Antibiotic therapy in acute diarrhea associated with Shigella: what is the best option?

LETTER TO THE EDITOR

Antibiotic therapy in acute diarrhea associated with Shigella: what is the best option?

Marina H. C. Carrari^I; Soraia Tahan^II; Mauro B. Morais^III

^IPediatrician. Universidade Federal de São Paulo (UNIFESP), São Paulo, SP, Brazil

^IIPhysician. PhD, Disciplina de Gastroenterologia Pediátrica, Departamento de Pediatria, UNIFESP, São Paulo, SP, Brazil. Professor, Instituto de Pesquisa Unolab, Departamento de Ciências da Saúde, Centro Universitário Fundação e Instituto de Educação de Osasco (UNIFIEO), Osasco, SP, Brazil

^IIIAssociate professor, tenured professor and chief, Disciplina de Gastroenterologia Pediátrica, Departamento de Pediatria, UNIFESP, São Paulo, SP, Brazil

Dear Editor,

Nunes et al.¹ highlight the finding of 77.1% of bacterial resistance in Shigella samples isolated from children with acute diarrhea in Teresina, state of Piauí, Brazil.¹

International and national guidelines recommend antibiotics as a supplementary measure in the treatment of children with acute diarrhea and blood in stool (dysentery presumably caused by Shigella),^2-4 respecting the profile of regional sensibility to antimicrobials.^2,3 However, usually antimicrobials are prescribed before the results of coproculture and antibiogram are available. In Brazil, combined trimethoprim-sulfamethoxazole therapy is recommended for diarrhea caused by Shigella.⁴

The World Health Organization (WHO)² recommends the use of ciprofloxacin at any age.

As options, other fluoroquinolones are suggested, as well as ceftriaxone in cases of multidrug resistance. Azithromycin is an alternative option in adults.² The European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN)³ recommends azithromycin as a first choice, and third-generation cephalosporin (ceftriaxone), nalidixic acid, and fluoroquinolones as alternative options. Fluoroquinolones are reserved for patients over 17 years old.³ Neither WHO² nor ESPGHAN³ recommend the use of trimethoprim-sulfamethoxazole.

The Office of Health Surveillance of the Brazilian Ministry of Health⁴ recommends trimethoprim-sulfamethoxazole as the first choice in severe cases of Shigella infection. The prescription of quinolones is reserved for cases of bacterial resistance and is contraindicated in children and pregnant women.⁴

In this context, in 2011, we decided to conduct a literature review in the MEDLINE and LILACS databases on the susceptibility to trimethoprim-sulfamethoxazole of Shigella samples isolated in Brazil. Five articles were retrieved, published between 1995 and 2006^5-9; all of them had antibiograms performed by the disk method.

The Shigella samples analyzed in those articles,^5-9 together with the ones analyzed in the article published in Jornal de Pediatria,¹ totalize 658. Of these, 86.6% (570/658) were resistant to trimethoprim-sulfamethoxazole. Resistance to other antibiotics was as follows: 50.0% (330/658) for ampicillin, 7.0% (47/658) for ceftriaxone, 4.7% (22/465) for nalidixic acid, and 1.0% (6/552) for ciprofloxacin. Thus, considering in vitro sensitivity results, it is possible to infer that the trimethoprim-sulfamethoxazole association should not be used to treat infections by Shigella. As a result, one question remains: what is the best antimicrobial available to treat Shigella infections?

Considering that the samples of Shigella in Brazil were not tested for azithromycin and that about 90% were resistant to trimethoprim-sulfamethoxazole, it can be concluded that the best therapeutic options are nalidixic acid (55 mg/kg/day divided into four oral doses) and ceftriaxone (50-100 mg/kg/day intravenously or intramuscularly for 3-5 days). WHO recommends the use of ciprofloxacin rather than nalidixic acid due to its low cost (open patent), ease of administration (two rather than four oral doses), absence of quinolone-induced arthropathy seen in animals but not in humans, and also because nalidixic acid-resistant Shigella strains may show cross-resistance to ciprofloxacin and other quinolones in areas where nalidixic acid is used as the first choice. However, ciprofloxacin has not been approved for pediatric use in Brazil.

In our experience, especially in hospitalized cases with acute dysentery, ceftriaxone has been used for a few years already.

References

• 1. Nunes MR, Magalhães PP, Penna FJ, Nunes JM, Mendes EN. Diarrhea associated with Shigella in children and susceptibility to antimicrobials. J Pediatr (Rio J). 2012;88:125-8.
• 2. World Health Organization. Guidelines for the control of shigellosis, including epidemics due to Shigella dysenteriae 1. Geneva: World Health Organization; 2005. 64p.
• 3. Guarino A, Albano F, Ashkenazi S, Gendrel D, Hoekstra JH, Shamir R, et al. European Society for Paediatric Gastroenterology, Hepatology, and Nutrition/European Society for Paediatric Infectious Diseases evidence-based guidelines for the management of acute gastroenteritis in children in Europe. J Pediatr Gastroenterol Nutr. 2008;46:S81-122.
• 4. Brasil. Ministério da Saúde. Secretaria de Vigilância em Saúde. Departamento de Vigilância Epidemiológica. Doenças infecciosas e parasitárias: guia de bolso. 8Ş ed. rev. Brasília: Ministério da Saúde; 2010. 444p. Série B. Textos Básicos de Saúde.
• 5. Lima AA, Lima NL, Pinho MC, Barros Juñior EA, Teixeira MJ, Martins MC, et al. High frequency of strains multiply resistant to ampicillin, trimethoprim-sulfamethoxazole, streptomycin, chloramphenicol, and tetracycline isolated from patients with shigellosis in northeastern Brazil during the period 1988 to 1993. Antimicrob Agents Chemother. 1995;39:256-9.
• 6. dos Santos BA, Pires A de A, de Souza AR, Vives C, Barcellos SH, Dal Bo DJ. Estudo da resistência antimicrobiana in vitro das coproculturas positivas para Shigella sp. J Pediatr (Rio J). 1997;73:395-400.
• 7. Oplustil CP, Nunes R, Mendes C; RESISTNET Group. Multicenter evaluation of resistance patterns of Klebsiella pneumoniae, Escherichia coli, Salmonella spp and Shigella spp isolated from clinical specimens in Brazil: RESISTNET Surveillance Program. Braz J Infect Dis. 2001;5:8-12.
• 8. Diniz-Santos DR, Santana JS, Barretto JR, Andrade MG, Silva LR. Epidemiological and microbiological aspects of acute bacterial diarrhea in children from Salvador, Bahia, Brazil. Braz J Infect Dis. 2005;9:77-83.
• 9. Peirano G, Souza FS, Rodrigues DP; Shigella Study Group. Frequency of serovars and antimicrobial resistance in Shigella spp. from Brazil. Mem Inst Oswaldo Cruz. 2006;101:245-50.

Publication Dates

• Publication in this collection
  18 Sept 2012
• Date of issue
  Aug 2012