Abstract
BackgroundThe clinical response to ceftriaxone in patients with typhoid fever is significantly slower than with ofloxacin, despite infection with Salmonella enterica serovar Typhi (S. Typhi) isolates with similar susceptibilities (MIC 0.03–0.12 mg/L). The response to ofloxacin is slower if the isolate has intermediate susceptibility (MIC 0.25–1.0 mg/L).ObjectivesTo determine the bactericidal activity and post-antibiotic effect (PAE) of ceftriaxone and ofloxacin against S. Typhi.MethodsThe mean time to reach a 99.9% reduction in log10 count (bactericidal activity) and PAE of ceftriaxone and ofloxacin were determined for 18 clinical isolates of S. Typhi in time–kill experiments (MIC range for ofloxacin 0.06–1.0 mg/L and for ceftriaxone 0.03–0.12 mg/L).ResultsThe mean (SD) bactericidal activity of ofloxacin was 33.1 (15.2) min and 384.4 (60) min for ceftriaxone. After a 30 min exposure to ofloxacin, the mean (SD) duration of PAE was 154.7 (52.6) min. There was no detectable PAE after 1 h of exposure to ceftriaxone. For ofloxacin, bactericidal activity and PAE did not significantly differ between isolates with full or intermediate susceptibility provided ofloxacin concentrations were maintained at 4×MIC.ConclusionsInfections with S. Typhi with intermediate ofloxacin susceptibility may respond to doses that maintain ofloxacin concentrations at 4×MIC at the site of infection. The slow bactericidal activity of ceftriaxone and absent PAE may explain the slow clinical response in typhoid.
Highlights
Typhoid fever, caused by Salmonella enterica serovar Typhi
This study has shown that an ofloxacin concentration of 4%MIC is rapidly bactericidal and has a prolonged post-antibiotic effects (PAEs) in time–kill experiments against S
In adult healthy volunteers given 200 mg of ofloxacin, a dose used in a number of the clinical trials, the serum level at 2 h was 2.07 mg/L with an estimated unbound concentration of
Summary
Typhoid (enteric) fever, caused by Salmonella enterica serovar Typhi Typhi in South Asia between 2015 and 2018 of 70% (38%–94%).[2] A large outbreak of ciprofloxacin- and ceftriaxone-resistant typhoid has affected the Sindh province in Pakistan since 2016.3 The S. Typhi clade H58 has been dominant in the spread of these resistant strains across Asia and some parts of Africa.[4]. The clinical response to ceftriaxone in patients with typhoid fever is significantly slower than with ofloxacin, despite infection with Salmonella enterica serovar Typhi Typhi) isolates with similar susceptibilities (MIC 0.03–0.12 mg/L). The response to ofloxacin is slower if the isolate has intermediate susceptibility (MIC 0.25–1.0 mg/L)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
