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

Abstract

We read with interest the article entitled "Ciproß oxacin 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 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 signiÞ cantly 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 ciproß oxacin 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 ciproß oxacin is 31.06 μg/mL with 750 mg twice daily dose of ciproß oxacin, 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 ciproß oxacin, 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.

Revised Ciprofloxacin Breakpoints for Salmonella : Is it Time to Write an Obituary?

“…Ciprofloxacin brings about concentration dependent killing and is 30% protein bound. Keeping the pharmacokinetic and pharmacodynamic properties for Gram negative bacteria in mind (AUC/MIC>125), a higher dose of 750mg twice daily has been successfully used in treating enteric fever [6,16]. This holds true only if the isolate has an MIC <0.176 μg/ml as the AUC at this dose would be 22.…”

Cryptosporidium and Strongyloides stercoralis infections among people with and without HIV infection and efficiency of diagnostic methods for Strongyloides in Yirgalem Hospital, southern Ethiopia

“…This is possibly because clinical staging may not be accurate to show the level of patient immune status. Studies have reported that the host immune status is one of the important determinants to influence Cryptosporidium [16,19,23,27] and S. stercoralis infection [16]. Patients with CD4 T-cell count less than 200 cells/μl of blood are in excess risk of having these infections [16].…”

Current perspectives on the spread of dengue in India

“… 2 , 12 Concurrent infection with multiple serotypes of dengue was also seen. 35 , 36 Thus, it is evident that now in India there is a definite increase in the frequency and number of outbreaks along with co-circulation of all four serotypes, hinting toward hyperendemicity of dengue in India.…”