DRUG UTILIZATION EVALUATION OF PIPERACILLIN AND TAZOBACTUM AT A

TERTIARY CARE CENTRE IN HYDERABAD, INDIA

A Dissertation submitted to

JAWAHARLAL NEHRU TECHNOLOGICAL UNIVERSITY HYDERABAD

In partial fulfillment for the award of

BY

S. VENKATESH (15Z91R0041)

P.SHIVANI (15Z91R0031)

M.SHAILAJA (15Z91R0028)

K.SWAPNA (15Z91R0038)

UNDER THE GUIDANCE OF

DR. ANUP JAGARLAMUDI

DEPARTMENT OF PHARMACY PRACTICE

KVK COLLEGE OF PHARMACY

SURMAIGUDA(V), HAYTHNAGAR (M)

RANGAREDDY (DIST)

APRIL-2019
 CERTIFICATE

This is to certify that this dissertation work titled ‘‘Drug utilization evaluation of
PIPARACILLIN AND TAZOBACTUM Technological University, Hyderabad in partial
fulfillment of the requirement for the award of Bachelor of Pharmacy is a record of research
performed by S.VENKATESH (15Z91R0041),P.SHIVANI (15Z91R0031),M.SHAILAJA
(15Z91R0028), K.SWAPNA (15Z91R0038) during the academic year 2018 – 2019 under my
guidance and supervision.

Dr.ANUP JAGARLAMUDI M.Pharm.Ph.D.

Department of Pharmacy Practice

KVK college of Pharmacy

SURMAIGUDA (V), HAYTHNAGAR (M)

RANGAREDDY (Dist).

DATE:

PLACE:
 CERTIFICATE

This is to certify that this dissertation work titled ‘‘Drug utilization evaluation of
PIPERACILLIN AND TAZOBACTUM at a tertiary care in Hyderabad’’ was carried out by
S.VENKATESH (15Z91R0041),P.SHIVANI (15Z91R0031), M.SHAILAJA (15Z91R0028),
K.SWAPNA (15Z91R0038) during the academic year 2018-2019 under the guidance Dr.Anup
Jagarlamudi, M.Pharm, Ph.D. Head of department (HOD) department of pharmacy practice, in
partial fulfillment of the requirement for the award of Bachelor of Pharmacy, Jawaharlal Nehru
Technological University, Hyderabad.

Principal,

Dr.Ravi pratap pulla M.Pharm.P.hD

KVK COLLEGE OF PHARMACY

SURMAIGUDA (V), HAYTHNAGAR (M) , RANGAREDDY (Dist).

DATE:

PLACE:
 DECLARATION

This to certify that the project work entitled “DRUG UTILIZATION EVALUATION OF
PIPERACILLIN AND TAZOBACTUM AT A TERTIARY CARE IN HYDERABAD” has been
carried out under the supervision of Dr. Anup Jagarlamudi M.Pharm, Ph.D., (HOD), Department
of Pharmacy Practice, KVK college of pharmacy, and that we have not submitted these results in
any form previously for the award of any degree.

By

S.VENKATESH (15Z91R0041)

P.SHIVANI (15Z91R0031)

M.SHAILAJA (15Z91R0028)

K.SWAPNA (15Z91R0038)

DATE:

PLACE:
 DEDICATION

TO GOD BE ALL THE GLORY.

I dedicate my dissertation work to My Loving Parents, Who Guided Me to Where I

Am Today, thank you for telling me what I’m capable of. For giving me the support that I
needed to build a dream to chase after. And for believing that I have the talent to reach my
goals.

DATE:

PLACE:
 ACKNOWLEDGEMENTS

We wish to express our sincere gratitude to Dr.B.Nageshwar reddy Asian institute of

gastroenterology, Dr.sravan sir Gandhi hospital, Dr.Anup jagarlamudi sir (HOD) of Kvk College

of pharmacy for providing us an opportunity to do our project work on

“DRUG UTILIZATION EVALUATION OF PIPERACILLIN AND TAZOBACTUM AT

A TERTIARY CARE CENTRE IN HYDERABAD, INDIA”

This project bears an imprint of many people’s work. We sincerely thank to our project guide

Mr. J. ANUP (HOD) sir, M.pharm, PhD department of pharmacy Practice, KVK College

of pharmacy, Hyderabad for guidance an encouragement in carrying out this project work. I

sincerely and wholeheartedly thank to, staff of hospital, for supporting us in carrying out our

project. Without their constant encouragement and support, this wouldn’t have materialized. We

also wish to express our gratitude to the officials and other staff members, who rendered their

help during the period of our project work. Our special thanks to all staff members, of Kvk

College of pharmacy for rendering their kind co-operation for completion of our project work.

Last but not least we wish to express our sincere gratitude and love to all our friends

for their manual support, strength, and help and for everything.

My sincere”THANKS TO ALL”

Sincerely,
ABBREVATIONS:

ABECB – Acute bacterial exacerbation of chronic bronchitis

ABS – Acute bacterial sinusitis
ADR – Adverse drug reactions
CAP – Community acquired pneumonia
COPD – chronic obstructive pulmonary disease
DDD – Defined daily dose
DTC – Drug therapeutic committee
DUE – Drug utilization evaluation
DUR – Drug utilization Review
FDA – Food drug administration
FQs – Fluroquinolones
LRTI – Lower respiratory tract infections
MDRSP – Multiple drug resistance streptococcus pneumonia
MVC – Monovalent cations
STG – Standard treatment guidlines
TB - Tuberculosis
URTI – Upper respiratory tract infection
UTI – Urinary Tract Infection
VEN – Vital Essential Non-essential anlaysis
WHO – World health organization
 TABLE OF CONTENTS

SL.NO CONTENTS PAGE NO.

1 INTRODUCTION 1-8

2 LITRATURE REVIEW 9-30

3 AIMS,OBJECTIVE AND PLAN OF WORK 31-36

4 RESULTS 37-44

5 DISCUSSION 45-54

6 STATASTICS 55

7 CONCLUSION 56

8 ANNEXURE 57-59

9 REFERENCE 60-65
INTRODUCTION:

Drug use evaluation (DUE):

Drug use evaluation is an ongoing, systematic, criteria-based program of medicine evaluations

that will help ensure appropriate medicine use. If therapy is determined to be inappropriate,
interventions with providers or patients will be necessary to optimize Pharmaceutical therapy. A
DUE can be structured so that it will assess the actual process of administering or dispensing a
medicine (i.e., appropriate indications, dose, medicine interactions) or assess the outcomes.

Objectives of a DUE are as follows—

• Ensuring that the pharmaceutical therapy meets current standards of care

• Promoting optimal medication therapy
• Preventing medication-related problems
• Identifying specific medicine use problems that require further evaluation
• Creating guidelines (criteria) for appropriate medicine use
• Defining thresholds for quality of medicine use
• Enhancing accountability in the medicine use process
• Controlling pharmaceutical cost.

Indicators Suggesting a Need for DUE Analysis

Certain events (indicators) serve as “flags” of potential opportunities to improve drug use. Some
are
• Adverse drug events, including medication errors, preventable adverse drug reactions, and
toxicity.
• Signs of treatment failures, such as unexpected readmissions and bacterial resistance to anti-
infective therapy.

• Pharmacist interventions to improve medication therapy, categorized by medication and type of

intervention.

• Non formulary medications used or requested.

• Patient dissatisfaction or deterioration in quality of life.

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Classification:
 Prospective DUE
 Concurrent DUE
 Retrospective DUE
Types of DUE:
Quantitative
 Quantify current state of drug use
 Study trends of drug use
 Study time course of drug usage at national, regional, local or institutional levels
Qualitative (DUR)
 Study appropriateness of drug utilization
 Links prescription data with drug indications
 Uses of Quantitative Drug Utilization Studies:
 To estimate drug utilization in populations by
 Demographic characteristics
 Used as denominators to calculate rates of ADRs
 To monitor
_ Specific therapeutic categories
_ Effects of regulatory activities
 Markers for crude estimates of disease prevalence
 To plan importation, production & distribution
 To estimate drug expenditures
Uses of Qualitative Studies:
 To study appropriateness of drug uses
_ Indications
_ Daily dose
_ Length of therapy
 To asses clinical efficacy (high intrinsic value) of most common sold drugs

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Steps involved in DUE:

The following eight steps outline the basic information necessary to start and maintain a DUE
Program.
Step1. Establish Responsibility
Responsibility falls to the DTC or a subcommittee of the DTC that functions only to monitor
DUEs In the hospital or clinic. The DTC should undertake this responsibility with considerable
Interest, because this process can solve many medicine use problems, as has proven to be the
Case in many countries where this quality assurance function has been fully utilized. The DTC or
a subcommittee must establish procedures that will govern the committee in its activities
concerning medicine use review and evaluation. As part of the responsibility of the DUE
function, the DTC must establish a plan, outlining which medicines will be a part of the DUE
process. This plan needs to be updated and evaluated each year.
Step2. Develop Scope of Activities
The DTC should assess and identify medicine use problems and using this information to
develop a scope of activity for the DUE program. The scope can be extensive or it can focus on a
single aspect of pharmaceutical therapy. Methods to identify medicine use problems include and
ABC or vital, essential, nonessential (VEN) analysis, defined daily dose analysis, ADR reports,
medication error reports, antibiotic sensitivity results, procurement studies, hospital and primary
care clinic indicator studies, patient complaints or feedback, and staff feedback. These screening
mechanisms serve to provide the DTC with information concerning medicine use that would
need further evaluation in a DUE. Because of the large number of medicines available at a
hospital or clinic, the DTC must concentrate on the most important medicines, those with the
highest potential for problems, to get the most return on the work involved. These high priority
areas would include—
• High-volume medicine use
• Medicines with a low therapeutic index
• Medicines with a high incidence of ADRs
• Expensive medicines
• Medicines that are critically important, including those in the following categories:
Cardiovascular, emergency, toxicology, oncology, intravenous medicines, and narcotic
Analgesics

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• Antimicrobial medicines, both prophylactic and therapeutic
• Injections
• Medicines undergoing evaluation for addition to the formulary
• Medicines used for off-label indications
• Medicines used for high-risk patients
Steps 3and 4. Establish Criteria, Define and Establish Thresholds
Criteria are statements that define correct medicine use. Establishing criteria is the single most
Important procedure in a DUE. Criteria for the use of any medicine should be established by the
DTC using relevant evidence-based literature sources and recognized international and local
experts. The criteria for any DUE should reflect what is in the country’s STGs (assuming that
they have been developed correctly) and any medicine-use protocols that exist. Credibility of the
DUE relies on criteria that are based on evidence-based medicine. Criteria must be developed
with and accepted by the medical staff for the process to be credible. Criteria should be
developed for three to five of the most important indicators for each aspect of medicine use.
Reviewing larger numbers of indicators will make for a more difficult DUE process and may
significantly impair the outcomes of the review. This is not to say that more extensive use of
indicators should not be reviewed, only that results are more easily obtained and possibly more
meaningful when the scope is narrowed to include only the most important aspects of care. After
developing criteria, the DTC must establish a threshold or standard (benchmark) against which
the criteria will be judged. A threshold refers to the percentage of charts or records that will meet
or exceed the established criteria for the medicine. Ideally, this threshold will be 100 percent, but
realistically, a smaller percentage will be more appropriate to account for exceptions to routine
medicine prescribing. Therefore, a threshold of 90 to 95 percent is typically used for many
criteria, but each instance must be carefully analyzed before reaching a conclusion. A
comprehensive list of indicators for appropriate medicine use includes the following
components-
• Process indicators
 Indications—specific uses for the medicine in question
 Dose—specific doses for any approved indication for appropriate duration
 Quantity dispensed—correct number of doses administered
 Preparation—steps involved with preparing a medication for administration

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  Monitoring—laboratory test necessary and intervals of testing during the use of the
Medicine
 Contraindications—known contraindications
 Drug interactions—significant medicine interactions, including medicine-medicine,
Medicine-food and medicine-laboratory
 Administration—specific steps necessary to administer a medicine, especially for
Injectables
 Patient education—instructions and education that a patient should receive with the
medicine
 Outcome indicators—specific outcomes to be realized from medicine use
 Lowered blood pressure, stabilized blood glucose, and fewer migraine and asthma
attacks
 Decreased visits to the emergency room, decreased hospitalizations
 improved patient quality of life (obtained from questionnaires)

• Pharmacy administration indicators

 Correct cost to patient
 Accurate billing records
 Accurate dispensing records
 Appropriate use of generic medicines or therapeutic equivalents
 Appropriate use of formulary medicines
 Appropriate quantity dispensed
Step 5. Collect Data and Organize Results.
DUEs can be accomplished as prospective evaluations, or they can be performed retrospectively.
A prospective analysis involves the collection of data as the medicine is being prepared or
dispensed to the patient. Retrospective analysis is done using chart reviews or other data sources
to review medicine use according to indicators and criteria prepared in advance. The advantage
of a prospective review is that the pharmacist (or other reviewer) can intervene at the time the
medicine is dispensed to prevent errors in, for example, dosage, indications, or interactions.
Retrospective evaluation, which may involve more of the reviewer’s time or require access to
medical records, is best accomplished when the reviewer has time away from the patient care

5
areas and distractions. Typically, medicine-related criteria that are reviewed in these types of
evaluations are as follows—
• Prospective studies (obtained from prescription records)
 Indication
 Dose
 Duration of therapy
 Dosage form and route of administration
 Potential medicine interactions
 Appropriate therapy and medicine selection (corresponds to STGs)
 Therapeutic duplication
 Contraindications
 Quantity dispensed
• Retrospective studies (obtained from prescription, medical records, laboratory records)
 Laboratory monitoring
 Monitoring therapeutic use of high-cost medicines
 ADRs to medications
 Correct use of generic or therapeutic equivalents
 Patient outcomes from pharmaceutical therapy
Collection of the data is performed by reviewing a suitable sample of charts or prescription
records from the health care facility, usually by selected pharmacy personnel. At a minimum, 50
to 75 records should be reviewed at each health care facility. The larger the facility and the more
practitioners who are available, the larger the percentage of records that would need to be
reviewed and analyzed.
Step 6. Analyze Data
Data are collected, tabulated, and analyzed to see if criteria and thresholds are met.The following
important steps should be completed when analyzing data—
 Tabulate results for each indicator
 Analyze results to see if the criteria are met and the thresholds are not exceeded
 Determine why thresholds are not met
 Analyze data quarterly or more frequently if a threshold is not met, it may indicate a
medicine use problem that requires the attention of the DTC.

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Step 7. Develop Recommendations and Action Plan
After completing the data analysis, information is presented to the DTC and a decision is made
as to the appropriateness of the information in the DUE. The DTC also must decide on whether
to continue, discontinue, or expand the functions of the DUE in question. All medicines that do
not meet the thresholds must be evaluated carefully and plans must be made to improve the use
of the medicine relative to the criteria.
Recommendations should be prepared for the DTC to address the following—
 Inappropriate medicine use
 Unacceptable patient outcomes
 Methods to resolve any medicine use problem
Recommendations should include specific steps to correct any medicine use problem that is
evident from performing the DUE. For example, if a specific medicine is being prescribed at a
high dose, then the recommendations need to reflect this and how the DTC might improve the
dosing of this medicine. Interventions to improve medicine use might include—
 Education, including letters to practitioners, in-service education, workshops, newsletters,
and face-to-face discussions
 Implementation of medicine order forms
 Prescribing restrictions
 Formulary manual changes
 Change (or better enforcement) of the STGs
Step 8. Conduct DUE Follow-up
Follow-up in every DUE is critical to ensure resolution of any unresolved medicine use
problems. The DUE may have identified new problems that need to be resolved within the health
care system. If the problems are not resolved, then the DUE will have little usefulness to the
health care system. As a part of a follow-up plan, the DTC must assess the need to continue,
modify, or stop the DUE activity depending on the results of each specific medicine review. A
DUE should be an ongoing process in which medicine-related problems are regularly addressed.
Medicine review should be considered a long-term program, one that is continuously updated
and revised to reflect current situations and needs within the health care institution. All programs
within the DTC should be evaluated yearly. This complete evaluation is necessary to look
comprehensively at the entire program and analyze its merits and its utility in improving

7
medicine use. Programs that do not have a significant impact on medicine use should be
redesigned so that they can provide measurable improvements. Without improvements in
medicine use and patient outcomes, the time spent on DUE will be of no value. It must be
stressed that indicators and criteria for a DUE can be highly individualized depending on the
specific needs of the health care facility. (1)(2)

8
LITERATURE REVIEW:

1. Young-Mo Yang

Piperacillin/tazobactam (TZP) is an antibiotic against a broad spectrum of gram-positive, gram

negative, and aerobic and anaerobic strains of bacteria. Due to changes in its pharmacokinetic
and pharmacodynamic parameters by TZP - treated patients’ renal functions and obesity, it is
important to administrate and monitor TZP based on their renal functions and body mass Index
(BMI) levels. The purpose of this study was to determine the appropriateness of administration
doses of TZP based on renal functions of obese cancer patients in a tertiary hospital.

2. Perry CM (4)

Piperacillin/tazobactam is a beta-lactam/beta-lactamase inhibitor combination with a broad

spectrum of antibacterial activity encompassing most Gram-positive and Gram- negative aerobic
bacteria and anaerobic bacteria, including many pathogens producing beta-lactamases. Evidence
from clinical trials in adults has shown that piperacillin/tazobactam, administered in an 8:1 ratio,
is an effective treatment for patients with lower respiratory tract, intra-abdominal, urinary tract,
gynecological and skin/soft tissue infections, and for fever in patients with neutropenia.
Combination regimens of piperacillin/tazobactam plus an amino glycoside are used to treat
patients with severe nosocomial (hospital-acquired) infections.

3. Min E, et al

Evaluation of 140 surgical ICU patients over the course of a year who received vancomycin +/-
pip-tazo for at least 48 hours. AKI was defined as an increase in serum creatinine more than 1.5
times baseline during antibiotic therapy. The authors controlled for severity of illness and
concomitant use of other nephrotoxic antibiotics. The incidence of AKI was higher in the
vancomycin + pip-tazo group (40.5%) compared to the vancomycin alone group (9.0%, p &
lt; 0.001).

9
4. Maria F (5)

PIP/TAZO may safely be used in pediatric patients as an empiric treatment for serious infections
in hospital environments where resistance to common first-line antimicrobials has emerged. The
most common indications in pediatric patients are nosocomial infections owing to resistant
Gram-negatives, exacerbation of pulmonary colonization with Pseudomonas aeruginosa in
patients with cystic fibrosis, intra-abdominal infections, fever and neutropenia in pediatric cancer
patients. The influence of PIP/TAZO routine use on the selection of extended-spectrum beta
lactamase producing Gram-negatives and on the prevalence of vancomycin-resistant enterococci
is still a matter of debate. In particular the use of PIP/TAZO in neonates and PIP/TAZO
monotherapy in pediatric cancer patients with fever and neutropenia should be investigated in
prospective randomized studies including a sufficient number of patients.

5. Young M (6)

Piperacillin/tazobactam is a beta-lactam/beta-lactamase inhibitor combination with a broad

spectrum of antibacterial activity against most Gram-positive and Gram-negative aerobic
bacteria and anaerobic bacteria. Piperacillin/tazobactam is effective and well- tolerated in
patients with lower respiratory tract infections (LRTI), intra-abdominal infections, skin and soft
tissue infections, and febrile neutropenia. Piperacillin /tazobactam is likely to reduce overall
treatment costs of moderate to severe bacterial infections by increasing initial treatment success,
thereby reducing the length of hospital stay and the use of additional antibacterials. Although
more complete published data are needed to confirm these results. Present data regarding clinical
efficacy, bacterial resistance and costs would support the use of piperacillin /tazobactam as an
empirical first-line option in moderate to severe bacterial infections.

6. Fahmi Yousef Khan

This retrospective study was designed to involve all patients admitted to Hamad General
Hospital and prescribed piperacillin/tazobactam as an empiric therapy from January 1 to March
31, 2008. The medical records of such patients were retrospectively reviewed and studied. Our
study showed that there was an injudicious use of piperacillin/tazobactam at our hospital,
evidenced by the significant number of inappropriate empiric prescriptions and inappropriate
drug modifications, based on the results of microbial cultures and antibiograms.

10
7. Gin A (7)

Piperacillin-tazobactam is a beta-lactam/beta-lactamase inhibitor combination with a broad

spectrum of antibacterial activity that includes Gram-positive and –negative aerobic and
anaerobic bacteria. Piperacillin-tazobactam has recently been reformulated to include
ethylenediaminetetraacetic acid and sodium citrate; this new formulation has been shown to be
compatible in vitro with the two aminoglycosides, gentamicin and amikacin, allowing for
simultaneous Y-site infusion, but not with tobramycin. Multicenter, randomized, double-blinded
clinical trials have demonstrated piperacillin-tazobactam to be as clinically effective as relevant
comparator antibiotics. Clinical trials have demonstrated piperacillin-tazobactam to be effective
for the treatment of patients with intra-abdominal infections, skin and soft tissue infections,
lower respiratory tract infections, complicated urinary tract infections, gynecological infections
and more recently, febrile neutropenia.

8. Fedullo P

To determine the frequency and cause of inadequate initial antibiotic therapy with vancomycin
and piperacillin-tazobactam in patients with severe sepsis and septic shock in the emergency
department (ED), characterize its impact on patient outcomes, and identify patients who would
benefit from an alternative initial empiric regimen. Vancomycin and piperacillin-tazobactam
were an inappropriate antibiotic combination for approximately 24% of patients with either
severe sepsis or septic shock in the ED. Patients with known COPD, residence at a skilled
nursing facility, a history concerning for Clostridium difficult, and immunosuppression would
benefit from an alternative regimen. Future prospective studies are needed to validate these
findings.

9. Nowé P (8)

Piperacillin/tazobactam, at a dosage of 4 g/500 mg every 8 h, was administered intravenously to

217 patients with complicated urinary tract infections. The most common diagnosis was
pyelonephritis. The most common pathogen was Escherichia coli (47%) followed by
Pseudomonas aeruginosa (13%), and enterococci (8%). Among clinically evaluable patients,
86% (115/134) were cured or improved at the study endpoint and 14% (19/134) were clinical
failures or relapsed. Among bacteriologically evaluable patients, 85% (95/112) had a favorable

11
clinical response at endpoint. The bacteriological response rate was 73% (82/112) at endpoint.
Overall, 82% of all pathogens were eradicated. Therapy was associated with a low incidence of
side effects, and adverse experience were mild and of short duration.

10. Attivi D (9)

Piperacillin/Tazobactam is a time-dependent antimicrobial combination (beta- lactam/beta-

lactamase inhibitor) commonly used in the treatment of severe Gram- negative infections. The
optimization of its time-dependent bactericidal activity via continuous infusion could improve
clinical outcomes. Several studies have been realized on the relevance of a continuous infusion,
but, to date, no definitive position can be adopted on the matter and a well-designed randomized
controlled trial is warranted. In other articles, continuous infusion regimens are also more cost
efficient. This article is an update, including the most recent trials about this subject.

11. Schoonover LL (10)

To discuss the antimicrobial activity, pharmacokinetics, clinical efficacy, and adverse effect
profile of piperacillin/tazobactam, a new beta-lactam/beta-lactamase inhibitor combination. The
combination of tazobactam with piperacillin results in an antimicrobial agent with enhanced
activity against most beta-lactamase-producing organisms. Preliminary data indicate that
piperacillin/tazobactam has proven clinical efficacy in the treatment of a variety of infections,
especially polymicrobic infections.

12. Hellwig T, et al

Retrospective evaluation of all adult patients admitted to Sanford USD Medical Center over a 6
month period who received vancomycin +/- pip-tazo for more than 48 hours. AKI was defined as
an increase of serum creatinine > 0.5 mg/dL or a 50% increase from baseline. Of the 735
patients evaluated, the incidence of AKI for vancomycin alone, pip-tazo alone, and combination
of vancomycin + pip-tazo were 4.9%, 11.1%, and 18.6%, respectively (vancomycin vs. pip-tazo,
p = 0.014; vancomycin vs. combination, p = 0.005). When looking at just the ICU patients, a
similar result was seen. Incidence of AKI was 6.0%, 12.2%, and 21.2%, respectively
(vancomycin vs. pip-tazo, p = 0.279; vancomycin vs. combination, p = 0.005).

12
13. Moenster RP, et al

A retrospective cohort study was conducted of all diabetic patients with osteomyelitis treated
with vancomycin plus either pip-tazo or cefepime for at least 72 hours at a VA Medical Center
between January 2006 and December 2011. The primary outcome was development of AKI,
defined as an increase in SCr of 0.5 mg/dL or 50% of baseline. 139 patients met inclusion
criteria; 109 in the pip-tazo group and 30 in the cefepime group. In patients receiving
vancomycin + pip-tazo, 29.3% (32/109) developed AKI compared to 13.3% (4/30) treated with
vancomycin + cefepime (p=0.099). A multiple logistic regression analysis identified weight and
average vancomycin trough as the only significant predictors of AKI. The authors were unable to
detect a statistically significant difference in AKI between groups; however, power was not met.

14. EmanYoussif (11)

The appropriate use of broad-spectrum antibiotics, including appropriate de-escalation, is

essential to reduce the emergence of antibiotic resistance. In this study, we aimed to evaluate the
use of broad-spectrum antibiotics based on requests for cultures and de-escalation based on
sensitivity results of culture tests at tertiary care hospital. The use of broad-spectrum antibiotics
in surgical floors at a tertiary care hospital in Saudi Arabia was largely unjustified by culture-test
result. Interventions are needed to enforce culture and sensitivity test requests within 24 h of
starting the broad spectrum antibiotics therapy with further follow up to ensure appropriate de-
escalation and discontinuation whenever indicated.

15. Venu Gopal D et al (2014)

Conducted a prospective observational study in a tertiary care teaching hospital for six months
in general medicine and screened 555 antibiotic prescriptions. The study concluded that the
clinical pharmacists and Clinicians need to play vital role in minimizing the antibiotic problems
by conducting continual awareness programs regarding up-to-date prescribing guidelines in the
hospital and also minimizing the antibiotic resistance. The active participation of clinical
Pharmacists in the clinical ward rounds and documentation of Pharmacist observation on
prescription in patient folder is highly recommended for safety and drug monitoring.

13
16. M. Shamna et al (2014)

Carried out a prospective study in all departments for a period of one year to detect and analyse
adverse drug reaction of antibiotics in inpatients of a tertiary care hospital. The study concluded
that adverse drug reaction to antibiotics is getting common and it resulted in increased health
care cost and length of hospital stay. Therefore study suggest that health system should promote
the spontaneous reporting of adverse drug reaction to antibiotics , proper Literature Review
Department of Pharmacy Practice 22 documentation and periodic reporting to regional
pharmacovigilance centers to ensure drug safety.

17. Ehsan Elahi

This study was conducted to estimate the rationality of Piperacillin /Tazobactam utilization in
our hospital. The data came out with 76 prescriptions which were ordered for 73 patients. Main
indications for utilization of Piperacillin/ Tazobactam were febrile neutropenia (34/76; 44.73%).
Overall percentage of rational and irrational use of empiric therapy was (49/76; 64.47%) and
(27/76; 35.52%) respectively (P- value 0.001). Cases of wound/surgery/skin/soft tissue infections
(WSSSTI), abdominal infections and pneumonia and unit of palliative care, showed higher
trends of irrational prescribing. Microbiology data was positive for (40/76; 52.63%)
prescriptions. This study showed that there was an unwise use of Piperacillin/Tazobactam at our
hospital, as supported by significant proportion of irrationality in the view of empiric
prescriptions and drug modifications even in the presence of microbial culture results.

18. Bryson HM (12)

Combining tazobactam, a beta-lactamase inhibitor, with the ureidopenicillin, piperacillin,

successfully restores the activity of piperacillin against beta-lactamase-producing bacteria.
Tazobactam has inhibitory activity, and therefore protects piperacillin against Richmond and
Sykes types II, III, IV and V beta-lactamases, staphylococcal penicillinase and extended-
spectrum beta-lactamases. However, tazobactam has only species-specific activity against class I
chromosomally-mediated enzymes. Resistant organisms include some Citrobacter spp.,
Enterobacter spp., Serratia spp., Xanthomonas maltophilia and Enterococcus faecium. Consistent
with its in vitro activity, preliminary clinical data indicate that the fixed combination of
piperacillin/tazobactam (dose ratio 8:1) is effective in the treatment of moderate to severe

14
polymicrobial infections, including intra-abdominal, skin and soft-tissue and lower respiratory
tract infections.

19. Schønning K (13)

The antibiotic piperacillin/tazobactam has recently been licensed for use in Denmark.
Piperacillin/tazobactam combines a well known beta-lactam antibiotitic, piperacillin, and an
inhibitor of bacterial beta-lactamase, tazobactam. The combination of piperacillin and
tazobactam compared to piperacillin alone has an expanded antimicrobial spectrum, which
includes Klebsiellae, Escherichia coli, and Proteus vulgaris resistant to ampicillin, as well as
beta-lactamase-producing Staphylococcus aureus. As piperacillin in itself possesses
antimicrobial activity against streptococci, enterococci, and Pseudomonas aeruginosa, the
antimicrobial activity of piperacillin/tazobactam indicates that the combination may constitute an
alternative to third generation cephalosporins and carbapenems in the treatment of complicated
intra-abdominal infections infections in critically ill patients and for the empirical treatment of
acute neutropenic febrile patients, as indicated by clinical studies.

20. Charbonneau P (14)

One method of resistance to beta-lactam antimicrobials involves production of beta- lactamases,

enzymes that render the beta-lactam ineffective. Beta-lactamase inhibitors have been combined
with beta-lactam antibiotics to combat beta-lactamase producing organisms. One such agent,
piperacillin/tazobactam, has been shown to be safe and effective therapy for infections usually
treated with a combination of antibiotics such as polymicrobial and nosocomial infection, and
has been used for empiric therapy in cases of serious infection. A survey of the literature shows
that piperacillin/tazobactam is a safe and efficacious therapy for bacteremia as well as soft tissue,
intra-abdominal, and lower respiratory tract infections. When combined with an aminoglycoside,
it is also useful in the treatment of severe nosocomial respiratory infections.

21. File TM Jr

Piperacillin/tazobactam has excellent in vitro activity against the most pathogens involved in
skin infections. Two large multicentre studies recently evaluated the efficacy and safety of
piperacillin/tazobactam in the treatment of skin and soft tissue infections in patients in hospital.

15
The efficacy and safety of piperacillin/tazobactam (4 g/500 mg every 8 hours) have been
assessed in an open study in Europe. Among 120 evaluable patients, 93% were clinically cured
or improved. Only six patients were withdrawn from the study because of side effects.
Piperacillin/tazobactam seems to be both effective and safe in the treatment of skin and soft
tissue infections in patients confined to hospital.

22. Alzahrani M

Pipercillin-tazobactam is a frequently used antibiotic that has a broad spectrum of antibacterial

activity. The development of severe thrombocytopenia following the use of piperacillin-
tazobactam is unusual. Several mechanisms have been proposed for the pathogenesis of
thrombocytopenia in this setting which includes immune and non- immune causes. Multiple case
reports have shown the ability of piperacillin-tazobactam to cause drug-induced immune
thrombocytopenia, likely through formation of antibodies that recognize platelets in the presence
of soluble piperacillin. In both cases, thrombocytopenia improved immediately and dramatically
following withdrawal of piperacillin-tazobactam with initiation of steroids and intravenous
immunoglobulin’s, suggesting and immune related drug-induced thrombocytopenia.

23. Sanders WE Jr (15)

Piperacillin/tazobactam is the most recently approved combination of a beta-lactam agent with

an inhibitor of bacterial beta-lactamases. It has a broader spectrum than do preceding inhibitor-
drug combinations, and it is generally more potent. In terms of clinical and microbiological
outcomes, comparative studies have shown that piperacillin/tazobactam was comparable to
imipenem (1.0 g q8h) and to clindamycin plus gentamicin for intra abdominal infections, to
clindamycin plus gentamicin for infections of the skin and skin structures and pelvic tissues in
women, and to ticarcillin/clavulanate for skin and soft-tissue infections. Piperacillin/tazobactam
may be especially useful for the treatment of infections that are likely to be polymicrobial or to
be due to any one of an array of aerobic or anaerobic bacteria; this agent may also be useful in
situations where organisms with plasmid-mediated beta-lactamases have become problematic.

16
24. A. Simon (16)

Piperacillin-Tazobactam (Pip-Taz) is an evidence-based empirical treatment of febrile

neutropenia in adolescents and adults. No data are available in pediatric cancer patients &
lt; 25 months of age. In this retrospective, multicenter data survey, the analysis focuses on safety,
tolerance, and efficacy. The daily dose administered was 240 mg/kg given in three equally
divided doses. Data on 156 Pip-Taz treatment courses in 69 children & lt; 25 months from
five pediatric cancer treatment centers (2001–2005) were analyzed. The median duration of
treatment with Pip-Taz was 5 days (range, 1–23 days; 1–12 Pip-Taz courses per patient). Pip-Taz
was started on the first day of fever in 90% of all courses, in 6% in the first 72 h, and in 4% as
second- or third- line agent. Forty-five percent of all patients were neutropenic. In all patients,
the outcome was favorable independent whether Pip-Taz was given as monotherapy (42 courses;
27%) or in combination. Overall, Pip-Taz was well tolerated and discontinued due to adverse
events in only two patients who experienced non-life- threatening allergic reactions (skin rash
and wheezing).

25. Will Fry

Piperacillin/tazobactam is a commonly used antibiotic for the empirical treatment of severe

diabetic foot infections. One of the most feared complications of this drug is the development of
pancytopenia. The aim of this study was to determine whether the use of piperacillin/tazobactam
caused any hematological changes in patients admitted with severe diabetes-related foot
infections from a specialist multidisciplinary foot clinic. Specifically, looking at whether it
caused anemia, leukopenia, neutropenia, or thrombocytopenia. In this relatively small cohort,
pancytopenia did not occur. As such, piperacillin/tazobactam appeared to have a low risk of
adverse hematological outcomes and remains the treatment of choice for severe diabetes-related
foot infections.

26. Sanders CV Jr (17)

Investigators assessed the efficacy and safety of piperacillin/tazobactam therapy in a study of

patients with community-acquired lower respiratory tract infections and a study of patients with
nosocomial, severe lower respiratory tract infections. Piperacillin 4n g/tazobactam 500 mg was
given intravenously every 8 h to 193 hospitalized lower respiratory tract infection patients for a

17
minimum of 5 days. There was a favorable response rate of 97% and eradication of the causative
pathogen was documented or presumed in 93% of patients. Seventy-one intensive care patients
with severe lung disease received 4 g piperacillin/500 mg tazobactam intravenously every 6 h;
afterward they were given amikacin 7.5 mg/kg every 12 h. Minimum duration of treatment was 5
days. Therapy with piperacillin/tazobactam plus amikacin was well- tolerated, produced a 74%
favorable clinical response rate, and eradicated the responsible pathogen in 70% of patients.

27. Erasmo AA (18)

Treatment of intra-abdominal infections remains a challenge because of their polymicrobial

nature and associated mortality risk. Broad-spectrum empiric coverage is usually required. This
randomized study compared the efficacy and safety of intravenous piperacillin/tazobactam with
those of intravenous impanel/cilastatin in the treatment of 293 hospitalized patients with intra-
abdominal infection. These results suggest that the safety and efficacy of piperacillin/tazobactam
administered every 8 hours are equivalent to those of impanel/cilastatin administered every 6
hours for the treatment of intra-abdominal infections.

28. R Selvaraj et al (2015) (19)

Conducted a study to assess rational use of antimicrobials in the medicine outpatient department
of a teaching hospital. A total of 650 prescriptions were collected from the medicine OPD.
Prescriptions containing antimicrobial were grouped using the anatomical therapeutic chemical
(ATC) codes. They concluded that higher frequency of irrational antimicrobial prescriptions
suggests that antimicrobial restriction policies and a multidisciplinary effort to reduce usage are
urgently required.

29. Mohanraj Rathinavelu et al (2015) (20)

Conducted a study to evaluate the pattern of drug utilization in inpatients of general medicine
department. The data for study was obtained from 80 inpatients prescriptions and the DDD/100
bed days were calculated. The study indicates that there improvement in prescribing pattern of
antibiotics is possible by adhering to standard guidelines of treatment and restriction policies to
promote rational drug use.

18
30. Admane PD et al (2015) (21)

Carried out a study to assess the use of antimicrobials in tertiary care hospital. A prospective
cross sectional study was conducted in outpatient department over a period of 8 months and total
1942 prescriptions were collected. The study results analysed that the rational use of
antimicrobial agents is needed to control antibacterial resistance, side effects and reduced cost of
the treatment.

31. Greeshma Hanna Varghese et al (2015) (22)

Carried out a prospective observational study over a period of months and screened 1139
prescription to assess the patterns of drug utilization evaluation by WHO prescribing indicators
among special population in a tertiary care government teaching hospital retrospectively and
prospectively. The study concluded that it is necessary to avoid over prescription, follow
guidelines while prescribing drugs generic name, reduce the use of antibiotics after susceptibility
testing , to minimize the use of injections and to confine to the National essential drug list are
necessary to further improve rational use of drugs.

32. Maheshwari P et al (2015) (23)

Studied on the patient’s awareness on the rational use of antibiotics and its resistance by
developing a questionnaire. The study revealed that there was a very high consumption of
antibiotics mainly cephalosporin’s. Dispensing of antibiotics is very high in community
pharmacy despite of federal regulations. They proposed health education programmes should be
given to the patients regarding antibiotics.

33. Venu Gopal D et al (2014) (24)

Conducted a prospective observational study in a tertiary care teaching hospital for six months in
general medicine and screened 555 antibiotic prescriptions. The study concluded that the clinical
pharmacists and Clinicians need to play vital role in minimizing the antibiotic problems by
conducting continual awareness programs regarding up-to-date prescribing guidelines in the
hospital and also minimizing the antibiotic resistance. The active participation of clinical
Pharmacists in the clinical ward rounds and documentation of Pharmacist observation on
prescription in patient folder is highly recommended for safety and drug monitoring.

19
34. M. Shamna et al (2014) (25)

Carried out a prospective study in all departments for a period of one year to detect and analyse
adverse drug reaction of antibiotics in inpatients of a tertiary care hospital. The study concluded
that adverse drug reaction to antibiotics is getting common and it resulted in increased health
care cost and length of hospital stay. Therefore study suggest that health system should promote
the spontaneous reporting of adverse drug reaction to antibiotics , proper documentation and
periodic reporting to regional pharmacovigilance centers to ensure drug safety.

35. Mujtaba Hussain et al (2014) (26)

Conducted a prospective, observational study of antibiotic prescribing patterns at admission in

an open, mixed medical surgical, adult, ICU in a tertiary care hospital including 110 patients to
determine the group of antibiotics that are prescribed for various illnesses, average number used
and the cost of antibiotics per prescription. The study concluded that there is a need for
guidelines and protocol for treatment at all levels of health care especially with respect to
antibiotics.

36. Meher B. R. et al (2014) (27)

Conducted a prospective study in 200 patients in general medicine department to obtain

information about demographic profiles of patients, prevalence of infectious diseases and
prescribing pattern of antibiotics of a tertiary care teaching hospital. The study concluded that a
strict protocol for prescribers is required to promote rational use of antibiotics which would not
only prevent antibiotic resistance but also reduce the treatment expenditure in hospitals.

37. Shalini et al (2011) (28)

Studied on antibiotic sensitivity pattern in urinary tract infection at a hospital. The most
common samples isolated were Escherichia coli, Klebsiella, Pseudomonas, and Staphylococcus
aureus.E.coli showed high sensitivity to Amikacin and Nitrofurantoin. E.coli isolates were also
sensitive to Minocycline, showing a good utility of this drug for the treatment for patients with
urinary tract infections.

20
38. Mayadah Shehadeh et al (2011) (29)

Studied on the knowledge, attitudes and behavior regarding antibiotics use and misuse among
adults in the community of Jordan. The study showed that knowledge of when antibiotics should
be used, the efficacy of antibiotics as well as the risk of antibiotic resistance is inadequate in
study population. To prevent the inappropriate antibiotics consumption the health authorities had
to implement their regulations to prohibit the selling of Prescription Only Medicine (POM)
without prescription.

39. Estela Louro et al (2007) (30)

Studied on adverse events to antibiotics in inpatients of a university hospital. The aim of the
study was to evaluate the occurrence of adverse events to antibiotics in inpatients of a hospital.
The study results indicate that an inadequate knowledge on antibiotics or lack of information
about the patient at the time of prescription were the major factors involved in the occurrence of
adverse event

40. M.V. Srishyla, et al (2007) (31)

Conducted a study including 556 in patients to assess prescription on the basis of type of use,
specialty, site of infection, route of administration and the antimicrobial agent used. The study
showed that 56% of in-patients were prescribed antimicrobial agents and 44% of them received a
combination of antimicrobials and concluded that there is need of review of antimicrobial
prescribing practices.

41. David L Peterson (2005) (32)

Studied on the role of antimicrobials management programs in optimizing antibiotic prescribing

within hospital. The study was mainly done on patients receiving a broad spectrum antimicrobial
agent, fluroqunolones, vancomycin and cephalosporin for a period of 48 hours. It was found that
the spectrum was too broad on the basis of result of microbiological testing and the use of
vancomycin was unnecessary in certain cases.

21
42. Ravi Pathiyil Shankar et al (2003) (33)

Carried out a over a period of 3 month including 203 patients study to collect demographic
information, antibiotic prescribing patterns, and common organism isolated including antibiotic
sensitivity patterns. The study concluded that antibiotic resistance is getting common, therefore
formulation of policy for hospital antibiotic use and should organize educational programs
especially for junior doctors.

43. Sarah Mousavia et al (34)

Conducted a study named Drug Utilization Evaluation of Imipenem and Intravenous

Ciprofloxacin in a Teaching Hospital. The aim of study is to evaluate the drug utilization of
intravenous ciprofloxacin and imipenem, two of the broad spectrum antibiotics that consume a
significant proportion of our hospitals’ outlay, in different wards of a teaching hospital in Zabol.
During a 5 months period (December 2010 to May 2011), 263 patients who received imipenem
or intravenous ciprofloxacin were assigned to this study. Retrospective review of patient’s
records was carried out. Data were converted to Defined Daily Dose (DDD) and the ratio of
prescribed daily dose per DDD was calculated. Among these records, 100 patients received
either imipenem or ciprofloxacin. The ratio of prescribed daily dose to DDD was 1.5 for both
antibiotics. Almost all patients received empiric therapy in both groups. Only 13 patients (26%)
in ciprofloxacin group and 4 patients (8%) in imipenem group received their antibiotics
consistent with American Hospital Formulary System (AHFS) mentioned indication. Baseline
Blood Urea Nitrogen (BUN) and serum Creatinine were ordered for only 37 patients (74%) in
both groups with 15 abnormal results but dose adjustment performed just in one case with
decreased renal function. In conclusion, the majority of courses with both drugs were empirically
selected and continued and required lab tests for drug monitoring and dose adjustments were not
performed in most cases. Educational interventions, developing a local formulary and a strict
antibiotic prescribing policy for example by prior approval by an infectious disease consultant
can help significantly to overcome these problems.

44. Jennifer A. E. Samilski et al (35)

Conducted a review on moxifloxacin usage which has increased at Vancouver General Hospital.
It is unclear, however, whether the use of the drug is optimal according to its indication. They

22
hypothesized that moxifloxacin was over utilized and that opportunities existed to optimize its
use and study was designed to characterize moxifloxacin use in concordance with evidence-
based assessment criteria. An observational DUE was conducted over a 4-week period (from
February 17 to March 16, 2007) at Vancouver General Hospital, a 955-bed tertiary care hospital.
In patients who received at least one dose of moxifloxacin were enrolled. Evidence-based
assessment criteria were developed to evaluate the appropriateness of moxifloxacin use, and
PDA database was developed for data collection. The primary endpoint was the proportion of
moxifloxacin use for approved first-line indications. Results showed that Results: A total of 132
patients were included. Eighty-nine patients (67%) received moxifloxacin for first-line
indications, including community-acquired pneumonia (57%) and acute exacerbation of chronic
bronchitis (10%). Forty-three patients (33%) had alternative indications, primarily hospital-
acquired

45. Essema Tsechay biru et al (36)

Conducted a DUR on ciprofloxacin in the outpatient department of Boru Meda Hospital,

Objective of current study is to evaluate retrospectively of ciprofloxacin use from outpatient
medical records by using pre- set criteria in Boru Meda hospital. Data was collected from
January 18 to January 25, 2010 using appropriate data collection format. Results: Twenty six
(65%) patients were in the age group of 15 to 49 years and twenty (50%) were females. Thirty
eight (95%) and each of thirty seven(92.5%) cases were consistent with the Ethiopian National
Standard Treatment Guideline & drug formulary regarding indication, dose &
frequency of ciprofloxacin use in the outpatient department of Boru Meda hospital.
47.5%ciprofloxacin use has problem in duration of treatment . There were potential drug
interactions with the drug in 40% of the cases. 10% of ciprofloxacin use was against
contraindication. Conclusions: Due From the retrospective Drug Use Evaluation (DUE) study, it
was identified that there was inappropriate ciprofloxacin use in the outpatient department of
Boru Meda hospital even though the drug’s use regarding indications was a better performance
and dosing practices were almost appropriate as per the criteria used for the study (assuming that
there were no dose adjustments). There was a great problem concerning the duration of
ciprofloxacin drug therapy. Ciprofloxacin use along with potentially interacting drugs and
against contraindications was also another problem indicated in the study.

23
46. Juno J. Joel et al (37)

Carried out DRUG UTILIZATION STUDY OF FLUOROQUINOLONE ANTIBIOTICS IN A

UNIVERSITY TEACHING HOSPITAL. It is well known that antibiotics are prescribed
abundantly in hospitalized patients especially in critical care settings. The antibiotic usage will
also vary depends on the type of therapy, physicians perceptions and availability of the drug. Our
aim was to study the drug utilization pattern of Fluoroquinolone (FQs) antibiotics in medicine
and surgery wards of a tertiary care hospital. A total of 100 patients who received FQs were
enrolled in the study and the FQ utilization was measured in terms of DDD/100 bed days. Mean
± SD number of drugs prescribed and length of hospital stay were 8.23 ± 3.33 and 11.54 ± 7.57
respectively. Ciprofloxacin was the most commonly prescribed drug. Overall Fluoroquinolone
utilization was found to be 33.55 DDD/100 bed-days.

47. E.H. Shim et al (38)

Carried out Drug Use Evaluation on Ofloxacinn for the purpose of presenting the more
reasonable drug therapy. Fifty eight cases of patients, who had been treated with ofloxacin in
Korea University Kuro Hospital from September 1. 1994 to April 30. 1995 were reviewed
retrospectively. The applicated criteria for ofloxacin was " Criteria for Drug Use
Evaluation" established by ASHP report 1993. The results of the analysis show that 34
cases (59%) were met with the criteria for the justification of use, while 24 cases (41%) were
not. In critical indicators, several criteria including culture & sensitivity test, vital sign,
WBC monitoring and urinalysis were relatively well performed showing the accepted level
above 70%, while serum creatinine monitoring and administration time were infrequently
performed with low accepted level. Accepted level of ofloxacin was relatively high, while notice
about drug interaction and complications were low, which indicate that medication were being
performed under the insufficient information about each drug in clinic. The cased met with all
criteria were 13 cases (22%), all included of which were in internal medicine. From the results, it
could be concluded that medical staff should get the more information on general area of
antimicrobial agents include complication, duration of therapy and characteristics of each drugs.

24
48. Rattanaumpawan P et al (39)

Performed a review on Effectiveness of drug use evaluation and antibiotic authorization on

patients' clinical outcomes, antibiotic consumption, and antibiotic expenditures.
Effectiveness of drug use evaluation and antibiotic authorization on patients' clinical
outcomes, antibiotic consumption, and antibiotic expenditures .METHODS: Hospitalized
patients who were prescribed piperacillin/tazobactam, imipenem, or meropenem from August to
November 2007 were randomly allocated to antibiotic authorization group and no-authorization
group. The data on clinical outcomes, antibiotic consumption, and antibiotic expenditures of the
patients who received and who did not receive antibiotic authorization were compared.
RESULTS: The patients who received antibiotic authorization (512 prescriptions) had more
favorable clinical outcomes (68.9% vs. 60.5%, respectively, P < .01), shorter duration of target
antibiotics (7.5 days vs. 9.3 days, respectively, P < .01), shorter duration of all antibiotics
(12.7 days vs. 16.4 days, respectively, P < .01), and lower mortality because of infections
(29.4% vs. 35.4%, respectively, P=.05) than those who did not receive antibiotic authorization
(516 prescriptions). The costs of target antibiotics and all antibiotics in the authorization group
were much less than those in the no- authorization group. The annual antibiotic cost savings from
DUE and antibiotic authorization requirement could be extrapolated to US $862,704.
CONCLUSION: DUE and antibiotic authorizations are effective strategies in reducing antibiotic
consumption and antibiotic expenditures without compromising the patients' clinical
outcomes

49. Wasam Liaqat Tarar et al (40)

Conducted review on Drug Utilization Evaluation of Vancomycin in Teaching Hospitals of

Lahore.Vancomycin is the drug of choice in treating severe Gram-positive infections. Drug
utilization evaluation is an effective method to promote interventions that will endorse patient
outcomes and cost-effectiveness of the drug therapy. The objective of the study undertaken was
to observe the utilization of vancomycin in different teaching hospitals of Lahore. A data
collection form was designed and distributed among the healthcare providers gathering
information about its prescribing pattern. It was found that vancomycin was being used rationally
yet special precautions should be followed. The brand Vancomycin (76%) was used in majority
of the hospitals. 96% of the prescribers was well aware of its antibacterial spectrum. According

25
to 68% of prescribers the therapy was cost-effective. Redman’s syndrome was reported in 44%
of the cases. This study concludes that vancomycin is being used appropriately in right doses and
for right indications and is cost effective to the majority of patients. Yet the special precautions
must be followed such as prolonged infusion time and measuring the plasma drug concentration
after administration. ADRs and the possibility of any untoward medical occurrence or the risks
of drug related morbidity and mortality can be avoided under the supervision of a pharmacist.

50. Kiran Nagaraju et al (41)

Conducted review on drug utilization evaluation of cephalosporins, macrolides, quinolones

antibiotics in Kims hospital. Drug Utilization Review (DUR), or Drug Use Evaluation (DUE),
which is recognized as an effective tool for detecting and improving drug use and patient care.
The aim of study is to determined the prescribing pattern of cephalosporins, macrolides and
quinolones antibiotics and to monitor and report the adverse drug reaction and drug interaction if
any. Methodology: The study was conducted in KIMS Hospital, Bangalore. It is a 1200 bedded
tertiary care teaching, super specialty hospital, providing specialized health care services to all
strata of people in and around Bangalore. It is a hospital based prospective and retrospective
study conducted for a period of six months from January to June 2013, to study the utilization
pattern of cephalosporins, macrolides and quinolones antibiotics. We have attempted to observe
the utilization pattern of cephalosporins, macrolides and quinolones in our hospital. Result:
Among160 patients included during the study, we observed that 114(71.25%) patients were been
prescribed with cephalosporins, which was high compared with other class of antibiotics
followed by 38(23.75%) patients were been used with quinolones and the remaining eight (5%)
patients were on macrolides antibiotics. Conclusion: We concluded from our observation that the
utilization pattern of cephalosporins was seen more in patients compared with quinolones and
macrolides antibiotics.

51. Getasew Amogne Ayinalem et al (42)

Performed a review on Drug Use Evaluation of MCeftriaxone in Medical Ward of Dessie

Referral Hospital, North East Ethiopia. The aim of the study is Drug use evaluation which is a
performance improvement method that focuses on evaluation and improvement of drug use
processes to achieve optimal patient outcomes. The objective of this study was to evaluate the

26
rational use of ceftriaxone in Medical ward of Dessie referral Hospital, Dessie-Ethiopia.
Retrospective systematic study was used to assess rational use of ceftriaxone. The study was
conducted by reviewing medication records of 316 patients, who received ceftriaxone during
hospitalization at Medical ward of Dessie referral Hospital from December 30, 2011 to January,
2013. A systematic sampling method was used to select inpatient prescriptions in this ward with
ceftriaxone and patient cards were located based on the medical record number on the
prescription papers. Data was collected by using structured format and evaluated against WHO
criteria for drug use evaluation as per standard treatment guideline of Ethiopia. Most patients
were dosed as 2 g/day (79.4%). The duration of therapy was found to be high in the range 2-7
days (51.69%). Ceftriaxone was mainly used as pneumonia treatment (38.8%). Maintenance
fluids were the most commonly co- administered medications with a frequency of 62.16%. The
use of ceftriaxone was appropriate only in 170 cases (55.8%) for the justification of use. Most of
inappropriate uses were seen in terms of duration during treatment of pneumonia followed by
frequency for the treatment of meningitis. Consistency of prescriber to the national standard
treatment guideline was found to be low. To improve rational use and prevent the development
of resistance; prescribers should adhere to the national standard treatment guideline.
Intensification of short term trainings and antibiotic control systems are some of the possible
solutions the hospital has to do. ceftriaxone therapy does not meet the current STG of Ethiopia.

52. Tariku Shimels et al (43)

Study on evaluation of Ceftriaxone utilization in internal medicine wards of general hospitals in

Addis Ababa, Ethiopia: a comparative retrospective study. Objectives: The irrational use of
reserved antimicrobials, such as ceftriaxone, is one of the global public health issues particularly
to low income countries like Ethiopia, leading to high costs of treatment or therapeutic failure.
The purpose of the present study, thus, is to evaluate the appropriateness of ceftriaxone
utilization in the medicine wards of general hospitals in Addis Ababa, with reference to the
standard treatment guideline of Ethiopia for general hospitals. Methods: An institution based
retrospective cross sectional study design was conducted in the internal medicine wards of Hayat
and Zewditu Memorial hospital from 20 January to 20 February, 2014. Medication records of all
patients who were admitted and prescribed with ceftriaxone during the previous one year to the
study period were evaluated in reference to the Ethiopian Standard Treatment Guideline (STG

27
2010) for general hospitals. Results: The proportion of patients who received ceftriaxone was
59.3 % and 49 % in the public & the private hospital, respectively. Pneumonia, meningitis
and sepsis were the common diagnoses in which ceftriaxone was prescribed in both hospitals.
Maintenance fluids were the top ranked co prescribed drugs in either hospital. Only 48.9 % in the
public hospital and 44.6 % of records in the private hospital showed overall ceftriaxone use
compliance to the guideline. Days of hospital stay was associated with appropriateness of
ceftriaxone therapy. Conclusions: Even though ceftriaxone is one of the most commonly
prescribed drugs in both hospitals, appropriateness of its use, according to the Ethiopian standard
treatment guideline, was less than expected. This was so mainly from its indication and duration
of therapy. Increasing the duration of hospital stay, however, showed to improve the
appropriateness of ceftriaxone utilization.

53. Bambang Subakti Zulkarnain et al (44)

Conducted review on the adherence to prescribing guidelines: a drug utilization evaluation of

tramadol. Objective: To evaluate the adherence to the Guidelines for Prescribing Tramadol as a
potent narcotic analgesic. Methods: A drug utilization evaluation was performed to identify
whether the prescribing of tramadol meeting the guideline criteria. The primary objective was to
assess whether the tramadol was prescribed appropriately i.e. clinical situations, oral doses, and
whether it was used with any other concurrent opioids. A secondary objective was to monitor
either side effects and/or drug interactions occurred. The primary outcome measure was the
number of prescriptions meeting current guidelines. Results: A total of 75 patients on tramadol
were identified. The adherence was identified for 52% of tramadol prescriptions. Those were not
complying guidelines (48%) mostly from patients not under the care of the Acute Pain
Management Service (APMS). Failing to prescribe in the appropriate clinical situations and the
use of concurrent opioids were the two most common reasons. No serious reported adverse
events of tramadol were found even for the patient exceed intravenous daily dose. Likewise,
there were some patients on tramadol and other drugs that could possibly interact. Conclusions:
The improvement for prescribing tramadol under guidelines criteria at RBH particularly those
not under the care of the APMS through education to medical staff should be addressed. The
issue of potential drug interactions and adverse events associated with tramadol should not be
left unaware.

28
54. Alemayehu Sileshi et al (45)

Conducted review on Evaluation of ceftriaxone utilization in medical and emergency wards of

Tikur Anbessa specialized hospital. The aim of this study was to evaluate prospectively the
appropriateness of ceftriaxone use in medical and emergency wards of Tikur Anbessa
Specialized Hospital. Methods: A prospective cross- sectional study was conducted by reviewing
medication records of patients receiving ceftriaxone during hospitalization at Tikur Anbessa
Specialized Hospital between February 1 and June 30, 2014. Drug use evaluation was conducted
to determine whether ceftriaxone was being used appropriately based on six criteria namely
indication for use, dose, frequency of administration, duration of treatment, drug-drug
interaction, culture and sensitivity test. The evaluation was made as per the protocol developed
from current treatment guidelines. Results: The total of 314 records of patients receiving
ceftriaxone was reviewed. The prescribing rate of ceftriaxone was found to be very high (58 %
point prevalence). Ceftriaxone use was empiric in 274 (87.3 %) cases. The most common
indication for ceftriaxone use was pneumonia; observed in 110 (35.0 %) cases. The most
common daily dosage, frequency of administration and duration of treatment with ceftriaxone
were 2 g (88.9 %), twice-daily (98.4 %) and 8-14 days (46.2 %), respectively. Inappropriate use
of ceftriaxone was observed in most of cases (87.9 %), the greatest proportion of which was
attributed to inappropriate frequency of administration (80.3 %), followed by absence of culture
and sensitivity test (53.2 %).Conclusion: This study revealed that the inappropriate use of
ceftriaxone was very high in the medical and emergency wards of Tikur Anbessa Specialized
Hospital. This may lead to emergence of resistant pathogens which in turn lead to treatment
failure and increased cost of therapy. Therefore, adherence to current evidence-based guidelines
is recommended.

55. Sandra Walker et al (46)

Carried out drug utilization of named An Assessment of Linezolid Utilization in Selected

Canadian Provinces Linezolid is approved for the treatment of designated infections caused by
methicillin-resistant and -susceptible Staphylococcus aureus and vancomycin-resistant
Enterococcus faecium. Its objective is to characterize linezolid utilization since its launch in
Canada in 2001.Demographics, antimicrobial regimens, and clinical and resource utilization data
for linezolid-treated patients were collected retrospectively by hospital pharmacists at nine

29
tertiary care hospitals in four provinces. Statistics describing linezolid utilization were calculated
and the appropriateness of use was assessed according to a treatment algorithm based on
recommendations of the Infectious Diseases Pharmacy Specialty Network in 2001.Results
revealed that Ninety-nine linezolid courses were prescribed for 103 infections in 95 patients
(mean age 57.8 years, 52.6% male) with an average length of hospital stay of 40.6 days. Fifty-
three per cent of patients had an allergy to at least one antibiotic other than linezolid. The major
use of linezolid was for treatment of skin and soft tissue infections (32.0%), followed by
bacteremia (15.5%). The most prevalent pathogen was methicillin-resistant S aureus, identified
in 44.7% of infections. Linezolid was primarily prescribed as the oral form following other
intravenous anti-infectives (55.6% of courses) for an average duration of 14.4 days. The rate of
appropriate utilization was 53% (range 25% to 75% by site). In 93.5% of courses deemed
inappropriate, recommended first-line therapies were not attempted before linezolid.Conclusions
Linezolid was prescribed appropriately in approximately one-half of cases reviewed. The rate of
appropriate utilization is similar to those rates reported in other Canadian antibiotic reviews.

56. Ebrahim Salehifar et al (47)

Conducted review on Meropenem at a tertiary care university hospital: A report from Northern
Iran The inappropriate use of antibiotics remains the primary factor in antimicrobial drug
resistance. In this study, we evaluate the use of meropenem in surgical/medical wards of Imam
Khomeini Tertiary Referral Hospital, Sari, Iran. This retrospective observational study was used
to assess rational use of meropenem. The study was conducted by reviewing medical records of
100 admitted patients who received meropenem during March 2013 to January 2014.Meropenem
was prescribed most frequently in Intensive Care Unit (22%), and pneumonia was the most
common diagnosis (35%). The third-generation cephalosporins were the most frequently
prescribed antimicrobials after meropenem (53%). In 21% of the patients, imipenem was
changed to meropenem. Most of the inappropriate uses were seen in terms of frequency of
meropenem use (34%), followed by duration of meropenem therapy (28%).Comparing our study
results has shown higher inappropriate use. It is necessary to take action to improve prescribing
habit in order to reduce the unnecessary usage of antibiotic thus enhance rational antibiotic use.

30
METHODOLOGY:

Aims, objective And Plan of Work

Aim:
To assess the usage of piperacillin and tazobactum at a tertiary care center in Hyderabad
compared to the indications for piperacillin and tazobactum use and standard treatment
guidelines and provide recommendations to improve rational use of piperacillin and tazobactum
at these hospitals and reduce the development of further antibiotic resistance, prevent ADRs
associated with the drug, and to reduce the economic burden on the patient with inappropriate
use.
Objective:
 To analyse the pattern of piperacillin and tazobactum use among patient categories
identified by age.
 To identify the illnesses most frequently treated with piperacillin and tazobactum.
 To determine whether piperacillin and tazobactum was appropriately prescribed in
respect of dose, dose frequency, and dose duration.
 To identify areas in which further information and education was needed by health care
provider.
 To evaluate reason for stopping (discontinue) the drug is based on guide line or not.
 To assess whether the indication of piperacillin and tazobactum is on par with standard
guidelines or not.
 To assess the frequency of ADRs associated with the drug use.
 To assess the potential and actual Drug-Drug interactions associated with piperacillin
and tazobactum.

WORK PLAN:
Piperacillin/tazobactam, sold under the brand names piptaz among others, is a combination
medication containing the antibiotic piperacillin and the β-lactamase inhibitor tazobactam. The
combination has activity against many Gram-positive and Gram-negative bacteria including
Pseudomonas aeruginosa. It is used to treat pelvic inflammatory disease, intra-abdominal
infection, pneumonia, cellulitis, and sepsis. It is given by injection into a vein. Now a days

31
piperacillin and tazobactum is irrationally prescribed globally particularly in India. Hence it
facilitates the development of resistant strains to piperacillin and tazobactum. It is more prone to
cause complications (ADR’s) like fever, neuropenia and it is usually contraindicated in patients
with a history of allergic reactions to any of the penicillins, cephalosporins, or β­lactamase
inhibitors.
Study Design:
A retrospective evaluation of piperacillin and tazobactum usage patterns was carried out at a
tertiary care hospital for the period of 3 months corresponding to the dates 1-1-2018 to 31-3-
2018 for conducting the evaluation process we had followed the standard guide lines formulated
by WHO.
 Step 1 : Responsibility
The hospital where the study was conducted don't have DTCs and moreover the
study is for academic purposes and hence the responsibility lied entirely with the
students and guide.
 Step 2. Scope of Activities
During the process of evaluation, the prescriptions were analyzed for correct
indication, correct dose, frequency, ADRs, Drug-Drug interactions, and contra-
indications.
 Step 3.Criteria
Standard prescribing guidelines for piperacillin/tazobactam as formulated by
FDA.
 Step 4. Establishing Threshold
Taking into consideration, the prescribing habits (KAP) of the doctors at these
centers, the indicators are assigned with a threshold of 90-100 %.( 3)

Indicator Criteria Threshold%

Indication Appendicitis (complicated by rupture or abscess) and
peritonitis caused by piperacillin­resistant, β­lactamase
producing strains of Escherichia coli or the following
members of the Bacteroides fragilis group: B. fragilis, B. 90
ovatus, B. thetaiotaomicron, or B. vulgatus. The individual

32
 members of this group were studied in less than 10 cases.
Uncomplicated and complicated skin and skin structure
infections, including cellulitis, cutaneous abscesses and
ischemic/diabetic foot infections caused by
piperacillin-resistant, β­lactamase producing strains of
Staphylococcus aureus. Postpartum endometritis or pelvic
inflammatory disease caused by piperacillin-resistant,
β­lactamase producing strains of Escherichia coli.
Community acquired pneumonia (moderate severity only)
caused by piperacillin­resistant, β­lactamase producing
strains of Haemophilus influenza. Nosocomial pneumonia
(moderate to severe) caused by piperacillin-resistant,
β­lactamase producing strains of Staphylococcus aureus
and by piperacillin/tazobactam-susceptible Acinetobacter
baumanii, Haemophilus influenza, Klebsiella pneumonia,
and Pseudomonas aeruginosa (Nosocomial pneumonia
caused by P. aeruginosa should be treated in combination
with an aminoglycoside
Dose and Piperacillin and Tazobactam for Injection should be
frequency and administered by intravenous infusion over 30 minutes. The
duration usual total daily dose of Piperacillin and Tazobactam for
Injection for adults is 3.375 g every six hours totaling 13.5 g
(12 g piperacillin/1.5 g tazobactam).
Nosocomial Pneumonia: Initial presumptive treatment of 95
patients with nosocomial pneumonia should start with
Piperacillin and Tazobactam for Injection at a dosage of 4.5
g every six hours plus an aminoglycoside, totaling 18 g (16 g
piperacillin/ 2 g tazobactam)
Renal impairment patients:
For patients on hemodialysis, the maximum dose is 2.25 g
every twelve hours for all indications other than nosocomial

33
 pneumonia and 2.25 g every eight hours for nosocomial
Pneumonia. Since hem dialysis removes 30% to 40% of the
administered dose, an additional dose of 0.75 g Piperacillin
and Tazobactam for injection (0.67 g piperacillin/0.08 g
tazobactam) should be administered following each dialysis
Period on hemodialysis days. No additional dosage of
Piperacillin and Tazobactam for injection is necessary for
CAPD patients.
Pediatric patients:
For children with appendicitis and/or peritonitis 9 months of
age or older, weighing up to 40 kg, and with normal renal
function, the recommended Piperacillin and Tazobactam for
injection dosage is 100 mg piperacillin/12.5 mg tazobactam
per kilogram of body weight, every 8 hours. For pediatric
patients between 2 months and 9 months of age, the
recommended Piperacillin and Tazobactam for injection
dosage based on pharmacokinetic modeling, is 80 mg
piperacillin/10 mg tazobactam per kilogram of body weight,
every 8 hours

contraindications Piperacillin and Tazobactam for Injection is contraindicated 100

in patients with a history of allergic reactions to any of the
penicillins, cephalosporins, or β­ lactamase inhibitors.
Medicine Drug Interactions Aminoglycosides The mixing of
interactions beta-lactam antibiotics with aminoglycosides in vitro can
result in substantial inactivation of the aminoglycoside.
However, amikacin and gentamicin have been shown to be
compatible in vitro with piperacillin and tazobactam in 90
certain diluents at specific concentrations for a simultaneous
Y-site infusion. (See DOSAGE AND ADMINISRATION.)

34
The inactivation of aminoglycosides in the presence of
penicillin-class drugs has been recognized. It has been
postulated that penicillin-aminoglycoside complexes form;
these complexes are microbiologically inactive and of
unknown toxicity. Sequential administration of piperacillin
and tazobactam with tobramycin to patients with normal
renal function and mild to moderate renal impairment has
been shown to modestly decrease serum concentrations of
tobramycin but does not significantly affect tobramycin
pharmacokinetics. When aminoglycosides are administered
in combination with piperacillin to patients with end stage
renal disease requiring hemodialysis, the concentrations of
the aminoglycosides (especially tobramycin) may be
significantly altered and should be monitored. Since
aminoglycosides are not equally susceptible to inactivation
by piperacillin, consideration should be given to the choice
of the aminoglycoside when administered in combination
with piperacillin to these patients. Probenecid administered
concomitantly with Piperacillin and Tazobactam for
Injection prolongs the half-life of piperacillin by 21% and
that of tazobactam by 71%.Vancomycin No pharmacokinetic
interactions have been noted between Piperacillin and
Tazobactam for Injection and vancomycin. Heparin
Coagulation parameters should be tested more frequently and
monitored regularly during simultaneous administration of
high doses of heparin, oral anticoagulants, or other drugs that
may affect the blood coagulation system or the thrombocyte
function. Vecuronium Piperacillin when used concomitantly
with vecuronium has been implicated in the prolongation of
the neuromuscular blockade of vecuronium. Piperacillin and
Tazobactam for Injection could produce the same

35
 phenomenon if given along with vecuronium. Due to their
similar mechanism of action, it is expected that the
neuromuscular blockade produced by any of the
non-depolarizing muscle relaxants could be prolonged in the
presence of piperacillin. (See package insert for vecuronium
bromide.) Methotrexate Limited data suggests that
co-administration of methotrexate and piperacillin may
reduce the clearance of methotrexate due to competition for
renal secretion. The impact of tazobactam on the elimination
of methotrexate has not been evaluated. If concurrent therapy
is necessary, serum concentrations of methotrexate as well as
the signs and symptoms of methotrexate toxicity should be
frequently monitored.
Outcome Negative culture/Improved symptomatology
No treatment failure 90

 Step 5. Data collection and organization.

The data was collected in data collection forms and organized according to
the threshold percentage. A total of 65 case sheets were obtained that contained
piperacillin and tazobactum in the prescription between the period of 1-1-2018 to 31-3-
2018.
 Step 6. Data analysis.
Microsoft Excel 2007 was used for statistical data analysis.
 Step 7 .Develop recommendations and Action plan:
Based on the results obtained, problematic areas were identified and appropriate
recommendations were developed and shared with the concerned doctors and hospital
authorities.

36
Results

A total of 65 case sheets were obtained that contained piperacillin and tazobactum as one
of the drug in the treatment plan during the course of their stay at hospital. The 65
number of cases were obtained from the following dates 1-1-18 to 30-3-18. Month wise the
number of case sheets that contains piperacillin and tazobactum are as follows

Months nephrology gynecology pediatrics gastroenterology pulmonology Total

jan 24 2 3 3 1 33

Feb 13 2 2 1 2 21

March 8 1 2 1 0 12

Piperacillin and tazobactum usage percentage in each department:

nephrology gynecology paediatrics

gastroenterology pulmonology

3%
9%
9%
6%

73%

37
DEPARTMENTS:

nephrology 45
pediatrics 7
gynecology 5
gastroenterology 5
pulmonology 3

Piperacillin and tazobactum usage in each department:

50
45
40
35
30
25
20
15
10
5
0

38
Age wise the number of case sheets that contain piperacillin and tazobactum are as follows

AGE NO.OF CASES

0-10 4

11-20 4

21-30 7

31-40 14

41-50 8

51-60 21

61-70 5

71-80 0

81-90 2

91-100 0

39
Piperacillin and tazobactum usage according to age:

druguse
25

20

15

10 druguse

Sex wise the number of case sheets that contain piperacillin and tazobactum are as follows

Males = 42
Female = 23
Indication wise number of case sheets that contain piperacillin and tazobactum areas
follows:
Nephrology indications:
Hemodialysis – 12
Peritoneal dialysis – 7
Septic shock – 11
IJV -12
Pcnl + djs – 1
PCN -1
Obstructive uropathy – 3

40
Ckd – acute deterioration – 19
AKI – 10
LRIT-1
UTI – 1
Cellulitis – 1
Renal biopsy -1
Diabetic foot infection – 1

Pediatrics:
Blunt injury with pneunomediastinum – 1
Endotracheal tube – 1
Preoperative prophylaxis, of biliary tree surgery – 1
Central venous catheter with fever – recent abdominal surgery -1
Tracheitis -1
Nasocomial pneumonia -1
Post operative purulent wounds -1
Gynecology:
Pelvic peritonitis -1
Bartollins abscess -1
Abdominal hysterectomy -1
UTI -1
Acute salpingitis -1

Gastroenterology:
Foleys catheter -1
EVL -1
BILIARY STENT REMOVED, HILAR STRICTURE -1
Post adjunct chemotherapy -1
Acute cholangitis -1

Pulmonology:

41
 Rt – synpneumonic effusion, CAP, kochs -2
Pulmonary hypertension -1

Age v/s duration of piperacillin and tazobactum therapy is as follows:

Age Min(days) Max(days)

0-10 1 7

11-20 1 19

21-30 3 14

31-40 1 19

41-50 3 19

51-60 1 15

61-70 3 18

71-80 0 0

81-90 4 5

91-100 0 0

42
 Duration:

20
18
16
14
12
10
8
6
4
2
0
0-10 11-20 21-30 31-40 41-50 51-60 61-70 71-80 81-90 91-100

Age v/s dose per day

Age Min (g) Max(g)

0-10 1500mg 2.5g

11-20 2.25g 3g

21-30 2.25g 5g

31-40 2.25g 5g

41-50 2.25g 4.5g

51-60 2.25g 4.5g

61-70 2.25g 5g

71-80 0 0

81-90 2.25g 2.25g

91-100 0 0

43
Dose:

0
0-10 11-20 21-30 31-40 41-50 51-60 61-70 71-80 81-90 91-100

44
DISCUSSION:
Piperacillin/tazobactam, sold under the brand names piptaz among others, is a combination
medication containing the antibiotic piperacillin and the β-lactamase inhibitor tazobactam. The
combination has activity against many Gram-positive and Gram-negative bacteria including
Pseudomonas aeruginosa.
THREATS OF RESISTANCE DEVELOPMENT TO PIPERACILLIN AND
TAZOBACTUM

The development of resistance by microorganisms is of global concern. This is because

microorganisms that were susceptible to some anti-infective agents have now become resistant.
Unfortunately, irrational prescribing is a global problem. Studies on medicine prescribing in
India have concluded that much of it is irrational. Making a prescribing decision is vital in the
prevention of morbidity and mortality. The physician’s prescribing decision is the result of input
from patients, commercial sources, professional colleagues, academic literature, and government
regulations. Ineffective use of these sources of information can result in a wide variety of
prescribing errors. Medicine utilization review is the most common and structured approach used
to examine patterns of medicine use and to determine levels of appropriateness in prescribing.
Medicine usage reviews are essential in order to establish the extent of rational and irrational
prescribing and to deliver better healthcare services. Antimicrobials, like any other medicines,
may be used inappropriately.

A prescriber may choose an inappropriate type of antimicrobial, taking into account

the clinical condition, resistance patterns and cost. Continuing antimicrobial misuse leads not
only to poor patient outcome, unnecessary adverse reactions and wasted resources, but also to
emerging resistance of bacteria to antimicrobials. Antimicrobials can also be very expensive, and
in most facilities they constitute a major portion of the drug budget. The phenomenon of
resistance is seen not only in bacteria and mycobacteria (multidrug resistant TB, for example),
but also in protozoal infections (resistance to chloroquine as an antimalarial) and viral infections
(HIV and antiretroviral). This study provides the data on the use of piperacillin and tazobactum
at a tertiary care centre in Hyderabad. The considered parameters are age, gender, indication,
dose, frequency, duration of therapy, contraindications and drug interacting with piperacillin and
tazobactum.

45
Drug utilization pattern according to gender:

A total of 65 cases of piperacillin and tazobactum use were identified between the period from
1/1/18 - 30/3/18 patient. The distribution of cases on gender basis is males (35.38%) and females
(64.61%).

Piperacillin and tazobactum usage according to gender

druguse

50
40
30 druguse
20
10
0
male female

druguse

80.00%
60.00%
druguse
40.00%
20.00%
0.00%
male female

46
Drug utilization pattern according to age:

The age range was between 5yrs to 85yrs. The usage pattern of piperacillin and tazobactum
among various age groups are as follows: of 0-10 (6.15%), 11-20 (6.15%), 21-30yrs (10.76%)
and 31-40 (21.53%), 41-50 (12.30%), 51-60 (32.30%), 61-70 (7.69%), 71-80 (0%), 81-90
(3.07%) and 91-100 (0%). As per STGs, the percentage of piperacillin and tazobactum used
among it has’nt met the established criteria, and the rest met the criteria.

Piperacillin and tazobactum usage percentage according to age:

druguse
91-100
81-90
71-80
61-70
51-60
41-50 druguse
31-40
21-30
11-20
0-10
0.00% 10.00% 20.00% 30.00% 40.00%

47
90

80

70

60

50

40

30

20

10

0
1 3 5 7 9 11 13 15 17 19 21 23 25 27 29 31 33 35 37 39 41 43 45 47 49 51 53 55 57 59 61 63 65

48
Drug utilization pattern according to indication:

In our study, the percentage of piperacillin and tazobactum indicated in the conditions are:-

Culture sensitivity test of Piperacillin and tazobactum:

culture sensitivity test

nephrology pulmonolgy gastroenterology gynecology paediatrics without culture test

1% 3% 5% 2%
0%

89%

Nephrology indications:
 Hemodialysis – 12(18.46%)
 Peritoneal dialysis – 7(10.76%)
 Septic shock – 11(16.92%)
 IJV -12(18.46%)
 Pcnl + djs – 1(1.53%)
 PCN -1(1.53%)
 Obstructive uropathy – 3(4.61%)
 Ckd – acute deterioration – 19(29.23%)
 AKI – 10(15.38%)
 LRIT-1(1.53%)
 UTI – 1(1.53%)
 Cellulitis – 1(1.53%)
 Renal biopsy -1(1.53%)

49
 Diabetic foot infection – 1(1.53%)

Piperacillin and tazobactum indications:

1.53%
Hemodialysis
Peritoneal dialysis
15.38% 18.46%
Septic shock
IJV
10.76%
Pcnl + djs
29.23% PCN
16.92% Obstructive uropathy
Ckd – acute deterioration

18.46% AKI
4.61% LRIT
1.53%
1.53%

1.53% 1.53% Post operative purulent

wounds
Pelvic peritonitis
1.53% 1.53%
Bartollins abscess

Abdominal hysterectomy
1.53% 1.53%
Acute salpingitis

Foleys catheter
1.53% 1.53%
EVL
1.53% 1.53%
BILIARY STENT REMOVED,
HILAR STRICTURE

50
Pediatrics:
 Blunt injury with pneunomediastinum – 1(1.53%)
 Endotracheal tube – 1(1.53%)
 Preoperative prophylaxis, of biliary tree surgery – 1(1.53%)
 Centralvenous catheter with fever – recent abdominal surgery -1(1.53%)
 Tracheitis -1(1.53%)
 Nasocomial pneumonia -1(1.53%)
 Post operative purulent wounds -1(1.53%)

Gynecology:
 Pelvic peritonitis -1(1.53%)
 Bartollins abscess -1(1.53%)
 Abdominal hysterectomy -1(1.53%)
 UTI -1(1.53%)
 Acute salpingitis -1(1.53%)

Gastroenterology:
 Foleys catheter -1(1.53%)
 EVL -1(1.53%)
 BILIARY STENT REMOVED, HILAR STRICTURE -1(1.53%)
 Post adjunct chemotherapy -1(1.53%)
 Acute cholangitis -1(1.53%)

Pulmonology:
 RT – synpneumonic effusion, CAP, kochs -2(1.53%)
 Pulmonary hypertension -1(1.53%)

51
 Rt – synpneumonic
effusion , CAP , kochs
1.53% 1.53%
Pulmonary hypertension

Out of 65 cases 65 (99%) has met the established criteria, they are as per STGs. Illness most
frequently treated with piperacillin and tazobactum is ckd with acute deterioration (29.23%) .

Drug utilization pattern according to dose, ROA, Frequency, and the potential for
interaction

In this research, the criteria of appropriateness of piperacillin and tazobactum use at the dose,
dose frequency, dose duration were

1. The dose of piperacillin and tazobactum based on indication and duration given was
in all the indications studied, they met the benchmark requirement of 95%. Therefore
piperacillin and tazobactum was used appropriately so far as dose was concerned.
2. Out of 65 cases, dose frequencies were eight hours and 24 hours in 6cases (9.23%) and
59cases (90.76%) respectively.
3. Dose durations were mostly inappropriate for all the justified indications studied.

52
Frequency:

TID

OD

0.00% 20.00% 40.00% 60.00% 80.00% 100.00%

According to STGs for hemodialysis patients average duration of therapy is

7 to 14 days, results showed minimum of three days and maximum of fourteen days were given,
on an average the results are appropriately meeting the STGs (100%).

As per standards, the duration of piperacillin and tazobactum in hemodialysis is

given for nineteen days hence duration of therapy fails to meet the standards. There would be a
lot of carriers in the system and the disease would continue to be transmitted from person to
person. Hence, it facilitates the development of resistant strains to piperacillin and tazobactum.

4. Drug interactions

The potential for piperacillin and tazobactum interaction with microlide antibiotics .Out of
65cases (100%), cases (87.69%) are reported without any potential interaction and cases (9.93%)
reported with interaction.

Drug interacting with piperacillin/tazobactam are

no interactions 87.69%
Doxycycline 3.01%
Azithromycin 3.46%
Clarithromycin 3.46%

53
Piperacillin and tazobactum interactions

drug interactions
no interactions doxycycline azithromycin clarithromycin

3% 4%
3%

90%

Drug utilization pattern according to contraindication

In our study, out of 65 cases, all cases met the threshold of 100% as per STG’s.

Outcomes: 89% drug is given without culture test. Dose, duration as per STG’s.patients
improved symatomatically and infection resolved almost cases. 33.84% are non indicated.

Piperacillin and tazobactum duration of therapy thresholds measured:

piperacillin and tazobactum is given less than 53.84%

thershold limit

piperacillin and tazobactum is given according to 23.07%

thershold limit

piperacillin and tazobactum is given more than 23.07%

thershold limit

54
Descriptive Statistics:

SAMPLE
PARAMETERS SIZE MIN MAX MEAN SD VARIANCE MEDIAN
AGE 65 5 85 44.1846 ±18.67 348.77 48
DURATION 65 1 22 7.6 ±5.31 28.275 7
FREQUENCY 65 1 3 2.8153 ±0.583 0.340 3
DRUGINTERACTIONS 65 0 1 0.1230 ±0.33108 0.10961 0

CONCLUSIONS AND RECOMMENDATION

55
CONCLUSION:

All patient folders evaluated with regards to HD,SEPTIC SHOCK, PNEMOMEDIATINM etc
were found to meet the standard criteria appropriate for piperacillin and tazobactum use with
respect to dose, and dose frequency.

However, in the case of dose duration the evaluation was found to be largely inappropriate for all
the justified indications. In addition,33.84% of piperacillin and tazobactum use for unjustified
indications was noted. This means that piperacillin and tazobactum has been deviated from
standard treatment guidelines hence it facilitates the development of resistant strains to
piperacillin and tazobactum and of no use in the near future, and it also effect the patient
economically.

RECOMMENDATION:

Health care providers must be periodically updated with the national standard treatment
guidelines. It is further recommended that the hospital’s management attention be drawn to the
draw backs observed regarding the inappropriate use and duration of piperacillin and
tazobactum, so that specific interventions could be initiated to improve its use for excellent
outcomes. Following the implementation of the interventions, another DUE should be conducted
to determine the level of adherence to the acceptable standards and its impact on patient
outcomes.

56
Name:

ANNEXURE

57
Ip no:
Department
Weight:
DOA:
DOD:
Diagnosis:
Indication:

Dose(mg):
Route : Oral IV
Frequency : OD BD TDS QID
Other(specify)
Date started _/_/2018 Date ended_/_/2019
Reason for ceasing : infection resolved
Side effects
Others (specify)

Contraindications:
Drug interactions: For
Culture and sensitivity test: m 1:
Outcome achieved:
Data collectors Name and Sign:

Form 2:

Patient name: IP/Reg .No.

58
Age: Sex: Weight: Dept:

Diagnosis:

Comments on Criteria and Threshold:

Dose, ROA , and Frequency:

Comments on Threshold of Dose, ROA, and Frequency:

Total Duration of piperacillin/tazobactam therapy:

Comments on Threshold of Duration of therapy:

Contraindications and comments on Threshold:

Drug interactions and comments on Threshold:

Outcome and comments on Threshold:

REFERENCE:

59
1. http://apps.who.int/medicinedocs/en/d/Js4882e/8.5.html drug and Therapeutics Committees -
Practical Guide (2003; 155 pages)

2. www.who.int/.../tbs/11-PG_Drug-Use-Evaluation_final-08.pdf

3. https://www.accessdata.fda.gov prescribing guidelines piperacillin/tazobactam

4 .Piperacillin /tazobactam: an updated review of its use in the treatment of bacterial infections.
Perry CM, Markham A. Drugs. 1999 May; 57(5):805-43. Review.
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