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Brief Original Article In vitro activity of azithromycin in Salmonella isolates from Pakistan
Farhana Butt1 and Faisal Sultan2
Department of Pathology1 and Department of Medicine2, Shaukat Khanum Memorial Cancer Hospital and Research Center, Lahore, Pakistan Abstract
Introduction: Enteric fever is caused by Salmonella enterica serovars Typhi and Paratyphi A, B and C. It is a significant publichealth issue in Pakistan, which is exacerbated by a high level of resistance some isolates display to drugs routinely used in treatment. Azithromycin may be a treatment option for such isolates. Methodology: We determined the minimum inhibitory concentrations (MICs) of Salmonella Typhi and Paratyphi isolates against azithromycin in an attempt to gauge its feasibility as a therapeutic option. TheMICs were also compared with corresponding disc diffusion zone sizes to see if there was consistency between the two tests. We tested 45 Salmonella enterica isolates using E-tests for MIC detection and azithromycin discs with a concentration of 15µg/ml for disc diffusion testing. Results: Salmonella Typhi, Salmonella Paratyphi A, and Salmonella Paratyphi C isolates demonstrated MICs of 2-12mg/Lagainst azithromycin, suggesting that the antibiotic could be used for therapeutic purposes. For Salmonella Paratyphi B, the MICs were 2-48 mg/L. The higher MIC indicates a need for caution when considering use of azithromycin for Salmonella Paratyphi B infections without first testing for the MIC. There was a close correlation between MICs and zone sizes which was statistically significant.Conclusions: Our results indicate azithromycin is a potential therapeutic option for enteric fever. Standardized laboratory testing methods and interpretation for azithromycin against Salmonella enterica would allow laboratories to report upon this antibiotic with confidence. Key words: Salmonella enterica; typhoid; enteric fever; azithromycin; resistance; Pakistan J Infect Dev Ctries 2011; 5(5):391-395.(Received 23 February 2010 – Accepted 06 October 2010) Copyright © 2011 Butt and Sultan. This is an open-access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Introduction Enteric fever is caused by Salmonella enterica serovars Typhi and Paratyphi A,B and C. The World Health Organization has calculated the crude incidence of typhoid fever alone (caused by Salmonella Typhi) for South East Asia to be 110/100,000 persons per year [1]. Studies from Pakistan indicate the incidence here may be even higher [2,3]. In addition to the high incidence of disease, Pakistan also has a high incidence of reduced quinolone susceptibility, with isolates ofminimum inhibitory concentration (MIC) ≥ 1mg/L accounting for up to 64% Salmonella Typhi (S. Typhi) [3]. Within our own hospital, of the 85 Salmonella enterica isolates cultured between 2007 and 2008, 79% were resistant to nalidixic acid, a good indicator of poor response to ciprofloxacin (unpublished data). Multi-drug resistance which includes resistance to ampicillin, chloramphenicol andco-trimoxazole is also high in Pakistan (45% for S. Typhi) [3]. Treatment options for multi-drug resistant (MDR) and quinolone-resistant isolates include

parenteral ceftriaxone, oral cefixime, and oral azithromycin [4]. Increased use of cephalosporins for treatment of typhoid fever by clinicians familiar with them may be contributing to increased resistance to thirdgeneration cephalosporins [4,5,6].Azithromycin is an attractive alternative to the cephalosporins used (parenteral ceftriaxone and oral cefixime) in view of its single daily dosing, possibility of use in β-lactam allergic patients, and lower cost. Several studies have documented the efficacy of azithromycin in the treatment of uncomplicated enteric fever. However, these results have been based mainly upon clinical criteria without...