What do systematic reviews say?

Mechanical debridement plus local antimicrobial (minocycline microspheres or doxycycline gel) vs Mechanical debridement alone

• Supportive periodontal therapy (SPT) for maintaining the dentition in adults treated for periodontitis 2018 · Cochrane All outcomes

  12 months
  See comment. Killeen 2016 reported no adverse events at follow-up examinations in either study arm. Tonetti 2012 reported that there were no serious adverse events.
  2 studies · 251 participants
  GRADE not reported

Doxycycline + SRP vs Metronidazole + SRP

The review found no eligible studies for this question.

• Adjunctive systemic antimicrobials for the non‐surgical treatment of periodontitis 2020 · Cochrane All outcomes

  Long-term (≥ 1 year)
  Included studies have not reported adverse events
  Studies not reported
  No studies found

Amoxicillin + clavulanate + SRP vs Tetracycline + SRP

Amoxicillin + clavulanate + SRP showed no clear difference in adverse events compared with tetracycline + SRP; GRADE not reported.

• Adjunctive systemic antimicrobials for the non‐surgical treatment of periodontitis 2020 · Cochrane All outcomes
  The only included trial (Abu Fanas 1991) reported there were no adverse events.
  1 study · 8 participants
  GRADE not reported

Amoxicillin + clavulanate + SRP vs SRP

It is very uncertain whether amoxicillin + clavulanate + SRP changes adverse events compared with SRP (very low certainty).

• Adjunctive systemic antimicrobials for the non‐surgical treatment of periodontitis 2020 · Cochrane All outcomes

  Long-term (≥ 1 year)
  Included study reported diarrhoea in 2 participants from both groups.
  1 study · 21 participants
  Very low

Clindamycin + SRP vs SRP

The review found no eligible studies for this question.

• Adjunctive systemic antimicrobials for the non‐surgical treatment of periodontitis 2020 · Cochrane All outcomes

  Long-term (≥ 1 year)
  Included study has not reported adverse events
  Studies not reported
  No studies found

Metronidazole + SRP vs Amoxicillin + metronidazole + SRP

Metronidazole + SRP showed no clear difference in adverse events compared with amoxicillin + metronidazole + SRP; GRADE not reported.

• Adjunctive systemic antimicrobials for the non‐surgical treatment of periodontitis 2020 · Cochrane All outcomes
  All three included trials (Matarazzo 2008; Silva 2011; Xajigeorgiou 2006) reported adverse events in both MTZ + SRP and AMOX + MTZ + SRP groups (nausea, vomiting, diarrhoea, headache, metallic taste, irritability, mild…
  3 studies · 84 participants
  GRADE not reported

Amoxicillin + metronidazole + SRP vs Clarithromycin + SRP

Amoxicillin + metronidazole + SRP showed no clear difference in adverse events compared with clarithromycin + SRP; GRADE not reported.

• Adjunctive systemic antimicrobials for the non‐surgical treatment of periodontitis 2020 · Cochrane All outcomes
  Two patients were reported to have vomiting and unbearable stomach pain in the AMOX + MTZ + SRP group (Araujo 2019).
  1 study
  GRADE not reported

Moxifloxacin + SRP vs SRP

Moxifloxacin + SRP showed no clear difference in adverse events compared with SRP; GRADE not reported.

• Adjunctive systemic antimicrobials for the non‐surgical treatment of periodontitis 2020 · Cochrane All outcomes
  The included trial (Ardila 2015) had no adverse events amongst the participants.
  1 study · 40 participants
  GRADE not reported

Clarithromycin + SRP vs SRP

Clarithromycin + SRP showed no clear difference in adverse events compared with SRP; GRADE not reported.

• Adjunctive systemic antimicrobials for the non‐surgical treatment of periodontitis 2020 · Cochrane All outcomes
  Both included trials reported adverse events in the clarithromycin + SRP group: unpalatable taste and mild gastric intolerance in 2 patients (Pradeep 2011); mild gastrointestinal discomfort in 2 patients (Rebelatto…
  Studies not reported
  GRADE not reported

Levofloxacin + SRP vs SRP

Levofloxacin + SRP showed no clear difference in adverse events compared with SRP; GRADE not reported.

• Adjunctive systemic antimicrobials for the non‐surgical treatment of periodontitis 2020 · Cochrane All outcomes
  Both included trials (Pradeep 2014; Pradeep 2015) reported dizziness and diarrhoea in the levofloxacin + SRP group.
  2 studies
  GRADE not reported

Cefixime + SRP vs SRP

Cefixime + SRP showed no clear difference in adverse events compared with SRP; GRADE not reported.

• Adjunctive systemic antimicrobials for the non‐surgical treatment of periodontitis 2020 · Cochrane All outcomes
  The only included trial (Dukic 2016) reported nausea, dizziness and/or anorexia in the cefixime + SRP group.
  1 study · 60 participants
  GRADE not reported

Metronidazole + SRP vs SRP

It is very uncertain whether metronidazole + SRP changes adverse events compared with SRP (very low certainty).

• Adjunctive systemic antimicrobials for the non‐surgical treatment of periodontitis 2020 · Cochrane All outcomes

  Long-term (≥ 1 year)
  No severe adverse effects were reported by any of the participants in 1 study. 2 studies have not reported adverse events.
  3 studies · 71 participants
  Very low

Tetracycline + SRP vs SRP

The review found no eligible studies for this question.

• Adjunctive systemic antimicrobials for the non‐surgical treatment of periodontitis 2020 · Cochrane All outcomes

  Long-term (≥ 1 year)
  Included study has not reported adverse events
  Studies not reported
  No studies found

Doxycycline + SRP vs SRP

The review found no eligible studies for this question.

• Adjunctive systemic antimicrobials for the non‐surgical treatment of periodontitis 2020 · Cochrane All outcomes

  Long-term (≥ 1 year)
  Included study has not reported adverse events
  Studies not reported
  No studies found

Clindamycin + SRP vs Metronidazole + SRP

The review found no eligible studies for this question.

• Adjunctive systemic antimicrobials for the non‐surgical treatment of periodontitis 2020 · Cochrane All outcomes

  Long-term (≥ 1 year)
  Included study has not reported adverse events
  Studies not reported
  No studies found

Azithromycin + SRP vs SRP

It is very uncertain whether azithromycin + SRP changes adverse events compared with SRP (very low certainty).

• Adjunctive systemic antimicrobials for the non‐surgical treatment of periodontitis 2020 · Cochrane All outcomes

  Long-term (≥ 1 year)
  1 study reported diarrhoea, headache or dizziness, metallic taste, and general unwellness by 4 participants from the intervention group and 3 from the control group. In 1 study none of the participants reported any…
  2 studies · 110 participants
  Very low

Amoxicillin + metronidazole + SRP vs SRP

It is very uncertain whether amoxicillin + metronidazole + SRP changes adverse events compared with SRP (very low certainty).

• Adjunctive systemic antimicrobials for the non‐surgical treatment of periodontitis 2020 · Cochrane All outcomes

  Long-term (≥ 1 year)
  Most common adverse events were mild gastrointestinal disturbances, nausea and vomiting, metallic taste, and diarrhoea in the intervention group. Control group reported adverse events like hypothermia, mild…
  2 studies · 389 participants
  Very low

Clindamycin + SRP vs Doxycycline + SRP

The review found no eligible studies for this question.

• Adjunctive systemic antimicrobials for the non‐surgical treatment of periodontitis 2020 · Cochrane All outcomes

  Long-term (≥ 1 year)
  Included study has not reported adverse events
  Studies not reported
  No studies found

Doxycycline + SRP vs Amoxicillin + metronidazole + SRP

Doxycycline + SRP showed no clear difference in adverse events compared with amoxicillin + metronidazole + SRP; GRADE not reported.

• Adjunctive systemic antimicrobials for the non‐surgical treatment of periodontitis 2020 · Cochrane All outcomes
  One trial (Akincibay 2008) did not report this outcome; Xajigeorgiou 2006 reported mild gastrointestinal discomfort in 2 subjects from the AMOX + MTZ + SRP group.
  1 study
  GRADE not reported