CDC Issues Health Advisory on Shigella

Strains Emerging With Possible Reduced Susceptibility to Ciprofloxacin

April 20, 2017 04:30 pm News Staff

With temperatures rising and more patients participating in outdoor activities, including water sports and other water-related pursuits, it's important to heed a recent CDC Health Alert Network (HAN) health advisory(emergency.cdc.gov) warning clinicians about emerging Shigella strains that demonstrate possible reduced susceptibility to ciprofloxacin.

Under the low-power magnification of 10X on a digital Keyence scope, this photograph depicts the colonial growth displayed by gram-negative Shigella sonnei bacteria.

Specifically, the CDC has identified strains of Shigella with elevated minimum inhibitory concentration (MIC) values for ciprofloxacin (i.e., values of 0.12-1 μg/mL). Despite current Clinical and Laboratory Standards Institute (CLSI) criteria that categorize Shigella isolates with a ciprofloxacin MIC of ≤1 μg/mL as susceptible to ciprofloxacin, recent data from the CDC and state and local public health partners indicate these emerging strains frequently have a quinolone-resistant gene that can lead to clinically significant reduced susceptibility to fluoroquinolone antibiotics.

The agency said Shigella isolates without a quinolone-resistance gene typically have a ciprofloxacin MIC of 0.015 μg/mL or less.

"Clinicians treating patients with multidrug-resistant shigellosis for whom antibiotic treatment is indicated should avoid prescribing fluoroquinolones if the ciprofloxacin minimum inhibitory concentration (MIC) is 0.12 μg/mL or higher, even if the laboratory report identifies the isolate as susceptible," the HAN advisory recommended.

Story highlights
  • The CDC has released a Health Alert Network health advisory warning clinicians about emerging Shigella strains that show possible reduced susceptibility to ciprofloxacin.
  • The CDC has identified strains of Shigella with elevated minimum inhibitory concentration values for ciprofloxacin.
  • The agency's advisory offers background on its findings and outlines new recommendations for clinical diagnosis, management and reporting of Shigella infections.

Furthermore, the CDC said physicians should work closely with clinical microbiology laboratories and infectious disease specialists to determine appropriate antimicrobial therapy. All cases of shigellosis should be reported to local health departments.

HAN Advisory Background

The HAN advisory stated that in Salmonella isolates, ciprofloxacin MICs of 0.12-1 μg/mL have been associated with reduced susceptibility, prolonged clinical illness and treatment failures, and such isolates are now categorized by CLSI as intermediate or resistant to ciprofloxacin.

"Fluoroquinolone resistance is of particular concern given that data from the National Antimicrobial Resistance Monitoring System indicate that many Shigella isolates with a quinolone-resistance gene also are resistant to many other commonly used treatment agents, such as azithromycin, trimethoprim-sulfamethoxazole, amoxicillin-clavulanic acid and ampicillin," the advisory noted.

The CDC said rising fluoroquinolone MIC values among Shigella isolates may be related to the emergence of plasmid-mediated quinolone-resistance (PMQR) genes in Shigella species in the United States.

Shigella strains harboring PMQR genes were identified earlier this year following whole-genome sequencing of isolates from a multistate outbreak of multidrug-resistant Shigella flexneri infections that predominantly affected adult men -- many of whom identified as men who have sex with men, according to epidemiologic data collected by the CDC's Shigella program as part of the outbreak response. PMQR genes have also been identified in sporadic cases of Shigella sonnei infection.

"Plasmid-mediated resistance genes are of particular concern because of their ability to spread between bacteria and their ability to promote chromosomal mutations conferring quinolone resistance, potentially resulting in rapid spread of fluoroquinolone resistance within or between populations of bacteria," the HAN said.

The prevalence of PMQR genes among all U.S. Shigella isolates is currently unknown.

The emergence of Shigella species with ciprofloxacin MICs of 0.12-1 μg/mL and their association with quinolone-resistance genes raises concerns that fluoroquinolone treatment of Shigella infection with a strain harboring such a gene may

  • be less effective and increase the risk of a more severe clinical course for patients (e.g., increased duration or severity of symptoms, increased need for hospitalization or admission to an ICU, increased length of hospitalization, or increased risk of death); and
  • increase the risk of secondary cases if the treatment prolongs the duration or increases the quantity of organisms shed in the stool, given the very low infectious dose required for transmission of Shigella bacteria.

Recommendations for Family Physicians

The CDC's HAN advisory offered a series of recommendations family physicians can use when working with patients suspected of having Shigella infection.

First, for diagnosis, the agency recommended that clinicians order a stool culture to obtain isolates for antimicrobial susceptibility testing. The HAN advisory noted that culture-independent diagnostic testing doesn't provide an isolate and therefore, cannot be used to assess susceptibility.

Next, the CDC recommended ordering antimicrobial susceptibility testing when ordering a stool culture for Shigella.

Specifically, the advisory recommended the following:

  • When antimicrobial susceptibility testing is performed by broth microdilution, request ciprofloxacin testing that includes dilutions of 0.12 μg/mL or lower.
  • Even when treatment is not indicated, identifying patients with drug-resistant infections (i.e., by ordering susceptibility testing) will help inform public health management decisions, such as when to return to work, school and group settings.

For patients diagnosed with Shigella infection, the CDC offered five major recommendations:

  • Don't routinely prescribe antibiotic therapy for Shigella infection. Instead, reserve antibiotic therapy for patients for whom it's clinically indicated or when public health officials advise treatment in an outbreak setting.
  • When antibiotic treatment is indicated, tailor antibiotic choice to antimicrobial susceptibility results as soon as possible, with special attention given to the MIC for fluoroquinolone antibiotics.
  • Obtain follow-up stool cultures in shigellosis patients who have continued or worsening symptoms despite antibiotic therapy.
  • Consult your local or state health department for guidance on when patients may return to childcare, school or work.
  • Counsel patients with active diarrhea on how they can prevent spreading the infection to others, regardless of whether antibiotic treatment is prescribed.

Finally, when reporting Shigella cases to local health departments, the CDC recommended that for patients with shigellosis and a ciprofloxacin MIC of 0.12-1 μg/mL, clinicians include this finding along with other information regarding the case to facilitate further testing of the isolate.

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(7/1/2015)