Antimicrobial therapy for enteric infections and typhoid fever: state of the art.

Increasing antimicrobial resistance of enteric pathogens represents a significant barrier to therapy for bacterial enteritis and, to a lesser extent, typhoid fever. Poor study design limits the value of many of the clinical trials that suggest drug efficacy. Studies are often not placebo-controlled, randomized, or blind comparative trials; clinical criteria for response are frequently not stated; and the numbers of subjects are small. Among the known therapeutic principles for choosing drugs for enteric infections is that the agent be active in vitro against the isolate, that for treating infections due to invasive pathogens both lumenal and tissue levels be adequate, that drugs with good enterohepatic circulation may be especially well suited for the treatment of infections due to noninvasive pathogens, and that drugs active intracellularly may have particular value in therapy for typhoid, especially in reducing the relapse rate. The new 4-quinolones are not only highly active in vitro against a broad range of enteric pathogens but generally also exhibit most of the other properties desirable for the treatment of these infections. Although further clinical trials are necessary to assess the comparative efficacy of the quinolones, the present clinical data already indicate that they will be of great utility, and particularly important in the treatment of drug-resistant shigellosis, which is currently a major problem in many developing nations in Asia and Africa.