In January 2007, Robert Debré Hospital reported a case of acute gastroenteritis (AGE) caused by Shigella sonnei resistant to amoxicillin (AMX) and cotrimoxazole (SXT) (S. sonnei RR) but also to azithromycin (AZM), an antibiotic recommended by the French Health Products Safety Agency for the treatment of S. sonnei gastroenteritis. An investigation was then conducted to describe the cases, determine the antibiotic susceptibility of the strains in collaboration with the National Reference Center (NRC), and monitor the effectiveness of control measures. Confirmed cases were defined as individuals residing in Île-de-France who presented with acute gastroenteritis (AG) confirmed by a stool culture positive for S. sonnei RR, and probable cases as individuals presenting with AG who had been in contact with a confirmed case. Cases were identified retrospectively and prospectively through surveillance system laboratories, the NRC, schools, and families. Families were interviewed by telephone using a standardized questionnaire. In total, 103 cases (including 81 confirmed cases) of GEA caused by S. sonnei RR were identified between January 10 and April 24, 2007. Of these, 98 were investigated. The outbreak primarily affected two private Jewish schools located in Paris and Val-de-Marne, with 60 and 7 cases, respectively. AZM resistance was detected in 38 of the 41 strains received and tested by the CNR, necessitating a revision of treatment recommendations by experts and the establishment of a specific hospital care pathway for these cases. This new resistance necessitates the systematic testing of all S. sonnei RR isolates for AZM susceptibility by the CNR and, in the future, once a validated method has been developed, by private clinical laboratories. It requires the initiation of antibiotic treatment in a hospital setting for children when such treatment is indicated. (R.A.)