GRAM-NEGATIVE BACTEREMIA

In the 1960s, almost all patients who developed gram-negative bacterem ia during granulocytopenia died; death occurred before blood culture r esults were available in about 50% of cases; many patients received an tibiotics that were, at best, suboptimal and frequently inactive again st the invading pathogen. In the early 1970s epidemiological studies d emonstrated that more than 50% of gram-negative bacteremias were cause d by hospital-acquired strains which colonized along the alimentary ca nal and caused infection in a limited number of locations, especially the pharynx, lungs, colon, and perianum. Surveillance culture studies have demonstrated that among acquired gram-negative bacilli, Pseudomon as aeruginosa will almost invariably proceed to bacteremia if the pati ent becomes profoundly neutropenic, with Estherichia coli and Klebsiel la pneumoniae leading to bacteremia in only a moderate number of patie nts and other gram-negative bacilli rarely progressing to bacteremia d espite colonization. Hence, the leading causes of bacteremia in the gr anulocytopenic patient are E. coli, K. pneumoniae and P. aeruginosa. F urther investigations demonstrated that gram-negative bacilli were acq uired from hands, food, and water, thus leading to approaches to infec tion prevention which included careful handwashing, low-microbial-cont ent diet, and attention to water sources, including ice machines. Anot her basic approach to infection prevention has been to suppress gram-n egative bacilli colonizing the alimentary canal with oral nonabsorbabl e antibiotics or, more recently and more effectively, with agents such as the fluoroquinolones which, unlike previous regimens, do not concu rrently suppress the anaerobic flora, hence maintaining colonization r esistance. The third basic approach to infection prevention is to impr ove the host defense factors, principally by a more rapid-return of ci rculating granulocytes with the use of colony-stimulating factors such as granulocyte/macrophage colony-stimulating factor or granulocyte co lony-stimulating factor. As to therapy, the fundamental approach with presumed gram-negative bacteremia is the prompt institution of empiric antibiotic therapy when fever first develops in the setting of granul ocytopenia. There is a short ''window of opportunity'' after which no therapy will be effective. Combinations of antibiotics such as a beta- lactam and an aminoglycoside are used for multiple reasons: to afford coverage in the event the pathogen proves resistant to one of the agen ts, to afford a synergistic activity thus improving and prolonging the serum bactericidal activity, and to reduce the development of resista nce. However, patients can be divided into two risk groups: those with granulocytopenia and a regenerating bone marrow and those with an apl astic marrow who will have persistent, profound (< 100 mul) granulocyt openia. Those in the former group can often be treated with a single b road-spectrum beta-lactam antibiotic. Those in the latter group have a poor prognosis but appear to respond better to a combination of agent s, preferably a synergistic combination that achieves a high serum bac tericidal activity. It is with this latter group of patients that the therapeutic addition of colony-stimulating factors may prove to be mos t valuable and, likewise, although there are no definitive data among granulocytopenic patients as yet, monoclonal antibodies, such as HA-1A or E5, may prove to be of added value.