Clinical Response and Outcome of Infection with Salmonella enterica Serotype Typhi with Decreased Susceptibility to Fluoroquinolones: a United States FoodNet Multicenter Retrospective Cohort Study

Abstract

Patients with typhoid fever due to) were compared with patients infected with isolates with ciprofloxacin MICs <0.12 g/ml for fever clearance time and treatment failure. Of 71 patients, 30 (43%) were female and 24 (34%) were infected with Salmonella serotype Typhi with DCS; the median age was 14 years (range, 1 to 51 years). Twenty-one (88%) of 24 isolates with DCS were resistant to nalidixic acid. The median antimicrobial-related fever clearance times in the DCS and non-DCS groups were 92 h (range, 21 to 373 h) and 72 h (range, 19 to 264 h) (P ‫؍‬ 0.010), respectively, and the fluoroquinolone-related fever clearance times in the DCS and non-DCS groups were 90 h (range, 9 to 373 h) and 64 h (range, 34 to 204 h) (P ‫؍‬ 0.153), respectively. Four (17%) of 24 patients in the DCS group and 2 (4%) of 46 patients in the non-DCS group (relative risk, 2.5; 95% confidence interval, 1.2 to 5.1) experienced treatment failure. Associations persisted after adjustment for potential confounders. We demonstrate that patients infected with Salmonella serotype Typhi isolates with DCS show evidence of a longer time to fever clearance and more frequent treatment failure. Nalidixic acid screening does not detect all isolates with DCS.

A Comparative Study of Efficacy and Safety of Azithromycin and Ofloxacin in Uncomplicated Typhoid Fever: A Randomised, Open Labelled Study

“…In vitro studies have shown that it is more potent than traditional first-line drugs and other macrolides against Salmonella spp. with an average MIC of 8μg/ mL (range 4 to 16μg/mL) [9].There are no reports of resistance of S. Typhi to azithromycin, and recent studies have shown that it is effective both clinically and bacteriologically in treating enteric fever even in those caused by MDR strains [6]. So, the present study was conducted to compare the efficacy and safety of azithromycin with ofloxacin in patients with uncomplicated typhoid fever.…”

“…These strains are associated with point mutations in the gyrA gene and occasionally the parC gene [5]. Enteric fever caused by S. Typhi strains with an elevated MIC to ciprofloxacin and ofloxacin have been coupled with the failure of treatment with these antimicrobials and increased disease severity [6]. There are also reports from the Indian subcontinent of isolates that are fully resistant to fluoroquinolones and the extended spectrum cephalosporins [7].…”

Is nalidixic acid screening still valid for the detection of reduced susceptibility of fluoroquinolone with SalmonellaTyphi?

“…The clinical relevance of these strains was not evaluated in any of the previous studies [11][12][13]; however, one can assume therapeutic failure in these cases, as also seen with the nalidixic acid resistant strains with decreased ciprofloxacin susceptibility [19].…”

“…Studies from the United Kingdom, United States, and Kuwait [11][12][13] reported a higher percentage of discordant nalidixic acid and ciprofloxacin susceptibility results in their Southeast Asian immigrants or travellers (i.e., 7%, 12.5%, and 13.8%). Cooke et al report 5% S. Typhi isolates from Pakistan with discordant results [14].…”

“…The method of screening with nalidixic acid has been validated and reported to be efficient for endogenous isolates and is currently in use by many laboratories in Pakistan [9,10]. However the recent emergence of nalidixic acid susceptible S. Typhi strains with high fluoroquinolone minimum inhibitory concentration (MIC) is of great concern [11][12][13][14]. According to recent publications, the majority of reported nalidixic acid susceptible and fluoroquinolone resistant strains originated from India, Pakistan or Bangladesh [12].…”