Background Shigella dysentery is a relatively common illness and occasionally causes death, worldwide. Mild symptoms are self-limiting but in more severe cases, antibiotics are recommended for cure and preventing relapse. The antibiotics recommended are diverse, have regional differences in sensitivity, and have side effects. Objectives To evaluate the efficacy and safety of antibiotics for treating Shigella dysentery. Search strategy In June 2009 we identified all relevant trials from the following databases: Cochrane Infectious Diseases Group Specialized Register; Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2008, issue 4), MEDLINE, EMBASE, LILACS and the metaRegister of Controlled Trials (mRCT). We also checked conference proceedings for relevant abstracts, and contacted researchers, organizations, and pharmaceutical companies. Selection criteria Randomized controlled trials of antibiotics for Shigella dysentery. Data collection and analysis Four authors, working in pairs, independently assessed trial eligibility, methodological quality, and extracted data. We calculated risk ratios (RR) with 95% confidence intervals (CI) for dichotomous data, and used the random-effects model for significant heterogeneity. We explored possible sources of heterogeneity, when present, in subgroup analyses of participant age and percentage of participants with confirmed Shigella infection. Main results Sixteen trials (1748 participants), spanning four decades and with differing sensitivity to Shigella isolates, met the inclusion criteria. Seven were judged to be at risk of bias due to inadequate allocation concealment or blinding, and 12 due to incomplete reporting of outcome data. Limited data from one three-armed trial of people with moderately severe illness suggest that antibiotics reduce the episodes of diarrhoea at follow-up (furazolidone versus no drug RR 0.21, 95% CI 0.09 to 0.48, 73 participants; cotrimoxazole versus no drug RR 0.30, 95% CI 0.15 to 0.59, 76 participants).There was insufficient evidence to consider any class of antibiotic superior in efficacy in treating Shigella dysentery, but heterogeneity for some comparisons limits confidence in the results. All the antibiotics studied were safe. There was inadequate evidence regarding the role of antibiotics in preventing relapses. Authors' conclusions Antibiotics reduce the duration of Shigella dysentery.Regularly updated local or regional antibiotic sensitivity patterns to different species and strains of Shigella are required to guide empiric therapy. More trials adhering to standard guidelines are required to evaluate the role of antibiotics in the treatment of severe forms of Shigella dysentery and in groups who are at high risk of complications.

Antibiotic therapy for Shigella dysentery

Identification and management of Shigella infection in children with diarrhoea: a systematic review and meta-analysis.

Since the introduction of sulfonamides in the late 1930s, selective pressure and the widespread dissemination of mobile genetic elements conferring antimicrobial resistance have forced clinicians to seek successive agents for the treatment of multidrug-resistant shigellosis. Over the decades, the principal antibiotics used to treat Shigella infections have included tetracycline, chloramphenicol, ampicillin, trimethoprim-sulfamethoxazole, and nalidixic acid. Presently, ciprofloxacin, azithromycin, and ceftriaxone serve as the mainstays of treatment, although growing evidence has documented decreased susceptibility or full resistance to these agents in some regions. With diminishing pharmaceutical options available, there is an enhanced need for preventive measures in the form of improved sanitation and hygiene standards, strict use of currently effective agents, and a safe and effective licensed vaccine.

Treatment of drug-resistant Shigella infections

Traveling with infants and young children. Part III: travelers' diarrhea.

Shigella flexneri is a facultative intracellular pathogen responsible for endemic shigellosis especially in developing countries. Furazolidone, a nitrofuran derivative, is very effective against the infection with S. flexneri. To examine potential effects of furazolidone on this germ, a whole-genome DNA microarray was constructed and transcriptional profiles of the responses to furazolidone were determined. The expressing data revealed adaptive responses of S. flexneri to oxidative stress induced by furazolidone treatment. Iron metabolism was found to be disturbed by furazolidone through derepression of the iron uptake regulon. In addition, energy metabolism, amino acid metabolism, cofactors metabolism, and DNA repair system were also affected by the drug. These data establish a potential for furazolidone to enhance free radical reactions through reductive activation by oxygen-sensitive nitroreductase. Moreover, we provide evidence that furazolidone is able to cause metabolic dysfunction, which cannot always be attributed to oxidative stress, and interactions between reductive metabolites of furazolidone and S. flexneri should be considered.

Transcriptional profile induced by furazolidone treatment of Shigella flexneri

Efficacy of furazolidone and nalidixic acid was compared in a randomized trial involving 72 children with acute invasive diarrhea. Thirty six children received furazolidone (7.5 mg/kg/day) and 36 children received nalidixic acid (55 mg/kg/day). Clinical characteristics of the two treatment groups were comparable on admission. Of these, 34 children in furazolidone treated group and 29 children in nalidixic acid treated group completed the full course of treatment and were analyzed finally for clinical efficacy. Clinical cure was observed in 29(85.3%) children treated with furazolidone and 29(100.0%) children treated with nalidixic acid. Nalidixic acid treated group had statistically significantly higher cure rate (p = 0.039) as compared to furazolidone treated group. However, 85% cure rate in furazolidone treated group may be potentially useful for the treatment of acute invasive diarrhea because of decreasing efficacy of nalidixic acid against shigellosis in many countries.

Comparative efficacy of furazolidone and nalidixic acid in the empirical treatment of acute invasive diarrhea: randomized clinical trial.

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Comparative efficacy of furazolidone and nalidixic acid in the empirical treatment of acute invasive diarrhea: randomized clinical trial.