ANTIINFECTIVE STRATEGIES IN NEUTROPENIC PATIENTS

In spite of considerable progress in clinical care and supportive meas ures, infection remains by far the principal cause of morbidity and mo rtality in febrile neutropenic patients, especially following intensiv e myelosuppressive therapy for haematological malignancies. The concep t of empirical therapy, dating from the early 1970s and referring to t he use of broad-spectrum antibiotics without or before definite proof of infection, was of paramount importance for the elimination of early infectious deaths, mainly due to Gram-negative bacteria, and has dram atically reduced mortality figures by infection to about 6%. However, over the last two decades, consecutive trials have witnessed marked sh ifts, both in the spectrum of offending pathogens, bacterial as well a s non-bacterial, and in the clinical presentations. Although most clin ical studies completed by international groups have advocated the use of combination therapy on theoretical grounds, including a beta-lactam plus an aminoglycoside or double betalactams, no single recent trial comparing monotherapy with the newer extended-spectrum compounds versu s combination therapy could demonstrate relevant differences in outcom e. Contrary, combinations were hampered by associated toxicity. We cur rently accept monotherapy with agents such as carbapenems and third-ge neration cephalosporins (ceftazidime) as standard of empirical care in neutropenic patients while the results of ongoing trials with 'fourth -generation' cephalosporins and fluoroquinolones are awaited with impa tience. However, the universally adopted and indiscriminate implementa tion of broad-spectrum therapy has undoubtedly taken a toll of current anti-infective strategies, including the emergence of highly resistan t isolates and the disastrous shift towards invasive mould and yeast i nfections. Consequently, empirical therapy has evolved towards a plann ed-progressive modification in persistent neutropenic febricity, espec ially aiming at early antifungal coverage. However, randomised data on second- and third-line modifications of empirical regimens are sparse ;moreover, significant divergence exists between European and North-Am erican centres. The exact place and need for glycopeptide antibiotics remains another controversial issue, certainly, in view of the alarmin g isolation of resistant enterococci. The improved identification of p atient subgroups by the development of accurate risk assessment models based on prognostic factors, such as age, underlying disorder, durati on of neutropenia, intensity of treatment and offending pathogen, shou ld result in a more rational application of antimicrobial agents and m ay pave the way to a patient-tailored (rather than a planned-progressi ve) and modifiable anti-infective approach with respect to hospitalisa tion and need for extended-spectrum empirical therapy.