Improvement of Parenteral Antibiotic use in a

University Hospital in Colombia

Clinical Epidemiology and Biostatistics Unit, Pontificia Universidad Javeriana, Bogotá,

Colombia

Pérez A, Dennis RJ, Rodriguez B, Castro AY, Delgado V, Lozano JM

ABSTRACT

• Problem Statement: In Colombia, there has been no incentive in the past for continuing quality assessment, by ongoing monitoring, of antibiotic prescription practices.

• Objectives: To evaluate the effect of an intervention to improve antibiotic prescribing practices in a University- based hospital.

• Design: Quasi-experimental before/after study with a planned intervention; interrupted time series analysis.

• Setting: Tertiary care hospital caring for private and institutional patients.• Study Population: Hospitalized patient prescription census from 10 clinical services, including

Gynecology and Obstetrics, Surgery, Medicine, and Pediatrics. A total of 2716 prescriptions were collected between June, 1997 and April, 2000.

• Intervention: A structured antibiotic order form implemented between two data collection phases between week 82 and week 102. All hospitalized and prescribed patients completed the form since week 82.Physicians in charge of grup prescription in each service completed the forms. The Hospital designed the form with the help of the research tem. We also implemented an educational campaign with conferences for physicians and posters for all the clinical services, and blood pressure cuffs for anaesthesiologists.

• Outcome Measures: Hospital weekly rate of incorrect prescriptions of (A) aminoglycosides in dose interval less than 24 hours (gentamicin, amikacin, streptomycin and netilmicin); (B) cephradine and cephalothin in dose interval greater than 6 hours; (C) ceftazidime and cefotaxime in dose interval greater than 8 hours; and (D) any antibiotic prescribed one hour before or after incision in surgery.

• Results: Interrupted time series intervention analysis was conducted for three antibiotic groups of the hospital’s weekly rate of incorrect prescriptions. Pre-intervention Auto-Regressive Integrated Moving Average (ARIMA) models were identified, estimated and diagnosed for the four time series (A,B,C,D). Time series (A) was an ARIMA (0,1,2) with corresponding estimates and standard error (SE) as theta1=0.36 (SE=0.102) and theta2=0.49 (SE=0.101), respectively. Time series (B) was an ARIMA (0,1,1) with corresponding estimate =0.82 and SE=0.07. Time series (C) was an ARIMA (0,0,1) with corresponding estimate=-0.72 and SE=0.08. Time series (D) was an ARIMA (0,1,1). These models were used in the post-intervention series to test for pre-post series level differences. An abrupt constant change was significant in A, C and D time series, indicating a 47%, 7.3% and 20% reduction on incorrect prescriptions after intervention.

• Conclusions: High rates of incorrect prescription were reduced after the intervention. This intervention, consisting of both an educational campaign and introduction of a structured prescription form with built-in deterrents of selection of inappropriate dosing intervals, can be implemented in a teaching hospital in Latin America. Such an intervention leads to measurable decreases in the proportion of incorrectly prescribed antibiotics.

BACKGROUND• Uncontrolled use of antibiotics abuse

and potential unwarranted events and costs

• Need for:• Ongoing monitoring of antibiotic

prescription practices• Implementation of interventions to improve

inappropriate behavior

• Pharmacy and Infection Control Committees identified a critical area as:• Use of expensive antibiotics

BACKGROUND• Pharmacy and Infection Control

Committees identified critical areas:• Use of expensive IV antibiotics• Implementation of an adverse drug

reaction surveillance program• Use of sedatives and hypnotics• Drug modification as a function of renal

condition• Adequate pharmacological prevention of

UGI bleeding and thromboembolism

RESEARCH OBJECTIVES• To assess the appropriateness of the

observed antibiotic prescription patterns.

• To implement a hospital wide intervention aimed to improve inappropriate practices.

• To assess the potential cost/savings profile of the intervention from the payer point of view.

RESEARCH DESIGN• Quasi-experimental pre-post time

series design• Reasons for not using an RCT:Reasons for not using an RCT:

• Permanent rotation of residents, interns Permanent rotation of residents, interns and nurses very high potential for and nurses very high potential for contamination bias within and between contamination bias within and between wards, which would attenuate any wards, which would attenuate any perceived effectsperceived effects

• Selection of one other hospital as control: Selection of one other hospital as control: unfeasible control of measurable unfeasible control of measurable confoundersconfounders

METHODS

SETTING

• San Ignacio’s Hospital, Bogotá, Colombia. June, 1997

• Hospitalized patients• Obstetrics-Gynecology, Surgery, Medicine,

Pediatrics, Intensive Care Unit, others wards.

EXPERT PANELPI, infectologist, representatives from G&O, Pediatrics, PI, infectologist, representatives from G&O, Pediatrics, Internal Medicine, Surgery and NursingInternal Medicine, Surgery and Nursing• Identifying tracer conditionsIdentifying tracer conditions• Developing expected norms regarding the appropriate Developing expected norms regarding the appropriate

use of antibiotics in selected conditionsuse of antibiotics in selected conditions• Developing data collection formsDeveloping data collection forms• Delineating interventionDelineating intervention

INTERVENTION

1. Implementation of a new antibiotic order form

• 80% in US hospitals, 79% in British hospitals

2. Join educational intervention by researchers

and infectologist (lectures and posters)

3. Logo band:blood pressure cuffs “Do not forget

the prophylactic antibiotic one hour before

surgical incision”.

Started in January/1999

OUTCOMES

Condition

1. Aminoglycosides

2. Cephradine/Cephalothin

3. Ceftazidime/Cefotaxime

4. Prophylactic prescription

in surgery

Incorrect prescription

1. Dose interval < 24 h

2. Dose interval > 6 h

3. Dose interval > 8 h

4. Prescription > 1 hour

before and/or after

incision

Hospital weekly proportion of incorrect prescriptions

SAMPLE SIZE = 0.05, two sided test = 0.10• ARIMA (2,0,0) 1 = 0.3

2 = 0.2

20 months of observation before and after intervention = 80 weeks pre-post

Gottman JM (1981) Time series analysis. Cambridge Univ. Press, 335-67

HYPOTHESIS

Abrupt Constant Change

Abrupt Temporary Change

tttt aBBIZZ 11

i tif 1

ior t i tif 0tI

ttt aBBIZ 1

i tif 1

i tif 0tI

B B

Stationary series (discrete and equally spaced intervals)

Moving average process

tZ

ta

Auto-regression process

Random shocks Estimated from time series

ETHICAL ISSUE

• Identification of pre-intervention ARIMA model

• Diagnosis checks over residuals

• Akaike Information Criterion

• No seasonal component expected

• SAS 6.12 TSO 51, Unix

STATISTICAL ANALYSIS

• Informing staff about prescription pitfalls outside the intervention period may produce temporary changes in habits that may attenuate results

• Data collector will not make staff aware of “minor” prescription errors

• Data collector will make staff aware of “major” prescription errors

RESULTS

Anti

bio

tic

Ord

er

Form

RESULTS: 1.Aminoglucosides

Abrupt Constant Change was statistically significant.

0.0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

1 7 13 19 25 31 37 43 49 55 61 67 73 79 85 91 97 103 109 115 121 127 133 139 145

Week

Pro

port

ion

of I

ncor

rect

Pre

scrip

tions

tt aBBZ )49.036.01( 2 102.011 se 101.012 se

Pre-Intervention: ARIMA (0,1,2)

=-0.477 SE=0.064 p<0.001

RESULTS: 2.Cephradine/Cephalothin

0.0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

1 7 13 19 25 31 37 43 49 55 61 67 73 79 85 91 97 103 109 115 121 127 133 139 145

Week

Pro

port

ion

of I

ncor

rect

Pre

scrip

tons

Pre-Intervention: ARIMA (0,1,1)

Neither abrupt constant nor temporary change were statistically significant.

tt aBZ )82.01(

07.0ˆ21 se

RESULTS: 3.Ceftazidime/Cefotaxime

Pre-Intervention: ARIMA (0,0,1)

Abrupt Constant Change was statistically significant.

0.0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

1 7 13 19 25 31 37 43 49 55 61 67 73 79 85 91 97 103 109 115 121 127 133 139

Week

Pro

port

ion

of I

ncor

rect

Pre

scrip

tions

tt aBZ )72.01( 08.031 se

=-0.073 SE=0.03 p<0.05

RESULTS: 4.Prophylactic P. in Surgery

Pre-Intervention: ARIMA (0,1,1)

Abrupt Constant Change was statistically significant. =-0.199 SE=0.069 p=0.004

0.0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

1 7 13 19 25 31 37 43 49 55 61 67 73 79 85 91 97 103

109

115

121

127

133

139

145

Week

Pro

port

ion

of I

ncor

rect

Pre

scrip

tions

tt aBZ )79.01( 062.041 se

DISCUSSION• This study confirms previous reports of

reductions in the proportion of incorrect antibiotic prescriptions by use of an educational campaign and a structured antibiotic order form.

• We believe that our structured prescription form improved the quality of the prescriptions by increasing the awareness of physicians about correct dose intervals which is consistent with previous studies reported in the literature.

DISCUSSION

Reduction in incorrectPrescriptions:

47% : Aminoglycosides7.3%: Ceftazidime

Cefotaxime20%: Prophylactic P. in

surgery

• No enough reduction in Prophylactic Prescriptions in Surgery.

• RCT not feasible due to permanent rotation of residents/nurses, etc.

• Ethical Issue: informing staff about prescription pitfalls.

ACKNOWLEDGMENTS

This work was supported by INCLEN, INC (grant # 1004-97-6501) and Pontificia Universidad Javeriana (grant # 12-24-01-31).