RESEARCH REPORT
RESEARCH TITLE
‘AN EVALUATION OF ANTIBIOTIC DOSING
ACCORDING TO RENAL FUNCTION OF
PATIENTS IN INTENSIVE CA...
CONTENTS
1) Introduction…………………………………………………………………………….1
1.1 Definition……………………………………………………………………..........3
2) Problem Sta...
1) Introduction
Patients who are admitted in Intensive Care Unit (ICU) include representative of all
age groups with a ran...
When selecting potential candidate of renal dose regimens, the first consideration is
the creatinine clearance (CrCl).Pati...
1.1 Definition
a) Renal impairment
1) Mild to severe
All categories of renal function other than the baseline category, wh...
2) Problem Statement
1) Patients with acute or chronic renal failure treated in ICU require adjustment of antibiotic
dose ...
3) Literature Review
From the previous study of Fahimi et al, findings show that two hundreds and ninetyone instructions (...
and the desired plasma concentration but independent of renal function. Doses of
hydrophilic agents such as b-lactams shou...
4) Objectives
General
To evaluatethe antibiotic doseadjustment according to renal function of patient of intensive
care un...
5) Methodology
Study design and location
-

A cross-sectional study, conducted retrospectively.

Sample population
-

All ...
5) Methodology
Guideline
1. The Malaysian Society of Anaesthesiology (MSA) Guide to Antimicrobial Therapy in
Adult ICU, Se...
6) Result and Discussion
Demographic data
Frequency, n

Percent

Male

72

63.7

Female

41

36.3

Total

113

100.0

Tabl...
Samples according to different stages of Creatinine Clearance (CrCl) and renal condition.

Number of Samples

Stages of Cr...
Percentage of Antibiotics Adherence to Guideline
Adherence of Antibiotics to Guideline
10.6%
n=12
High doses

Yes

89.4% n...
Frequency of antibiotics prescribed and its adherence to recommended guideline

Number of samples

30
25
20

3

15

1

10
...
be further compounded in the intensive care unit (ICU) as they typically harbor the most
resistantpathogens within a given...
Outcomes of samples
SIRS parameters were used to evaluate the outcome of this study whereby the mean of each
parameter wer...
Type of
antibiotics

Mean
T

Mean
WBC

Mean
WBC

Mean
RR

Mean
RR

Mean
HR

Mean
HR

After

Before

After

Before

After

...
b) Adherence of antibiotics towards guidelines and patient outcomes

Table 6.3: Adherence of antibiotics towards guideline...
7) Conclusion
-

Almost 90 % samples adhere to guideline MSA Guide to Antimicrobial Therapy in
Adult ICU, September 2006 a...
8) Limitation
-

Clinical improvement of patient cannot be evaluated solely based on septic parameters
instead prospective...
9) References
1. Scaglione, F. and Luca, P. (2008). Pharmacodynamics/Pharmacokinetics of Antibacterials
in ICU, 294-301.
2...
14. Grace L. Smith et al. Renal Impairment and Outcomes in Heart Failure Systematic Review
and Meta-Analysis.
15. KDOQi Cl...
31. Federico, P and Pierluigi, V. Review Bench-to-bedside review: Appropriate antibiotic
therapy insevere sepsis and septi...
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Provisional Registered Pharmacist research presentation 2013

  1. 1. RESEARCH REPORT RESEARCH TITLE ‘AN EVALUATION OF ANTIBIOTIC DOSING ACCORDING TO RENAL FUNCTION OF PATIENTS IN INTENSIVE CARE UNIT (ICU), HOSPITAL SULTANAH NUR ZAHIRAH, KUALA TERENGGANU’ Prepared by: Nurfatihah Nasiha Binti Bahagia Preesha A/P Nagalingam Preceptors: Erney Binti Mohd Shah Che Wan Mohd Hafidz Pharmacy Department, Hospital SultanahNurZahirah, Kuala Terengganu, Terengganu
  2. 2. CONTENTS 1) Introduction…………………………………………………………………………….1 1.1 Definition……………………………………………………………………..........3 2) Problem Statement……………………………………………………………………..4 3) Literature Review…………………………………………………………………........5 4) Objectives…………………………………………………………………………........7 4.1 General……………………………………………………………………………… 4.2 Specific……………………………………………………………………………… 5) Methodology……………………………………………………………………….........9 6) Results and discussion………………………………………………………………...10 7) Conclusion……………………………………………………………………………..18 8) Limitation………………………………………………………………………………19 9) References……………………………………………………………………………..20
  3. 3. 1) Introduction Patients who are admitted in Intensive Care Unit (ICU) include representative of all age groups with a range of organ dysfunction related to severe acute illness, which may complicate long term illness[1]. Twenty-two to thirty-two percent of ICU patients die from infections caused by gram-negative pathogens, despite appropriate antimicrobial therapy. These patients are at very high risk of developing severe nocosomial infections, with incidence rates five to ten fold higher than in general medical wards [2-5]. Serious infections and sepsis whether community or hospital acquired are common in critically ill patients and require rapid treatment to limit mortality and morbidity [1]. Antibiotics are among the most important and commonly prescribed drugs in the management of critically ill patients[6]. ICU patients are frequently affected by acute kidney injury (AKI) accompanied by dysfunction of other systems and organs while other cases are further complicated by a secondary infection. Continuous renal replacement therapy (CRRT) is frequently used to treat critically ill patients with acute or chronic renal failure. Since the prognosis in these patients are very poor due to severe infection and the mortality rate reaching from 80% to 90%, selecting appropriate antibiotic regimen is crucial for the clinical outcome. Choice of antibiotic used for empirical treatment of bacterial infections in the intensive care unit (ICU) is based predominantly on the identity and susceptibility pattern of bacteria isolated. Administering sub-therapeutic doses of antibiotics may lead to a decreased efficiency of therapy and development of resistant bacterial strains. On the other hand, high doses can be harmful to vital organs such as the kidneys, bone marrow and liver, resulting in a significantly worse prognosis [7]. Dosage adjustment of antibiotics to renal function is recommended for many antibiotics especially those that are eliminated by the kidney.Changes in renal function, whether associated with normal aging or disease, can have profound effects on the pharmacology of antibiotics since kidney is the major organ for maintaining fluid and electrolyte homeostasis. Renal function should always be taken into account because majority of drugs are excreted by the kidney[8,9]. Therefore, an estimation of their kidney function is crucial for appropriate drug dosing.
  4. 4. When selecting potential candidate of renal dose regimens, the first consideration is the creatinine clearance (CrCl).Patients with kidney disease, antibiotic dose adjustment are commonly made to maintenance dose, or the dosing interval based on pharmacodynamics effects of the drug. The most important information used for the prescribing of these antibiotics includes dose recommendation based on Cockroch-Gault estimate creatinine clearance (CrCl). Estimation of creatinine clearance is the most practical approach for assessing kidney function while CockrochGault equation remains the most appropriate method to determine drug dosage individualisation based on kidney function in clinical setting[10]. Since most drugs require dosing adjustment at a creatinine clearance of <50mL/min, therefore, the antibiotic dosing being prescribed for these patients need to be monitored frequently[1, 11].Identification of optimal dosage adjustments among patients with compromised renal function requires careful consideration of the relationships between antibiotic exposure, efficacy, toxicity and the potential for antibiotic resistance [12]. However, several factors may contribute to the increasing difficulties in establishing proper dosing regimen in critically ill patients [8]. Pathophysiological alterations associated with critical illness can lead to both an increase in the apparent volume of distribution (Vd) of an antibiotic as well as in clearance, thus, potentially leading to subtherapeutic plasma concentrations at the site of infection, treatment failure and the development of antibiotic resistance. Volume of distribution (Vd) and drug clearance (Cl) may be increased in ICU patients contributing to the altered concentration-time relationship of many drugs. When drug concentration is reduced, it might proportionally increase the halflife. The development of renal and/or hepatic impairment may be associated with the rapid onset of toxic drug concentrations. Therefore, antibiotic dose should be reviewed daily in the ICU and dosage adjustment is necessary to prevent accumulation and toxicity based on patient’s condition[13]. In this small study, our primary aim is focused on assessing antibiotics dosing being adjusted appropriately in patient with kidney disease according torecommended guideline as well as to study the outcomes of dosage adjustment of antibiotics in critically ill patients.
  5. 5. 1.1 Definition a) Renal impairment 1) Mild to severe All categories of renal function other than the baseline category, which corresponded to creatinine >1.0 mg/dl, creatinine clearance (CrCl) or GFR <90 ml/min.[14] 2) Moderate to severe Worst category of renal function which corresponded to creatinine ≥1.5 mg/dl, CrCl or GFR <53 ml/min[14] Stages [15] CrCl (ml/min) Stage 1 - Kidney damage with normal or Stage 2 - Kidney damage with mild or Stage 3 – Moderate Stage 4 – Severe GFR GFR Stage 5 – Kidney failure GFR GFR >90 60-89 30-59 15-29 <15 b) Renal condition 1) Acute renal failure (ARF) : Sudden loss of the ability of the kidneys to excrete wastes, concentrate urine, conserve electrolytes, and maintain fluid balance. [16] 2) Chronic kidney disease (CKD): Kidney damage or GFR <60ml/minute for 3 months or more, irrespective of cause.[17] 3) Acute-on-chronic renal failure : Acute renal failure (ARF) occurs in the background of pre-existing chronic kidney disease. [18]
  6. 6. 2) Problem Statement 1) Patients with acute or chronic renal failure treated in ICU require adjustment of antibiotic dose based on the patient’s renal function. If the dosage of antibiotic regimen given to these patients is not well adjusted, it can lead to accumulation and toxicity of the drugs with leads to increase in morbidity and mortality rates[19]. 2) In some critically-ill patients who are suffering with renal impairment, they are given large dose of antibiotics to fight the bacterial infections as their major priority, rather than adjusting the dosage according to the patient’s renal function and creatinine clearance (CrCl) [20]. 3) Dose adjustment of antibiotics according to renal function is crucial as it largely contributes to the clinical outcomes of patients[13].
  7. 7. 3) Literature Review From the previous study of Fahimi et al, findings show that two hundreds and ninetyone instructions (79.9%) of 364 antibiotic prescriptions required dosage adjustment based on the patient’s renal condition. These adjustments were rationally performed in 43.7% and 61.4% of prescriptions, according to the two guidelines used. Ciprofloxacin (29.1% of cases) and Vancomycin (33.6% of cases), were the most inappropriate prescribed antibiotics in terms of dose administration. The results demonstrate a significant need to develop a unanimous drug dosing system for patients with renal dysfunction. As conclusion from the study, finding a reliable and easily applied dosing guideline is highly recommended since lack of uniformity exists among dosing recommendations of commonly used drug information handbooks. The results of their study may not be extrapolated to other clinical settings, since they represent a unique situation. Therefore, further research is still required to reveal the clinical importance of drug dosage adjustment in renal failure patients. [21] Review by Eyler R. F and Mueller B. A, found that appropriate dosing of antibiotics in these patients is essential since the common cause of acute kidney injury (AKI) is sepsis. Drug dosing in critically ill patients with AKI, however, can be complicated. Critical illness and AKI can both substantially alter pharmacokinetic parameters as compared with healthy individuals or patients with end-stage renal disease. Furthermore, drug pharmacokinetic parameters are highly variable within the critically ill population. In addition, volume of distribution (Vd) of hydrophilic agents can increase as a result of fluid overload and decreased binding of the drug to serum proteins, and antibiotic loading doses must be adjusted upwards to account for these changes. Although renal elimination of drugs is decreased in patients with AKI, residual renal function in conjunction with renal replacement therapies (RRTs) result in enhanced drug clearance, and maintenance doses must reflect this situation. Antibiotic dosing decisions should be individualized to take into account patient-related, RRT-related, and drug-related factors. Efforts must also be made to optimize the attainment of antibiotic pharmacodynamic goals in this population. [22] According to the study done by Cathrine McKenzie on 2011, her finding shows that antibiotics factor and patient factors affect antibiotic dosing. Early and effective antibiotic therapy is essential in the management of infection in critical illness. The loading dose is probably the most important dose and is a function of the volume of distribution of the drug
  8. 8. and the desired plasma concentration but independent of renal function. Doses of hydrophilic agents such as b-lactams should be increased in the early stages of sepsis as the extravascular space increases while lipophilic agents such as macrolides, the inflammatory process is less important, although factors such as obesity will affect dosing. Concentrationdependent antibiotics such as aminoglycosides should be administered by extended interval regimens, which maximize bactericidal effect, minimize nephrotoxicity and allow time between doses for the post-antibiotic effect. The critical factor for time-dependent agents, such as b-lactams, is time above the MIC. Ideally administration of these agents should be continuous, although vascular access availability can restrict infusion time to between 4 and 6 h, which is probably adequate. Besides, patient factors such as hepatic and renal failure also will affect dosing. Hepatic failure will affect antibiotic metabolism, although it is most important in end-stage failure. Renal failure and support will affect drug elimination. According to the authors, knowledge of these factors is essential. Patient safety and prevention of unnecessary harm is a weighty consideration in critical illness. Therapy should be reviewed daily and adjusted in the light of changes in patient organ function and underlying pathology to ensure effective treatment and minimize adverse effects. [23]
  9. 9. 4) Objectives General To evaluatethe antibiotic doseadjustment according to renal function of patient of intensive care unit (ICU), Hospital SultanahNurZahirah(HSNZ), Kuala Terengganu. Specific 1. To determine the percentage of prescribed antibiotics being appropriately adjusted according to recommended guideline. 2. To compare the clinical outcomes of critically ill patient receiving antibiotic requiring dose adjustment in ICU based on its adherence.
  10. 10. 5) Methodology Study design and location - A cross-sectional study, conducted retrospectively. Sample population - All patients aged 12 years and above in intensive care unit, ICU, Hospital SultanahNurZahirah, Kuala Terengganu. - Patients were recruited by using inclusion and exclusion criteria. Inclusion criteria All renal impaired patients. Exclusion criteria 1) Patient on continuous renal replacement therapy (CRRT). 2) Patient admitted during weekend and was transferred out/passed away during the same weekend. 3) Patient that has incomplete data - Data collection 1. Clerked CP2 sheet of each patient in ICU starting from July to December 2012 (6months) were used to review patient information. 2. HIS system to collect extra information such as progress note of the patient and laboratory parameters during their admission in ICU. 3. All the data that were collected using Microsoft Excel 2007. Data analysis - The data collected wereanalyzed using the SPSS® (Statistical Package for the Social Sciences) software program for Windows® Version (20.0). - For all tests, a p value of < 0.05 will be defined as statistically significant.
  11. 11. 5) Methodology Guideline 1. The Malaysian Society of Anaesthesiology (MSA) Guide to Antimicrobial Therapy in Adult ICU, September 2006. 2. Antibiotic product pamphlet was used for evaluation of Piperacillin + Tazobactam (Tazosin) and Amoxycillin + Clavulanic Acid (Augmentin) doses. The MSA Guide to Antimicrobial Therapy in Adult ICU, September 2006were used for all antibiotic that need dose adjustment except Tazosin and Augmentin. Product pamphlets were used forTazosinsince we use the product from the company itself and there is no dose adjustment in recommended guideline for IV Augmentin. Adherence to guideline Dose of antibiotic prescribed in accordance to recommended dose based on CrCl of patients as stated in the guideline. Outcome [24] Systemic Inflammatory Response System (SIRS) were used to evaluate the samples after receiving antibiotic regimen. SIRS : Two or more of the following indicates no improvement : 1) Temperature >38°C or <36° C 2) Heart rate > 90 b/min, 3) Respiratory rate > 20 b/min, or PaCO2 <32mmHg 4) White blood count >12000/mm3 or <4000/mm3 or >10% band form
  12. 12. 6) Result and Discussion Demographic data Frequency, n Percent Male 72 63.7 Female 41 36.3 Total 113 100.0 Table 1: Gender From our study, 63.7% from total sample consists of male, n = 72 and 36.3% constitute female patient, n = 41. Type of antibiotic treatment Frequency, n Percent Empirical 77 68.1 Definitive 36 31.9 113 100.0 Total Table 2: Type of antibiotic treatment About 68.1 % of total samples, n= 77 treated with antibiotic as empirical and the rest of them treated as definitive.
  13. 13. Samples according to different stages of Creatinine Clearance (CrCl) and renal condition. Number of Samples Stages of Creatinine Clearance According to KDOQi Clinical Practice Guidelines, 2013 [15] 40 7 8 3 7 24 28 20 0 0 0 2 Stage 2 (60-89) 8 16 10 Stage 3 (30-59) Stage 4 (15-29) Acute on Chronic Chronic Acute Stage 5 (0-14) Stages of Creatinine Clearance (CrCl) Chart 6.1 : Samples according to different stages of Creatinine Clearance (CrCl) and renal condition. Chart 6.1 shows the number of samples according to different stages of creatinine clearance and renal condition. The stages of creatinine clearance is according to KDOQi clinical practice guideline,2013[15]. From the chart, 2 out of 2 samples in stage 2 creatinine clearance contributed to acute kidney disease, whereas, in stage 3, 24 samples are acute, 8 and 7 samples are chronic and acute on chronic respectively. For stage 4, 28 samples are acute, 7 chronic and 3 acute on chronic. Lastly, stage 5, 16 samples are chronic, followed by 10 samples acute and 8 samples acute on chronic. The chart showed that majority of samples contributed to acute kidney disease and having stage 4 creatinine clearance which consisted of 28 samples.
  14. 14. Percentage of Antibiotics Adherence to Guideline Adherence of Antibiotics to Guideline 10.6% n=12 High doses Yes 89.4% n=101 No Total sample, n = 113 Chart 6.2 : Percentage of Antibiotics Adherence to Guideline Chart 6.2 shows the percentage of antibiotics adherence to recommended guideline. From the pie chart, 89.4 % constituting of 101 out of 113 samples adhere to recommended guideline whereas 10.6% constituting 12 out of 113 samples did not adhere to recommended guideline whereby they were prescribed with high doses of antibiotics despite renal function and creatinine clearance stages.
  15. 15. Frequency of antibiotics prescribed and its adherence to recommended guideline Number of samples 30 25 20 3 15 1 10 5 0 1 5 4 10 8 2 2 5 5 17 3 3 24 13 3 2 2 No Yes Types of antibiotics Chart 6.3: Frequency of antibiotics prescribed and its adherence to recommended guideline Chart 6.3 shows the frequency of different types of antibiotics prescribed. Based on our result, 12 samples did not adhere to guideline consisting of 5 types of antibiotics that include Ampicillin + Sulbactam (Unasyn), Ciprofloxacin, Imipenem + Cilastation (Tienem), Meropenem and Metronidazole. Many previous studies suggested that dose of those antibiotics should be higher than recommended guideline. From our result, it was found that dose of Ciprofloxacin were prescribed with a high dose of 400mg BD comparing to the recommended 200mg BD as stated in recommended guideline based on creatinine clearance. From the study of Zanteen et al (2008), IV Ciprofloxacin 400 mg BD leads to adequate AUC/MIC and Cmax/MIC ratios in many cases. Effective killing concentrations were only achieved in pathogens with MIC less than 0.25. As bacteria in intensive care unit patients often exceed this threshold, it is recommended to use higher doses of ciprofloxacin (1200 mg daily) to ensure optimal bacterial killing and avoid antibiotic resistance[25]. Besides that, meropenem is another antibiotic that did not adhere to recommended guideline consisting of 3 samples that did not adhere. Study by Eggiman, P and Pittet, D found that there is potential inadequacies noted for standard doses of meropenemwhich may
  16. 16. be further compounded in the intensive care unit (ICU) as they typically harbor the most resistantpathogens within a given population[26]. Furthermore, another study found that the pharmacokinetics of the critically ill may differ from non-critically ill patients, often resulting in a reduction in exposure of meropenem [27]. For these reasons, higher empiric doses may be required to adequately achieve pharmacodynamic targets against pathogens encountered within the ICU[28]. This study also found that there is only 1 from 6 samples of Ampicillin + Sulbactam (Unasyn) that did not adhere to guideline, which administered 1.5 g TDS instead of 3g OD as stated in recommended guideline. Study from Adnan, S et al. suggested that for optimization of therapy higher dose for treatment of infection is recommended since alteration of pharmacokinetics are common inβ-lactam agents in critical illness[29]. The need of higher dosage of antibiotics in critically ill patients was supported by few studies. According to Nathwani D and Davey P, they suggest that the highest dose in the range should be given in severe sepsis since low doses may not only be ineffective but have been shown to contribute to resistance [30]. Another study by Federico P and Pierluigi conclude that selecting higher dosage and alternative dosing regimens focused at maximizing the pharmacodynamics of antimicrobials might be worthwhile, in order to increase clinical cure rates among critically ill patients.[31]
  17. 17. Outcomes of samples SIRS parameters were used to evaluate the outcome of this study whereby the mean of each parameter were calculated before and after the initiation of antibiotics and the respective means were compared to evaluate the outcome. (a) Improvement of outcomes based on SIRS parameters (T = temperature, WBC = White Blood Cells, RR= Respiratory rate, HR= Heart Rate) Type of antibiotics Sample, n Mean T Mean T Mean WBC Mean WBC Mean RR Mean RR Mean HR Mean HR Before After Before After Before After Before After Cefepime 2 38.1 37.5 7.6 8.7 16.5 18.2 81.2 83.4 Cefotaxime 2 39.6 36.7 8.9 6.9 21.4 17.0 85.6 76.5 Vancomycin 2 36.7 36.4 13.3 8.5 20.3 18.4 78.4 68.7 Polymyxin E 2 37.9 36.9 8.3 9.6 18.1 17.6 84.5 79.6 Amoxycillin + Clavulanic Acid (Augmentin) 5 (8) 38.6 37.8 11.0 14.6 18.9 17.6 80.5 77.0 Ceftazidime 7 (10) 37.8 36.8 8.4 7.5 18.3 16.7 89.3 87.5 Piperacillin + Tazobactam (Tazosin) 18 (24) 37.3 37.8 9.5 8.3 18.5 16.0 90.4 88.3 Table 6.1 :Antibiotics that 100 % adhere to guideline Table 6.3 shows the antibiotics which 100% adhere to guideline and showed improvement based on SIRS parameters which includes Cefepime, Cefotaxime, Vancomycin, Polymyxin E, Amoxycillin + Clavulanic Acid, Ceftazidime and Piperacillin + Tazobactam. As for Cefepime, Cefotaxime, Vancomycin and Polymyxin E, 2 out of 2 samples adhere to guideline and showed improvement contributing to 100% adherence and 100% positive outcome. The rest of the antibiotics, Amoxycillin + Clavulanic Acid, Ceftazidime and Piperacillin + Tazobactam 100 % adhere to guideline but did not 100% show positive outcome whereby only 5 out of 8 for Amoxycillin + Clavulanic Acid, 7 out of 10 for Ceftazidime and 18 out of 24 for Piperacillin + Tazobactam showed improvement based on SIRS parameters.
  18. 18. Type of antibiotics Mean T Mean WBC Mean WBC Mean RR Mean RR Mean HR Mean HR After Before After Before After Before After 4 37.9 37.3 13.5 10.3 18.8 19.1 92.9 86.0 1 5 (9) Mean T Before Ciprofloxacin Sample, n 38.1 36.7 14.6 12.5 23.6 18.9 87.3 86.5 Imipenem + Cilastatin (Tienem) 2 (6) 2 37.7 37.8 11.4 9.0 19.5 17.6 88.4 77.0 Meropenem 17 (20) 14 37.4 38.1 8.9 11.7 18.4 18.9 98.7 89.9 3 38.7 36.4 11.3 13.9 20.2 18.7 89.7 85.3 3 38.1 37.3 9.0 10.3 23.4 19.1 94.4 91.3 1 37.5 37.1 13.7 10.4 19.3 22.4 94.5 89.1 5 38.4 37.4 8.2 7.9 25.4 17.2 82.7 86.7 Ampicillin + Sulbactam (Unasyn) 4 (6) Metronidazole 5 (14) Table 6.2 :Antibiotics that did not 100% adhere to guideline Table 6.2 focused on the antibiotics that did not 100% adhere to guideline but however showed improvement based on SIRS parameters. From the table, 5 out of 9 samples of Ciprofloxacin showed improvement, 4 out of 5 samples adhere to guideline whereas 1 sample did not adhere to guideline and yet showed improvement. As for Imipenem + Cilastatin, 2 out of 6 samples showed improvement, 2 out 6 samples showed improvement whereby both the samples adhere to guideline. Next, Meropenem, 17 out of 20 samples showed improvement whereby 14 samples adhere to guideline and 3 samples did not adhere to guideline. As for Ampicillin + Sulbactam, 4 out of 6 samples showed improvement, 3 samples adhere to guideline and 1 sample did not adhere to guideline. Lastly, Metronidazole consist of 5 out 14 samples that showed improvement based on SIRS parameters and all 5 adhere to recommended guideline.
  19. 19. b) Adherence of antibiotics towards guidelines and patient outcomes Table 6.3: Adherence of antibiotics towards guidelines and patient outcomes Table 6.4: Pearson Chi-Square test: Association of antibiotics adherence towards guidelines and patient outcomes Data was analysed using SPSS version 20 and p value less than 0.05 indicate significant. From table 6.3 and 6.4, statistical analysis using Chi-Square test found that there was no significant between adherence of antibiotics towards guidelines and patient outcomes (p = 0.53) in this study.
  20. 20. 7) Conclusion - Almost 90 % samples adhere to guideline MSA Guide to Antimicrobial Therapy in Adult ICU, September 2006 and product pamphlet. - Although high percentage of improvement seen in adhere group compare to nonadhere group, there was no significant between adherence of antibiotics towards guidelines. - Therefore, we recommend to adjust dose in order to save renal function whereby dosing of antibiotic in critically ill patients should be individualized and not solely based on creatinine clearance or renal function.
  21. 21. 8) Limitation - Clinical improvement of patient cannot be evaluated solely based on septic parameters instead prospective study should be proposed to evaluate the outcomes of this study.
  22. 22. 9) References 1. Scaglione, F. and Luca, P. (2008). Pharmacodynamics/Pharmacokinetics of Antibacterials in ICU, 294-301. 2. Vincent, J. L., Bihari, D. J., Suter, P.M., Bruning, H. A., White, J., Nicolas- Chanoin, M. H., et al. (1995). The prevalence of nosocomial infection in intensive care units in Europe. Results of the European Prevalence of Infection in Intensive Care (EPIC) Study. EPIC International Advisory Committee. JAMA, 274:639–44. 3. Weber, D.J., Raasch, R., Rutala, W.A. (1999). Nosocomial infections in the ICU: the growing importance of antibiotic-resistant pathogens, 115,34S–41S 4. Vincent, J. L. (2003). Nosocomial infections in adult intensive-care units. Lancet, 361, 2068–77. 5. Paterson, D. L. (2003). Restrictive antibiotic policies are appropriate in intensive care units. Critical Care Medicine, 31, S25–8. 6. Joao, G.P. and Pedro, P. (2011). Antibiotics in critically ill patients : A systematic view of pharmacokinetics of β-Lactams. 7. Joanna, M., Rowińska, Jolanta, M., Ewa, W., Paweł, K. (2011). Dosing of antibiotics in critically ill patients: are we left to wander in the dark? Journal Antimicrobial Chemotherapy. 8. National Kidney Foundation. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. (2002). American Journal Kidney of Disease,39, S1–266. 9. Bonapace, C.R., White, R. L., Frich, L. V. et al. (2002). Differences in antimicrobial drug exposure in patients with various degrees of renal function based on recommendations from dosing references. Pharmacotherapy, 22, 1097–104. 10. Cockcroft, D. W., Gault, M. H.(1976). Prediction of creatinine clearance from serum creatinine. Nephrology, 16, 31–41. 11. Van, D. E. et al. (2006) Drug dosage adjustments according to renal function at hospital discharge. Annals Pharmacotherapy, 40, 7-8, 1254-60. 12. Nimish, P. et al. Determination of antibiotic dosage adjustments in patients with renal impairment: elements for success. 13. Jason, A. R., Jeffrey, L. (2009). Critical Care Medicine,.Pharmacokinetic issues for antibiotics in the critically ill patient.
  23. 23. 14. Grace L. Smith et al. Renal Impairment and Outcomes in Heart Failure Systematic Review and Meta-Analysis. 15. KDOQi Clinical Practice Guidelines(2013) 16. Robert W. Et al. Acute renal failure: definitions, diagnosis, pathogenesis, and therapy, 2004 17. S.W Andrew et al. Definition and classification of chronic kidney disease: A position statement from Kidney Disease: Improving Global Outcomes (KDIGO) 18. Andrew S.L et al. Definition and classification of chronic kidney disease; A position statement from KDIGO,Kidney International, 2005. 19. Swan, S. K. and Bennett, W. M. (1992). Drug dosing in patients with renal failure. Western Journal Medicine, 156, 633-8. 20. Moore, R., Lietman, P., Smith, C. (1987). Clinical response to Aminoglycoside therapy: importance of the ratio of peak concentration to minimal inhibitory concentration. Journal Infectious Disease, 155, 93–9. 21. Fahimi et al. The Rate of Antibiotic Dosage Adjustment in Renal Dysfunction, Iranian Journal of Pharmaceutical Research (2012) 22. Eyler, R. F., and Mueller, B. A. Nature Review of Nephrology, April 2011 23. Cathrine McKenzie. Antibiotic dosing in critical illnes, Journal of Antimicrobial Chemotherapy, 2011. 24. N.D Madala, Acute renal failure in patients with chronic kidney disease, American College of Chest Physicians (ACCP) and the Society of Critical Care Medicine (SCCM) 25. Zanteen et al. (2008). Ciprofloxacin pharmacokinetics in critically ill patients: A Prospective cohort study, Journal of Critical Care, 23, 422-430 26. Eggimann,P. andPittet, D. (2001).Journal of Infection control in ICU. Chest Journal, 120, 2059–2093 27. Roberts J.A. and Lipman, J. (2009) Pharmacokinetic issues for antibiotics in the critically ill patient. Critical Care Medicine, 37, 840–851. 28. Jared L et al. (2010). Optimization of meropenem dosage in the critically ill population based on renal function, Intensive Care Medicine. 29. Adnan S et al. (2013) Ampicillin/sulbactam: Its potential use in treating infections in critically ill patients. Journal International Antimicrobial Agents. 30. Nathwani D, Davey P. Antibiotic prescribing—are therelessons for physicians? QJM 1999;92(5):287–92.
  24. 24. 31. Federico, P and Pierluigi, V. Review Bench-to-bedside review: Appropriate antibiotic therapy insevere sepsis and septic shock - does the dose matter?

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