DISCUSSION
Sub optimal dosing of antibiotics has been associated with less than appropriate clinical outcomes and increased resistance. With a smaller number of drugs in the pipeline, careful consideration is required to provide appropriate dosing to improve clinical efficacy and safety16. The current study was designed to identify the dose optimization of antibacterial in CKD patients. A similar study conducted by Udani et al., which aimed to follow the dosing guidelines in critically ill patients with renal impairment, presented a mean age of 58 years, which was more than our study population. Further, 58% of the study population were males as compared to 83% in ours17. Kerr et al. estimated mean number of hospitalization days for CKD was 6.78 days as compared to 6±2 days in our study and 6±3 in AKI18. Studies specific to antimicrobial dosing in renal impairment were minimal. However, a study by Prajapathi et al. investigated dose appropriateness of all drugs in CKD. The findings showed that 18.89% of drugs were dosed appropriately, and 81.11% were not within the dose limit. Similarly, in our study, 63.3% of the drugs were appropriately dosed, whereas 36.7% of the drugs did not meet the criteria. The drug which was most inappropriately dosed was levofloxacin in the previously mentioned study whereas in our study, cefoperazone sulbactam was frequently prescribed19. Kumar et al. evaluaed antibiotic dosing in a tertiary care hospital and found piperacillin-tazobactam to be most widely used antibiotic in renal impairment followed by meropenem, amoxicillin potassium clavulanate, ciprofloxacin, and ceftriaxone. In our study, the most commonly used antibiotic was cefoperazone-sulbactam followed by ceftriaxone, vancomycin, meropenem, and levofloxacin20. The difference observed possibly could be attributed to difference in local sensitivity pattern and institutional guidelines on antibiotic use. Even though, the dosing was assessed to be inappropriate or different compared to recommendations in patients with lower CrCl, around 47% of patients attained a favorable clinical outcome.85% of such patients were diagnosed with CKD. This trend shows that there is a divergence in terms of required doses compared to standard recommendations. This poses a great challenge in the identification of predictors for inappropriate dosing of antibiotics for its effective optimisation21,22. Frazee et al. and colleagues measured GFR in critically ill patients by six different methods and the estimates were significantly (p < 0.001) different among the methods. The GFR measured was often overestimated, with patients being at higher risk of inadequate dosing23. In our study, we found that CrCl estimated by Cockroft Gault overestimates the value in comparison with the Jelliffe method.
The current study had its limitations. Measurement of CrCl by collecting urine samples and measuring the creatinine clearance would enable better validation of the methods of CrCl estimation. In CKD, plasma concentration of antibiotics at different time intervals would help us predicting inaccuracies of dosage regimen if any.
The development of electronic calculators or convenient applications for CrCl estimation should be considered. Newer methods should be implemented or studied for the estimation of CrCl, specifically in AKI for better dosing optimization and improved clinical outcome.