partly because the differential diagnosis is wide and choosing the right treatment depends on knowing the causative organism, and partly because it is not uncommon for multiple organisms of different types to be involved.

Particular clinical syndromes

Fever of unknown origin—this is common in patients with neutropenia, with the risk of bacteraemia being most acute when the neutrophil count falls to less than 0.1 × 10⁹/litre; in 50% of cases an organism is never identified. Empirical antibiotic therapy is vital and needs to be directed against both Gram-negative and Gram-positive organisms. The risk of invasive fungal infection rises if fever persists, in which case empirical antifungal therapy is justified.

Fever and new pulmonary infiltrates—this is a challenging problem with a wide range of potential causes depending on the clinical setting, including conventional respiratory pathogens, nosocomial pathogens, ‘atypical’ organisms, mycobacteria and related organisms, viruses, fungi, parasites, and also noninfectious causes such as pulmonary oedema, pulmonary haemorrhage, pulmonary emboli/infarction and drug toxicity. The clinical and radiological features are very rarely pathognomonic, hence a diagnostic procedure such as bronchoalveolar lavage should be performed whenever possible.

Acute neurological syndromes—these include both (1) meningoencephalitis—associated with conventional bacterial infections, listeriosis and tuberculosis, as well as fungi such as cryptococcus and candida; and (2) space-occupying lesions—caused by e.g. toxoplasma, aspergillus and nocardia. Once again there is a wide differential diagnosis and a low threshold of diagnostic suspicion is needed.

Gastrointestinal syndromes—these are frequent and include (1) stomatitis—the three commonest causes (candida, herpes simplex virus and chemotherapy-induced mucositis) are clinically indistinguishable and can coexist; (2) diarrhoea—graft-versus-host disease is very difficult to distinguish from infective causes in bone marrow transplant recipients; (3) abnormalities of liver function tests—mild derangements are a common accompaniment to many systemic infections, but hepatitis is a particular feature of both toxoplasmosis and cytomegalovirus infection.

Prevention

This is an integral part of the management of patients who are immunosuppressed and, depending on context, comprises interventions such as nursing them in single rooms and chemoprophylaxis, e.g. co-trimoxazole to prevent pneumocystis and valganciclovir to prevent cytomegalovirus, but perhaps the single most important factor is being aware of the different and often subtle presentations of infection in this vulnerable group of patients.