Failure of Ciprofloxacin Therapy for Invasive Nontyphoidal Salmonellosis

Vasallo, Francisco J.; Martín‐Rabadán, Pablo; Alcalá, Luís; García-Lechuz, J.M.; Rodríguez‐Créixems, Marta; Bouza, Emilio

doi:10.1086/517087

Cited by 68 publications

(54 citation statements)

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“…This resistance pattern may possibly be due to the presence of an efflux pump mechanism [12,13] or mutations at locations other than gyrA [11]. Fluoroquinolone resistance in non-typhoidal Salmonella has emerged as a threat to the health community in the past few years [14,15,16]; therefore, invasive infections with serious complication caused by non-typhoidal Salmonella should be treated with increased caution to avoid treatment failures [17].…”

Section: Resultsmentioning

confidence: 99%

High Level of Resistance to nalidixic acid in Salmonella enterica serovar Typhi in Central India

Kumar

Sharma

Mani

2009

J Infect Dev Ctries

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Background: Fluoroquinolones are the drugs of choice for the treatment of typhoid fever. But the recent increase in minimum inhibitory concentration (MIC) values of ciprofloxacin in Salmonella Typhi may result in delayed response and serious complications. Nalidixic acid resistance has been used as an indirect evidence of increased minimum inhibitory concentration for ciprofloxacin in Salmonella Typhi. Methods: We evaluated the isolates received at the National Salmonella and Escherichia Centre for nalidixic acid and ciprofloxacin susceptibility using standard methods. Minimum inhibitory concentrations have also been evaluated. Results: Ninety-six percent of the isolates were found to be nalidixic acid resistant while all isolates were found to be ciprofloxacin sensitive. The difference between minimum inhibitory concentration values of ciprofloxacin for nalidixic acid resistant and nalidixic acid sensitive isolates was found to be statistically significant. Conclusion: The study may be helpful in revising treatment strategies for the infections caused by nalidixic acid resistant Salmonella Typhi in the country.

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Section: Resultsmentioning

confidence: 99%

High Level of Resistance to nalidixic acid in Salmonella enterica serovar Typhi in Central India

Kumar

Sharma

Mani

2009

J Infect Dev Ctries

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“…However, the incidence of nalidixic acid resistance in Salmonella isolates from humans and food animals has increased, with these isolates showing decreased susceptibility to fluoroquinolones (6,27). Of paramount concern to public health are reports of therapeutic failure of ciprofloxacin in cases of invasive salmonellosis associated with isolates displaying reduced fluoroquinolone susceptibility (26,30,48).…”

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confidence: 99%

Multiple Regulatory Pathways Associated with High-Level Ciprofloxacin and Multidrug Resistance in Salmonella enterica Serovar Enteritidis: Involvement of ramA and Other Global Regulators

O'Regan

Quinn

Pagès

et al. 2009

Antimicrob Agents Chemother

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Mechanisms of antibiotic resistance were examined in nalidixic acid-resistant Salmonella enterica serovar Enteritidis field isolates displaying decreased susceptibility to ciprofloxacin and in in vitro-derived ciprofloxacin-resistant mutants (104-cip and 5408-cip). All field isolates harbored a single gyrA mutation (D87Y). Deletion of acrB and complementation with wild-type gyrA increased quinolone susceptibility. Selection for ciprofloxacin resistance was associated with the development of an additional gyrA (S83F) mutation in 104-cip, novel gyrB (E466D) and parE (V461G) mutations in 5408-cip, overexpression of acrB and decreased susceptibility to nonquinolone antibiotics in both mutants, and decreased OmpF production and altered lipopolysaccharide in 104-cip. Complementation of mutated gyrA and gyrB with wild-type alleles restored susceptibility to quinolones in 104-cip and significantly decreased the ciprofloxacin MIC in 5408-cip. Complementation of parE had no effect on quinolone MICs. Deletion of acrB restored susceptibility to ciprofloxacin and other antibiotics tested. Both soxS and marA were overexpressed in 104-cip, and ramA was overexpressed in 5408-cip. Inactivation of each of these global regulators lowered ciprofloxacin MICs, decreased expression of acrB, and restored susceptibility to other antibiotics. Mutations were found in soxR (R20H) and in soxS (E52K) in 104-cip and in ramR (G25A) in 5408-cip. In conclusion, both efflux activity and a single gyrA mutation contribute to nalidixic acid resistance and reduced ciprofloxacin sensitivity. Ciprofloxacin resistance and decreased susceptibility to multiple antibiotics can result from different genetic events leading to development of target gene mutations, increased efflux activity resulting from differential expression of global regulators associated with mutations in their regulatory genes, and possible altered membrane permeability.

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“…Mutations of gyrB and parC of Salmonella are not normally found in nalidixic acid-resistant isolates (8,24,34) although they may contribute to high-level resistance to fluoroquinolones (27). There are several studies suggesting that fluoroquinolones may have an impaired effect for treating infections due to Salmonella isolates that are resistant to nalidixic acid (20,30). These isolates normally have decreased susceptibility to fluoroquinolones, and therefore, standard dosages of these drugs may not be sufficient to treat clinical infections.…”

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confidence: 99%

Comparison of gyrA Mutations, Cyclohexane Resistance, and the Presence of Class I Integrons in Salmonella enterica from Farm Animals in England and Wales

Liébana¹,

Clouting²,

Cassar³

et al. 2002

J Clin Microbiol

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This study is focused on real-time detection of gyrA mutations and of the presence of class I integrons in a panel of 100 veterinary isolates of Salmonella enterica from farm animals. The isolates were selected on the basis of resistance to nalidixic acid, representing a variety of the most prevalent serotypes in England and Wales. In addition, organic solvent (cyclohexane) resistance in these isolates was investigated in an attempt to elucidate the presence of efflux pump mechanisms. The most prevalent mutation among the isolates studied was Asp87-Asn (n ‫؍‬ 42), followed by Ser83-Phe (n ‫؍‬ 38), Ser83-Tyr (n ‫؍‬ 12), Asp87-Tyr (n ‫؍‬ 4), and Asp87-Gly (n ‫؍‬ 3). Two distinct subpopulations were identified, separated at the 1-mg/liter breakpoint for ciprofloxacin: 86% of isolates with mutations in codon 83 showed MICs of >1 mg/liter, while 89.8% of isolates with mutations in codon 87 presented MICs of <0.5 mg/liter. Cyclohexane resistance was more prevalent among Ser83 mutants than among Asp87 mutants (34.7 and 4%, respectively), and in 79% of isolates that presented both gyrA mutations and cyclohexane resistance, the level of ciprofloxacin resistance was >2.0 mg/liter. Thirty-four isolates contained class I integrons, with 71% of the S. enterica serovar Typhimurium isolates and 6.9% of isolates belonging to other serotypes containing such elements. The methods used represent sensitive ways of investigating the presence of gyrA mutations and of detecting class-I integrons in Salmonella isolates. The results can be obtained in less than 1 h from single colonies without the need for purifying DNA.

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Failure of Ciprofloxacin Therapy for Invasive Nontyphoidal Salmonellosis

Cited by 68 publications

References 0 publications

High Level of Resistance to nalidixic acid in Salmonella enterica serovar Typhi in Central India

High Level of Resistance to nalidixic acid in Salmonella enterica serovar Typhi in Central India

Multiple Regulatory Pathways Associated with High-Level Ciprofloxacin and Multidrug Resistance in Salmonella enterica Serovar Enteritidis: Involvement of ramA and Other Global Regulators

Comparison of gyrA Mutations, Cyclohexane Resistance, and the Presence of Class I Integrons in Salmonella enterica from Farm Animals in England and Wales

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