silverstein-effects of local tetracycline

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    ClinicalndMicrobiologicffects f Local etracyclinelrrigationn Periodontitis.LeeSilverstein,abilBissada, . Manouchehr-PourndHenryGreenwell

    Acceptedorpublication3July1987

    Turs lNvrsrrcATroN wAs coNDUCTED N sEvEN NDtvtounLs referred for treatment ofmoderate dult periodontitis. wenty-eight iteswith an average robingdepthof 5.6+ 0.9mm were evaluated.One tooth per aw quadrant was randomly assigned o receiveone ofthe following treatments: I) no treatment, .e., control; (II) saline rrigation; (III) tetracyclineirrigationand (IV) scaling nd root planing SC/RP).A plaquecontrol programwas nstituted oneweekprior to the experimentalperiod andreinforced hroughout the eight-week tudy. rrigation wasperformedevery48 hours duringthe hrst two weeksof the experiment or Groups II and III, and the single reatment of SC/RP wascarriedout immediately ollowing he baseline xamina tion or Group IV. C linicaland microbiologic changeswere monitored every two weeks using plaque and gingivalindices,gingival fluid flow, probing depths,bleedingon probing and dark-freld microscopicexamination of the subgingivalmicrobial flora.The tetracycline and SC/RP treatment modalities resulted in statistically significantclinical and microbiological improvementswhen comparedwith the control. Tetracyclineirrigation alone and SC/RP alone had a similar effect n changing he subgingivalmicroflorafrom one associatedwith disease o one associatedwith health. Thus, these treatmentmodalities are effective methods of producing statistically significant alterations in thesubgingival microflora. The property of substantivity may contribute to the sustainedduration of the eflect of locallv delivered etracvcline.

    Several n vitro investigationshave shown that tetra-cycline hydrochloride is highly eflective against themajor suspectedperiodontal pathogensof both adultand uvenile periodontitis.t-3 ven when administeredas an adjunct in the treatment of c linical entities hatfail to respond o conventional therapy(i.e., refractoryperiodontitis), tetracycline has produced clinical andmicrobiological mprovements.r'an general, uantita-tive as well as qualitative changescan be expected nthe subgingival microbial flora of patientswith adultperiodontitis following a course of systemic tetracy-cnne.''"Listgarten et al.7 evaluated the eflects of systemictetracycline lone and in conjunction with scalingandroot planing (SC/RP). In a group of patientswho hadreceived etracycline n addition to meticulousscalingand root planing, the improvement in clinical andmicrobial parameterswas not significantly differentfrom that seenwith SC/RP alone. Administration of* Department of Periodontics, CaseWestern Reserve University,Cleveland.Ohio 44106.

    tetracyclinealone resulted n improvementssimilar tothoseseenwith SC/RP alone,althoughall clinical andmicrobialparametersended o relapseoward thebase-line values at a faster rate than that seen n groupsreceivingSC/RP.Systemicuseof antibioticscan nterfere with normalbody systemsand cause several adverseeffects.8Thelocal administration of antibiotics appears o be anellectivemeansof preventing heseadverse eactions.eThere are numerous reports on the effect of packingthe pocket with tetracycline containing hollow fibers,monolithic fibersor acrylic stripse-r2 heseapproacheshave resulted n marked changesn the composition ofthe subgingival lora of diseased eriodontal pockets.Daily irrigationsof pocketswith a 5-mg/ml tetracyclinesolution has also resulted n favorablechangesn gin-gival luid flow andproved o beeffectiveagainstseveralpotentially periodontopathicmicroorganisms.3In con-trast, there are reports that irrigation with antimicro-bials s of little benefit n thepresence f thoroughSC/Rp.la,15The present nvestigationcompared he eflect of SC/

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    Volume59Number5 Effectsof Tetracycline rrigatiol? 303Table IMean Plaque Index lSE for the Control and All Treatment Modalilies at Zero, Two, Four and EightWeeks

    Time in weeks Control Saline TCN SC/RP0246

    0.681-0.240.57 r 0.430.54+ 0.390.46 r 0.42

    0.61+ 0.280.54+ 0.430.64 f 0.350.61 r 0.20

    0.71+ 0.30 0.57+ 0.310.29+ 0.11 0.42+'0.400.36+ 0.24 0.54 f 0.510.61 f 0.13 0.36 f 0.28

    Table 2Mean Gingival Index lSE for the Control and All Treatment Modalilies at Zero, Two,Four andEight LVeeksTime in weeks Control Saline TCN SC/RP

    028

    1.43 F0.31 1.50 0.351.07 0.28 l .2 l + 0.22l . l8+0. 12* 1.29+0.27*1.25 0.20* 1.25 0.32** Statistical ly ignificantwhencomparedwith controlvalues P < 0.05).

    Table3Mean Gingival Fluid Flow Values+SE for the Control and AII Treatment Modalities at Zero, Two,Four and Eight Weeks

    Time in weeks Control Saline

    1.64 0.281.54 f 0.60t.7t + 0.271.82 0.t2

    t.79+ 0.291.29 0.30t .6 -f 0.281.61 f 0.20

    TCN SC/RP028

    t9.7t + 6.6528.71r- 3.2423.42 1.2129.42 7.79

    23.86-t- .3820.14 8.5526.t4+ tt .6I24.29 t 1.45

    21.57 r 8.28 20.29 7.59l l . l4 + 9.46 18.00r 9.9511.57 4.24 16.29 4.21416.28F8.34 20.51 7.48* Statistically significant when compared with control values (P < 0.05).

    Table 4Mean Bleeding Time Index Yalues lSE for the Control and All Treatment Modalities at Zero, Two,Four and Eight Weeks

    Time in weeks Control Saline TCN SC/RP028

    2.43 r O.tg1.43 1.40t.51 r | .272.51+ t.t3

    2.14+ 1.071.29 0.95t. '7t+ 1.252.29+ 0.76

    l .7 l + 0.95 1.57 0.980.86+ 0.69 l . l4 + l .2 l0.71+ 0.49* t.29+ 1.25*l .14+0.90 l . I4+ l .2 l** Statisticall y ignificantwhencomparedwith controlvalues P < 0.05).

    Table5Mean Probing Depth Yalues SE for the Control and All TreotmentModalities at Zero, Two, Fourand Eight WeeksTime in weeks Control Saline TCN SC/RP

    028

    5.21+ 0.465.22+ 0. '105.10+ 0.625.33+ 0.53

    6.24+ t.Ol5.94+ t.025.59+ 0.925.60+ 0.95

    5.78+ 0.93 5.19+ 0.674.81+ 0.78 5.17+ 0.684.90+0.71 4.19+0.745.31+ 0.87 4.1 ' ,7 0.70

    in the percentage f sp irochetes t two, four and eightweeks Fig. ).DISCUSSION

    Previous nvestigations avedemonstratedhat tet-racyclineplus SC/RP, using either systemicor localdelivery methods, s no more effective han SC/RPalone.T'raistgartenet al.7 eported ha t systemic etra-cyclinealonehad a significant eflectwhile the drug wasbeing administered but that effect was shortlived.These studiesare in generalagreementhat the antibi-

    otic without SC/RP is not an effectivemeansof pro-ducing a clinical or microbial resultof any significantduration. In the present study local irrigation withtetracyclinewithout prior SC/RP had an effecton theclinicaland microbiologicalndicatorshat wassimilarto that of SC/RP alone. This eflect s consistentwiththat reported y Listgarten t al.7The duration of the effect of tetracycline rrigationon the subgingivalmicroflora was onger than wouldbe expected ith systemic dministralion.This pro-longedperiod of effectiveness ay have been due to

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    Volume59Number 5hygieneprocedures,which is reflectedby the ow plaqueindex. Magnussonet a1.28 ave demonstrated hat thepresenceof supragingivalplaquemay promote a morerapid repopulationofthe pocketby spirochetes.Other investigatorshave reported hat signifrcantm-provements from baseline usually occur for clinicalindicators following treatmentwith tetracyclineor SC/pp.s'7'2e'30This was not the case n the presentstudy.These reatmentsdid producesignihcant changeswhencomparedwith the control group but not when com-paredwith baseline alues.This effectmay be attributedto the commencement f intensiveoral hygieneeffortsoneweekprior to the baseline xamination.The reduc-tion in clinical indicesprior to baselinemeasurements,in this case, may have decreased he magnitude ofchangesufficiently to precludestatistical significance.The objectiveof this studywas o document he com-parativeeffect of tetracycline rrigation alone and SC/RP alone,with minimal influence rom oral hygienemeasures.Therefore all changeswere measuredafteroral hygieneprocedureswere nstituted.Resultsof this investigation ndicate hat tetracyclineirrigation without prior SC/RP hasan effect similar tothat of SC/RP alone n convertinga disease-associatedsubgingival lora to one associatedwith a healthy state.Irrigation, therefore,may be an acceptablemethod ofdelivery when a local effect s desired.However, tetra-cycline irrigation, in the absenceof SC/RP, is notrecommended s a treatmentprocedure or periodon-titis. Although MacAlpine and coworkers'oeportednoadditive effects of SC/RP plus tetracycline irrigation,further investigation with large numbers of subjects swarranted o verify this result.

    REFERENCESl. Genco,R. J.: Antibiotics n the reatment [human periodontaldiseases. Periodontol 52:.545,1981.2. Baker,P. J., Evans,R. T., Slots, ., and Genco,R. J.: Suscepti-bility of human oral anaerobicbacteria to antibiotics suitablefortopicaluse. Clin Periodontol 2 201, 1985.3. Walker,C., Gordon, J., and Socransky,S.: Antibiotic suscepti-bility testing of subgingivalplaque samples. Clin Periodontol 0:422,1983.4. Lundstrom, 4.., ohansson, .-A., and Hamp, S.-E.:Effectofcombined systemic antimicrobial therapy and mechanicalplaque

    control in patientswith recurrentperiodontaldisease. CIin Perio-dontol l:321, 1984.5. Slots, ., Mashimo,P., Levine,M., and Genco,R. : Periodontaltherapy n humans.L Microbiological and clinical effectsof a singlecourse of periodontal scaling and root planing and of adjunctivetetracycline herapy.J Periodontol 5O:.495,1979.6. Lindhe,J. ,Liljenberg,B., and Adielsson, .: Effectof long-termtetracycline herapyon humanperiodontaldisease. Clin Periodontol10:590,1983.7. Listgarten,M., Lindhe, J., andHelld6n, L.: Eflect of tetracycline

    and/or scalingon human periodontaldisease. linical, microbiolog-ical and histologicalobservations. Clin Periodontol5':246, 1978.8. McGhee,J. R., Michalek,S. M., and Cassell,G. H.: DentalMiuobiology, p 155,Philadelphia,Harper and Row Publishers, nc.,t982.9. Goodson, . M. , Offenbacher, .,Farr,D. H., and Hogan,P. E.:

    Effectsof Tetracyclinerrigation 305Periodontaldisease reatment by local drug delivery. J Periodontol56:265.1985.10.Goodson, . M., Haffajee, ., and Socransky, .:Periodontaltherapyby local delivery of tetracycline.J Clin Periodontol6: 83,t979.ll. Lindhe, J., Heijl, L., Goodson,J. M., and Socransky, . S.:Local tetracyclinedelivery usinghollow fiber devices n periodontaltherapy. CIin Periodontol6: 4l, 1979.

    12 .Addy, M., and Langeroudi,M. : Comparison f the mmediateeflectson the subgingivalmicroflora of acrylic stripscontaining40%chlorhexidine,metronidazoleor tetracycline.J CIin Periodontol l:379,1984.13. Alflant,M., Walker,C. B., and Bhaskar, .: Local deliveryoftetracyclineasa possible djunct o conventionalperiodontal herapy(Abstr.No. 1083). Dent Res62:289, 1983.14. MacAlpine,R., Magnusson,., Kiger,R. ,et al.:Antimicrobialirrigation of deep pockets o supplement oral hygiene nstructionsand root debridement. . Biweekly rrigation. J Clin Periodontol12:568. 985.15. Braatz, ., Garrett,S., Claffey,N. , and Egelberg, .: Antimi-crobial irrigation of deep pockets o supplement non-suryicalperi-odontal herapy. I. Daily rri gation. Clin Periodontol 2:630,1985.16 .Listgarten,M., and Helld6n,L.: Relativedistributionof bac-teria at clinically healthyand periodontallydiseased ites n humans.J CIin Periodontol : ll5, 1918.17 .Listgarten,M. , and Levin,S. :Positive orrelation etween heproportions f subgi ngival pirochetes nd motile bacteria nd sus-ceptibility of human subjects o periodontal deterioration. .I C/inPeriodontol : 122,1981.18 .Mosques, ., Listgarten, ., andStoller,N.: EfIectof samplingon the compositionof the human subgingivalmicrobial flora. JPeriodonlRes15: 137,1980.19.Silness,., and Loe, H.: The gingival ndex, he plaque ndex,and the retention syslem. Periodontol38: 610, 1967.20. Garnick. J.. Pearson. .. and Harrell. D.: The evaluationofthe Periotron. Periodontol 0:424, 1979.21. Hinrichs, ., Bandt,C. ,and Smith,J.: Relative rror (variabil-ity) associated ith an improved nstrument or measuring ingivalcrevicular luid.J Periodontol 5:.294,1984.22. Tsuchida,K., and Hara, K.: Clinical significance f gingivalfluid measurement y "Periotron." J Periodontol52: 691, 1981.23.Nowicki,D., Vogel,R., Melcer,S. ,andDeasy,M.: Thegingivalbleedingime index. Periodontol 2:260, 1981.24. Baker,P., Evans,R. , Cobrun,T. , and Genco,R.: Tetracyclineand its derivative strongly bind to and are released rom the toothsurfacen active orm. J Periodontol54:580, 983.25. Magnusson,., Liljenberg,B., Yoneyama,T., and Blomqvist,N. Samplingof subgingivalmicrobiota for darkfield microscopy.-/Clin Periodontol12:.209, 1985.26. Greenwell,H., and Bissada,N. Variations n subgingivalmicroflora from healthy and intervention sites using probing depthand bacteriologicdentificati on riteria. Periodontol 5:391, 1984.27. Mosques, ., Listgarten,M. , and Phillips,R.: Effectof scalingand root planing on the composition on the human subgingivalmicrobial flora.J Periodont Res.15: 144, 1980.28. Magnusson,., Liljenberg,B. , Lindhe,J., and Yoneyama,T. :The effectof supragingival laquecontrol on microbial repopulationand clinicalhealing fpockets. Clin Periodontoll: 193, 1984.29. T^ege,D. , O'Leary,T., and El-Kafrawy,A.: The clinicalandhistological esponse f periodontal pockets o root planingand oralhygiene. Periodontol46: 527 197 .

    30. Hughes,T., and Caffesse, . Gingival changesollowing scal-ing, root planingand oral hygiene. Periodontol 49:245, 1978.

    Send reprint requests o: Dr- Nabil F. Bissada,ProfessorandChairman,Department of Periodontics,CaseWestern ReserveUni-versity,2123 bingtonRoad,Cleveland,OH 44106.