INTRODUCTION
Appropriate antibiotic dosing is fundamental to achieve favourable
clinical outcomes. Optimum dosing ensures adequate therapeutic drug
concentrations at the site of infection. Acute Kidney Injury (AKI) and
Chronic Kidney Disease (CKD) substantially alter drug
pharmacokinetics.1 High mortality has been reported in
hospitalized patients with AKI. Diverse etiology makes treatment
challenging2. Quality of life in CKD decreases with
declining GFR3.
Antibiotics are the most common drugs that require dose optimization but
are often dosed inappropriately in patients with renal
impairment4. Appropriate dosing schedules at right
intervals helps in reducing morbidity, mortality, and length of hospital
stay5. An inappropriate dose adjustment could result
in elevated plasma concentrations of the drug leading to adverse drug
reactions, thus increasing the patient’s burden6.
Antibiotic dose optimization is an essential part of clinical practice
for better clinical management and delayed
resistance7. Antibiotic resistance not only increases
healthcare costs but also worsens severity of
infection8. Creatinine clearance (CrCl) and estimated
glomerular filtration rate (eGFR) are universally used clinical
parameters in renally impaired patients. Variations in drug clearance
are proportional to the changes in CrCl. This association can serve as a
basis for modifying the dosing interval of drugs that undergo renal
elimination.
Regardless of the published guidelines, there is insufficient evidence
on dosing decisions on many commonly used drugs for patients with
deranged kidney function9. Definitive conclusions on
the pharmacokinetic parameters of metabolized medications in AKI remains
unanswered. Physicians and pharmacists commonly use Cockroft-Gaults
formula (also recommended by USFDA) for estimating
CrCl10,11. However, in AKI, a steady state kidney
function is not maintained. Therefore, the Jelliffe method was developed
to ascertain GFR in settings of non-steady-state kidney function.
Calculation using the Jelliffe equation, modified by consideration of
patient volume status, yielded a more consistent and precise valuation
of kidney function when equated with planned collection of urine in AKI
patients12. The Acute Disease Quality Initiative
(ADQI) recommends the use of short timed urine collections or the
modified Jelliffe equation for estimating kidney function in persistent
AKI13.
The current study aimed to assess the different aspects of antibiotics
dosage in patients with renal impairment, and the objectives were to
evaluate the impact of dose appropriateness on the clinical outcome of
antibiotic therapy in renal impairment.