Use of cephalosporins in the immunologically compromised patient

Infection is a major threat to patients with neutropenia, particularly those with haematological malignancies who are undergoing chemotherapy. Early use of an empirical antibiotic regimen with the broadest possible spectrum of activity is recommended until culture data can guide the choice. A standard combination in many centres is an amino-glycoside and a semisynthetic penicillin with antipseudomonal activity or a cephalosporin. However, no regimen can adequately cover all potential pathogens and in these patients, who are exposed to many toxic insults, the choice of antibiotics may significantly increase the incidence of side effects, particularly nephrotoxicity. There has, therefore, been considerable interest in simpler, less toxic (and less expensive) regimens and the concept of monotherapy has been explored. Although recent studies using ceftazidime alone have supported this as an effective approach, there remain several issues to resolve; and on a more cautionary note preliminary results from the latest EORTC study, which recruited more than 1200 patients, suggest that in Gram-negative bacteraemia, conventional combination therapy remains the treatment of choice in neutropenia. While monotherapy is attractive in an environment of low drug resistance when exposure to third generation cephalosporins is infrequent, this is rarely the case. In addition, the widespread use of tunnelled catheters for venous access had led to an increase in Gram-positive infections, and the more intensive immunosuppression to the emergence of fungal infections. Although these tend not to be rapidly fatal, their presence must be considered in designing treatment strategies. The influence of the host and treatment on the type of infection and the relative merits of the differing concepts in therapy are explored in detail in this article.