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ANTIBIOTIC STEWARDSHIP PROGRAMME

co ordinated interventions to measure appropriate use of antibiotics

to help control infections by drug resistant pathogens in hospitals

Study Supported By Tamil Nadu State Planning Commission

Cancer Institute (WIA), Adyar, Chennai - 600020

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ACKNOWLEDGEMENT

Cancer Institute(WIA) & Rajiv Gandhi Government General Hospital would like to thank

Tamil Nadu State Planning Commission for supporting this study.We thank the members of the

Multidisciplinary core team who have contributed directly or indirectly towards the completion of this

study.

Principle Investigators:

• Mrs. V. Varalakshmi

Head, Microbiology

Cancer Institute(WIA), Chennai

• Dr.ThasneemBanu

Professor, Microbiology

Rajiv Gandhi General Hospital, Chennai

Antibiotic resistance has the ability of transforming the simplest of treatments

into complicated ones

Misuse of antibioticshas led to Antibiotic Resistance which is a global challenge today. The increase in hospital infections and antibiotic resistance is the direct result of non-compliance to basic guidelines and non-compliance to disciplined practice of hospital hygiene. Reliance on antibiotics without hospital hygiene is bound to fail” - Dr. V. Shanta, Chairman Cancer Institute(WIA)

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TABLE OF CONTENTS

Cancer Institute(WIA)

Summary………………………………………………………………………................................5

Introduction & Background.......................................................................................................6 - 12

Method…………………………………………………………………………................................13 - 15

Microbiologist Strategy…………………………………………………........................................16 – 28

Clinicians Strategy………………………………………………………........................................29 - 38

Pharmacists Strategy…………………………………………………….......................................39 - 48

Stewardship metrics………………………………………...........................................................49

Results & Impact of Study…………………………………………………....................................50 - 52

Conclusion…………………………………………………………………………...........................53

Reference………………………………………………………………………….............................54 - 55

Rajiv Gandhi Hospital……………………………………………………………................56

Methods & Materials……………………………………………………………...........................…58 - 60

Results……………………………………………………………………………..........................…61 - 63

Antibiotic Consumption………………………………………………………...........................……64 - 71

Discussion................................................................................................................................72 - 74

Summary…..........................…………………………………………………………………………75

Reference…………………….........................………………………………………………………76

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TABLES & FIGURES

1. Time of Antibiotic Resistance

2. Bacterial enzymes promote resistance

3. Global Antibiotic Consumption

4. Antibiotic stewardship

5. Bundle care check list

6. Data on Prevalence of MDR

7. Tracking sheet

8. Drug Formulary

9. Antibiotic monitoring

10. Defined Daily Dose

11. Dose Optimization

12. Antibiotic Expenditure

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SUMMARY

The discovery of antibiotics has lead to improved outcomes in healthcare as early as 20th century

whereby infections that were fatal became curable(1). However continued antibiotic use promotes the

development of resistance which is a natural phenomenon and bacteria often develop resistance due to

selective pressure. Resistance has become a major public health problem and is often attributed to

inappropriate use of antibiotics (2), leading to emergence of multidrug-resistant pathogens and

increased morbidity and mortality. The problem of resistance has existed for a long time however it is

gaining importance recently because of the lack of new antimicrobial agents in research and

development.

Global antibiotic consumption between 2000 and 2010, grew by more than 30 percent, from

approximately 50 billion to 70 billion standard units and corollary of this increase in consumption is

increase in resistance(3). For many years, the emergence of resistance in bacteria caused little alarm,

because new antibiotics were developed, but now the pipe line is dry urging us to use the currently

available antibiotics much more wisely(4).

Without effective antibiotics for prevention and treatment of infections, medical procedures such as

organ transplantation, chemotherapy, major surgery etc would be compromised. Also in recent years

antibiotic resistance has become a major public health threat, with increased prevalence of multidrug

resistant bacterial infections that are resistant to one or more classes of antibiotics. These highly

resistant organisms deserve special attention in hospitals as they are associated with increased lengths

of stay, costs, morbidity and mortality, hence clinicians are forced to use broad spectrum antibiotics &

older antibiotics like colistin with limited pharmacodynamics guidance to treat seriously ill

patients.Resistant bacteria are found in humans, animals and environment and poor infection control

and inadequate sanitary conditions encourage their spread easily(5). Infection control is a powerful

means to control spread of multi drug resistant bacterial infections(6).

An effective approach to improving antibiotic use in hospitals is an organized program known as

antibiotic stewardship which involves a systematic approach to optimizing the use of antibiotic.The

current need is to develop a antibiotic stewardship programme which would reduce indiscriminate use

of antibiotics. Antibiotic stewardship and hospital infection control are two broad strategies which have

been employed to contain the problem of resistance and infections.

The integration of antibiotic stewardship into hospital infection control is the most effective way to slow

down resistance. Successful programs have been shown to improve the appropriateness of antibiotic

use and reduce resistance rates & mortality. A coordinated action by hospitals, policy makers, decision

makers in both public and private hospitals is vital to tackle growing resistance. It is time we take

immediate measures to conserve the currently available antibiotics.

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INTRODUCTION AND BACKGROUND OF THE STUDY

Antibiotic resistance is a greatest public health threat today and resistant infections lead to increased

health care costs, morbidity and mortality.Resistance is often attributed to inappropriate use of

antibiotics, leading to emergence of multidrugresistant pathogens(7). Antibiotic selection pressure kills

the susceptible bacteria and helps in selective replication of drug resistant bacteriathat multiply

abundantly and entirely replace the susceptible bacterial population. This results in treatment failure or

ineffective management of such infected patients. Resistance has gained importance because of the

rapid emergence of multidrugresistant bacterial infections for which there is no effective antibioticsas

there is paucity of newerdrugs in research and development(8,9).As soon as a new drug is put to use,

resistant bacteria start emerging, several enzymes that deactivate the drug are produced by bacteria.

Time of Antibiotic ResistanceBacterial enzymes promote resistance

Antibiotic Discovery Resistance

Penicillin 1945 1950

Tetracycline 1950 1956

Erythromycin 1953 1960

Gentamycin 1967 1973

Vancomycin 1972 1982

Imipenem 1985 1994

Penicillin 1950

Broad-spectrum 1960

Cephalosporin 1970

Carbapenem 1985

• Penicillinase 1952 • Beta lactamases 1960-70 • ESBL 1980-90 Carbapenemase 1999

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Resistance Mechanism

Bacteria break the drug by any one of the following modes:

Modifying the site where antibiotic attaches

Reducing antibiotic entry

Pushing the drug out

Producing – Penicillinase, cephalosporinase, carbapenamace

This limits the treatment options

This limits the treatment options

• Cefepime

• Beta Lactum Inhibitor drugs CS / PT

• Carbapenem

• CS / PT

• Carbapenem

• Colistin

• Tigecycline

CARBAPENAMASE

1.KPC - KB, EC

2.MBL - Acineto / Pseudo

ESBLKB, EC

Amp C Pseudo, EC

TREATMENT OPTIONS

Major groups of enzymes involved in hydrolyzing the drug are:

AmpC - class C Cephalosporinase ESBL - Extended Spectrum Beta Lactamase Carbapenamase 3. KPC - Class A 4. Metallo β lactamase - Class B

Major groups of enzymes involved in hydrolyzing the drug are:

AmpC - class C Cephalosporinase ESBL - Extended Spectrum Beta Lactamase Carbapenamase 1. KPC - Class A 2. Metallo β lactamase - Class B

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In the early days of antibiotics, drug development meant that even when resistance developed, a new

drug was always available. 14 new classes of antibiotics were introduced between 1935 and 2001,

however the pace of antibiotic development has slowed markedly in the past 15 years, we are

eventually left without any effective antibiotic(10).Increasing resistance is due to widespread, irrational

and indiscriminate use of antibiotics and this haslead to the use of second or thirdline drugs which are

less effective against MDR bugs.

Use antibiotics appropriately until pharma companies can catch up

Declining FDA Antibiotics New US FDA drugs - 2015

Failed in India

• Ceftazidime/avibactum

• Ceftolozane/tazobactum

They were found to be

ineffective – GNB when

tested against laboratory

isolates at CMC

Resistance mechanism seen

in U.S, Europe are different

in India

To address the lack of antimicrobial agents in the research and development pipeline, the Infectious Diseases Society of America (IDSA) launched the “10 x ’20 initiative,” a call to action to develop10 new antimicrobial drugs by the year 2020(11,12).

Strategies to Address Antimicrobial Resistance Act (STAAR)—was introduced in May 2009 to encourage the development of new antimicrobial agents as well as strengthen federal antimicrobial resistance surveillance, prevention and control.

The wise use of antimicrobial agents is a key strategy in the Centers for Disease Control and Prevention Campaign to Prevent Antimicrobial Resistance in Healthcare Settings.

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Antibiotic use is a major driver of resistance. In 2010, India was the world’s largest consumer of antibiotics for human health at 12.9 x 109 units (10.7 units per person). The next largest consumers were China at 10.0 x109 units (7.5 units per person) and the US at 6.8 x109 units (22.0 units per person). Seventy-six percent of the overall increase in global antibiotic consumption between 2000 and 2010 was attributable to BRICS countries, i.e., Brazil, Russia, India, China, and South Africa. The % change in antibiotic consumption ranges from 41% to 80% in India and South America.

Antimicrobial Prescribing Facts: The 30% Rule

➤~ 30% of all hospitalized inpatients at any given

time receive antibiotics

➤ Over 30% of antibiotics are prescribed

inappropriately in the community

➤ Up to 30% of all surgical prophylaxis is

inappropriate

➤~ 30% of hospital pharmacy costs are due to

antimicrobial use

➤10-30% of pharmacy costs can be saved by

antimicrobial stewardship programs [Hoffman et al., 2007; Wise et al., 1999; John et al., 1997]

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Worldwide increases were significant for two “last-resort” antibiotic classes: carbapenems- whichare a class of beta-lactams effective against Gram-negative infections, (approximately 40 %) and polymixinswhich are last-resort drugs used to treat multidrug-resistant infections, (approximately 13%). The growth in retail carbapenem sales was particularly steep in India, Pakistan, and Egypt.ESBL and Carbapenamace producers has been increasing overtime in India(13). New Delhi metallo-β-lactamase (NDM) enzymes, first reported in 2008, are now found worldwide. With diminishing options for treating multidrug resistant infections, colistin use is increasing and resistance to colistin is on the rise(14). Gram-positive infections are also a problem, increasing rates of methicillinresistant Staphylococcus aureus (MRSA) in clinical isolates from various studies in India have been documented. Pathogens: Klebsiella pneumonia, E coli, Pseudomonas aeruginosa, Acinetobacter, Staphylococcus aureus, Enterococcus faeciumetc are the most troublesome bacterial pathogens in hospitals because they often are resistant to currently available antibiotics and cause hospital acquired infections.

Overthecounter access to antibiotics is a problem, Central Drugs Standard Control Organization (CDSCO) implemented Schedule H1 in India in 2014 to prevent over the counter sales of important antibiotics. The H1 list includes 24 antibiotics, such as third- and fourth-generation cephalosporins, carbapenems, antituberculosis drugs, and newer fluoroquinolones. Schedule H1 specifies that the drugs covered by it carry a prominent Rx symbol in red and contain a box with red borders with a printed warning on their packaging. In 2016 Union Health Minister launched a campaign called "Medicines with the Red Line" to raise awareness.Moreover, drugs included in Schedule H1 can only be sold with the prescription of a registered medical practitioner and require that pharmacist maintain a separate register with the patient’s name, contact details of the prescribing doctor, and the name and dispensed quantity of the drug and may be subjected to sudden checks by government officials.

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What are the factors fuelling Resistance?

Self medication

Consuming left over drugs

Prescribing antibiotics for viral infections

Unregulated Non – therapeutic use

Over the counter sales of antibiotics without prescription

Antibiotics are used in poultry, swine and cattle to promote growth of these farm animals. In India, the use of antibiotics in pre-mixed feed for livestock is going up a lot, we are not even aware that antibiotics are going inside our system, Significant amounts of the antibiotics used for animals eventually find their way into the environment, particularly in ground water and in soil resulting in antibioticresistant bacteria spread causing human disease.

Poultry industries in Tamil Nadu displaying Antibiotic free chicken for sale

Growing antibiotic use in the animal sector is resulting in a greater selection of pathogens and is being driven by increased demand for meat and poultry(15,16). The extreme growth in consumption of chickens is primarily the result of the expansion of this sector in India alone, where areas of high consumption (30 kg per km2) are expected to grow 312% by 2030. Currently, India does not have regulatory provisions for the use of antimicrobials in cattle, chickens, and pigs raised for domestic consumption. All efforts should be taken by government to phase out antibiotic growth promoters from livestock especially when these drugs are medically important.

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ANTIBIOTIC STEWARDSHIP An effective approach to improving antimicrobial use in hospitals is known as Antibiotic stewardship. Antibiotic stewardship refers to coordinated interventions designed to improve and measure the appropriate use of antibiotics – right dose, right duration of therapy, and right route of administration(17). The primary goal of stewardship is to raise awareness among health care workers about the escalating problem of resistance in hospitals and community. There is evidence to show that the reduction in the use of antibiotics also brings down the incidence of resistance(18). It then becomes possible to reduce antibiotics use without compromising patient safety. Antibiotic stewardship is the effort to improve antibiotic prescribing by clinicians. Hospitals can influence antibiotic use with improved, prudent antibiotic prescription, as up to 50% of prescribed antibiotics may be inappropriate or even unnecessary(19). To curb the increasing resistance, hospitals should start antibiotic stewardship programs as quality initiatives for infection control.

Good antibiotic stewardship involves selecting an appropriate drug and optimizing its dose and duration to cure an infection while minimizing toxicity and conditions for selection of resistant bacterial strains. Compliance with hand hygiene and other infection prevention and control measures is vital for controlling antibiotic resistance(20). Implementation of an effective stewardship requires a multidisciplinary approach with core team staff working together to achieve good outcomes. It is recommended that the core team should include a clinician, pharmacist, microbiologist and an infection control specialist. These programs help clinicians improve the quality of patient care by reducing hospital infection rates and antibiotic resistance thereby decreasing treatment failures significantly(21,22).IDSA has issued “Combating Antimicrobial Resistance: Policy Recommendations to Save Lives”,Pediatric Infectious Diseases Society (PIDS) has developed a stewardship programme for children. PIDS and SHEA have partnered to form a joint antibiotic stewardship committee to address inpatient antibiotic use, outpatient antibiotic use, antibiotic stewardship in special populations, education involving antibiotic use, and research on antibiotic use and stewardship. Antibiotic Stewardship Programscan both optimize the treatment of infections and reduce adverse events associated with antibiotic use.

De escalation

Right Drug

Right Duration

Right Dose

Stewardship is a way to optimize use of

antibiotics.

Stewardship is a method to measure

consumption.

Stewardship is smart use of antibiotics &

conserves antibiotics.

Stewardship helps patients receive

appropriate antibiotic following ‘4 D’s of

optimal therapy.

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Method &Study design

Correlation between antibiotic misuse and increasing antibiotic resistance is widely acknowledged. In recent years there is increased prevalence of infections caused by multidrug resistant organisms like MDR GNB – ESBL, CRE, MRSA, VRE etc that are associated with increased lengths of stay, costs, morbidity and mortality. The Asia Pacific SMART study 2009 showed high prevalence of Amp C, ESBL, &CREin India.

Asia-Pacific SMART Study Report India leading the way…

The study question?

Will disciplined & appropriate use of antibiotics help tackle growing resistance

Rationale of the study:

Antibiotic resistance has become a major public health problem and is often

attributed to inappropriate use of antibiotics, leading to emergence of

multidrugresistant pathogens and increased morbidity and mortality.

The problem of resistance has existed for a long time, however it is gaining

importance recently because of the paucity of new antimicrobial agents in

research and development.

Studies have shown that hospital based programs dedicated to improving

antibiotic use referred to as “Antibiotic Stewardship Programs, can both

optimize the treatment of infections and reduce adverse events associated

with antibiotic use.

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Objectives and Scopes:

1. The primary objective is to have uniform standard guidelines and policies for control of infections in hospitals as per accreditation standards.

2. To formulate a multidisciplinary infection control committeethat ensures implementation of infection control policies.

3. To initiate and execute Antibiotic Stewardship Program, form a multidisciplinary core team - clinicians, microbiologists, pharmacologists & nurses working together to achieve good outcomes for optimal patient care.

4. To establish formulary restriction and approval systems especially for broad‐spectrum antibiotics.

Methodology: Twohospitals, Cancer Institute(WIA) and Rajiv Gandhi Government General Hospital were included in the study and Cancer Institute(WIA) was the resource centre for the study.A core Antibiotic Stewardship Team was formed consisting of 1 senior clinician from medical, surgical & radiation oncology departments, 1 microbiologist, 1 pharmacist and 1 infection control nurse. Both hospitals implemented the policies and procedures laid down & compliance was monitored by checklist and audits.The hospitals generated Microbiology data - infection rates of hospital acquired infections namely blood stream infection, surgical site infection, urinary tract infection and respiratory tract infection &incidence of multidrug-resistant bacterial infection and monthly reports were presented to the Infection Control Committee in each of the hospitals. The Steward team of each hospital conducted prospective audit of the interventions in the hospital, tracked the compliance in their hospitals & reviewed their data monthly.

Role of each of the core team members

1. Clinician - Supervises therapeutic guidelines, antimicrobial restriction policies, gives second opinion on higher-end antibiotic usage.

2. Microbiologist – Accurate reporting of susceptibility, dissemination of antibiograms to clinicians for better selection of empirical therapy, surveillance of hospital acquired infections and tracking the incidence of multidrug-resistant bacterial infection.

3. Pharmacist - Collects and analyzes consumption of antibiotics and expenditure, measures antibiotic use as defined daily dose, enforce the approval system of restricted antibiotics, play a role in processing medication orders, keeps track on the usage of higher-end antibiotics.

4. Infection control nurse - Liaise between microbiology department & wards for control of hospital acquired infections, monitors implementation of infection control measures, collects data on nosocomial infections & assist stewardship team to evaluate outcomes.

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We understand that Hospital infection control & Antibiotic stewardship are 2 strategies which have been employed globally to contain the problem of resistance.

Many guidelines like WHO, CDC, IDSA etc have shown that “Antibiotic Stewardship Programs” can both optimize the treatment of infections and reduce adverse events associated with antibiotic use. In India, awareness about antibiotic stewardship for controlling the escalating problem of antibiotic resistance has to be increased. We felt the need to develop a workable antimicrobial stewardship programme suitable to our institute practices, which would reduce inappropriate antibiotic use, enhance clinical outcomes, reduce healthcare costs etc.

We started our study in 2015 end, Cancer Institute(WIA) being the resource center and Rajiv Gandhi Government General Hospital(RGGGH) as the participating center.

.

• Primary objective uniform policies for infection control

.

• Multidisciplinary ICC emphasizing stringent guidelines on unit specific antibiotic use

.

• Organized Surveillance – OT, ICU, BMT, Wards, personnel

2 Academic Institutes, CI and RGGGH – keeping in mind, both having

different patient population, changes in infection control practices

We tailored stewardship interventions to our institute practice

Infection Control

Antibiotic Stewardship

Antibiotic Resistance Control

We followed a 3 pillar approach to limit resistance

1. Improve sanitation, Hand hygiene

2. Active surveillance of infections to prevent the transmission

3. Optimise the use of antibiotics

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Core Team Member

Microbiologist strategies

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Microbiologist are integral members of the core team because of the close relationship between antibiotic stewardship and infection control efforts. The microbiologist involves in dissemination of antibiotic profile to doctors for better selection of empirical therapy, surveillance of hospital acquired infections and tracking the incidence of multidrug resistance bacterial infectiona. Laboratory plays a critical role in the timely identification of microbial pathogens and the performance of susceptibility testing. A major role of the microbiology laboratory is to provide antibiotic susceptibility testing data on bacterial isolates to guide clinicians in their choice of antibiotic. They work closely with the attending clinician, infection control nurse & pharmacist in the management of patients with infections.

Strategies followed at Microbiology laboratory to help clinicians with rational antibiotic

prescribing:

Early identification of the pathogen and susceptibility using automated microbiology system

keeping in mind that clinicians must strike a early administration of appropriate antibiotic

knowing the likely pathogen & resistance percentage.

We developed a system to recognize trends in antibiotic resistance and to report them promptly to doctors, to help with rational antibiotic prescribing - direct, personalized communication to clinicians / duty nurses was done for MDR infections.All this was apart from the reports typed in the hospital information system.

Monthly surveillance of antibiotic resistance was done & discussed in infection control meetings, this helped clinicians know their unit specific local data.

We prepared cumulative antibiogram which summarizes the susceptibility of microorganisms to antibiotics helpful in formulating antibiotic policy.

Auditing compliance with care bundles CLABSI, SSI, UTI & VAP was done.

Care bundles like SSI, CRBSI, UTI, VAP, are groups of evidence-based best practices that improve

care, with a greater improvement achieved when the practices are used as a group within a specific

time frame than when each practice is used alone. The use of care bundles ensures a systematic

approach so that the delivery of care is consistent for all patients based on established local evidence-

based guidelines.

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Auditing compliance with care bundles serves as a means for performance monitoring of processes of

care that can lead to quality improvement. Care bundles have been used successfully to reduce

Hospital acquired infection (30,31)

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Automated culture methods available at the Institute gave results in a shortened incubation

time, this helped clinicians to quickly review the antibiotics started empirically

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Targeted surveillance was regularly carried out:

Site-oriented surveillance: Priorities will be to monitor frequent infections with significant impact in

mortality& morbidity.

Common priority sites are:

Bloodstream infections

Surgical site infections

Ventilator associated pneumonia

Urinary tract infections

Infection with multiple-drug resistant bacteria Unit -oriented surveillance: surveillance of high risk units such as OT, BMT, ICU, POWcarried out

periodically.

1.No: of central lineassociated blood stream infections (A)

No: of patients on Central line (B)

No: of Central line days in that month (sum of B)

Blood stream infection Rate QI 26= A/Sum of B X 1000

2.No: of ventilator associated pneumonia (A)

No: of ventilated patients (B)

No: of ventilator days in that month (sum of B)

Ventilator associated pneumonia rate QI 26 = A/Sum of B X 1000

3.No: of surgical site infections (A) Total No : of surgeries performed (B)

Surgical Site Infection rate = Sum of A in a given month/Sum of B in that month x 100

4.No: of urinary catheter associated UTIs (A)

No: of patients on urinary catheter (B)

Urinary Tract infection Rate QI

25 = A/Sum of B X 1000

Quality Indicator - Incidence of BSI, VAP, UTI / 1000 days & SSI / 100 surgerieswas captured on a

monthly basis to analyse the rates & trends in infection. Corrective / preventive action - CAPA done

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ANTIBIOTIC RESISTANCE

AMPICILLIN R

PIPERACILLIN R

AZTREONAM R

CEFEPIME R

CEFTAZIDIME R

CEFTRIAXONE R

AMIKACIN S

PIP / TAZO S

CEF/SULB S

IMIPENEM S

MEROPENEM S

ESBL PROFILE CARBAPENAMASE PROFILE

ANTIBIOTIC RESISTANCE

AMPICILLIN R

PIPERACILLIN R

AZTREONAM R

CEFEPIME R

CEFTAZIDIME R

CEFTRIAXONE R

AMIKACIN R

PIP/TAZO R

CEF/SULB R

IMIPENEM R

MEROPENEM R

0

10

20

30

40

50

60

ICU WARD OPD

43.7

53.9

16.5

41.6

37.8

9.6

KLEB E COLI

• ESBL producing Kleb >50% ESBL frequent in Urine & Sputum

• 16% of OP isolates are ESBL Carbapenamase 21%

Prevalence of ESBL / CARBAPENAMASE

0

5

10

15

20

25

BLOOD PUS URINE SPUTUM

7.5

11.3

22.5

13.6

3.1

5.7

9.4

4.1

ESBL CARBAPENAMASE

They are encoded on extra chromosomal DNA – cross infection is easy

Prevalence of ESBL / CARBAPENAMASE producing bacteria at the Institute are increasing

and treatment options are limited

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What is worrying?

High MDR prevalence in the community, patients are coming with the bug.

Infected or colonized patients move between hospitals.

Commensals like Acinetobacter, Burkholderia, Alkaligens,Stenotrophomonas are now

becoming killer organisms.

Clinicians are forced to use antibiotics with unfavourable toxicity, last resort antibiotics,Colistin

and Tigecyclineare the choice.

Treatment options are limited for neutropenic patients with greater attributable mortality.

CDDPE study 2013 on Global resistance trends in 5 continents has shown that India and South

Africa are facing acute resistance problem.

CDDPE study 2013 Global AMR Trends - GNB

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Institutional data was compared with bench mark data from other hospitals and found to be similar or sometimes much better, especially with higher end antibiotic resistance, reason may be the antibiotic approval system strictly followed by all units. An ICMR study in 2015, published high resistance to high end antibiotics reported from 4 teaching institutes in India as shown as below.

ICMR Study Published:November 18, 2015

At the Cancer Institute, the resistance percentage is comparable with CMC / JIPMER and much better

than AIIMS / PGI.

Treatment Guidelines for Antimicrobial Use in

Common Syndromes,

Indian Council of Medical Research (ICMR) 2017

CANCER INSTITUTE DATA – Klebsiella profile comparison

0

10

20

30

40

50

60

70

80

CI CMC JIPMER PGI AIMS

31

37

49

14

63

53

45

73 7377

34

39

44

56

70

I PT AK

Pip/Taz resistance is increasing. CI – 53% of

isolates are Resistant

Amikacin is comparable to Imipenem

AIIMS – High R rates especially Carbapenem 63%

PGI – Carb R is low

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ICMR Study Published:November 18, 2015

CANCER INSTITUTE DATA – Pseudomonas profile comparison

0

10

20

30

40

50

60

70

CI CMC JIPMER PGI AIMS

19

25

48

17

54

31

25

58

44

67

02

0 0

34

I PT AK CL

Alarming resistance rate - colistin

At CI – nil

Imipenamresistance 25% to 54%

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High Colistin resistance reported from AIIMS & CMC among Acinetobacter.Colistin resistance at

Cancer Institute is NIL, showing the disciplined use of the drug only when really needed.

ICMR Study Published:November 18, 2015

Cef/Sul & Pip/Taz

0

10

20

30

40

50

60

32

2321

58

42

37

CS PT

0

5

10

15

20

25

30

35

27

11 10

35

18

10

I ME

Imipenem Vs Meropenem

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Colistin and Tigecycline must be carefully used, remember the black box warning issued to Tigecycline.

Colistin & Tigecycline

0

10

20

30

40

50

60

70

80

90

100

0 0 0 2

100

0 0

100

15

0

CL TGL

Tigecycline – Black Box warning

issued by FDA – 2010

due to increased risk of death

We planned monitoring and analysis of antibiotic usage in hospital and devised a tracking sheet

consisting of - Microbiology data, Pharmacist data and Clinicians notes all in one, this was for our

patients in ICU both medical, surgical, pediatric& induction wards.

Tracking and reporting clinician antibiotic prescribing - audit and feedback, can guide changes in

practice and help in improving antibiotic prescribing.

As the study was going on we realized Stewardship is not policing.

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28

WHO DDD

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Core Team Member Clinician strategies

30

Clinician supervises therapeutic guidelines, antimicrobial restrictions policies, gives second option on higher end antibiotic usage and ensures dose optimization for life saving antibiotics used in treating MDR infections, enforces the approval system of restricted antibiotics and ensures safe use of medication to reduce adverse events. It is now imperative for the clinicians to play a greater role in conserving the efficiency of the currently available agents for which containment of resistance is required. Clinicians carry out the following:

Review of indication for antibiotic and compliance with antibiotic policy.

Review appropriateantibiotic choice, dose, route and duration.

Review drug allergies& adverse events.

Review therapy based on culture results.

At the Institute we have a hospital formulary – containing an overview of indications and favourable

antibiotic treatment& stringent policy for use of broad‐spectrum antibiotics with approval for restricted

antibiotics by consultants.

Drug Formulary at the Institute

CANCER INSTITUTE (W.I.A) - DRUG FORMULARY

2016Generic name Route Dose Storage condition Drug interaction Adverse reaction

Amoxycillin and

potassium clavulanate

Inj 1.2g

Store below 25°C.

Allopurinol may reduce renal

tubular secretion of amoxicillin

thus increasing the serum levels

of amoxicillin. Concurrent use

may reduce the efficacy of oral

contraceptives.

Anaphylactic reaction with CV collapse esp

with parenteral use.

Linezolid

Iv 300mlInfusion: store at 25°C.

Protect from lightMAOI; avoid concurrent use or

use within 2 wk of stopping

another MAOI to reduce risk of

hypertensive crisis.

Reversible myelosuppression including

anaemia, leukopenia, pancytopenia and

thrombocytopenia (particularly if using > 10-

14 days), transient ischaemic attacks, renal

failure, stevens-johnson syndrome.

Imipenem cilastatin

Inj 500 mg

Store at 15-30°C.

Concurrent admin with

probenecid may increase the

half-life of cilastatin. Increased

risk of generalised seizures

when used concurrently with

ganciclovir.

Stevens-johnson syndrome, toxic epidermal

necrolysis.

Piperacilin and

tazobactum

Inj 4.5gm

Inj vials should be

stored at 20-25°C prior

to reconstitution.

Interacts with heparin and other

oral anticoagulants. Prolongs

the neuromuscular blockade of

vecuronium and non-

depolarizing muscle relaxants.

Serious, anaphylactic reactions.

At the Institute stringent Antibiotic policy is followed for febrile neutropenia in hemato lymphoid malignancy - AML induction/ BMT/ salvage treatment leukemias, patients with gut focus, MDR colonisation, ICU admissions, previous history of MDR sepsis and surgical patients.

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Unit specific Antibiotic Policy based on local data – Most prevalent bacteria &itsAntibiogram

DEPARTMENT OF MEDICAL ONCOLOGY

Non-neutropenic fever Amoxicillin + clavulinic acid+/-levofloxacin (out patient)

Ceftriaxone (for inpatients)

Anaerobic infection Metronidazole

Antibiotic prophylaxis (bmt) Levofloxacin

Pneumocystesjiroveci – steroid exposure, perihilar infiltration in lungs

Cotrimoxazole

Suspected rickettsial infection - eschar, puo

Doxycycline

Tuberculosis Anti-tuberculous treatment

Atypical pneumonia Azithromycin, levofloxacin

Fungal sinusitis Amphotericin

Fungal pneumonia Voriconazole For patients on pre-existing voriconazolepx: amphotericin

Invasive candidiasis Caspofungin

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Descalate /escalate based on your culture pattern

Do not delay antibiotics, to be given as soon as cultures taken, try to keep door to needle time

of < 60 minutes.

Do not escalate antibiotics just for fever; wait for the cultures to come, if the patient is stable.

Blood - 2 sets of central line and 2 from the peripheral line, repeat once in 48-72 hours if fever

is persisting.

Antifungal prophylaxis Fluconazole for bmt Voriconazole/ posaconazole for aml and all

Cmv infection Gancyclovir, valgancyclovir

Herpes simplex, herpes zoster, varicella zoster

Acyclovir

Pediatric patients with bacterial infection, stable, non neutropenic

Cefixime

Febrile neutropenia in hematolymphoid malignancy

1st line Cefoperazone + sulbactum&amikacin

2nd LINE IMIPENEM/MEROPENEM

Gram positive cover Central line infection, mucositis, perianal infection, pneumonia, hypotension, skin/ soft tissue focus

Teicoplanin

Patients with renal compromise Substitute amikacin with dose modified levofloxacin Avoid sublactam – use magnamycin

Multidrug resistant infection Colistin (oral/iv), tigecycline Consider polymyxin for renal compromise

Gut colonisation with mdr gram negative in leukemia induction/ bmt

Consider first line colistin for febrile neutropenia

Aml induction/ bmt/ salvage rx in leukemias- patients with gut focus, mdrcolonisation. Hypotension, icu admission, previous h/o of mdr sepsis

Consider first line colistin and de-escalate based on culture reports

Low risk febrile neutropenia opd based management

Very stable, cortical patients, who can be on daily follow up, iv magnex and twice daily follow up in ward. Escalate and admit in case of any signs of worsening.

Out patient infection/ low risk infections

Pneumonia/ lri

Uti

Skin and soft tissue

Diarrhea/ enteritis

Azithromycin/ levofloxacin

Ciprofloxacin/ norfloxacin/ cefixime

Amoxy-clave

Ciproflox/ norflox+/- metronidazole

33

DEPARTMENT OF SURGICAL ONCOLOGY

Antibiotic prophylaxis is indicated irrespective of the type and duration of surgery for patients with A) an ASA score > 2 B) with medical conditions resulting in decreased host defenses C) Where preoperative stay exceeds 3 days in whom an implant or graft is inserted.

(I) MINOR PROCEDURES

In relation to type of surgery antibiotic prophylaxis is not indicated for procedures performed as minor biopsies/surgery, except when procedure is performed through inflamed skin/open-infected wound/ulcers/Bone biopsies.For the above mentioned wounds except bone biopsies, empirical prophylaxis will be with oral cefuroxime x 3 days. For bone biopsies, prophylaxis will be with, single injectable perioperative dose of cefuroxime followed by post operative cefuroxime for 3 days.

(II) ENDOSCOPY No antibiotic prophylaxis for diagnostic endoscopic procedures. For therapeutic endoscopic procedures

A) Single dose of cefuroxime with low risk of bacteremia eg : Oesophageal dilatation or ERCP in a non dilated system

B) Peri-procedural Cefuroxime continued postoperatively for procedures with high risk of bacteremia, eg : ERCP in an obstructed system.

For minor biopsies that are performed through body cavities antibiotic prophylaxis is not indicated. For Trans-Rectal prostate biopsies oral ciprofloxacin with metronidazole for 3 days will be prescribed, starting day before procedure and continuing for day after procedure. Trans urethral resections :

a) Aim to perform procedures with sterile urine b) With persistent positive urine cultures, sensitive antibiotic to be started day before procedure

and to be continued till catheter removal. MAJOR SURGERY

(I) IN THE ABSENCE OF ESTABLISHED INFECTION

Type of Wound

CLEAN CLEAN CONTAMINATED

CONTAMINATED (LIMITED)

EXTENSIVE CONTAMINATION/

INFECED

Prophylactic

Drug

Cefuroxime

Cefuroxime+ Metronidazole

Cefuroxime+ Metronidazole

Cefoperazonesulbactam+

Metronidazole

Duration (days)

1 3 5 5

Escalation

Cefoperazonesulbactam

Cefoperazonesulbactam+

Metronidazole

Cefoperazonesulbactam+

Metronidazole

Imipenam/ Meropenam+ Metronidazole

34

DRUG HOLIDAY X 6 MONTHS

Type of Wound

Clean Clean contaminated

Contaminated (limited)

Extensive contamination/

Infeced

Prophylactic

Drug

Ceftriaxone

Ceftriaxone+ Metronidazole

Ceftriaxone+ Metronidazole

Piperacillintazobactam+

Metronidazole

Duration

1 3 5 5

Escalation

Piperacillintazobactam

Piperacillintazobactam+

Metronidazole

Piperacillintazobactam+

Metronidazole

Imipenam/ Meropenam+ Metronidazole

Duration Till culture reports are obtained

Till culture reports are obtained

Till culture reports are obtained

Till culture reports are obtained

Patients allergic to beta Lactamases a) Emperical Antibiotic : Levofloxacin b) Emperical Escalation : Linezolid + Amikacin/Ceftazidime.

Combination of antibiotics Indications:

a) Neutropenia b) Sepsis/Septic shock c) Suspected serious infection like bacteremia/pneumonia/urosepsis.

Drug :PiperacillinTazobactam + Amikacin. Ventilator associated pneumonia Diagnosis : New infiltrates in the Chest X ray with any two of the following

a) Fever b) Leucocytosis c) Purulent trachea-bronchial secretions

Early :</= 5 days : PiperacillinTazobacam, 6mo Cefoperazone/ Sulbactam, 6 mo Late :> 5 days : Imipenam/Meropenam All relavent Cultures to be sent at the first suspicion of infection to identify focus and sensitivity to direct therapy.Further Investigations based on focus of infection. Do not delay antibiotics, to be given as soon as cultures taken.

Minor fat necrosis/discharge from surgical wounds need not be cultured unless clinically indicated.

For patients having metal prosthesis :

Perioperative prophylactic injectable cefuroxime(6mo)/ceftriaxone(6mo) continuing till drain removal followed by oral cefuroxime(6mo)/amoxicillin-clavilunic acid(6mo) till suture removal.

35

ANTIBIOTIC POLICY- RADIATION ONCOLOGY

Condition Principle Antibiotic and recommendation

Radiation induced mucositis

No antibiotic recommended unless in patients with neutropenia or infected mucositis.

No antiseptic is recommended

For infected mucositis. Tab Amoxycillin-clavunate 625 mg twice a day for 7 days.

If total count is elevated (>10000) or if patient unable to take orally then Inj Ceftriaxone 2gm iv twice a day for 1 week.

Radiation induced dermatitis

No antibiotic recommended unless in patients with neutropenia or infected dermatitis.

No antiseptic is recommended

For infected dermatitis. Tab Amoxycillin-clavunate 625 mg twice a day for 7 days.

If total count is elevated (>10000) then Inj Ceftriaxone 2gm iv twice a day for 1 week.

Radiation induced pharyngitis and laryngitis

No antibiotic recommended unless in patients with neutropenia or fever

Tab levofloxacin 500 mg once a day for 5 days if infection is suspected

Radiation induced cystitis

Antibiotics not recommended unless in patients with fever or TC more than 10,000

Tab Ciprofloxacin 500 mg twice a day for 5 days. If patient is having fever more than 100 F then Inj Ceftriaxone 2gm iv twice a day.

Radiation induced enteritis

No antibiotic recommended unless in patients with neutropenia or diarrhea episodes more than 5 episodes per day

Tab ciprofloxacin 500 mg twice a day for 5 days. Tab metronidazole 400mg thrice a day for 5 days.

Parental route if indicated.

General procedures and prophylactic antibiotics For intracavitary application

Tab Norfloxacin 400 mg twice a day for 3 days

For oral interstitial brachytherapy insertions Inj Ceftriaxone 2 gm iv twice a day for 5 days Common ailments Cough with expectoration

Tab levofloxacin 500 mg once a day for 5 days Tab Azithromycin 500 mg once a day for 3 days

Skin infection Tab Amoxycillin-clavunate 625 mg twice a day for 7 days.

Common cold No antibiotics recommended Pyometra collection

Inj ciprofloxacin 500mg iv twice a day for 5 days .Inj metronidazole 500mg iv thrice a day for 5 days

Urinary tract infection Tab Ciprofloxacin 500 mg twice a day for 5 days Verified by: Dr.PrasanthGanesan Dr.Anandh Raja Dr.Vasanth Christopher Mrs.Varalakshmi

36

Antibiotic Prescribing - Good Practices at Cancer Institute

1. There is bedside chart - antibiotic order forms with justification

2. Combination therapy is started empirically when delay in initiating therapy to await culture

results would be life threatening

3. Antibiotic Time Out: Clinicians revisit selection of empiric antibiotics after more clinical data are

available by 48 hrs

4. Second opinion of a senior consultant for high end antibiotics, Doctors are careful not to treat

colonization or contamination

5. Antibiotic initiations is done after sending cultures. Clinician steps down to narrow spectrum, if

there is no step down availed, the reason is documented

6. Compliance with antibiotic policy & formulary is reviewed, any exception is recorded

7. Antibiotic related adverse events, factors affecting drug choice & dose - renal function,

interactions, allergy etc are reviewed

8. Core team clinician along with pharmacist reviewed patients

9. The stewardship study patient tracking forms with clinician notes were reviewed weekly by the

core team clinician along with the pharmacist. This exercise improved the communication

between the core team

*All efforts are made in reducing overall antibiotic use, although we seem to have no end to the

immunosuppression of the patient

Study Hypothesis Audit and feedback

Prospective audit and feedback is proven to be one of the most promising antibiotic stewardship

intervention strategies reducing antibiotic use in randomized-controlled trials. Audits are interactions

with prescribers to influence the way they prescribe for antibiotic therapy. These audits can be

prospective, thus directly influence therapy with feedback at patient level, or retrospective where the

prescribed antibiotics are assessed and reported back to prescribers.

We hypothesized that implementation of audit and feedback would lead to reduced antibiotic use in wards and followed 2 standard guidelines as per IDSA:

1. Prospective audit with direct intervention and feedback evaluating the appropriateness of

orders for antibiotics.

2. Formulary restriction and preauthorization involves limiting the use of certain antibiotics to

specific indications, durations of therapy.

Clinicians followed front end and back end approach

Front end - pre prescription - Pre authorization, formulary restriction & reduction in unnecessary

use. Restriction implemented : Consultant approval, preapproval, telephonic consent etc

Back end – post prescription - Prospective audit, review of broad-spectrum empirical therapy

&timely de-escalation based on culture and clinical status of patient.

37

Antibiotics are divided into 3 categories:

I. Antibiotics that require preauthorization by the consultant

II. Antibiotics that can be prescribed only for specific indications

III. Antibiotics that do not require approval

Preauthorization

category I

Conditional

category II

Available

Category III

Colistin Imipenem Cefoperazonesulbactum

Tigecycline Meropenem Piperacillintazobactum

Daptomycin Vancomycin Amikacin

Escalating & Deescalating Strategy

38

No complication, colonization or infection

Start with broad spectrum cover

Escalate

Complication, colonization or infection

Start Carbapenem, Colistin upfront to cover MDR

Step down after 48-72 hrs

39

Core Team Member Pharmacists Strategy

40

Pharmacist have a responsibility to take prominent roles in antibiotic stewardship programs in

hospitals.In our study the pharmacist collected and analyzed consumption of antibiotics, measured

antibiotic use as defined daily dose, kept track on usage of higher end antibiotics in wards. Data

collection and analysis of antibiotic use and expenditure was undertaken regularly.Pharmacist reviewed

antibiotic orders, provide feedback to doctors, and coordinated the activities of hospitals antibiotic

stewardship program in collaboration with the antibiotic stewardship core members.

Pharmacist discusses with core team clinicians and gives feedbacks and in implementing and auditing

activities that promote safe and appropriate use of antibiotics.Generating and analyzing quantitative

data on antibiotic drug use to perform clinical outcome analyses is a major responsibility. Pharmacist

worked closely with the microbiology department to ensure that appropriate microbial susceptibility tests

are reported on individual patient in timely manner and collaborates with the laboratory and utilizes

hospital information technology to enhance antibiotic stewardship program.

Collection and analysis of local consumption in particular wards was correlated with the infection rates

in that ward using microbiology data, antibiotics raised against patient hospital number but suspended

(i.e. returned to the stores) was analyzed to get the actual consumption of antibiotics by that particular

patient. Data on antibiotics suspended was collected with the help of Hospital Information System. The

role of pharmacists is useful for any stewardship programme as he/ she contributes to monitoring the

effective use of antibiotics & 1Pharmacist was appointed specifically for this study.

Patients admitted in the following wards were included in the study:

ICU – Medical oncology block, Post operative ward, Children ward, it is well known that the particular area within any hospitals that have the highest rates of antibiotic resistance are the various intensive care units, that’s the main reason for tracking the ICU patients. Moreover increase in the duration of patient exposure to antibiotics increases the likelihood of colonization with resistant organisms endogenously and their propensity to spread to other patients and into the community as well upon their discharge. Other Wards – Induction &BMT were also been tracked.

Antibiotic use data was collected and analyzed by us as follows:

Antibiotic use by patients through the Hospital Information System (electronic prescription) i.e total grams of antibiotic used for specific duration were captured for 11 antibiotics & 3 antifungals.

Monthly data from pharmacy computer was collected, this showed antibiotics indented by each ward for patients.

Any increase in antibiotic consumption in a particular ward was correlated with infection rates in that ward using Microbiology data.

Antibiotics raised against patients UHID but suspended was analyzed to get the actual consumption by a patient. Data on antibiotics suspended was collected with the help of TCS.

41

Resistance and sensitivity percentage ward wise for major antibiotics has been analyzed for both adults and children.

DDD - Defined Daily Dose for adults and pediatric patients is being calculated. DDD represents the average daily maintenance dose of an antibiotic, this is already there in the tracking sheet, this was used as a reference to calculate the DDD actually delivered for few restricted antibiotics like Colistin, Tigecycline, Carbapenem, Extended spectrum beta lactum antibiotics (piperacillin/Cefoperaone).

Monthly expenditure on antibiotics – report item wise from pharmacy.

Antibiotic audit was conducted for: a. Surgical prophylaxis b. Empirical therapy where patient’s clinical conditions, supported by laboratory findings are executed c. Definitive therapy, whereby antimicrobial is prescribed following the availability of microbiological results

Wards with high Antibiotic use - Medical, Surgical, Paediatric ICU &Induction ward were included in the

study with 202 study patients.

69

18

41 38 36

01020304050607080

STUDY PATIENTSDuring this study period, pharmacist

along with consultant medical

oncologist, pediatric oncologist &

surgical oncologist reviewed patients

included in the study weekly.

Patients who remained in the ICU

were reassessed every day until ICU

discharge. Prescribed antibiotics, as

well as microbiology, laboratory and

diagnostic imaging results were

reviewed for all the study patients.

This exercise is not normally done, it

improved the communication

between the core team members.

42

Prospective monitoring of 11 antibiotics was done with special attention to restricted antibiotics

Monthly Antibiotic Consumption – unit specific consumptionof vials

Monthly antibiotic consumption – unit specific consumption of antibiotic vials

ANTIBIOTIC NAME Medical ICU Induction ward Surgical ICU

Amikacin50mg 60 80 10

Amoxycillin 625mg 30 37 -

Cefaperazonesulbac 1gm 35 304 163

Ceftriaxone 1gm 30 14 -

Cefuroxime Sodium 1.5 - - 947

Colistimethate Sodium

88 225 4

Imipenem 500 mg

26 42 21

Piperacillintazobactum 4.5gm

29 54 40

43

Tracking of monthly Ward wise consumption

Individual patient electronic medical record was linked with electronic prescribing for better

medical management

44

Total grams of antibiotic delivered with duration was tracked

he gram amounts of antibiotics were converted to “defined daily doses” (DDDs)

Quantifying Antibiotic Use

Defined Daily Dose – DDD best quantifies antibiotic use, it is calculated as the total number of grams of

antibiotic agent used divided by the number of grams in an average daily dose.

DDD is defined by the World Health Organization

Eg: DDD of oral amoxicillin is1000 mg, so a patient receiving 500 mg every 8 hours for 5 days

consumes 7.5 DDDs.

Advantage of DDD - is the ability to compare standardized doses among hospitals.

Disadvantage of DDD – it does not account for alternative dosing regimens due to renal dysfunction,

age, or regimens that optimized pharmacokinetic or pharmacodynamic dosing.

Therefore, in many cases the administered dose is different from the DDD recommended by the World

Health Organization. This can result in either overestimation or underestimation of drug consumption.

Number of DDD’s used by patient =

Items issued X Amount of drug per item / WHO DDD

45

We performed periodic assessments of the use of antibiotics or the treatment of infections to determine the quality of antibiotic use. Examples, include determining if prescribers have accurately applied diagnostic criteria for infections; prescribed recommended agents for a particular indication; documented the indication and planned duration of antibiotic therapy; obtained cultures and relevant tests prior to treatment; and modified antibiotic choices appropriately to microbiological findings.

Patient IMIPENEM MEROPENEM

Items issued X amount of drug / WHOassigned DDD

DDD’S IItems issued X amount of drug / WHOassigned DDD.

DDD’S

1 36X500 /2

9DDD’S

2 29X500/2

7DDD’S

3 41X1/2 20DDD’S

4 33X1/2 16DDD’S

Imipenem DDD per 1000 patient days

2013

DDDs allows hospitals to compare their antibiotic use

year wise & with other hospitals

Imipenem DDD per 1000 patient days

2013

Stewardship Metrics

Imipenem DDD per 1000 patient days

We calculated the total grams of antibiotics used for patients to find out if we were able to follow

WHO DDD. DDDs allows hospitals to compare antibiotic use year wise

269

455

547

135

339

571

107

0

100

200

300

400

500

600

PT CS IM ME TGL TAR LINEZ

46

Dose Optimization

We checked whether our antibiotic dose delivered per day has been as per WHO DDD

Antibiotic WHO DDD Institute - Mean Administered

DDD

Colistin 3MIU 11 MIU

Tigecycline 50 mg 50 mg

Imipenem 2 gms 2.2gms

Meropenem 3 gms 3 gms

Piperacillintazobactum 13.5 gms 13.5gms

Cefoperazonesulbactum 0.5 gms 0.5 gms

Amikacin 6 gms 4 gms

Most of the time our antibiotic dose delivered per day has been as per WHO DDD, however for

Amikacin&Colistin delivered dose was exceeding standard DDD.

Some antibiotics were usually administered at a dosage that exceeded the WHO, recommended DDD,

the most extreme example of this was colistin at our Institute.

Among the AML patients, in 86% of patients treated with colistin, DDD was 9 MIU, 3 times more than

WHO DDD and in 37% of patients Amikacin DDD 4 gms, less than WHO DDD.

Dose Optimization - Alternative dosing regimens was followed Colistin&Amikacin, due to renal

dysfunction, regimens that optimized pharmaco kinetic or pharmaco dynamic dosing of both the drugs

47

Usage of Colistin&Tigecycline in wards 2015 - 2016

Tigecycline usage

0

200

400

600

800

1000

AU

G

SEP

OC

T

NO

V

DEC

JAN

FEB

MA

RC

H

AP

RIL

MA

Y

JUN

E

MOB II

MOB I ICU

POW

Induction

0

20

40

60

80

100

120

48

Antibiotic Expenditure

We looked into the costs savings, keeping in mind that continuous decreases in antibiotic use and cost

should not be expected, however we found that monthly cost savings was fluctuating and expenditure

decreased when infections were less.

The cost of treating a MDR infection – Colistin&Tigecycline may be used for a week would be a lakh of

rupees and even more if a third antibiotic is added.

Antibiotic Cost of treatment

Per day Per week

Cefoperazone/Sulbctum 778 2,436

Piperacillin/Tazobactum 1284 8,988

Imipenem, 2 gms 4452 31,164

Meropenem, 3 gms 7488 52,416

Colistin 9MIU 7704 53,928

Tigecycline, 50 mg 6460 45,220

Teicoplanin 1533 10,731

Amikacin 70 490

49

Stewardship Metrics Measurement is critical to identify opportunities for improvement and assess the impact of improvement efforts. Monitoring and analysis of antibiotic usage is critical to understanding antibiotic resistance and measuring the effects of stewardship interventions. Data on bacterial susceptibilities to antibiotics & infection rates were compared before and after

stewardship implementation and we did not find any significant difference in resistance percentage,

resistance rates did not decrease, however there was more disciplined use of antibiotics and

accountability was there.

We wanted to measure what we were doing:

Antibiotic usage data was interpreted together with infection data & clinical foci

Prospective audit of prescription was conducted by the concerned core team doctor

Monthly data on antibiotics issued by pharmacy to wards was collected

Hospital Information System was used to collect data on antibiotic use of ward

Any increase in antibiotic consumption in a particular ward was correlated with infection rates in

that ward using Microbiology data

Antibiotic raised for individual patients was captured using electronic prescribing system

Antibiotic raised for a patient but returned back to pharmacy was also captured

50

Impact of Antibiotic

Stewardship Study

51

Before evaluating the Outcome measures we designed study questions to check optimal

antibiotic use:

Does our hospital produce an antibiogram - cumulative antibiotic susceptibility report, and distribute

to clinicians periodically?

1. Do concerned ward / clinician receive direct communication from lab on MDR susceptibility.

2. Does our hospital have a policy that requires doctors to document in the medical record-

dose, duration, and indication for all antibiotic prescriptions?

3. Does our hospital have treatment recommendations, based on national guidelines and local

susceptibility, to assist with antibiotic selection for common clinical conditions?

4. Is there a formal procedure for all clinicians to review the appropriateness of all antibiotics

48 hours after the initial orders - antibiotic time out?

5. Do specified antibiotic agents need to be approved by senior consultants prior to

administering - pre-authorizationl?

6. Does a clinician or pharmacist review courses of therapy for specified antibiotic agents -

prospective audit with feedback?

7. Is dose adjustments done in our hospital for patients with organ dysfunction?

8. Does our stewardship program monitor adherence to hospital antibiotic policy-

dose, duration and indication?

9. Does our stewardship program monitor antibiotic use-consumption at the ward by one of the

following metrics:

By number of grams of antibiotics used-Defined Daily Dose, DDD?

By direct expenditure for antibiotics-purchasing costs?

We found that during the course of this study we complied with most of the questions raised.

52

Impact of antibiotic stewardship study:

In our experience infection control interventions was the main strategy for antibiotic resistance containment. We saw the reduction in incidence of MDR infections whenever infection control measures were stepped up.

The study increased the awareness about resistance among all clinicians and post graduates, it gave us a scope to continuously monitor the infection control practices& better adherence to guidelines.

Accountability - Unit wise antibiotic purchases were monitored & antibiotics used for patients were quantified and this was discussed with concerned units.

Decreased inappropriate antibiotic use - we have antibiotic order form with prescriber to justify antibiotic use.

Continues discussion on handling infections caused by MDR bacteria was happeningbetween the core members& clinicians.

Periodic review of resistance data, surveillance of MDR infections & clinical outcomes – improvement at the level of individual infected patient.

Close monitoring of empirical high end antibiotics was done. De escalation was done meticulously - once laboratory results are available with

identification of pathogen along with susceptibility data, every attempt was made to deescalate the antibiotics.

Ongoing monitoring and prospective audits helped us whether guidelines are followed as expected. Adherence to institutional antibiotic policy with evidence based antibiotic choice.

Initially we felt it as an additional burden to our already heavy workload, but as the study proceeded we were seeing the benefits for ourselves and realized that it should be regarded as a routine standard of care.

Study increased awareness about resistance among us, clinicians started working closely with Pharmacist and Microbiologist, we are talking!!

Study Question

Did resistance decrease?This is little bit difficult to show as an outcome measure, at the institute

stewardship helped us improve adherence with our policies, infection rates decreased.

Did susceptibility % change after implementation of stewardship – not really, early to expect.

Did formulary restriction and preauthorization help in reducing resistance - both approaches have

helped in disciplined antibiotic use.

53

Conclusion

No single intervention can solve resistance, our experience has shown that improving infection control practices &the appropriate use of antibiotics plays an important role in addressing this issue. Only 10 new antibiotics have been approved in last 15 years, antibiotic discovery is not as profitable as drugs discovered for treating chronic diseases, with this in mind we have a duty of conserving antibiotics through responsible use & being a responsible steward.It is estimated that 50% or more of hospital antibiotics use is inappropriate, making antimicrobial stewardship a part of patient safety would be meaningful, as resistance is closely linked to inappropriate antibiotics use. Use of medically important antibiotics as growth promoters in livestock has to be immediately addressed. The State government can launch a campaign focusing on improving antibiotic use in hospitals & medical institutions and implement stewardship programs. Healthcare providers & policy makers should work together to employ effective prevention strategies.National surveillance programme for antibiotic use across the country would help. The Indian Council of Medical Research has established a National Programme on Antimicrobial Surveillance in ten laboratories, covering priority pathogens identified by the World Health Organization. Efforts by groups like CDC, IDSA, ICMR, CDDEP,Global Antibiotic Resistance Partnership, Chennai Declaration, IIMAR & policies-National Antibiotic Policy, CDSCO Schedule H1, National Treatment Guidelines for Antimicrobial Use, 2016 etcare to be mentioned however awareness about the problem among policy makers and the general public with continuing education for healthcare personnel has to increase. An effective infection control program can make a significant contribution to limiting the spread of resistance. An important first step in stewardship study is to streamline all the infection control practices and identify the problem pathogens and antibiotic use at the institution. Core teams effort is paramount to raise awareness & tackle the increasing resistance crisis, we believed that the involvement of microbiology and infection control nurses and the effective participation of the clinicians and pharmacist had a valuable contribution in the study success.The first lesson learned was the need for communication among the clinicians, pharmacist, microbiologist & core team members, disconnect was overcome & we discussed the management of complicated MDR infections. One of the greatest challenges of antibiotic stewardship study is demonstrating a clear association between implementation of stewardship and decreased rates of antibiotics resistance. Early studies that achieved decreased cephalosporin use were successful in controlling the incidence of resistant gram-negative infections to cephalosporins, but resulted in an increase in carbapenem use and resistance to carbapenems, an example of the “squeezing the balloon” phenomenon, in which decreasing use of one antibiotic results in increasing use of another, often with associated resistance. Stewardship programme does not have to fit a particular model, we can tailor it to our own hospital policy & practices, and it would be a excuse to simply delay implementation of this program because of a lack of availability of resources. In our experience infection control interventions was the main strategy for containment of resistance, whenever we tightened infection control measures resistance decreased. We at the Institute see this study as an antibiotic management study and the study becomes even more significant when we look beyond just saving money, when patients are out of infection completing treatment successfully, discharge early& the bed available for another patient. We believe that our work has brought about tangible benefits and we wish to subject it to further study.

54

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20. Camins BC, King MD, Wells JB, et al. Impact of an antimicrobial utilization program on

antimicrobial use at a large teaching hospital: a randomized controlled trial. Infection

control and hospital epidemiology :the official journal of the Society of Hospital

Epidemiologists of America. Oct 2009;30(10):931-938.

21. Centers for Disease Control and Prevention. Get Smart: Know When Antibiotics Work.

http://www.cdc.gov/getsmart/healthcare/ Accessed 2/24/2014.

22. Fridkin SK, Steward CD, Edwards JR, et al. Surveillance of antimicrobial use and

antimicrobial resistance in United States hospitals: Infectious Diseases Society of

America. Aug 1999;29(2):245-252.

23. Griffith M, Postelnick M, Scheetz M. Antimicrobial 5. stewardship programs: methods

of operation and suggested outcomes. Expert Rev Anti Infect Ther2012; 10 : 63-73.

24. Morris AM, Stewart TE, Shandling M, McIntaggart S, Liles WC. Establishing an

antimicrobial stewardship program. Healthcare quarterly. 2010;13(2):64-70.

25. Ibrahim OM, Polk RE. Benchmarking antimicrobial drug use in hospitals. Expert review

of anti-infective therapy. Apr 2012;10(4):445-457.

56

STUDY REPORT OF RAJIV GANDHI

GOVERNMENT HOSPITAL

57

Name of the study : Antibiotic Stewardship –coordinated interventions to measure appropriate use of

antibiotics to help control of infections in hospitals.

Study setting : Intensive medical care unit and Surgical Intensive care unit in Rajiv Gandhi

Govt.General Hospital,Chennai-3

Type of study : Prospective and retrospective cross sectional study

Duration of study : 1year

Objectives of the study

Primary objectives

1.To develop uniform standard guidelines and policies for control of infections in hospitals.

2.To formulate a multidisciplinary infection control committee that ensures implementation of infection

control policies.

3.To initiate and execute Antibiotic Stewardship Programme.

4. To establish formulary restriction and approval systems especially for broad spectrum antibiotics.

Secondary objectives

1. Health care associated infections rates will be studied ,using surveillance definitions of CDC

and IDSA.

2. After implementation of infection control guidelines,the changes in the rates of Health Care

Associated Infections( HCAI) will be studied.

3. To correlate the pharmacy data with the infection rates.

4. To promote optimal antibiotic use within hospital

5. To find out defined daily dose (DDD),for high end antibiotics against gram positive and gram

negative bacteria.

58

Materials and Methods

All inpatients admitted in both medical and surgical care units ,satisfying the criteria will be

taken for study.

Base line study of 3months duration (Oct/15 to dec 15) ,applying surveillance definitions for the

following health care associated infections was done.

1.Catheter Associated Urinary Tract Infection(CAUTI)

2.Ventilator Associated Pneumonia(VAP)

3.Catheter Related Blood Stream Infection(CRBSI)

4.Surgical Site Infection (SSI)

The infection rate of Health care associated infections were calculated by using

Surveillance definitions of Health care associated infections

CATHETER ASSOCIATED URINARY TRACT INFECTION(CAUTI)

• Indwelling Urinary Catheter in place >2days

AND

One of the foll.signs and symptoms

• Fever >38⁰C,Suprapubictenderness,Costovertebral angle pain or tenderness.

AND

• A positive urine culture of ≥10 5 CFU/ml and with not more than 2 species of microorganisms.

The incidence rate of CAUTI per 1000 catheter days=

Total Number of cases with Symptomatic CAUTI / Total Duration of catheterisation

(days)X1000

VENTILATOR ASSOCIATED PNEUMONIA(VAP)

Criterion 1: Positive culture of one of the following specimens,

Endotracheal aspirate, ≥105CFU/ml· Bronchoalveolar lavage, ≥104 CFU/ml or

Bronchial brush specimen ≥103 CFU /ml

(or)

Criterion 2: Purulent respiratory secretions (defined as secretions from the lungs, bronchi, or

trachea that contain >25 neutrophils plus organisms.

Ventilator Associated Pneumonia per 1000 patient days =

No.of Ventilator associated pneumonia events/X1000

No.of Ventilator days

59

CATHETER RELATED BLOOD STREAM INFECTION(CRBSI)

The same organism grow from at least 1 percutaneous blood culture and from a culture of the

catheter tip , or

2 blood samples be drawn (one from a catheter hub and the other from a peripheral vein) that,

when cultured, meet CRBSI criteria for quantitative blood cultures or differential time to

positivity (DTP) .

Alternatively, 2 quantitative blood cultures of samples obtained through 2 catheter lumens in

which the colony count for the blood sample drawn through one lumen is at least 3-fold greater

than the colony count for the b .

CRBSI rate per 1000 device days = No.of culture positive cases/No.of catheter days

X 1000

SURGICAL SITE INFECTION (SSI)

Superficial Incisional SSI

SSI Infection occurs within 30 days after any operative procedure, involves only skin and

subcutaneous tissue of the incision

AND

patient has at least one of the following:

a. purulent drainage from the superficial incision.

b. organisms isolated from an aseptically-obtained culture from the superficial incision or

subcutaneous tissue.

c.patient has at least one of the following signs or symptoms: pain or tenderness; localized

swelling; erythema; or heat.

SSI rate = No.of surgical site infections/No.of patients operated X100.

Under clean surgeries mastectomy,thyroidectomy,hernioplasty,exploratory laparotomy were

included.Contaminated surgeries included cholecystectomy,appendicectomy and colon

surgery.

Infection control measures and Antibiotic stewardship measures put into practice

Various measures implemented are as follows

1.Promotion of hand hygiene in between patients and use of appropriate personal protective

equipment for procedures as recommended by CDC.

2..Appropriate samples for culture to be collected before initiation of antibiotic therapy

3.Awaiting culture results ,presumptive antibiotics to be started based on antibiotic

guidelines(annexure)

4..With the availability of antibiotic susceptibility reports from the microbiology

Laboratory,escalation or de-escalation will be done.

5.To ensure correct dosage and appropriate time interval between administration of parenteral

antibiotics,in order to achieve adequate drug concentration. Right dose of the drug at right

time,and duration of therapy to be monitored

60

6.Pre authorization for restricted antibiotics which includes

Inj.Piperacillin-Tazobactam

Inj.Meropenem

Inj.Imipenem

Inj.Vancomycin

Inj.Amphotericin –B

T.Linezolid.

With implementation of infection control measures,follow up data was collected for 6 months

duration from Jan/2016 to june 2016.

Antibiotic consumption

Monthly antibiotic consumption data of 6months from Mar/16 to Aug /16was obtained from the

manual records of our pharmacy and to calculate DDD for specified drugs, information was

tracked from indent of medical intensive care units.

One Defined Daily Dose is defined as the assumed average maintenance dose per day for a

drug for its main indication in adult.

DDD was calculated for total four antibiotics ,of which 2 were of the gram negative

spectrum(Inj.Piperacillin-Tazobactam,Inj.Meropenem) and two antibiotics against gram positive

bacteria(Inj.Vancomycin ,T.Linezolid)

DDD was calculated applying the following formula

Total consumption of antibiotic / DDD X 1000

As per WHO, DDD for drugs is as follows

Inj.Vancomycin 2

Inj.Meropenem 2

Inj.Piperacillin-Tazobactam 14

T.Linezolid 1.2

61

RESULTS

Base line and follow up data on health care associated infections are as follows

CATHETER ASSOCIATED URINARY TRACT INFECTIONS

Before interventions

Incidence of CAUTI per 1000catheter days = 26/1013 X 1000

= 26 cases

After interventions

Incidence of CAUTI per 1000catheter days=40/1980 X1000

=20 cases

The commonest organism isolated was E.coli ,followed by kleb.pneumoniae.Among the gram positive

pathogens, Enterococcus faecalis was the commonest followed by Staph aureus.

Drug resistance pattern in Gram Negative Bacilli

ESBL 40%

AMP C BETA LACTAMASE 22%

CARBAPENAMASE producers 11%

Drug resistance pattern in Gram positive Cocci

MRSA 20%

VRE 4%

VAP RATE

Before interventions

No.ofpts on mechanical ventilation

Duration of mechanical ventilation(in days)

No.of VAP cases VAP rate per 1000ventilator days

318 681 11 16

6MONTHS CAPTURE DATA

No.ofpts on mechanical ventilation

Duration of mechanical ventilation(in days)

No.of VAP cases VAP rate per 1000ventilator days

708 1378 19 13.8

62

The age and gender distribution of confirmed VAP cases were studied and was found out that

incidence of VAP was highest in patients of age between 51-60 yrs.Males were commonly affected

than females..

The most frequently isolated organism was Acinetobacterbaumanii followed by Pseudomonas

aeruginosa.With regard to gram positive bacteria, Methicillin Resistant Staphylococcus aureus was the

commonest and had MIC within the susceptible range.

Antibiotic susceptibility testing report

Acinetobacterbaumanii

Name of the Antibiotic %susceptibility

Amikacin 44

Ciprofloxacin 33

Ceftazidime 11

Meropenem 67

Pip-Taz 44

Pseudomonas aeruginosa

Name of the Antibiotic %susceptibility

Amikacin 67

Ciprofloxacin 17

Ceftazidime 33

Meropenem 70

Pip-Taz 50

Pattern of drug resistance in gram negative bacteria

ESBL 83 %

AMP-C beta lactamase producers 33%

Metallobetalactamaseproducers 27%

CENTRAL LINE ASSOCIATED BLOOD STREAM INFECTIONS

Common indications for Central Catheterization

Fluid replacement during surgery

To resuscitate the patient from shock

Lack of peripheral venous access

Blood transfusion and Total parenteral nutrition

Central venous pressure monitoring

63

Before intervention

No.of patients on central line

No.of culture positive

No.of catheter days

Infection rate per 1000 device days

105 16 1126 14.20

After intervention

No.of patients on central line

No.of culture positive

No.of catheter days

Infection rate per 1000 device days

230 26 2318 11.21

Bacteriology of CRBSI

Non fermenters were found to be the commonest pathogen among gram negative bacteria ,followed by

Klebsiella pneumonia and S.aureus.

AmongNonfermenters ,Pseudomonasaeruginosa was the commonest isolate showing multi

drugresistance ,sensitive only to PiperacillinTazobactam and Meropenem.

S.aureus showed 66% resistant to methicillin(MRSA),and 100% sensitive to vancomycin. .

SURGICAL SITE INFECTIONS

After 3months of base line data collection,surgeons ,post graduates and staff nurses were sensitized on

the importance of presurgical prophylaxis 1 hr before surgery.If duration of surgery exceeded 4 hours

a second dose of antibiotic was considered.

Duration Type of surgery No.of cases suspected to have SSI

Culture positive SSI rate%

Prior interventions

Clean and contaminated(n-260)

112 44 16.9

Post interventions

Clean and contaminated(n=900)

200 140 15.66

Among contaminated surgeries,Appendicectomy had higher infection rate followed by Laparotomy and

mesh repair ,Hemicolectomy with segmental resection and cholecystectomy.

Among clean surgeries hernioplasty and mastectomy had higher infections ,thyroidectomy and

adrenalectomy had lesser infection rates.

E.coli was the commonest pathogen isolated followed by S.aureus and K.pneumoniae.

Among the gram negative bacteria ESBL production was seen with 80% of the isolates and among

S.aureus 28% were MRSA.

All the MRSA isolates were sensitive to vancomycin( MIC≤ 2µg/l)by macrobroth dilution method.

64

Antibiotic consumption

Antibiotic consumption data for four commonly used parenteral antibiotics from March2016 to

August2016 from medical and surgical intensive care units(IMCU and SICU)

TABLE-1

Months March April May June July Aug

WARD-IMCU Cefotaxime 38 22 27 31 34 64

WARD-SICU Cefotaxime 110 130 198 162 184 318

Note : Numbers depicted in all tables represent the total no.of injections/vials

0

50

100

150

200

250

300

350

March April May June July Aug

ward-212 Cefotaxime

ward-213 Cefotaxime

65

TABLE-2

Months March April May June July Aug

WARD-IMCU Ceftriaxone 180 174 218 403 326 357

WARD-SICU Ceftriaxone 14 24 204 92 168 178

TABLE-3

Months March April May June July Aug

WARD-IMCU Ciprofloxacin 18 12 51 55 48 74

WARD-SICU Ciprofloxacin 9 32 16 18 22 68

0

50

100

150

200

250

300

350

400

450

March April May June July Aug

ward-212 Ceftriaxone

ward-213 Ceftriaxone

66

TABLE-4

Months March April May June July Aug

WARD-IMCU Amikacin 33 16 36 57 62 42

WARD-SICU Amikacin 74 15 52 71 89 37

0

10

20

30

40

50

60

70

80

March April May June July Aug

ward-212 Ciprofloxacin

ward-213 Ciprofloxacin

0

10

20

30

40

50

60

70

80

90

100

March April May June July Aug

ward-212 Amikacin

ward-213 Amikacin

67

Total consumption of regularly used antibiotics in both units

TABLE-5

Months March April May June July Aug

WARD-IMCU Cefotaxime 38 22 27 31 34 64

WARD-SICU Cefotaxime 110 130 198 162 184 318

WARD-IMCU Ceftriaxone 180 174 218 403 326 357

WARD-SICU Ceftriaxone 14 24 204 92 168 178

WARD-IMCU Ciprofloxacin 18 12 51 55 48 74

WARD-SICU Ciprofloxacin 9 32 16 18 22 68

WARD-IMCU Amikacin 33 16 36 57 62 42

WARD-SICU Amikacin 74 15 52 71 89 37

ward-212 Cefotaxime

ward-213 Cefotaxime

ward-212 Ceftriaxone

ward-213 Ceftriaxone

ward-212 Ciprofloxacin

ward-213 Ciprofloxacin

ward-212 Amikacin

ward-213 Amikacin

68

The total Antibiotic consumption of high end antibiotics in IMCU is as follows

TABLE-6

Months Cefo-Sul (CS) Pip-Taz(pz) Imipenem(Im) Meropenem(mp) vancomycin(vc)

Mar-16 232 320 150 268 145

Apr-16 260 801 210 189 88

May-16 459 504 149 213 160

Jun-16 255 248 151 195 157

Jul-16 440 76 57 211 108

Aug-16 64 280 172 129 60

The total Antibiotic consumption of high end antibiotics in SICU is as follows

TABLE-7

Months Parenteral Antibiotic Consumption(CS)

Pip-Taz(CS) Imipenem(CS) Meropenem(CS) vancomycin(CS)

Mar-16 138 345 - 138 9

Apr-16 170 370 - 178 20

May-16 58 291 10 113 6

Jun-16 60 387 2 47 6

Jul-16 123 40 16 178 20

Aug-16 62 367 12 4 4

0

100

200

300

400

500

600

700

800

900

Mar/16 Apr/16 May/16 Jun/16 Jul/16 Aug/16

Cefo-Sul (CS)

Pip-Taz(pz)

Imipenem(Im)

Meropenem(mp)

vancomycin(vc)

69

In order to calculate DDD,monthly Antibiotic consumption of individual patients was obtained from

daily drug indents from IMCU .

TABLE-8

Monthwise DDD for antibiotics

Months MEROPENEM

PIP - taz VANCOMYCIN T.Linezolid

Total number of patients

Mar-16 523 97 104 0 258

Apr-16 243 99 86 136 292

May-16 398 98 178 163 276

Jun-16 333 61 172 187 378

Jul-16 388 28 93 51 356

Aug-16 183 85 82 319 354

0

50

100

150

200

250

300

350

400

450

Parenteral AntibioticConsumption(CS)

Pip-Taz(CS)

Imipenem(CS)

Meropenem(CS)

vancomycin(CS)

70

IMCU-DDD

0

100

200

300

400

500

600

Mar/16 Apr/16 May/16 Jun/16 Jul/16 Aug/16

MEROPENEM

PIP - taz

VANCOMYCIN

T.Linezolid

Total number of patients

0

100

200

300

400

500

600

MEROPENEM DDD

MEROPENEM DDD

71

0

20

40

60

80

100

120

Mar/16 Apr/16 May/16 Jun/16 Jul/16 Aug/16

PIP - TAZ DDD

PIP - TAZ DDD

0

20

40

60

80

100

120

140

160

180

200

VANCOMYCIN DDD

VANCOMYCIN DDD

0

50

100

150

200

250

300

350

Mar/16 Apr/16 May/16 Jun/16 Jul/16 Aug/16

T.Linezolid DDD

T.Linezolid DDD

72

DISCUSSION

CAUTI

Among health care associated infections CAUTI was found to be the commonest .The indication of catheterisation was found to be valid in all patients and majority of the patients developed after 2weeks of catheterization. Prior infection control measures the CAUTI rate was 26 which was reduced to 20 ,with adoption of

simple measures.In addition to duration of catheterization risk factors including Age of the patient (50

years and above), Co morbid conditions like diabetes mellitus, long term corticosteroids therapy were

contributory to CAUTI.

Escherichia coli was found to be the commonest pathogen causing CAUTI,followed by

Klebseillapneumonia.ESBL production was seen with 40% of the isolates,AMP C production

22%,andCarbapenamase producers 11%.

Among the gram positive cocci MRSA was 20% and VRE 5%.Though the percentage of VRE is

minimal,stringent infection control measures including contact precautions and early treatment is

essential to prevent the spread of vancomycin resistance from Enterococcus to Staphylococcus aureus.

VAP

Ventilator Associated Pneumonia per 1000 ventilator days was 16 ,which got reduced to 13.8,with

implementation of infection control measures. It was found highest among 51-60 of age.Males were

commonly affected than females.

Acinetobacterbaumanii was the commonest pathogen followed by pseudomonas aeruginosa.

MDR pattern was seen with 67% of A.baumaniiand P.aeruginosa

Overall 27% were Metallobeta lactamase producers.

Methicillin Resistant Staphylococcus aureus was the commonest among gram positive bacteria,and

had vancomycin MIC within the susceptible range(<2µg/l).

CRBSI

The CRBSI rate was 14.20 per 1000 catheter days as shown by baseline data ,which got reduced to

11.21% after infection control measures.

As microorganisms may originate from the skin of patients or hands of health care providers,standard

precautions including hand hygiene,aseptic technique and maximal sterile barrier precautions were

made mandatory.

Systemic antibiotic prophylaxis was discouraged before insertion to prevent colonization or CRBSI.

73

Most common age group was between 50-59 yrs of age.Infection was common with emergency mode

of insertion and femoral site was found to be the commonest site associated with CRBSI.

The commonest bacteria isolated was P.aeruginosa ,followed by S.aureus and K.pneumoniae.

Majority of the P.aeruginosa were MDR and among gram positive cocci 66% were MRSA.

With regard to K.pneumoniae ,all were (100%) ESBL producers ,showing sensitive pattern to

carbapenems.

SSI

The most common pathogens associated with SSI were E.coli,andstaph.aureus .

In the present study SSS rate was higher in clean contaminated surgeries than clean surgeries.The

other risk factors included age of the patient(≥55yrs),existing comorbid illness,and duration of surgery

(≥2hrs).The increase in SSI rate with increasing duration of surgery may be due to longer exposure

time leading to more contamination and hence more damage to the tissues,and also due to fatigue in

workers leading to breaks in sterile technique.

Among the gram negative isolates,all were sensitive to carbapenems.There was moderate to high

level resistance to ciprofloxacin(33%)About 80% of the bacteria were ESBL producers,but susceptible

to betalactam inhibitor combinations.

P.aeruginosa ,the second commonest gram negative bacteria associated with infection,was found less

sensitive to 3rd generation cephalosporins(28%),but sensitive to piperacillin-tazobactam combination.

MRSA constituted 28% of all the S.aureusisolates.All these were sensitive to vancomycin by

macrobroth dilution method (MIC<2µg/l) .

Among the surgeries,Appendicectomy had the highest rate of infection,followed by laparotomy with

mesh repair..SSI was least in patients who underwent thyroidectomy and adrenalectomy.

74

Antibiotic consumption

As per pharmacy data,with regard to the consumption of unrestricted parenteral antibiotics,it was found

that medical intensive care unit(IMCU)had more consumption of Inj.Ceftriaxone than

Inj.Cefataxime,Inj.CiprofloxacinandInj.Amikacin. The increased use of Inj.Ceftriaxone in medical

intensive care unit would be due to increased admission of patients with central nervous system

infections and its better penetration to Cerebrospinal fluid(CSF),when compared to other

antibiotics.(Tables 1-5)

In surgical intensive care unit(SICU),there was wide usage of Inj.Cefataxime,followed by

Inj.Ceftraiaxone.With increasing incidence of Extended Spectrum Betalactamaseproducers,the usage

of Cefataxime need to be brought down and alternate drugs to be prescribed.(Tables1-5)

In IMCU,with regard to restricted antibiotis (Table 6)Inj.Pip-Taz consumption was highest during april

2016,then it got reduced in the following months.Inj.Meropenem was highly prescribed than imipenem

and Inj.Meropenem was highly consumed in March2016,and slowly it started declining from April to Aug

2016.Inj.Vancomycin usage hows little variation in 6 months period,with slight increase in may 2016.

With restricted antibiotics in ISCU,it was found that the antibiotic consumption of

Inj.PiperacillinTazobactam to be high during march and reduced in may 2016.Among

carbapenems,Meropenem was widely used than Imipenem.Inj.Meropenem usage was similar in most

of the months ,with slight increase in July 2016 and it stabilized in august2016.Usage of Vancomycin

was consistent from march to august 2016.(Table 7).

Defined daily dose(DDD) is used as an alternative to days of therapy(DOT) to measure antibiotic

use.This is used to compare drug usage between different health care environments..

In medical intensive care unit(table 8) it was found that,DDD for meropenem was highest during

March/2016 and then it stabilized from april to august/2016. For pip-taz lowest DDD per 1000 patient

days was seen in june/2016.

With regard to antibiotics against gram positive bacteria ,DDD of vancomycin was high during may and

june 2016.The DDD of T.Linezolid showed 1.5 times increase during Aug/16,which could be due to

shortage of vancomycin in that particular month.

75

Summary

The rates of health care associated infections pre and post interventions showed a change as infection

control measures were implemented.In future time bound goals can be set to bring more marked

reduction of these infections in hospital .

Syndrome specific interventions like urinary bundle,VAP bundle can be put in to practice,to reduce

health care associated infections(HCAI).

Antibiotic stewardship interventions can be extended to nephrology,haematology wards in order to

improve the appropriate prescribing of antifungal drugs in immunocmpromised patients.

Studies indicate that 30-50% of antibiotics prescribed in hospitals are unnecessary or inappropriate.

There is no doubt that overprescribing and misprescribing is contributing to the growing challenges

posed by Clostridium difficile and antibiotic-resistant bacteria. Studies demonstrate that improving

prescribing practices in hospitals can not only help reduce rates of infection and antibiotic resistance,

but can also improve individual patient outcomes, all while reducing healthcare costs.

Hence all clinicians and other health care staff can be sensitized time to time on HCAI, appropriate

prescribing and effective management to tackle antibiotic resistance,which may not onlycut down

expenditure on antibiotics,but the valuable resource can be protected for future.

The limitation of this study had been lack of electronic data,due to which correlation of infection rates in

terms of gram positive,gram negative bacteria with consumption of respective spectrum of antibiotics

could not be made.

With implementation of Hospital Management Information System(HMIS),we would be able to carry out

studies reflecting the above parameters in future.

76

References

1.https://www.cdc.gov/hai/May 27, 2016 2.www.cdc.gov › Healthcare-associated Infections (HAI) › Types of Infections,Oct 16, 2015

3.https://www.whocc.no/atc_ddd_index/Dec 16, 2015.

4.https://www.idsociety.org/New_Antimicrobial_Stewardship_Guideline_2016/

5.American Thoracic Society, Infectious Diseases Society of America: Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia. Am J RespirCrit Care Med 2005, 171.

6..Can J Infect Dis. 2004 Jan-Feb; 15(1): 29–35.Measurement of antibiotic consumption: A practical

guide to the use of the Anatomical Therapeutic Chemical classification and Definied Daily Dose system

methodology in CanadaJames M Hutchinson, MD FRCPC,1 David M Patrick, MD MHSc FRCPC.

7.WHOCC_ATC/DDD INDEX,www.whocc.no/atc_ddd_indexApr 14, 2016 .