14 February 2013

Outbreak of Infections Caused by Shigella sonnei with Reduced Susceptibility to Azithromycin in the United States

LETTER

Shigellosis is the third most common enteric bacterial infection in the United States (1). The disease is caused by Shigella bacteria, and symptoms include abdominal cramps, diarrhea that sometimes contains blood, nausea, vomiting, and fever. Shigella sonnei has a very low infectious dose, and the infection may spread from person to person or via contaminated objects, food, or water. In the United States, the incidence is highest among children who are <5 years old, and multiple outbreaks of S. sonnei infections have been associated with daycare centers (2, 3).
In the United States, shigellosis is frequently treated with antimicrobial drugs because they can slightly shorten the duration and severity of illness (4). Increasing resistance to ampicillin and trimethoprim-sulfamethoxazole has led physicians to prescribe azithromycin for treatment of shigellosis (3, 5). Azithromycin is currently recommended by the American Academy of Pediatrics and the Infectious Diseases Society of America for the treatment of multidrug-resistant shigellosis, although azithromycin susceptibility testing guidelines and interpretive criteria are lacking for Shigella (6, 7). A study by Howie et al. showed the susceptible wild-type distribution of MICs to range from 4 to 16 μg/ml (8). Isolates with higher azithromycin MICs have been confirmed to harbor mphA, a macrolide resistance gene encoding a macrolide-2′-phosphotransferase (8, 9).
In May 2012, the Los Angeles County Department of Public Health (Los Angeles County, CA) investigated an outbreak caused by S. sonnei that sickened 43 people. Four representative isolates (2012C-3667 to 2012C-3670) were submitted to the Centers for Disease Control and Prevention (CDC). Two isolates were obtained from asymptomatic, male employees of a bridge club, one of whom was a food handler. Two isolates were obtained from women in the same club. Both women were hospitalized with nonbloody diarrhea; one was ill for 7 days and reported vomiting and fever of 102°F; the duration of illness was not reported for the other. The ages of these four individuals ranged from 60 to 89 years.
The isolates yielded indistinguishable patterns by pulsed-field gel electrophoresis (PFGE) using XbaI (PulseNet pattern J16X01.0756). Susceptibility to 14 antimicrobial agents was determined by broth microdilution (Sensititre; Trek Diagnostics, Westlake, OH). All four isolates displayed resistance to streptomycin, sulfisoxazole, tetracycline, and trimethoprim-sulfamethoxazole. In addition, all four isolates displayed azithromycin MICs of >16 μg/ml (Table 1). PCR screening confirmed the presence of mphA in all four isolates (8). Plasmid DNA from two isolates was electroporated into Escherichia coli DH10B cells. E. coli transformants with elevated MICs to azithromycin (MIC > 16 μg/ml) confirmed the mphA gene to be located on a plasmid. The plasmid type could not be determined by inc/rep typing (10).
Table 1
Table 1 MICs for Shigella sonnei and Escherichia coli isolatesa
Antimicrobial agentbMIC (μg/ml) for isolate:
2012C-36672012C-36682012C-36692012C-3670DH10B-3668DH10B-3670DH10B
Ampicillin2244444
Amoxicillin-CLA4444242
Azithromycin>16>16>16>16>16>162
Cefoxitin2222888
Ceftriaxone≤0.25≤0.25≤0.25≤0.25≤0.25≤0.25≤0.25
Chloramphenicol4444≤2≤2≤2
Ciprofloxacin≤0.016≤0.016≤0.016≤0.016≤0.016≤0.016≤0.016
Gentamicin21110.50.50.5
Kanamycin≤8≤8≤8≤8≤8≤8≤8
Nalidixic acid1111111
Streptomycin>64>64>64>64>64>64>64
Sulfisoxazole>256>256>256>256>256>256≤16
Tetracycline>32>32>32>32≤4≤4≤4
Trimethoprim-sulfamethoxazole>4>4>4>4>4>4≤0.125
a
The Shigella sonnei and Escherichia coli isolates tested were four 2012 outbreak isolates of Shigella sonnei (2012C-3667 to 2012C-3670), two Escherichia coli DH10B transformants (DH10B-3668 and DH10B-3670), and E. coli DH10B.
b
CLA, clavulanic acid.
To our knowledge, this is the first outbreak caused by Shigella isolates displaying elevated azithromycin MICs to be documented within the United States. The circulation of Shigella isolates with high azithromycin MICs is worrisome, since it may limit the treatment options for multidrug-resistant infections, especially among children.

REFERENCES

1.
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Antimicrobial Agents and Chemotherapy cover image
Antimicrobial Agents and Chemotherapy
Volume 57Number 3March 2013
Pages: 1559 - 1560
PubMed: 23274665

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Published online: 14 February 2013

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Authors

Maria Sjölund Karlsson
Division of Foodborne, Waterborne and Environmental Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
Anna Bowen
Division of Foodborne, Waterborne and Environmental Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
Roshan Reporter
Los Angeles County Department of Public Health, Los Angeles, California, USA
Jason P. Folster
Division of Foodborne, Waterborne and Environmental Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
Julian E. Grass
Division of Foodborne, Waterborne and Environmental Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
Rebecca L. Howie
IHRC, Inc., Atlanta, Georgia, USA
Julia Taylor
IHRC, Inc., Atlanta, Georgia, USA
Jean M. Whichard
Division of Foodborne, Waterborne and Environmental Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA

Notes

Address correspondence to Maria Sjölund Karlsson, [email protected].

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