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Year : 2008  |  Volume : 26  |  Issue : 4  |  Page : 406

Ciprofloxacin breakpoints in enteric fever: Time to revise our susceptibility criteria

1 Department of Pharmacology, Lady Hardinge Medical College and SSKH, New Delhi - 110001, India
2 Department of Microbiology, Lady Hardinge Medical College and SSKH, New Delhi - 110001, India

Date of Submission26-Mar-2008
Date of Acceptance03-May-2008

Correspondence Address:
L K Gupta
Department of Pharmacology, Lady Hardinge Medical College and SSKH, New Delhi - 110001
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0255-0857.43556

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How to cite this article:
Gupta L K, Randhawa V S. Ciprofloxacin breakpoints in enteric fever: Time to revise our susceptibility criteria. Indian J Med Microbiol 2008;26:406

How to cite this URL:
Gupta L K, Randhawa V S. Ciprofloxacin breakpoints in enteric fever: Time to revise our susceptibility criteria. Indian J Med Microbiol [serial online] 2008 [cited 2020 Jul 11];26:406. Available from:

Dear Editor,

We read with interest the article entitled "Ciprofloxacin breakpoints in enteric fever-time to revise our susceptibility criteria" by Rodrigues et al, [1] published in Jan-Mar 2008 issue of the Indian Journal of Medical Microbiology. The article is thought provoking but certain critical aspects have been overlooked, which if mentioned would be enriching for the various investigators and decision makers in this crucial area.

Firstly, this study only mentions the number of nalidixic acid resistant strains isolated in 2005, but does not mention the total number of  Salmonella More Details typhi isolates from which they have been characterized. This does not allow us to calculate the prevalence of nalidixic acid resistant strains in a geographical area, which in this study happens to be Mumbai. Secondly, the methodology used in obtaining the results has not been mentioned. The MIC values are known to vary significantly with the methodology used. [2] To revise the susceptibility criteria in our country all the centers working on S. typhi should follow same methodology. Thirdly, this study does not comment on the clinical outcome of the cases from which the 96 nalidixic acid resistant strains have been isolated. The increased MIC values of ciprofloxacin in S. typhi in India have been reported since many years, [3],[4] but the important issue that has not been adequately addressed in many of these studies is the extent of clinical failure. Fourthly, this article mentions that the attainable AUC of ciprofloxacin is 31.06 μg/mL with 750 mg twice daily dose of ciprofloxacin, which is a satisfactory PK-PD value for the treatment of S. typhi enteric fever. However, there is evidence to suggest that free drug AUC and not the total AUC is more predictive of clinical success. [2] Considering plasma protein binding of approximately 30% for ciprofloxacin, for 750 mg b.d. daily dose, AUC free gets reduced to 22, and at MIC = 0.25µg/mL, AUC free :MIC ratio becomes 88. [5] This implies a dose of 750 mg b.d. daily would also be inadequate, as the recommended AUC free : MIC ratio for gram negative microorganisms is >100.

 ~ References Top

1.Rodrigues C, Kumar NJ, Lalwani J, Mehta A. Ciprofloxacin breakpoints in enteric fever--time to revise our susceptibility criteria. Indian J Med Microbiol 2008;26:91.  Back to cited text no. 1  [PUBMED]  Medknow Journal
2.Wikler MA, Ambrose PG. The breakpoint. In: Lorian V, editor. Antibiotics in laboratory medicine. 5 th ed, Chapter 1. Lippincott Williams and Wilkins; 2005. p. 1-7.   Back to cited text no. 2    
3.Mehta G, Randhawa VS, Mohapatra NP. Intermediate susceptibility to ciprofloxacin in Salmonella enterica serovar Typhi strains in India. Eur J Clin Microbiol Infect Dis 2001;20:760-1.  Back to cited text no. 3  [PUBMED]  [FULLTEXT]
4.Jesudason MV, Malathy B, John TJ. Trend of increasing levels of minimum inhibitory concentration of ciprofloxacin to Salmonella typhi . Indian J Med Res 1996;103:247-9.  Back to cited text no. 4  [PUBMED]  
5.Wright DH, Brown GH, Peterson ML, Rotschafer JC. Application of flouroquinolone pharmacodynamics. J Antimicrob Chemother 2000;46:669-83.  Back to cited text no. 5  [PUBMED]  [FULLTEXT]

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