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.