Local anti-infective therapy: pharmacological agents. A systematic review

It is well recognized that periodontal diseases are bacterial in nature. An essential component of therapy is to eliminate or control these pathogens. This has been traditionally accomplished through mechanical means (scaling and root planing [SRP]), which is time-consuming, difficult, and sometimes ineffective. Over the past 20 years, locally delivered, anti-infective pharmacological agents, most recently employing sustained-release vehicles, have been introduced to achieve this goal.

This systematic review evaluates literature-based evidence in an effort to determine the efficacy of currently available anti-infective agents, with and without concurrent SRP, in controlling chronic periodontitis.

In patients with chronic periodontitis, what is the effect of local controlled-release anti-infective drug therapy with or without SRP compared to SRP alone on changes in clinical, patient-centered, and adverse outcomes?

MEDLINE, the Cochrane Central Trials Register, and Web of Science were searched. Hand searches were performed of the Journal of Clinical Periodontology, Journal of Periodontology, and Journal of Periodontal Research. Searches were performed for articles published through April 2002. In addition, investigators contacted editors of the above-mentioned journals and companies sponsoring research on these agents for related unpublished data and studies in progress.

Studies included randomized controlled clinical trials (RCT), and case-controlled and cohort studies at least 3 months long. Therapeutic interventions had to include 1) SRP alone; 2) local anti-infective drug therapy and SRP; or 3) local anti-infective drug therapy alone. Included studies had to report patient-based mean values and measures of variation for probing depth (PD) and/or clinical attachment levels (CAL) for both test and control groups.

Studies were excluded if they: 1) included data from a previously published article; 2) included daily rinsing with chlorhexidine (CHX); or 3) had unclear descriptions of randomization procedures, examiner masking, or concomitant therapies.

For the meta-analysis, PD and CAL were expressed as summary mean effects with 95% confidence intervals (CI) for the effect, and analyzed using a standardized difference between SRP alone and experimental agent groups. The results were assessed with both fixed-effects and random-effects models. Studies were ranked according to the York system.

1. Thirty-two studies were included (28 RCT, 2 cohort, and 2 case-control), incorporating a total patient population of 3,705 subjects. 2. Essentially all studies reported substantial reductions in gingival inflammation and bleeding indices, which were similar in both control and experimental groups. 3. A meta-analysis completed on 19 studies that included SRP and local sustained-release agents compared with SRP alone indicated significant adjunctive PD reduction or CAL gain for minocycline (MINO) gel, microencapsulated MINO, CHX chip and doxycycline (DOXY) gel during SRP compared to SRP alone. 4. Use of antimicrobial irrigants or anti-infective sustained-release systems as an adjunct to SRP does not result in significant patient-centered adverse events.

1. In some populations, anti-infective agents in a sustained-release vehicle alone can reduce PD and bleeding on probing (BOP) equivalent to that achieved by SRP alone. 2. No evidence was found for an adjunctive effect on reduction of PD and BOP of therapist-delivered CHX irrigation during SRP compared to SRP alone. 3. Additional RCTs are needed which evaluate the effectiveness of these therapies in all forms of periodontitis. 4. The study protocol for future RCTs should include appropriate statistical analyses and complete data sets to facilitate future evidence-based reviews. 5. Alternative surrogate parameters to PD and CAL need to be identified and validated such as microbial, inflammatory, or tissue-destructive markers that could be used in conjunction with clinical parameters to help determine the patient's response to emerging technologies that target the infectious and/or inflammatory aspects of periodontitis. 6. Future Phase IV clinical trials should be designed that evaluate local anti-infective therapies in conjunction with SRP in a manner consistent with current standards of care and evaluate cost-effectiveness. 7. The use of local anti-infective agents in at-risk patient populations and for the treatment of at-risk disease sites needs to be validated in randomized controlled clinical trials. 8. Several local anti-infective agents combined with SRP appear to provide additional benefits in PD reduction and CAL gain compared to SRP alone. The decision to use local anti-infective adjunctive therapy remains a matter of individual clinical judgment, the phase of treatment, and the patient's status and preferences.