[Antimicrobial prophylaxis and therapy in neutropenia]

Cytostatic chemotherapy of hematological malignancies if often complicated by neutropenia, which increases the risk of infections, especially if the neutrophil count is below 500/ml. Frequently, fever is the first and in most patients the only sign of an infection. Unexplained fever is defined as follows: temperature of > or = 38.3 degrees C or > or = 38.0 degrees C for at least one hour, or measured twice within 12 hours, if the neutrophil count is < 500/ml or < 1.000/ml with predicted decline to 500/ml. Different risk categories can be identified according to the duration of neutropenia: low risk < or = 5 days, intermediate risk 6-9 days, high risk > or = 10 days. An empirical mono- or duotherapy with antipseudomonal and antistreptococcal agents should be initiated immediately. In the low risk patient group, oral therapy with cipro-, levo-, or ofloxacin combined with amoxicillin/clavulanic acid is permissible. For standard and high risk patients, monotherapy can be carried out with either ceftazidime, cefepime, piperacillin with a beta-lactam-inhibitor or a carbapenem. In duo-therapy, a single dose of an aminoglycoside is combined with acylaminopenicillin or a cephalosporin of the third or fourth generation. The addition of glycopeptides in empirical therapy should only be considered in the presence of severe mucositis, or if a catheter-associated infection is suspected. If fever persists after 72-96 hours of first-line therapy with antibiotics, the regimen should be modified (with the exception of e.g. coagulase-negative staphylococci infections, because these infections take longer to respond). Intermediate risk patients should additionally receive an aminoglycoside after monotherapy (penicillin or a cephalosporin). If a carbepenem was administered for monotherapy, this can be followed by a quinolone and/or a glycopeptide. In the high risk group, the same modifications should be made as in the intermediate risk group but with additional systemic antifungal treatment. In the presence of unexplained fever, fluconazole can be administered at first, but if this fails, amphotericin B (conventional or liposomal), voriconazole, itraconazole or caspofungin should be started. After defervescence to < 38 degrees C, treatment should be continued for seven days if the neutrophil count is < 1.000/ml, and for two days if the neutrophil count is > 1.000/ml. In documented infections treatment is directed against the responsible pathogen, however maintaining the broad spectrum activity. Lung infiltrates are often caused by fungal organisms, therefore an empiric antifungal therapy is necessary which is active against Aspergillus species. Antibacterial prophylaxis can reduce the incidence of bacterial infections, but not the mortality by infections. If the risk of fungal infections exceeds 15%, an antifungal prophylaxis with resorbable drugs can be given.