PHARMACOLOGICAL, TOXICOLOGIC, AND MICROBIOLOGICAL CONSIDERATIONS IN THE CHOICE OF INITIAL ANTIBIOTIC-THERAPY FOR SERIOUS INFECTIONS IN PATIENTS WITH CIRRHOSIS OF THE LIVER

Infection remains a leading cause of death among patients with cirrhosis of the liver. The high level of susceptibility of these patients to septicemic infection is accounted for by decreased reticuloendothelial function and impairment of several components of cell-mediated and humoral immunity. Escherichia coli and Streptococcus pneumoniae are the pathogens most frequently involved and must be covered by any empirical antibiotic regimen administered to seriously ill cirrhotic patients. In addition, antibiotic therapy in this situation must take into account cirrhosis-induced changes in the kinetic and dynamic behavior of antibacterial agents. Given the great toxic potential of aminoglycosides in liver cirrhosis, these agents should be used very cautiously. The third-generation cephalosporins are currently advocated for the treatment of severe infections in cirrhotic patients because of their high level of intrinsic activity against the most commonly encountered pathogens as well as their safe use at high doses for patients with liver insufficiency. The role of the quinolones deserves further clinical evaluation; the limited activity of these agents against S. pneumoniae is undoubtedly a drawback to their use as empirical monotherapy. Despite the potent antibacterial agents that have recently become available, the overall prognosis of these patients is difficult to improve because it remains closely related to the severity of their underlying liver disease.