FIRST REPORT OF MACROLIDE RESISTANCE AMONG SHIGELLA ISOLATES IN ISRAEL CAUSED BY THE erm(B) AND mphA GENES

Shigella species remain an infection agent of public concern, affecting mostly children, with high incidence in developing areas as well as in industrialized countries. Although azithromycin is recommended for treatment of shigellosis, there are currently no CLSI susceptibility breakpoints. Recently, cases of Shigella flexneri with decreased susceptibility to azithromycin (DSA) have been reported globally. We aimed to assess the prevalence of macrolide resistance genes among Shigella flexneri in Israel.

All 162 Shigella flexneri isolates, received at the National Reference Center during 2014, were serotyped, and screened by PCR for the presence of macrolide resistance genes erm(B) and mphA that are commonly plasmid-encoded. Azithromycin minimum inhibitory concentration (MIC) values were assessed by the Broth Microdilution (BMD) method. Antimicrobial susceptibility to additional drugs (ampicillin, trimethoprim-sulfamethoxazole, ceftriaxone, tetracycline, nalidixic acid and chloroamphenicol) was tested by the disk diffusion method according to the CLSI guidelines. Clonal relatedness was assessed by Pulsed-Field Gel Electrophoresis (PFGE).

The mphA gene was detected in 11 isolates (7%), 4 of which harbored erm(B) as well. The presence of mphA or erm(B) correlated with high azithromycin MIC values (>256 μg/ml). Among the 11 isolates, 3 were MDR and 2 were XDR, and all were sensitive to ciprofloxacin. The strains displaying high azithromycin MIC values included different Sh. flexneri serotypes (1b, 1a, 3a, and 6) and different PFGE patterns, indicating different lineages. Among Sh. flexneri, 34 isolates (20%) were resistant to nalidixic acid.

Tracing antimicrobial resistance trends has direct impact on the outcome of shigellosis. The emergence of DSA Shigella reinforces the necessity of the establishment of clinical breakpoints that would warrant routine testing, reporting and surveillance for this drug of choice.