Spiramycin resistance in human periodontitis microbiota

Spiramycin resistance in human periodontitis microbiota Thomas E. Rams Sebastien Dujardin Jacqueline D. Sautter , John E. Degener ,Arie J. van Winkelhoff , a Department of Periodontology and Oral Implantology, and Oral Microbiology Testing Service Laboratory, Temple University School of Dentistry, 3223 North Broad Street,Philadelphia, PA 19140, USAb Department of Microbiology and Immunology, Temple University School of Medicine, 3500 North Broad Street, Philadelphia, PA 19140, USAc Center for Dentistry and Oral Hygiene, Department of Oral Microbiology, University Medical Center Groningen, University of Groningen, Antonius Deusinglaan 1,9713 AV Groningen, The Netherlandsd Department of Medical Microbiology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands Purpose: The occurrence of in vitro resistance to therapeutic concentrations of spiramycin, amoxicillin, and metronidazole was determined for putative periodontal pathogens isolated in the United States.
Materials and methods: Subgingival plaque specimens from 37 consecutive adults with untreated severe periodontitis were anaerobically cultured, and isolated putative periodontal pathogens were identified to a species level. In vitro resistance to spiramycin at 4 mg/ml, amoxicillin at 8 mg/ml, and/or metronidazole at 16 mg/ml was noted when putative periodontal pathogen growth was noted on the respectiveantibiotic-supplemented primary culture plates.
Results: A total of 18 (48.7%) subjects yielded antibiotic-resistant putative periodontal pathogens with spiramycin at 4 mg/ml in drug-supplemented primary isolation plates, as compared to 23 (62.2%) subjects with amoxicillin at 8 mg/ml, and 10 (27.0%) subjects with metronidazole at 16 mg/ml. Spiramycin in vitro resistance occurred among species of Fusobacterium nucleatum (44.4% of organism-positive subjects), Prevotella intermedia/nigrescens (11.1%), Parvimonas micra (10.8%), Streptococcus constellatus (10%), Streptococcus intermedius (10%), Porphyromonas gingivalis (6.7%), and Tannerella forsythia (5.3%). Amox-icillin in vitro resistance was found in P. intermedia/nigrescens (55.5%), T. forsythia (15.8%), S. constellatus(10%), F. nucleatum (5.6%), and P. micra (2.7%). Only S. constellatus (70%) and S. intermedius (40%) exhibitedin vitro resistance to metronidazole. When subject-based resistance data for spiramycin and metroni-dazole were jointly considered, all isolated putative periodontal pathogens were inhibited in vitro by oneor the other of the antibiotic concentrations, except for one strain each of S. constellatus andS. intermedius from one study subject. Similarly, either amoxicillin or metronidazole at the drugconcentrations tested inhibited in vitro all recovered putative periodontal pathogens, exceptS. constellatus in one subject.
Conclusions: In vitro spiramycin resistance among putative periodontal pathogens of United States originoccurred in approximately one-half of severe periodontitis patients evaluated, particularly among sub-gingival F. nucleatum species. In vitro resistance patterns also suggest that therapeutic concentrations ofspiramycin plus metronidazole may have potential antimicrobial efficacy in non-Aggregatibacter acti-nomycetemcomitans-associated periodontitis similar to amoxicillin plus metronidazole, which may bebeneficial, where spiramycin is clinically available, for patients hypersensitive to amoxicillin or otherbeta-lactam antibiotics.
Ó 2011 Elsevier Ltd. All rights reserved.
Spiramycin is a medium-spectrum, 16-membered, macrolide antibiotic widely used in the treatment of respiratory infections , * Corresponding author. Department of Periodontology and Oral Implantology, except in the United States, where it is available by special Temple University School of Dentistry, 3223 North Broad Street, Philadelphia, PA permission for treatment of toxoplasmosis in women during the 19140, USA. Tel.: þ1 215 707 2941; fax: þ1 215 707 4223.
first trimester of pregnancy. Since the drug enters the oral cavity 1075-9964/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi: T.E. Rams et al. / Anaerobe 17 (2011) 201e205 through gingival crevicular fluid and saliva, and persists for supplemented with either spiramycin at 4 mg/ml, amoxicillin at extended periods at potentially therapeutic concentrations , 8 mg/ml, or metronidazole at 16 mg/ml (all antimicrobials were spiramycin is also prescribed in some countries for various odon- obtained as pure powder from SigmaeAldrich, St. Louis, MO). These togenic infections, including endodontic abscesses, pericoronitis, antimicrobial concentrations represent non-susceptible/resistant and destructive forms of periodontal disease (periodontitis) breakpoint concentrations for anaerobic bacteria recommended A number of studies have assessed the antimicrobial activity of by the French Society for Microbiology for spiramycin, and the spiramycin on putative periodontopathic bacteria in subgingival Clinical and Laboratory Standards Institute (CLSI) for amoxi- plaque biofilms eExcept for ones completed over 25 years cillin and metronidazole. All EBBA and Hammond’s selective ago these studies focused on clinical isolates from perio- medium plates were incubated at 35 C for seven days in a Coy dontitis patients located outside of the United States. Since anaerobic chamber (Coy Laboratory Products, Ann Arbor, MI) con- geographic differences , and emergence of drug-resistant taining 85% N2-10% H2-5% CO2, and TSBV plates were incubated at strains over time may markedly alter antibiotic susceptibility 35 C for three days in 5% CO2-95% air.
patterns of subgingival bacterial species, the present-day antimi-crobial effects of spiramycin on putative periodontal pathogens in the United States remain speculative.
The present study examined, using fresh subgingival isolates On non-selective EBBA plates examined with a ring-light from periodontitis patients in the United States, the occurrence of magnifying loupe and a dissecting stereomicroscope, the presence in vitro resistance among putative periodontal pathogens to ther- and levels of total anaerobic viable counts, Porphyromonas gingivalis, apeutic concentrations of spiramycin, as well as amoxicillin and Prevotella intermedia/nigrescens, Parvimonas micra, staphylococci and enterococci were determined using presumptive phenotypicmethods previously described ; Tannerella forsythia was identified as gram-negative, non-motile, anaerobic rods exhibitinggrey-pink speckled, convex, pinpoint colonies seen with a stereo- microscope, lack of long-wave ultraviolet light autofluorescence,and a positive CAAM test for trypsin-like activity ; Fusobacterium A total of 37 adults (17 males, 20 females; aged 35e85 years; nucleatum was identified as long-wave ultraviolet light auto- mean 57.5 Æ 12.0 (SD) years), diagnosed with severe periodontitis fluorescent charteuse-positive gray, iridescent colonies of by periodontists in United States private dental practices, were gram-negative, filamentous, spindle-shaped, non-motile rods; consecutively included in the present study as their microbiological Streptococcus intermedius was recognized as gram-positive, lactose samples were received by the testing laboratory. Persons identified MUG-test positive , non-motile, facultative cocci exhibiting with aggressive periodontitis, or antibiotic use within the past six small dry, white, raised colonies with wrinkled edges; and Strepto- months, were excluded. Only 4 (10.8%) of the study subjects were coccus constellatus was defined as gram-positive, lactose MUG-test negative, non-motile, facultative cocci demonstrating small white,opaque, circular, beta-hemolytic, surface colonies with irregular edges, and positive for a-D-glucosidase enzyme activity, with orwithout b-D-fucosidase, b-D-glucosidase positive reactions, as Subgingival plaque specimens were obtained by each study determined with the Fluo-Card Milleri test kit (Key Scientific Prod- subject’s periodontist, following a standardized sampling protocol, ucts Co., Stamford, TX) Campylobacter rectus was quantitated on prior to treatment from the 3-5 deepest periodontal pockets (mean Hammond’s medium, and Aggregatibacter actinomycetemcomitans, 7.5 Æ 0.3 (SE) mm) per subject which exhibited bleeding on probing.
gram-negative enteric rods, pseudomonads, and Candida species on In brief, after isolation with cotton rolls, and removal of saliva and TSBV agar, as previously described . Proportional subject supragingival deposits, one to two sterile, absorbent paper points recovery of the various test putative periodontal pathogens was (Johnson & Johnson, East Windsor, NJ) were advanced into each calculated as the percent recovery of the test species colony forming selected periodontal site for approximately 10 s. Upon removal, all units (CFU) among the total subgingival anaerobic viable CFU count paper points per study subject were pooled into a glass vial con- as determined on non-selective EBBA plates.
taining 6-8 small glass beads and 2.0 ml of anaerobically preparedand stored VMGA III transport medium which possesses a high 2.5. In vitro antibiotic resistance testing preservation capability for oral microorganisms during post-sampling transit to the laboratory The subgingival samples In vitro resistance to the antibiotic breakpoint concentrations of were then transported within 24 h to the Oral Microbiology Testing spiramycin (4 mg/ml), amoxicillin (8 mg/ml), or metronidazole (16 mg/ Service (OMTS) Laboratory at Temple University School of Dentistry, ml) was recorded per subject when test putative periodontal path- which is licensed for high complexity bacteriological analysis by the ogen growth was noted on antibiotic-supplemented and non- supplemented primary isolation EBBA plates Bacteroidesthetaiotaomicron ATCC 29741, Clostridium perfringens ATCC 13124, and a multi-antibiotic-resistant clinical periodontal isolate of F. nucleatumwere employed as positive and negative quality controls for all anti- At the OMTS Laboratory, the specimen vials were warmed to biotic resistance testing on drug-supplemented EBBA plates.
35 C to liquefy the VMGA III transport medium, and sampledmicroorganisms were mechanically dispersed from the paper points with a Vortex mixer at the maximal setting for 45 s. Serial10-fold dilutions of dispersed bacteria were prepared in Möller’s Recovered test putative periodontal pathogens were grouped VMG I anaerobic dispersion solution . Appropriate dilution for reporting purposes into subgingival bacterial clusters (i.e., red aliquots were plated onto non-selective enriched Brucella blood complex, orange complex, and other species) described by Soc- agar (EBBA) , Hammond’s selective Campylobacter medium ransky et al. Descriptive analysis was used to calculate the , and TSBV agar . Aliquots were also plated onto EBBA subject occurrence and proportional cultivable recovery of test T.E. Rams et al. / Anaerobe 17 (2011) 201e205 putative periodontal pathogens on non-selective EBBA, and the in primary isolation plates (. Between 10 and 11% of subject subject occurrence of in vitro test putative periodontal pathogen strains each of P. intermedia/nigrescens, P. micra, and S. intermedius antibiotic resistance. In vitro data was also combined post-hoc for demonstrated in vitro spiramycin resistance, and one subject strain spiramycin and metronidazole, and for amoxicillin and metroni- each of P. gingivalis and T. forsythia were resistant in vitro to non- dazole, to determine the number and proportion of organism- susceptible breakpoint concentrations of spiramycin ).
positive study subjects where test putative periodontal pathogens Amoxicillin at 8 mg/ml in primary isolation plates inhibited all exhibited in vitro resistance to both antibiotics at the employed subject strains of P. gingivalis, C. rectus, and S. intermedius. In non-susceptible breakpoint concentrations.
contrast, 55.5% of P. intermedia/nigrescens subject strains, and2.7e15.8% of T. forsythia, S. constellatus, F. nucleatum, and P. micra subject strains displayed in vitro resistance to 8 mg/ml of amoxicillinin primary isolation plates All microbiological procedures were performed on a standard- All subject strains of P. gingivalis, T. forsythia, P. intermedia/ ized, blinded basis without knowledge of the clinical status of the nigrescens, P. micra, C. rectus, and F. nucleatum were inhibited in vitro study subjects, or their inclusion in the present analysis. Approval by 16 mg/ml of metronidazole in primary isolation plates. However, for the study was provided by the Temple University Human 70% of S. constellatus, and 40% of S. intermedius subject strains, Subjects Institutional Review Board.
revealed in vitro resistance to 16 mg/ml of metronidazole ( When subject-based in vitro resistance data for 4 mg/ml of spi- ramycin and 16 mg/ml of metronidazole were jointly considered post-hoc, all isolated test periodontal pathogens were inhibitedin vitro by one or the other of the antibiotic concentrations, except 3.1. Total cultivable counts and putative periodontal pathogen for one strain each of S. constellatus and S. intermedius in one (2.7%) study subject. Similarly, either 8 mg/ml of amoxicillin or 16 mg/ml ofmetronidazole inhibited in vitro all recovered test periodontal Total subgingival anaerobic viable counts on non-antibiotic- pathogens, except S. constellatus in one (2.7%) subject ().
supplemented EBBA plates averaged 7.32 Â 107 Æ 1.6 Â 107 (SE)organisms/ml of sample in the study subjects (range ¼ 2 Â 106 to lists the distribution of recovered subgingival test The present study findings represent the first data in over 25 putative periodontal pathogens in the 37 study subjects.
years on in vitro spiramycin resistance in putative periodontal Among red complex bacterial species, P. gingivalis was isolated pathogens in the United States. In vitro resistance among recovered from 15 (40.5%) subjects, and T. forsythia from 19 (51.4%) subjects, at putative periodontal pathogens to spiramycin at 4 mg/ml was found mean subgingival proportions of 14.4% and 1.4%, respectively, in in 48.7% of severe periodontitis patients evaluated, which was less culture-positive subjects. Among orange complex and other in vitro resistance than occurred with amoxicillin at 8 mg/ml (62.2% species, P. micra was isolated from all 37 subjects, P. intermedia/ of subjects), but more than was found with metronidazole at 16 mg/ nigrescens and F. nucleatum were each found in 36 (97.3%) subjects, ml (27.0%). These findings highlight the considerable subject vari- C. rectus was recovered from 20 (54.1%) subjects, and S. constellatus ation seen across single antibiotic drugs in their antimicrobial and S. intermedius were each present in 10 (27.0%) subjects effects against putative periodontal pathogens, which can mark- Cultivable subgingival A. actinomycetemcomitans, gram- edly influence the selection and efficacy of periodontal antibiotic negative enteric rods, pseudomonads, staphylococci, enterococci and Candida species were not detected in any of the study subjects.
Among individual microbial species, most red and orange complex organisms, which are associated with increasingly more 3.2. In vitro antibiotic resistance testing severe forms of periodontitis were inhibited in vitro by spi-ramycin at 4 mg/ml in primary isolation plates ). However, A total of 18 (48.7%) subjects yielded antibiotic-resistant puta- F. nucleatum was frequently resistant in vitro to spiramycin (44.4% of tive periodontal pathogens with spiramycin at 4 mg/ml in drug- subject strains), consistent with previous reports on periodontitis supplemented primary isolation plates, as compared to 23 (62.2%) subjects with amoxicillin at 8 mg/ml, and 10 (27.0%) subjects with Some subject strains of P. gingivalis, T. forsythia, P. intermedia/nigrescens and P. micra also exhibited in vitro resistance F. nucleatum most frequently exhibited in vitro spiramycin resis- to spiramycin, but at lower proportions than homologous species tance, with 44.4% of subject strains resistant to 4 mg/ml of spiramycin strains previously isolated and tested in France . For reasons tobe determined, all C. rectus in the present study were inhibited Occurrence and proportional subgingival recovery of selected putative periodontal bacterial pathogens in 37 adults with severe periodontitis.
compared to 80% C. rectus resistance to spiramycin at the samein vitro concentration in France No. (%) of culture- Mean % Æ SE recovery Range % Since there is negligible spiramycin use in the general United States population, it is unlikely that the spiramycin resistance detected in the present study subjects is the result of prior spi- ramycin drug exposures promoting selection of resistant microbial species, in contrast to persons in countries where spiramycin is extensively prescribed. Instead, the increasing dissemination among gram-negative bacteria, via mobile plasmids and/or con- jugative transposons, of various drug resistance genes active against all macrolide-class antibiotics may account for in vitro spiramycin resistance among periodontal microorganisms not previously exposed to spiramycin However, the molecular T.E. Rams et al. / Anaerobe 17 (2011) 201e205 Table 2Occurrence of in vitro resistance among subgingival test putative periodontal pathogens to non-susceptible antibiotic breakpoint concentrations in primary isolation plates.
a No. (%) of species-positive subjects with strains resistant in vitro to non-susceptible antibiotic breakpoint concentrations in primary isolation plates.
b Joint post-hoc consideration of in vitro resistance data for each antibiotic.
basis for the in vitro spiramycin drug resistance detected in the in some previous studies . However, these favorable present study remains to be determined.
microbiological effects are consistent with the results of a double- In vitro resistance to amoxicillin included most P. intermedia/ blind clinical trial finding systemic spiramycin plus metronidazole nigrescens subject strains, and a smaller subset of T. forsythia, to significantly enhance gains of clinical periodontal attachment on S. constellatus, F. nucleatum, and P. micra, with metronidazole resis- initially deep periodontal pockets at 6 months post-treatment on tance found only among most S. constellatus and some S. intermedius clinical isolates, similar to previous reports A similar post-hoc joint analysis also found either amoxicillin at The direct plating method used in this study to detect antibiotic 8 mg/ml or metronidazole at 16 mg/ml in primary isolation plates resistance on primary culture plates has been previously used in inhibited all recovered putative periodontal pathogens, except a number of periodontal microbiology studies , and S. constellatus in one (2.7%) subject, which is also consistent with shown to highly correlate (r2 ¼ 0.99) with the CLSI-approved clinical trials demonstrating enhanced therapeutic benefits of multiple agar dilution assay in successfully identifying antibiotic- systemic amoxicillin plus metronidazole in aggressive and chronic resistant periodontal microorganisms Similarly, Lewis et al.
reported a 94% agreement between primary versus secondary While the periodontists who performed clinical examinations in (subculture) antibiotic susceptibility plate testing of acute den- the present study were not formally calibrated, support for their toalveolar abscess bacterial isolates. The relatively high viable severe periodontitis diagnoses was evidenced by their identifica- anaerobic counts (on average in excess of 107 organisms/ml) tion in the study subjects of three or more periodontal sites with recovered on non-selective EBBA media in the present study deep probing depths with bleeding on probing (mean 7.5 mm at suggests that an adequate subgingival sample inocula was spread microbiologically-sampled periodontal sites), which strongly on antibiotic-supplemented primary isolation plates examined for correlates (94.1% positive predictive value) with the presence of resistant species growth. However, the inability to determine exact severe periodontal attachment loss in adult patients minimal inhibitory concentration (MIC) values of antimicrobials Overall, these findings suggest that the in vitro effectiveness of tested against microbial species is a shortcoming of this approach, spiramycin against putative periodontal pathogens can be enhanced since only non-susceptible/resistant breakpoint concentrations, as by broadening its antimicrobial spectrum with metronidazole, and recommended by the French Society for Microbiology for that the joint in vitro antimicrobial effects of spiramycin plus spiramycin, and the Clinical and Laboratory Standards Institute metronidazole against a wide range of putative periodontal patho- for amoxicillin and metronidazole, were employed per antibiotic in gens appears to be similar to that seen with amoxicillin plus the in vitro resistance testing. Nevertheless, identification of metronidazole. Thus, a clinical periodontitis treatment strategy in vitro periodontal pathogen resistance to therapeutic concen- involving systemic spiramycin plus metronidazole, but not spi- trations of antimicrobials contemplated for patient care is highly ramycin alone, may have potential therapeutic efficacy similar to the relevant and clinically practical to dentists striving to avoid combination of amoxicillin plus metronidazole, and may be prescribing antibiotics ineffective against drug-resistant pathogens.
particularly beneficial as an alternative for periodontitis patients Since increasing interest has developed on use of combination hypersensitive to amoxicillin or other beta-lactam antibiotics, and systemic antibiotic regimens in periodontitis treatment, where two not colonized by A. actinomycetemcomitans strains resistant to spi- antibiotics with complementary antibacterial activity are adminis- tered to broaden the spectrum of antimicrobial effects against sub-gingival and soft tissue-invading bacterial pathogens the present study also jointly considered subject-based resistance datapost-hoc for spiramycin at 4 mg/ml plus metronidazole at 16 mg/ml.
In vitro spiramycin resistance among putative periodontal path- Interestingly, all isolated putative periodontal pathogens were ogens of United States origin was found in approximately one-half of inhibited in vitro by one or the other of the antibiotic concentrations in primary isolation plates, except for one strain each of F. nucleatum species. In vitro resistance patterns also suggest that S. constellatus and S. intermedius from one (2.7%) study subject. Since therapeutic concentrations of spiramycin plus metronidazole may the two antibiotic concentrations were not incorporated together have potential antimicrobial efficacy in non-A. actinomycete- into antibiotic-supplemented primary isolation plates, no conclu- mcomitans-associated periodontitis similar to amoxicillin plus sions can be drawn about synergistic drug effects of spiramycin plus metronidazole, which may be beneficial, where spiramycin is clini- metronidazole against oral bacterial species, which have been noted cally available, for patients hypersensitive to amoxicillin or other T.E. Rams et al. / Anaerobe 17 (2011) 201e205 beta-lactam antibiotics. Further clinical and microbiological studies [20] Armitage GC. Periodontal diagnoses and classification of periodontal diseases.
of spiramycin, particularly in combination with metronidazole, are [21] Möller AJR. Microbiological examination of root canals and periapical tissues indicated to further clarify its potential value in treatment of human of human teeth. Odontol Tidskr 1966;74:1e380.
[22] Dahlén G, Pipattanagovit P, Rosling B, Möller AJR. A comparison of two transport media for saliva and subgingival samples. Oral Microbiol Immunol [23] Slots J, Rams TE, Listgarten MA. Yeasts, enteric rods and pseudomonads in the subgingival flora of severe adult periodontitis. Oral Microbiol Immunol 1988; Support for this research was in part provided by funds from the Paul H. Keyes Professorship in Periodontology at Temple University [24] Hammond BF, Mallonee D. A selective/differential medium for Wolinella recta.
School of Dentistry held by Thomas E. Rams.
mycetemcomitans. J Clin Microbiol 1982;15:606e9.
[26] Comité de l’Antibiogramme de la Société Française de Microbiologie, Les recommandations du comité de l’antibiogramme. Recommandations. Last [1] Rubinstein E, Keller N. Spiramycin renaissance. J Antimicrob Chemother 1998; [27] Clinical and Laboratory Standards Institute. Methods for antimicrobial [2] Rotzetter PA, Le Liboux A, Pichard E, Cimasoni G. Kinetics of spiramycin/ susceptibility testing of anaerobic bacteria, approved standard. 7th ed. Wayne, metronidazole (Rodogyl) in human gingival crevicular fluid, saliva and blood.
Pennsylvania; 2007. CLSI document M11eA7.
[28] Rams TE, Listgarten MA, Slots J. Utility of 5 major putative periodontal [3] Al-Haroni M, Skaug N. Incidence of antibiotic prescribing in dental practice in pathogens and selected clinical parameters to predict periodontal Norway and its contribution to national consumption. J Antimicrob Chemo- breakdown in patients on maintenance care. J Clin Periodontol 1996;23: [4] Rodriguez-Núñez A, Cisneros-Cabello R, Velasco-Ortega E, Llamas-Carreras JM, [29] Rams TE, Feik D, Young V, Hammond BF, Slots J. Enterococci in human Tórres-Lagares D, Segura-Egea JJ. Antibiotic use by members of the Spanish periodontitis. Oral Microbiol Immunol 1992;7:249e52.
endodontic society. J Endod 2009;35:1198e203.
[30] Rams TE, Feik D, Listgarten MA, Slots J. Peptostreptococcus micros in human [5] Sixou JL, Magaud C, Jolivet-Gougeon A, Cormier M, Bonnaure-Mallet M.
periodontitis. Oral Microbiol Immunol 1992;7:1e6.
Evaluation of the mandibular third molar pericoronitis flora and its suscep- [31] Rams TE, Feik D, Slots J. Staphylococci in human periodontal diseases. Oral tibility to different antibiotics prescribed in France. J Clin Microbiol 2003;41: [32] Brazier JS. Yellow fluorescence of fusobacteria. Lett Appl Microbiol 1986;2: [6] Bain CA, Beagrie GS, Bourgoin J, Delorme F, Holthuis A, Landry RG, et al. The effects of spiramycin and/or scaling on advanced periodontitis in humans.
[33] Alcoforado GAP, McKay TL, Slots J. Rapid method for detection of lactose fermenting oral microorganisms. Oral Microbiol Immunol 1987;2:35e8.
[7] Mashimo PA, Yamamoto Y, Slots J, Evans RT, Genco RJ. In vitro evaluation of [34] Clarridge III JE, Osting C, Jalali M, Osborne J, Waddington M. Genotypic and antibiotics in the treatment of periodontal disease. Pharmacol Ther Dent phenotypic characterization of "Streptococcus milleri" group isolates from a Veterans Administration hospital population. J Clin Microbiol 1999;37: [8] Baker PJ, Slots J, Genco RJ, Evans RT. Minimal inhibitory concentrations of various antimicrobial agents for human oral anaerobic bacteria. Antimicrob [35] Rams TE, Feik D, Slots J. Campylobacter rectus in human periodontitis. Oral [9] Baker PJ, Evans RT, Slots J, Genco RJ. Antibiotic susceptibility of anaerobic [36] Feres M, Haffajee AD, Goncalves C, Allard KA, Som S, Smith C, et al. Systemic bacteria from the human oral cavity. J Dent Res 1985;64:1233e44.
doxycycline administration in the treatment of periodontal infections (II).
[10] Quee TC, Roussou T, Chan EC. In vitro activity of rodogyl against putative Effect on antibiotic resistance of subgingival species. J Clin Periodontol 1999; periodontopathic bacteria. Antimicrob Agents Chemother 1983;24:445e7.
[11] Mouton C, Dextraze L, Mayrand D. Susceptibility of potential periodontopathic [37] van Winkelhoff AJ, Herrera Gonzales D, Winkel EG, Dellemijn-Kippuw N, bacteria to metronidazole, spiramycin and their combination. J Biol Buccale Vandenbroucke-Grauls CM, Sanz M. Antimicrobial resistance in the subgingival microflora in patients with adult periodontitis. A comparison [12] Chan EC, al-Joburi W, Cheng SL, Delorme F. In vitro susceptibilities of oral bacterial between the Netherlands and Spain. J Clin Periodontol 2000;27:79e86.
isolates to spiramycin. Antimicrob Agents Chemother 1989;33:2016e8.
[38] Socransky SS, Haffajee AD, Cugini MA, Smith C, Kent RL. Microbial complexes [13] Williams JD, Maskell JP, Shain H, Chrysos G, Sefton AM, Fraser HY, et al.
in subgingival plaque. J Clin Periodontol 1998;25:134e44.
Comparative in-vitro activity of azithromycin, macrolides (erythromycin, [39] van Winkelhoff AJ, Rams TE, Slots J. Systemic antibiotic therapy in peri- clarithromycin and spiramycin) and streptogramin RP 59500 against oral odontics. Periodontol 2000 1996;10:45e78.
organisms. J Antimicrob Chemother 1992;30:27e37.
[40] Roche Y, Yoshimori RN. In-vitro activity of spiramycin and metronidazole [14] Andrés MT, Chung WO, Roberts MC, Fierro JF. Antimicrobial susceptibilities of alone or in combination against clinical isolates from odontogenic abscesses.
Porphyromonas gingivalis, Prevotella intermedia, and Prevotella nigrescens spp.
J Antimicrob Chemother 1997;40:353e7.
isolated in Spain. Antimicrob Agents Chemother 1998;42:3022e3.
[41] Roberts MC. Distribution of macrolide, lincosamide, streptogramin, ketolide [15] Madinier IM, Fosse TB, Hitzig C, Charbit Y, Hannoun LR. Resistance profile and oxazolidinone (MLSKO) resistance genes in gram-negative bacteria. Curr survey of 50 periodontal strains of Actinobacillus actinomyectomcomitans.
Drug Targets Infect Disord 2004;4:207e15.
[42] Roberts MC. Update on macrolide-lincosamide-streptogramin, ketolide, and [16] Lakhssassi N, Elhajoui N, Lodter JP, Pineil JL, Sixou M. Antimicrobial oxazolidinone resistance genes. FEMS Microbiol Lett 2008;282:147e59.
susceptibility variation of 50 anaerobic periopathogens in aggressive [43] Lewis MA, MacFarlane TW, McGowan DA. Reliability of sensitivity testing of periodontitis: an interindividual variability study. Oral Microbiol Immunol primary culture of acute dentoalveolar abscess. Oral Microbiol Immunol 1988; [17] Poulet PP, Duffaut D, Barthet P, Brumpt I. Concentrations and in vivo anti- [44] van Winkelhoff AJ, Winkel EG. Antibiotics in periodontics: right or wrong? bacterial activity of spiramycin and metronidazole in patients with perio- [45] Quee TC, Chan EC, Clark C, Lautar-Lemay C, Bergeron MJ, Bourgouin J, et al.
metronidazole combination. J Antimicrob Chemother 2005;55:347e51.
The role of adjunctive Rodogyl therapy in the treatment of advanced peri- [18] van Winkelhoff AJ, Herrera D, Oteo A, Sanz A. Antimicrobial profiles of peri- odontal disease. A longitudinal clinical and microbiologic study. J Periodontol odontal pathogens isolated from periodontitis patients in The Netherlands and Spain. J Clin Periodontol 2005;32:893e8.
[46] Machtei EE, Christersson LA, Zambon JJ, Hausmann E, Grossi SG, Dunford R, [19] Walker CB. The acquisition of antibiotic resistance in the periodontal micro- et al. Alternative methods for screening periodontal disease in adults. J Clin flora. Periodontol 2000 1996;10:79e88.

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