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Alert

CDC RECOMMENDATIONS FOR MANAGING AND REPORTING SHIGELLA INFECTIONS WITH POSSIBLE REDUCED SUSPECTIBILITY TO CIPROFLOXACIN

Forwarded by the Delaware Division of Public Health

This is an official
CDC HEALTH UPDATE

Distributed via the CDC Health Alert Network
June 7, 2018 1100ET (11:00 AM ET)
CDC HAN-00411

Summary

This Health Alert Network (HAN) Update provides current recommendations on management and reporting of

Shigella infections that have been treated with ciprofloxacin or azithromycin and resulted in possible

clinical treatment failure. This is a follow-up to HAN 401: CDC Recommendations for Diagnosing and Managing

Shigella Strains with Possible Reduced Susceptibility to Ciprofloxacin.

The Centers for Disease Control and Prevention (CDC) continues to identify an increasing number of Shigella

isolates that test within the susceptible range for the fluoroquinolone antibiotic ciprofloxacin (minimum inhibitory

concentration [MIC] values of 0.12-1 µg/mL), but harbor one or more resistance mechanisms. CDC remains concerned

about potential clinical failures with fluoroquinolone treatment.

Clinicians should carefully monitor patients with Shigella infections who require fluoroquinolone treatment

and report any possible treatment failures. If treatment failure is suspected, clinicians should submit a stool specimen

for antimicrobial susceptibility testing and consider consulting an infectious disease specialist to identify best treatment

options.

CDC has also identified an increasing number of Shigella isolates with azithromycin MICs that exceed the

epidemiological cutoff value (ECV), and is requesting reports of any possible treatment failures occurring among patients

with Shigella infections treated with azithromycin (see below).

Shigellosis is a nationally notifiable condition; all cases should be reported to local health departments.

Recommendations for Clinicians

1.  If antibiotic treatment is necessary, monitor patients carefully.
2.  If you identify or receive a report of a patient with Shigella infection and possible fluoroquinoloneor azithromycin treatment failure:
   •  Consider consulting an infectious disease specialist to identify other treatment options, because someShigella isolates with susceptible ciprofloxacin MICs may harbor one or more quinolone resistance mechanisms.
   •  Contact your local health department to coordinate reporting treatment failure information. This informationshould be reported to CDC at EntericBacteria@cdc.gov.
   •  Collect a stool specimen for culture, and work with your clinical microbiology laboratory to submit foradditional antimicrobial susceptibility testing.
   •  Request that your laboratory expedite submission of the Shigella isolate to your state public healthlaboratory. Your state laboratory should notify CDC at EntericBacteria@cdc.gov

     to coordinate additional laboratory testing and/or shipment of the isolate to CDC.

Background

In April 2017, CDC identified an increase in the percentage of Shigella isolates in the United States with MIC

values of 0.12–1 µg/mL for the fluoroquinolone antibiotic ciprofloxacin; this percentage continues to rise.

Preliminary surveillance data from 2016 show that 8.2% of Shigella isolates tested by the National Antimicrobial

Resistance Monitoring System laboratory (https://www.cdc.gov/narms) had a ciprofloxacin

MIC in the 0.12–1 µg/mL range, and 9.5% had an azithromycin MIC greater than the ECV (i.e., non-wild-type; reduced

susceptibility). Testing of 2017 surveillance isolates is ongoing. Among those tested, 16.5% have a ciprofloxacin MIC in the

0.12–1 µg/mL range, and 22.1% have reduced susceptibility to azithromycin. Molecular data indicate that most

Shigella isolates with ciprofloxacin MICs in the noted range harbor at least one quinolone resistance mechanism.

Shigella isolates without a quinolone resistance mechanism typically have a ciprofloxacin MIC of =0.015 µg/mL.

Clinical and Laboratory Standards Institute (CLSI) criteria categorize Shigella isolates with a ciprofloxacin MIC

of =1 µg/mL as susceptible to ciprofloxacin. Currently, clinical laboratories have limited ability to differentiate

the ciprofloxacin MIC values within the reduced susceptibility range, =1 µg/mL. Additionally, CLSI does not have

established azithromycin clinical breakpoints for Shigella isolates, only ECVs, which do not predict clinical

outcome (2).

CDC is particularly concerned about people who are at high risk for multidrug-resistant Shigella infections and

are more likely to require antibiotic treatment, such as men who have sex with men, patients who are homeless, and

immunocompromised patients. These patients often have more severe disease, prolonged shedding, and recurrent infections.

In response to data and concerns presented by CDC, CLSI formed an ad hoc working group in June 2017 to assess any available

and relevant clinical, pharmacologic, and microbiologic data. The workgroup found that no data are available on the high-risk

populations of concern. CDC has not received any reports of clinical treatment failures in patients with Shigella infections.

Therefore, it is unclear whether fluoroquinolone treatment of a Shigella infection with a ciprofloxacin MIC of 0.12–1 µg/mL

is associated with a worse clinical outcome or whether such treatment increases the risk of transmission. At this time, CLSI

ciprofloxacin MIC breakpoints for the Enterobacteriaceae family (excluding Salmonella) will continue to apply

to Shigella isolates.

CDC is working with CLSI and other partners to collect isolates and clinical information from people with Shigella infection

and possible clinical treatment failure occurring after treatment with a fluoroquinolone or azithromycin. If treatment failure is suspected,

clinicians should consider consulting an infectious disease specialist to identify best treatment options, and submit a stool specimen for

antimicrobial susceptibility testing. Clinicians should monitor patients carefully and report cases of possible clinical treatment failure

to CDC.

Reporting

To report cases of Shigella in Delaware, call 302-744-4990 (24/7).

For More Information

1.  For general information about Shigella or shigellosis, visit https://www.cdc.gov/shigella/index.html
2.  For general information about Shigella or shigellosis in Spanish, visit https://www.cdc.gov/shigella/esp/index.html
3.  For technical information about Shigella or shigellosis, including information about national surveillance and other educational resources for medical and public health professionals, visit https://www.cdc.gov/shigella/resources.html
4.  For information about prevention and control of shigellosis, including recommendations for men who have sex with men, visit https://www.cdc.gov/shigella/audience-sexually-active.html
5.  For more information about the serious public health threat posed by antimicrobial-resistant Shigella, refer to “Antibiotic Resistance Threats in the United States, 2013” available at https://www.cdc.gov/drugresistance/threat-report-2013/pdf/ar-threats-2013-508.pdf
6.  For specific inquiries related to this HAN Update, email EntericBacteria@cdc.gov

References

1.  HAN 401: CDC Recommendations for Diagnosing and Managing Shigella Strains with Possible Reduced Susceptibility to Ciprofloxacin
2.  CLSI. Performance Standards for Antimicrobial Susceptibility Testing. 28th ed. CLSI supplement M100. Wayne, PA: Clinical and Laboratory Standards Institute; 2018

The Centers for Disease Control and Prevention (CDC) protects people’s health and safety by preventing and controlling diseases and injuries; enhances health decisions by providing credible information on critical health issues; and promotes healthy living through strong partnerships with local, national, and international organizations

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