Systemic moxifloxacin vs amoxicillin/metronidazole adjunct to non-surgical treatment in generalized aggressive periodontitis

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1 Journal section: Oral Meicine an Pathology Publication Types: Research oi: /meoral Systemic moxifloxacin vs amoxicillin/metroniazole ajunct to non-surgical treatment in generalize aggressive perioontitis Esra Guzelemir-Akcakanat 1, Cem-Abulkair Gurgan 2 1 Department of Perioontology, Faculty of Dentistry, Kocaeli University, Kocaeli, Turkey 2 Department of Perioontology, Faculty of Dentistry, Erciyes University, Kayseri, Turkey Corresponence: Kocaeli University Dis Hekimligi Fakultesi Perioontoloji AD. Yuvacik Yerleskesi Yuvacık-Başiskele-Kocaeli Turkey, esrag@yahoo.com Receive: 16/12/2014 Accepte: 12/03/2015 Guzelemir-Akcakanat E, Gurgan CA. Systemic moxifloxacin vs amoxicillin/metroniazole ajunct to non-surgical treatment in generalize aggressive perioontitis. Me Oral Patol Oral Cir Bucal Jul 1;20 (4):e Article Number: Meicina Oral S. L. C.I.F. B pissn eissn: meicina@meicinaoral.com Inexe in: Science Citation Inex Expane Journal Citation Reports Inex Meicus, MEDLINE, PubMe Scopus, Embase an Emcare Inice Méico Español Abstract Backgroun: The objective of this ranomize clinical stuy was to evaluate the effect of systemic aministration of moxifloxacin compare to amoxicillin an metroniazole, combine with non-surgical treatment in patients with generalize aggressive perioontitis (GAgP) in a 6- follow-up. Material an Methos: A total of 39 systemically healthy patients with GAgP were evaluate in this ranomize clinical trial. Perioontal parameters were recore at the baseline uring the 1 st, 3 r an 6 th. Patients receive either 400 mg of moxifloxacin per os once aily or 500 mg of metroniazole an 500 mg amoxicillin per os three times aily for 7 ays consecutively. Results: No significant ifferences groups were foun in any parameters at the baseline. Both groups le to a statistically significant ecrease in all clinical perioontal parameters compare to the baseline (PI, p<0.001 an GI, PD, BOP, CAL, p<0.01). There were no ifferences the 1 st an 3 r s or the 3 r an 6 th s for clinical parameters in the groups. Also, no intergroup ifference was observe in any parameters at any time, except the gingival inex at 6 th s. Conclusions: Systemic aministration of moxifloxacin as an ajunct to non-surgical treatment significantly improves clinical outcomes an provies comparable clinical improvement with less averse events to that of combination of amoxicillin an metroniazole in the treatment of GAgP. Key wors: Aggressive perioontitis, amoxicillin, metroniazole, moxifloxacin, nonsurgical perioontal ebriement. e441

2 Introuction Aggressive perioontitis (AgP) is an inflammatory perioontal isease, which is complex, multifactorial, an estructive. AgP has been treate like other forms of perioontitis. The establishe treatment of perioontitis involves cause-relate therapy, which inclues: maintenance of oral hygiene, scaling an root planing (SRP), an surgeries of affecte sites. Contrary to gingivitis an chronic perioontitis, mechanical non-surgical treatment oes not always provie expecte results in the treatment of AgP. In these cases, antibiotics may be use as an ajunct to treatment for eliminating or reucing the number of specific microorganisms an improving clinical parameters when compare with SRP alone (1-4). The American Acaemy of Perioontology (AAP) an the European Feeration of Perioontology (EFP) were reporte that patients with GAgP may have benefit from the ajunctive systemic aministration of antibiotics (1,5,6). Amoxicillin is a moerate spectrum; bacteriolytic β-lactam antibiotic, an metroniazole is active against anaerobic bacteria. SRP combination with metroniazole an amoxicillin therapy was foun to be more effective in suppressing P.g. an eraication of A.a. an preventing re-colonization of A.a. because of the synergistic effect of this combination an their wie spectrum of activity. It was foun to be superior to azithromycin, oxycycline, an metroniazole in the treatment of GAgP. Moxiflocaxin is a fourth generation fluoroquinolone antibiotic an exhibits goo tissue penetration an high oral bioavailability. It has improve activity against Gr (-), aerobic an anaerobes an has goo activity against putative perioontal pathogens locate within biofilm or intracellulary (7). To the best of our knowlege, there is no stuy that evaluates the effect of moxifloxacin ajunct to SRP in the treatment of GAgP. The aim of this stuy was to evaluate the impact of ajunctive systemic moxifloxacin; compare to the use of ajunctive systemic amoxicillin an metroniazole uring full-mouth SRP base on the success of the treatment of patients with GAgP along with a 6- follow-up. Material an Methos This stuy was a single-center, ranomize, parallelesign clinical trial with 6 follow-up. The stuy protocol was approve by the Ethics Committee of the Meical Faculty of Kocaeli University (KOU KAEK 5/9). This clinical trial is registere; the ientifier number is NCT ( The stuy protocol explaine to the patients. From patients who willing to participate to the stuy, written informe consent was obtaine an inclue the stuy. The perioontal iagnosis of subjects with GAgP was performe accoring to the 1999 International Worl Workshop for a Classification of Perioontal Diseases an Conitions. Patients were inclue if they were 18 an 35 years of age an otherwise healthy. Subjects were exclue if they ha any known systemic iseases or conitions that can/coul influence the perioontal status, allergies to quinolones, penicillin or metroniazole, a history of antibiotic therapy, or perioontal treatment within the preceing six s. - Perioontal Examination The full-mouth clinical perioontal measurements were recore at 6 sites per tooth, incluing plaque inex (PI), gingival inex (GI), probing epth (PD), bleeing on probing (BOP) an clinical attachment loss (CAL). - Nonsurgical treatment Prior to treatment, all subjects ha gone through motivation sessions for oral hygiene. Following perioontal measurements, full-mouth supragingival scaling using an ultrasonic scaler an polishing was performe. A toothbrush, toothpaste an an interproximal toothbrush were provie to all subjects. One week later, the patients were examine for plaque accumulation an oral hygiene. The patients who cannot maintain proper oral hygiene were exclue from the stuy. Only 39 patients fulfille the qualification criteria for enrollment for the present stuy. Subjects were ranomly assigne to receive one of the two treatment groups. The moxifloxacin (MXF) group receive SRP an ajunctive systemic antibiotic, 400 mg MXF (1x1, 7 ays). The amoxicillin an metroniazole (AMX+MET) group receive a combination of 500 mg of amoxicillin an 500 mg metroniazole (3x1, 7 ays). The subjects were instructe to take the first ose of the antibiotics in the morning of the first session. SRP were performe uring 2 consecutive ays in 24-h uner the local anesthesia. On each ay, SRP were performe in 2 quarants using ultrasonic scalers an manual instruments. The enpoint of SRP was a tactile, smooth root surface. Patients use a 0.2% chlorhexiine igluconate rinse (2x1, 30 ays) an brushe their teeth by toothbrushes an interproximal toothbrushes twice a ay. Patients aske to report any averse events an sie effects of the antimicrobial agents. Subjects were monitore one week after the secon SRP session. At this session, antibiotic intake an averse events were questione; oral hygiene was controlle. Subjects were screene at 1, 3 an 6 s after completion of SRP. During these sessions, perioontal inices an any meical history change; especially whether antibiotic therapy ha been prescribe for any reason was recore. - Statistical Analysis The reliability of continuous variables was expresse as the SD of the ifferences ivie by 2. Accoring to the reliability analysis for PD an CAL, the measurement e442

3 errors were 0.13 an 0.11, respectively. Cohen s K was employe to escribe the reliability of iscrete PI an GI values. Base on the uplicate measurements, the kappa values of PI an GI were 0.76±0.04 an 0.86±0.05, respectively. Depening on the normality in the istribution of the clinical parameters, Mann-Whitney-U an inepenent T-test were use for the ifferences the groups. The changes in clinical parameters among ifferent evaluation perios for each group were analyze using Frieman an the repeate measure ANOVA test, where applicable. Aitionally, when the p value from the Frieman test was statistically significant, multiple comparison tests were use to ascertain which evaluation time point iffere from the others. Results Figure 1 shows flow iagram of the present stuy. A total of 39 subjects were enrolle into the present stuy; baseline emographic variables an clinical perioontal parameters are shown in table 1. A total of subjects applie to ental school Enrollment 120 subjects screene as GAgP 60 GAgP patients examine for eligibility Allocation Ranomize (n= 39) Exclue (n= 21) X Not meeting inclusion criteria, ecline to participate an other reasons Allocate to intervention (n= 19) Receive SRP mg Moxiflocaxin (7 ays, 1X1) Allocate to intervention (n= 20) Receive SRP mg Amoxicillin (7 ays, 3X1) mg Metroniazole (7ays, 3X1) 1 st Month Follow-Up Lost to follow-up (n=2) Antibiotic intake (n= 1) Di not return to follow-up (n=1) Lost to follow-up (n=1) Move to another city (n= 1) No lost to follow-up 3 r Month Follow-Up No lost to follow-up Lost to follow-up (n=2) Di not return to follow-up (n=2) 6 th Month Follow-Up No lost to follow-up Analyse (n=15) Analysis Analyse (n=19) Fig. 1. Flow iagram of the stuy accoring to CONSORT e443

4 While one subject from AMX+MET group was withrawn at 1st visit, four subjects from MXF group were withrawn at 1 st an 6 th visits. Fifteen subjects in the MXF group (7 males an 9 females; mean age, 30.32±3.81 years; range, yrs) an 19 subjects in the AMX+MET group (9 males an 10 females; mean age, 30.95±3.66 yrs; range, years) complete the stuy (Table 1). There were no significant ifferences the groups at any point relate to age, gener, an smoking status. (p>0.05) (Table 1). Each subject of the MXF group receive 7 tablets of MXF 400 mg an each subject of the AMX+MET group receive a total of 21 tablets of AMX 500 mg an MET 500 mg. in the MXF group an in the 3 r in the AMX+MET group compare to the baseline (p<0.01). However, these ifferences were not significant compare to other follow-up visits. No ifference was foun groups at any point in 6 s. The mean PD reuction an the mean clinical attachment gain at the 6 th were 1.17±0.16 mm an 0.64±0.12 mm, respectively, in MXF group an 1.42±0.41 an 0.70±0.20 mm, respectively, in AMX+MET group. No significant ifferences were observe groups. The changes as percentage in PD an CAL are also evaluate uner 3 categories, as <4 mm (shallow), 4-6 mm (moerate) an >6 mm (severe) (8). Percentage of PD was increase to 27.56% in pockets initially <4 Table 1. Demographic an clinical characteristics of the GAgP patients. Parameters MXF AMX + MET (N=19) (N=20) p-value Age (mean years ± SD) ± ± 3.90 (min-max) (24 35) (25 35) NS Female / Male (n) 9/10 10/10 NS Smokers (n) 5 (26%) 6 (30%) NS Plaque Inex * 2.39 ± ± 0.42 NS Gingival Inex * 1.41 ± ± 0.29 NS Probing Depth * (mm) 4.19 ± ± 1.08 NS Bleeing on Probing * (%) 66 ± ± 0.17 NS Clinical Attachment Loss * (mm) 4.94 ± ±1.14 NS Demographic features of AgP MXF AMX + MET patients completing the stuy (n=15) (n=19) p-value Age * (mean years ± SD) ± ± 3.66 NS (min-max) (24-35) (25-35) Female / Male (n) 9/7 10/9 NS Smokers (n, %) 4, % , % 42.1 NS * Mean ± SD, NS= groups is not statistically significant (p-value>0.05). While none of the test subjects reporte any averse event associate with MXF, two subjects reporte a stomachache an one subject reporte gastrointestinal problems relate to AMX+MET intake. Both groups emonstrate statistically a significant ecrease in all clinical perioontal parameters at the en of the 1 st, 3 r an 6 th s compare to the baseline (PI; p<0.001 an GI, PD, BOP, CAL, p<0.01, Tables 2 an 3). There were no significant ifferences the 1 st an 3 r, an 3 r an 6 th in the groups whereas none of the perioontal parameters showe intergroup ifferences in any time points (p>0.01), except GI at 6 th s (p<0.05) (Tables 2 an 3) As shown in table 3, both groups emonstrate statistically a significant ecrease in PD an CAL at the 1 st, 3 r an 6 th compare to the baseline (p<0.01). While the greatest reuction in the mean PD was seen at the 3 r, compare to the baseline in both groups ( p<0.01), but this ifference was not statistically significant compare to the 1 st an the 6 th. The greatest reuction in the mean CAL was seen uring the 1 st mm in MXF group an 33.61% in AMX+MET group (Table 4), an no ifference was seen groups. Percentage of PD was ecrease by 14.99% in pockets initially 4-6 mm, in pockets initially >6 mm in MXF group, an 14.75% an 17.80% % in AMX+MET group, respectively (Table 4) an no ifferences were seen groups. Percentage of CAL was increase by 46.70% in pockets initially <4 mm in MXF group an by 42.10% in AMX+MET group (Table 5), an there was no significant ifference the groups. Percentage of CAL was ecrease by 26.70% in CAL initially >6 mm, 20.00% in CAL initially 4-6 mm in MXF group, an 26.30% an 15.8% in AMX+MET group, respectively. No ifferences were observe the groups; however, there was a significant ifference the 1 st an the 3 r in CAL 4-6 mm category in MXF group (p<0.05). There were no ifferences groups in any categories at any time. e444

5 Table 2. Meian (25th-75th percentiles) values for plaque inex (PI), gingival inex (GI) an bleeing on probing (BOP) of MXF an AMX+MET groups for each recalls. PI GI BOP MXF 2.39 ( ) 0.07 (0-0.11) 0.22 ( ) 0.22 ( ) 1.38 ( ) 0.14 (0-0.19) 0.14 (0-0.19) 0.35 (0-0.67) 0.65 ( ) 0.11 ( ) 0.24 ( ) 0.27 ( ) AMX + MET 2.53 ( ) a 0.07 (0-0.21) b 0.27 (0-0.41) c 0.18 ( ) 1.27 (1-1.54) a (0-0.14) b 0.03 (0-0.14) c 0.14 * ( ) 0.72 ( ) a 0.14 ( ) b 0.16 ( ) c 0.14 ( ) a: Significant ifference baseline an (p<0.01) for MXF group b: Significant ifference baseline an (p<0.01) ) for MXF group c: Significant ifference baseline an (p<0.01) ) for MXF group *: Significant ifference groups for GI at (p<0.05) : Significant ifference baseline an (p<0.01) for AMX + MET group e: Significant ifference baseline an (p<0.01) for AMX + MET group f: Significant ifference baseline an (p<0.01) for AMX + MET group : No significant ifference 1 st an 3 r s an 3 r an 6 th s in an AMX + MET an MXF groups. Table 3. Mean ± stanar eviation (minimum-maximum) values for probing epth (PD) an clinical attachment loss (CAL) of each recall. PD CAL MXF 4.18 ±0.62 ( ) 2.91±0.38 ( ) a 2.79 ±0.33 ( ) b 3.01 ±0.46 ( ±0.81 ( ) 4.14±0.87 ( ) 3.98±0.82 ( ) 4.3±0.93 ( ) a b c c e445 AMX + MET 4,57 ± 1.08 ( ) 3.12 ±0.68 ( ) 3.11±0.6 ( ) 3.15±0.67 ( ) 5.03±1.14 ( ) 4.37±0.87 ( ) 4.41±0.93 ( ) 4.33±0.94 ( ) a: Significant ifference baseline an (p<0.01) for MXF group b: Significant ifference baseline an (p<0.01) ) for MXF group c: Significant ifference baseline an (p<0.01) ) for MXF group : Significant ifference baseline an (p<0.01) for AMX + MET group e: Significant ifference baseline an (p<0.01) for AMX + MET group f: Significant ifference baseline an (p<0.01) for AMX + MET group : No significant ifference 1 st an 3 r s an 3 r an 6 th s in an AMX + MET an MXF groups.

6 Table 4. Alterations of probing epth (PD) (a) an clinical attachment loss (CAL) (b) categories as percentage among recall perios for the groups. (a) Probing epth (PD) categories (%). PD <4 mm (Shallow) PD 4-6 mm (Moerate) PD > 6 mm (Severe) MXF AMX + MET MXF AMX + MET MXF AMX + MET 1 st -1 st 3 r -3 r 6 th -6 th ** ** *** ** ** ** * * * * * * * * * * * * * : Significant ifference baseline an 1 st m, 3 r m an 6 th m (p< 0.05) ** : Significant ifference baseline an 1 st m, 3 r m an 6 th m (p< 0.01) *** : Significant ifference baseline an 1 st m, 3 r m an 6 th m (p< 0.001) Table 5. Alterations of probing epth (PD) (a) an clinical attachment loss (CAL) (b) categories as percentage among recall perios for the groups. (b) Clinical attachment loss (CAL) categories (%). CAL <4 mm CAL 4-6 mm CAL > 6 mm 1 st -1 st 3 r - 3 r 6 th -6 th MXF *** *** *** AMX + MET ** ** ** MXF a 13.40* * * AMX + MET * MXF ** * ** AMX + MET ** ** ** *: Significant ifference baseline an 1 st m, 3 r m an 6 th m (p< 0.05) **: Significant ifference baseline an 1 st m, 3 r m an 6 th m (p< 0.01) ***: Significant ifference baseline an 1 st m, 3 r m an 6 th m (p< 0.001) a: Significant ifference 1 st an 3 r s (p< 0.05) Discussion To our knowlege, this stuy was the first clinical stuy, which evaluates the effects of systemic moxifloxacin compare to the ajunctive systemic amoxicillin an metroniazole as an ajunct to nonsurgical treatment in the treatment of patients with GAgP. On the basis of the present finings, it can be conclue that ajunctive moxifloxacin provies comparable clinical improvement to that of the combination of amoxicillin an metroniazole in the treatment of GAgP. All perioontal clinical parameters were ramatically ecrease in both groups at the 1 st compare to the baseline an all patients maintaine goo hygiene an post-treatment follow-ups. In the present stuy, although no effort was mae to control the smoking; smokers were equally istribute groups an the results i not change (ata not shown). Management of AgP is always challenging for clinicians since every case is unique an there are no establishe treatment guielines or protocols. In the treatment of AgP, a number of antimicrobial regimens have been investigate, which aim to potentiating the effects of SRP. It was shown that nonsurgical treatment together with systemic use of antibiotics in AgP yiels better clinical results an less surgery nees (9-11) when comparing nonsurgical treatment alone (1,2,12). e446

7 In the present stuy, there were no ifferences in, an the groups at any time. Then, we categorize the parameters as slight, moerate, an severe (Tables 4 an 5). There was also no ifference the groups. However, when each patient was evaluate as a separate entity, it was foun that the alterations in the frequencies of CAL categories were significantly ifferent at all times in both groups. The mean for the full-mouth PD reuction an the clinical attachment gain were better (13) or comparable (4,8,10-12) to those reporte in patients with GAgP at the 6 th. However, it is not convenient to make irect comparisons the stuies ue to iscrepancies among the stuy methoologies. In the treatment of AgP, ifferent antibiotic regimens, length of antibiotic therapy, timing of the aministration, ifferent osages, evaluation parameters an clinical outcome assessments have been stuie, however there is no consensus or efinite conclusion, yet (2,9). As state by Mombelli et al. (9); Useful antibiotic regimes for istinct clinical or microbiological conitions coul not be clearly ientifie base on available evience, The optimal timing for antibiotic aministration is still controversial, hence, There are no evience base guielines for the use of systemically aministere antibiotics (14). Different amoxicillin an metroniazole osages use by the researchers in the stuies. In the present stuy, 500 mg of both amoxicillin an metroniazole, three times a ay were prescribe for each person to reach a minimum effective concentration of antibiotics in gingival crevicular flui an bloo. The timing of the antibiotic regime is still unclear, however, base on stuies an reviews, Consensus Report of the Sixth European Workshop on Perioontology conclue that antibiotic intake shoul start on the ay of non-surgical treatment (15). Duration of the antibiotic regime also changes the stuies. Nevertheless, to ate, there is no clear statement about the uration of the antibiotic use. It is conclue that the SRP shoul be carrie out in the shortest time possible, preferably less than 7 ays in AgP (15,16). Hence, in the present stuy, antibiotic aministration was starte after the initial perioontal treatment; in the morning of the same ay of SRP, an the treatment was complete in 24 hours, using 7-ay systemic antibiotic regimes for both groups. Moxifloxacin is a fourth-generation fluoroquinolone with a broa spectrum of activity against microorganisms an pathogens with resistance to penicillin, macrolies, an tetracyclines. It contains a C-8 methoxy substitute that increases bactericial activity an there is a marke the time-kill kinetics an post-antibiotic effect (17). Moxifloxacin is effective an generally very well tolerate by patients an the reporte sie effects are very low. It is expecte that the patient s compliance might be enhance since prescribing a single-ose per ay is possible, ue to its pharmacokinetics. Efficacy of moxifloxacin in ental research is mostly evaluate in the treatment of oontogenic abscesses or infiltrates an promising in vitro activity against oontogenic pathogens was reveale over amoxicillin-clavulanic aci, clinamycine, oxycycline an penicillin. Moxifloxacin has a favorable bacterial activity against putative perioontal pathogens incluing P.g., A.a. an T. forsythia (7,18). In an in vitro stuy, the activity of moxifloxacin was compare with ofloxacin an oxycycline against single-species biofilms of two P.g. an two A.a. strains an a multispecies biofilm consisting of 12 species an a topical formulation of moxifloxacin as an ajunct to mechanical treatment is suggeste (19). The goo penetration of moxifloxacin into soft an har tissues in Wistar rats was also shown (20). Moxifloxacin was foun to be comparable to that of amoxicillinclavulanate however superior to those of clinamisin, metroniazole, oxycycline or penicillin (21-23). In a stuy by Müller et al. (7), it showe that A.a. strains were highly susceptible to fluoroquinolones, ciprofloxacin an moxifloxacin. Some of the ajunctive antibiotics are secrete in saliva in insufficient concentrations to inhibit A.a. Moxifloxacin seems to be secrete in saliva at higher levels than in plasma an may also concentrate at the site of infection since it penetrates polymorphonuclear granulocytes an epithelial cells (7). In the present stuy, to potentiate the outcomes of nonsurgical perioontal treatment, SRP performe in 24-h perio in combination with chlorhexiine igluconate mouthrinse an systemically aministere antibio tics by reucing the number of perioontopathogen not only from perioontal pockets but also from their other habitats such as saliva, the tongue, an by retaring recolonization of the bacteria. AgP patients might have benefits from this approach. The present stuy is the use of only one type of antibiotic with less amounts of tablets; instea of two ifferent types of antibiotics with a lot more tablets taken. This treatment alternative might cause fewer sie effects with similar clinical outcomes an enhance patient compliance. In the contrary to previous reports, three patients who use AMX+MET, reporte averse effects (4,12). However, other stuies are reporte varying sie effects relate to AMX+MET (11,24,25). There is no report regaring averse effects of moxifloxacin in perioontal treatment. One woul consier why a control group (without antibiotics) i not think to be inclue in the present stuy. This might be a one of the limitations of the present stuy. However, as we summarize an iscusse in this section, the antibiotic use as an ajunct to SRP is approve with research an accepte with consensus e447

8 reports release by EFP an AAP in the treatment of GAgP. Hence, we thought that it woul not be ethical to monitor the nonsurgical treatment of patients with GAgP without an ajunct antibiotic. While the effect of ajunctive AMX+MET in the treatment of GAgP is well efine (4,11,12,26), antibiotic combination of AMX+MET was consiere as control. Another limitation of the present stuy woul be the lack of microbiological evaluation. There are two major inications for microbiological testing in Perioontology; first, to etect subgingival microbial flora for accurate iagnosis. It was state that all patients with GAgP may not have an ientical an specific microbial profile relate with GAgP (27). Moreover, subgingival microbial factors in GAgP o not seem ifferent from patients with chronic perioontitis. Prevalence an behaviors of perioontopathogens may not aapt to ifferent populations an ethnicities (28,29). It was reporte that A.a.-positive patients ha no specific benefit from AMX+MET (24), which means combinations or specific antibiotic regimens may not work in all cases (14). On the other han, Heller et al. (26) emphasize interiniviual varieties of perioontopathogens in the subgingival microbial flora of patients with GAgP an conclue that not all GAgP patients ha greater microbial benefits from AMX+MET combination. The patients ha species associate with GAgP were more affecte from this combination. Secon, was to etermine the antibiotic susceptibility/ resistance of perioontopathogenic profiles for proper treatment. It was note that European an South American countries have significant ifferences in their antibiotic susceptibility profiles of perioontal bacteria (30). van Winkelhoff et al. (30) conclue that it may not be possible to evelop uniform protocols in the aministration of antibiotics an in the treatment of severe type of perioontitis. More accurate approach might be as follows: to analyze the subgingival microflora, to characterize perioontopathogens, to ecie for prescribing antimicrobial regime or not, an to test that antimicrobial rugs for bacterial resistance an susceptibility. Otherwise, antibiotics are not always clinically effective. Nevertheless, in most of the stuies, bacterial resistance an susceptibility are isregare an bacterial counts are reporte; following aministration of any antimicrobial regimes. The most optimal antibiotic regime woul be etermine with antibiotic susceptibility testing. On the other han, ifferent microbiology laboratory set-ups, hence ifferent test reports, complex microbial flora, empiric an the misuse of antibiotics may limit to use of microbial test. Having taken together all the provie ata from other stuies, it is ifficult to compare an conclue ajunctive benefits of antimicrobial treatments ue to both the paucity of ranomize controlle stuies an the ifferent methoologies of the stuies. Moreover, suppression/eraication of targete microorganisms oes not mean to achieve clinical efficacy (9). Conclusions Within the limitation of the present stuy, we conclue that: although both antibiotic regimes together with nonsurgical treatment provie similar an favorable en results at 6 s, moxifloxacin use coul be preferre by both entists an the patients ue to compliance because of the reuce number of tablets an the single-ose per ay, as well as in patients with allergies, intolerance, or lack of response to amoxicillin an metroniazole. Nevertheless, antimicrobial treatment shoul be base on iniviual characteristics of the patients. Further researches may involve iniviual risk assessments, an iniviual treatment protocols. References 1. 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