Skip directly to site content Skip directly to page options Skip directly to A-Z link Skip directly to A-Z link Skip directly to A-Z link
Volume 13, Number 4—April 2007
Letter

Novel Extended-spectrum β-Lactamase in Shigella sonnei

On This Page
Article Metrics
4
citations of this article
EID Journal Metrics on Scopus

Cite This Article

To the Editor: A 38-year-old French man with a history of chronic juvenile arthritis was referred to the Necker-Enfants Malades University hospital (Paris, France) with a dysenteric syndrome. The patient had returned the day before from a 1-month stay in Port-au-Prince, Haiti, where he spent most of his time in close contact with young children from an orphanage, most of whom had diarrhea. Clinical examination at admission showed fever (39°C), chills, diffuse abdominal pain, bloody diarrhea, and vomiting. The patient received ceftriaxone, which was stopped on day 4 because initial blood and stool cultures were negative for pathogens and clinical signs had completely resolved.

Ten days later, he reported the recurrence of diarrhea without fever. A novel stool culture grew Shigella sonnei. An extended-spectrum β-lactamase (ESBL) was detected by double-disk synergy test; the isolate was also resistant to aminoglycosides (except amikacin), tetracycline, and cotrimoxazole. The strain was susceptible to fluoroquinolones and fosfomycin. It also appeared susceptible to azithromycin (MIC 4 μg/mL), although azithromycin MIC for Shigella spp. should be interpreted with caution (1). The patient was successfully treated with azithromycin at a dose of 500 mg/d for 5 days. Azithromycin was preferred to fluoroquinolones to avoid the risk for tendinopathy because of the patient’s history of chronic juvenile arthritis and because this antimicrobial agent was shown to be effective in the treatment of shigellosis caused by multidrug-resistant strains (2).

To identify the molecular basis of this ESBL, a series of PCR primers were used for detection of TEM-, SHV-, or CTX-M–type ESBL (3). Only the TEM PCR showed positive results. Sequencing of 2 independent PCR products showed a new allele (www.lahey.org/studies/temtable.asp). Analysis of the deduced amino acid sequence allowed characterization of TEM-137, derived from TEM-1 with 2 substitutions, Arg-16→Ser and Glu-240→Arg. This ESBL (and resistance to aminoglycosides and tetracyclines) was easily transferred to Escherichia coli J53-2 by conjugation.

MICs of β-lactams alone or in association with clavulanic acid, were determined by E-test, according to manufacturer’s instructions (AB Biodisk, Solna, Sweden). High-level resistance to ceftazidime (MIC 32 μg/mL) and intermediate resistance to cefotaxime (MIC 8 μg/mL) were observed; the strain remained susceptible to cefepime and imipenem (MIC 0.5 and 0.25 μg/mL, respectively). Clavulanic acid did not restore susceptibility to ceftazidime (MIC 4 μg/mL) but did restore susceptibility to cefotaxime (MIC 0.5 μg/mL). With clavulanic acid, the MIC of cefepime was 0.06 μg/mL.

ESBL in S. sonnei is rare worldwide. In Argentina, a CTX-M-2 was found in an isolate of S. sonnei resistant to cefotaxime but not to ceftazidime (4). In South Korea, TEM-15, TEM-17, TEM-19, TEM-20, TEM-52, and CTX-M-14 were characterized in S. sonnei (5); TEM-52 and CTX-M-14 were also widely distributed, particularly in Salmonella spp. (6,7). In Turkey, an isolate of S. sonnei producing CTX-M-3 was reported (8). In Hong Kong, sequencing of 2 S. sonnei isolates showed the presence of CTX-M-14 and CTX-M-15 (9). Finally, in Bangladesh, 2 isolates of S. sonnei with a class A ESBL were reported; they were not characterized at the molecular level, but the resistance phenotypes suggested a CTX-M type (10).

In our case, little information on antimicrobial drug resistance could be obtained from Haiti because no systematic investigation on resistance in Enterobacteriaceae is performed. Nevertheless, the emergence of TEM-137 (GenBank accession no. AM286274) harbored by this imported S. sonnei isolate clearly demonstrates that ESBL-associated shigellosis has emerged in Haiti and that potentially large and severe shigellosis outbreaks could occur, for which the use of azithromycin could be beneficial, as illustrated in our patient. Because treating shigellosis is becoming problematic, it is essential to focus on prevention measures such as simple rules of personal hygiene that might drastically decrease the risk of transmission.

Top

Acknowledgment

This study was supported in part by a grant from the European Community, contract LSHM-CT 2003-503335.

Top

Agnes Lefort*†Comments to Author , Guillame Arlet‡, Olivier F. Join-Lambert*†, Marc Lecuit*†, and Olivier Lortholary*†
Author affiliations: *Hôpital Necker-Enfants Malades, Université Paris V, Paris, France; †Centre d'Infectiologie Necker-Pasteur, Paris, France; ‡Unité de Formation et de Recherche de Médecine Pierre et Marie Curie, Université Paris VI, Paris, France;

Top

References

  1. Jain  SK, Gupta  A, Glanz  B, Dick  J, Siberry  GK. Antimicrobial-resistant Shigella sonnei: limited antimicrobial treatment options for children and challenges of interpreting in vitro azithromycin susceptibility. Pediatr Infect Dis J. 2005;24:4947. DOIPubMedGoogle Scholar
  2. Khan  WA, Seas  C, Dhar  U, Salam  MA, Bennish  ML. Treatment of shigellosis: V. Comparison of azithromycin and ciprofloxacin. A double-blind, randomized, controlled trial. Ann Intern Med. 1997;126:697703.PubMedGoogle Scholar
  3. Eckert  C, Gautier  V, Saladin-Allard  M, Hidri  N, Verdet  C, Ould-Hocine  Z, Dissemination of CTX-M-type beta-lactamases among clinical isolates of Enterobacteriaceae in Paris, France. Antimicrob Agents Chemother. 2004;48:124955. DOIPubMedGoogle Scholar
  4. Radice  M, Gonzealez  C, Power  P, Vidal  MC, Gutkind  G. Third-generation cephalosporin resistance in Shigella sonnei, Argentina. Emerg Infect Dis. 2001;7:4423.PubMedGoogle Scholar
  5. Kim  S, Kim  J, Kang  Y, Park  Y, Lee  B. Occurrence of extended-spectrum beta-lactamases in members of the genus Shigella in the republic of Korea. J Clin Microbiol. 2004;42:52649. DOIPubMedGoogle Scholar
  6. Lee  K, Yong  D, Yum  JH, Kim  HH, Chong  Y. Diversity of TEM-52 extended-spectrum β-lactamase-producing non-typhoidal Salmonella isolates in Korea. J Antimicrob Chemother. 2003;52:4936. DOIPubMedGoogle Scholar
  7. Yong  D, Lim  YS, Yum  JH, Lee  H, Lee  K, Kim  EC, Nosocomial outbreak of pediatric gastroenteritis caused by CTX-M-14-type extended-spectrum β-lactamase-producing strains of Salmonella enterica serovar London. J Clin Microbiol. 2005;43:351921. DOIPubMedGoogle Scholar
  8. Acikgoz  ZC, Gulay  Z, Bicmen  M, Gocer  S, Gamberzade  S. CTX-M-3 extended-spectrum beta-lactamase in a Shigella sonnei clinical isolate: first report from Turkey. Scand J Infect Dis. 2003;35:5035. DOIPubMedGoogle Scholar
  9. Cheung  TK, Chu  YW, Tsang  GK, Ngang  JY, Hui  IS, Kam  KS. Emergence of CTX-M-type beta-lactam resistance in Shigella spp. in Hong Kong. Int J Antimicrob Agents. 2005;25:3502. DOIPubMedGoogle Scholar
  10. Rahman  M, Shoma  S, Rashid  H, Siddique  AK, Nair  GB, Sack  DA. Extended-spectrum beta-lactamase–mediated third-generation cephalosporin resistance in Shigella isolates in Bangladesh. J Antimicrob Chemother. 2004;54:8467. DOIPubMedGoogle Scholar

Top

Cite This Article

DOI: 10.3201/eid1304.061160

Related Links

Top

Table of Contents – Volume 13, Number 4—April 2007

EID Search Options
presentation_01 Advanced Article Search – Search articles by author and/or keyword.
presentation_01 Articles by Country Search – Search articles by the topic country.
presentation_01 Article Type Search – Search articles by article type and issue.

Top

Comments

Please use the form below to submit correspondence to the authors or contact them at the following address:

Agnes Lefort, Service de Médecine Intern, Hôpital Beaujon, 100 Bd du Général Leclerc, 92110 Clinchy, France;

Send To

10000 character(s) remaining.

Top

Page created: June 28, 2010
Page updated: June 28, 2010
Page reviewed: June 28, 2010
The conclusions, findings, and opinions expressed by authors contributing to this journal do not necessarily reflect the official position of the U.S. Department of Health and Human Services, the Public Health Service, the Centers for Disease Control and Prevention, or the authors' affiliated institutions. Use of trade names is for identification only and does not imply endorsement by any of the groups named above.
file_external