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Uso di antibiotici in ospedale: epidemiologia e misure di controllo

Dr. Nicola PetrosilloDirettore, 2^ Divisione Malattie Infettive

Istituto Nazionale per le Malattie Infettive“Lazzaro Spallanzani”, IRCCS - Roma

ANTIBIOTIC PRESSURE: EFFECT on COLONIZATION BURDEN Shentag, Crit Care Med

2001

Cefazolin Ceftazidime Glycopeptides

101055

MSSAMSSA

101033

MSSA MSSA BSSA BSSA MRSAMRSA

101066

MRSAMRSA

101066

VRE VRE CandidaCandidaHRSA HRSA GISAGISA

community hospital

PrevalencePrevalence and and PatternsPatterns of of AntibioticAntibioticPrescribingPrescribing in in ItalianItalian HospitalsHospitals

• INF-NOS 15 hospitals (2001), size 384-1809 beds

• Pharmacy records for the year 2000 wereused to describe and compare antimicrobialusage density and costs

• DDD, as defined by the WHO, were used(treatment days/100 pts days/year)

Porretta A et al. Infection 2003:31(S2):16-21


-- InterventionIntervention forfor the Control of the Control of AntibioticAntibiotic PrescriptionsPrescriptions --

• In 13 hospitals hospital drug formularycommittee had been instituted;

• in only 4 hospitals it met >3t in 2000

• Periodic drug usage review with data feedbackto the wards in 13 hospitals (10 of themperformed a quarterly review)



-- InterventionIntervention forfor the Control of the Control of AntibioticAntibiotic PrescriptionsPrescriptions --


• In 7 hospitals a cycling protocol

• In 4 hospitals reporting of antimicrobialsusceptibility testing results

• In 6 hospitals prescription of 2nd line orhigh cost antimicrobials was allowed on thebasis of susceptibility testing results (in 4upon the advice of ID consultant)

• Automatic stop order (absence of activeintervention by clinician or ID consultant)


-- Data on Data on AnnualAnnual AntibioticAntibiotic ConsumptionConsumption --


Density of prescription 55.3 DDDx100 pt/d

02468

10121416

tetracyclinesamphenicols

cotrimoxmacrolidesaminoglicquinoloneothersantifungalsantiTB

parenteraloraltotal

parenteral oral35,91 19,41

DDDx100 pt/d

cephalosporins, carbapenems

glycopeptides




ICU -2 or> AB- DDD : 232.8

010203040506070



parenteraloral

DDDx100 pt/d




Surgery DDD: 37.9

02468

101214



parenteraloral

DDDx100 pt/d




Medicine DDD: 27.5

0123456789



parenteraloral

DDDx100 pt/d




Infectious Diseases

0

5

10

15

20

25



parenteraloral

DDDx100 pt/d


-- DifferenceDifference in in prescriptionprescription byby wardward (%) on the day of the (%) on the day of the surveysurvey--

05

101520253035

Medicine Surgery ID ICU

ES ß-lactam Fquin Glyco Carbap Aminogcephal. +ß-lact

inhib.



-- SurveySurvey --


• Of 2.165 pts 985 (45.5%) were receivingat least 1 antibiotic (76% single – 24% combo)

• Reasons:

15%

27%

22%

36%

HAI

CAI

surgicalprophycoverage

La politica antibioticaLa politica La politica antibioticaantibiotica

Dati INFNOS

•1/3 circa dei pazienti senza infezione è in trattamento antibiotico

•Di questi il 5% è in trattamento con glicopeptidi e il 3,5% con carbapenemici

• Il giorno dello studio sono registratipiù di 60 antibiotici usati

•In Chirurgia nel 50% dei casi di IO non èstato utilizzato il laboratorio

Antibiotic usage in intensive care units: a pharmaco-epidemiological multicentre study

Malacarne P et al. JAC 2004; 54:221-4

153 had sepsis

164 pts (20.9%)

979 pts in 43 ICU

Combination 31%Mean duration 3d

3rd gen. cephal. 42%Mean duration 4.6d

Hospital-acquired infections in Italy: a region wide prevalence study

Zotti CM et al. J Hosp Infect 2004; 56:142-9

•Between October and December 2000, a region-wide prevalence study of HAI wasconducted in all public hospitals (59 facilitieswith ca. 16 000 beds; 560 000 admissionyearly) in Piemonte Region, Italy, and in the one hospital of the neighbouring autonomousregion of Valle d’Aosta.

•The study population comprised a total of 9467 patients.

•The prevalence of HAI was 7.84%.


- the day of the survey -


• 3456 pts (36.5%) received at least one antibiotic

2555

687

168 460

500

1000

1500

2000

2500

3000

1 AB 2 AB 3 AB 4 AB


- the day of the survey -


surgical proph

other reasons

infection

0

5

10

15

20

25

3rd ceph

penicilFquin

glyc1-2nd ceph

Ag Carbap

0

5

10

15

20

25

30

35

3rd ceph

penicilFquin

glyc1st cephal

2nd cephal

Ag

All hospital Surgical prophylaxis


- inappropriate use -• Glycopeptides: enterobacteria, Ps. aeruginosa, MSSA

• 3rd and 4th gen. cephalosporins: enterococci

• 3rd generation cephalosporins: 35% in surgical prophylaxis

• Glycopeptides: 5% surgical prophylaxis (only 26.4% -prosthetic device – complied with GL)

• Clean surgery: 512 pts (30.9%) received prophylaxis

• Mean duration of surgical prophylaxis: 3.1 d (31% more than 4 d)


Antibiotic policy in the hospital settingAntibiotic policy in the hospital setting

d. Implementation, with human and economic resources, of an antibiotic restriction programme, and identification of antibiotic molecules that need restriction;

e. Adoption of antibiotic cycling strategies, for empiric therapy, in “hot” hospital zones and based on local antibiotic resistance surveillance system programmes, better defining the molecular basis of antibiotic resistance;

f. Establishment of cost-effective surveillance systems using existing laboratory generated data.

Petrosillo & Struelens, ESCMID 2002

Antibiotic policy in the hospital setting

a. Implementation of educational programmes on use of antimicrobial agents (including pharmacokinetics and pharmacodynamics);

b. Establishment of guidelines and antibiotic audits for an evidence-based and standardized use of

antimicrobials;

c. Identification of those procedures that need and do not need antimicrobial prophylaxis either for surgical or non-surgical purpose (select the drugs for prophylaxis which are not needed for subsequent therapy);

Petrosillo & Struelens, ESCMID 2002

Education

There is a large body of evidence from databases such as the Cochrane database which indicates that the following interventions have a significant effect on healthcare provider behaviour:

•Education •Guidelines •Outreach visits and academic detailing •Audit and feedback

Controversies on the effect of educational programs onantimicrobial use in hospitals

There is a need of continuous reinforcement, supplementedby the feedback of audits of antibiotic use within a specifichospital setting

Prophylaxis

Diffusione di protocolli scrittiDiffusione di protocolli scrittiDiffusione di protocolli scritti

0 10 20 30 40 50 60 70

Pulizia

Precauz. Universali

Disinfezione

Mani

Sterilizzazione

Endoscopi

Isolamento

Vie urinarie

Esami laboratorio

Profilassi antib.

Cateteri vascolari

Ferita Chirurgica

Polmonite

%

Moro ML, Petrosillo N, et al. Infect Control Hosp Epidemiol 2004;25:36-40

Incidence of SSI in Italian Surgical SettingsIncidence of SSI in Italian Surgical SettingsIncidence of SSI in Italian Surgical Settings

Petrosillo N, et al. ECCMID 2004

Restriction

Restriction of hospital formulary through pharmacyand therapeutics committeeRestrictionRestriction of hospital of hospital formularyformulary through through pharmacypharmacyand and therapeuticstherapeutics committeecommittee

Methods

• Cyclic rotation of antimicrobials within a class• Antibiotic order forms• Antibiotic stop orders –therapeutic use

-prophylactic use• Restriction of use• Removal of specific agents• Review of medical records by pharmacists• Usage feedback to physicians• Computerized review• Group purchasing practices• Generic substitution

Shlaes et al. CID 1997;25:584-99

EffectivenessEffectiveness of a of a vancomycinvancomycin restrictionrestriction policypolicy in in changingchanging the the prescribingprescribing patternspatterns of house staffof house staff((RichardsonRichardson LP, LP, etet al. al. MicrobMicrob DrugDrug ResistResist 2000;6:3272000;6:327--30)30)

• Intervention to reduce the rise in VRE infections

• 1995: Encouraging house staff to follow hospital guidelines had little impact.

• 1996: Review of vancomycin orders and one-to-onediscussion with the house staff regarding the rationalefor the order.

• Decrease of inappropriate use (39% to 16.8% p.005)This change was primarily due to a decrease invancomycin prophylaxis in cardiosurgery.

• VRE infections decreased from 0.29/100 pts to0.13/100 pts.

Impact of Impact of antibioticantibiotic changeschanges in in empiricalempiricaltherapytherapy on on antimicrobialantimicrobial resistanceresistance in in ICUICU--

acquiredacquired infectionsinfections

MRSA 93% MRSE 79% PIP/TZ res Ps aerug. 67%

PIP/TZ Carbapenem in nosocomial pneumoniaPIP/TZ cefepime+metronidazole in peritonitisNo antibiotic at admission without feverAM/CL TMP/SMX

MRSA 73% (p=0.003) MRSE 64% (p=0.09)PIP/TZr-Ps aer 29% (p<0.001) Carb-r Ps aer 41% (p=0.06)

Allegranzi B et al. J Hosp Infect 2002;52:136-40

Impact of an antimicrobial formulary and restriction policy in the largest hospital in Italy

Bassetti M, et al. Int J Antimicrob Chemother 2000;16:295-99

• Therapeutic Committee for Hospital Formulary (TCHF)handbook, with reasons for antibiotic choice

• 31 antibiotics without restricted use

• Tazobactam/piperacillin, ceftazidime, cefepime,meropenem -> restricted (ID specialist or microbiology)

• 22 antibiotics erased

• 10.5% decrease of costs for antibiotics

Impact of an antimicrobial formulary and restriction policy in the largest hospital in Italy

Bassetti M, et al. Int J Antimicrob Chemother 2000;16:295-99

ESBLESBL--producingproducing KlebsiellaKlebsiella pneumoniapneumonia outbreaksoutbreaksduringduring a a thirdthird generation generation cephalosporincephalosporin

restrictionrestriction policypolicy

In spite of the adoption of 3rd generation cephalosporinrestriction policies, two independent outbreaks by ESBL-producing Klebsiella pneumonia occurred in two differentwards (NICU and neurosurgery).

Conte MP et al. J Chemother 2005; 17:66-73

AntibioticAntibiotic PoliciesPolicies in in ItalianItalian HospitalsHospitals: : StillStill a a LotLot toto AchieveAchieve

• Questionnaire survey (2000): response rate 80% (428/535)

• Hospital formulary 89%• Hospital pharmacy committee 73.1%

(50% met at least one in 1999)• Written justification for a list of AB 41.4%

(No. of antibiotics in the list 7 [1-49])• Hospitals with periodical pharmacy reports->54%• Data on DDD - 12%• Written protocols for surgical prophylaxis 37%

Moro ML, Petrosillo N, Gandin C. Microb Drug Resist 2003;9:219-22.

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