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Interventions for replacing missing teeth: antibiotics at dental implant placement to prevent complications

  1. Marco Esposito1,*,
  2. Maria Gabriella Grusovin2,
  3. Helen V Worthington1

Editorial Group: Cochrane Oral Health Group

Published Online: 31 JUL 2013

Assessed as up-to-date: 17 JUN 2013

DOI: 10.1002/14651858.CD004152.pub4


How to Cite

Esposito M, Grusovin MG, Worthington HV. Interventions for replacing missing teeth: antibiotics at dental implant placement to prevent complications. Cochrane Database of Systematic Reviews 2013, Issue 7. Art. No.: CD004152. DOI: 10.1002/14651858.CD004152.pub4.

Author Information

  1. 1

    School of Dentistry, The University of Manchester, Cochrane Oral Health Group, Manchester, UK

  2. 2

    Private practice, Gorizia, Italy

*Marco Esposito, Cochrane Oral Health Group, School of Dentistry, The University of Manchester, Coupland 3 Building, Oxford Road, Manchester, M13 9PL, UK. espositomarco@hotmail.com.

Publication History

  1. Publication Status: New search for studies and content updated (no change to conclusions)
  2. Published Online: 31 JUL 2013

SEARCH

 
Characteristics of included studies [ordered by year of study]
Esposito 2008a

MethodsMulticentre, placebo-controlled, parallel RCT of 4 months' duration. 7 exclusions from each group for various explained reasons


ParticipantsPartially- and fully-edentulous participants. Adults treated in 11 private Italian dental practices. Participants excluded if they were: allergic to penicillins, needing prophylaxis for endocarditis, immunodeficient, diabetic, had implanted prostheses, required bone augmentation at implant placement with infections in the vicinity of the implant site(s), had been irradiated in the head and neck area, were already receiving antibiotic treatment, had been treated or receiving treatment with intravenous amino-bisphosphonates, were pregnant or lactating. 165 participants included in each group and results given for 158


Interventions2 g of amoxicillin given 1 h preoperatively versus identical placebo tablets. Operators were allowed to place and restore the implants according to their routine procedures. 1 week prior to implant placement, all participants underwent at least 1 session of oral hygiene instruction and professionally-delivered debridement, if required. All participants rinsed with chlorhexidine digluconate 0.2% for 1 minute just prior to surgery and postoperatively twice a day for at least 1 week. Operators were allowed to place and restore the implants according to their routine procedures. Postoperative complications were assessed at 1 and 2 weeks, and implant success at 4 months. Various implant systems brands were used (Zimmer Dental, Dentsply Friadent, Nobel Biocare, Intra-Lock, Camlog, Dyna, Biomet 3i, and Endopore)


OutcomesProsthesis and implant failures, postoperative complications, adverse events. Postoperative complications assessed 1 and 2 weeks after placement, and implant stability at 4 months


NotesAntibiotics and placebo donated by a drug company manufacturing generic drug; the company was not involved in the design of the study, in the data evaluation, or in commenting on the manuscript.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuoted from the article: "Twelve computer generated restricted randomization lists with equal groups of participants were made."

Allocation concealment (selection bias)Low riskQuoted from the article: "Only one of the investigators (Dr Marco Esposito), not involved in the selection and treatment of the patients, was aware of the randomization sequence and could have access to the randomization lists stored in his password protected portable computer. The randomized codes (1 or 2) were enclosed in sequentially numbered, identical, opaque, sealed envelopes. Envelopes were opened sequentially 1 hour prior to implant placement and patients assumed 2 tablets taken from identical white plastic containers labelled with the same code of the envelopes (1 or 2), containing the antibiotic or identical placebo tablets. Therefore treatment allocation was concealed to the investigators in charge of enrolling and treating the patients . . . "

Blinding (performance bias and detection bias)
All outcomes
Low riskQuoted from the article: " . . . and both patients and operators/outcome assessors were blinded to the tested intervention. Also the statistician was kept blind and performed all analyses without knowing to which group the patients were allocated."

Incomplete outcome data (attrition bias)
All outcomes
Low riskAll exclusions and missing data reported and explained

Selective reporting (reporting bias)Low riskAll outcome measures reported

Other biasLow riskNo other bias identified

Abu-Ta'a 2008

MethodsSingle centre parallel RCT of 5 months duration. No drop-outs


ParticipantsPartially- and fully-edentulous participants. Adults treated at the Department of Periodontology of the University Hospital of the Catholic University Leuven, Belgium. Participants were excluded if they were: allergic to penicillins, needing prophylaxis for endocarditis, immunodeficient, with uncontrolled diabetes mellitus, or irradiated in the head and neck area. 40 participants included in each group and results given for 40


Interventions1 g of amoxicillin given 1 h preoperatively plus 500 mg of amoxicillin 4 times a day for 2 days versus no antibiotics. All participants rinsed with chlorhexidine digluconate for 1 minute just prior to surgery and postoperatively twice a day for 7 to 10 days. The perioral skin was disinfected for 30 s with cetrimonium bromide 0.5% and chlorhexidine 0.05% in water. Measures of asepsis included use of sterile drapes around the participant's mouth, head, and over the supine body of the participant, a meshed nose guard, and 2 suction tips (1 only for the mouth and 1 only for the wound). Postoperative complications were assessed at 7 to 10 days and implant success at 5 months. An unknown type of dental implant was used


OutcomesImplant failures, postoperative infections, adverse events, microbiological evaluation. Postoperative infections were assessed 7 to 10 days after placement, and implant success at 5 months


NotesNo external funding was received


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuoted from the article: "These patients were randomly assigned into one of two groups (with and without antibiotics = AB) of 40 patients each using random sampling with masking of the person performing the randomization."

Author's reply: "After verification of the inclusion criteria, 80 patients were enrolled into the study. All patients were assigned a patient number, and were randomly assigned to one of the two treatment regimens. Assignment was performed by one of our department's nurses using a randomization table and by applying the simple randomization method."

Allocation concealment (selection bias)Unclear riskNo information provided in the article.

Author's reply: "Masking: It was maintained up to the day of implant installation. Afterwards, of course, it was difficult to maintain the masking since patients were asked about their postoperative experiences and any side effect of the antibiotic when removing the stitches."

Blinding (performance bias and detection bias)
All outcomes
High riskQuoted from the article: "Both the surgical team and the patients were blinded to the groups."

Author's reply: "No, see above."

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo missing data or excluded patients

Selective reporting (reporting bias)Low riskAll outcome measures reported

Other biasLow riskNo other bias identified

Anitua 2009

MethodsPlacebo-controlled parallel RCT of 3 months' duration. No drop-outs


ParticipantsOnly included people needing single implants in medium bone quality and all implants were inserted after flap elevation. Adults treated in 8 private Spanish dental practices. Participants were excluded if: they were allergic to beta-lactam antibiotics; had concurrent local or systemic infections requiring antibiotic treatment; had systemic diseases that contraindicated the surgery including cardiovascular diseases, respiratory diseases, haematological and metabolic disorders, bone diseases, collagenosis, immunodeficiencies and renal insufficiency; or had received irradiation to the head and neck (> 5000 rads). 52 participants included in the antibiotic group and 53 in the placebo group with results given for 52 and 53 participants, respectively


Interventions2 g of amoxicillin given 1 h preoperatively versus identical placebo tablets. During the days prior to the intervention participants received appropriate prophylaxis and adequate oral hygiene instructions. Antibiotics and other medications were not allowed 15 days before the surgery. All participants rinsed with 0.2% chlorhexidine digluconate for one minute just prior to surgery. Only single implants in medium bone quality were included and all implants were inserted after flap elevation. Before installation, implants were carefully humidified with liquid plasma rich in growth factors (PRGF). Peripheral blood (20 ml to 30 ml) from each participant was taken by venipuncture before surgery and placed directly into 9 ml tubes containing 3.8% (wt/vol) sodium citrate as anticoagulant. Liquid PRGF was prepared by centrifugation (PRGF System®, BTI) at 460 × g for 8 minutes at room temperature; 1 ml plasma fraction was collected and deposited in a glass dish. In order to initiate clotting, PRGF activator (calcium chloride) was added to the liquid PRGF preparation (50 μl PRGF activator per ml of preparation). Postoperative infections were assessed at days 3, 10, 30 and 60. Implant stability was also evaluated at 3 months using Osstell. BTI dental implants were used


OutcomesImplant failures (assessed with Ostell at 3 months), postoperative infections, adverse events, microbiological evaluation. Postoperative infections assessed at days 3, 10, 30 and 90 after implant placement


NotesTrial supported by the implant manufacturer


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuoted from the article: "The randomisation was performed using a random numbers table, assigning each patient to one of two treatment groups (active or placebo). Each of the enrolled patients had a patient number and, according to the randomisation table, was assigned to each treatment group."

Allocation concealment (selection bias)Low riskQuoted from the article: "Both researchers and patients remained blinded to the received treatment group. For this purpose, the tablets corresponding to each patient were included in a package identified only by the study number and the patient code. Researchers had a sealed envelope for each patient to establish the randomly assigned treatment if necessary. The envelope was opened at the end of the study. Only in those situations in which the clinician observed any side-effect was the envelope opened before."

Blinding (performance bias and detection bias)
All outcomes
Low riskSee above

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo missing data or excluded participants

Selective reporting (reporting bias)Low riskAll outcome measures reported

Other biasLow riskNo other bias identified

Esposito 2010a

MethodsMulticentre, placebo-controlled, parallel RCT of 4 months' duration. 2 exclusions from the antibiotic group and 1 from the placebo group for various, explained reasons


ParticipantsPartially- and fully-edentulous participants. Adults treated in 10 private Italian dental practices. Participants excluded if: they were allergic to penicillins, immunodeficient, diabetic, needing prophylaxis for endocarditis, had implanted prostheses, required bone augmentation at implant placement and had infections in the vicinity of the implant site(s), irradiated in the head and neck area, already receiving antibiotic treatment, treated or receiving treatment with intravenous amino-bisphosphonates, were pregnant or lactating. 254 participants included in the antibiotic group and 255 in the placebo group; results given for 242 and 254 participants, respectively


Interventions2 g of amoxicillin given 1 h preoperatively versus identical placebo tablets. Operators were allowed to place and restore the implants according to their routine procedures. 1 week prior to implant placement, all participants underwent at least 1 session of oral hygiene instruction and professionally-delivered debridement, if required. All participants rinsed with chlorhexidine digluconate 0.2% for 1 minute just prior to surgery and postoperatively twice a day for at least 1 week. Operators were allowed to place and restore the implants according to their routine procedures. Postoperative complications were assessed at 1 and 2 weeks, and implant success at 4 months. Various implant systems brands were used (Zimmer Dental, Dentsply Friadent, Nobel Biocare, Intra-Lock, Camlog, Dyna, Biomet 3i, Endopore, Z-system, PF Tecom, Ghimas, Silpo, MegaGen and Geass)


OutcomesProsthesis and implant failures, postoperative complications, adverse events. Postoperative complications assessed 1 and 2 weeks after placement, and implant stability at 4 months


NotesAntibiotics and placebo donated by a drug company manufacturing generic drug; the company was not involved in the design of the study, in the data evaluation, or in commenting on the manuscript.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuoted from the article: "Thirteen computer generated restricted randomization lists with equal groups of participants were made."

Allocation concealment (selection bias)Low riskQuoted from the article: "Only one of the investigators (Dr Marco Esposito), not involved in the selection and treatment of the patients, was aware of the randomization sequence and could have access to the randomization lists stored in his password protected portable computer. The randomized codes (1 or 2) were enclosed in sequentially numbered, identical, opaque, sealed envelopes. Envelopes were opened sequentially 1 hour prior to implant placement and patients assumed 2 tablets taken from identical white plastic containers labelled with the same code of the envelopes (1 or 2), containing the antibiotic or identical placebo tablets. Therefore treatment allocation was concealed to the investigators in charge of enrolling and treating the patients . . . "

Blinding (performance bias and detection bias)
All outcomes
Low riskQuoted from the article: ". . . and both patients and operators/outcome assessors were blinded to the tested intervention. Also the statistician was kept blind and performed all analyses without knowing to which group the patients were allocated."

Incomplete outcome data (attrition bias)
All outcomes
Low riskAll exclusions and missing data reported and explained

Selective reporting (reporting bias)Low riskAll outcome measures reported

Other biasLow riskNo other bias identified

Caiazzo 2011

MethodsMulticentre parallel RCT with 4 arms, of 3 months' duration. No drop-outs


ParticipantsAdult treated in 2 private Italian dental practices. Participants were excluded if they had: a history of systemic diseases contraindicating surgical treatment, long-term nonsteroidal anti-inflammatory drug therapy, medically necessary antibiotic therapy, a history of antibiotic therapy 6 months prior to the study, a history of allergic reactions to penicillins or related drugs, or were pregnant. 25 participants included in each group and results given for 100


Interventions4 interventions compared: 2 g of amoxicillin given 1 h preoperatively; 2 g amoxicillin given 1 h preoperatively + 1 g twice a day for 7 days; 1 g of amoxicillin given immediately after implantation twice a day for 7 days; and no antibiotic. All participants had at least 1 session of oral hygiene instruction and professionally-delivered debridement 1 week prior to implant placement. All participants rinsed with chlorhexidine digluconate 0.2% for 1 minute just prior to surgery and postoperatively twice a day for 15 days. Clinicians placed implants according to their routine procedures. Postoperative complications were assessed at 1, 2, 4 and 8 weeks, and implant success at 3 months. Used Biomet 3i Osseotite implants with external connection


OutcomesImplant failures, postoperative complications, adverse events. Postoperative complications assessed 1, 2, 4 and 8 weeks after placement, and implant stability at 3 months


NotesNo external funding was received


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuoted from the article: "The patients were randomly allocated - using a computer-generated randomisation list - to 4 different groups: . . . "

The authors also informed us that they used the Random Allocation Software to prepare the randomisation schedule

Allocation concealment (selection bias)High riskNo information provided in the article

The authors kindly informed us that no allocation concealment procedures were implemented

Blinding (performance bias and detection bias)
All outcomes
High riskNo information provided in the article

The authors kindly informed us that the operators recorded the outcome measures, so they were not blinded

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo missing data or excluded patients

Selective reporting (reporting bias)Low riskAll outcome measures reported

Other biasLow riskNo other bias identified

Nolan 2013

MethodsSingle centre placebo-controlled parallel RCT of 3-4 months' duration


ParticipantsPartially- and fully-edentulous participants. Adults treated in the Dublin Dental University Hospital, Department of Restorative Dentistry and Periodontology, Dublin, Ireland. Participants were excluded if they had medical conditions that required antibiotic premedication such as prosthetic heart valve replacement, skeletal or joint replacement, previous history of infective endocarditis and a history of rheumatic fever; metabolic diseases such as type I or II diabetes mellitus; past or present neoplastic disease; previous radiotherapy in the head and neck area; were immunosuppressed; had blood coagulation impairment; had a history of systemic steroid medication or recent systemic antibiotic therapy; were pregnant or lactating; or had an allergy to the antibiotic chosen. 83 participants randomised but results given for only 27 of the antibiotic group and 28 of the placebo group


Interventions3 g of amoxicillin given 1 h preoperatively versus identical placebo tablets. All participants rinsed with 0.2% chlorhexidine digluconate for 1 minute just prior to surgery. Implants were placed according to the manufacturers guidelines using standard surgical procedures. Participants were instructed to use a chlorhexidine 0.2% mouthwash 4 to 5 times daily for the first postoperative week. Postoperative complications and adverse events were assessed at 2 and 7 days, and implant success at 3 to 4 months. Various implant brands were used (Biomet 3i, Nobel Biocare, Ankylos, Dentsply Friadent, Germany, Straumann SLA Implants)


OutcomesImplant failures, postoperative complications, adverse events, pain and interference with daily activities. Postoperative complications were assessed 2 and 7 days after implant placement, and implant stability at 3-4 months


NotesNo external funding was received


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuoted from the article: "Every patient that agreed to participate was randomly assigned to one of the following two groups"

The authors kindly informed us that envelopes and random computer generated numerical codes were prepared Stickers with these codes were placed outside sealed opaque envelopes

Allocation concealment (selection bias)Low riskQuoted from the article: "Consecutively treated patients received consecutive numbers correlating with the number of an envelope. This envelope contained either the 3 g amoxicillin, or similar placebo capsules. A master file held the key to whether an envelope contains the 3 g amoxicillin or the placebo capsules. An independent person administered the antibiotic or the placebo. Neither the surgeon nor the patient knew which has been taken to ensure a double-blind approach"

Blinding (performance bias and detection bias)
All outcomes
Low riskThe article reported that two independent examiners, performed all assessment

The authors kindly informed us that assessors were masked to the interventions

Incomplete outcome data (attrition bias)
All outcomes
High riskPartcipants who did not attend the 2 and 7 day postoperative examinations (16 patients) were excluded from the study, so the fate of their implants is unknown

Selective reporting (reporting bias)High riskThe authors could not supply information about whether some of the prostheses could not be placed after implant failures without placing additional implants for replacing the failed ones. This was due to the fact that participants were assigned a unique number to identify their sample at the beginning of the study and the participants' names were not be used after assignment of this number (as per ethics committee requirements). The list identifying participants had been deleted recently, so their records could not be identified to see what happened with their prostheses

Other biasLow riskNo other bias identified

 
Characteristics of excluded studies [ordered by year of study]

StudyReason for exclusion

Tan 2013Follow-up too short (8 weeks post-implantation)

 
Comparison 1. Antibiotics versus placebo/no antibiotics

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Implant failures61162Risk Ratio (M-H, Random, 95% CI)0.33 [0.16, 0.67]

 2 Prosthesis failures51107Risk Ratio (M-H, Random, 95% CI)0.44 [0.19, 1.00]

 3 Postoperative infections61162Risk Ratio (M-H, Random, 95% CI)0.69 [0.36, 1.35]

 4 Adverse events61162Risk Ratio (M-H, Fixed, 95% CI)1.0 [0.06, 15.85]

 
Summary of findings for the main comparison.

Antibiotics compared with no antibiotics at placement of dental implants

Patient or population: people requiring dental implants

Settings: dental practice

Intervention: prophylactic antibiotics

Comparison: no antibiotics or placebo

OutcomesIllustrative comparative risks* (95% CI)Relative effect
(95% CI)
No of participants
(studies)
Quality of the evidence
(GRADE)
Comments

Assumed riskCorresponding risk

Without antibioticAntibiotic

Implant failure at 4 monthsLow risk populationRR 0.33 (0.16 to 0.67)1162
(6)
⊕⊕⊕⊝2
moderate quality

10 per 100014 per 1000
(2 to 7)

High risk population

100 per 100040 per 1000
(16 to 67)

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).

 1The median risk in the control arm was 6% so low risk of 1% and high risk of 10% assumed
2 Downgraded due to three of the six studies being at high risk of bias
CI = confidence interval; RR = risk ratio
GRADE Working Group grades of evidence:
High quality (⊕⊕⊕⊕): further research is very unlikely to change our confidence in the estimate of effect
Moderate quality (⊕⊕⊕⊝): further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate
Low quality (⊕⊕⊝⊝): further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate
Very low quality (⊕⊝⊝⊝): we are very uncertain about the estimate