Notes from the Field: Emergence of Shigella flexneri 2a Resistant to Ceftriaxone and Ciprofloxacin --- South Carolina, October 2010

On October 20, 2010, the South Carolina Department of Health and Environmental Control and CDC began investigating a cluster of three diarrheal illnesses caused by multidrug-resistant Shigella flexneri 2a. The index case occurred in a girl aged 2 years who experienced the onset of diarrhea on September 25 and was hospitalized the next day because of a seizure and fever. On September 30, her brother, aged 6 years, was hospitalized with vomiting, bloody diarrhea, and hyponatremia. Three days later, her father was hospitalized with vomiting, bloody diarrhea, and hyponatremia.

S. flexneri 2a was isolated from all three patients and tested for antimicrobial susceptibility using semi-automated broth microdilution panels. Interpretations of susceptible, intermediate, or resistant were based on the most recently approved standards published by the Clinical and Laboratory Standards Institute (1). The isolates were found susceptible to imipenem, had intermediate susceptibility or were resistant to ceftazidime and cefepime, and were resistant to ampicillin, aztreonam, cefotaxime, ceftriaxone, chloramphenicol, ciprofloxacin, nalidixic acid, streptomycin, sulfisoxazole, tetracycline, and trimethoprim/sulfamethoxazole. Azithromycin inhibited the isolates at a minimum concentration of 2 or 4 µg/mL, which is similar to the azithromycin minimum inhibitory concentrations among Shigellae in the United States during 2005--2007 (no breakpoint for Shigella susceptibility to azithromycin has been established) (2).

The two children were treated sequentially with ceftriaxone, piperacillin/tazobactam, azithromycin, and clarithromycin, for a total of 25 days of treatment per child. The father received piperacillin/tazobactam and azithromycin for 6 days. The younger child's diarrhea persisted for ≥16 days; Shigella organisms were isolated from every stool specimen tested until 24 days after diarrhea onset. All three patients recovered fully.

The index patient was born in China and lived there until being adopted and brought to the United States in August 2010. A playmate of hers, also adopted from China and believed to be aged 2 years, had diarrhea at approximately the same time as the index patient, but no further information was available. None of the other eight family members of the girl nor any social contacts have reported diarrhea since September 2010.

Besides being associated with severe disease, the S. flexneri isolates were resistant to most clinically useful antibiotics and demonstrated a combination of resistance to extended-spectrum cephalosporins and quinolones rarely seen among Shigella organisms isolated in the United States (3). Transmission of this difficult-to-treat pathogen can be prevented by scrupulous hygiene, including thorough handwashing. Shigellosis therapy should be guided by the results of antimicrobial susceptibility testing, and cases should be reported promptly to public health officials so that control measures can be implemented.

Although the source of these isolates is unknown, internationally adopted children can be a source of highly resistant enteric pathogens (4). When newly arrived adoptees have diarrhea, stool culture for bacterial pathogens should be strongly considered (5).

Reported by

S Jue, MD, Univ Medical Center/Greenville Hospital System; R Hardee, MPH, M Overman, DO, E Mays, South Carolina Dept of Health and Environmental Control. A Bowen, MD, J Whichard, DVM, K Greene, G Pecic, Div of Foodborne, Waterborne, and Environmental Diseases, National Center for Emerging and Zoonotic Infectious Diseases; E Taylor, DVM, EIS Officer, CDC.

References

1. Clinical and Laboratory Standards Institute. Performance standards for antimicrobial susceptibility testing; twentieth informational supplement (June 2010 update). CLSI document M100-S20-U. Wayne, PA: Clinical and Laboratory Standards Institute; 2010.
2. Howie RL, Folster JP, Bowen A, Barzilay EJ, Whichard JM. Reduced azithromycin susceptibility in Shigella sonnei, United States. Microb Drug Resist 2010;16:245--8.
3. CDC. National Antimicrobial Resistance Monitoring System: enteric bacteria. Human isolates final report, 2008. Atlanta, GA: US Department of Health and Human Services, CDC; 2010. Available at http://www.cdc.gov/narms/annual/2008/narms_2008_annual_report.pdf. Accessed December 10, 2010.
4. Hendriksen RS, Mikoleit M, Kornschober C, et al. Emergence of multidrug-resistant Salmonella Concord infections in Europe and the United States in children adopted from Ethiopia, 2003--2007. Pediatr Infect Dis J 2009;28:814--8.
5. American Academy of Pediatrics. Shigella infections. In: Pickering LK, Baker CJ, Kimberlin DW, Long SS, eds. Red book: 2009 report of the Committee on Infectious Diseases. 28th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2009:593--6.

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