Time Kill Studies of Antibiotics against a Nalidixic Acid Resistant Salmonella enterica serotype Typhi

Dong-Min Kim; Na Ra Yun; Jong Hoon Chung; Hyun Ho Ryu

doi:10.3947/ic.2008.40.4.207

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Kim, Yun, Chung, and Ryu: Time Kill Studies of Antibiotics against a Nalidixic Acid Resistant Salmonella enterica serotype Typhi

ORIGINAL ARTICLES

Infection and Chemotherapy

Infection and Chemotherapy 2008; 40(4): 207-211.

Published online: 25 August 2008

DOI: https://doi.org/10.3947/ic.2008.40.4.207

Time Kill Studies of Antibiotics against a Nalidixic Acid Resistant Salmonella enterica serotype Typhi

Dong-Min Kim, M.D.¹, Na Ra Yun, M.D.¹, Jong Hoon Chung, M.D.¹, Hyun Ho Ryu, M.D.²

¹Department of Internal Medicine, Chosun University College of Medicine, Gwangju, Korea.

²Department of Emergency Medicine, Chonnam University Hospital, Korea.

Correspondence: Jong Hoon Chung, M.D. Department of Internal Medicine, Chosun University College of Medicine 588 Seosuk-dong, Dong-gu, Gwangju, 501-717, Korea. Tel:+82-62-220-3016, Fax:+82-62-234-9653, jhchung@mail.chosun.ac.kr

Received 18 June 2008 Accepted 12 August 2008

(open-access):

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background

We recently encountered a case of typhoid fever in a patient who visited us after travelling India. The patient received ciprofloxacin therapy, but developed typhoid pneumonia and typhoid hepatitis, and nalidixic acid resistance Salmonella Typhi (NARST) was identified. The aim of this study was to assess the in vitro efficacy of several antimicrobial combinations, which are commonly used in clinical practice.

Materials and Methods

Time-kill studies were performed for a clinical NARST strain to evaluate synergy. Synergy was defined as a ≥ 2 log₁₀ decrease (100-fold drop) in CFU per mL at 24 hours by a drug combination compared to the most active constituent.

Results

The combination regimen of cefotaxime plus ciprofloxacin significantly reduced the bacterial counts (> 3 log CFU) at 3/4 MIC and at 24 hours compared to the ciprofloxacin or cefotaxime alone and showed synergistic effect against a NARST strain.

Conclusion

In conclusion, our time-kill studies showed that ciprofloxacin plus cefotaxime was the best in vitro combination against a NARST. This combination may improve efficacy compared to fluoroquinolone alone in typhoid fever patient with NARST. Time kill studies with more NARST strains and clinical studies are required to test the relevance of our findings

Keywords: Typhoid fever, Salmonella Typhi, Cefotaxime, Ciprofloxacin

Figures and Tables

Figure 1

Chest images of the patient with typhoid fever. A) Chest PA image on admission. B) Chest PA on hospital day 4, as the patient presented with dyspnea and dry caugh.

Figure 2

Time-kill curves for a clinical isolate of Salmonella Typhi after incubation with cefotaxime, azithromycin or ciprofloxacin alone and the combination of cefotaxime plus ciprofloxacin, azithromycin plus cefotaxime and azithromycin plus ciprofloxacin at 3/4 MIC.

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