Effect of host factors in the cure of gram-negative bacterial infections

Abstract

It has been shown among patients with gram negative bacterial infections, either life-threatening bacteraemia or common urinary tract infections, that categorical host factors markedly impinge on the observed effects of treatment with antimicrobial drugs. These factors have statistical significance in predicting the results that will be obtained with any particular chemotherapeutic regimen. The mechanisms mediating the host effects are not known, but in bacteraemia some conditions such as those that cause a decrease in circulating phagocytes, deficient function of fixed macrophages, delayed bacterial clearance and a reduced tolerance to shock, can be assumed to be important. In others, such as urinary tract infections, the finality of the eradication of bacteria from infected tissues may be paramount. The host factors are independent of, but also influence and integrate the effect of specific bacterial and drug features of infection and treatment. Readily recognizable clinical conditions permit some grouping of patients by host categories in order to make comparable analysis of antimicrobial drugs and regimens. In the search for clinical measures of synergy, host effects may dominate and obscure differences observed in vitro or in experimental infections in animals. However, the treatment of infection in host comparable groups of patients provides the opportunity to examine critically the clinical applicability of in vitro synergy and to devise more meaningful tests and procedures to achieve synergy in the treatment of infection in persons with unfavourable host conditions.