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Antimicrobial therapy for enteric infections and typhoid fever: state of the art
1Department of Medicine, New England Medical Center Hospitals-Tufts University School of Medicine, Boston, Massachusetts.
Abstract:
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.
Insights
Antimicrobial resistance in enteric pathogens complicates treatment. New fluoroquinolones show promise for treating bacterial enteritis and typhoid fever, especially drug-resistant shigellosis.
Area of Science:
- Microbiology
- Infectious Diseases
- Pharmacology
Background:
- Antimicrobial resistance in enteric pathogens poses a significant therapeutic challenge for bacterial enteritis and typhoid fever.
- Many existing clinical trials assessing drug efficacy suffer from poor study design, limiting their reliability.
Purpose of the Study:
- To evaluate the potential of new fluoroquinolones in treating enteric infections, considering their in vitro activity and pharmacokinetic properties.
- To address the growing problem of drug-resistant shigellosis in developing nations.
Main Methods:
- Review of therapeutic principles for selecting antimicrobial agents for enteric infections.
- Assessment of in vitro activity and desirable pharmacokinetic properties of new fluoroquinolones against enteric pathogens.
- Evaluation of existing clinical data on fluoroquinolone efficacy.
Main Results:
- New fluoroquinolones demonstrate high in vitro activity against a broad spectrum of enteric pathogens.
- These agents possess desirable pharmacokinetic properties for treating various enteric infections.
- Fluoroquinolones are particularly valuable for treating drug-resistant shigellosis.
Conclusions:
- Fluoroquinolones are a promising class of antimicrobials for enteric infections.
- Further clinical trials are needed to confirm comparative efficacy.
- These drugs are expected to be highly useful, especially for drug-resistant shigellosis in Asia and Africa.