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The Medical Journal of Australia ISSN:0025-729X 21 April 2003 178 8 386-390©The Medical Journal of Australia 2003www.mja.com.auResearch

PRUDENT USE OF ANTIBIOTICS is cen-tral to controlling the increasing prob-lem of antibiotic resistance in bacteria.Promoting prudent use is a core strategyadvocated by the Australian JointExpert Advisory Committee on Antibi-otic Resistance (JETACAR)1 and is ofmajor public health significance.

Use of broad-spectrum antibioticshas been repeatedly linked to the emer-gence of antibiotic-resistant organisms.In particular, use of third-generationcephalosporins is a risk factor for infec-tion with methicillin-resistant Staphylo-coccus aureus, Clostr idium difficile,enterococci and resistant gram-negativebacilli.2,3 These antibiotics, along withvancomycin and metronidazole, havebeen significantly associated with van-comycin-resistant enterococci (VRE).4

Periods of increased cephalosporin usehave coincided with increased rates ofVRE isolation.5

In 1999, a statewide evaluation of useof the third-generation cephalosporinscefotaxime and ceftriaxone (CEFX)was undertaken in Victorian hospitals.6

These antibiotics were found to be usedmore frequently at the Royal MelbourneHospital than at other comparableteaching hospitals, with only 26% ofcourses being concordant with acceptedindications in the national antibioticguidelines.9 The agents were often usedfor surgical prophylaxis, with all these

courses non-concordant with guide-lines. The most common indication wasrespiratory tract infections, with most ofthese courses non-concordant withguidelines (50% of cases showed noabnormality on chest x-ray, and 11%did not meet the criteria for severepneumonia) (unpublished data).

We sought to improve CEFX use atthe Royal Melbourne Hospital by devel-oping a computerised antimicrobialapproval system with an educationalcomponent. We assessed CEFX usebefore and after introduction of thisintervention.

METHODS

Intervention

A multidisciplinary subcommittee ofthe hospital’s Drug and TherapeuticsCommittee was formed, comprising adrug usage evaluation pharmacist, aclinical pharmacist (infectious diseases),an infectious diseases physician, aninfectious diseases registrar, an emer-gency physician and information tech-nology specialists. This subcommitteedeveloped a multifaceted strategy toimprove CEFX prescribing.

Impact of a web-based antimicrobial approval system on broad-spectrum cephalosporin use at a teaching hospital

Michael J Richards, Marion B Robertson, Jonathan G A Dartnell, Margarida M Duarte, Nicholas R Jones,Dale A Kerr, Lyn-Li Lim, Peter D Ritchie, Graham J Stanton and Simone E Taylor

ABSTRACTObjective: To achieve sustained improvement in use of cefotaxime and ceftriaxone (CEFX) in a major teaching hospital, as measured against national antibiotic guidelines.

Design and setting: Pre- and post-intervention survey of CEFX use in the Royal Melbourne Hospital, a tertiary hospital in Melbourne, Victoria.

Intervention: Web-based antimicrobial approval system linked to national antibiotic guidelines was developed by a multidisciplinary team and implemented in March 2001.

Main outcome measures: Change in rate of CEFX use (defined daily doses [DDDs] per 1000 acute occupied bed days) over 8 months pre- and 15 months post-intervention; concordance of indication for CEFX with national antibiotic guidelines pre- and post-intervention.

Results: CEFX use decreased from a mean of 38.3 DDDs/1000 bed days pre-intervention to 15.9, 18.7 and 21.2 DDDs/1000 bed days at 1, 4 and 15 months post-intervention. Concordance with national antibiotic guidelines rose from 25% of courses pre-intervention to 51% within 5 months post-intervention (P < 0.002). Gentamicin use also increased, from a mean of 30.0 to 48.3 DDDs/1000 bed days (P = 0.0001).

Conclusion: The web-based antimicrobial approval system achieved a sustained reduction in CEFX use over 15 months as well as increased prescribing concordance with antibiotic guidelines. It has potential for linking to electronic prescribing and for wider

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use for other drugs, as well as for research into the epidemiology of antibiotic use.

Royal Melbourne Hospital, Parkville, VIC.Michael J Richards, FRACP, Infectious Diseases Physician, Victorian Infectious Diseases Service, Centre of Clinical Research Excellence in Infectious Diseases; Lyn-Li Lim, MB BS, Infectious Diseases Registrar; Marion B Robertson, BPharm, MSc, Drug Usage Evaluation Pharmacist; Nicholas R Jones, BPharm, Grad Dip Clinical Pharmacy, Clinical Teacher (Pharmacy); Simone E Taylor, PharmD, Grad Cert CRM, Clinical Pharmacy Coordinator and Infectious Diseases Clinical Pharmacist; currently, Senior Clinical Pharmacist – Emergency Medicine, Austin and Repatriation Medical Centre, Melbourne, VIC; Margarida M Duarte, BA (CompSci), BEng (partial) , Web Based Delivery Team Leader; Dale A Kerr, BBus (Information Systems) , Senior Database Administrator; Graham J Stanton, Senior Web Based Delivery Team Member; Peter D Ritchie, MPubHlth, FACEM, Emergency Physician.

Therapeutic Guidelines Limited, North Melbourne, VIC.Jonathan G A Dartnell, BPharm, PhD, Production Manager. Reprints will not be available from the authors. Correspondence: Dr Michael J Richards, Victorian Infectious Diseases Service, c/- Post Office, Royal Melbourne Hospital, VIC 3050.Michael.Richards@mh.org.au

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CEFX was added to thehospital’s list of restrictedantimicrobial agents. It wasremoved from operating thea-tres and general wards, butnot from the emergencydepartment (ED), intensivecare unit (ICU) or infectiousdiseases ward. Prescriptionsfor CEFX were required to beendorsed with an Antimicro-b ia l Approva l Number(AAN). This is a code com-prising the authoriser’s ini-tials, date of prescription andduration of approved use.

A web-based form for gen-erating these numbers wasintroduced for CEFX pre-scriptions for indications rec-ommended in the nationalantibiotic guidelines.7 Thisform was interactive andlinked to the antibiotic guide-lines. It required prescribersto choose the drug and indi-cation from drop down lists(Box 1).

Computer-generated AANswere not provided for indica-tions not listed. Prescribersseeking AANs for these indi-cations were asked to tele-phone the infectious diseasesregistrar.

A 24-hour grace periodwas allowed if prescriberswere unable to gain approvalthrough the web-based sys-tem or to contact an infec-tious diseases registrar. Theantimicrobial approval sys-tem did not apply to theICU, where other initiatives wereundertaken to assist antimicrobialprescribing.

Introduction of the intervention

The antimicrobial approval system wasintroduced on 20 March 2001, after twomonths of educational sessions anddemonstrations for prescribers, phar-macists and administrators. A compu-ter-assisted aminoglycoside dosingservice was introduced at the same timeto minimise the risk of toxicity, inexpectation of increased use of theseagents.

Monitoring

Feedback was sought from hospital med-ical staff to identify problems twomonths after the system was introduced.

The progress of the system was mon-itored in two ways. Firstly, monthlygross use figures for CEFX (defineddaily doses [DDDs] per 1000 occupiedacute case bed days) were generatedfrom the pharmacy dispensing systemand reported to the Antimicrobial Sub-committee.

Secondly, a concurrent, observationalevaluation of CEFX use in patientscommencing a course of these drugs

was conducted during sevendays in September 1999 (pre-intervention) and 14 days inJuly 2001 (about four monthspost-intervention) using themethods described by Robert-son et al.6 Courses wereassessed for concordance withthe current edition of Thera-peutic guidelines: antibiotic (ver-sion 10 in 1999, and version11 in 2001).7,9

Prescribing data were fedback to doctors once theapproval system was estab-lished. Hospital units weregiven reports on their useof broad-spectrum cepha-losporins and the proportionof use for which approvalnumbers were obtained inthe previous month. Sub-sequently, the correlationbetween the indication “severecommunity-acquired pneu-monia” and abnormal chestx-ray was examined. Letterswere sent to prescribers whotwice or more entered severepneumonia as the indicationwhen the chest x-ray was for-mally reported as normal atthe time of prescribing.

Statistical analysis

Mean CEFX use was com-pared before and after theintervention using the non-parametric Kruskal–Wallistest.10 Proportions were com-pared using Fisher’s exacttest.11

RESULTS

Cephalosporin use

Monthly CEFX use in the hospital fellto about half previous use on introduc-tion of the system, a result sustained for15 months (Box 2). While there was nosignificant change in CEFX use in theICU (where the intervention was notundertaken) (P = 0.68), there was a sig-nificant reduction in use in the wards(mean, 38.3 DDDs/1000 bed days pre-intervention v 17.6 DDDs/1000 beddays post-intervention; P = 0.002).

1: Web-based form for generating Antimicrobial Approval Numbers for ceftriaxone/cefotaxime prescriptions

Prescribers were required to log into the form using their hospital network log-in code as identification, to enter the patient’s medical record number and check that correct patient details were displayed, and then to choose the drug and indication from drop down lists.

Each listed indication was linked to the relevant section of the antibiotic guidelines accessible on the Clinicians Health Channel,8 a health information portal provided by the Victorian Department of Human Services. The form was interactive. For example, prescribers who wished to use ceftriaxone for community-acquired pneumonia had to indicate that the chest x-ray showed a pulmonary infiltrate and that specified criteria for severe pneumonia were met.

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The number of AANs per monthranged from 39 to 71, accounting for36% to 62% of grams of CEFX pre-scribed. However, despite regular feed-back in the ED, only 4%–17% of gramsof CEFX prescribed were accounted forby AANs.

The proportion of approvals that wereobtained using the web-based formrather than by telephone increased from56% in April 2001 (one month afterintroduction of the system) to 90% inSeptember 2001 (six months after itsintroduction) and remained in the85%–95% range thereafter.

Results of the indication-linkedaudits of CEFX use are summarisedin Box 3. After the intervention, usebecame more consistent with nationalantibiotic guidelines (P < 0.002), anduse for surgical prophylaxis was nil. Inparticular, the proportion of patientstreated empirically with CEFX forrespiratory tract infection who did nothave an abnormality on chest x-raydecreased from 50% (18/36) pre-intervention to 27% (11/41) post-intervention.

Feedback to staff

Reports to units regarding their compli-ance with the approval system weregenerally thoughtfully received, oftenwith written requests for more informa-tion. The initiative of contacting pre-

scribers who misreported severepneumonia is too recent to evaluate. Inthe first month of this assessment, fourprescribers incorrectly indicated thatpneumonia was present on the chestfilm when the chest x-ray was reportedby a radiologist as normal.

Use of other antibiotics

Use of other broad-spectrum �-lactamantibiotics and quinolones showed noconsistent increase. In contrast, bothgentamicin and benzylpenicillin useincreased significantly — gentamicinfrom a mean of 30.0 DDDs/1000 beddays pre-intervention to 48.3 DDDs/1000 bed days post-intervention(P = 0.0001), and benzylpenicillin froma mean of 20.7 DDDs/1000 bed days to28.4 DDDs/1000 bed days (P = 0.01)(Box 2).

DISCUSSION

We found that introduction of a multi-faceted strategy, including a simplecomputerised antimicrobial approvalsystem with an educational compo-nent, was successful in reducingCEFX use in our hospital and increas-ing concordance with prescribingguidelines. CEFX use for surgicalprophylaxis was effectively eliminated,while CEFX use for respiratory infec-tions without evidence of pneumoniaon ches t x - ray wa s ma rk ed ly

2: Use of ceftriaxone/cefotaxime and other antibiotics at Royal Melbourne Hospital before and after introduction of the antimicrobial approval system

DDD = defined daily dose. After introduction of the approval system in March 2001, there was a significant decrease in use of ceftriaxone/cefotaxime (P = 0.002) and significant increases in use of gentamicin (P = 0.0001) and benzylpenicillin (P = 0.01).

0

10

20

30

40

50

60

Gentamicin Ciprofloxacin

Piperacillin/ticarcillin

Imipenem/meropenem

BenzylpenicillinCeftriaxone/cefotaxime

MayMarJanNovSepJulMayMarJanNovSepJul

2000 2001 2002

DD

Ds/

1000

bed

day

s

Approval system

introduced

3: Ceftriaxone/cefotaxime use and concordance with national antibiotic guidelines at Royal Melbourne Hospital and other hospitals

Royal Melbourne Hospital

Other Melbourne teaching hospitals6

A B C D

Study date Jul 2001 Sep 1999 Sep 1999 Sep 1999 Sep 1999 Sep 1999

Length of enrolment (days) 14 7 7 7 7 7

Number of courses 74 79 45 39 39 22

Defined daily doses/1000 bed days

22 35 26 22 39 12

Number of courses started in operating theatres

0 17 (22%) 16 (36%) 0 0 0

Concordance with guidelines*

All courses 51%† 26%† 33% 28% 18% 45%

Empirical courses for respiratory tract infection

17/41 (41%)

8/36 (22%)

11/27 (41%)

8/23 (35%)

4/20 (20%)

6/13 (46%)

* Therapeutic guidelines: antibiotic (11th edition7 in 2001 and 10th edition9 in 1999).† P < 0.002 Fisher’s exact test.

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decreased. The changes were sus-tained over 15 months of follow-up.

Features of the strategy that may havecontributed to its success include edu-cational programs, restrictions onCEFX availability in the wards, and theantimicrobial approval system itself.Education alone (lectures and tutorials)has been generally ineffective in achiev-ing sustained change,12 but was essen-tial to our strategy to ensure thatchanges in prescribing practice wereacceptable and understood by prescrib-ers. Restricted availability on wards hadmore direct effects on pharmacists andnurses who obtained the drugs, remind-ing them of the new process, than pre-scribers. The approval system aims tobe a disincentive to non-considered useof broad-spectrum agents, to educatethrough links to national guidelines, andto act as a surveillance tool allowingfeedback to clinicians. Sustainability isone of the greatest challenges in modify-ing prescribing. We believe the ongoingapproval system together with feedbackto clinicians explained much of the sus-tained improvement.

Commitment to the program by keystaff, adequate staff time for educationalprograms and endorsement by seniorhospital clinicians and managementwere fundamental to its success.

Antimicrobial approval and restric-tion systems have been effective in con-trolling antibiotic use elsewhere, butmay require significant resources and, ifinefficient, can cause great inconven-ience.13 Some hospitals in the UnitedStates have successfully used computer-assisted decision support systems linkedwith electronic prescribing to imple-ment antibiotic practice guidelines.14,15

These sophisticated systems generatealerts if inappropriate agents are chosenfor identified pathogens and give rec-ommended antibiotic choices by indica-tion and local consensus guidelines.However, these systems were “purposebuilt”, extremely costly to implement,and not easily set up elsewhere. Oursystem is simpler and has been inexpen-sive to develop to this stage. However, itwould benefit from expansion to otherrestricted drugs and improved reportingcapacity.

A recent review of strategies toimprove hospital prescribing reportedthat “multifaceted interventions aimed

at barriers to good prescribing have thegreatest chance of success”.13 Multifac-eted strategies have been recommendedto contain antibiotic resistance by theWorld Health Organization16 and JET-ACAR.1 Such a strategy, includingguidelines, educational activities, andrapid feedback to prescribers aboutinappropriate use, was successful inreducing overuse of third-generationcephalosporins at the John Hunter Hos-pital, Newcastle, NSW.17

We developed our strategy with theknowledge that many experienced hos-pital clinicians disagreed with some rec-ommendations of the national antibioticguidelines. The pre-intervention audithelped identify non-controversial areasof inappropriate use. These were tar-geted by educational programs. Weaccepted less than full compliance, hop-ing that it would increase with time andeducation. There has been little appar-ent resentment by clinicians.

The approval system was least used inthe ED. As ED consultants predictedthat time pressures in this departmentwould make a web-based approval sys-tem impractical, a simple paper-basedalternative was developed, and educa-tional sessions arranged, but compli-ance was limited. We tried to improveparticipation through involving a clini-cal pharmacist in the ED and throughphysician feedback, with little success.As many antibiotic courses were com-menced in the ED, this is an importantongoing challenge.

Introduction of the system was com-plicated by non-standardised softwarein ward computers, which was over-come relatively easily. For routine indi-cations, prescribers overwhelminglyused the web-based rather than the tele-phone approval system. Informal feed-back on acceptability to prescribers ateducational meetings showed that theyoccasionally “cheated”, particularlywhen consultants indicated to juniorstaff a preference for CEFX for non-standard indications.

A concern is that a computerisedsystem may diminish discussion aboutantimicrobial resistance and usebetween prescribers and infectious dis-eases physicians. However, the systemaimed to encourage discussion of non-standard indications, and use of infec-tious diseases consultative services did

not decrease, while the “presence” ofinfectious diseases physicians at educa-tional meetings increased.

Although we did not incorporate theeffects of autocorrelation or any sea-sonal effects in our analysis, we believethe reduction in cephalosporin use iscompelling. The greatest potential ben-efit of improved prescribing is in reduc-ing the development of antibiotic-resistant organisms, but surveillance ofthis resistance would have requiredmore resources than were available.

We did not attempt detailed costing ofthe intervention, but note that softwaredevelopment costs were about $6000,while education was included in theroutine activities of the Infectious Dis-eases Service, Pharmacy and DrugUsage Evaluation Program. The post-intervention audit involved about 12person-weeks, and ongoing mainte-nance and audit occupy one person-dayper month. The increase in gentamicinuse increased demand on the aminogly-coside dosing service.

The approval system has potentialbenefits beyond improving use ofbroad-spectrum cephalosporins. Theweb-based form may save time for bothprescribers and authorising doctorscompared with telephone-based sys-tems. Other hospitals have expressedinterest in the system; a multicentresystem would potentially allow researchon the epidemiology of antibiotic useand its relationship to antibiotic resist-ance genes. The system is a potentialmodel for promoting optimal use ofother restricted or expensive pharma-ceuticals within the hospital. Anexpanded system incorporating otherrestricted antibiotics and linking pre-scribing to laboratory results and deci-sion support systems is currently beingdeveloped.

ACKNOWLEDGEMENTS

We acknowledge the assistance of Dr Jim Black (Victo-rian Infectious Diseases Service, Royal Melbourne Hospi-tal) in performing the statistical analysis.

COMPETING INTERESTS

None identified. Development of the antimicrobialapproval system was funded within the budget of theRoyal Melbourne Hospital.

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REFERENCES1. Joint Expert Technical Advisory Committee on Anti-

biotic Resistance (JETACAR). The use of antibioticsin food-producing animals: antibiotic-resistant bac-teria in animals and humans. Report of JETACAR.Commonwealth Department of Health and AgedCare and Commonwealth Department of Agriculture,Fisheries and Forestry — Australia. Canberra: Aus-info, 1999. Available at: http://www.health.gov.au/pubs/jetacar.pdf (accessed Mar 2003).

2. Paterson DL, Playford EG. Should third-generationcephalosporins be the empirical treatment of choicefor severe community-acquired pneumonia inadults? Med J Aust 1998; 168: 344-348.

3. Ferguson JK. Vancomycin-resistant enterococci:causes and control. Med J Aust 1999; 171: 117-118.

4. Dahms RA, Johnson EM, Statz CL, et al. Third-generation cephalosporins and vancomycin as riskfactors for postoperative vancomycin-resistant ente-rococcus infection. Arch Surg 1998; 133: 1343-1346.

5. Quale J, Landman D, Atwood E, et al. Experience witha hospital-wide outbreak of vancomycin-resistantenterococci. Am J Infect Control 1996; 24: 372-379.

6. Robertson MB, Korman TM, Dartnell JGA, et al.Ceftriaxone and cefotaxime use in Victorian hospi-tals. Med J Aust 2002; 176: 524-529.

7. Writing Group. Therapeutic guidelines: antibiotic.11th ed. Melbourne: Therapeutic Guidelines Lim-ited, 2000.

8. Clinicians Health Channel. Victorian GovernmentDepartment of Human Services. Available at: http://www.clinicians.vic.gov.au/ (accessed Mar 2003).

9. Writing Group. Therapeutic guidelines: antibiotic.10th ed. Melbourne: Therapeutic Guidelines Lim-ited, 1998.

10. Dean A, Dean J, Coulombier D, et al. Epi Info,version 6: a word processing, database, and statis-tics program for public health on IBM-compatiblemicrocomputers. Atlanta: Centers for Disease Con-trol and Prevention, 1996.

11. Altman D. Practical statistics for medical research.London: Chapman and Hall, 1991.

12. Bero LA, Grilli R, Grimshaw JM, et al. Closing thegap between research and practice: an overview ofsystematic reviews of interventions to promote theimplementation of research findings. The Cochrane

Effective Practice and Organization of Care ReviewGroup. BMJ 1998; 317: 465-468.

13. Dartnell JGA. Activities to improve hospital prescrib-ing. Aust Prescriber 2001; 24: 29-31.

14. Pestotnik SL, Classen DC, Evans RS, Burke JP.Implementing antibiot ic practice guidelinesthrough computer-assisted decision support : clini-cal and financial outcomes. Ann Intern Med 1996;124: 884-890.

15. Shojania KG, Yokoe D, Platt R, et al. Reducingvancomycin use utilizing a computer guideline:results of a randomized controlled trial. J Am MedInform Assoc 1998; 5: 554-562.

16. World Health Organization. WHO global strategy forcontainment of antimicrobial resistance 2001. Avail-a b le at : h ttp : / /www.who .in t /e mc/a mrpd fs /WHO_Global_Strategy_English.pdf (accessed Mar2003).

17. MacDonald J, Ferguson J. Hospital education influ-ences prescribing at John Hunter Hospital. AustPrescriber 2001; 24: 32.

(Received 2 Sep 2002, accepted 6 Feb 2003) ❏