Decreased ciprofloxacin susceptibility in Salmonella Typhi and Paratyphi infections in ill-returned travellers: the impact on clinical outcome and future treatment options

Abstract

The emergence of decreased ciprofloxacin susceptibility (DCS) in Salmonella enterica serovar Typhi and serovar Paratyphi A, B or C limits treatment options. We studied the impact of DCS isolates on the fate of travellers returning with enteric fever and possible alternative treatment options. We evaluated the clinical features, susceptibility data and efficacy of empirical treatment in patients with positive blood cultures of a DCS isolate compared to patients infected with a ciprofloxacin-susceptible (CS) isolate in the period from January 2002 to August 2008. In addition, the pharmacokinetic and pharmacodynamic parameters of ciprofloxacin, levofloxacin and gatifloxacin were determined to assess if increasing the dose would result in adequate unbound fraction of the drug 24-h area under the concentration-time curve/minimum inhibitory concentration (ƒAUC(0-24)/MIC) ratio. Patients with DCS more often returned from the Indian subcontinent and had a longer fever clearance time and length of hospital stay compared to patients in whom the initial empirical therapy was adequate. The mean ƒAUC(0-24)/MIC was 41.3 ± 18.8 in the patients with DCS and 585.4 ± 219 in patients with a CS isolate. For DCS isolates, the mean ƒAUC0-24/MIC for levofloxacin was 60.5 ± 28.7 and for gatifloxacin, it was 97.9 ± 28.0. Increasing the dose to an adequate ƒAUC(0-24)/MIC ratio will lead to conceivably toxic drug levels in 50% of the patients treated with ciprofloxacin. Emerging DCS isolates has led to the failure of empirical treatment in ill-returned travellers. We demonstrated that, in some cases, an adequate ƒAUC(0-24)/MIC ratio could be achieved by increasing the dose of ciprofloxacin or by the use of alternative fluoroquinolones.

Indolent Non-Typhoidal <i>Salmonella</i> Vertebral Osteomyelitis in a Diabetic Patient

“…It has been reported that ceftriaxone therapy is associated with a higher rate of treatment failure and relapse than fluoroquinolone therapy, especially in enteric fever (27)(28)(29)(30). However, it has been well established that bacterial isolations susceptible for ciprofloxacin, but showing resistance to nalidixic acid, can lead to poor clinical outcomes and treatment failure (31,32). According to the increasing number of isolated strains of Salmonella with decreased fluoroquinolone-susceptibility, the breakpoints for extraintestinal Salmonella were revised in the CLSI guidelines in 2012 and 2013 (33).…”

Epidemiology, Clinical Presentation, Laboratory Diagnosis, Antimicrobial Resistance, and Antimicrobial Management of Invasive Salmonella Infections

“…Over time, physicians in areas of endemicity and those treating returning travelers began to report cases of fluoroquinolone failure when treating enteric fever despite the laboratory reporting a susceptible isolate (343,419,(511)(512)(513)(514)(515)(516)(517)(518)(519). It became clear that a subset of strains of Salmonella serovars Typhi and Paratyphi A had emerged that were less susceptible to the fluoroquinolones.…”

Epidemiological Characteristics and Clinical Treatment Outcome of Typhoid Fever in Ningbo, China, 2005–2014: Pulsed-Field Gel Electorophoresis Results Revealing Great Proportion of Common Transmission Sources

“…Particular concern for the development of resistance to first-line antimicrobials has arisen in recent decades (5). Decreased ciprofloxacin (CIP) susceptibility has been reported, which has a significant impact on clinical outcomes and future treatment options (6). Furthermore, international travel increases the spread of resistant S. Typhi isolates (6).…”