Rising Minimum Inhibitory Concentration of Azithromycin: A Therapeutic Challenge in Treating Enteric Fever

Introduction: Enteric fever continues to be endemic in the Indian subcontinent carrying with it significant morbidity, despite available antibiotics. With changing trends in antibiotic use, concern for emerging resistance to many common pathogens is very common. Taking enteric fever, as a case in point, there is evidence of increased use of azithromycin and third-generation cephalosporins. Documenting evidence of increasing concentrations of antibiotics, required to inhibit the organism, is necessary to alter the prescribing practice and to adopt course correction. This is required to modify antibiotic policies in health care setups both for the management of antibiotic susceptible and resistant cases of enteric fever.

Aim: To document the rising Minimum Inhibitory Concentration (MIC) of azithromycin among Salmonella isolates.

Materials and Methods: A cross-sectional study was conducted in Pondicherry Institute of Medical Sciences for a period of seven years (January 2014 to December 2020). A total of 168 clinical isolates from enteric fever cases were tested for drug resistance to azithromycin by disk diffusion as per Clinical and Laboratory Standards Institute (CLSI) guidelines. The MIC was estimated using the Epsilometer test. Results were interpreted as per CLSI 2020 guidelines. Spearman’s rank correlation coefficient (r) and two-tailed p-values were estimated to note the trend.

Results: Out of 168 Salmonella isolates, 65 were Salmonella Typhi and 103 were Salmonella Paratyphi A. The MIC of these isolates ranged from 1.5-64 μg/mL and three isolates were resistant to azithromycin with MIC ≥32 μg/mL and nine isolates had a high level of MIC of 24 μg/mL. Disc diffusion test results were consistent with MIC of azithromycin against Salmonella isolates from enteric fever. Regression coefficient for MIC for the given value of zone diameter for 65 Salmonella Typhi isolates was -0.579 (p<0.001, considered highly significant) and -0.475 (p<0.01, considered as significant) for Salmonella Paratyphi A isolates. Rising MIC to azithromycin was observed among Salmonella isolates over a period of seven years.

Conclusion: There is a need to monitor the rising trend of MIC, which may pose a therapeutic challenge for treating enteric fever cases in near future. Regular MIC estimation can pre-empt overt resistance. Hence, MIC testing should be routinely done where facilities are available than doing only disk diffusion testing for enteric fever isolates.