Journal Information
Vol. 83. Issue 5.
Pages 346-347 (01 November 2015)
Vol. 83. Issue 5.
Pages 346-347 (01 November 2015)
Scientific Letter
DOI: 10.1016/j.anpede.2015.09.019
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Is azithromycin really a therapeutic option in intestinal salmonellosis?
¿Es realmente la azitromicina una opción terapéutica en la salmonelosis intestinal?
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V. Pérez-Doñatea, M. Borrás-Máñeza, V. Domínguez-Márquezb, D. Navalpotro-Rodríguezc, J. Colomina-Rodrígueza,
Corresponding author
jcolomina@hospital-ribera.com

Corresponding author.
a Servicio de Microbiología, Hospital Universitario de la Ribera, Alzira, Valencia, Spain
b Servicio de Microbiología, Hospital General Universitario de Castellón, Castellón, Spain
c Servicio de Microbiología, Consorcio Hospital General Universitario de Valencia, Valencia, Spain
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Dear Editor:

Acute gastroenteritis (AGE) is a common disease and a major cause of morbidity and mortality in children, and it is the most frequent reason for paediatric emergency room visits following respiratory infections. In Spain, the bacteria most frequently involved in AGE are Campylobacter and Salmonella species, which are also the most frequently involved in cases of foodborne illness in developed countries.1 While antibiotic treatment is not always indicated, the growing resistance to antimicrobial drugs calls for the surveillance of in vitro susceptibility and for the periodical review of sensitivity data to update treatment guidelines.

The European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) and the European Society for Paediatric Infectious Diseases (ESPID) recently published an update to the Guidelines for the Management of Acute Gastroenteritis in Children that featured azithromycin as an alternative treatment against nontyphoidal Salmonella (NTS) species.2 Azithromycin is a semisynthetic macrolide antibiotic of the azalide class that acts by inhibiting bacterial protein synthesis, and has shown a similar or superior efficacy than third-generation cephalosporins and fluoroquinolones in the treatment of uncomplicated typhoid fever in several clinical trials.3 The scarceness of data on bacterial sensitivity to this antibiotic in Spain, and the lack of clinical breakpoints for interpreting minimum inhibitory concentration (MIC) values for azithromycin against Salmonella species mean that we have no information on the actual effectiveness of this antimicrobial agent in the treatment of salmonellosis. The aim of our study was to assess the in vitro activity of azithromycin against clinical isolates of NTS.

We conducted a descriptive, prospective multicentre study with the participation of three hospitals of the Autonomous Community of Valencia. Each participating hospital was randomly selected and submitted NTS clinical isolates from patients with suspected AGE to the microbiology department of the Hospital Universitario de La Ribera in the first four months of 2014. The coordinating hospital confirmed the bacterial identification by means of NC52 panels for the MicroScan® WalkAway® system (Siemens, Germany). Then, antibiotic sensitivity was assessed by determining the MIC for azithromycin using E-test® strips (bioMerieux, Spain); the results were interpreted applying the epidemiological cut-off value established by the European Committee on Antimicrobial Susceptibility Testing (EUCAST) for NTS (MIC16mg/L).4

We analysed a total of 136 NTS isolates (69 came from Alzira, 15 from Valencia and 52 from Castellón). The median age of patients was 7 years (range, 1–74), and 81% were male and 58% female. When tested for azithromycin sensitivity, 99% of isolates were found to be sensitive and only one isolate was resistant. The identified MICs ranged between 1.5 and 24mg/L. The MIC50 (concentration needed to inhibit 50% of the isolates) and the MIC90 (concentration needed to inhibit 90% of the isolates) were 6mg/L and 8mg/L, respectively.

The results we obtained are consistent with several European studies that have described a distribution of MICs that ranges between 4 and 8mg/L for most isolates.5 To date, the Clinical and Laboratory Standards Institute (CLSI) has not defined breakpoints for macrolides and Enterobacteriaceae6; in Europe, EUCAST has only established an epidemiological cut-off value for Shigella and Salmonella typhi according to which strains with a MIC of 16mg/L or less are considered wild strains (with no resistance mechanisms) and thus susceptible to treatment with azithromycin.4

In light of these MIC results, azithromycin could be used for treatment of AGE caused by NTS, although it would be preferable if international committees were to establish clinical breakpoints for Salmonella enterica and azithromycin. If we only take into consideration the paediatric population, azithromycin covers the two main causes of bacterial AGE with an excellent sensitivity profile; also, its easy dosage (once a day) and good tolerability make it an interesting alternative for the first-line empirical treatment of bacterial AGE in cases in which there is a strong suspicion of a NTS aetiology and microbiological tests cannot be performed.

References
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C. Gavilán Martín, B. García Avilés, R. González Montero.
Gastroenteritis aguda. Hospital Clínico Universitario de San Juan.
Alicante, (2008),
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A. Guarino, S. Ashkenazi, D. Gendrel, A. Lo Vecchio, R. Shamir, H. Szajewska.
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: Update 2014.
J Pediatr Gastroenterol Nutr, 59 (2014), pp. 132-152
[3]
C.M. Parry, V.A. Ho, T. Phuong le, P.V. Bay, M.N. Lanh, T. Tung le, et al.
Randomized controlled comparison of ofloxacin, azithromycin, and an ofloxacin-azithromycin combination for treatment of multidrug-resistant and nalidixic acid-resistant typhoid fever.
Antimicrob Agents Chemother, 51 (2007), pp. 819-825
[4]
The European Committee on Antimicrobial Susceptibility Testing. Break point tables for interpretation of MICs and zone diameters. Version 3.0. European Society of Clinical Microbiology and Infectious Diseases, 2013.
[5]
M. Sjölund-Karlsson, K. Joyce, K. Blickenstaff, T. Ball, J. Haro, F.M. Medalla, et al.
Antimicrobial susceptibility to azithromycin among Salmonella enterica isolates from the United States.
Antimicrob Agents Chemother, 55 (2011), pp. 3985-3989
[6]
Clinical Laboratory Standards Institute. Performance standards for antimicrobial susceptibility testing; Twenty-third informational supplement.
CLSI Document M100-S23, Clinical and Laboratory Standards Institute, (2013),

Please cite this article as: Pérez-Doñate V, Borrás-Máñez M, Domínguez-Márquez V, Navalpotro-Rodríguez D, Colomina-Rodríguez J. ¿Es realmente la azitromicina una opción terapéutica en la salmonelosis intestinal? An Pediatr (Barc). 2015;83:346–347.

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