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HERRERA ET AL .
Background
Number and design of included studies RCTs ( n = 2) with a double-blind, placebo-controlled, parallel design with follow-up up to 12 months (Blanco et al., 2022; Shibli et al., 2019). One evaluated amoxicillin plus metronidazole ( n = 40 patients/40 implants) (Shibli et al., 2019), and the other, metronida- zole alone ( n = 32 patients/62 implants) (Blanco et al., 2022). Risk of bias Risk of bias was low for one study, while the other study presented some concerns. Effect sizes and their clinical relevance Systemic antimicrobials showed a greater PD reduction when com- pared with mechanical debridement alone at 6 months and up to the 12 months follow-up ( ≈ 1.5 mm). These results were more pro- nounced when the deepest site of each implant was considered for the analysis.
Intervention
The adjunctive use of systemic antimicrobials has been extensively evaluated in the treatment of periodontitis (Teughels et al., 2020). The same principles may apply for its adjunctive use in the non-surgical step of the treatment of peri-implantitis. The expert group evaluated, first, the adjunctive benefit of sys- temic antibiotics to sub-marginal instrumentation alone. The effect was both statistically significant and clinically relevant. In the included studies (Blanco et al., 2022; Shibli et al., 2019), the effect tended to be more pronounced at cases with initially deeper lesions and to improve over time up to 1 year. At least in one study (Blanco et al., 2022), the benefit included improvements in MBLs. The size of the benefit may allow achievement of the stipulated treatment end points in a significant number of cases and hence avoid surgical inter- vention. The clinical recommendation that antibiotics cannot be recommended as a routine is, therefore, based on the general princi- ples of antibiotic stewardship and the public health objective of limit- ing unnecessary use of antibiotics in dentistry. Rationale for limitation is twofold: the public health considerations related to spread of antibiotic resistance and the potential individual harms related to dysbiosis of the individual patient microbiome. The panel felt that clinicians should avoid use of systemic antibiotics for the manage- ment of peri-implantitis and limit it to cases at the end of the sever- ity spectrum (e.g., deep pockets ≥ 7 mm, extensive suppuration) and/or with multiple and/or strategically affected implants that could respond well and be retained over time (the suggested proto- col in these cases would be metronidazole 500 mg/8 h/7 days). However, the use of systemic antimicrobials should be avoided in palliative care of lost implants.
Consistency Not applicable.
Balance of benefit and harm One study assessed the potential side effects of systemic antibiotics, with six subjects (38%) in the test group (systemic metronidazole) and five (31%) in the control group (placebo) reporting either gastrointesti- nal disorders, headaches or metallic taste, without significant differ- ences among groups. Global concerns regarding the overuse of antibiotics and the development of antibiotic resistance must be con- sidered. Benefit versus harm analysis includes considerations on the overall use of antibiotics for the individual patient and public health. Systemic antibiotic regimens have shown long-lasting impacts on the faecal microbiome, including an increase in genes associated with anti- microbial resistance.
Available evidence
Overall certainty of the evidence Limited evidence is available.
Two studies were included in the SR (Liñares et al., 2023), both show- ing statistically significant benefits in PD reduction at 6 months and up to 12 months after the prescription of systemic antimicrobials. These results were more pronounced when the deepest site of each implant was considered for the analysis. A significant effect for the use of systemic antimicrobials in radiographic bone gain ( ≈ 1.2mm) was observed on rough-surface implants (Blanco et al., 2022). How- ever, no changes in MBLs were reported on machined implants (Shibli et al., 2019). In both studies, PD reductions improved from 3 to 12 months, suggesting that, if at the re-evaluation (6 – 12 weeks) the recom- mended endpoints are not achieved at implant level (i.e., residual PD ≤ 5 mm with no BOP at more than one site point and no suppura- tion), but a clear improvement in PD reduction is detected, it may be adequate to wait longer before a decision to perform additional treat- ment is made.
From evidence to recommendation — additional considerations
Acceptability Due to concerns for patient's health and the impact of systemic anti- biotic use on public health, its routine use as an adjunct to sub- marginal peri-implant instrumentation in patients with peri-implantitis is not recommended. Feasibility Adjunct systemic antimicrobials to non-surgical peri-implant therapy are a feasible procedure since these antimicrobials may be prescribed in most countries. Moreover, the procedure does not demand high clinical skills.
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