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Worldwide, shigellosis is estimated to cause more than 188 million cases of diarrhea each year, including about 500,000 cases in the United States.1,2 “Bacillary dysentery,” a term used to describe a diarrheal illness with fever, abdominal pain, and blood and pus (leukocytes) in the stool, is often used to refer to shigellosis in lower income countries. Transmission of Shigella spp. is most likely when there is crowding and hygiene and sanitation are insufficient. Shigellosis is predominantly caused by S. sonnei in industrialized countries, whereas S. flexneri prevails in lower income countries; there is evidence that S. sonnei is increasing in industrializing regions in Asia, Latin America, and the Middle East.3 Infections caused by S. boydii and S. dysenteriae are uncommon globally but can make up a substantial proportion of Shigella spp. isolated in sub-Saharan Africa and South Asia.
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In the United States, outbreaks and sporadic disease typically occur among young children in childcare centers,4–7 international travelers,8–11 men who have sex with men (MSM),12–22 persons with weakened immune systems,23 and those in small social groups such as traditionally observant Jewish communities.24–27 Antibiotic resistance among Shigella is a serious and growing worldwide problem that is limiting options for effective treatment. The Centers for Disease Control and Prevention (CDC) has categorized drug-resistant Shigella as a serious threat to public health, and the World Health Organization (WHO) has included fluoroquinolone-resistant Shigella on its global priority list of antibiotic-resistant pathogens.28,29
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The Shigella species are a fairly homogeneous group of Gram-negative, facultatively anaerobic, nonmotile, nonlactose-fermenting bacilli classified in the family Enterobacteriaceae. The genus Shigella has 4 species or subgroups (A, B, C, and D) and 43 serotypes. Subgroups A, B, C, and D have historically been treated as species: subgroup A is referred to as S. dysenteriae; subgroup B as S. flexneri; subgroup C as S. boydii, and subgroup D as S. sonnei. Subgroups and serotypes are differentiated from each other by biochemical characteristics (e.g., ability to ferment D-mannitol) and antigenic properties. The most recently recognized serotype belongs to subgroup C.30–32
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Shigella species are becoming increasingly resistant to first-line treatment agents, including ciprofloxacin and azithromycin, and, in some areas, cephalosporins.33–40 The mechanisms underlying these resistance phenotypes in Shigella include mobile genetic elements with resistance genes [e.g., plasmids with mph(A) and CTX-M genes conferring resistance to azithromycin and cephalosporins, respectively], and chromosomal mutations (e.g., gyrA and parC mutations conferring fluoroquinolone resistance).33,34,41–45 Both clonal expansion of resistant strains and horizontal transfer of resistance determinants have contributed to the spread of clinically important resistance.43,46 Genetic studies suggest that fluoroquinolone resistance in Shigella sonnei has been largely driven by the expansion of a clone that emerged and spread in South Asia before disseminating intercontinentally to Europe, America, and other areas.33,46 In contrast, the genes conferring ...