Skip to main content
Top
Published in: Clinical Oral Investigations 6/2015

01-07-2015 | Original Article

Development of resistance of mutans streptococci and Porphyromonas gingivalis to chlorhexidine digluconate and amine fluoride/stannous fluoride-containing mouthrinses, in vitro

Authors: Eva M. Kulik, Tuomas Waltimo, Roland Weiger, Irene Schweizer, Krystyna Lenkeit, Elisabeth Filipuzzi-Jenny, Clemens Walter

Published in: Clinical Oral Investigations | Issue 6/2015

Login to get access

Abstract

Objective

The aim if this study was to determine the minimal inhibitory concentrations of chlorhexidine digluconate and an amine fluoride/stannous fluoride-containing mouthrinse against Porphyromonas gingivalis and mutans streptococci during an experimental long-term subinhibitory exposition.

Material and methods

Five P. gingivalis strains and four mutans streptococci were subcultivated for 20–30 passages in subinhibitory concentrations of chlorhexidine digluconate or an amine fluoride/stannous fluoride-containing mouthrinse.

Results

Pre-passaging minimal inhibitory concentrations for chlorhexidine ranged from 0.5 to 2 mg/l for mutans streptococci and from 2 to 4 mg/l for the P. gingivalis isolates. For the amine fluoride/stannous fluoride-containing mouthrinse minimal inhibitory values from 0.125 to 0.25 % for the mutans streptococci and from 0.063 to 0.125 % for the P. gingivalis isolates were determined. Two- to fourfold increased minimal inhibitory concentrations against chlorhexidine were detected for two of the five P. gingivalis isolates, whereas no increase in minimal inhibitory concentrations was found for the mutans streptococci after repeated passaging through subinhibitory concentrations. Repeated exposure to subinhibitory concentrations of the amine fluoride/stannous fluoride-containing mouthrinse did not alter the minimally inhibitory concentrations of the bacterial isolates tested.

Conclusion

Chlorhexidine and the amine fluoride/stannous fluoride-containing mouthrinse are effective inhibitory agents against the oral bacterial isolates tested. No general development of resistance against chlorhexidine or the amine fluoride/stannous fluoride-containing mouthrinse was detected. However, some strains showed potential to develop resistance against chlorhexidine after prolonged exposure.

Clinical relevance

The use of chlorhexidine should be limited to short periods of time. The amine fluoride/stannous fluoride-containing mouthrinse appears to have the potential to be used on a long-term basis.
Literature
1.
2.
go back to reference Albandar JM, Tinoco EM (2002) Global epidemiology of periodontal diseases in children and young persons. Periodontol 2000 29:153–176 Albandar JM, Tinoco EM (2002) Global epidemiology of periodontal diseases in children and young persons. Periodontol 2000 29:153–176
3.
go back to reference Bostanci N, Belibasakis GN (2012) Porphyromonas gingivalis: an invasive and evasive opportunistic oral pathogen. FEMS Microbiol Lett 333:1–9PubMedCrossRef Bostanci N, Belibasakis GN (2012) Porphyromonas gingivalis: an invasive and evasive opportunistic oral pathogen. FEMS Microbiol Lett 333:1–9PubMedCrossRef
4.
go back to reference Bridier A, Briandet R, Thomas V, Dubois-Brissonnet F (2011) Resistance of bacterial biofilms to disinfectants: a review. Biofouling 27:1017–1032PubMedCrossRef Bridier A, Briandet R, Thomas V, Dubois-Brissonnet F (2011) Resistance of bacterial biofilms to disinfectants: a review. Biofouling 27:1017–1032PubMedCrossRef
5.
go back to reference Clinical and Laboratory Standards Institute (2007) Methods for antimicrobial susceptibility testing of anaerobic bacteria; approved standard M11-A7. CLSI, Wayne, USA Clinical and Laboratory Standards Institute (2007) Methods for antimicrobial susceptibility testing of anaerobic bacteria; approved standard M11-A7. CLSI, Wayne, USA
7.
go back to reference Davies GE, Francis J, Martin AR, Rose FL, Swain G (1954) 1:6-Di-4'-chlorophenyldiguanidohexane (hibitane); laboratory investigation of a new antibacterial agent of high potency. Br J Pharmacol Chemother 9:192–196PubMedCentralPubMedCrossRef Davies GE, Francis J, Martin AR, Rose FL, Swain G (1954) 1:6-Di-4'-chlorophenyldiguanidohexane (hibitane); laboratory investigation of a new antibacterial agent of high potency. Br J Pharmacol Chemother 9:192–196PubMedCentralPubMedCrossRef
8.
go back to reference de Lastours V, Cambau E, Guillard T, Marcade G, Chau F, Fantin B (2012) Diversity of individual dynamic patterns of emergence of resistance to quinolones in Escherichia coli from the fecal flora of healthy volunteers exposed to ciprofloxacin. J Infect Dis 206:1399–1406PubMedCrossRef de Lastours V, Cambau E, Guillard T, Marcade G, Chau F, Fantin B (2012) Diversity of individual dynamic patterns of emergence of resistance to quinolones in Escherichia coli from the fecal flora of healthy volunteers exposed to ciprofloxacin. J Infect Dis 206:1399–1406PubMedCrossRef
9.
go back to reference De Soete M, Dekeyser C, Pauwels M, Teughels W, van Steenberghe D, Quirynen M (2005) Increase in cariogenic bacteria after initial periodontal therapy. J Dent Res 84:48–53PubMedCrossRef De Soete M, Dekeyser C, Pauwels M, Teughels W, van Steenberghe D, Quirynen M (2005) Increase in cariogenic bacteria after initial periodontal therapy. J Dent Res 84:48–53PubMedCrossRef
10.
go back to reference Do LG (2012) Distribution of caries in children: variations between and within populations. J Dent Res 91:536–543PubMedCrossRef Do LG (2012) Distribution of caries in children: variations between and within populations. J Dent Res 91:536–543PubMedCrossRef
11.
go back to reference Eick S, Rodel J, Einax JW, Pfister W (2002) Interaction of Porphyromonas gingivalis with KB cells: comparison of different clinical isolates. Oral Microbiol Immunol 17:201–208PubMedCrossRef Eick S, Rodel J, Einax JW, Pfister W (2002) Interaction of Porphyromonas gingivalis with KB cells: comparison of different clinical isolates. Oral Microbiol Immunol 17:201–208PubMedCrossRef
12.
go back to reference Eick S, Goltz S, Nietzsche S, Jentsch H, Pfister W (2011) Efficacy of chlorhexidine digluconate-containing formulations and other mouthrinses against periodontopathogenic microorganisms. Quintessence Int 42:687–700PubMed Eick S, Goltz S, Nietzsche S, Jentsch H, Pfister W (2011) Efficacy of chlorhexidine digluconate-containing formulations and other mouthrinses against periodontopathogenic microorganisms. Quintessence Int 42:687–700PubMed
13.
go back to reference el Moug T, Rogers DT, Furr JR, el-Falaha BM, Russell AD (1985) Antiseptic-induced changes in the cell surface of a chlorhexidine-sensitive and a chlorhexidine-resistant strain of Providencia stuartii. J Antimicrob Chemother 16:685–689PubMedCrossRef el Moug T, Rogers DT, Furr JR, el-Falaha BM, Russell AD (1985) Antiseptic-induced changes in the cell surface of a chlorhexidine-sensitive and a chlorhexidine-resistant strain of Providencia stuartii. J Antimicrob Chemother 16:685–689PubMedCrossRef
14.
go back to reference Fang CT, Chen HC, Chuang YP, Chang SC, Wang JT (2002) Cloning of a cation efflux pump gene associated with chlorhexidine resistance in Klebsiella pneumoniae. Antimicrob Agents Chemother 46:2024–2028PubMedCentralPubMedCrossRef Fang CT, Chen HC, Chuang YP, Chang SC, Wang JT (2002) Cloning of a cation efflux pump gene associated with chlorhexidine resistance in Klebsiella pneumoniae. Antimicrob Agents Chemother 46:2024–2028PubMedCentralPubMedCrossRef
15.
go back to reference Flisfisch S, Meyer J, Meurman JH, Waltimo T (2008) Effects of fluorides on Candida albicans. Oral Dis 14:296–301PubMedCrossRef Flisfisch S, Meyer J, Meurman JH, Waltimo T (2008) Effects of fluorides on Candida albicans. Oral Dis 14:296–301PubMedCrossRef
16.
go back to reference Flötra L, Gjermo P, Rolla G, Waerhaug J (1971) Side effects of chlorhexidine mouth washes. Scand J Dent Res 79:119–125PubMed Flötra L, Gjermo P, Rolla G, Waerhaug J (1971) Side effects of chlorhexidine mouth washes. Scand J Dent Res 79:119–125PubMed
17.
go back to reference Gnanadhas DP, Marathe SA, Chakravortty D (2013) Biocides–resistance, cross-resistance mechanisms and assessment. Expert Opin Investig Drugs 22:191–206PubMedCrossRef Gnanadhas DP, Marathe SA, Chakravortty D (2013) Biocides–resistance, cross-resistance mechanisms and assessment. Expert Opin Investig Drugs 22:191–206PubMedCrossRef
18.
go back to reference Guggenheim B, Schroeder HE (1967) Biochemical and morphological aspects of extracellular polysaccharides produced by cariogenic streptococci. Helv Odontol Acta 11:131–152PubMed Guggenheim B, Schroeder HE (1967) Biochemical and morphological aspects of extracellular polysaccharides produced by cariogenic streptococci. Helv Odontol Acta 11:131–152PubMed
19.
20.
go back to reference Jarvinen H, Tenovuo J, Huovinen P (1993) In vitro susceptibility of Streptococcus mutans to chlorhexidine and six other antimicrobial agents. Antimicrob Agents Chemother 37:1158–1159PubMedCentralPubMedCrossRef Jarvinen H, Tenovuo J, Huovinen P (1993) In vitro susceptibility of Streptococcus mutans to chlorhexidine and six other antimicrobial agents. Antimicrob Agents Chemother 37:1158–1159PubMedCentralPubMedCrossRef
21.
go back to reference Kapil V, Haydar SM, Pearl V, Lundberg JO, Weitzberg E, Ahluwalia A (2013) Physiological role for nitrate-reducing oral bacteria in blood pressure control. Free Radic Biol Med 55:93–100PubMedCentralPubMedCrossRef Kapil V, Haydar SM, Pearl V, Lundberg JO, Weitzberg E, Ahluwalia A (2013) Physiological role for nitrate-reducing oral bacteria in blood pressure control. Free Radic Biol Med 55:93–100PubMedCentralPubMedCrossRef
22.
go back to reference Kosutic D, Uglesic V, Perkovic D, Persic Z, Solman L, Lupi-Ferandin S, Knezevic P, Sokler K, Knezevic G (2009) Preoperative antiseptics in clean/contaminated maxillofacial and oral surgery: prospective randomized study. Int J Oral Maxillofac Surg 38:160–165PubMedCrossRef Kosutic D, Uglesic V, Perkovic D, Persic Z, Solman L, Lupi-Ferandin S, Knezevic P, Sokler K, Knezevic G (2009) Preoperative antiseptics in clean/contaminated maxillofacial and oral surgery: prospective randomized study. Int J Oral Maxillofac Surg 38:160–165PubMedCrossRef
23.
go back to reference Kulik E, Lenkeit K, Meyer J (2000) Antimicrobial effects of tea tree oil (Melaleuca alternifolia) on oral microorganisms. Schweiz Monatsschr Zahnmed 110:125–130PubMed Kulik E, Lenkeit K, Meyer J (2000) Antimicrobial effects of tea tree oil (Melaleuca alternifolia) on oral microorganisms. Schweiz Monatsschr Zahnmed 110:125–130PubMed
24.
go back to reference Kulik EM, Lenkeit K, Chenaux S, Meyer J (2008) Antimicrobial susceptibility of periodontopathogenic bacteria. J Antimicrob Chemother 61:1087–1091PubMedCrossRef Kulik EM, Lenkeit K, Chenaux S, Meyer J (2008) Antimicrobial susceptibility of periodontopathogenic bacteria. J Antimicrob Chemother 61:1087–1091PubMedCrossRef
25.
go back to reference Kulik Kunz EM, Lenkeit K, Waltimo T, Weiger R, Walter C (2004) Combinatorial effects of amoxicillin and metronidazole on selected periodontal bacteria and whole plaque samples. Arch Oral Biol 59:608–615CrossRef Kulik Kunz EM, Lenkeit K, Waltimo T, Weiger R, Walter C (2004) Combinatorial effects of amoxicillin and metronidazole on selected periodontal bacteria and whole plaque samples. Arch Oral Biol 59:608–615CrossRef
26.
go back to reference Meurman JH, Jousimies-Somer H, Suomala P, Alaluusua S, Torkko H, Asikainen S (1989) Activity of amine-stannous fluoride combination and chlorhexidine against some aerobic and anaerobic oral bacteria. Oral Microbiol Immunol 4:117–119PubMedCrossRef Meurman JH, Jousimies-Somer H, Suomala P, Alaluusua S, Torkko H, Asikainen S (1989) Activity of amine-stannous fluoride combination and chlorhexidine against some aerobic and anaerobic oral bacteria. Oral Microbiol Immunol 4:117–119PubMedCrossRef
27.
go back to reference Micheelis W (2011) Oral health in Germany: an oral epidemiological outline. Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz 54:1022–1026PubMedCrossRef Micheelis W (2011) Oral health in Germany: an oral epidemiological outline. Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz 54:1022–1026PubMedCrossRef
28.
29.
go back to reference Morrissey I, Oggioni MR, Knight D, Curiao T, Coque T, Kalkanci A, Martinez JL (2014) Evaluation of epidemiological cut-off values indicates that biocide resistant subpopulations are uncommon in natural isolates of clinically-relevant microorganisms. PLoS One 9:e86669PubMedCentralPubMedCrossRef Morrissey I, Oggioni MR, Knight D, Curiao T, Coque T, Kalkanci A, Martinez JL (2014) Evaluation of epidemiological cut-off values indicates that biocide resistant subpopulations are uncommon in natural isolates of clinically-relevant microorganisms. PLoS One 9:e86669PubMedCentralPubMedCrossRef
30.
go back to reference Nagai I, Ogase H (1990) Absence of role for plasmids in resistance to multiple disinfectants in three strains of bacteria. J Hosp Infect 15:149–155PubMedCrossRef Nagai I, Ogase H (1990) Absence of role for plasmids in resistance to multiple disinfectants in three strains of bacteria. J Hosp Infect 15:149–155PubMedCrossRef
31.
go back to reference Nakahara H, Kozukue H (1981) Chlorhexidine resistance in Escherichia coli isolated from clinical lesions. Zentralbl Bakteriol Mikrobiol Hyg A 251:177–184PubMed Nakahara H, Kozukue H (1981) Chlorhexidine resistance in Escherichia coli isolated from clinical lesions. Zentralbl Bakteriol Mikrobiol Hyg A 251:177–184PubMed
32.
go back to reference Nakahara H, Kozukue H (1982) Isolation of chlorhexidine-resistant Pseudomonas aeruginosa from clinical lesions. J Clin Microbiol 15:166–168PubMedCentralPubMed Nakahara H, Kozukue H (1982) Isolation of chlorhexidine-resistant Pseudomonas aeruginosa from clinical lesions. J Clin Microbiol 15:166–168PubMedCentralPubMed
33.
go back to reference Netuschil L, Weiger R, Preisler R, Brecx M (1995) Plaque bacteria counts and vitality during chlorhexidine, Meridol and Listerine mouthrinses. Eur J Oral Sci 103:355–361PubMedCrossRef Netuschil L, Weiger R, Preisler R, Brecx M (1995) Plaque bacteria counts and vitality during chlorhexidine, Meridol and Listerine mouthrinses. Eur J Oral Sci 103:355–361PubMedCrossRef
34.
go back to reference Nicoletti G, Boghossian V, Gurevitch F, Borland R, Morgenroth P (1993) The antimicrobial activity in vitro of chlorhexidine, a mixture of isothiazolinones ('Kathon' CG) and cetyl trimethyl ammonium bromide (CTAB). J Hosp Infect 23:87–111PubMedCrossRef Nicoletti G, Boghossian V, Gurevitch F, Borland R, Morgenroth P (1993) The antimicrobial activity in vitro of chlorhexidine, a mixture of isothiazolinones ('Kathon' CG) and cetyl trimethyl ammonium bromide (CTAB). J Hosp Infect 23:87–111PubMedCrossRef
35.
go back to reference Quirynen M, Mongardini C, Pauwels M, Bollen CM, Van Eldere J, van Steenberghe D (1999) One stage full- versus partial-mouth disinfection in the treatment of chronic adult or generalized early-onset periodontitis. II. Long-term impact on microbial load. J Periodontol 70:646–656PubMedCrossRef Quirynen M, Mongardini C, Pauwels M, Bollen CM, Van Eldere J, van Steenberghe D (1999) One stage full- versus partial-mouth disinfection in the treatment of chronic adult or generalized early-onset periodontitis. II. Long-term impact on microbial load. J Periodontol 70:646–656PubMedCrossRef
36.
go back to reference Rohrer N, Widmer AF, Waltimo T, Kulik EM, Weiger R, Filipuzzi-Jenny E, Walter C (2010) Antimicrobial efficacy of 3 oral antiseptics containing octenidine, polyhexamethylene biguanide, or Citroxx: can chlorhexidine be replaced? Infect Control Hosp Epidemiol 31:733–739PubMedCrossRef Rohrer N, Widmer AF, Waltimo T, Kulik EM, Weiger R, Filipuzzi-Jenny E, Walter C (2010) Antimicrobial efficacy of 3 oral antiseptics containing octenidine, polyhexamethylene biguanide, or Citroxx: can chlorhexidine be replaced? Infect Control Hosp Epidemiol 31:733–739PubMedCrossRef
37.
go back to reference Schürch E Jr, Lang NP (2004) Periodontal conditions in Switzerland at the end of the 20th century. Oral Health Prev Dent 2:359–368PubMed Schürch E Jr, Lang NP (2004) Periodontal conditions in Switzerland at the end of the 20th century. Oral Health Prev Dent 2:359–368PubMed
38.
go back to reference Socransky SS, Haffajee AD, Cugini MA, Smith C, Kent RL Jr (1998) Microbial complexes in subgingival plaque. J Clin Periodontol 25:134–144PubMedCrossRef Socransky SS, Haffajee AD, Cugini MA, Smith C, Kent RL Jr (1998) Microbial complexes in subgingival plaque. J Clin Periodontol 25:134–144PubMedCrossRef
39.
go back to reference Solmaz G, Korachi M (2012) Inhibition and disruption properties of chlorhexidine gluconate on single and multispecies oral biofilms. Jundishapur J Microbiol 6:61–66CrossRef Solmaz G, Korachi M (2012) Inhibition and disruption properties of chlorhexidine gluconate on single and multispecies oral biofilms. Jundishapur J Microbiol 6:61–66CrossRef
41.
go back to reference Stickler DJ (2002) Susceptibility of antibiotic-resistant Gram-negative bacteria to biocides: a perspective from the study of catheter biofilms. J Appl Microbiol 92:163S–170SPubMedCrossRef Stickler DJ (2002) Susceptibility of antibiotic-resistant Gram-negative bacteria to biocides: a perspective from the study of catheter biofilms. J Appl Microbiol 92:163S–170SPubMedCrossRef
42.
go back to reference Tambe SM, Sampath L, Modak SM (2001) In vitro evaluation of the risk of developing bacterial resistance to antiseptics and antibiotics used in medical devices. J Antimicrob Chemother 47:589–598PubMedCrossRef Tambe SM, Sampath L, Modak SM (2001) In vitro evaluation of the risk of developing bacterial resistance to antiseptics and antibiotics used in medical devices. J Antimicrob Chemother 47:589–598PubMedCrossRef
44.
go back to reference van Winkelhoff AJ, Herrera D, Oteo A, Sanz M (2005) Antimicrobial profiles of periodontal pathogens isolated from periodontitis patients in The Netherlands and Spain. J Clin Periodontol 32:893–898PubMedCrossRef van Winkelhoff AJ, Herrera D, Oteo A, Sanz M (2005) Antimicrobial profiles of periodontal pathogens isolated from periodontitis patients in The Netherlands and Spain. J Clin Periodontol 32:893–898PubMedCrossRef
45.
go back to reference Walter C, Zahlten J, Schmeck B, Schaudinn C, Hippenstiel S, Frisch E, Hocke AC, Pischon N, Kuramitsu HK, Bernimoulin JP, Suttorp N, Krull M (2004) Porphyromonas gingivalis strain-dependent activation of human endothelial cells. Infect Immun 72:5910–5918PubMedCentralPubMedCrossRef Walter C, Zahlten J, Schmeck B, Schaudinn C, Hippenstiel S, Frisch E, Hocke AC, Pischon N, Kuramitsu HK, Bernimoulin JP, Suttorp N, Krull M (2004) Porphyromonas gingivalis strain-dependent activation of human endothelial cells. Infect Immun 72:5910–5918PubMedCentralPubMedCrossRef
46.
go back to reference Walter C, Purucker P, Bernimoulin JP, Suttorp N, Meyer J, Weiger R (2005) Critical assessment of microbiological diagnostics in periodontal diseases with special focus on Porphyromonas gingivalis. Schweiz Monatsschr Zahnmed 115:415–424PubMed Walter C, Purucker P, Bernimoulin JP, Suttorp N, Meyer J, Weiger R (2005) Critical assessment of microbiological diagnostics in periodontal diseases with special focus on Porphyromonas gingivalis. Schweiz Monatsschr Zahnmed 115:415–424PubMed
47.
go back to reference Walter C, Weiger R (2006) Antibiotics as the only therapy of untreated chronic periodontitis: a critical commentary. J Clin Periodontol 33:938–939PubMedCrossRef Walter C, Weiger R (2006) Antibiotics as the only therapy of untreated chronic periodontitis: a critical commentary. J Clin Periodontol 33:938–939PubMedCrossRef
48.
go back to reference Walter C, Buset S, Thillainathan L, Weiger R, Zitzmann NU (2013) Evaluation of periodontal therapy in undergraduate courses of the University of Basle. A retrospective study. Schweiz Monatsschr Zahnmed 123:861–877PubMed Walter C, Buset S, Thillainathan L, Weiger R, Zitzmann NU (2013) Evaluation of periodontal therapy in undergraduate courses of the University of Basle. A retrospective study. Schweiz Monatsschr Zahnmed 123:861–877PubMed
49.
go back to reference Westbrook SD, Wiederhold NP, Vallor AC, Kotara S, Bernardo S, Lee SA, Kirkpatrick WR, Toro JJ, Freytes C, Patterson TF, Redding SW (2010) Loss of in vitro resistance in Candida glabrata following discontinuation of fluconazole prophylaxis in a hematopoietic stem cell transplantation patient. Med Mycol 48:557–560PubMedCentralPubMedCrossRef Westbrook SD, Wiederhold NP, Vallor AC, Kotara S, Bernardo S, Lee SA, Kirkpatrick WR, Toro JJ, Freytes C, Patterson TF, Redding SW (2010) Loss of in vitro resistance in Candida glabrata following discontinuation of fluconazole prophylaxis in a hematopoietic stem cell transplantation patient. Med Mycol 48:557–560PubMedCentralPubMedCrossRef
50.
go back to reference Zahlten J, Riep B, Nichols FC, Walter C, Schmeck B, Bernimoulin JP, Hippenstiel S (2007) Porphyromonas gingivalis dihydroceramides induce apoptosis in endothelial cells. J Dent Res 86:635–640PubMedCrossRef Zahlten J, Riep B, Nichols FC, Walter C, Schmeck B, Bernimoulin JP, Hippenstiel S (2007) Porphyromonas gingivalis dihydroceramides induce apoptosis in endothelial cells. J Dent Res 86:635–640PubMedCrossRef
51.
go back to reference Zhang TT, Tang SS, Fu LJ (2013) The effectiveness of different concentrations of chlorhexidine for prevention of ventilator-associated pneumonia: a meta-analysis. J Clin Nurs 23:1461–1475PubMedCrossRef Zhang TT, Tang SS, Fu LJ (2013) The effectiveness of different concentrations of chlorhexidine for prevention of ventilator-associated pneumonia: a meta-analysis. J Clin Nurs 23:1461–1475PubMedCrossRef
Metadata
Title
Development of resistance of mutans streptococci and Porphyromonas gingivalis to chlorhexidine digluconate and amine fluoride/stannous fluoride-containing mouthrinses, in vitro
Authors
Eva M. Kulik
Tuomas Waltimo
Roland Weiger
Irene Schweizer
Krystyna Lenkeit
Elisabeth Filipuzzi-Jenny
Clemens Walter
Publication date
01-07-2015
Publisher
Springer Berlin Heidelberg
Published in
Clinical Oral Investigations / Issue 6/2015
Print ISSN: 1432-6981
Electronic ISSN: 1436-3771
DOI
https://doi.org/10.1007/s00784-014-1379-y

Other articles of this Issue 6/2015

Clinical Oral Investigations 6/2015 Go to the issue