Abstract
Background
An outbreak of extended-spectrum β-lactamase (ESBL)-producing Shigella sonnei enteritis, especially in pediatric populations, was unprecedented not only in Korea, but also throughout the world in the past. This study was intended to devise a management guideline for shigellosis caused by an ESBL-producing strain based on analysis of the clinical manifestations and response to therapy.
Methods
We examined 24 strains of S. sonnei isolated from stool cultures of patients with acute enteritis, between November 2004 and February 2005, for antimicrobial susceptibility and ESBL production, and we also performed DNA sequencing with PCR for the typing of ESBL genes. In addition, we retrospectively analyzed the clinical characteristics, laboratory results, and therapeutic responses to antibiotics of the 103 patients who grew S. sonnei on stool cultures.
Results
All 24 isolates showed a very similar antibiotic sensitivity pattern and were ESBL gene type of CTX-M-14. The most frequent clinical symptom in the 103 patients was a fever, followed by diarrhea, abdominal pain, headache, vomiting, and nausea. Leukocytosis and CRP were positive in 53.4% and 78.6% of the patients, respectively. On stool direct smears, 11.7% showed more than 50 WBCs per HPF and 71% were positive on stool occult blood. Microbiological eradication rates were as follows: azithromycin and ciprofloxacin, 100%; imipenem-cilastatin, 68.8%; ampicillin-sulbactam, 42.9%; amoxicillin-clavulanic acid, 20%; ceftizoxime, 12.5%; cefdinir, 6.9%; and ceftriaxone and trimethoprim-sulfamethoxazole, 0%.
Conclusions
We presumed that, given its cost-effectiveness and safety, azithromycin can be an attractive option for the treatment of ESBL-producing S. sonnei enteritis in pediatric populations. Although ciprofloxacin is another cost-effective agent, its use in pediatric populations is not recommended.
References
1. Pai H, Choi EH, Lee HJ, Hong JY, Jacoby GA. Identification of CTX-M-14 Extended-Spectrum β-Lactamase in Clinical Isolates of Shigella sonnei, Escherichia coli, and Klebsiella pneumoniae in Korea. J Clin Microbiol. 2001; 39:3747–9.
2. Kim S, Kim J, Kang Y, Park Y, Lee B. Occurrence of extended-Spectrum β-lactamase in members of the genus Shigella in the Republic of Korea. J Clin Microbiol. 2004; 42:5264–9.
3. The Korea Center for Disease Control and Prevention. The outbreak of ESBL producing Shigella sonnei. Communicable Diseases Monthly Report. 2005; 16:1–5.
4. Genobile D, Gaston J, Tallis GF, Gregory JE, Griffith JM, Valcanis M, et al. An outbreak of shigellosis in a child care centre. Commun Dis Intell. 2004; 28:225–9.
5. Lee JC, Oh JY, Kim KS, Jeong YW, Cho JW, Park JC, et al. Antimicrobial resistance of Shigella sonnei in Korea during the last two decades. APMIS. 2001; 109:228–34.
6. National Committee for Clinical Laboratory Standards. Performance standards for antimicrobial disk susceptibility tests. 7th ed.Approved standard M2-A7.Wayne, Pa.: National Committee for Clinical Laboratory Standards;2000.
7. Clinical and Laboratory Standards Institute. Performance standards for antimicrobial susceptibility testing. 15th informational supplement, M100-S15. Wayne, Pa.: Clinical and Laboratory Standards Institute;2005.
8. Hanson ND, Thomson KS, Moland ES, Sanders CC, Berthold G, Penn RG. Molecular characterization of a multiply resistant Klebsiella pneumoniae encoding ESBLs and a plasmid-mediated AmpC. J Antimicrob Chemother. 1999; 44:377–80. 9. Thielman NM and Guerrant RL. Clinical practice. Acute infectious diarrhea. N Engl J Med 2004;350:38–47.
10. Dupont HL. Shigella species (Bacillary dysentery). Mandell GL, Bennett JE, Dolin R, editors. Principles and practice of infectious diseases. 6th ed.Philadelphia: Elsevier Churchill Livingstone Co;2004. p. 2655–61.
11. Kang CI, Kim SH, Park WB, Lee KD, Kim HB, Kim EC, et al. Blood stream infections due to extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae: risk factors for mortality and treatment outcome, with special emphasis on antimicrobial therapy. Antimicrob Agents Chemother. 2004; 48:4574–81.
12. Nakamura T, Komatsu M. Susceptibility of ESBL-producing Escherichia coli and Klebsiella pneumoniae to various antibiotic agents. Jpn J Antibiot. 2005; 58:1–10.
13. Salam MA, Bennish ML. Therapy for shigellosis. I. Randomized, double-blind trial of nalidixic acid in childhood shigellosis. J Pediatr. 1988; 113:901–7.
14. Salam MA, Seas C, Khan WA, Bennish ML. Treatment of shigellosis: IV. Cefixime is ineffective in shigellosis in adults. Ann Intern Med. 1995; 123:505–8.
15. 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; 126:697–703.
16. Salam MA, Dhar U, Khan WA, Bennish ML. Randomized comparison of ciprofloxacin suspension and pivmecillinam for childhood shigellosis. Lancet. 1998; 352:522–7.
17. Helvaci M, Bektaslar D, Ozkaya B, Yaprak I, Umurtak B, Ertugrul A. Comparative efficacy of cefixime and ampicillin-sulbactam in shigellosis in children. Acta Paediatr Jpn. 1998; 40:131–4.
18. Pitout JD, Sanders CC, Sanders WE Jr. Antimicrobial resistance with focus on β-lactam resistance in gram-negative bacilli. Am J Med. 1997; 103:51–9.
19. Rice L. Evolution and clinical importance of extended-spectrum β-lactamases. Chest. 2001; 119:391S–6S.
20. Burkhardt JE, Walterspiel JN, Schaad UB. Quinolone arthropathy in animals versus children. Clin Infect Dis. 1997; 25:1196–204.
21. The Zimbabwe, Bangladesh, South Africa (Zimbasa) Dysentery Study Group. Multicenter, randomized, double blind clinical trial of short course versus standard course oral ciprofloxacin for Shigella dysenteriae type 1 dysentery in children. Pediatr Infect Dis J. 2002; 21:1136–41.