An introduction to evidence-based practice and the effectiveness of antibiotic prophylaxis

MARCO ESPOSITOSenior Lect rer in Oral and Ma illofacial S rgerSenior Lecturer in Oral and Maxillofacial Surgery

Director of the Postgraduate Courses in Dental ImplantologyEditor of the Cochrane Oral Health GroupEditor of the Cochrane Oral Health Group

The University of Manchester, UKAssoc Prof in Biomaterials, Göteborg University, SwedenAssoc Prof in Biomaterials, Göteborg University, Sweden

Editor-in-Chief or the European Journal of Oral Implantology (EJOI)Editor of the Rivista Italiana di Stomatologia (RIS)Editor of the Rivista Italiana di Stomatologia (RIS)

Conflict of interests - consultant for:Conflict of interests consultant for:Apollonia e Fama Implants srl Nano Bridging Molecules SAApollonia e Fama Implants srl Biomax srlBiomet 3i

Nano Bridging Molecules SANobel BiocareRicerfarma srlo e 3

Bioteck srlBone System srl

ce a a sSaint Jude Medical IncSouthern Implantsy

Brånemark Integration ABCMS Dental

S pTecnoss Dental srlThommen Medical AG

Dentsply-Friadent AGGeistlich Pharma AG

Tutogen Medical GmbHZimmer Dental

Geass srlMegaGen Implant Co

Z-System AGg p

Why we do clinical research?1. To get an academic promotion?

2. To show colleagues how good we are?

3. To show how good is the product I wish to sell?

4. To save money for national health services?y

5 To solve clinical problems for helping patients?5. To solve clinical problems for helping patients?

Why reliable clinical research isWhy reliable clinical research is needed?

Evidence-based clinical research should help people to take the right clinical decisions:

- Which is the best implant surface?

- May I load the implants immediately?

- Is GBR needed to cover an implant fenestration?fenestration?

What is evidence-based practiceWhat is evidence-based practice(EBP)?( )

The integration ofThe integration of best clinical research evidence

with individual clinical expertise

and ti t lpatient values

How does the process of EBP work?How does the process of EBP work?

• Formulate a clinical question

• Find the evidence

• Critically appraise the evidence

• Act on the evidenceAct on the evidence

Why EBP is needed?

Cli i l d i i h ld b b dClinical decisions should be based on updated and reliable evidence andupdated and reliable evidence and

not on personal opinions p p(opinion-biased practice)

YOU CANNOT MAKE AN INFORMED DECISION

WITHOUT INFORMATIONBUTBUT

NOT ALL INFORMATION ISNOT ALL INFORMATION IS CREATED EQUALCREATED EQUAL

Wh t i th li i l ti ?What is the clinical question?• Diagnosis

• Prognosis

• Treatment

• Risk / BenefitRisk / Benefit

• Cost effectiveness• Cost effectiveness

How do we discriminate betweenHow do we discriminate between reliable and poor clinical research?p

CRITICAL APPRAISAL

The process of assessing and interpretingThe process of assessing and interpreting evidence through the systematic consideration f i (i l) lidi d lof its (internal) validity and relevance

INTERNAL VALIDITYINTERNAL VALIDITYTh d t hi h th lt f t dThe degree to which the results of a study are

likely to approximate to the ‘truth’y pp

How well the study is conductedy

EXTERNAL VALIDITYEXTERNAL VALIDITYThe degree to which the results of a trial holdThe degree to which the results of a trial hold

true in another setting

IS CRITICAL APPRAISAL NECESSARY?

is ABSOLUTELY necessary to limit BIAS since there are so many poor quality studies whose

claims should be discountedclaims should be discounted

Critical appraisal is a very difficultCritical appraisal is a very difficult process since there are no “absolute rules”p

BIASBIASA systematic error or deviation in the

results occurring in a study determining a difference between thedetermining a difference between the

obtained results and the results weobtained results and the results we should have obtained in absence of bias

TYPES OF BIASTYPES OF BIAS• Publication bias: bias towards positive results• Selection bias: systematic differences in groups that are comparedp• Performance bias: exposures to other factors apart from the intervention of interestfrom the intervention of interest

• Attrition bias: withdrawals or exclusion of subjects jentered into a study• Detection bias: how outcomes are measuredDetection bias: how outcomes are measured

• Commercial bias: the tendency for the sponsored y pintervention to be more effective than what actually is

Different study designs answer different questionsy g qQUESTION IDEAL STUDY DESIGN

Therapy Randomised controlled trial (RCT)

S i C ti l ( l )Screening Cross-sectional survey (prevalence)RCT to assess efficacy

Diagnosis Cohort study (incidence)RCT to assess efficacyRCT to assess efficacy

Prognosis Cohort studyg y

Causation Cohort study (in the case of very rare diti f l i f ti b d i dconditions useful information may be derived

from case control studies and case reports)

The most common clinical studyThe most common clinical study designs aredesigns are

- Case report/case seriesCross sectional surveys- Cross-sectional surveys

- Case-control studies- Cohort studies- Randomized controlled clinical trials (RCTs)

Case reports/case seriesCase reports/case seriesdescribes the medical history of a single patientdescribes the medical history of a single patient (case report) or a series of patients (case series)

i h i l di iwith a particular condition

Appropriate for describing rare adverse events:- 2 newborn babies do not have limbs (phocomelia) and both (p )mothers took a new drug (talidomide)

Inappropriate for describing treatment efficacy:- A technique to rebuild the interdental papilla worksq p p

Cross sectional surveysCross sectional surveysSynonyms: prevalence study, disease frequency y y p y, q y

survey

A representative samples of subjects is examined t ifi li i l ti (ito answer a specific clinical question (i.e. prevalence of a disease at a particular time)- How many implants are affected by peri-implantitis 5 years after their placement?years after their placement?

Cause effect relationships cannot be establishedCause-effect relationships cannot be established

Case control studiesCase-control studiesPatients with a particular disease (or other outcome variables)Patients with a particular disease (or other outcome variables) of interest are “matched” with suitable controls without the disease despite having or not the suspected risk factors of thedisease despite having or not the suspected risk factors of the disease

Concerned with the aetiology of a disease (what cause the disease and not how to treat it)disease and not how to treat it)Less reliable than cohort studies but are the only option for

ditirare conditions

Retrospective by definition since it starts after the onset of theRetrospective by definition since it starts after the onset of the disease and looks back to the postulated casual factors

E l f t l t dExample of a case-control study

Can talidomide cause limb malformations (phocomelia) in newborns?

Select a group of phocomelic babies and matchit with a group of healthy babies calculatingit with a group of healthy babies calculating

the proportion of mothers who took talidomide during pregnancy for both groups

Cohort studiesCohort studiesSynonyms: concurrent, follow-up, incidence, y y , p, ,longitudinal, prospective studies

2 or more groups of people are selected on the basis of differences in their exposure to abasis of differences in their exposure to a particular agent and followed up to see how

i h d l ti lmany in each group develop a particular disease or other outcome

Large number of patients followed up for long periods (years)

Cohort studiesCohort studies- Ideal study design to determine the prognosis of- Ideal study design to determine the prognosis of

a disease (i.e. what is likely to happen to someone who has it) and “cause-effect” relationshipsrelationships

- In the 1950, 40.000 doctors were divided into 4 cohorts (non-smokers, light, moderate and heavy smokers) a “dose-response” relation washeavy smokers), a dose-response relation was found (i.e. the more you smoke, the greater are the chances to get lung cancer)

Randomised controlled clinical trialsRandomised controlled clinical trials- Is a controlled trial in which participants are

allocated at random to receive one of theallocated at random to receive one of the several clinical interventions

- Ideal study design to assess treatment efficacysince randomisation is the only way to control for confounding factors which are not knownfor confounding factors which are not known or measured, thus minimizing bias

Why not using other types of t d d i t ffi ?study design to assess efficacy?

- More uncertainty with non-RCTsMore uncertainty with non RCTs

- Non-RCTs are much more difficult to assess

Types of RCTs- Explanatory RCT: aimed to understand how things happen

(efficacy of a bone substitute to form more bone in a sinus)- usually single centre- strict inclusion criteria- complex surrogate outcomes: quantification of subtle tissue volume

changes, histomorphometry, bacteriological evaluation

- Pragmatic RCT: aimed to evaluate how things go in clinical practice (effectiveness of antibiotic prophylaxis)practice (effectiveness of antibiotic prophylaxis)- Usually large multicentre trials including many patients

broad inclusion criteria- broad inclusion criteria- using few primary outcomes: prosthesis and implant failures,

complicationsp

HIERARCHY OF EVIDENCE FOR THERAPEUTIC EFFICACY

STRONG Randomized controlled clinical trials- Systematic review of IPD RCTs- Systematic review of RCTs- multiple confirmatory RCTs- single RCT multicenter-monocenter

Controlled clinical trialsControlled observational studiesControlled observational studiesObservational studies without controls

WEAK C i iWEAK Case reports, expert opinions, consensus

The choice of a correct study design is not a synonymous of study qualitysynonymous of study quality

Withi ti l t d d i th i hWithin a particular study design there is a huge variability between studies with regard to their

execution

It is the task of the reader to evaluate the quality of the study and to identify flawsquality of the study and to identify flaws

Essential questions to evaluate RCTsEssential questions to evaluate RCTs

- Was the sample size calculated?

- Were the treatments randomly allocated ( ll i l ?)(allocation concealment?)

- Were outcomes assessed blind?

- Were all the patients accounted for?

BLINDINGBLINDING

Used to keep the study subjects, therapy providers, outcome assessors and statisticians ignorant about gthe interventions participants received (PLACEBO)

Not always possible to blind those providing/receiving care (surgical interventions)providing/receiving care (surgical interventions)

i d d t h ld b d i t dindependent assessors should be used instead

PRIMARY AND SECONDARY OUTCOMESPRIMARY AND SECONDARY OUTCOMES

PRIMARY or TRUE OUTCOMES: those having aPRIMARY or TRUE OUTCOMES: those having a tangible influence on the patient’s life (function of the

h i b f i h i )prosthesis, absence of pain, aesthetics, etc)

SECONDARY or SURROGATE OUTCOMES: those which may predict the primary outcomes (plaque, y p p y (p q ,bleeding, pocket depths, marginal bone levels, etc)Be careful since they can induce to wrong conclusionsBe careful since they can induce to wrong conclusions

What implications for your practice?- How big was the effect?

Was the effect clinically important?- Was the effect clinically important?- Is the paper of good quality?- Are the findings likely to be true?

Is your patient similar to those evaluated in the trial?- Is your patient similar to those evaluated in the trial?- The conditions in which the study was carried out resemble the circumstances of your practice?

Where to find the best evidence?Where to find the best evidence?A k ith “ i ”?• Ask someone with more “experience”? usually “opinion biased practice”usually opinion biased practice

• Consult a textbook? not peer reviewednot peer reviewed

• Search an electronic database for articlesP bM d E b Th C h Lib- PubMed, Embase, The Cochrane Library

Where to easily access scientificWhere to easily access scientific evidence?evidence?

U d d i f h liUpdated review of the literature

Unfortunately the quality of many narrative reviews is not optimal, since oftenreviews is not optimal, since often - not structured in a systematic way- do not follow the scientific principles of objectivity in data collection and interpretationobjectivity in data collection and interpretation

Systematic reviews and meta-analysesSystematic reviews and meta analyses

• Systematic reviews (SRs) employ explicit and rigorous methods to identify, critically appraiserigorous methods to identify, critically appraise and synthesize relevant research for limiting bias t h id b d l ito reach evidence-based conclusions

• A meta-analysis is a statistical technique for combining quantitative data to estimate acombining quantitative data to estimate a common pooled effect with increased precision used in a systematic review

When systematic reviews areWhen systematic reviews are particularly useful?particularly useful?

- Results from several studies disagree regarding magnitude or direction of effect

- Individual sample sizes are too small to detect a statistical significance

How should be a systematic review?How should be a systematic review?

• If dealing with therapies/prevention, it mustb b d RCT i th ff th hi h tbe based on RCTs, since they offer the highest chance to provide more reliable informationp

N RCT t d t ti t i t ti• Non RCTs tend to overstimate intervention effects

Who makes systematic reviews?

The COCHRANE COLLABORATION(www cochrane org): an international(www.cochrane.org): an international

collaboration aimed to help people making well informed decisions by preparing and

maintaining SRs on risks/benefits ofmaintaining SRs on risks/benefits of healthcare interventions

MAIN QUESTIONS ANSWERED BY A META ANALYSISA META-ANALYSIS

1) In which direction goes the treatment effect?

2) How big is the treatment effect?

3) I th t t t ff t i t t t di ?3) Is the treatment effect consistent among studies?

SUMMARY 1SUMMARY 1• Evaluate the appropriateness of the study design to answerEvaluate the appropriateness of the study design to answer

your question

• When evaluating the effectiveness of an intervention look for SYSTEMATIC REVIEWS of RCTs or RCTs

• If SR/RCTs are not available then consider the next best level of “inferior” evidence (cohort studies) with extremelevel of inferior evidence (cohort studies) with extreme caution!

• Whichever level of evidence you consider, the validity and the clinical utility of the study have to be critically evaluated

SUMMARY 2SUMMARY 2• Identify the main flaws which may actually alter• Identify the main flaws which may actually alter

significantly the results

• Decide whether the results are transferable to your population of interest

• Use your head, read all the paper carefully, do not trust what is written in the conclusions alonenot trust what is written in the conclusions alone

Wh t i d d?What is needed?- Better research

- Balanced information (benefits/harms)

“We need less research, better research, and research done for the right reasons”

Altman DG 1994Altman DG 1994

SUGGESTED READING1) The pocket guide to clinical appraisal. Crombie IK.

B iti h M di l J l P bli hi G L dBritish Medical Journal Publishing Group, London,1996

2) Cochrane Handbook for Systematic Reviews ofinterventions. Higgins JPT, Green S, editors. Wiley-Blackwell, Chichester, 2008http://www.cochrane.org/resources/handbook/hbook htmok.htm

3) ….. and especially for clinicians seeking for3) ….. and especially for clinicians seeking forevidence-based answers to clinical questions……

Reliable clinical articles related to the practice of oral implantology and related disciplinesand related disciplines

Updated evidence-basedUpdated evidence-based information to help clinicians take th b t d i i f th ithe best decisions for their patients

Systematic reviews, RCTs, cohort and case-control studies

h // i d / j ihttp://quintessenz.de/ejoi

Clinical questionClinical question

Are antibiotics effective in reducing li ti d i l t f il ?complications and implant failures?

BackgroundBackgroundOsseointegrated dental implants used since 1965Osseointegrated dental implants used since 1965

Various antibiotic prophylactic types/regimensVarious antibiotic prophylactic types/regimens have been recommended ranging from:

2 g of penicillin-V 1 hour preop + 2 g twice a day for 10 days

tto

no antibioticsno antibiotics

B k dBackgroundThere could be adverse events associated with

antibiotics ranging from:antibiotics ranging from:

di h h l if i idiarrhoea, erythema multiforme, urticaria, etctoto

life-threatening allergic reactionsrisk of selecting antibiotic-resistant bacteria

WHERE TO FIND THE EVIDENCE?

Esposito, Cannizzaro, Bozzoli, Checchi, Ferri Landriani Leone Todisco TorchioFerri, Landriani, Leone, Todisco, Torchio,

Testori, Galli, Felice

Effectiveness of prophylactic antibiotics at placement of dental implants: a pragmatic multicentre placebo-controlled randomised

clinical trial2010; 3: 101-110

Conflict of Interest: self-funded study Antibiotics & placebo kindly donated by Merk Generics ItaliaAntibiotics & placebo kindly donated by Merk Generics Italia

AiAimTo evaluate the effectiveness of a single dose 2 g amoxicillin administered orally 1 hour2 g amoxicillin administered orally 1 hour

before implant placementp p

STUDY DESIGNSTUDY DESIGNPragmatic multicenter placebo controlledPragmatic multicenter placebo-controlled

randomised clinical trial

Inclusion/exclusion criteriaAny patient undergoing implant placement Apr 2008 – Nov 2009Excluded if:1) at risk of bacterial endocarditis (as decided by the cardiologist)2) having implanted biomaterials (hip or knee prostheses, etc.)3) immunosuppressed or immunocompromised3) immunosuppressed or immunocompromised4) affected by controlled or not diabetes5) radiotherapy in the head and neck area) py6) need of augmentation procedure at implant placement7) allergic to penicillin8) chronic/acute infections at implant sites9) already under antibiotic treatment10) treated or under treatment with intravenous amino bisphosphonates10) treated or under treatment with intravenous amino-bisphosphonates11) pregnant and lactating12) less than 18 year old or not able to sign an informed consent) y g13) already included once in the present study

Outcome measuresOutcome measures1) Prosthesis failure2) Implant failure:2) Implant failure:

- implant mobilityany infection dictating implant removal- any infection dictating implant removal

Implant stability was tested at 4 months by tightening the abutment with a 20-30 Ncm torqueabutment with a 20 30 Ncm torque

3) Any complication4) Any adverse event4) Any adverse event

Outcomes recorded at 1, 2 weeks and 4 months

All assessments made by treating dentists who remained unaware of group allocation for the entire study durationunaware of group allocation for the entire study duration

Methodological aspects• Computer generated randomisation lists with equal

b f ti i tnumber of participants • Randomised codes enclosed in envelopes opened 1 h p p

prior to implant placement (concealed allocation)• Triple blind:Triple blind:

– Patientoperator/outcome assessor– operator/outcome assessor

– statisticianS l i f d i diff i i l f il• Sample size for detecting a difference in implant failurefrom 1 to 5%: 333 patients per group

Clinical proceduresClinical procedures• Patients recruited in experienced Italian private

clinics• All patients underwent at least 1 session of oral p

hygiene • 1 h prior to implant placement patients were• 1 h prior to implant placement patients were

randomised to receive amoxicillin (2 1g tablets) or 2 identical placebo tabletsidentical placebo tablets

• All patients rinsed for 1 min prior to implant l t ith hl h idi 0 2%placement with chlorhexidine 0.2%

• Operators were allowed to place and restore the p pimplants according to their routine procedures

ResultsResults• 13 centres agreed to participate g p p• Each centre had to recruit 50 patients: 25 per group

f t t l f 650 ti tfor a total of 650 patients• 1 centre withdrew from the studyy• 1 centre did not deliver any data

1 t ll th t d t i l t th• 1 centre gave all the study material to another centre that therefore recruited 100 patients

• 2 centres recruited only 34 and 25 patients

ResultsResults781 patients screened for eligibility183 patients did not meet the inclusion criteria89 patients did not want to join the trial89 patients did not want to join the trial

509 patients randomised and treated at the 10 centresbut 3 patients had to be excluded because:but 3 patients had to be excluded because: – 1 included twice in the study (only data of the 1st

intervention evaluated)intervention evaluated)– In 1 patient was not possible to place the implant

D f 1 i l b h i– Data of 1 patient was lost by the treating centre

506 patients evaluated: 252 antibiotic - 254 placebo506 patients evaluated: 252 antibiotic - 254 placebo

PROTOCOL DEVIATIONSPROTOCOL DEVIATIONSA i i i (3)Antibiotic group (3):

2 patients received post-op antibiotics (1 was augmented)p p p ( g )1 insulin-dependent diabetic was included

Placebo group (9):5 patients received post-op antibiotics (1 was augmented)4 non-insulin dependent diabetics were included4 non insulin dependent diabetics were included

A single centre accounted for 67% exclusions & 50% deviationsA single centre accounted for 67% exclusions & 50% deviations

ResultsResults• All patients treated according to the allocated• All patients treated according to the allocated

interventions, none dropped out

• No apparent baseline imbalances between the 2 groups

• Implants used: Zimmer Dental, Dentsply, Friadent, Nobel Biocare, Intra-Lock, Camlog, Dyna, BiometNobel Biocare, Intra Lock, Camlog, Dyna, Biomet 3i, Endopore, Z-system, PF Tecom, Ghimas, Silpo, MegaGen GeassMegaGen, Geass

Patient/intervention characteristicsAmoxicillin

n = 252Placebon = 254n = 252 n = 254

Females 138 (54.8%) 132 (52.0%)Mean age at implant insertion (range) 49 1 (18 85) 47 6 (18 86)Mean age at implant insertion (range) 49.1 (18-85) 47.6 (18-86)Non-smokers 171 (67.9 %) 166 (65.4%)Smoking up to 10 cigarettes/day 55 (21 8%) 60 (23 6%)Smoking up to 10 cigarettes/day 55 (21.8%) 60 (23.6%)Smoking more than 10 cigarettes/day 26 (10.3%) 28 (11.0 %)Duration of the intervention in min (range) 32 (4-190) 31 (5-180)Duration of the intervention in min (range) 32 (4 190) 31 (5 180)

Total number of inserted implants 489 483Implants in fresh extraction sockets 60 76Took post-op antibiotics 2 (0.8%) 5 (2.0%)Intra-op complications 8 (3.2%) 7 (2.8%)

Di t ib ti f f il d li tiDistribution of failures and complications

Amoxicillinn = 252

Placebon = 254 P values

Patients who had a prosthesis failure 4 (1.6%) 10 (3.9%) 0.11

Patients who had implant failures 5 (2.0%) 12 (4.7%) 0.09

Patients who had adverse events at 1 week 0 (0%) 0 (0%) 1.00

Patients who had complications at 1 week 6 (2.4%) 7 (2.8%) 1.00

Patients who had complications at 2 weeks 2 (0.8%) 4 (1.6%) 0.69

Patients who had complications at 4 months 3 (1.2%) 2 (0.8%) 0.69

No significant difference for any outcome – no adverse events

R ltResults• No centre effect

• Immediate post-extractive implants were more likely to fail (9% versus 2%, P<0.001) post-hoc analysis

• Antibiotics did not help to reduce failures in the 99 ti t i i i di t i l t (P 0 48)patients receiving immediate implants (P=0.48)

ConclusionsConclusionsN t ti ti ll i ifi t diff h• No statistically significant differences, however more than the double of patients (12 versus 5) experienced

l i l t l i th l bearly implant losses in the placebo group • No reported adverse events p• This trial may be underpowered, therefore a meta-

analysis of similar RCTs or further trials are neededanalysis of similar RCTs or further trials are needed to provide the definitive answer

• Immediate post extractive implants were more likely• Immediate post-extractive implants were more likely to fail

• Please, keep in mind the big pictures…

WHERE TO FIND ADDITIONAL EVIDENCE?

Esposito Grusovin Loli Coulthard Worthington

WHERE TO FIND ADDITIONAL EVIDENCE?

Esposito, Grusovin, Loli, Coulthard, Worthington Interventions for replacing missing teeth:Interventions for replacing missing teeth:

antibiotics at dental implant placement to avoid complicationscomplications

The Cochrane Library 2010, issue 7Last literature search: January 2010

2010; 3: 101-110

I l i it iInclusion criteriaAny RCT with a follow-up of at least 3 months Any RCT with a follow up of at least 3 months including patients receiving or not antibiotic prophylaxis at implant placementprophylaxis at implant placement

O tOutcome measures• Prosthesis success• Implant success• InfectionsInfections• Adverse events

Literature search strategygyElectronic databases:1) The Cochrane Oral Health Group Register ++2) The Cochrane Central Register of Controlled Trials +3) MEDLINE ++4) EMBASE +

Handsearching:gBr J Oral Maxillofac Surg, Clin Implant Dent Rel Res, COIR,EJOI, Implant Dent, IJOMI, Int J Oral Maxillofac Surg, Int JEJOI, Implant Dent, IJOMI, Int J Oral Maxillofac Surg, Int JPeriodont Rest Dent, Int J Prosthod, J Clin Periodontol, J DentRes, J Oral Implantology, J Oral Maxillofac Surg, JRes, J Oral Implantology, J Oral Maxillofac Surg, JPeriodontol, J Prosthet Dent ++

Strategies for the identification of gunpublished or ongoing RCTs

- Checked reference lists of RCTs +- Checked reference lists of SRs +- Personal contacts ++Personal contacts- Contacted all authors of RCTs ++

C t t d th 55 f t- Contacted more than 55 manufacturers -- Contacted a discussion group on internet -- No language restriction +

Study selection, qualityStudy selection, quality assessment, data extraction

In duplicateIn duplicate

In case of disagreement a 3rd reviewer consultedgAll RCT authors contacted

Statistical unit the patient and not the implant

QUESTIONSQUESTIONSIs antibiotic prophylaxis effective? 4 RCTsIs antibiotic prophylaxis effective?Which is the most effective antibiotic?

4 RCTs0

Which is the most effective dose?When should antibiotic administered?

00When should antibiotic administered?

For how long should be administered? 0

4 incl ded RCTs ith 1007 patients:4 included RCTs with 1007 patients:E i 2008 (EJOI) 2 i illi l b 1 h i• Esposito 2008 (EJOI): 2 g amoxicillin vs placebo 1 h prior to

placement in 316 patients • Abu-Ta’a 2008 (JCP): 1 g amoxicillin preoperatively + 500 mg x 4 times a day for 2 days vs no antibiotics in 80 patients• Anitua 2009 (EJOI): 2 g amoxicillin vs placebo 1 h prior to placement in 105 patients (only single implants in bone of p p ( y g pmedium hardness)• Esposito 2010 (EJOI): 2 g amoxicillin vs placebo 1 h prior toEsposito 2010 (EJOI): 2 g amoxicillin vs placebo 1 h prior to placement in 506 patients

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RESULTS

• Prosthesis failures = no statistically significant difference • Infections = no statistically significant difference y g• Adverse events = no statistically significant difference

only 2 minor adverse events 1 in the placebo grouponly 2 minor adverse events, 1 in the placebo group

RESULTS: IMPLANT FAILURESStudy or SubgroupAbu-Ta'a 2008

Events0

Total40

Events3

Total40

Weight6.6%

M-H, Random, 95% CI0.14 [0.01, 2.68]

Antibiotics No antibiotics Risk Ratio Risk RatioM-H, Random, 95% CI

Anitua 2009Esposito 2008aEsposito 2010

Total (95% CI)

225

52158252

502

28

12

53158254

505

15.4%24.2%53.8%

100 0%

1.02 [0.15, 6.97]0.25 [0.05, 1.16]0.42 [0.15, 1.17]

0 40 [0 19 0 84]Total (95% CI)Total eventsHeterogeneity: Tau² = 0.00; Chi² = 1.77, df = 3 (P = 0.62); I² = 0%Test for overall effect: Z = 2.41 (P = 0.02)

9502

25505 100.0% 0.40 [0.19, 0.84]

0.001 0.1 1 10Favours antibiotics Favours no antibioti

•• Significantly more implant failures in the placebo/no antibiotic group• NNT = by giving antibiotics to 33 patients we avoid 1 patient experiencing early implant losses• Absence of relevant adverse events

It i ht b d i bl t ti l h l ti tibi ti• It might be advisable to routinely use prophylactic antibiotics

THANK YOUTHANK YOUComments to

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