|Year : 2019 | Volume
| Issue : 4 | Page : 600-601
Will the recently reinstated clsi 2020 breakpoints of norfloxacin for urinary isolates work for India? – Tertiary care experience and evidence
Rani Diana Sahni, Balaji Veeraraghavan, MS Dhiviya Prabaa, Jobin John Jacob
Department of Clinical Microbiology, Christian Medical College, Vellore, Tamil Nadu, India
|Date of Submission||03-Apr-2020|
|Date of Acceptance||29-Apr-2020|
|Date of Web Publication||18-May-2020|
Dr. Rani Diana Sahni
Department of Clinical Microbiology, Christian Medical College, Vellore - 632 004, Tamil Nadu
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Sahni RD, Veeraraghavan B, Dhiviya Prabaa M S, Jacob JJ. Will the recently reinstated clsi 2020 breakpoints of norfloxacin for urinary isolates work for India? – Tertiary care experience and evidence. Indian J Med Microbiol 2019;37:600-1
|How to cite this URL:|
Sahni RD, Veeraraghavan B, Dhiviya Prabaa M S, Jacob JJ. Will the recently reinstated clsi 2020 breakpoints of norfloxacin for urinary isolates work for India? – Tertiary care experience and evidence. Indian J Med Microbiol [serial online] 2019 [cited 2020 Jun 2];37:600-1. Available from: http://www.ijmm.org/text.asp?2019/37/4/600/284524
Norfloxacin (NOR), an oral broad-spectrum, second-generation fluoroquinolone (FQ), has been reinstated in the M-100CLSI 2020 guidelines for urinary tract infections (UTI) after its complete removal in 2019, with the same clinical breakpoints as in the earlier editions. NOR with a half-life of 2.3–5.5 h reaches a peak serum concentration of 1.5–2.0 μg/ml in 1–1.5 h, and 30% of the drug gets excreted renally, unchanged. FQs with their excellent bioavailability are, however, second-line options in the management of UTI (IDSA, 2011) due to collateral damage on the intestinal microbiota and their contraindications in pregnancy and children. Yet, in comparison with pivmecillinam, a first-line choice, NOR, is preferred due to its more pronounced effect with no major disturbances on the periurethral and vaginal microbiota. Currently, the increased use of FQ's, in general, led to the gradual development of resistance over time. Studies have, therefore, recommended that FQs be reserved for the use in patients who have no alternative treatment options.
In India, where the antimicrobial resistance burden is already high, the efficacy of NOR for treating UTI is uncertain as most contemporary urinary pathogens showed decreased susceptibility to this drug class. To demonstrate the current efficacy of NOR, we carried out susceptibility testing on contemporary, consecutive urinary isolates between February 24th and March 24th, 2020, at Christian Medical College, Vellore, Tamil Nadu, India. Urinary bacterial isolates of Escherichia coli, Klebsiella spp., Pseudomonas spp., Serratia spp., Morganella spp., Providencia spp., Proteus spp., Enterobacter spp., Citrobacter spp., Staphylococcus spp. and Enterococcus spp. were tested by the Kirby–Bauer disk diffusion method with 10 μg NOR and compared with 5 μg ciprofloxacin. The antimicrobial susceptibility testing reveals a 91.3% concordance with ciprofloxacin and an overall 64.4% resistance to the agents. Specifically, among our major pathogens, >70% of the E. coli, >80% of Enterococcus spp. and 50% of Klebsiella and Pseudomonas isolates were resistant to the FQ's. A 10-year analysis of uropathogens at our centre reveals non-susceptibility to FQ between 63.2% and 52.2%. Similarly, Varughese et al. reported high-level resistance to NOR among E. coli clinical isolates. Another study showed a high rate of resistance to NOR among Enterococcus sp., with higher resistance among Enterococcus faecium isolates than Enterococcus faecalis (85 vs 58.8%).
A detailed analysis of the FQ resistance mechanism among clinical isolates of E. coli, Klebsiella spp. and Staphylococcus spp. from our centre revealed double/triple mutations in quinolone resistance-determining regions. E. coli mutations in gyr A (S83L, D87N and D87Y) and par C (S80I) were found to be the primary cause of quinolone resistance, whilst efflux-mediated FQ resistance (oqx A/B) seems to be the common mechanism in Klebsiella spp. Remarkably, previous studies from India have shown that NOR Minimum inhibitory concentrations (MICs) for most of the double mutants (codons 83 and 87 of gyrase A) were >1024 μg/ml, whereas that of ciprofloxacin is 256 μg/ml. However, among Gram-positive organisms, stepwise mutations play a crucial role in raising MICs to NOR. In Staphylococcus, strains with gyr A (S84L) and grl A (S80F, S80Y) substitutions resulted in quinolone resistance. The first step mutation occurs in parC (Ser-80-Phe) for Staphylococcus aureus raising NOR MIC level to 4 μg/ml. Additional mutation at Ser-84-Leu further raises MIC to 16 μg/ml, and a third step mutation in gyrA pushes the MIC further up to 128 μg/ml. The higher MIC for NOR compared to ciprofloxacin, ofloxacin and levofloxacin in both Gram-negative and Gram-positive probably evidence the inappropriateness of NOR for contemporary clinical isolates.
In conclusion, NOR testing may not be useful due to the current FQ resistance among contemporary uropathogens. It is suggested that antimicrobial testing guidelines be based on geographical locations, as this scenario may not be the same globally.
Financial support and sponsorship
This work received no specific external funding, and the work was carried out depending on the resources of the Department of Clinical Microbiology, Christian Medical College, Vellore, Tamil Nadu, India.
Conflicts of interest
There are no conflicts of interest.
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