|Year : 2015 | Volume
| Issue : 3 | Page : 85-89
A Study on the Drug Utilization Pattern in Patients with Chronic Kidney Disease with Emphasis on Antibiotics
Soumya Santra1, Divya Agrawal2, Sanjay Kumar1, Sudhanshu Sekhar Mishra1
1 Department of Pharmacology, IMS and SUM Hospital, SOA University, Bhubaneswar, Odisha, India
2 Department of Anatomy, IMS and SUM Hospital, SOA University, Bhubaneswar, Odisha, India
|Date of Web Publication||24-Jul-2015|
Dr. Soumya Santra
Department of Pharmacology, IMS and SUM Hospital, Ghatikia, Bhubaneswar, Odisha - 751 003
Source of Support: None, Conflict of Interest: None
Objective: To study and describe the utilization pattern of various classes of drugs including antibiotics in patients with chronic kidney disease (CKD). Materials and Methods: A total of 185 CKD patients were finally recruited after strictly obeying the selection criteria in this cross-sectional, observational study that was conducted over a period of 6 months in Nephrology Department of a tertiary care teaching hospital. Relevant data were extracted by interviewing the patients and from prescriptions, case records, and investigational reports. Results: Mean age of CKD patients was 45.81 ± 11.16 with male predominance (58%). CKD Stage III comprised of the maximum number (28%) of patients. Polypharmacy was executed in 83% of these patients. Hypertension (95%), diabetes (87%), and anemia (86%) are the most common co-morbidities. The five most frequently prescribed drugs were diuretics (100%), anti-ulcer agents like proton pump inhibitors and H 2 blockers (98%), anti-hypertensives (95%), vitamins and minerals supplements including calcium (92%), and hematinics (85%). Infectious diseases like respiratory tract infection (37%) and urinary tract infection (34%) had shown to have a high prevalence in CKD patients. Cefoperazone, metronidazole, piperacillin + tazobactam were the most prescribed parenteral antibiotics. Azithromycin and levofloxacin were the extensively used oral antibiotics. Conclusion: This study demonstrates the variability of drug utilization in CKD patients. Drug utilization studies on a regular basis give a framework to pharmaceutical companies and healthcare providers and help to build management strategies. However, the right choice of drugs and inappropriate doses will reduce the incidence of nephrotoxicity and ultimately result better clinical outcomes. Managing infections and prescribing antibiotics in CKD are crucial and hence claim rationalization of the use of antibiotics to improve the quality of life of CKD patients.
Keywords: Antibiotics, chronic kidney disease, drug utilization study
|How to cite this article:|
Santra S, Agrawal D, Kumar S, Mishra SS. A Study on the Drug Utilization Pattern in Patients with Chronic Kidney Disease with Emphasis on Antibiotics. J Integr Nephrol Androl 2015;2:85-9
|How to cite this URL:|
Santra S, Agrawal D, Kumar S, Mishra SS. A Study on the Drug Utilization Pattern in Patients with Chronic Kidney Disease with Emphasis on Antibiotics. J Integr Nephrol Androl [serial online] 2015 [cited 2019 Jun 16];2:85-9. Available from: http://www.journal-ina.com/text.asp?2015/2/3/85/161435
| Introduction|| |
Chronic kidney disease (CKD) is characterized by multiple disorders affecting the morphology and function of kidneys.  It is estimated on the basis of a decrease in the number of nephrons, which ultimately decreases the glomerular filtration rate (GFR) for a period more than 3 months.  Hypertension and diabetes, recurrent infections along with an inappropriate prescription of drugs are the leading factors resulting in the increasing incidence of CKD. , CKD accounts for 850,000 deaths worldwide as reported by World Health Organization. 
Pharmacokinetics in renal compromised patients is altered and often results in drug accumulation and toxicity.  Diabetes, hypertension, and renovascular diseases are the common causes of CKD in developing countries, whereas in the tropical countries, infection induced glomerular disease contributes the most to CKD. , Hence, the utilization pattern, marketing and distribution of drugs widely varies with time, geographical distribution, health economics, and sociomedical parameters. 
Due to diverse co-morbid conditions and complications, physicians have to use multiple drugs in the management of CKD, which, on the contrary, results to drug interaction and suboptimal action. CKD patients are more susceptible to infections and are likely to be prescribed with antimicrobial agents. The dosing of all drugs, including antibiotics should be optimized and monitored so as to prevent adverse drug reactions, avoid further renal injury and to facilitate treatment outcomes. ,,
Variation in treatment and absence of any data or fixed protocol prompted my study on the utilization pattern of drugs in patients with CKD and to analyze the prescribing trends of antibiotics in this special group of patients.
| Materials and Methods|| |
A prospective, cross-sectional observational study was conducted in the Department of Nephrology of a teaching hospital in October, 2014 to March, 2015. This study was approved by Institutional Ethics Committee. After obtaining written consent, patients diagnosed with CKD within the age group of 18-60 years were recruited in the study.
Pregnant ladies, breastfeeding mothers, terminally ill-patients (patients with malignancy or having positive HIV, HCV, HBsAg) and patients planned for or postrenal transplant were excluded from this study. The patients were interviewed, and their prescriptions, clinical, and laboratory data were abstracted, reviewed, and recorded in a clinical data form.
The data of the drug utilization of 185 patients were analyzed using GraphPad Prism version 5 (2015 GraphPad Software, Inc. USA). Results were expressed as mean ± standard deviation. Nonparametric values were expressed as a percentage.
| Results|| |
Among 185 CKD patients, 108 (58%) were males and 77 (42%) females [Figure 1]. The mean age of the study population was 45.81 ± 11.16. [Table 1] portrays the established five-stage classification of CKD and the distribution pattern of this study population to each stage.  About 28% patients reported in Stage III CKD, followed by 24% in Stage II CKD. However, most of the patients among the 34% of the study population with CKD Stage IV and V were either admitted in a hospital or were on dialysis.
|Figure 1: Age and sex distribution of chronic kidney disease patients in the study population|
Click here to view
|Table 1: Chronic kidney disease staging and number of patients from this study population belonging to each stage|
Click here to view
All the patients had some or the other co-morbid illnesses. [Figure 2] depicts the distribution of most common associated diseases prevailing in CKD patients. One hundred and seventy five patients (95%) were hypertensives and 161 (87%) were diabetic. 159 (86%) patients were anemic, which included all 82 patients with CKD Stage IV and V having a mean Hb% of 7.24 ± 2.32. Ninety-seven (52%) CKD patients were diagnosed with hypothyroidism and dyslipidemia was associated with 83% of the patients.
On reviewing the prescriptions, we found that 153 (83%) patients were advised more than 5 drugs at a time. [Figure 3] highlights the most prescribed groups of drugs in the management of CKD. Diuretics were advised in all 185 patients. One hundred and seventy-five patients were receiving anti-hypertensives among which angiotensin converting enzyme-inhibitors were extensively used. Usage of drugs such as clinidipine and prazosin individually or in combination was also marked to be 36%.
|Figure 3: Overall drug utilization pattern in chronic kidney disease patients|
Click here to view
One hundred and sixty-one (87%) patients were diagnosed to be diabetic among which 154 patients are on medical treatment. Insulin preferably short-acting insulin was advised in 117 (76%) patients and oral hypoglycemic agents in 37 patients. Sulfonylureas, biguanides, and gliptins were used individually or in combinations to manage diabetes in CKD Stage I to III patients and in others who were unwilling to take insulin. Hormone replacement therapy with thyroxine was used in 95 out of the 97 patients diagnosed with hypothyroidism. Anti-ulcer agents like H 2 blockers and proton pump inhibitors (PPIs) were rampantly used in 182 patients. Other commonly utilized drugs were mineral and calcium supplements, hematinics, prokinetics, and antibiotics. Keto-analogs were prescribed in those 37 CKD patients whose serum creatinine was in the range of 3-8 mg/dL and mostly among CKD Stage II to IV.
CKD patients due to their co-morbidities and immuno-compromised status are susceptible to infections. [Figure 4] illustrates the most common infectious diseases prevailing among CKD patients. One hundred and seven (58%) patients suffering from infections were either managed in outdoors or were admitted in hospital. It has been recorded that 28 patients were admitted with recurrent infections. Forty (37%) patients had respiratory tract infection, 36 (34%) had urinary tract infections, 11 patients had either gastrointestinal infections or eye and ear infection and 8 patients were diagnosed with tuberculosis. Twelve (11%) patients were having other types of infections. Two patients were diagnosed to have herpes, and 1 had a fungal infestation and other 9 patients presented either with pyrexia or leukocytosis predominantly neutrophilia or raised C-reactive protein or all. One patient presented with sepsis and 2 patients later developed sepsis even after rigorous treatment. [Figure 5] depicts the overall utilization pattern of antimicrobials in the management of infections in CKD patients.
|Figure 4: The most common infectious diseases prevailing in the study population|
Click here to view
|Figure 5: Utilization pattern of antimicrobials in chronic kidney disease patients|
Click here to view
Antimicrobials especially antibiotics were prescribed directly or modified after assessing the culture and sensitivity reports in most patients. Parenteral antibiotics like piperacillin + tazobactam or meropenem were initiated in patients with high leukocyte count, sepsis or multiple co-morbid conditions. The dose of antibiotics administered in this study population in comparison with normal adult dose as shown in [Table 2]. Macrolides like azithromycin in normal adult doses, quinolones like ciprofloxacin and levofloxacin in renal adjusted doses were among the antibiotics most utilized. Twenty-one patients were prescribed 3 rd generation cephalosporins like ceftriaxone and cefoperazone. More than one antibiotic was utilized in 28 patients. Metronidazole in reduced doses was preferred to combat infections caused by Gram-negative and anaerobic micro-organisms. A single dose of 250 mg of amikacin through dialysis port was advised once a week for 4 weeks in patients with port site infection. Eight patients were diagnosed with tuberculosis. Six patients who were in the intensive phase were prescribed normal adult doses of isoniazid and rifampicin and reduced doses of pyrazinamide. Ethambutol was not used in any of the patients. The other 2 patients were on continuation phase and were receiving isoniazid and rifampicin.
|Table 2: The renal adjusted doses of antimicrobials prescribed in the study population and its comparison with normal adult doses|
Click here to view
Antiviral namely acyclovir was utilized in the dose of 200 mg thrice daily. Fluconazole was the only antifungal that has been advised in 1 patient in the dose of 200 mg once daily.
| Discussion|| |
In this series, most of the patients were in the age group of 41-50 years with male predominance which correlates with previous studies.  Most patients belonged to Stage III CKD, however, it was marked that there was late presentation among patients, that is, they were first diagnosed in an advanced stage of CKD. Co-morbid conditions and complications like hypertension, diabetes, dyslipidemia and anemia were most common among these patients and found relevant with concomitant studies. ,,
Polypharmacy or use of more than 5 or more drugs at a time is an unavoidable predicament faced while managing CKD patients due to the prevalence of co-existing illnesses. The average number of drugs utilized was 8.1 ± 3.2 which is at par with earlier studies. , All the drugs were prescribed in trade/brand names, and this practice should be discouraged.
Of all drugs prescribed, the five most commonly used drugs were diuretics (mostly loop diuretics), anti-hypertensives (like calcium channel blockers, Angiotensin converting enzyme inhibitors and β-blockers), anti-ulcer agents, mineral supplements including calcium and hematinics. The diabetic patients were mostly on insulin therapy; however, oral hypoglycemic agents were successfully utilized among this study population. Sulfonylureas like glipizide and gliclazide were used in usual doses and biguanides (metformin) and gliptins (vildagliptins) were prescribed in reduced doses.
There happens to be a mismatch between patients diagnosed with peptic ulcer and number of patients on anti-ulcer agents like H 2 blockers and PPIs. This may be either due to the prevention of stress ulcers or symptomatic treatment for dyspepsia. Hematinics were extensively used along with mineral supplements including calcium. However, hematopoietic agents like erythropoietin and darbepoetin were under-used due to low patient compliance and high cost. Keto-analogs were mostly prescribed in CKD Stages II to IV as recommended so as to decrease renal injury. Phosphate binders and potassium binders were also significantly used among this study population.
CKD patients are at a high risk of infections and land up in recurrent hospital admissions. Reduced or absence of excretion by kidneys in renal failure causes an increase in the volume of distribution (V d ) and ultimately increases half-life (T½ ) of drug leading to accumulation of drug metabolites resulting in toxicity.
Respiratory tract infections still remain the most common infection. Hence, protocols are being developed to vaccinate these high-risk patients with pneumococcal and influenza vaccines. Urinary tract infections were more common in females as expected, but most of them were bearing multi-drug resistant species. Depending on the severity of the infection, virulence and sensitivity pattern of bacteria, various dosage forms of antibiotics were used. Most patients were treated with oral antibiotics on an outdoor basis. Azithromycin and levofloxacin were the two drugs most frequently prescribed among the oral antibiotics. Cefoperazone, piperacillin + tazobactum, on the other hand, were the most utilized parenteral antibiotics. Doses were reduced in all CKD patients though previous studies report that patients with GFR <60 mL/min/1.73 m 2 require an adjustment in dose.  The combination of more than one antibiotics was also advised in patients who were suspected with mixed infections and in patients who were not responding to a single antibiotic. Usage of antibiotics such as metronidazole, linezolid, vancomycin, and clarithromycin was marked in this population without reporting of appreciable adverse reactions. Hence, this will give confidence to physicians to employ these antibiotics to combat the emergence of bacteria resistance. 
Anti-tubercular therapy was initiated in 6 patients with normal adult doses of isoniazid and rifampicin and a renal adjusted dose of pyrazinamide. Use of ethambutol in CKD patients is not recommended and so not used.
| Conclusion|| |
Management of renal compromised patients possesses a challenge to physicians. This study illustrated the present day scenario of CKD patients in India and the prescribing trends of physicians in managing these patients with co-morbidities and complications. It will provide an outline for management strategies and will be influential in healthcare decision making. Drug-induced nephrotoxicity initiates progression of renal failure leading to morbidity and mortality. Appropriate dosing of drugs including antibiotics is vital as it can prevent adverse effects, toxicities and will lead to better clinical consequences.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Levey AS, Coresh J. Chronic kidney disease. Lancet 2012; 379:165-80.
National Kidney Foundation. K/DOQI clinical practice guidelines for chronic kidney disease: Evaluation, classification, and stratification. Am J Kidney Dis 2002;39:S1-266.
Manley HJ, Drayer DK, Muther RS. Medication-related problem type and appearance rate in ambulatory hemodialysis patients. BMC Nephrol 2003;4:10.
Kappel J, Calissi P. Nephrology: 3. Safe drug prescribing for patients with renal insufficiency. CMAJ 2002;166:473-7.
Roberts JA, Lipman J. Pharmacokinetic issues for antibiotics in the critically ill patient. Crit Care Med 2009;37:840-51.
Wanigasuriya KP, Peiris-John RJ, Wickremasinghe R, Hittarage A. Chronic renal failure in North Central Province of Sri Lanka: An environmentally induced disease. Trans R Soc Trop Med Hyg 2007;101:1013-7.
Le Grand A, Hogerzeil HV, Haaijer-Ruskamp FM. Intervention research in rational use of drugs: A review. Health Policy Plan 1999;14:89-102.
Levey AS, Coresh J, Balk E, Kausz AT, Levin A, Steffes MW, et al.
National Kidney Foundation practice guidelines for chronic kidney disease: Evaluation, classification, and stratification. Ann Intern Med 2003;139:137-47.
Long CL, Raebel MA, Price DW, Magid DJ. Compliance with dosing guidelines in patients with chronic kidney disease. Ann Pharmacother 2004;38:853-8.
Manley HJ, Cannella CA, Bailie GR, St Peter WL. Medication-related problems in ambulatory hemodialysis patients: A pooled analysis. Am J Kidney Dis 2005;46:669-80.
Wazny L, Moist L. Chronic kidney disease. In: Gray J, editor. E-Therapeutics +. Ottawa, ON: Canadian Pharmacists Association; c2012. Available from: http://www.e-therapeutics.ca
. [Last cited on 2012 Apr 20].
Manley HJ, Garvin CG, Drayer DK, Reid GM, Bender WL, Neufeld TK, et al.
Medication prescribing patterns in ambulatory haemodialysis patients: Comparisons of USRDS to a large not-for-profit dialysis provider. Nephrol Dial Transplant 2004;19:1842-8.
USRDS 1998 Annual Data Report. Bethesda, National Institutes of Health, National Institutes of Diabetes and Digestive and Kidney Disease; 1998.
Khan SS, Kazmi WH, Abichandani R, Tighiouart H, Pereira BJ, Kausz AT. Health care utilization among patients with chronic kidney disease. Kidney Int 2002;62:229-36.
Bailie GR, Eisele G, Liu L, Roys E, Kiser M, Finkelstein F, et al.
Patterns of medication use in the RRI-CKD study: Focus on medications with cardiovascular effects. Nephrol Dial Transplant 2005;20:1110-5.
McCormack J, Carleton B, Calissi P. Dosage adjustment in renal impairment. In: Gray J, editor. E-Therapeutics+. Ottawa, ON: Canadian Pharmacists Association; c2012. Available from: http://www.e-therapeutics.ca
. [Last cited on 2012 Apr 20].
Leung E, Weil DE, Raviglione M, Nakatani H, World Health Organization World Health Day Antimicrobial Resistance Technical Working Group. The WHO policy package to combat antimicrobial resistance. Bull World Health Organ 2011;89: 390-2.
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
[Table 1], [Table 2]