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S. enterica ser. Typhi and Quinolone Resistance | CDC EID

EID Journal Home > Volume 17, Number 6–June 2011

Volume 17, Number 6–June 2011
Salmonella enterica Serotype Typhi with Nonclassical Quinolone Resistance Phenotype
Marie Accou-Demartin, Valérie Gaborieau, Yajun Song, Philippe Roumagnac, Bruno Marchou, Mark Achtman, and François-Xavier Weill
Author affiliations: Institut Pasteur, Paris, France (M. Accou-Demartin, F.-X. Weill); Hôpital Purpan, Toulouse, France (V. Gaborieau, B. Marchou); University College Cork, Cork, Ireland (Y. Song, M. Achtman); and Centre de Coopération International en Recherche Agronomique pour le Développement, Montpellier, France (P. Roumagnac)

Suggested citation for this article

We report Salmonella enterica serotype Typhi strains with a nonclassical quinolone resistance phenotype (i.e., decreased susceptibility to ciprofloxacin but with susceptibility to nalidixic acid) associated with a nonsynonymous mutation at codon 464 of the gyrB gene. These strains, not detected by the nalidixic acid disk screening test, can result in fluoroquinolone treatment failure.

Typhoid fever caused by Salmonella enterica serotype Typhi (hereafter referred to as Salmonella Typhi) remains a major health problem in the developing world (1). Treatment with appropriate antimicrobial drugs has become hampered by gradual plasmid-mediated resistance to ampicillin, chloramphenicol, and cotrimoxazole, particularly in southern and Southeast Asia (2). Consequently, since the early 1990s, fluoroquinolones (such as ofloxacin and ciprofloxacin [Cip]) have been widely used. However, multidrug-resistant Salmonella Typhi isolates that are also resistant to nalidixic acid (NalR) (MIC >256 μg/mL) and show decreased susceptibility to Cip (CipDS) (MIC range, 0.125 μg/mL–1 μg/mL) have emerged and become endemic on the Indian subcontinent and in Southeast Asia (3–5). This resistance to quinolones was caused by amino acid substitutions in the quinolone resistance–determining region (QRDR) of the DNA gyrase subunit gyrA, a key target of quinolones. Because these NalR–CipDS Salmonella Typhi strains have been associated with slower clinical responses to fluoroquinolones and treatment failures, clinical laboratories should attempt to identify these isolates (3,6,7). However, despite the accumulation of clinical, microbiologic, and pharmacokinetic–pharmacodynamic studies suggesting a resistance breakpoint of >0.125 μg/mL for ciprofloxacin, the clinical breakpoints published by the Clinical and Laboratory Standards Institute (CLSI) (susceptibility <1 μg/mL, resistance >4 μg/mL) and those from the antibiogram committee of the French Society for Microbiology (susceptibility <0.5 μg/mL, resistance >1 μg/mL) (www.sfm.asso.fr/nouv/general.php?pa=2) have not been reevaluated (6–9). Use of these standard breakpoints has probably resulted in the underreporting of CipDS Salmonella Typhi strains. The NalR screening test has been proposed as an alternative since the mid–1990s and recommended since 2004 by CLSI and 2010 by the French Society for Microbiology (3,7). This screening test is based on the fact that CipDS Salmonella Typhi isolates with nonsynonymous (NS) mutations in codons 83 or 87 of gyrA are uniformly NalR. However, recent reports have indicated that this approach cannot identify the newly described Salmonella Typhi isolates that are Nal susceptible (NalS)–CipDS for which mechanisms of resistance are not linked to mutations in gyrA (7,10,11). Recently, NS mutations in codons 464 (Ser to Phe) and 466 (Glu to Asp) of gyrB were found in 7 NalS–CipDS Salmonella Typhi isolates (12). We present data on the occurrence and characterization of the resistance mechanisms of NalS–CipDS isolates in 685 Salmonella Typhi isolates of the French National Reference Center for Salmonella (FNRC-Salm).

S. enterica ser. Typhi and Quinolone Resistance | CDC EID

Suggested Citation for this Article
Accou-Demartin M, Gaborieau V, Song Y, Roumagnac P, Marchou B, Achtman M, et al. Salmonella enterica serotype Typhi with nonclassical quinolone resistance phenotype [expedited]. Emerg Infect Dis [serial on the Internet]. 2011 Jun [date cited].

DOI: 10.3201/eid1706.101242

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

François-Xavier Weill, Centre National de Référence des Salmonella, Unité des Bactéries Pathogènes Entériques, Institut Pasteur, 28 rue du Docteur Roux, 75724 Paris CEDEX 15, France
; email: fxweill@pasteur.fr

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