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.