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Antibiotic dosage prescribed in oral implant surgery: A meta-analysis of cross-sectional surveys

• Fabio Rodríguez Sánchez,
• Iciar Arteagoitia,
• Wim Teughels,
• Carlos Rodríguez Andrés,
• Marc Quirynen

x

• Published: Baronial 18, 2020
• https://doi.org/x.1371/journal.pone.0236981

Figures

Abstract

This written report aimed to assess the dosage and types of antibiotics prescribed in oral implant surgery, compare them among the different subpopulations (country and prescription regimens) and against the show-based recommended dosage: a 2-gram single preoperative dose of amoxicillin. A meta-analysis of cross-sectional surveys was conducted, which reports the overall dosage (and blazon) of antibiotics prescribed in combination with implant placement. PubMed, Cochrane, Science, Direct, and EMBASE via OVID were searched until April 2019. Three reviewers independently undertook information extraction and risk of bias cess. The outcome variable was set on the average of prophylactic antibiotics prescribed per oral implant surgery. Overall, 726 participants from five cross-sectional surveys, representing five unlike countries were finally included. Amoxicillin was the near prescribed antibiotic. On boilerplate, 10,724 mg of antibiotics were prescribed per implant surgery. This average was significantly (p<0.001) higher than 2,000 mg. Overall, amoxicillin doses were significantly higher than ii,000 mg (9,700 mg, p<0.001). All prescribed amoxicillin regimens independently contained more than 2,000 mg, including those comprising simply preoperative amoxicillin (2,175 mg, p = 0.006). Sectional preoperative antibiotic regimens were the only subgroup with prescription dosages below this threshold (p = 0.091). Pregnant variations in antibiotic prescriptions were found amidst different countries and antibiotic regimens (p<0.001). In decision, the average dose of antibiotics prescribed per oral implant surgery was larger than the evidence-based recommended dose in healthy patients and straightforward conditions. In addition, variations in the average antibiotic dosages were establish among different countries and prescription regimens.

Commendation: Rodríguez Sánchez F, Arteagoitia I, Teughels W, Rodríguez Andrés C, Quirynen Grand (2020) Antibiotic dosage prescribed in oral implant surgery: A meta-assay of cantankerous-sectional surveys. PLoS 1 15(8): e0236981. https://doi.org/ten.1371/periodical.pone.0236981

Editor: Andrej K. Kielbassa, Danube Private Academy, AUSTRIA

Received: May 15, 2020; Accepted: July 18, 2020; Published: August 18, 2020

Copyright: © 2020 Rodríguez Sánchez et al. This is an open admission article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: All relevant data are within the newspaper and its Supporting Information files.

Funding: The author(s) received no specific funding for this work.

Competing interests: The authors accept declared that no competing interests exist.

Introduction

Oral implant therapy has developed into a very predictable treatment for the rehabilitation of a partial or complete edentulous oral cavity [1–iii]. Nevertheless, oral implant failures do occur [4]. Postoperative infection subsequently bacterial contamination of the surgical site is believed to be one of the main sources of early implant failures; however, it is too known to be associated to sure delayed implant failures [five]. Therefore, perioperative antibiotics have been studied and recommended to prevent these complications [6–eleven].

Reviews published in this field found that antibiotics were not effective in reducing the incidence of postal service-operative infections; nonetheless, preoperative antibiotics were establish to be benign in preventing oral implant failures [8,ix,12]. Esposito et al. [9] suggested that routinely prescribing a single pre-operative dose of 2,000 mg of amoxicillin might prevent implant failures in healthy patients and in straightforward conditions. However, 25 patients would need to receive this treatment in order to preclude just ane patient from having an implant failure [9].

The prescription of safety antibiotics in oral implant surgery remains controversial [thirteen]. Numerous cross-sectional surveys have been conducted to appraise prescription habits in oral implant surgery among dental professionals in different countries [14–26]. These studies reported a wide range of dissimilar antibiotic prescriptions and a wide selection of antibiotic types. Recommendations published in recent meta-analyses are often not followed. This emphasizes the need to institute standardized guidelines to support clinicians' decision-making practices [15,22–25].

Irrational use of antibiotics may atomic number 82 to an unjustified increment in economical costs and agin reactions such as allergies, toxicity, gastrointestinal disorders and bacterial resistance [27,28]. The latter condition has become a major threat worldwide. Contempo studies have shown a directly human relationship between antibiotic consumption and the emergence and dissemination of resistant bacterial strains [29].

This alarming situation, coupled with the substantial growth of the oral implant market in recent years [xxx], predicates an important public health concern. The prescription of antibiotics in dentistry is nonetheless rising despite many campaigns to forestall their excessive use [31,32]. Moreover, boosted studies have been requested to better assess antibiotic prescription behaviors in dentistry [33]. Consequently, it was deemed necessary to evaluate the prophylactic antibody treatments prescribed in oral implant therapy and to make up one's mind the quantity of antibiotics that may be considered as overtreatment. As a result, this would permit u.s. to gauge the potential run a risk caused by the irrational use of prophylactic antibiotics in this situation.

This meta-assay of cross-sectional surveys primarily aimed to appraise the dosage and types of antibiotics prescribed per oral implant surgery. The secondary aim was to dissimilarity the boilerplate dosage of prescribed antibiotics against the evidence-based recommended regimen in healthy patients and in straightforward atmospheric condition: a single 2-g preoperative dose of amoxicillin [9].

An boosted aim of this report was to assess the differences in dosage and antibody type between countries and prescription regimens.

The naught hypotheses were postulated every bit follows: (1) the average dosage of condom antibiotics prescribed per oral implant surgery is equal to a single dose of 2,000 mg and (2) there are no variations in the average dosage of prescribed antibiotics among the different countries and prescription regimens.

Methods

The study was conducted and reported in accordance with the Meta-assay of Observational Studies in Epidemiology group [34]. Details of the protocol for this meta-analysis were registered on the International Prospective Register of Systematic Reviews (PROSPERO) with the following register identification: CRD42020156885.

Eligible studies included all articles evaluating antibody prescriptions in association with oral implant surgery and in adherence with the following Participants; Intervention; Comparison; Consequence and Study type (PICOS) framework:

Participants: General dental practitioners or specialists placing oral implants.

Intervention: Antibiotic prescriptions in association with oral implant surgery.

Comparisons:

1. Evidence-based recommended dosage in healthy patients and in routine conditions: single pre-operative dose of 2,000 mg [nine].
2. Comparisons among different subpopulations (countries, antibody types and prescription regimens).

Outcomes: Average dosage and types of antibiotics prescribed per oral implant surgery.

Study type: Cross-exclusive survey.

Publications were excluded if they were clinical trials, case series or retrospective studies. At that place were no restrictions on language or publication yr. Publications that did not study enough data to calculate the full dosage of antibiotics contained in their participants' prescriptions were also excluded.

Searches were conducted in the following electronic databases up to June four, 2020: Embase, PubMed, Ovid Medline, Scopus, Science-Direct, Web of Cognition, as well as the Castilian General University Lath database of doctoral theses in Espana, the Spanish National Research Council bibliographic databases, and the Castilian Medical Index.

Iii independent investigators carried out the search in the databases. The searched terms were descriptors of the PICO components: antibiotics, oral implant surgery, dental implant surgery, oral implant placement, dental implant placement, and cross-sectional survey.

MeSH and search algorithms connected with Boolean operators were used as keywords for the electronic search. No filters were applied in the Ovid Medline and PubMed search: (antibody) AND (((oral OR dental) implant AND surgery) OR ((oral OR dental) implant AND placement)) AND (survey). In Scopus, the search was limited to "Dentistry" and "Commodity" for subject area and certificate type: (antibiotic) AND (((oral OR dental) implant AND surgery) OR ((oral OR dental) implant AND placement)) AND (survey) AND (LIMIT-TO (DOCTYPE, "ar")) AND (LIMIT-TO (SUBJAREA, "Dent")). The search in In Web of Cognition was filtered by "Article": TS = (antibody "AND" oral implant surgery "OR" dental implant surgery "AND" survey). In Scientific discipline Direct, "Research manufactures" filtered the search: (antibody) AND (((oral OR dental) implant AND surgery) OR ((oral OR dental) implant AND placement)) AND (survey).

The search in Embase was express to "Article", "Short Survey", "Article in Press" and "Questionnaire": (antibiotic) AND (((oral OR dental) implant AND surgery) OR ((oral OR dental) implant AND placement)) AND (survey) AND ('article'/it OR 'article in press'/information technology OR 'short survey'/information technology) AND 'questionnaire'/de.

For databases in Spanish, the following terms were used: (antibioticos) AND (implante dental O implante oral) AND (encuesta).

The references of all retrieved papers were reviewed as well. No potentially unpublished material could be identified.

Two independent reviewers (F.R.S. and C.R.A.) screened the titles and abstracts from the records identified from the search past using Cochrane's online software [35]. Full-text manufactures were caused for records that fulfilled the inclusion criteria. The researchers contacted every corresponding writer when extra information was required in the selection process. All discrepancies were discussed with a tertiary researcher (I.A.). The reasons for exclusion were reported (Fig 1).

The recorded data included the following: antibiotic type, regimen (preoperative, postoperative or both), dose, treatment duration and country. If the original dataset of an included study could not be obtained, information relating to the antibiotic blazon, safe regimen (preoperative, postoperative or both), dose and treatment elapsing were extracted from the published paper by two contained researchers (F.R.S. and C.R.A.). A tertiary political party was consulted to resolve any disagreement (I.A.). Calculations using data from tables were performed if the data on any variable were non explicitly stated in the text. The corresponding authors of eight different studies were contacted because the necessary information from their studies were unclear [14–20,26].

1 study surveyed 133 Swedish dental professionals [21]. Of these, 98 prescribed antibiotics while 35 did not prescribe any prophylactic antibiotics. This written report completely described 85 antibiotic regimens; notwithstanding, there were unfortunately 13 missing antibiotic regimens. Afterwards contacting the authors, no extra information was obtained. Therefore, the 85 dentists who prescribed antibiotics were included with a proportionate number of non-prescribing professionals (due north = 22) in identify of the 35 at the start.

The same adjustment was practical to other included studies with 29 participants who were unfortunately excluded because they did not provide a description of their prescription regimens (14 from Kingdom of spain, vi from Italy and 9 from the Netherlands). The newly calculated and proportionate numbers of non-prescribing professionals in these cases were 3.75, 0.96 and 4.7 respectively, while the original numbers were iv, 1 and 5 respectively. As the calculated values were very close to the original ones, information technology was decided to keep the initial numbers in order to perform the virtually conservative analysis possible [24–26].

The authors of the other five manufactures were unsuccessfully contacted in social club to collect necessary information for inclusion in the meta-analysis [15,17–xix]. The authors of two articles were successfully contacted; all the same, data requested on prescription dosage was insufficient for inclusion in the meta-analysis because their surveys did not collect this information [14,20].

Two independent reviewers (F.R.Southward. and C.R.A.) assessed the quality of the included studies using the National Heart, Lung, and Blood Institute Quality Assessment Tool for Observational Cohort and Cantankerous-Exclusive Studies [36]. All discrepancies were discussed with a third researcher (I.A.). The studies were categorized every bit low, moderate or loftier quality if the percentage of affirmative answers to the checklist was less than fifty%, between 50% and fourscore% or more than 80% respectively.

Each included report presented different datasets and information codifications. This heterogeneous presentation of information was for a limitation to performing a proper quantitative assay (meta-assay). To overcome this limitation and accomplish the report objectives, a uniform database with the original dataset from each study was created. The software STATA version 15 (StataCorp LLC, College Station, TX, Us) was used to generate this database and to perform all statistical analyses.

The boilerplate dosage (mg) of rubber antibiotics prescribed per implant surgery was calculated according to the individual prescription regimens (multiplying the treatment dose, dosage and the corresponding elapsing) with an interpretation of the standard deviation (SD). Participants who never prescribe prophylactic antibiotics for oral implant surgery were besides included in this assay. The normal distribution of the event data was graphically assessed using quantile-quantile plots (Q-Q plots).

Educatee's t-exam was used to compare the ways of the prophylactic antibiotics prescribed per study, country and prescription regimen against the bear witness-based recommended regimen: single pre-operative dose of 2,000 mg. In this analysis, prescriptions were included only if they contained antibiotics with a Defined Daily Dose (DDD) equal to the testify-based recommended regimen (2,000 mg) or equal to the DDD of amoxicillin (i,500 mg) according to the Anatomical Therapeutic Chemical system of the World Health Organization [37].

Multiple f-tests were used to compare the variations in different groups. Depending on the variance analysis, multiple t-tests for equal or diff variances were performed to compare the means of the antibiotics prescribed in the included studies. Bonferroni standard corrections were performed in both, f- and t-tests. In both tests, the α-value was calculated by dividing 0.05 past the total number of performed comparisons.

Results

V cross-sectional surveys were finally included in this meta-analysis [21–25]. Table one shows the descriptive information for of each study included in the quantitative assay. A menstruum chart describes the selection process, records and full-text exclusions with their justifications (Fig 1).

Four studies were judged as existence of moderate quality [21–25] and one of depression quality [22]. The percentage of affirmative answers to the National Health Index checklist was 75% for the study performed in Sweden, 54.5% for the other 3 studies (Espana, kingdom of the netherlands and Italy) and 45.5% for the study performed in the United Kingdom. The data distribution of the outcome variable is shown in the Q–Q plots (S1 Fig).

Overall, 726 participants were enrolled in this meta-analysis. All condom prescriptions consisted of oral antibiotics. Fig two illustrates the antibiotic types and regimens prescribed per country (Fig two).

On boilerplate, 10,724 mg of prophylactic antibiotics were prescribed per oral implant surgery. This average dose of antibiotics was found to be significantly college (p<0.001) than the testify-based recommended dose (2,000 mg).

Table ii shows the average dose of prophylactic antibiotics prescribed per antibiotic type and country. Amoxicillin was the most frequently prescribed antibiotic type, followed by amoxicillin in association with clavulanic acrid. Almost professionals from the Italian survey, followed by the participants from the Spanish survey prescribed clavulanic acid (Table 2).

The overall dose of the prescribed amoxicillin was significantly higher than 2,000 mg (9,700 mg, p<0.001). All the regimens with only amoxicillin independently comprised a significantly college dose than the reference of 2,000 mg, including those with but pre-operative amoxicillin (2,175 mg, p = 0.006). Nonetheless, the participants from United Kingdom prescribing exclusively pre-operative amoxicillin were the only ones that significantly (p<0.001) did it above the level of 2,000 mg per oral implant surgery (Tabular array three).

Amid the different subpopulations (state and prescription regimen), professionals prescribing just pre-operative antibiotics were the simply ones whose antibiotic prescriptions (two,110 mg) were non significantly (p = 0.091) above this threshold (Table 4). A wood plot taking the outcome variable into account is shown in Fig three (Fig 3).

Fig 3. Forest plot.

The forest plot represents the estimates of the hateful values and 95% conviction intervals for each outcome variable. The area of the squares around the mean values is proportional to the weight of the study in the assay. A continuous horizontal line indicates the 95% confidence intervals, while a rhombus and a dotted line signal the overall mean value.

https://doi.org/10.1371/journal.pone.0236981.g003

Bartlett's examination was found to be statistically meaning (p<0.001) amid the different countries and condom prescription regimens. Moreover, I² was found to be low (18.vii%). Therefore, low heterogeneity was found between countries (Tabular array 5).

The multiple-comparison assay of variances showed that all comparisons of variances were statistically meaning, except for three: Italy against the netherlands, Italy against the United Kingdom, and the Great britain against the netherlands. Therefore, both countries in each of these comparisons were found to exist homogeneous, relating to the dosages of prescribed antibiotics.

In addition, hateful comparisons were found to be statistically significant, except for Italia against Sweden, the Netherlands against Sweden, the U.k. against the Netherlands, Sweden against the Great britain and only mail service-operative confronting pre- and postoperative. Consequently, both countries in each of these comparisons were found to prescribe a similar boilerplate dosage of safe antibiotics (Table five).

Discussion

This meta-assay quantitatively assessed the prescriptions of rubber antibiotics in association with oral implant surgery and compared them to the existing scientific recommendations. In addition, this study provides quantitative comparisons of the boilerplate dosage of antibiotics and the regimens prescribed in oral implant surgery by professionals from different countries.

This meta-analysis indicates that the average dosage of safety antibiotics prescribed in conjunction with oral implant surgery is approximately five times larger than the evidence-based recommendations for healthy patients and straightforward weather condition: a 2-gram unmarried preoperative dose. Even for prescriptions of only pre-operative antibiotics, the boilerplate dosage was higher than the bear witness-based recommended dose [ix]. Countries presented neat variability in their average dosage of prescribed antibiotics and prescription regimens. These findings may be the consequence of a lack of consensus on the use of antibiotics in oral implant surgery among clinicians. Furthermore, the prescription variances found among the different countries included in this meta-assay may be attributed to this clinician's disagreement coupled with the idiosyncratic and cultural prescription habits of each state.

Cantankerous-sectional studies may be the nigh advisable study design to estimate the antibiotics prescribed in oral implant surgery, due to the lack of official records. Nevertheless, participants' statements in this kind of study may differ from their real behavior and the included participants may accept changed their conduct over time, since the included surveys were performed over the past years. In improver, patient interviews are required to measure the real drug intake at the patient level considering they do not always follow the prescriptions.

Despite all the efforts made to include the largest number of cross-sectional surveys in this meta-analysis, just five studies from five countries could be included. Moreover, the cross-sectional surveys did not reach all practitioners placing oral implants in each country, which may represent a source of bias. The combined analysis of all included studies in this meta-analysis increased the sample size and consequently, the power of the planned hypothesis analysis. The variability found amid the surveys did non cause heterogeneity in the results. The quality analysis performed through each of the included surveys suggests that the quality of this meta-analysis may be moderate, which could represent an important limitation. Consequently, the findings of this report must be considered cautiously due to the inherent limitations of whatever cross-sectional survey and the intrinsic weakness of the included papers, coupled with the limitations of this meta-analysis. These facts must be contemplated with utmost intendance to correctly interpret the outcomes of this meta-assay.

Regardless of the conclusion of the authors, non all participants of the included surveys could be enrolled in this meta-assay considering of missing information. This may correspond only a minor limitation in the data collection procedure every bit this problem was later solved by including a proportionated sample of non-prescribing professionals.

The average dosage of prescribed antibiotics was compared against a unmarried pre-operative dose of two,000 mg, which was considered the evidence-based recommendation in healthy patients and straightforward conditions despite its relative effectiveness [9]. This recommended dose was suggested for amoxicillin; nonetheless, but other antibiotic types have unlike assumed maintenance dosages for their main indications for adults. This could correspond significant limitation when contrasting the prescriptions against this recommendation, despite the fact that most majority of the prescriptions included in this meta-analysis involved amoxicillin with or without clavulanic acrid or antibiotic types coming from the family of penicillin.

Therefore, only antibiotics types with equal DDDs to amoxicillin or the prove-based recommendations were included in this comparison. The DDD is the assumed average maintenance dose per day for a drug used for its master indication in adults. The DDDs for anti-infectives are the main rule based on their utilize in infections of moderate severity [37].

In addition, ii cross-sectional surveys (Sweden and the Uk) were performed before these recommendations were published [21,22]. The time lapse since the publication of these studies may accept increased the possibilities of changes in the participants' antibiotic prescription habits for oral implant surgery. This ways that the current prescriptions could have varied over time and, therefore, the results of this study should be considered charily.

The professionals included in this study may present differences in their makeup, with possible variations in the proportion of specialists and general dentists between each country. This could atomic number 82 to the presence of longer and more frequent antibody prescriptions among participants depending on their degree of specialization and the complexity of the surgeries performed.

Nonetheless, three of the cross-sectional surveys, comprising the majority of the participants included in this meta-analysis (seventy%), contained prescriptions exclusively made for oral implant surgery in healthy patients and straightforward conditions [23–25]. Although the other two surveys may take included some prescriptions based on unlike circumstances, the majority of their participants (72% and 74% respectively) reported that they routinely prescribed antibiotics regardless of whatsoever specific conditions [21,22]. Despite these limitations, the lack of a clinical consensus, rather than the performance of complex surgeries or in patients with compromised health, is most probable the reason for the large differences found between prescribed antibiotics and scientific recommendations.

The findings reported by this meta-assay propose that an important number of antibody prescriptions might non be based on scientific testify. This situation may unreasonably increase the risk of adverse events such as allergies, toxicity, gastrointestinal disorders and the development of bacterial resistance [27,28]. This last consequence must exist regarded every bit an extraordinary concern every bit drug-resistant diseases already crusade at least 700,000 deaths a year worldwide [38]. In the most alarming scenario, this effigy could rise to 10 million deaths a year by 2050 if no action is taken. The economic impairment caused past uncontrolled antimicrobial resistance could be devastating, as information technology could drive 24 meg people into extreme poverty [38]. Moreover, the economic cost of antibiotic prophylaxis for an private is low just the potential costs for the healthcare system may exist substantial and definitely groundless if they are made through irrational prescriptions [39].

Consequently, this written report might reveal clinically relevant information for professionals placing oral implants in order to increase their adherence to recommendations when prescribing safe antibiotics and preventing their misuse. The present meta-assay should inspire new clinical research to amend the guidelines on this topic. This written report could also encourage the dissemination of methodologically strong evidence-based guidelines over antibody prophylaxis in oral implant surgery, as this may induce behavioral changes in professionals that may eventually correct their prescription patterns [twoscore].

Conclusions

In conclusion, the boilerplate dose of antibiotics prescribed per oral implant surgery was higher than that of the bear witness-based recommended regimen in salubrious patients and in straightforward weather condition. Additionally, there were variances in the average dose of prescribed antibiotics amongst dissimilar countries and prescription regimens.

Supporting data

S1 Fig. Q-Q plots.

A dot on the plot corresponds to ane of the quantiles of the outcome information distribution (y-coordinate) plotted against the aforementioned quantile of the normal distribution (x-coordinate). *Antibody types in which DDD is equal to the testify-based recommended regimen (ii,000 mg) or to the DDD of amoxicillin (ane,500 mg).

https://doi.org/10.1371/journal.pone.0236981.s003

(TIF)

Acknowledgments

The authors would like to give thanks Prof. Dr. Robert Ireland and Dr. Rahul Datta for their collaboration in the data collection process by sending the raw data of their articles and Dr. Julio C. Rincon A. for providing more information about his article.

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