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ToolsWain, John, Simpson, Julie A., Thi Diem Nga, Luong, Song Diep, To, Thanh Duy, Pham, Baker, Stephen, Day, Nicholas P.J., White, Nicholas J. and Parry, Christopher M. (2021) Bactericidal activities and post-antibiotic effects of ofloxacin and ceftriaxone against drug-resistant Salmonella enterica serovar Typhi. Journal of Antimicrobial Chemotherapy, 76 (10). pp. 2606-2609. ISSN 0305-7453
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Abstract
Background: The 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). Objectives: To determine the bactericidal activity and post-antibiotic effect (PAE) of ceftriaxone and ofloxacin against S. Typhi. Methods: The 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). Results: The 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. Conclusions: Infections 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.
| Item Type: | Article |
|---|---|
| Additional Information: | Funding information: The study was supported by the Wellcome Trust of Great Britain. J.A.S. is funded by an Australian National Health and Medical Research Council (NHMRC) Senior Research Fellowship (1104975). S.B. is funded by a Wellcome Trust Senior Research Fellowship (215515/Z/19/Z). |
| Uncontrolled Keywords: | pharmacology,microbiology (medical),pharmacology (medical),infectious diseases,sdg 3 - good health and well-being ,/dk/atira/pure/subjectarea/asjc/3000/3004 |
| Faculty \ School: | Faculty of Medicine and Health Sciences > Norwich Medical School |
| Related URLs: | |
| Depositing User: | LivePure Connector |
| Date Deposited: | 29 Oct 2024 09:30 |
| Last Modified: | 11 Dec 2024 01:42 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/97240 |
| DOI: | 10.1093/jac/dkab215 |
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