RESUMO
BACKGROUND: Recommended treatment for travelers' diarrhea includes the combination of an antibiotic, usually a fluoroquinolone or azithromycin, and loperamide for rapid resolution of symptoms. However, adverse events, postdose nausea with high-dose azithromycin, effectiveness of single-dose rifaximin, and emerging resistance to front-line agents are evidence gaps underlying current recommendations. METHODS: A randomized, double-blind trial was conducted in 4 countries (Afghanistan, Djibouti, Kenya, and Honduras) between September 2012 and July 2015. US and UK service members with acute watery diarrhea were randomized and received single-dose azithromycin (500 mg; 106 persons), levofloxacin (500 mg; 111 persons), or rifaximin (1650 mg; 107 persons), in combination with loperamide (labeled dosing). The efficacy outcomes included clinical cure at 24 hours and time to last unformed stool. RESULTS: Clinical cure at 24 hours occurred in 81.4%, 78.3%, and 74.8% of the levofloxacin, azithromycin, and rifaximin arms, respectively. Compared with levofloxacin, azithromycin was not inferior (P = .01). Noninferiority could not be shown with rifaximin (P = .07). At 48 and 72 hours, efficacy among regimens was equivalent (approximately 91% at 48 and 96% at 72 hours). The median time to last unformed stool did not differ between treatment arms (azithromycin, 3.8 hours; levofloxacin, 6.4 hours; rifaximin, 5.6 hours). Treatment failures were uncommon (3.8%, 4.4%, and 1.9% in azithromycin, levofloxacin, and rifaximin arms, respectively) (P = .55). There were no differences between treatment arms with postdose nausea, vomiting, or other adverse events. CONCLUSIONS: Single-dose azithromycin, levofloxacin, and rifaximin with loperamide were comparable for treatment of acute watery diarrhea. CLINICAL TRIAL REGISTRATION: NCT01618591.
Assuntos
Antibacterianos/uso terapêutico , Diarreia/tratamento farmacológico , Levofloxacino/uso terapêutico , Viagem , Doença Aguda/epidemiologia , Adulto , Afeganistão/epidemiologia , Antibacterianos/administração & dosagem , Antibacterianos/efeitos adversos , Azitromicina/administração & dosagem , Azitromicina/efeitos adversos , Azitromicina/uso terapêutico , Diarreia/microbiologia , Djibuti/epidemiologia , Método Duplo-Cego , Quimioterapia Combinada , Escherichia coli/efeitos dos fármacos , Infecções por Escherichia coli/tratamento farmacológico , Infecções por Escherichia coli/epidemiologia , Feminino , Honduras/epidemiologia , Humanos , Quênia/epidemiologia , Levofloxacino/administração & dosagem , Levofloxacino/efeitos adversos , Loperamida/administração & dosagem , Loperamida/efeitos adversos , Loperamida/uso terapêutico , Masculino , Militares/estatística & dados numéricos , Resultado do TratamentoRESUMO
Noroviruses are the leading cause of acute gastroenteritis in the United States and are responsible for at least 50 % of acute gastroenteritis outbreaks occurring worldwide each year. In addition, noroviruses have caused outbreaks on cruise ships, in nursing homes and hospitals, and in deployed military personnel, but its role in the etiology of travelers' diarrhea is not well defined. The aim of this review is to describe the role of noroviruses in travelers' diarrhea in terms of epidemiology, current diagnostics, treatment and vaccine development efforts. Studies have shown prevalence rates of noroviruses in travelers' diarrhea cases ranging from 10-65 %. It is likely that norovirus prevalence rates are highly underestimated in travelers' diarrhea due to rapid onset, short duration of the illness, limited availability of laboratory facilities, and the fact that most clinical laboratories lack the diagnostic capability to detect noroviruses in stool. Further, additional studies are needed to accurately determine the true prevalence rates of norovirus as an etiologic agent of diarrhea among travelers to different regions around the world. With the rapid progress in the development of a norovirus vaccine, travelers could serve as an ideal population for future norovirus clinical trials.