Early dental implant outcomes in patients with reported penicillin allergy: a retrospective study on clindamycin safety

Abstract

Objectives

The purpose of study is to compare early failure rate in patients with self-reported penicillin allergy (SRPA) who take clindamycin after implant surgery with non-allergic patients.

Materials and methods

This retrospective cohort study was conducted on patients who had dental implant surgery. The predictor variable was the type of antibiotics. SRPA patients who received clindamycin were obtained from database. The patients in non-allergic group were randomly selected to be identical to allergic patients in terms of age, gender, diabetes, and surface features of implant. Kruskal-Wallis tests were used analysis early implant failure rate between the two groups implant level. The Pearson chi-square test was used to compare categorical data. Multivariate logistic regression analysis was performed with Hosmer and Lemeshow Test.

Results

The study completed with 406 patients. The mean age was 49.64 ± 13.72 years. 104 were male and 302 were female. The patients in both groups were the same in terms of age, gender, and implant surface characteristics. The failure rate of the implant 10(4.93%) in clindamycin group and 4(1.97%) at patient level. The failure rate of the implant 17(1.56%) in amoxicillin group and 9(0.75%) at implant level. There was no statistically significant difference between the groups in terms of failure rate at patient (p = 0.172) and implant level (p = 0.106). The failure rate in male patients was 4.11 time higher than female patients (p = 0.011).

Conclusion

The results showed that clindamycin use in SRPA patients did not significantly increase the implant failure with the limitations of this study.

Clinical relevance

This is first study compared early implant failure rate in patients with who received clindamycin after implant surgery with non-allergic patients with similar age, gender, health status.

Introduction

Dental implants are the most up-to-date treatment method with a high success rate in replacing the missing tooth within the success rate over 95% [1]. Although owing high success rate, failure can be observed [2]. The implant failure has been defined by Chrcanovic et al. [3] as sign and symptoms that cause removal of implant. Implant failures are classified as “early” or “late” according to before or after prosthetic loading and the failure rate range around 0.7–3.8% [4].

Early implant failures can be linked to overheating of the bone during drilling, implant placement with over torque and cortical stress, and post-operative infections [5]. Post-operative antibiotics was first recommended by Adell et al. [6] Since then, this issue has been the subject of many studies. The timing of antibiotic usage (prophylactic or postoperative), single or repeated dosage always been a matter of debate [7–10]. One of the purposes of using antibiotics is to prevent bacterial contamination by ensuring adequate concentration in the blood [11, 12]. Penicillin’s are the first choice antibiotics for prophylaxis in implant surgery [13–15]. Diarrhea, nausea, rash, and vomiting are the most common side effects in patients receiving penicillin therapy. Only 0.01% of patients experience life-threatening side effects such as true anaphylaxis [16]. Clindamycin is the first choice in patients with penicillin allergy [17–21]. Recent studies show that clindamycin use after dental surgery may increase implant failure in self-reported penicillin allergic (SRPA) patients [17, 22–26]. These studies claimed the clindamycin for increasing early implant failure due to postoperative infection and lack of osseointegration. It is a known fact that failure in implant surgery has a multi-factorial and complex structure. It does not seem easy to investigate only the effects of penicillin allergy or clindamycin within the multifactorial structure. These factors can be summarized as patient related (age, sex, health status, smoking habits etc.), anatomic (location of implant and bone quality etc.), implant related (length, width, surfaces features, neck design etc.), surgical (immediate implantation etc.), simultaneous grafting procedures and prosthesis related (abutment type, occlusion, retention type etc.) factors. The present study was designed to answer the question of whether clindamycin use increases early implant failure before prosthetic loading in patients with SRPA. The authors hypothesized that clindamycin use in patients with SRPA may increase the rate of early implant failure. The authors aimed to create a sample group by trying to keep all possible variables constant within the multi-factor structure. The purpose of this study is to compare early implant failure rate in patients with SRPA who received clindamycin after implant surgery with non-allergic patients with similar age, gender, health status.

Materials and methods

Study design and sample

This retrospective single-center cohort study was conducted on patients who had dental implants at Erciyes University, Departmens of Oral and Maxillofacial Surgery between 2010 and 2023. Approval for the study was received from Erciyes University Clinical Studies Ethics Committee (2023 − 512). The study was conducted in accordance with the principles of the Declaration of Helsinki, and the requirement for informed consent was waived due to the retrospective nature of the study.

Inclusion criteria

• Patients who underwent dental implant placement.

• Patients with self-reported penicillin allergy (SRPA) who received clindamycin following implant surgery.

• Non-allergic patients who underwent implant placement without a history of penicillin allergy.

• Patients matched between groups based on age, sex, and systemic health status.

• Patients with complete and accessible surgical and follow-up records.

Exclusion criteria

• Patients with incomplete or missing clinical, surgical, or follow-up records.

• Patients who received antibiotics other than clindamycin (in the SRPA group) or standard prophylaxis (in the control group).

• Patients with a history of conditions that may significantly affect bone healing (e.g., head and neck radiotherapy, uncontrolled systemic diseases).

• Patients with missing or inconsistent demographic or clinical data required for matching (age, sex, systemic health status).

The samples include patient who had dental implant and implant failed before prosthetic loading. Patients with incomplete surgical records were not included in the study. This study was carried out under the guidance of Strengthening the reporting of observational studies in epidemiology.

Study variable

The predictor variable was the type of antibiotic used after dental implant surgery. The patients were divided into two groups: non-allergic and SRPA. Patients received clindamycin after dental implant surgery in SRPA group. First, the patients who had implant and received clindamycin were identified from the database. The selection of patients in the amoxicillin group was performed in a way to ensure similarity with the clindamycin group in terms of key confounding factors such as age, sex, diabetes mellitus (DM), and implant surface characteristics. This approach was not intended to influence or violate the principles of randomization but rather to control for major variables known to affect implant failure. By matching these factors, we aimed to more effectively isolate and evaluate the potential effects of the antibiotic type and implant surface on clinical outcomes. The implants used in this study were as follows: Implance (Trabzon, Turkey), Bilimplant (Istanbul, Turkey), Straumann (Basel, Switzerland), and Dyna (Halsteren, Netherlands). The surface of implant classified as resorbable blast media (RBM) surface, and sandblasted, large grit, acid-etched implant surface (SLA). Patients in the amoxicillin group received 1 gram of amoxicillin orally twice daily, while patients in the clindamycin group were prescribed 150 mg of clindamycin orally four times daily. The antibiotic regimen was continued for a total of five days.

The main study outcome was failure rate of the inserted implant before prosthetic loading in patient and implant level. Early implant failure was defined as any implant that required surgical removal before prosthetic loading due to clinical signs of infection, such as persistent pain, swelling, suppuration, mobility, and/or radiographic evidence of peri-implant bone loss. These cases were identified through clinical records and surgical notes. Failure rate was classified as present or absent at the patient level. At the implant level, the implant failure rate was calculated by dividing number of failure implant by the total number of implants placed on per a patient.

Data collection method

All data were obtained surgical records and hospital registry software (MedData Tic. ve San. Ltd. Şti., Ankara, Türkiye). All data was upload excel file and data set was created.

Statistical analysis

According to the findings of the relationship between implant failure and penicillin allergy at the implant level reported in the study of Salomo-Coll et al. [24], performed using G*Power software (Ver. 3.1.9.7, Franz Faul, Universität Kiel, Germany), according to the results of the chi-square test power analysis with a 95% confidence (1-α), 80% test power (1-β) and effect size of w = 0.143, it was determined that research should be conducted on at least 384 cases in total. Histograms, Q-Q plots, and the Shapiro-Wilk test were used to evaluate normal distribution of data. The descriptive data of implants and patients were presented as numbers and percentages. Data were expressed as the mean and standard deviation (SD) and median (1st quartil-3rd quartil) for quan- titative continuous variables, and as percentages for categorical variables. Descriptive statistics were calculated for each variable. The Levene’s test was used homogeneity of variance. Kruskal-Wallis tests were used analysis early implant failure rate between the two groups implant level. The Pearson chi-square test was used to compare to analysis relationship between early implant failure and clindamycin use at patient level.

Logistic regression models were used to evaluate the effect of implant-related and patient-related explanatory factors on the early failure of implants at the patient level. The factors were age and gender of patients, diabetes mellitus, Self-reported Penicillin Allergy, Surface features of implant. The results of the final model were presented as odds ratios (OR), including 95% confidence intervals (CI). p < 0.05 was considered statistically significant. The level of significance used in the analyses was 5% (α = 0.05). All data analysis were done with Turcosa statistical analysis program (Turcosa Ltd. Co., Kayseri, Türkiye). Differences were considered significant at p < 0.05.

Results

The records of 13,335 patients who had dental implant were scanned from department database. The study completed with 406 patients (104 male:304 female) with the mean age of 49.64 ± 13.72 years. 203 of these were in clindamycin group and 203 were in the amoxicillin group. Descriptive data was shown in Table 1. A total of 1554 dental implants were placed, and 26 (1.67%) implants in 14 patients failed prior to prosthetic loading. 290 (18.66%) of the implants had RBM surface, and 1364 (81.33%) had SLA surface. 773 of the implants were in the clindamycin group and 781 were in the amoxicillin group. The patients in both groups were same in terms of age, gender, and implant surface characteristics. Only samples that were as similar as possible in terms of diabetes were selected. 45 (11.08%) patients had diabetes mellitus; 361 (88.92%) patients did not have. 24 of the patients with diabetes were in the clindamycin group and 21 were in the amoxicillin group. There was no statistically significant difference between the groups in terms of presence of diabetes mellitus (p = 0.752). The distribution of the age, gender, systemic disease, and surface features of implant was shown in the Table 2.

Table 1.

The Descriptive Data

Variable	Total (n = 406)
Age (years)	49.64 ± 13.72
Gender
Male	104(25.62)
Female	302 (74.38)
DM
No	361 (88.92)
Yes	45(11.08)
Total Implant Failure at Patient Level
No	392 (96.5)
Yes	14 (3.45)
Total Number of Implant	1554
Total number of Failure at Implant Level	26(1.67)
Surface at Patient level
RBM	72(17.73)
SLA	334 (82.27)
Surface at Implant Level
RBM	290 (18.66)
SLA	1264 (81.33)

The data was shown mean± standard deviation and n(%)

DM Diabetes Mellitus, RBM resorbable blast media implant surface, SLA Sandblasted, large grit, acid-etched implant surface

Table 2.

The Distribution of the age, gender, diabetes mellitus and surface features between the groups

Variable	Clindamycin (n = 203)	Amoxicillin (n = 203)	P
Age	49.64 ± 13.74	49.64 ± 13.74	N/A
Gender
Male	52 (25.62)	52(25.62)	N/A
Female	151(74.38)	151(74.38)
Presence of DM
Yes	24 (11.82)	21(10.34)	0.752‡
No	179 (88.18)	182(89.66)
Surface Features
RBM	36(17.73)	36(17.73)	N/A
SLA	167(82.27)	167(82.27)

The data was shown mean± standard deviation and n (%)

DM Diabetes Mellitus, N/A not applicable, RBM resorbable blast media implant surface, SLA Sandblasted, large grit, acid-etched implant surface. ^‡, Pearson’s chi-square test

The distribution of the failure rate of the implant at patient and implant level between the groups was shown in Table 3. The failure rate of the implant was 10 (4.93%) in clindamycin group and 4 (1.97%) at patient level. There was no statistically significant difference between the groups in terms of failure rate at patient level (p = 0.172). The failure rate of the implant was 17 (1.56%) in clindamycin group and 9 (0.75%) in amoxicillin group at implant level. There was no statistically significant difference between the groups in terms of failure rate at implant level (p = 0.106).

Table 3.

The distribution of the failure rate of the implant at patient and implant level between the groups

Variable	Clindamycin (n = 203)	Amoxicillin (n = 203)	P
Implant Failure at Patient Level
Yes	10(4.93)	4(1.97)	0.172‡
No	193(95.07)	199 (98.03)
Failure rate at implant level	1.56 ± 8 0(0–0)	0.75 ± 5.40 0(0–0)	0.106ƞ

The data was shown mean± standard deviation, median (1st quartile- 3rd quartile), and n (%).^‡, Pearson’s chi-square test. ^ƞ, Kruskal–Wallis test

The result of multivariate logistic regression analysis at patient level was shown in Table 4. In the multivariate logistic regression analysis performed at the patient level, gender was identified as the only significant predictor of early implant failure. Male patients had a significantly higher risk of implant failure compared to females (B = 1.414, SE = 0.553, Wald = 6.543, p = 0.011), corresponding to an approximately fourfold increase in risk (OR: 4.11, 95% CI: 1.39–12.14). Although age, diabetes mellitus, self-reported penicillin allergy, and implant surface characteristics were initially included in the model, none of these variables remained statistically significant after the stepwise elimination process (p > 0.05).

Table 4.

Multivariate Logistic Regression Analysis for Failure Rate at Patient Level

	B	SE	WALD statistic	p	OR	%95 CI for OR
						Lower	Upper
Constant	-3.899	0.412	89.383		0.020
Gender(male)	1.414	0.553	6.543	0.011	4.111	1.392	12.145

Variables entered on step 1: Age, Gender, Self-reported Penicillin Allergy, Surface features

DM Elimination Method, Backward Wald. CI, confidence interval, DM diabetes mellitus, OR odds ratio

Discussion

Dental implants have become the first choice for replacing missing teeth, with a success rate of over 95%; however, various complications may still occur. Among these, postoperative infections represent an important factor that may lead to implant failure. Although the use of antibiotics to prevent infections after dental implant surgery is controversial, it is a common practice among dentist and oral surgeons to reduce risk of early failure. Another controversial issue regarding antibiotics was the type of agent to prescribe. This study focused on the relationship between the type of antibiotic and early failure in patients reporting penicillin allergy or not. The results of this study showed that there was no statistical difference in terms of early implant failure rate between clindamycin prescribed SRPA patients and amoxicillin prescribed non-allergic patients at patient and at implant level (p < 0.005).

Salomó-Coll et al. reported that penicillin allergic patients who received clindamycin were almost four times more likely to suffer dental implant failure than non-penicillin allergic patients [24]. The infection rate in the penicillin-allergic patients was found about 6-times higher than non-allergic group [23]. The reason for high failure rates in patients with SRPA is still unclear. Suboptimal efficacy of alternative antibiotics (such as clindamycin), allergy may be a genetic predisposing to an increased risk of implant failure, negative influence of clindamycin on osseointegration may be three mechanism that cause early implant failure in patients with SRPA [17]. The resistant Prevotella species number increases in saliva after clindamycin administration and is often isolated in cases of periimplantitis [27, 28]. It has been showed that Prevotella intermedia, Tannerella forsythia, and Aggregatibacter actinomycetemcomitans, may be resistant to clindamycin at therapeutic concentrations [29]. There is a small amount of evidence showing that the number of methicillin-resistant Staphylococcus aureus may increase as a result of the use of antibiotics other than beta-lactams [30]. Arteagoitia et al. [31] reported that clindamycin resulted ineffective in preventing post-operative complications in patients who extracted third molar. Salgado-Peralvo et al. [32] called for future clinical studies to evaluate the role of both the allergic profile and the effect of clindamycin in patients with SRPA.

The long-term survival of 4,591 dental implants showed that location of implant, length of implant, immediate implantation, bone grafting procedures, male sex, presence of autoimmune diseases, heavy smokers, and penicillin allergy were risk factors for early implant failure [33]. Clindamycin usually prefers for penicillin allergic patients as an alternative to penicillin. But recent reported that there is the poor quality clinical evidence for its use in oral implant surgery [17, 23, 24, 32, 34]. Wagenberg and Froum [22] reported that the risk of failure in patients who received clindamycin after implant surgery was 3.34 times higher than patients who received penicillin. French et al. investigated the relationship between implant failure and SRPA. Implant failure was found 3.1 times in SRPA patients who received clindamycin compared with nonallergic patients. In addition the failure rate for immediate implantation in extraction sockets was 10-times higher in SRPA patients [23]. Zahra et al. reported that patients who received clindamycin due to SRPA allergy experienced a higher rate of implant failure than the patients who received amoxicillin [25]. In contrast, Arrieta et al. performed a prospective study to evaluate the effect of preoperative oral clindamycin in reducing early implant failure. They concluded that preoperative clindamycin administration during implant surgery does not reduce implant failure or post-surgical complications [26]. In the present study the failure rate was higher in SRPA patients who received clindamycin than the non-allergic patients who received amoxicillin, but the difference was not statistically significant at patient and at implant level (p > 0.05). The sample design method of the present study may be responsible of the difference between the result of present study and the literature. It was aimed to determine a non-allergic patient group as similar as the SRPA group in terms of age, sex, implant surface characteristics and DM.

Age, sex, type of antibiotic, surface features and DM were analyzed with multivariate logistic regression analysis for failure rate at patient level. According to the results of this analysis, it was concluded that male gender increases the implant failure rate 4.11 times more than the other factors. The patient specific factors that include male gender, smoking, autoimmune disease and penicillin allergy was related high implant failure rates [33]. They reported that male gender was significant indicator for implant failure. This may be related the increased bite force expected in male patients. In addition, the failure risk was also higher before prosthetic loading in male gender.

There was a results of the gene analysis showed that carriers of the HLA-B*55:01 allele have a 33% higher relative risk of penicillin allergy than the rest of the population, which could point to a lymphocyte-mediated predisposition leading to a delayed penicillin reaction [35]. A link between polymorphisms in these genes and rheumatoid arthritis, a systemic autoimmune chronic inflammatory disease that has been identified as a risk factor for dental implant failure [36]. However, studies are needed to confirm the hypothesis of a possible link between genetic alterations and increased susceptibility to implant failure [34]. In all studies mentioned, all of the included patients reported penicillin allergy by themselves, and the diagnosis of allergy was not based on genetic or allergy tests.

Amoxicillin is the most used antimicrobial agent in dentistry and still the first line of defense for many tooth infections [37]. Clindamycin is the first choice in case of SRPA. There is a lack of simple decisional algorithms to select which antibiotic is suitable for dentists in SRPA patient [34]. A new protocol is needed to remove the label of penicillin allergy in SRPA patients undergoing dental implants. More research appears to be needed to elucidate the impact of penicillin allergy, clindamycin use, and the reliability and validity of the allergy label [34].

Another concern was clindamycin may negatively influence osteointegration. There are a very limited number of studies on this subject. High concentrations clindamycin reduces alkaline phosphatase activity and calcification of the extracellular matrix in a dose-dependent manner, while at lower concentrations [38]. Curiously, clindamycin has been reported to be cytotoxic or cytostatic in high concentrations for bone cells in vivo after local administration [39]. It seems that further in-vivo, in vitro, and clinical studies are needed to fully elucidate this relationship.

The main limitation of this study was the lack of comprehensive data regarding several critical variables, including the timing of the implantation protocol (immediate, early, or delayed), details of any bone grafting procedures performed, patients’ smoking habits, and their periodontal status prior to surgery. These limitations are primarily due to the retrospective design of the study, which restricted access to complete clinical documentation and standardized preoperative assessments. As a result, potential confounding factors that may influence implant success and outcomes could not be fully analyzed or controlled.

Additionally, according to Ikram J. et al. the current body of evidence regarding antibiotics use for preventing implant failure remains inconclusive and exhibits inherent weaknesses. The available evidence supports the administration of preoperative antibiotics as opposed to postoperative administration, as well as, indicating a lower incidence of complications associated with antibiotic administration compared to non- antibiotic regimens. Nevertheless, authors note the strength of the available evidence does not merit clear extrapolations [40]. We acknowledge that implant failure is a multifactorial and complex phenomenon and evaluating it solely through the lens of a single variable, such as antibiotic type or allergy status, has inherent limitations. To partially address this, we adopted a matched case design to ensure comparable baseline characteristics between groups. However, we do not claim to draw definitive conclusions. Rather, our aim is to offer practical insights that may assist clinicians in understanding possible associations, and to contribute to the existing literature by highlighting an underexplored area of clinical relevance.

Conclusion

There are ongoing concerns in the literature regarding the use of clindamycin before or after implant surgery in patients with SRPA. Within the limitations of the present retrospective study, clindamycin use was not associated with a statistically significant increase in implant failure rates. However, multivariate logistic regression analysis indicated that male gender was associated with a higher risk of implant failure (odds ratio: 4.11). These findings should be interpreted with caution due to the retrospective design and incomplete clinical data. Further prospective studies are needed to clarify the role of clindamycin in osseointegration and postoperative infection risk in dental implant surgery.

Authors’ contributions

Conception and Design: ES. and YNK conceived and designed the study, including defining the objectives, hypotheses, and methodology.Supervision: ES and AED provided overall supervision and critical guidance during all study phases and contributed to refining the research framework.Data Collection and/or Processing: TP, YNK, BY, and BA were responsible for patient recruitment, acquisition of clinical and radiological data, and ensuring the integrity and accuracy of data collection.Analysis and Interpretation: ES and YNK performed the statistical analyses and interpreted the results about existing literature and study aims.Literature Review and Manuscript Writing: TP, YNK, BY, and BA contributed to the comprehensive literature review and manuscript drafting, including preparing tables and figures.Critical Revision: ES, TP, YNK, and AED critically reviewed the manuscript for intellectual content, structure, and clarity, and approved the final version for submission.

Funding

None.

Data availability

The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.

Declarations

Ethics approval and consent to participate

The study protocol was reviewed and approved by Erciyes University Clinical Studies Ethics Committee (2023 − 512) and the need for informed consent was waived due to the use of the non-interventional, retrospective design. The procedures used in this study adhere to the tenets of the Declaration of Helsinki.

Consent for publication

Not Applicable.

Competing interests

All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest or non-financial interest in the subject matter or materials discussed in this manuscript.