Infect Chemother.  2008 Aug;40(4):207-211. 10.3947/ic.2008.40.4.207.

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

Affiliations
  • 1Department of Internal Medicine, Chosun University College of Medicine, Gwangju, Korea. jhchung@mail.chosun.ac.kr
  • 2Department of Emergency Medicine, Chonnam University Hospital, Korea.

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 > or = 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

Keyword

Typhoid fever; Salmonella Typhi; Cefotaxime; Ciprofloxacin

MeSH Terms

Anti-Bacterial Agents
Bacterial Load
Cefotaxime
Ciprofloxacin
Hepatitis
Humans
India
Nalidixic Acid
Pneumonia
Salmonella
Salmonella enterica
Salmonella typhi
Sprains and Strains
Typhoid Fever
Anti-Bacterial Agents
Cefotaxime
Ciprofloxacin
Nalidixic Acid

Figure

  • 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.


Reference

1. Frenck RW Jr, Nakhla I, Sultan Y, Bassily SB, Girgis YF, David J, Butler TC, Girgis NI, Morsy M. Azithromycin versus ceftriaxone for the treatment of uncomplicated typhoid fever in children. Clin Infect Dis. 2000. 31:1134–1138.
Article
2. Threlfall EJ, Ward LR, Skinner JA, Smith HR, Lacey S. Ciprofloxacin-resistant Salmonella typhi and treatment failure. Lancet. 1999. 353:1590–1591.
Article
3. Parry CM, Ho VA, Phuong le T, Bay PV, Lanh MN, Tung le T, Tham NT, Wain J, Hien TT, Farrar JJ. Randomized controlled comparison of ofloxacin, azithromycin, and an ofloxacin-azithromycin combination for treatment of multidrug-resistant and nalidixic acid-resistant typhoid fever. Antimicrob Agents Chemother. 2007. 51:819–825.
Article
4. Nkemngu NJ, Asonganyi ED, Njunda AL. Treatment failure in a typhoid patient infected with nalidixic acid resistant S. enterica serovar Typhi with reduced susceptibility to ciprofloxacin: a case report from Cameroon. BMC Infect Dis. 2005. 5:49.
Article
5. National Committee for Clinical Laboratory Standards. Approved standard M2-A8. Performance standards for antimicrobial disk susceptibility tests. 2003. 8th ed. Wayne, PA: NCCLS.
6. National Committee for Clinical Laboratory Standards. Approved standard M7-A6. Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically. 2003. 6. Wayne, PA: NCCLS.
7. Chuang YC, Liu JW, Ko WC, Lin KY, Wu JJ, Huang KY. In vitro synergism between cefotaxime and minocycline against Vibrio vulnificus. Antimicrob Agents Chemother. 1997. 41:2214–2217.
Article
8. George M, Eliopoulos RC, Moellering Jr. Lorian V, editor. Antimicrobial combination. Antibiotics in laboratory medicine. 1996. 4th ed. New York: Williams & Wilkins;338.
9. Wain J, Hoa NT, Chinh NT, Vinh H, Everett MJ, Diep TS, Day NP, Solomon T, White NJ, Piddock LJ, Parry CM. Quinolone-resistant Salmonella typhi in Viet Nam: molecular basis of resistance and clinical response to treatment. Clin Infect Dis. 1997. 25:1404–1410.
Article
10. Truong QC, Ouabdesselam S, Hooper DC, Moreau NJ, Soussy CJ. Sequential mutations of gyrA in Escherichia coli associated with quinolone therapy. J Antimicrob Chemother. 1995. 36:1055–1059.
Article
11. Rupali P, Abraham OC, Jesudason MV, John TJ, Zachariah A, Sivaram S, Mathai D. Treatment failure in typhoid fever with ciprofloxacin susceptible Salmonella enterica serotype Typhi. Diagn Microbiol Infect Dis. 2004. 49:1–3.
Article
12. White NJ, Parry CM. The treatment of typhoid fever. Curr Opin Infect Dis. 1996. 9:298–302.
Article
13. Butler T, Frenck RW, Johnson RB, Khakhria R. In vitro effects of azithromycin on Salmonella typhi: early inhibition by concentrations less than the MIC and reduction of MIC by alkaline pH and small inocula. J Antimicrob Chemother. 2001. 47:455–458.
Article
14. Frenck RW Jr, Nakhla I, Sultan Y, Bassily SB, Girgis YF, David J, Butler TC, Girgis NI, Morsy M. Azithromycin versus ceftriaxone for the treatment of uncomplicated typhoid fever in children. Clin Infect Dis. 2000. 31:1134–1138.
Article
15. Saha SK, Talukder SY, Islam M, Saha S. A highly ceftriaxone-resistant Salmonella typhi in Bangladesh. Pediatr Infect Dis J. 1999. 18:387.
Article
16. Chapman JS, Georgopapadakou NH. Routes of quinolone permeation in Escherichia coli. Antimicrob Agents Chemother. 1998. 32:438–442.
Article
17. Otsuki M, Nishino T. The synergic effects of quinolones and oral cephem antibiotics on Serratia marcescens. J Antimicrob Chemother. 1996. 38:771–776.
Article
18. Kim DM, Lym Y, Jang SJ, Han H, Kim YG, Chung CH, Hong SP. In vitro efficacy of the combination of ciprofloxacin and cefotaxime against Vibrio vulnificus. Antimicrob Agents Chemother. 2005. 49:3489–3491.
Article
Full Text Links
  • IC
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
Copyright © 2024 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr