Antibiotic Therapy in Clinical Periodontics

Dr. Dennis R. Hunt, Dr. Jin Y. Kim, Dr. Michael G. Newman,

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Literature Review



1. Newman, M.G.; Kornman, K.: Antibiotic/Antimicrobial Use in Dental Practice--Chapter 11, 136-147, Quintessence, 1990.
2. Genco, R.: Antibiotics in the Treatment of Human Periodontal Disease. J. Perio. 52:545-558, 1981.

Rationale:
A Studies of the microbial etiology of periodontal diseases. healthy gram+: streptococcus and facultative Actinomyces. advanced adult periodontitis
Mono-etiology and Koch's postulates do not fit most infections associated with anaerobic bacteria. Bacterial Synergy models are more applicable to mixed anaerobic infections such as periodontal disease.
B Antibiotic Susceptibility Patterns of Oral Organisms: MIC: minimum inhibitory concentration, Break point:conc in blood that will give optimal therapy. Table 1

Table 2 : Antibiotic susceptibility of cultured strains of potentially periodontopathic bacteria. In Vitro
Tetracyclines are effective against the major potential pathogens of periodontitis and of LJP. Metronidazole is effective against anaerobes but not against capnophilic or facultative organisms. PCN is effective against most except some strain of the Actinomyces species, it is not effective against half of the strains of Aa at concentration lower than 4ug/ml.
C Mechanism of Action and Pharmacodynamics of Antibiotics. Cidal: penicillin, metronidazole and cephalpatin Static: chloramphenicol, clindamycin erythromycin and the tetracyclines.
Tetracycline is concentrated in the gingival fluid from 2 to 10 times higher than in the blood. Adverse Reactions toxicity or allergy and development of resistance

table 3
penicillins: nontoxic clindimycin pseudomembranous colitis erythromycin tetracycline phototoxicity, allergy, staining of teeth, GI sx: N and V., opportunistic Candida, delayed fontanelle closure with increases intercranial pressure. Minocycline less phototoxicity and less renal toxicities Development of Resistance intrinsic or required. intrinsic acquired: result of mutation of chromosomally linked genes. This develops as a series of small steps, a 2 to 5 fold increase in resistance at each step. Plasmids are extrachromosomal DNA molecules that carry genetic information ( such as resistance) . The emergence of drug resistant bacteria has been traced to plasmids. Studies on the Use of Antibiotics for the treatment of Human Periodontal disease.


Guidelines
  1. for most patients with g-vitis, p-itis and no systemic disease, there is no advantage to using AB's: sc, rp and surg (debridement) are recommended.
  2. in adults with refractory sites 250mg tetracycline QID x14d, must monitor
  3. LJP: tetracycline useful adjunct to nonsurgical therapy
  4. DM, downs syndrome, neutrophil dyscrasia, endocrine disorders, or nutritional deficiencies which influence the severity of periodontal disease, AB's may be useful
  5. pts should be informed.
  6. pts should be monitored.

3. Van Palenstein Helderman, W. H.: Is antibiotic therapy justified in the treatment of human chronic inflammatory periodontal disease? J. Clinical Perio. 13:932-938, 1986.


A critical review of the rationale for the use of antibiotics in p. d. The use of antibiotics must meet several criteria in order to be effective in periodontal disease: A. It must be questioned whether the present microbial etiology of p. d. implies antibiotic therapy. B. Effective concentrations of ab must be reached in the perio pocket. C. Adverse effect of ab and induction of ab resistance must be taken into acct. D. The rationale for use of ab in an immunocompromised host is discussed.
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Microbial etiology of p. d.: The primary etiology of p.d. is bacterial. With time shifts in plaque composition occur. Subg. plaque originates from suprag. plaque. Subg. pl. is v. complex, >100 species. Most are considered to be potentially pathogenic with a few particular species, B. gingivalis, B. intermedius, A. actinomycetemcomitans, and Capnocytophaga sp. often predominating the flora and able to produce toxic substances. Yet it is unlikely and impossible to tell if any one particular species is an exclusive pathogen. Ideally, we would have to selectively eliminate a purported pathogen from the pocket and see if this arrested periodontal tissue loss. We are currently capable of doing this.
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Site of action; the pocket: Adverse effects of ab can be minimized when delivered topically. However, PCN derivatives can still sensitize. Ab in rinses, gum, dentifrices, ointments aren't effective subg because effective concentrations can't be reached in the pocket To be effective the drug must reach the active site in high enough concentrations for an adequate time period. Methods developed for periodontal pockets include subg irrigation (unfortunately pt. dependent), slow release devices, and systemic drugs which concentrate in the crevicular fluid at concentrations which are both bacteriostatic and higher than in the serum (TCN and minocycline).
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Rationale for use of antibiotics in periodontal disease: Ab are v. effective against the classical infectious dz. Most ab are bacteriostatic rather than bactericidal. All susceptible flora is suppressed and the host defense allows the preferential regrowth of normal flora. This may not hold in terms of perio dz; 1) Currently we don't know of a particular foreign bug or bugs which cause periodontitis, all potential pathogens seem to originate from the nl flora. 2) If a suspected pathogen belongs to the normal oral flora, permanent eradication by a short-term tx c ab will be difficult if not impossible to achieve because the indigenous pathogen will not easily be overgrown during re-establishment of the pocket microflora. 3) The host defense mechanism in the pocket seems to be of questionable quality.
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Bactericidal vs Bacteriostatic AB: There is little evidence to support the concept that Bcidal ab are more effective against bacterial infections in immunocompromised patients. Nevertheless, the bactericidals are generally considered the DOC in such cases. In pd, bcidal ab are preferred. TCN (bstatic) and metronidazole(MTN) (bcidal) have been tested in the treatment of pd. The effects of ab vs S/RP: As long as the etiologic agent(s) of pd has not been defined, application of ab to suppress the majority of the pocket flora may be justified. This non-selective approach is not unlike mechanical debridement. Ab tx alone is considered inferior to S/RP alone. The scaling will at least remove part of the subg flora whereas TCN will simply suppress the flora temporarily. MTN will kill bacteria in the pocket, anaerobes preferentially over the facultative anaerobes. Clinical studies support these ideas. TCN (systemic or slow-release) and MTN have been shown to result in less dramatic and less-long-lasting effects than mechanical debridement.
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Rationale for the use of ab as an adjunct to S/RP: It is impossible to sterilize a pocket by mechanical means. But this may remove sufficient numbers to retard regrowth in 2 ways: 1) A sig. reduction in numbers of pathogens may enable the host defense to defeat the remainders and hinder their regrowth; 2) the disturbed and reduced flora may loose some microbe dependent factors important for the growth of pathogens. A single S/RP can be successful in arresting the disease process for as long as 2 years (Badersten, 1984). It may begin to repopulate immediately however and we don't know exactly what the conditions are that allow repopulation and tissue destruction. Therefore the adjunctive use of ab c S/RP to enhance or prolong the effects of mechanical debridement in the avg periodontitis has questionable value.
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The effects of scaling and root planing with and without TCN: Long and short-term systemic TCN or short-term local TCN in combo c S/RP has not shown any additional benefit over S/RP alone.
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Metronidazole as an adjunct to scaling and root planing: May have some promise, but ineffective against Eikenella corrodens, Capnocytophaga and A. a. 2 studies are cited as showing benefit as an adjunct and 2 are cited as not.
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Adjunctive subg application of antimicrobial agents: Studies show no or little enhancement of S/RP c subg application of CHX, iodine, or the Keyes tech. And of course subg irrigation alone is inferior to S/RP alone.
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Ab in the treatment of juvenile periodontitis and recurrent periodontitis: Some studies claim additional benefit c adjunctive ab therapy in these diseases, however no studies have been performed with good controls and therefore definitive answers are lacking.
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Ab vs periodontal surgery as adjuncts to S/RP: Currently, successful treatment of pd appears to be achievable by scaling and root planing alone or with surgery to enable access to difficult to treat surfaces. Possible reasons for the failure of S/RP without surgery include 1) Inadequate debridement of difficult to reach surfaces. 2) the presence of bacteria in the adjacent epithelium and CT. S/RP c surg has been shown to be more effective in txng pd than S/RP alone.
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Conclusion:
The use of antibiotics in the treatment of periodontal diseases has failed with regard to the concept of suppressing the suspected periodontal pathogens. So far, antibiotics have been used as supplement to the nonspecific approach of S/RP and it can be doubted whether the antibiotic approach offers any benefit at all.

4. Slots, J.; Rams, T.E.: Antibiotics in Periodontal Therapy: Advantages and Disadvantages. J. Clin. Perio. 17:479-493, 1990.

5. Gordon, J.M.; Walker, C.B.: Current Status of Systemic Antibiotic Usage in Destructive Periodontal Disease. J. Periodontol. 64:760-771, 1993.

6. Walker, C.B.; Gordon, J.M.; Magnusson, I.; Clark, W.B.: A Role for Antibiotics in the Treatment of Refractory Periodontitis. J. Periodontol. 64:772-781, 1993.
7. Kornman, K.: Controlled-Release Local Delivery Antimicrobials in Periodontics: Prospects for the Future. J. Perioodontol. 64:782-791, 1993.
8. Williams, B.; Osterberg, S.; Jorgensen, J.: Subgingival Microflora of Periodontal Patients on Tetracycline Therapy. J. Clin. Perio. 6:210-221, 1979.
P to characterize the subgingival microflora isolated from periodontal patients using 1) 1g/d x14, 2)1g/d x7d plus 250mg/d for various time periods. MM n=13 no scaling or rp for 30 prior to the study. GI, Pocket depth, AAP classification sterile curette used for sample collection of subg plaque. Characterization of the isolates: Taxonomy: gram reaction, cell morphology, mobility, colony morphology, etc see table 2 Antibiotic sensitivity testing was done to test for the bact. susceptibility to TTC. R AAP: mostly Class 4 1) 1000mg/d x14d: cultivable microbial flora consisted mostly of Streptococcus and Actinomyces. see table 3 None of the gram + Actinomyces or Rothia could be classified as resistant except A odontolyticus. 2) The microbial flora in the group with 250mg/d after 1 week of 1g/d was very variable. Table 4. Fastidious or anaerobic Gram -negative rods were cultured rom all nine patients . This was in contrast to the low number of such organisms in group 1. All nine pts in this group also had resistant fac. streptococci. Serum levels for pts on 1g/d ttc are 2-4ug/ml Many of the organisms currently thought to be important to the pathogenesis of per. ds were retained by the 250mg/d group: Capnocytophaga, anaerobic vibrios and "corroders".

7. Hellden, L., M. Listgarten and J. Lindhe. The effect of tetracycline and/or scaling on human periodontal disease. J. Clin. Perio. 6:222, 1979.
P: To describe the effect on periodontal disease in young adults of TCN therapy alone or in combination with subgingival scaling MM: 12 pts.; severe dz, mean bone loss avg 52% via Schei tech.; age 27-42; at least 20 teeth left. 25 week placebo-controlled study. The following exam performed on day 0, 8w and 25w. GI, Pl I, Pd(not pressure sens.), attachment level (using splint border as reference). Pts. randomly assigned to control/test groups. Test patients were given 250 mg qid x 2w for two periods from day 0 to day 14 and from day 48 to day 64. All were given OHI. One half of the mouth in each patient was scaled initially and rescaled at weeks 15 and 22. therefore there were 4 test groups: Untreated control group; TOSO Scaling only; T0S1 TCN only; T1S0 TCN + Scaling; T1S1 R: Regardless of treatment method the oral hygiene and gingival conditions improved. (Hawthorne effect!?) No differences noted in Pl I between scaled and unscaled sides at 0 and 8 weeks, but more sig. plaque free surfaces noted on scaled sites at 25 weeks compared c unscaled sites. At both 8 and 25 weeks the scaled sites showed > # of GI=0 than unscaled sites. No diff. noted between TCN and NO TCN patients in the freq. of GI=0 sites. Sig. more reduction in probing depth at S vs UNS sites, but no sig diff between TCN and NO TCN pts. Slight gain in attachment in all treated sites, but none in the untreated sites. C: Intro of meticulous OH in patients with adv pd resulted in sig improvement in gingival health. In addition, the administration of TCN had only a minor effect on the parameters examined, even in quadrants subjected to S/RP. In the absence of scaling, the TCN had only a transient effect most marked at the 8w interval. The only beneficial effect with TCN was a significant improvement in attachment levels btwn and 25w. However the benefit was negligible in terms of the magnitude of the gain and in light of the fact that the levels of inflammation could have sig effects on the assessment of attachment levels.

9. Hellden, L.; Listgarten, M.; Lindhe, J.: The Effect of Tetracycline and/or Scaling on Human Periodontal Disease. J. Clin. Perio. 6:222-230, 1979.

10. Slots, J.; Mashimo, P.; Levine, M.; Genco, R.: Periodontal Therapy in Humans. I. Microbiological and Clinical Effects of a Single Course of Periodontal Scaling and Root Planing and of Adjunctive Tetracycline Therapy. J. Perio. 50:495-509, 1979.
P determine the rate of repopulation of the subgingiva microflora after treatment of pockets in patients with various forms of per.ds. MM n=6 clinical parameters:Pl index, GI, pocket depth, suppurative Index, Crev. fluid flow, alveolar bony changes on std. x-rays. Microbial parameters: sub ging microflora was taken with 3 paper points. The whole pocket microflora was analyzed. Phase contrast microscopy time course: clinical and microbial measurements were taken prior to day 0, day 0, Week,1,2,4,8,12,16,24, radiographs: prior to therapy, week 12 and week 24 Therapy: 2: sc,rp OHI and1.5gms TTC/d x14d at day 0 4: sc rp OHI only 2 or these 4 did not show any change in the microflora after sc and rp and were put on TTC at week 12 R: pre treatment: spirochetes and nonmotile rods 30% motile rods 25% cocci 15% gr- 45% anaerobic 45% The main finding in this study was that there were major differences in the composition of the pre and postreatment subgingival microflora. 3 repopulation patterns were observed over the 6 month period. 1) a rapid reduction and a slow repopulation for spirochetes and the total subgingival bacterial count and Capnocytophaga. 2)rapid increase followed by a slow return:Actinomyces naeslundii and Actinomyces viscosus and streptococci 3) Rapid reduction in proportions and a rebound return: Gram neg anaerobic including Bact. Veillonella parvula, Fuso nuc. There was a marked and long lasting changes in the subging. microflora after sc and rp. The total number of subgingival organisms after therapy decreases 10-100 fold. and the proportions of cultivable Grm- and ana. decreased 3-4x. Total cell count and the proportions of spirochetes and Capnocytophaga did not reach pretreatment levels even after 6 months. Other gram - species returned to pretreatment levels btwn 3 and 6 months. Microbial shifts paralleled clinical status: decreased pocket depth, GC fluid flow, GI and suppurative index and 9/33 interprox sites had and increase in bone ht. An orderly repopulation was observed suggesting a series of interrelated controlling mech. regulating the colonization. Major adjunctive effects of ttc were not seen. There was not any major prolongation of the repopulation time among pts treated with ttc. There as a reduction of 10 to 50% of he the pd of 5mm or more. Proposal: conventional therapy, monitoring and use of antimicrobial therapy in refractory cases.

11. Lindhe, J.; Liljenberg, B.; Adielsson, B.: Effect of Long-Term Tetracycline Therapy on Human Periodontal Disease. J. Clin. Perio. 10:590-601, 1983.
P: To study the effect of long-tern low dosage TCN therapy on adv. pd. MM: 14 subjects; 20 remaining teeth; > 6mm pd and >40% bone loss. Double blind, split-mouth design; 2 groups of seven patients; the test group received TCN 250mg qid x 2w and then 250mg qd x 48w. The control group received a similar regimen c placebos. 1000mg qd has been shown to give bacteriostatic concentrations in the GCF to most bacteria associated c periodontal dz (4-8ug/ml). All received OHI and 2 randomly chosen quadrants were S/RP while the remaining 2 were not. Baseline exam included PL I, GI, Pd, Al, and plaque sampling for darkfield analysis. Reexaminations were performed at 2, 10, 20, 30, and 50w. The groups were classed as follows: True Test- no S/RP, +TCN Pos. control- +S/RP, no TCN Neg. control- no S/RP, no TCN Combine Test- +S/RP, +TCN R: The OHI resulted in improved OH and gingival health in all pts. However at 30 and 50w, the distribution of Pl scores was similar in all groups, even though it was initially improved more dramatically in the S/RP group. Improvement in GI was most pronounced in the S/RP patients and could be detected earlier in the TCN patients. After 20w there was no difference in scores between the S/RP sites in the TCN and control groups. In the unscaled sites of the control group the freq. of GI=2 was between 11 and 27% from 30-50w while the unscaled areas in the TCN patients had no GI=2 or 3 during that time. Pd improved in all groups; Scaled=3.1mm TCN, 2.3mm control; Unscaled=1.9mm TCN, 0.9mm control. These were sig. reductions in all groups but the neg. control. Gain in attachment levels: Scaled=1.7mm TCN, 1.4mm control; Unscaled=0.7mm TCN, slight loss, control. Microbiologic analysis showed a sig. increase in coccoid forms in all three treatment groups and no changes in the untreated group. Similar findings were noted in the reduction of motile forms. C: Results demonstrated that in patients with adv. pd long-term TCN therapy in the absence of S/RP resulted in 1) the establishment of a subg microflora devoid of motile forms, 2) markedly reduced signs of gingivitis, 3) reduced pd and 4) slight gain of clinical attachment levels. The result of TCN in this group with excellent OHI was similar to those obtained by conventional scaling and root planing in the control group. The findings also indicated that in patients with good OHI the effect of subg scaling was somewhat improved and could be recognized earlier in the presence of adjunctive TCN therapy. Despite the fact that long-term TCN therapy appeared to be effective in the present trial there are reasons to express concern about the use of ab in the tx of adult periodontal disease. 1) conventional, non-surgical therapy results in the resolution of gingivitis and in the arrest of the progressive destruction of the attachment apparatus. 2) even adv, terminal cases of pd can be successfully treated without the use of ab. 3) TCN therapy has no prolonged effect on periodontal dz and a disease-associated microflora returns soon after the termination of ab therapy. 4) Long-term, low-dosage TCN may allow overgrowth of resistant species and may select for TCN resistant strains.

12. Golub, L.M.; McNamara, T.F.; D'Angelo, G.D.; Greenwald, R.A.; Ramamurthy, N.S.: A Non-Antibacterial Chemically Modified Tetracycline Inhibits Mamalian Collagenase Activity. J. Dent. Res. 66:1310-1314, 1987.

13. Ingman, T.; Sorsa, T.; Suomalainen, K.; Halinen, S.; Lindy, O.; Lauhio, A.; Saari, H.; Konttinen, Y.; Golub, L.: Tetracycline Inhibition and the Cellular Source of Collagenase in Gingival Crevicular Fluid Different Periodontal Diseases. A Review Article. J. Periodontol. 64:82-88, 1993.

14. Novak, M.J.; Stamatelakys, C.; Adair, S.: Resolution of Early Lesions of Juvenile Periodontitis with Tetracycline Therapy Alone: Long Term Observations of 4 Cases. J. Perioodontol. 62:628-633, 1991.

15. Kulkarni, G.V.; Lee, W.; Aitken, S.; Birek, P.; McCulloch, C.: A Randomized, Placebo-Controlled Trial of Doxycycline: Effect on the Microflora of Recurrent Periodontitis Lesions in High Risk Patients. J. Periodontol. 62:197-202, 1991.

16. Matisko, M.W.; Bissada, N.F.: Short-Term Sequential Administration of Amoxicillin/Clavulanate Potassium and Doxycycline in the Treatment of Recurrent/Progressive Periodontitis. J. Periodontol. 64:553-558, 1993.

17. Heijl, L.; Dahlen, G.; Sundin, Y.; Wenander, A.; Goodson, J.M.: A 4-Quadrant Comparative Study of periodontal Treatment Using Tetracycline-Containing Drug Delivery Fibers and Scaling. J. Clin. Perio. 18:111-116, 1991.

18. Goodson, J.M., et. al.: Multi-center Evaluation of Tetracycline Fiber Therapy. I. Experimental Design, Methods and Baseline Data. J. Perio. Res. 26:361-370, 1991.

19. Goodson, J.M., et. al.: Multi-center Evaluation of Tetracycline Fiber Therapy. II. Clinical Response. J. Perio. Res. 26:371-379, 1991.

20. Goodson, J.M., et. al.: Multi-center Evaluation of Tetracycline Fiber Therapy. III. Microbiological Response. J. Perio. Res. 26:440-451, 1991.

21. Morrison, S.; Cobb, C.; Kazakos, G.; Killoy, W.: Root Surface Characteristics Associated with Subgingival Placement of Monolithic Tetracycline-Impregnated Fibers. J. Periodontol. 63:137-143, 1992.

22. Loesche, W.; Syed, S.; Morrison, E.; Kerry, G.; Higgins, T.; Stoll, J.: Metronidazole in Periodontitis. Part I. Clinical and Bacteriological Results after 15-30 Weeks. J. Periodontol. 55:325-335, 1984.
This study reports on the short term results of Metronidazole (Met) treatment plus mechanical debridement in patients with advanced periodontal disease are presented and a double-blind clinical study in which met. plus debridement is compared to placebo plus debridement is described M&M Patients with clinical evidence of bone loss and anaerobic periodontal infection. 40 patients were assigned to two groups depending on severity of disease. Patient with 20, or more >7mm pockets were placed in one group and patients with 10 or less >7mm pockets were placed in the double blind study group. The double blind study group received either Met or placebo along with Sc/PR. The severe group received Met with Sc/PR. Met 250mg tid for 7 days Subgingival plaque was taken from one site in each quad from each patient. These were subject to both microscopic and cultural data. Clinically pocket depth and loss of attachment were evaluated. Results A few patients notice a metallic taste. Not all patients returned for the clinical evaluation. In the severe group, the number of >7mm pockets decreased from 22.8 to 4 and attachment from 25.3 to 14.6 after 10 to 20 weeks. In the group with initial 4-6mm in depth and attachment loss both the Met and placebo groups caused about 1mm decrease in pocket depth and 0.3mm gain in attachment. In the deeper site, placebo reduced 1.6mm in PD and 0.3mm gain in attachment in the deeper site, Met reduced 3.2mm and 1.4mm gain in attachment All treatment reduced the levels of bacteria in the plaque samples. The short term usage of systemic Met can optimize the clinical reduction of pockets and increase attachment gain in periodontitis patients who receive concurrent mechanical debridement of their root surfaces. In the extensive clinical involvement Met significantly reducted the number of sites showing pocket depth and attachment loss >7mm. Met was associated with a significant and sustained reduction of certain anaerobic organisms such as B. gingivalis and the large spirochetes.

23. Lekovic, V.; Kenney, E.B.; Carranza, F.A.Jr.; Endres, B.: The Effect of Metronidazole on Human Periodontal Disease. J. Periodontol. 54:476-480, 1983.

24. van Winkelhoff, A.; Tijhof, C.; de Graaff, J.: Microbiological and Clinical Results of Metronidazole plus Amoxicillin Therapy in Actinobacillus actinomycetemcomitans-Associated Periodontitis. J. Periodontol. 63:52-57, 1992.

25. Loesche, W.J.; Giordano, J.R.; Hujoel, P.; Schwarz, P.; Smith, B.A.: Metronidazole in Periodontitis: Reduced Need for Surgery. J. Clin. Periodontol. 19:103-112, 1992.

26. Magnusson, I.; Clark, W.B.; Low, S.B.; Maruniak, J.; Marks, R.G.; Walker, C.B.: Effect of Non-surgical Periodontal Therapy Combined with Adjunctive Antibiotics in Subjects with "Refractory" Periodontal Disease. I. Clinical Results. J. Clin. Perio. 16:647-653, 1989.

27. Walker, C.; Gordon, J.: The Effect of Clindamycin on the Microbiota Associated with Refractory Periodontitis. J. Periodontol. 61:692-698, 1990.

28. Stahl, S.: The Influence of Antibiotics on the Healing of Gingival Wounds in Rats. I. Alveolar Bone and Soft Tissue. J. Periodontol. 33:261-265, 1962.
P to observe the antibiotic effects on the healing of an acute gingival injury in adult rats MM 131 rats had the mesial gingiva of the maxillary left first molar removed. Immediately after the injury: 41/131 rats received 25% TTC for 30d 34/131 5d 56/131 rats received 100,000 units of Bicillin (PCN) for 5d 36/131 controls with wounds 10/131 control without wounds. sacrificed at some time during a 30d period after the wound Histological sections observed HISTO: initial inflammation and epithelialization was similar for all animals. Crestal bone repair occurred the fastest in the 5 and 30 day TTC rats. The PCN rats repaired faster than the non antibiotic rats. As the healing progressed, the ultimate extent of the crestal repair was the same in all groups. Epithelialization was the same for all groups and was not influenced by Antibiotics.

29. Ariaudo, A.: The Efficacy of Antibiotics in Periodontal Surgery: A Controlled Study with Lincomycin and Placebo in 68 Patients. J. Periodontol. 40:150-154, 1969. 68 patients requiring periodontal surgery were used to test the effectiveness of using Lincomycin in periodontal surgery. 66 patients underwent full mouth surgery with 2 patients only receiving half mouth. 33 patients were given placebo and 35 were given lincomycin. This study was conducted doubleblind according to a standard randomized list. Lincomycin or a placebo was administered qid for 6 days - 2 days prior to surgery. The following parameters were measured daily: temperature, malaise, edema, necrosis and pain. Mouth odor was incorporated as a measurement of effectiveness of the antibiotic. No perio pak and no controls were utilized. Due to the question of accuracy when evaluating necrosis, 10 more patients were incorporated into the study. The results showed that with lincomycin, there was a decrease in mouth odor (necrosis) and in postoperative symptoms at day 4. It was concluded that lincomycin is an effective aid in periodontal surgery. There was no matched, standardized groups with very subjective study criteria. A crossover study with controls would be more useful.

30. Pendrill, K.; Reddy, J.: The Use of Prophylactic Penicillin in Periodontal Surgery. J. Periodontol. 51:44-48, 1980.
P The purpose of this retarded study was to determine if PCN given after the placement of Coe-Pak would improve the the post op course. MM double blind placebo design 19 subjects with comparable bilateral per. ds. parameters: plaque index, gingival index, crevicular fluid, pain(questionnaire:none, moderate or severe), swelling and infection(necrosis, swelling, pus, lymphadenopathy) procedure: full thickness flaps, degranulation, osteoplasty or ostectomy prn, sutures, and pack, then the patient was given either the placebo or phenoxymethyl pcn 1q6h x5d, no mg stated. one month btwn surgeries R no differences in: infection, swelling GI, PlI, and pain by questionnaire. There was a difference in the amount of analgesics took after the surgery. The experimental group took less analgesics. D this study does not support the use of prophylactic antibiotics in preventing post-op infections. maybe they would have gotten results if they had established blood levels prior to incisions instead of giving the ab's after the surgery. How many mg's did they use? I couldn't find the dosage. Where are we going to eat lunch today?

31. Pack, P.; Haber, J.: The Incidence of Clinical Infection After Periodontal Surgery: A Retrospective Study. J. Periodontol. 54:441-443, 1983.

32. Dajani, A.S., et. al.: Prevention of Bacterial Endocarditis: Recommendations by the American Heart Association. JAMA, 264:2919-2922, 1990.
Because there are no controlled clinical trials, the choice of antibiotic regimens for prevention of endocarditis in humans must be based on indirect information. Antibiotic regimens used to prevent recurrence of acute rheumatic fever are inadequate for the prevention of bacterial endocarditis. Appropriate additional antibiotics should be prescribed at times of procedures associated with risk of development of endocarditis. Since endocarditis may occur despite antibiotic prophylaxis, we should maintain a high index of suspicion regarding any unusual clinical events following dental or surgical procedure. In patients receiving warfarin or heparin IM antibiotics should not be used. IV or oral regimens should be substituted. Patients at risk should maintain the best possible oral health to reduce potential sources of bacterial seeding, because poor dental hygiene or periodontal or periapical infections may induce bacteremia even in the absence of dental procedures. Prophylaxis is recommended with all dental procedures likely to cause bleeding. Shedding deciduous teeth and simple adjustment on orthodontic appliances are not indications. Alpha-hemolytic streptococci are the most common implicated in endocarditis following dental procedures. Upper resp.. tract procedures may also cause bacteremia with organisms having similar antibiotic susceptibilities to those producing bacteremia following dental procedures. Tables 1 and 2 given cardiac conditions and procedures for which antibiotic prophylaxis is indicated. Table 3 contains suggested regimens or prophylaxis for dental/respiratory tract procedures. -Standard regimen -For patients with prosthetic valves and others with highest risk of endocarditis -Standard regimen for patients allergic to Pen.- for those who cannot tolerate either pen. or erytho. an oral cephalsporin 1.0 gm 1 hr before, plus 500 mg 6 hrs later may be useful. TTC cannot be recommended. -Regimen for high risk patients allergic to pen. GU and GI tract surgery and instrumentation Patients at risk for endocarditis should receive prophylaxis Table 4. Standard - Ampillicin 2.0 gm IM or IV plus gentamicin 1.5 mg/kg IM or IV, 1/2-1 hr before procedure. One follow-up dose may be given eight hours later. Special- Amoxicillin 3.0 gm orally one hr before procedure and 1.5 gm 6 hrs later. Enterococci are most frequently responsible for endocarditis following GU and GI tract surgery or instrumentation. Cardiac Surgery- patients who undergo open heart surgery are at risk. Endocarditis with open heart surgery is most often due to Strephylococcus aureus, coagulase negative staphylococci or diphtheroids. No single antibiotic regimens is effective against all these organisms Prolong use of broad-spectrum antibiotics may predispose to superinfection with unusual or resistant microorganisms. Careful preoperative dental evaluation is recommended so that required dental treatment can be completed at least several weeks prior to cardiac surgery whenever possible. After cardiac surgery patients an isolated secundum atrial septal defect repaired w/o a prosthetic patch and those who have had ligation and division of a patent ductus arteriosus are not at increased risk of development endocarditis following a 6 month healing period after surgery. Other indications -In susceptible patients, for surgerical procedures on any infected or contaminated tissues, including incision and drainage of abscesses. -a previous episode of bacterial endocarditis, even in the absence of clinically detectable heart disease. -patients with indwelling transvenous cardiac pacemakers appear to present a low risk of endocarditis, also renal dialysis patients with arteriovenous shunt appliances. -Patients with ventriculo-atrial shunts for hydrocephaus -not required in cardiac catheterization and angiography b/c with adequate aseptic techniques.

33. Pallasch, T.J.; Slots, J.: Antibiotic Prophylaxis for Medical Risk Patients. J. Periodontol. 62:227-231, 1991.

34. Durack, D.; Kaplan, E.; Bisno, A.: Apparent Failure of Endocarditis Prophylaxis: Analysis of 52 Cases Submitted to a National Registry. JAMA 250:2318-2322, 1983.
P too attempt to answer the following questions: Do failure occur when antibiotics are given to prevent endocarditis: if so what are the etiologic organisms and are they susceptible or resistant t the antibiotics that were employed? Did these regimens confirm to our current concepts of optimal prophylaxis? What are he underlying cardiac lesions in these cases. MM AHA committee on Rheumatic Fever and Bacterial Endocarditis established a national registry to record examples of apparent failure of endocarditis prevention. Case reports were compiled by phone interview with the MD that was reporting it. The case report was only included if adequate data could be obtained. (see top paragraph of page 2319) R sex and age: 65%male, 55years med. age 35% female 23 years. Underlying heart disease: 33% mitral valve prolapse, 29% congenital 19% prosthetic valves Procedure that caused the endocarditis; 92% dental (simple cleaning and scaling to multiple extractions). Incubation Period: first recorded sx: 2 weeks after procedure in half of the cases and in 5 weeks with 4/5 of the cases. Choice of Antibiotic regimen: 79% used PCN V (most pop. reg was for 3 days) see table 4 15% Ery. only 12% used regimens recommended by the AHA Failures on the Regimens recommended by the AHA only 12 % used these regimens viridans streptococci Microbial Etiology strep accounted for 75% of the cases staphylococcus aureus 14% Prognosis 90% cured (possibly skewed since a good % of the pop. had only prolapse and other wise were not compromised) -seven required valve replacements -five died

35. Little, J.: The Need for Antibiotic Coverage for Dental Treatment of Patients with Joint Replacements. 0ral Surg, Oral Med, Oral Pathol. 55:20, 1983.