The risk of infection and predominant pathogens

When a patient is found to be neutropenic, the peripheral blood neutrophil count serves as a rough guide to the relative seriousness of the disorder. This degree of neutropenia can be 'mild' (1.0-1.8 x 109/l), 'moderate' (0.5-1.0 x 109/l), or 'severe' (< 0.5 x 109/l). Patients with severe neutropenia, particularly those with neutrophil levels exceeding 0.2 x 109/l, are at significant risk of infection, usually by bacterial invasion arising from the mouth and intestinal tract, such as the Gram-negative bacilli Escherichia coli, Klebsiella species, and Pseudomonas aeruginosa (T.a.bJe.1). These organisms are responsible for considerable morbidity and mortality as they can lead to overwhelming septic shock and disseminated intravascular coagulation (DIC).

Table 1 Immunological defects and associated pathogens in neutropenic patients

With the widespread use of indwelling catheters and the alteration of normal gut flora by prophylactic antibiotics, the spectrum of bacteria isolated during febrile neutropenia has changed in the last decade from predominantly Gram-negative to Gram-positive organisms such as Staphylococcus epidermidis and a-hemolytic streptococci. Although Gram-positive organisms have also been associated with the septic shock syndrome and DIC, they are generally regarded as less virulent than Gram-negative bacilli. Further changes in the microbiological flora have occurred because of the extensive use of third-generation cephalosporins, resulting in the emergence of multiresistant Enterobacter species and unusual bacteria (e.g. Stenotrophomonas maltophilia, Acinetobacter species, and other pseudomonads) as frequent pathogens in neutropenic patients.

Apart from the severity of neutropenia, other factors which have an important influence on the risk and type of infection include the duration of neutropenia, defects in other components of the immune system (due to either the underlying disease or treatment), nutritional status, previous splenectomy, the integrity of skin and mucous membranes, and the use of blood components because of the risk of blood-borne infection. For example, fungal infections are very common in patients with prolonged neutropenia and in those treated with broad-spectrum antibiotics or corticosteroids. Particularly vulnerable are bone marrow transplant patients, in whom the incidence of deep mycoses reaches 30 per cent. Similarly, the risk of opportunistic infections (e.g. Pneumocystis carinii) is much higher in neutropenic patients with human immunodeficiency virus (HIV) infection. In contrast, a defect of humoral immunity, as in chronic lymphocytic leukemia and multiple myeloma, will predispose neutropenic patients to infection from encapsulated organisms such as Streptococcus pneumoniae or Hemophilus influenzae because of lack of appropriate opsonization.

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