Antimicrobial Prophylaxis

In recent years, ciprofloxacin has been used most extensively for prevention of bacterial infections in patients with prolonged severe neutropenia. Although it has reduced the frequency of Gram-negative bacterial infections, its use has been associated with an increase in Grampositive infections and the emergence of resistance among Gram-negative bacilli. Also, in most studies, its use did not reduce the frequency of fever and empiric antibacterial therapy. Hence, its use should be restricted to those patients who are likely to experience severe neutropenia following chemotherapy. Outpatients at risk for pneumococcal or Listeria infections could be given a supply of amoxicillin-clavulanate to be initiated at the onset of fever, as should splenectomized patients (3). Since serious fungal infections occur rather infrequently in CLL patients, it is difficult to justify the routine use of antifungal prophylaxis, especially since it has been associated with colonization by resistant Candida species.

Herpes simplex infections are painful, interfere with nutrition, and may become superinfected with bacterial pathogens. Hence, patients who receive therapy with purine analogs should be considered for prophylaxis with acyclovir or valcyclovir if they have had previous infection (46). Long-term prophylaxis to prevent herpes zoster infections is probably not necessary since nearly all infection is localized to a few dermatomes.

Trimethoprim-sulfamethoxazole (TMP-SMX) has been used effectively to prevent P. carinii pneumonia in AIDS patients and also has activity against L. monocytogenes. Some physicians have suggested that CLL patients who are receiving fludarabine should be given TMP-SMX (1 double strength tablet 3 times weekly) until at least 2 mo after completion of therapy (46,83). However, the frequency of this infection was only 0.5% in a large group of patients treated with fludarabine, which suggests this is not necessary (50).

The use of growth factors [granulocyte and granulocyte/macrophage colony-stimulating factor (G-CSF, GM-CSF)] in patients receiving therapy resulting in severe neutropenia may be considered. In a group of patients receiving fludarabine plus G-CSF, the frequencies of neutro-

penia and severe neutropenia (<500 cells/|L) were 45 and 15% compared with 79 and 63%, respectively, in historical controls who received only fludarabine (84). The frequency of pneumonia was 8% versus 37%, but the frequencies of other infections were similar in both groups. In a small group of CLL patients with chronic neutropenia caused by hypersplenism and autoimmune problems, GM-CSF administration substantially increased patients' neutrophil counts and improved the chemoluminescence of neutrophils in vitro (85).

Some physicians have suggested that patients receiving fludarabine should avoid potential sources of L. monocytogenes such as unpasteurized milk and cheese, raw vegetables, and undercooked poultry or meat (46). It may be wiser to stress the importance of careful cleaning of raw vegetables rather than total abstention.

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