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Localized delivery of antimicrobial agents (003)

Number: 003


Subject: Local delivery of antimicrobial agents (LDAs) as adjunctive therapy in the treatment of adult periodontitis


Reviewed: June 20, 2023


Important note


This Clinical Policy Bulletin determines whether certain services or supplies are medically necessary, experimental, and investigational, or cosmetic. Aetna® has reached these conclusions based upon a review of currently available clinical information (including clinical outcome studies in the peer-reviewed published medical literature, regulatory status of the technology, evidence -based guidelines of public health and health research agencies, evidence-based guidelines and positions of leading national health professional organizations, views of physicians practicing in relevant clinical areas, and other relevant factors). 


Aetna makes no representations and accepts no liability with respect to the content of any external information cited or relied upon in the Bulletin.  The discussion, analysis, conclusions, and positions reflected in this Bulletin, including any reference to a specific provider, product, process or service by name, trademark, manufacturer, constitute an opinion by Aetna and are made without any intent to defame. 


Aetna expressly reserves the right to revise these conclusions as clinical information changes, and welcomes further relevant information including correction of any factual error. CPBs include references to standard HIPAA compliant code sets to assist with search functions and to facilitate billing and payment for covered services. New and revised codes are added to the CPBs as they are updated. When billing, you must use the most appropriate code as of the effective date of the submission. Unlisted, unspecified and nonspecific codes should be avoided.


Each benefit plan defines which services are covered, which are excluded, and which are subject to dollar caps or other limits. Members and their providers will need to consult the member's benefit plan to determine if there are any exclusions or other benefit limitations applicable to this service or supply.


The conclusion that a particular service or supply is medically necessary does not constitute a representation or warranty that this service or supply is covered (for example, will be paid for by Aetna) for a particular member. The member's benefit plan determines coverage. Some plans exclude coverage for services or supplies that Aetna considers medically necessary. If there is a discrepancy between this policy and a member's plan of benefits, the benefits plan will govern. In addition, coverage may be mandated by applicable legal requirements of a State, the Federal government or CMS for Medicare and Medicaid members. CMS's Coverage Database can be found on the following website: 


Visit the CMS coverage database




Aetna considers the use of local antimicrobial agents as experimental and investigational for the treatment of periodontal disease in all clinical settings.


Antimicrobial agents with implants 


The use of the antimicrobial agent Arestin has not been clinically tested for use in the regeneration of alveolar bone, either in preparation for or in conjunction with the placement of endosseous dental implants or in the treatment of failing implants. The use of Arestin in this application is considered by Aetna to be experimental and investigational.




Thorough scaling and root planing (SRP) is highly effective in the treatment of chronic periodontitis and is the standard approach to non-surgical periodontal therapy. In most cases, the majority of sites will respond and require no additional adjunctive or aggressive therapy.  Recent data suggests that patients treated with SRP alone have greater probing depth reductions than those treated with Arestin.


In 2015, the Journal of the American Dental Association published the findings of a multidisciplinary panel convened by the American Dental Association (ADA) Council on Scientific Affairs (CSA.) The CSA presented clinical practice guidelines on the nonsurgical treatment of chronic periodontitis by means of SRP with or without adjuncts on the basis of a systematic review of the evidence.  For patients with chronic periodontitis, the evidence-based review concluded SRP showed a moderate benefit, and the benefits were judged to outweigh potential adverse effects. The guidelines were in favor of SRP as the initial nonsurgical treatment for chronic periodontitis. Regarding adjuncts, however, the strength of recommendations for chlorhexidine chips was deemed to be “weak” and recommendations for doxycycline hyclate gel and minocycline microspheres were listed as “expert opinion for.”  (Note that “expert opinion for” does not imply endorsement but instead signifies that evidence is lacking and the level of certainty in the evidence is low.) 


The ADA CSA evidence-based review could not definitively support the use of these adjuncts in conjunction with or following SRP. Therefore, since 2016, Aetna’s current clinical policy decision is that locally applied antimicrobials are considered experimental and investigational under Aetna plans.  


CDT D4381 is not covered for members with a dental plan that became effective after October 1, 2016. Some Aetna members may still have coverage for D4381 if they are in a group dental plan or program that has not had a benefit modification since the 2016 policy change.




D4381 — Local Delivery of Antimicrobial Agents via a Controlled-Release Vehicle into Diseased Crevicular Tissue, per Tooth


Revision dates


Original policy: November 23, 2004
Updated: May 21, 2012; August 12, 2013; June 9, 2014; April 27, 2017; April 29, 2019; April 8 , 2020; July 11, 2022; June 20, 2023
Revised: December 5, 2005; November 28, 2007; October 13, 2008; September 22, 2009; December 21, 2009; April 25, 2011; October 19, 2015; April 8, 2016; April 26, 2018


The above policy is based on the following references:


Shurduk, Artem, "Adjunctive Therapy of Periodontal Disease with Minocycline Microspheres in Dental School Settings: A Retrospective Chart Review." (2020). Dental Theses. 55.


Evidence-based clinical practice guideline on the nonsurgical treatment of chronic periodontitis by means of scaling and root planing with or without adjuncts. JADA 2015:146(7):525-535


American Dental Association. CDT 2023 Dental Procedure Codes. 


Copyright  2023 American Dental Association. All rights reserved.


Property of Aetna. All rights reserved. Dental Clinical Policy Bulletins are developed by Aetna to assist in administering plan benefits and constitute neither offers of coverage nor medical/dental advice. This Dental Clinical Policy Bulletin contains only a partial, general description of plan or program benefits and does not constitute a contract. Aetna does not provide health care services and, therefore, cannot guarantee any results or outcomes. Participating health care professionals are independent contractors in private practice and are neither employees nor agents of Aetna or its affiliates. Treating health care professionals are solely responsible for medical/dental advice and treatment of members. This Clinical Policy Bulletin may be updated and therefore is subject to change.

Legal notices

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Health benefits and health insurance plans contain exclusions and limitations.

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