Antibiotic prophylaxis may not be indicated for prevention of dental implant infections in healthy patients. A systematic review and meta-analysis

Abstract

Objectives

The purpose of the present systematic review and meta-analysis is to determine the efficacy of antibiotic prophylaxis and specific antibiotic regimens in dental implant placement for prevention of post-operative infection (POI) in overall healthy patients.

Materials and methods

Electronic database and manual searches were independently conducted to identify randomized controlled trials (RCTs). Publications were selected on basis of eligibility criteria and then assessed for risk-of-bias using the Cochrane Handbook. The primary outcome was POI (total, early, and late). Wound dehiscence, pain, and adverse events were studied as secondary outcomes. Random-effects meta-analysis was conducted for risk ratios of dichotomous data. This systematic review was conducted in accordance with Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines.

Results

With duplicates removed, 1022 abstracts were screened and 22 full-text articles assessed; 10 RCTs of 1934 total patients were included. Meta-analysis did not detect statistically significant differences in total (P = 0.82), early (1–2 week post-op) (P = 0.57), or late (3–4 months post-op) (P = 0.66) POIs, wound dehiscence (P = 0.31), and adverse events (P = 0.21), between antibiotic and no-antibiotic groups. Confounding variables identified.

Conclusion

The results of this systematic review suggest that antibiotic prophylaxis may not be indicated for prevention of POIs following dental implant placement in overall healthy patients. These findings and in light of antibiotic-associated risks for individual and public health demand revaluation of routine prescription of antibiotic prophylaxis in dental implant placement procedures.

Clinical relevance

It is up to the clinicians to evaluate the benefits (or lack thereof) of antibiotic prophylaxis for each patient given medical history and surgical complexity, until new evidence becomes available.

Appendices

Appendix 1. Search protocol used in the systematic review

The following search terms, created by a medical-dental librarian, were used for database searches.

Primary concept

Keywords: endosseous implant OR endosseous implants OR dental implant OR dental implants OR dental implantation OR tooth implant OR tooth implants OR tooth implantation

Subject headings: PubMed and CINAHL: “dental implantation, endosseous”[MeSH Terms] OR “dental implantation”[MeSH Terms] OR “dental implants”[MeSH Terms]

EMBASE: tooth implant/ OR tooth implantation/(EMTREE)

DOSS: uses keywords only

Secondary concept

Keywords: antibiotic OR antibiotics OR (antibiotic prophylaxis) OR (prophylactic antibiotic) OR (prophylactic antibiotics) OR (antibiotic regimen) OR (pre-operative antibiotic) OR (post-operative antibiotic) OR (postoperative antibiotic) OR (perioperative antibiotics) OR (systemic antibiotic) OR (infection prevention)

Subject headings: PubMed and CINAHL: “antibiotic prophylaxis”[MeSH Terms] OR “anti-bacterial agents”[MeSH Terms]

EMBASE: antibiotics prophylaxis/ (EMTREE)

DOSS: uses keywords only

Detailed search queries were as follows:

PubMed: (((“antibiotic”[All Fields] OR “antibiotics”[All Fields] OR “antibiotic prophylaxis”[MeSH Terms] OR (“antibiotic”[All Fields] AND “prophylaxis”[All Fields]) OR “antibiotic prophylaxis”[All Fields] OR (prophylactic[All Fields] AND “antibiotic”[All Fields]) OR (prophylactic[All Fields] AND “antibiotics”[All Fields]) OR (“antibiotic”[All Fields] AND “regimen”[All Fields]) OR (pre-operative[All Fields] AND “antibiotic”[All Fields]) OR (pre-operative[All Fields] AND “antibiotics”[All Fields]) OR ((“postoperative period”[MeSH Terms] OR “postoperative”[All Fields] OR “postoperative period”[All Fields] OR “post operative”[All Fields]) AND “antibiotic”[All Fields]) OR ((“postoperative period”[MeSH Terms] OR “postoperative”[All Fields] OR “postoperative period”[All Fields] OR “post operative”[All Fields]) AND “antibiotics”[All Fields]) OR (perioperative[All Fields] AND “antibiotic”[All Fields]) OR (perioperative[All Fields] AND “antibiotics”[All Fields]) OR (systemic[All Fields] AND “antibiotic”[All Fields]) OR (systemic[All Fields] AND “antibiotics”[All Fields]) OR ((“infection”[MeSH Terms] OR “infection”[All Fields]) AND (“prevention and control”[Subheading] OR “prevention and control”[All Fields] OR “prevention”[All Fields]))))) AND ((“dental implants”[MeSH Terms] OR (“dental”[All Fields] AND “implants”[All Fields]) OR “dental implants”[All Fields] OR (“dental”[All Fields] AND “implant”[All Fields]) OR “dental implant”[All Fields] OR “dental implantation”[MeSH Terms] OR (“dental”[All Fields] AND “implantation”[All Fields]) OR “dental implantation”[All Fields] OR ((“tooth”[MeSH Terms] OR “tooth”[All Fields]) AND implant[All Fields]) OR ((“tooth”[MeSH Terms] OR “tooth”[All Fields]) AND implants[All Fields]) OR ((“tooth”[MeSH Terms] OR “tooth”[All Fields]) AND “implantation”[All Fields]) OR (endosseous[All Fields] AND implant[All Fields]) OR “endosseous implant”[All Fields] OR (“endosseous”[All Fields] AND “implants”[All Fields]) OR “endosseous implants”[All Fields] OR “dental implantation, endosseous”[MeSH Terms] OR “endosseous dental implantation”[All Fields]))

CINAHL: ((MH “Antibiotic Prophylaxis” OR MH “Antibiotics” OR Antibiotic OR antibiotics OR (antibiotic prophylaxis) OR (prophylactic antibiotic) OR (prophylactic antibiotics) OR (antibiotic regimen) OR (pre-operative antibiotic) OR (post-operative antibiotic) OR (postoperative antibiotic) OR (perioperative antibiotics) OR (systemic antibiotic) OR (infection prevention)) AND (endosseous implant OR endosseous implants OR dental implant OR dental implants OR dental implantation OR tooth implant OR tooth implants OR Tooth implantation OR MH “Dental Implants” OR MH “Dental Implantation”)

DOSS: (((Antibiotic OR antibiotics OR (antibiotic prophylaxis) OR (prophylactic antibiotic) OR (prophylactic antibiotics) OR (antibiotic regimen) OR (pre-operative antibiotic) OR (post-operative antibiotic) OR (postoperative antibiotic) OR (perioperative antibiotics) OR (systemic antibiotic) OR (infection prevention))) AND ((endosseous implant OR endosseous implants OR dental implant OR dental implants OR dental implantation OR tooth implant OR tooth implants OR Tooth implantation))

EMBASE: (exp antibiotic prophylaxis/ OR (Antibiotic OR antibiotics OR (antibiotic prophylaxis) OR (prophylactic antibiotic) OR (prophylactic antibiotics) OR (antibiotic regimen) OR (pre-operative antibiotic) OR (post-operative antibiotic) OR (postoperative antibiotic) OR (perioperative antibiotics) OR (systemic antibiotic) OR (infection prevention)).mp.)

AND (exp tooth implant/ OR exp. tooth implantation/ OR (endosseous implant or endosseous implants or dental implant or dental implants or dental implantation or tooth implant or tooth implants or Tooth implantation).mp.)

Appendix 2. Journals included in handsearch

The journals included in handsearch were as follows:

International Journal of Oral and Maxillofacial Implants, European Journal of Oral Implantology, Clinical Oral Implants Research, International Journal of Oral and Maxillofacial Surgery, British Journal of Oral and Maxillofacial Surgery, Journal of Oral and Maxillofacial Surgery, Oral Surgery Oral Medicine Oral Pathology Oral Radiology and Endodontology, International Journal of Oral and Maxillofacial Surgery Clinical Implant Dentistry and Related Research, Dental Clinics of North America, Journal of Prosthetic Dentistry, Journal of Clinical Periodontology, Journal of Oral Implantology, Journal of Craniofacial Surgery, Journal of Periodontology, Journal of Cranio-Maxillofacial Surgery.

Appendix 3. Extracted information on study characteristics

Extracted information on study characteristics included publication details (author(s), year of publication), trial study design/study design, source of funding, conflict of interest, study period, and location. Treatment group characteristics included the study group intervention (prophylactic antibiotic compound, dosage, and duration of treatment), comparative treatment (placebo or another prophylactic antibiotic with specification of regimen), number of patients and implants, mean age/range, number of females and males, and patient dental and medical history (periodontitis, smoking, diabetes). Treatment/surgical protocols specified additional protocol measures (administration of chlorohexidine, dexamethasone, etc.), implant placement stages (one or two stages), bone graft/graft type, implant platform, and healing/loading protocol. Study outcomes included a summary of outcomes assessed, follow-up times, and study conclusions as well as quantitative results for outcomes assessed: post-operative infection (total, early, and late infections), wound dehiscence, pain, and adverse events. All outcomes were reported in terms of patient number or as reported in the publications if patient number could not be obtained (e.g., pain was often recorded as a mean VAS score). Extracted data were categorized on the basis of antibiotic prophylaxis regimens: administration of only pre-operative antibiotics, pre- and post-operative antibiotics, only post-operative antibiotics, and no antibiotics and respective antibiotic dosage for each regimen.

Section/topic	No.	Checklist item	Reported on page no.
TITLE
Title	1	Identify the report as a systematic review, meta-analysis, or both.	1
ABSTRACT
Structured summary	2	Provide a structured summary including, as applicable: background; objectives; data sources; study eligibility criteria, participants, and interventions; study appraisal and synthesis methods; results; limitations; conclusions and implications of key findings; systematic review registration number.	2
INTRODUCTION
Rationale	3	Describe the rationale for the review in the context of what is already known.	3–4
Objectives	4	Provide an explicit statement of questions being addressed with reference to participants, interventions, comparisons, outcomes, and study design (PICOS).	4
METHODS
Protocol and registration	5	Indicate if a review protocol exists, if and where it can be accessed (e.g., Web address), and, if available, provide registration information including registration number.	4
Eligibility criteria	6	Specify study characteristics (e.g., PICOS, length of follow-up) and report characteristics (e.g., years considered, language, publication status) used as criteria for eligibility, giving rationale.	4–5
Information sources	7	Describe all information sources (e.g., databases with dates of coverage, contact with study authors to identify additional studies) in the search and date last searched.	5
Search	8	Present full electronic search strategy for at least one database, including any limits used, such that it could be repeated.	6
Study selection	9	State the process for selecting studies (i.e., screening, eligibility, included in systematic review, and, if applicable, included in the meta-analysis).	6
Data collection process	10	Describe method of data extraction from reports (e.g., piloted forms, independently, in duplicate) and any processes for obtaining and confirming data from investigators.	6
Data items	11	List and define all variables for which data were sought (e.g., PICOS, funding sources) and any assumptions and simplifications made.	6
Risk of bias in individual studies	12	Describe methods used for assessing risk of bias of individual studies (including specification of whether this was done at the study or outcome level), and how this information is to be used in any data synthesis.	6
Summary measures	13	State the principal summary measures (e.g., risk ratio, difference in means).	6–7
Synthesis of results	14	Describe the methods of handling data and combining results of studies, if done, including measures of consistency (e.g., I2) for each meta-analysis.	6–7
Risk of bias across studies	15	Specify any assessment of risk of bias that may affect the cumulative evidence (e.g., publication bias, selective reporting within studies).	6
Additional analyses	16	Describe methods of additional analyses (e.g., sensitivity or subgroup analyses, meta-regression), if done, indicating which were pre-specified.	6
RESULTS
Study selection	17	Give numbers of studies screened, assessed for eligibility, and included in the review, with reasons for exclusions at each stage, ideally with a flow diagram.	7
Study characteristics	18	For each study, present characteristics for which data were extracted (e.g., study size, PICOS, follow-up period) and provide the citations.	7
Risk of bias within studies	19	Present data on risk of bias of each study and, if available, any outcome level assessment (see item 12).	9–10
Results of individual studies	20	For all outcomes considered (benefits or harms), present, for each study: (a) simple summary data for each intervention group (b) effect estimates and confidence intervals, ideally with a forest plot.	9–10
Synthesis of results	21	Present results of each meta-analysis done, including confidence intervals and measures of consistency.	8–9
Risk of bias across studies	22	Present results of any assessment of risk of bias across studies (see Item 15).	9–10
Additional analysis	23	Give results of additional analyses, if done (e.g., sensitivity or subgroup analyses, meta-regression [see Item 16]).	9
DISCUSSION
Summary of evidence	24	Summarize the main findings including the strength of evidence for each main outcome; consider their relevance to key groups (e.g., healthcare providers, users, and policy makers).	10
Limitations	25	Discuss limitations at study and outcome level (e.g., risk of bias), and at review-level (e.g., incomplete retrieval of identified research, reporting bias).	12
Conclusions	26	Provide a general interpretation of the results in the context of other evidence, and implications for future research.	13
FUNDING
Funding	27	Describe sources of funding for the systematic review and other support (e.g., supply of data); role of funders for the systematic review.	1

Fig. 5

PRISMA flowchart of the screening process

Fig. 6

Differences in total post-operative infection at 1–2 weeks. a Pre-operative only antibiotic group. b Pre- and post-operative antibiotic group. c Pre- and post-operative/post-operative only antibiotic group. d Only antibiotic regimen versus placebo. e Pre-operative antibiotic only versus pre- and post-operative/post-operative only antibiotic

Fig. 7

Differences in total wound dehiscence outcomes of a no antibiotic/placebo versus all antibiotic regimens group, b pre-operative only regimen group, and c pre-operative only regimen versus pre- and post-operative/port-operative only

Fig. 8

Differences in total adverse events

Fig. 9

Open Meta-Analyst with cumalative analysis of forest plots organized by antibiotic dosing regimen

Table 3 Studies excluded after full-text review