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Herrera D, van Winkelhoff AJ, Matesanz P, Lauwens K, Teughels W. Europe's contribution to the evaluation of the use of systemic antimicrobials in the treatment of periodontitis. Periodontol 2000 2023. [PMID: 37314038 DOI: 10.1111/prd.12492] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2023] [Revised: 05/03/2023] [Accepted: 05/04/2023] [Indexed: 06/15/2023]
Abstract
This narrative review celebrates Europe's contribution to the current knowledge on systemically administered antimicrobials in periodontal treatment. Periodontitis is the most frequent chronic noncommunicable human disease. It is caused by dysbiotic bacterial biofilms and is commonly treated with subgingival instrumentation. However, some sites/patients do not respond adequately, and its limitations and shortcomings have been recognized. This has led to the development of alternative or adjunctive therapies. One is the use of antimicrobials to target bacteria in subgingival biofilms in the periodontal pocket, which can be targeted directly through the pocket entrance with a locally delivered antibiotic or systemically by oral, intravenous, or intramuscular methods. Since the early 20th century, several studies on systemic antibiotics have been undertaken and published, especially between 1990 and 2010. Europe's latest contribution to this topic is the first European Federation of Periodontology, S3-level Clinical Practice Guideline, which incorporates recommendations related to the use of adjuncts to treat stage I-III periodontitis. Understanding the etiopathogenesis of periodontal diseases, specifically periodontitis, has influenced the use of systemic periodontal antibiotic therapy. Randomized clinical trials and systematic reviews with meta-analyses have demonstrated the clinical advantages of adjunctive systemic antimicrobials. However, current recommendations are restrictive due to concerns about antibiotic misuse and the increase in microbial antibiotic resistance. European researchers have contributed to the use of systemic antimicrobials in the treatment of periodontitis through clinical trials and by providing rational guidelines. Nowadays, European researchers are exploring alternatives and directing clinical practice by providing evidence-based guidelines to limit the use of systemic antimicrobials.
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Affiliation(s)
- David Herrera
- ETEP (Etiology and Therapy of Periodontal and Peri-Implant Diseases) Research Group, University Complutense, Madrid, Spain
| | - Arie Jan van Winkelhoff
- Center for Dentistry and Oral Hygiene, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Paula Matesanz
- ETEP (Etiology and Therapy of Periodontal and Peri-Implant Diseases) Research Group, University Complutense, Madrid, Spain
| | - Katalina Lauwens
- Department of Oral Health Sciences, KU Leuven & Dentistry, University Hospitals Leuven, Leuven, Belgium
| | - Wim Teughels
- Department of Oral Health Sciences, KU Leuven & Dentistry, University Hospitals Leuven, Leuven, Belgium
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Rams TE, Slots J. Antimicrobial Chemotherapy for Recalcitrant Severe Human Periodontitis. Antibiotics (Basel) 2023; 12:265. [PMID: 36830176 PMCID: PMC9951977 DOI: 10.3390/antibiotics12020265] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2022] [Revised: 01/20/2023] [Accepted: 01/25/2023] [Indexed: 01/31/2023] Open
Abstract
This study evaluated a combined systemic and topical anti-infective periodontal treatment of 35 adults who had experienced ongoing periodontal breakdown following conventional surgical periodontics. The prescribed anti-infective therapy, based on microbiological testing, consisted of a single course of metronidazole plus ciprofloxacin (23 patients), metronidazole plus amoxicillin/clavulanic acid (10 patients), and metronidazole plus ciprofloxacin followed by metronidazole plus amoxicillin/clavulanic acid (2 patients). In addition, the study patients received 0.1% povidone-iodine subgingival disinfection during non-surgical root debridement and daily patient administered oral irrigation with 0.1% sodium hypochlorite. At 1 and 5 years post-treatment, all study patients showed gains in clinical periodontal attachment with no further attachment loss, and significant decreases in pocket probing depth, bleeding on probing, and subgingival temperature. The greatest disease resolution occurred in patients who at baseline harbored predominantly major periodontal pathogens which post-antibiotics became non-detectable and substituted by non-periodontopathic viridans streptococci. The personalized and minimally invasive anti-infective treatment regimen described here controlled periodontitis disease activity and markedly improved the clinical and microbiological status of the refractory periodontitis patients.
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Affiliation(s)
- Thomas E. Rams
- Department of Periodontology and Oral Implantology, Temple University School of Dentistry, Philadelphia, PA 19140, USA
| | - Jørgen Slots
- Division of Periodontology and Diagnostic Sciences, University of Southern California School of Dentistry, Los Angeles, CA 90089, USA
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Faveri M, Retamal-Valdes B, Mestnik MJ, de Figueiredo LC, Barão VAR, Souza JGS, Duarte PM, Feres M. Microbiological effects of amoxicillin plus metronidazole in the treatment of young patients with Stages III and IV periodontitis: A secondary analysis from a 1-year double-blinded placebo-controlled randomized clinical trial. J Periodontol 2022; 94:498-508. [PMID: 35869939 DOI: 10.1002/jper.21-0171] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2022] [Revised: 07/09/2022] [Accepted: 07/11/2022] [Indexed: 01/31/2023]
Abstract
BACKGROUND Despite the body of evidence supporting the clinical benefits of metronidazole (MTZ) and amoxicillin (AMX) in the treatment of young patients with periodontitis, the microbiological outcomes of this antibiotic protocol have been less explored. This study evaluated the microbiological effects of adjunctive MTZ+AMX in the treatment of young patients with periodontitis. METHODS Subjects with periodontitis Stages III or IV and ≤30 years old were randomly allocated to receive scaling and root planing (SRP) with placebo (n = 15) or with MTZ (400 mg) and AMX (500 mg) three times a day for 14 days (n = 15). Nine subgingival biofilm samples per subject (three samples from each probing depth (PD) category: ≤3, 4-6, and ≥7 mm) were collected at baseline and 3-, 6-, and 12-months post-treatment and individually analyzed for 40 bacterial species by checkerboard DNA-DNA hybridization. RESULTS Thirty subjects (15/group) with mean ages 27.6 ± 3.5 (control) and 26.8 ± 3.9 (test) were included. At 12 months post-therapy, the antibiotic group harbored lower proportions of red complex (1.3%) than the placebo group (12.5%) (p < 0.05). SRP + MTZ+AMX was more effective than mechanical treatment in reducing levels/proportions of several pathogens and increasing proportions of Actinomyces species (p < 0.05). Levels/proportions of Aggregatibacter actinomycetemcomitans were only reduced in the antibiotic group (p < 0.05). This group also exhibited greater reduction in the number of sites with PD ≥5 mm and higher percentage of subjects reaching the clinical end point for treatment (≤4 sites with PD ≥5 mm) than the control group (p < 0.05). CONCLUSION SRP+MTZ+AMX allowed for establishing a long-term healthier subgingival biofilm community and periodontal clinical condition, than SRP only.
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Affiliation(s)
- Marcelo Faveri
- Department of Periodontology, Dental Research Division, Guarulhos University, Guarulhos, São Paulo, Brazil
| | - Belen Retamal-Valdes
- Department of Periodontology, Dental Research Division, Guarulhos University, Guarulhos, São Paulo, Brazil
| | - Maria Josefa Mestnik
- Department of Periodontology, Dental Research Division, Guarulhos University, Guarulhos, São Paulo, Brazil
| | | | - Valentim Adelino Ricardo Barão
- Department of Prosthodontics and Periodontology, Piracicaba Dental School, University of Campinas (UNICAMP), Piracicaba, Brazil
| | - João Gabriel Silva Souza
- Department of Periodontology, Dental Research Division, Guarulhos University, Guarulhos, São Paulo, Brazil.,Dental Science School (Faculdade de Ciências Odontológicas-FCO), Montes, Claros, Brazil
| | - Poliana Mendes Duarte
- Department of Periodontology, Dental Research Division, Guarulhos University, Guarulhos, São Paulo, Brazil.,Department of Periodontology, University of Florida College of Dentistry, Gainesville, Florida, USA
| | - Magda Feres
- Department of Periodontology, Dental Research Division, Guarulhos University, Guarulhos, São Paulo, Brazil.,The Forsyth Institute, Cambridge, Massachusetts, USA
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Dabija‐Wolter G, Al‐Zubaydi SS, Mohammed MMA, Bakken V, Bolstad AI. The effect of metronidazole plus amoxicillin or metronidazole plus penicillin V on periodontal pathogens in an in vitro biofilm model. Clin Exp Dent Res 2018; 4:6-12. [PMID: 29744209 PMCID: PMC5813892 DOI: 10.1002/cre2.96] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2017] [Revised: 11/16/2017] [Accepted: 11/20/2017] [Indexed: 01/12/2023] Open
Abstract
A combination of metronidazole (MET) and amoxicillin (AMX) is commonly used as adjunct to mechanical therapy of periodontal disease. The use of broad spectrum antibiotics such as AMX may contribute to development of antibiotic resistance. The aim was to evaluate the in vitro effect of replacing AMX with penicillin V (PV) in combination with MET on a biofilm model. A biofilm model consisting of Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, and Fusobacterium nucleatum was developed. The biofilms were exposed to AMX + MET and PV + MET in two different concentrations. Bacterial viability in biofilms following antibiotic exposure was assessed by viable counts and by confocal microscopy. No live colonies of P. gingivalis nor F. nucleatum were retrieved from biofilms exposed to AMX + MET or PV + MET. The amount of A. actinomycetemcomitans was 4-5 logs reduced following antibiotic treatment; no statistical significance was achieved between AMX + MET or PV + MET treated biofilms. Replacement of AMX with PV at the same concentration, in combination with MET, resulted in similar effect on bacterial viability in this in vitro model. The option of using PV + MET instead of AMX + MET deserves further investigation, as this may contribute to reduce the risk of antibiotic resistance development.
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Affiliation(s)
- Gabriela Dabija‐Wolter
- Department of Clinical Dentistry, Faculty of MedicineUniversity of BergenNorway
- Department of Clinical Science, Faculty of MedicineUniversity of BergenNorway
| | | | | | - Vidar Bakken
- Department of Clinical Science, Faculty of MedicineUniversity of BergenNorway
| | - Anne Isine Bolstad
- Department of Clinical Dentistry, Faculty of MedicineUniversity of BergenNorway
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Mombelli A, Almaghlouth A, Cionca N, Cancela J, Courvoisier DS, Giannopoulou C. Microbiologic Response to Periodontal Therapy and Multivariable Prediction of Clinical Outcome. J Periodontol 2017; 88:1253-1262. [DOI: 10.1902/jop.2017.170286] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Affiliation(s)
- Andrea Mombelli
- Division of Periodontology, University of Geneva School of Dental Medicine, Geneva, Switzerland
| | - Adnan Almaghlouth
- Currently, Department of Dentistry, King Fahd Medical City, Riyadh, Saudi Arabia; previously, Division of Periodontology, University of Geneva School of Dental Medicine
| | - Norbert Cionca
- Division of Periodontology, University of Geneva School of Dental Medicine, Geneva, Switzerland
| | - José Cancela
- Division of Periodontology, University of Geneva School of Dental Medicine, Geneva, Switzerland
| | - Delphine S. Courvoisier
- Division of Rheumatology, Department of Medical Specialties, University Hospitals of Geneva, Geneva, Switzerland
| | - Catherine Giannopoulou
- Division of Periodontology, University of Geneva School of Dental Medicine, Geneva, Switzerland
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Mombelli A. Microbial colonization of the periodontal pocket and its significance for periodontal therapy. Periodontol 2000 2017; 76:85-96. [PMID: 29193304 DOI: 10.1111/prd.12147] [Citation(s) in RCA: 220] [Impact Index Per Article: 27.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/14/2016] [Indexed: 12/11/2022]
Abstract
The aim of this paper was to evaluate strategies for periodontal therapy from the perspective of periodontal disease being a consequence of microbial colonization of the periodontal pocket environment. In classic bacterial infections the diversity of the microbiota decreases as the disease develops. In most cases of periodontitis, however, the diversity of the flora increases. Most incriminating bacteria are thought to harm tissues significantly only if present in high numbers over prolonged periods of time. Clinical trials have repeatedly demonstrated that scaling and root planing, a procedure that aims to remove subgingival bacterial deposits by scraping on the tooth surface within the periodontal pocket, is effective. At present, for the therapy of any form of periodontal disease, there exists no protocol with proven superiority, in terms of efficiency or effectiveness, over scaling and root planing plus systemic amoxicillin and metronidazole. Some exponents advocate rationing these drugs for patients with a specific microbial profile. However, the evidence for any benefit of bacteriology-assisted clinical protocols is unsatisfactory. Treated sites are subject to recolonization with a microbiota similar to that present before therapy. The degree and speed of recolonization depends on the treatment protocol, the distribution patterns of periodontal microorganisms elsewhere in the oral cavity and the quality of the patient's oral hygiene. To limit the use of antibiotics and to avoid accumulation of harmful effects by repeated therapy, further efforts must be made to optimize procedures addressing the microbial colonization and recolonization of the periodontal pocket.
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7
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Feres M, Figueiredo LC, Soares GMS, Faveri M. Systemic antibiotics in the treatment of periodontitis. Periodontol 2000 2017; 67:131-86. [PMID: 25494600 DOI: 10.1111/prd.12075] [Citation(s) in RCA: 159] [Impact Index Per Article: 19.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/22/2014] [Indexed: 12/12/2022]
Abstract
Despite the fact that several clinical studies have shown additional benefits when certain systemic antibiotics are used as adjuncts to periodontal treatment, clear guidelines for the use of these agents in the clinical practice are not yet available. Basic questions concerning the use of systemic antibiotics to treat periodontitis remain unanswered, such as: which drug(s) should be used; which patients would most benefit from treatment; which are the most effective protocols (i.e. doses and durations); and in which phase of the mechanical therapy should the drug(s) be administered? Although not all of those questions have been directly addressed by controlled randomized clinical trials, recent concepts related to the ecology of periodontal diseases, as well as the major advances in laboratory and clinical research methods that have occurred in the past decade, have significantly broadened our knowledge in this field. This article endeavored to provide a 'state of the art' overview on the use of systemic antibiotics in the treatment of periodontitis, based on the most recent literature on the topic as well as on a compilation of data from studies conducted at the Center of Clinical Trials at Guarulhos University (São Paulo, Brazil) from 2002 to 2012.
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Krishna R, De Stefano JA. Ultrasonic vs. hand instrumentation in periodontal therapy: clinical outcomes. Periodontol 2000 2016; 71:113-27. [DOI: 10.1111/prd.12119] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/23/2015] [Indexed: 11/29/2022]
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Barca E, Cifcibasi E, Cintan S. Adjunctive use of antibiotics in periodontal therapy. J Istanb Univ Fac Dent 2015; 49:55-62. [PMID: 28955547 PMCID: PMC5573506 DOI: 10.17096/jiufd.90144] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2014] [Accepted: 03/13/2015] [Indexed: 11/24/2022] Open
Abstract
Periodontal diseases are infectious diseases with a
mixed microbial aetiology and marked inflammatory
response leading to destruction of underlying tissue.
Periodontal therapy aims to eliminate pathogens
associated with the disease and attain periodontal
health. Periodontitis is generally treated by nonsurgical
mechanical debridement and regular
periodontal maintenance care. Periodontal surgery
may be indicated for some patients to improve access
to the root surface; however, mechanical debridement
alone may not be helpful in all cases. In such cases,
adjunctive systemic antibiotic therapy remains the
treatment of choice. It can reach microorganisms
at the base of the deep periodontal pockets and
furcation areas via serum, and also affects organisms
residing within gingival epithelium and connective
tissue. This review aims to provide an update on
clinical issues regarding when and how to prescribe
systemic antibiotics in periodontal therapy. The
points discussed are the mode of antibiotic action,
susceptible periodontal pathogens, antibiotic dosage,
antibiotic use in treatment of periodontal disease, and
mechanism of bacterial resistance to each antibiotic.
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Affiliation(s)
- Ece Barca
- Department of Periodontology, Faculty of Dentistry, Istanbul University, Turkey
| | - Emine Cifcibasi
- Department of Periodontology, Faculty of Dentistry, Istanbul University, Turkey
| | - Serdar Cintan
- Department of Periodontology, Faculty of Dentistry, Istanbul University, Turkey
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10
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Bhansali RS. Non-surgical periodontal therapy: An update on current evidence. World J Stomatol 2014; 3:38-51. [DOI: 10.5321/wjs.v3.i4.38] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2014] [Revised: 11/06/2014] [Accepted: 11/19/2014] [Indexed: 02/06/2023] Open
Abstract
Periodontal disease is an inflammatory condition that involves a complex interaction between pathogenic bacteria, environmental and acquired factors and host related factors. Till recently periodontal treatment was directed primarily towards reduction of bacterial load by subgingival debridement of root surfaces and modification of environmental risk factors. The current paradigm of periodontal disease stresses greater role of host-mediated inflammatory response in tissue destruction characteristic of periodontal disease. Various therapeutic modalities have been developed adjuvant to mechanical periodontal therapy. The use of laser and photodynamic therapy show great promise but their effectiveness has still not been conclusively proven. Chemotherapeutic agents, either systemic and local antimicrobials or host modulating drugs, played pivotal role in better and more predictable management of periodontal disease. The present review focuses on the best available evidence, for the current management of the chronic periodontal patients, gathered from systematic reviews and meta-analysis of mechanical non surgical periodontal therapy (NSPT) (subgingival debridement, laser therapy and photodynamic therapy) and the adjunctive chemotherapeutic approaches such as systematic and local antibiotics and antiseptics, subgingival pocket irrigation and host modulation therapies. The review also attempts to briefly introduce future developments in some of these modalities. At the end, the review summarizes the analysis of the current evidence that suggests that thorough subgingival debridement remains the mainstay of NSPT and that adjunct use of chemotherapeutic agents may offer better management of clinical parameters in periodontitis patients.
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11
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Tomita S, Kasai S, Ihara Y, Imamura K, Kita D, Ota K, Kinumatsu T, Nakagawa T, Saito A. Effects of systemic administration of sitafloxacin on subgingival microflora and antimicrobial susceptibility profile in acute periodontal lesions. Microb Pathog 2014; 71-72:1-7. [PMID: 24747615 DOI: 10.1016/j.micpath.2014.04.003] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2014] [Revised: 04/07/2014] [Accepted: 04/08/2014] [Indexed: 01/08/2023]
Abstract
The aim of this study was to assess the effect(s) of systemic administration of sitafloxacin on subgingival microbial profiles of acute periodontal lesions. Antimicrobial susceptibility of clinical isolates was also investigated. Patients with acute phases of chronic periodontitis were subjected to clinical examination and microbiological assessment of their subgingival plaque samples by culture technique. Sitafloxacin was then administered (100 mg/day for 5 days) systemically. The clinical and microbiological examinations were repeated 6-8 days after administration. Susceptibilities of clinical isolates to various antimicrobials were determined using the broth and agar dilution methods. From the sampled sites in 30 participants, a total of 355 clinical isolates (34 different bacterial species) were isolated and identified. Parvimonas micra, Prevotella intermedia and Streptococcus mitis were the most prevalent cultivable bacteria in acute sites. Systemic administration of sitafloxacin yielded a significant improvement in clinical and microbiological parameters. Among the antimicrobials tested, sitafloxacin was the most potent against the clinical isolates with an MIC90 of 0.12 μg/ml at baseline. After administration, most clinical isolates were still highly susceptible to sitafloxacin although some increase in MICs was observed. The results suggest that systemic administration of sitafloxacin is effective against subgingival bacteria isolated from acute periodontal lesions.
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Affiliation(s)
- Sachiyo Tomita
- Department of Periodontology, Tokyo Dental College, 2-9-18 Misaki-cho, Chiyoda-ku, Tokyo 101-0061, Japan
| | - Shunsuke Kasai
- Department of Dentistry and Oral Surgery, School of Medicine, Keio University, 35 Shinanomachi, Sinnjuku-ku, Tokyo 160-8582, Japan
| | - Yuichiro Ihara
- Department of Dentistry and Oral Surgery, School of Medicine, Keio University, 35 Shinanomachi, Sinnjuku-ku, Tokyo 160-8582, Japan
| | - Kentaro Imamura
- Department of Periodontology, Tokyo Dental College, 2-9-18 Misaki-cho, Chiyoda-ku, Tokyo 101-0061, Japan
| | - Daichi Kita
- Department of Periodontology, Tokyo Dental College, 2-9-18 Misaki-cho, Chiyoda-ku, Tokyo 101-0061, Japan
| | - Koki Ota
- Department of Periodontology, Tokyo Dental College, 2-9-18 Misaki-cho, Chiyoda-ku, Tokyo 101-0061, Japan; Oral Health Science Center, Tokyo Dental College, 2-9-18 Misaki-cho, Chiyoda-ku, Tokyo 101-0061, Japan
| | - Takashi Kinumatsu
- Department of Periodontology, Tokyo Dental College, 2-9-18 Misaki-cho, Chiyoda-ku, Tokyo 101-0061, Japan
| | - Taneaki Nakagawa
- Department of Dentistry and Oral Surgery, School of Medicine, Keio University, 35 Shinanomachi, Sinnjuku-ku, Tokyo 160-8582, Japan
| | - Atsushi Saito
- Department of Periodontology, Tokyo Dental College, 2-9-18 Misaki-cho, Chiyoda-ku, Tokyo 101-0061, Japan; Oral Health Science Center, Tokyo Dental College, 2-9-18 Misaki-cho, Chiyoda-ku, Tokyo 101-0061, Japan.
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Kulik Kunz EM, Lenkeit K, Waltimo T, Weiger R, Walter C. Combinatorial effects of amoxicillin and metronidazole on selected periodontal bacteria and whole plaque samples. Arch Oral Biol 2014; 59:608-15. [PMID: 24727003 DOI: 10.1016/j.archoralbio.2014.03.007] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2013] [Revised: 02/13/2014] [Accepted: 03/18/2014] [Indexed: 02/02/2023]
Abstract
OBJECTIVE The aim of the present study was to analyze in vitro the combinatorial effects of the antibiotic combination of amoxicillin plus metronidazole on subgingival bacterial isolates. DESIGN Aggregatibacter (Actinobacillus) actinomycetemcomitans, Prevotella intermedia/nigrescens, Fusobacterium nucleatum and Eikenella corrodens from our strain collection and subgingival bacteria isolated from patients with periodontitis were tested for their susceptibility to amoxicillin and metronidazole using the Etest. The fractional inhibitory concentration index (FICI), which is commonly used to describe drug interactions, was calculated. RESULTS Synergy, i.e. FICI values ≤ 0.5, between amoxicillin and metronidazole was shown for two A. actinomycetemcomitans (FICI: 0.3), two F. nucleatum (FICI: 0.3 and 0.5, respectively) and one E. corrodens (FICI: 0.4) isolates. Indifference, i.e. FIC indices of >0.5 but ≤4, occurred for other isolates and the 14 P. intermedia/nigrescens strains tested. Microorganisms resistant to either amoxicillin or metronidazole were detected in all samples by Etest. CONCLUSION Combinatorial effects occur between amoxicillin and metronidazole on some strains of A. actinomycetemcomitans, F. nucleatum and E. corrodens. Synergy was shown for a few strains only.
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Affiliation(s)
- Eva M Kulik Kunz
- Department of Preventive Dentistry and Oral Microbiology, School of Dental Medicine, University of Basel, Switzerland.
| | - Krystyna Lenkeit
- Department of Periodontology, Endodontology and Cariology, School of Dentistry, University of Basel, Switzerland
| | - Tuomas Waltimo
- Department of Preventive Dentistry and Oral Microbiology, School of Dental Medicine, University of Basel, Switzerland
| | - Roland Weiger
- Department of Periodontology, Endodontology and Cariology, School of Dentistry, University of Basel, Switzerland
| | - Clemens Walter
- Department of Periodontology, Endodontology and Cariology, School of Dentistry, University of Basel, Switzerland
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Mombelli A, Cionca N, Almaghlouth A, Décaillet F, Courvoisier DS, Giannopoulou C. Are There Specific Benefits of Amoxicillin Plus Metronidazole inAggregatibacter actinomycetemcomitans-Associated Periodontitis? Double-Masked, Randomized Clinical Trial of Efficacy and Safety. J Periodontol 2013; 84:715-24. [DOI: 10.1902/jop.2012.120281] [Citation(s) in RCA: 43] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
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Mestnik MJ, Feres M, Figueiredo LC, Soares G, Teles RP, Fermiano D, Duarte PM, Faveri M. The effects of adjunctive metronidazole plus amoxicillin in the treatment of generalized aggressive periodontitis: a 1-year double-blinded, placebo-controlled, randomized clinical trial. J Clin Periodontol 2012; 39:955-61. [DOI: 10.1111/j.1600-051x.2012.01932.x] [Citation(s) in RCA: 67] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/19/2012] [Indexed: 11/28/2022]
Affiliation(s)
- Maria J. Mestnik
- Department of Periodontology; Dental Research Division; Guarulhos University; Guarulhos; São Paulo; Brazil
| | - Magda Feres
- Department of Periodontology; Dental Research Division; Guarulhos University; Guarulhos; São Paulo; Brazil
| | - Luciene C. Figueiredo
- Department of Periodontology; Dental Research Division; Guarulhos University; Guarulhos; São Paulo; Brazil
| | - Geisla Soares
- Department of Periodontology; Dental Research Division; Guarulhos University; Guarulhos; São Paulo; Brazil
| | - Ricardo P. Teles
- Department of Periodontology; The Forsyth Institute; Cambridge; MA; USA
| | - Daiane Fermiano
- Department of Periodontology; Dental Research Division; Guarulhos University; Guarulhos; São Paulo; Brazil
| | - Poliana M. Duarte
- Department of Periodontology; Dental Research Division; Guarulhos University; Guarulhos; São Paulo; Brazil
| | - Marcelo Faveri
- Department of Periodontology; Dental Research Division; Guarulhos University; Guarulhos; São Paulo; Brazil
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15
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Fernandez y Mostajo M, Zaura E, Crielaard W, Beertsen W. Does routine analysis of subgingival microbiota in periodontitis contribute to patient benefit? Eur J Oral Sci 2011; 119:259-64. [PMID: 21726285 DOI: 10.1111/j.1600-0722.2011.00828.x] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
In clinical periodontology it is common practice to sample subgingival plaque from periodontitis patients and to search for the presence of alleged periodontal pathogens using routine laboratory techniques such as culture, DNA-DNA hybridization or real-time PCR. Usually, special attention is given to the recognition of 'red complex' microorganisms and to Aggregatibacter actinomycetemcomitans. Recently, molecular open-ended techniques have been introduced which are distinct from the more 'classical' approaches in that they do not preselect for certain species. In this study, we investigated to what extent the outcome of these techniques has changed our insight into the composition of the subgingival microbiota and whether this has consequences on clinical decision making. The open-ended approaches showed that the composition of subgingival plaque is much more complex than previously thought. Next to the 'classical' putative periodontal pathogens, several non-culturable and fastidious species are now recognized as being associated with periodontitis, thus enlarging the group of suspected periodontal pathogens. We conclude that routine analyses of subgingival plaque in the clinic are not necessarily of benefit to the patient.
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Mombelli A, Cionca N, Almaghlouth A. Does adjunctive antimicrobial therapy reduce the perceived need for periodontal surgery? Periodontol 2000 2010; 55:205-16. [DOI: 10.1111/j.1600-0757.2010.00356.x] [Citation(s) in RCA: 58] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
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Mestnik MJ, Feres M, Figueiredo LC, Duarte PM, Lira EAG, Faveri M. Short-term benefits of the adjunctive use of metronidazole plus amoxicillin in the microbial profile and in the clinical parameters of subjects with generalized aggressive periodontitis. J Clin Periodontol 2010; 37:353-65. [PMID: 20447259 DOI: 10.1111/j.1600-051x.2010.01538.x] [Citation(s) in RCA: 127] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
AIM The aim of this study was to evaluate the clinical and microbiological effects of scaling and root planing (SRP) alone or combined with metronidazole (MTZ) and amoxicillin (AMX) in the treatment of subjects with generalized aggressive periodontitis (GAgP). MATERIALS AND METHODS A double-blind, placebo-controlled, randomized clinical trial was conducted in 30 subjects receiving SRP alone or combined with MTZ (400 mg 3 x per day) and AMX (500 mg 3 x per day) for 14 days. Clinical and microbiological examinations were performed at baseline and 3 months post-SRP. Nine subgingival plaque samples per subject were analysed using checkerboard DNA-DNA hybridization. RESULTS Subjects receiving MTZ and AMX showed the greatest improvements in the mean full-mouth probing depth and clinical attachment level and at initially intermediate and deep sites. The most beneficial changes in the microbial profile were also observed in the MTZ+AMX group, which showed the lowest proportions of the red complex as well as a significant decrease in the proportions of the orange complex after treatment. The antibiotic therapy also reduced the levels of Aggregatibacter actinomycetemcomitans at initially deep sites. CONCLUSION Subjects with GAgP significantly benefit from the adjunctive use of MTZ and AMX. The short-term advantages are observed in the clinical and microbiological parameters.
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Affiliation(s)
- Maria Josefa Mestnik
- Department of Periodontology, Dental Research Division, Guarulhos University, Guarulhos, São Paulo, Brazil
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Ardila CM, Granada MI, Guzmán IC. Antibiotic resistance of subgingival species in chronic periodontitis patients. J Periodontal Res 2010; 45:557-563. [PMID: 20546113 DOI: 10.1111/j.1600-0765.2010.01274.x] [Citation(s) in RCA: 40] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
BACKGROUND AND OBJECTIVE The increasing rate of resistance of microorganisms to penicillin and other antibiotics has generated concern among health authorities in Latin America. The present investigation determined the in vitro susceptibility of Porphyromonas gingivalis, Fusobacterium nucleatum, black-pigmented Prevotella spp. and Aggregatibacter actinomycetemcomitans to metronidazole, amoxicillin, amoxicillin/clavulanic acid, clindamycin and moxifloxacin in patients with chronic periodontitis. MATERIAL AND METHODS Subgingival plaque samples from patients with periodontitis were collected and cultured on selective and nonselective culture media. The antimicrobial susceptibility of periodontopathogenic isolates was studied in chronic periodontitis patients in Colombia. Metronidazole, amoxicillin, amoxicillin/clavulanic acid, clindamycin and moxifloxacin were tested on all bacterial isolates and the percentage of resistant strains was calculated. RESULTS Of the 150 bacteria identified, 51 were P. gingivalis, 45 were black-pigmented Prevotella spp., 36 were F. nucleatum and 18 were A. actinomycetemcomitans. All the isolates were sensitive to amoxicillin/clavulanic acid and to moxifloxacin, but exhibited variable susceptibility patterns to the other antimicrobial agents tested. CONCLUSION The results of the present study suggest that periodontal microorganisms in patients with chronic periodontitis can be resistant to the antimicrobial agents commonly used in anti-infective periodontal therapy. We suggest that the indiscriminate use of antimicrobials could result in the appearance of more highly antibiotic-resistant strains of bacteria associated with periodontal diseases in our population compared with the populations of other countries.
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Affiliation(s)
- C M Ardila
- Epidemiology Group, University of Antioquia, Medellín, Colombia.
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Cionca N, Giannopoulou C, Ugolotti G, Mombelli A. Microbiologic Testing and Outcomes of Full-Mouth Scaling and Root Planing With or Without Amoxicillin/Metronidazole in Chronic Periodontitis. J Periodontol 2010; 81:15-23. [DOI: 10.1902/jop.2009.090390] [Citation(s) in RCA: 72] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
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Cionca N, Giannopoulou C, Ugolotti G, Mombelli A. Amoxicillin and Metronidazole as an Adjunct to Full-Mouth Scaling and Root Planing of Chronic Periodontitis. J Periodontol 2009; 80:364-71. [DOI: 10.1902/jop.2009.080540] [Citation(s) in RCA: 126] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
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Perfiles Antimicrobianos de Bacterias Subgingivales en Pacientes con Periodontitis en Colombia. ACTA ACUST UNITED AC 2008. [DOI: 10.1016/s0718-5391(08)70010-7] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
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Rawal SY, Walters JD. Effect of biologic mediators on ciprofloxacin accumulation by gingival fibroblasts. J Periodontol 2005; 76:2254-9. [PMID: 16332237 PMCID: PMC2248705 DOI: 10.1902/jop.2005.76.12.2254] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
BACKGROUND Human gingival fibroblasts actively accumulate fluoroquinolone antimicrobials. Because fibroblasts are prevalent in gingiva, they may help sustain therapeutic fluoroquinolone levels at that site. The purpose of this study was to determine whether mediators associated with infection or injury can enhance ciprofloxacin accumulation by gingival fibroblasts. METHODS Quiescent fibroblast monolayers were treated for 1, 6, or 24 hours with several concentrations of tumor necrosis factor (TNF)-alpha, transforming growth factor (TGF)-beta1, platelet-derived growth factor (PDGF)-BB, fibroblast growth factor (FGF)-2, or insulin-like growth factor (IGF)-1. Transport was assayed by measuring cell-associated fluoroquinolone fluorescence. RESULTS All mediators significantly enhanced ciprofloxacin transport in a dose dependent manner (P < 0.05; ANOVA). Except for TNF, this enhancement was associated with a decrease in the Km of ciprofloxacin transport. Maximal enhancement was observed with 10 ng/ml PDGF or FGF and 30 ng/ml TNF, TGF, or IGF. Brief (1 hour) treatment with TNF or FGF upregulated ciprofloxacin accumulation by a maximum of 13% to 14%, whereas TGF, PDGF, and IGF enhanced this process by 19% to 24%. All of the mediators enhanced ciprofloxacin accumulation by a maximum of 19% to 24% after 6 hours and 30% to 38% after 24 hours. The accumulation of other fluoroquinolones (e.g., gatifloxacin) was also slightly enhanced. CONCLUSIONS Gingival fibroblasts treated with cytokines or growth factors accumulate significantly more ciprofloxacin than untreated controls. This provides a mechanism by which ciprofloxacin could be preferentially distributed to gingival wound or inflammatory sites, yielding local therapeutic levels that are more sustained than in serum.
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Affiliation(s)
- Swati Y. Rawal
- Section of Periodontology, College of Dentistry, The Ohio State University Health Sciences Center, Columbus, OH
| | - John D. Walters
- Section of Periodontology, College of Dentistry, The Ohio State University Health Sciences Center, Columbus, OH
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Walters JD, Nakkula RJ, Maney P. Modulation of gingival fibroblast minocycline accumulation by biological mediators. J Dent Res 2005; 84:320-3. [PMID: 15790736 PMCID: PMC2241671 DOI: 10.1177/154405910508400405] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
Gingival fibroblasts actively accumulate tetracyclines, thereby enhancing their redistribution from blood to gingiva. Since growth factors and pro-inflammatory cytokines regulate many fibroblast activities, they could potentially enhance fibroblast minocycline accumulation. To test this hypothesis, we treated gingival fibroblast monolayers for 1 or 6 hours with platelet-derived growth factor-BB (PDGF), fibroblast growth factor-2 (FGF), transforming growth factor-beta1 (TGF), or tumor necrosis factor-alpha (TNF). Minocycline uptake was assayed at 37 degrees by a fluorescence method. All 4 factors significantly enhanced minocycline uptake (P < or = 0.008, ANOVA), primarily by increasing the affinity of transport. Treatment for 6 hours with 10 ng/mL FGF, PDGF, TGF, or TNF enhanced fibroblast minocycline uptake by 19% to 25%. Phorbol myristate acetate enhanced fibroblast minocycline uptake by 28%, suggesting that protein kinase C plays a role in up-regulating transport. These effects on transport provide a mechanism by which systemic tetracyclines could be preferentially distributed to gingival wound or inflammatory sites.
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Affiliation(s)
- J D Walters
- Section of Periodontology, College of Dentistry, The Ohio State University Health Sciences Center, PO Box 182357, Columbus, OH 43218-2357, USA.
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Guerrero A, Griffiths GS, Nibali L, Suvan J, Moles DR, Laurell L, Tonetti MS. Adjunctive benefits of systemic amoxicillin and metronidazole in non-surgical treatment of generalized aggressive periodontitis: a randomized placebo-controlled clinical trial. J Clin Periodontol 2005; 32:1096-107. [PMID: 16174275 DOI: 10.1111/j.1600-051x.2005.00814.x] [Citation(s) in RCA: 207] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
BACKGROUND The objective of this study was to assess the adjunctive clinical effect of the administration of systemic amoxicillin and metronidazole in the non-surgical treatment of generalized aggressive periodontitis (GAP). METHODS Forty-one systemically healthy subjects with GAP were included in this 6-month double-blind, placebo-controlled, randomized clinical trial. Patients received a course of full-mouth non-surgical periodontal treatment delivered over a 24 h period using machine-driven and hand instruments. Test subjects received an adjunctive course of systemic antibiotic consisting of 500 mg amoxicillin and 500 mg metronidazole three times a day for 7 days. Clinical parameters were collected at baseline, and at 2 and 6 months post-treatment. RESULTS In both the test and the placebo groups, all clinical parameters improved at 2 and 6 months. In deep pockets (> or =7 mm), the test treatment resulted in an additional 1.4 mm (95% confidence interval 0.8, 2.0 mm) in full-mouth probing pocket depth (PPD) reduction and 1 mm (0.7, 1.3 mm) of life cumulative attachment loss (LCAL) gain at 6 months. In moderate pockets (4-6 mm), the adjunctive benefit was smaller in magnitude: PPD reduction was 0.4 mm (0.1, 0.7 mm) and LCAL gain was 0.5 mm (0.2, 0.8 mm). In addition, the 6-month data showed LCAL gains > or =2 mm at 25% of sites in test patients compared with 16% in placebo (p=0.028). Similarly, PPD reductions of 2 mm or more were observed in 30% of sites in test and 21% of sites in placebo patients. Seventy-four percent of pockets with PPD > or =5 mm at baseline were 4 mm or shallower at 6 months in the test group. This compared with 54% in the placebo group (p=0.008). Disease progression at 6 months was observed at 1.5% of test and 3.3% of sites in test and placebo, respectively (p=0.072). CONCLUSIONS These data indicate that a 7-day adjunctive course of systemic metronidazole and amoxicillin significantly improved the short-term clinical outcomes of full-mouth non-surgical periodontal debridement in subjects with GAP.
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Affiliation(s)
- Adrian Guerrero
- Department of Periodontology and Eastman Clinical Investigation Centre, Eastman Dental Institute and Hospital, University College London, London, UK
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van Winkelhoff AJ, Herrera D, Oteo A, Sanz M. Antimicrobial profiles of periodontal pathogens isolated from periodontitis patients in the Netherlands and Spain. J Clin Periodontol 2005; 32:893-8. [PMID: 15998275 DOI: 10.1111/j.1600-051x.2005.00782.x] [Citation(s) in RCA: 138] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
BACKGROUND AND AIM Antimicrobial resistance of periodontal pathogens towards currently used antibiotics in periodontics has been investigated in a previous study. Microbial resistance in the periodontal microflora was more frequently observed in Spanish patients in comparison with Dutch patients. The aim of the present study was to compare antimicrobial susceptibility profiles of five periodontal bacteria isolated from periodontitis patients in Spain and in The Netherlands. MATERIAL AND METHODS Subgingival plaque samples from adult patients with periodontitis were collected and cultured on selective and non-selective plates. Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, Prevotella intermedia, Fusobacterium nucleatum and Micromonas micros were isolated and used for minimal inhibitory concentration tests using the Epsilometer (E-test) technique. Eight different antibiotics were tested on all bacterial isolates. MIC50 and MIC90 values for each antibiotic and each species were determined and the percentage of resistant strains was calculated. RESULTS Significantly higher MIC values were noted in Spanish strains of F. nucleatum for penicillin, ciprofloxacin, of P. intermedia for penicillin, amoxicillin and tetracycline, of M. micros for tetracycline, amoxicillin and azithromycin, and of P. gingivalis for tetracycline and ciprofloxacin. Based on breakpoint concentrations, a higher number of resistant strains in Spain were found in F. nucleatum for penicillin, amoxicillin and metronidazole, in Prevotella intermedia for tetracycline and amoxicillin, and in A. actinomycetemcomitans for amoxicillin and azithromycin. Resistance of P. gingivalis strains was not observed for any of the antibiotics tested both in Spain and The Netherlands. CONCLUSIONS Differences exist in the susceptibility profiles of periodontal pathogens isolated from periodontitis patients in Spain and in The Netherlands. This implicates that antibiotic susceptibility testing is necessary to determine efficacy of antimicrobial agents. Also, clinical studies with antibiotics should take these differences into account. The information from the present study indicates that it may not be possible to develop uniform protocols for usage of antibiotics in the treatment of severe periodontitis in the European Union.
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Affiliation(s)
- A J van Winkelhoff
- Department of Oral Microbiology, Academic Centre for Dentistry Amsterdam, Amsterdam, The Netherlands.
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Abstract
This position paper addresses the role of systemic antibiotics in the treatment of periodontal disease. Topical antibiotic therapy is not discussed here. The paper was prepared by the Research, Science and Therapy Committee of the American Academy of Periodontology. The document consists of three sections: 1) concept of antibiotic periodontal therapy; 2) efficacy of antibiotic periodontal therapy; and 3) practical aspects of antibiotic periodontal therapy. The conclusions drawn in this paper represent the position of the American Academy of Periodontology and are intended for the information of the dental profession.
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Lavda M, Clausnitzer CE, Walters JD. Distribution of systemic ciprofloxacin and doxycycline to gingiva and gingival crevicular fluid. J Periodontol 2005; 75:1663-7. [PMID: 15732869 PMCID: PMC2254337 DOI: 10.1902/jop.2004.75.12.1663] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
BACKGROUND Systemic fluoroquinolones and tetracyclines reach steady-state levels in gingival crevicular fluid (GCF) that are several-fold higher than their levels in serum. The mechanism by which this occurs is unclear, but gingival fibroblasts are known to accumulate these agents. Uptake by fibroblasts could enhance their distribution to gingiva. To test this hypothesis, steady-state levels of these agents were assayed in serum, gingival connective tissue (GCT), and GCF. METHODS Healthy subjects who needed resective periodontal surgery participated in the study. Approximately 78 hours prior to the surgical appointment, each subject began a 3-day regimen of ciprofloxacin or doxycycline. At the surgical appointment (scheduled approximately 6 hours after the last dose), samples of blood and GCT were collected. GCF samples were collected on paper strips and measured with an electronic device. Samples were extracted and analyzed by high performance liquid chromatography. RESULTS Mean ciprofloxacin levels in serum, GCT, and GCF were 0.40 microg/ml, 1.38 microg/g, and 1.66 microg/ml, respectively (P<0.001, N=9). For doxycycline, these levels were 1.11 microg/ml, 2.03 microg/g, and 2.41 microg/ml, respectively (P=0.002, N=8). For both agents, the GCT and GCF levels were significantly higher than serum levels (P<0.05), but not significantly different from each other. CONCLUSIONS Our findings suggest that fibroblasts could play an important role in the distribution of fluoroquinolones and tetracyclines to the gingiva. By accumulating these agents in GCT, fibroblasts could contribute to the relatively high levels they attain in GCF.
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Affiliation(s)
- Maria Lavda
- Section of Periodontology, College of Dentistry, The Ohio State University Health Sciences Center, Columbus, OH
| | - C. Esther Clausnitzer
- Department of Operative Dentistry and Periodontology, University of Cologne, Cologne, Germany
| | - John D. Walters
- Section of Periodontology, College of Dentistry, The Ohio State University Health Sciences Center, Columbus, OH
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Tözüm TF, Yildirim A, Cağlayan F, Dinçel A, Bozkurt A. Serum and gingival crevicular fluid levels of ciprofloxacin in patients with periodontitis. J Am Dent Assoc 2004; 135:1728-32. [PMID: 15646608 DOI: 10.14219/jada.archive.2004.0127] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
BACKGROUND The use of antibiotics as an adjunctive therapy in the treatment of periodontal diseases is of special interest to dental practitioners. In addition to using an appropriate antibacterial agent, clinicians may find it useful to determine the local and systemic concentrations of antibiotics in infected periodontal sites to reduce the levels of bacteria. The purpose of this study was to determine the serum and gingival crevicular fluid, or GCF, concentrations of systemic ciprofloxacin in patients with periodontitis. METHODS Ten subjects with chronic periodontitis received ciprofloxacin (500 milligrams) twice daily for five days. The authors collected GCF and serum samples immediately after administering the first dose (baseline = 0 hours) and at consecutive time points. The orifice method was used for GCF sampling, and 5 milliliters of venous blood was drawn for serum analysis. The authors used high-performance liquid chromatography to determine ciprofloxacin concentrations in GCF and serum. RESULTS The authors found that ciprofloxacin concentrations in GCF were significantly higher than concentrations in serum at two, four, seven, 24 and 120 hours. Ciprofloxacin reached the maximum concentration, or Cmax (3.72 micrograms/ mL), in GCF two hours after the initial dose was administered. The concentration decreased to 2.06 microg/mL 24 hours after the initial administration of the drug. Serum Cmax was 2.58 microg/mL at 1.5 hours, and the concentration decreased to 0.26 microg/mL at 24 hours. CONCLUSION The results of this clinical study show that ciprofloxacin is found in GCF and its concentration in GCF is significantly higher than that in serum. CLINICAL IMPLICATIONS Ciprofloxacin may be useful in treating patients with periodontitis because it reaches higher concentrations in GCF than in serum.
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Affiliation(s)
- Tolga F Tözüm
- Department of Periodontology, Faculty of Dentistry, Hacettepe University, Sihhiye, Ankara, Turkey.
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Umeda M, Takeuchi Y, Noguchi K, Huang Y, Koshy G, Ishikawa I. Effects of nonsurgical periodontal therapy on the microbiota. Periodontol 2000 2004; 36:98-120. [PMID: 15330945 DOI: 10.1111/j.1600-0757.2004.03675.x] [Citation(s) in RCA: 79] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
Affiliation(s)
- Makoto Umeda
- Department of Hard Tissue Engineering, Tokyo Medical and Dental University Graduate School, JapanDepartment of Hard Tissue Engineering, Tokyo Medical and Dental University Graduate School, Japan
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Eick S, Pfister W. Efficacy of Antibiotics Against Periodontopathogenic Bacteria Within Epithelial Cells: An In Vitro Study. J Periodontol 2004; 75:1327-34. [PMID: 15562909 DOI: 10.1902/jop.2004.75.10.1327] [Citation(s) in RCA: 45] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
BACKGROUND Periodontopathogenic bacteria can invade and survive within epithelial cells, but susceptibility of intracellular infection to antibiotics used in periodontitis treatment has not been studied to date. METHODS KB cells were infected by Actinobacillus actinomycetemcomitans, strain NCTC 9710; Porphyromonas gingivalis, strains ATCC 33277 and JH16-1; or Streptococcus constellatus, strain J012b. After 2, 4, and 12 hours the bactericidal effect of antibiotics (clindamycin, doxycycline, metronidazole, and moxifloxacin) on intracellular microorganisms was tested at a concentration up to the 100-fold minimum inhibitory concentration (MIC) determined separately on planktonic bacteria. RESULTS The P. gingivalis strains differed in their invasiveness and ATCC 33277 was 100-fold more invasive than JH16-1. Doxycycline and clindamycin at a concentration 10-fold MIC had no effect, but P. gingivalis intercellular infection was significantly reduced by metronidazole at 10-fold MIC after 2 and 4 hours. Moxifloxacin was effective, but a 100-fold MIC concentration was necessary to reduce P. gingivalis strains intracellular growth to 7% of the control. Other bacterial species grown inside the KB cells were more susceptible to antibiotics. Clindamycin at 10-fold MIC reduced the number of intracellular S. constellatus after 4 and 12 hours. This bacterium was eliminated by moxifloxacin at 50-fold MIC. Intracellular A. actinomycetemcomitans was killed by 10-fold MIC of doxycycline and moxifloxacin after 4 hours incubation. CONCLUSIONS Moxifloxacin was the most efficient antibiotic to treat intracellular infection. However, taking into account the MIC values and the levels of antibiotics in gingival fluid, elimination of intracellular bacteria by antibiotics alone seems to be questionable.
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Affiliation(s)
- Sigrun Eick
- Department of Oral Microbiology, Institute of Medical Microbiology, University Hospital of Jena, Jena, Germany.
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Abstract
Both systemic and topical antibiotics are increasingly used in the management of periodontal infections. Whilst these drugs are used mostly on an empirical basis, some contend that rational use of antibiotics should be the norm due to their wide abuse and consequential global emergence of antibiotic resistance organisms. Here we review the rationale and principles of antimicrobial therapy, treatment goals, drug delivery routes and various antibiotics that are used in the management of periodontal diseases. The pros and cons of systemic and local antibiotic therapy are described together with practical guidelines for their delivery. The available data indicate, in general, that mechanical periodontal treatment alone is adequate to ameliorate or resolve the clinical condition in most cases, but adjunctive antimicrobial agents, delivered either locally or systemically, can enhance the effect of therapy in specific situations. This is particularly true for aggressive (early onset) periodontitis, in patients with generalised systemic disease that may affect host resistance and in case of poor response to conventional mechanical therapy. Locally delivered antibiotics together with mechanical debridement are indicated for non-responding sites of focal infection or in localised recurrent disease. After resolution of the periodontal infection, the patient should be placed on an individually tailored maintenance care programme. Optimal plaque control by the patient is of paramount importance for a favourable clinical and microbiological response to any form of periodontal therapy.
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Yang Q, Nakkula RJ, Walters JD. Accumulation of ciprofloxacin and minocycline by cultured human gingival fibroblasts. J Dent Res 2002; 81:836-40. [PMID: 12454098 PMCID: PMC2481382 DOI: 10.1177/154405910208101208] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023] Open
Abstract
Through a mechanism that is unclear, systemic fluoroquinolones and tetracyclines can attain higher levels in gingival fluid than in blood. We hypothesized that gingival fibroblasts take up and accumulate these agents, thereby enhancing their redistribution to the gingiva. Using fluorescence to monitor transport activity, we characterized the accumulation of fluoroquinolones and tetracyclines in cultured human gingival fibroblast monolayers. Both were transported in a concentrative, temperature-dependent, and saturable manner. Fibroblasts transported ciprofloxacin and minocycline with K(m) values of 200 and 108 micro g/mL, respectively, at maximum velocities of 4.62 and 14.2 ng/min/ micro g cell protein, respectively. For both agents, transport was most efficient at pH 7.2 and less efficient at pH 6.2 and 8.2. At steady state, the cellular/extracellular concentration ratio was > 8 for ciprofloxacin and > 60 for minocycline. Thus, gingival fibroblasts possess active transporters that could potentially contribute to the relatively high levels these agents attain in gingival fluid.
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Affiliation(s)
- Qing Yang
- Sections of Oral Biology, College of Dentistry, The Ohio State University Health Sciences Center
| | - Robin J. Nakkula
- Sections of Periodontology, College of Dentistry, The Ohio State University Health Sciences Center
| | - John D. Walters
- Sections of Periodontology, College of Dentistry, The Ohio State University Health Sciences Center
- *Address correspondence and reprint requests to: John D. Walters, College of Dentistry, The Ohio State University, 305 West 12th Avenue, P.O. Box 182357, Columbus, OH 43218-2357, Telephone: (614) 292-1169, Fax: (614) 292-2438, e-mail:
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Brayton JJ, Yang Q, Nakkula RJ, Walters JD. An in vitro model of ciprofloxacin and minocycline transport by oral epithelial cells. J Periodontol 2002; 73:1267-72. [PMID: 12479629 PMCID: PMC2483302 DOI: 10.1902/jop.2002.73.11.1267] [Citation(s) in RCA: 20] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
BACKGROUND Fluoroquinolones and tetracyclines can penetrate epithelial cells, but the mechanism by which they cross the plasma membrane is unclear. In this study, a cell line derived from oral epithelium was used as a model to demonstrate a role for active transport. METHODS Transport of ciprofloxacin and minocycline by confluent cell monolayers was assayed by measuring the increase in cell-associated fluorescence. RESULTS Uptake of both agents was saturable and was inhibited at low temperatures. At 37 degrees C, the cells transported ciprofloxacin and minocycline with Km values of 351 and 133 microg/ml, respectively, and maximum velocities of 5.11 and 13.4 ng/min/microg cell protein, respectively. When ciprofloxacin and minocycline were removed from the extracellular medium, the intracellular levels of both agents decreased. Ciprofloxacin efflux from loaded cells occurred more rapidly than with minocycline. Cells accumulated intracellular drug levels that were at least 8-fold higher than extracellular levels for ciprofloxacin and at least 40-fold higher for minocycline. Transport of ciprofloxacin and minocycline was significantly influenced by pH and was most favorable at pH 7.7 and 7.2, respectively. While ciprofloxacin transport was Na+ independent, minocycline transport was strongly inhibited when sodium in the medium was replaced with choline. Transport of both agents was inhibited by a variety of organic cations, but the pattern of inhibition was different. Papaverine, phenylephrine, and doxycycline competitively inhibited minocycline transport, but inhibited ciprofloxacin transport by a non-competitive mechanism. CONCLUSIONS Epithelial cells take up ciprofloxacin and minocycline via different active transport systems. These transporters may play an important role in enhancing the effectiveness of these agents against invasive pathogens.
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Affiliation(s)
- James J. Brayton
- Sections of Periodontology, The Ohio State University Health Sciences Center
| | - Qing Yang
- Sections of Oral Biology, College of Dentistry, The Ohio State University Health Sciences Center
| | - Robin J. Nakkula
- Sections of Periodontology, The Ohio State University Health Sciences Center
| | - John D. Walters
- Sections of Periodontology, The Ohio State University Health Sciences Center
- Department of Molecular and Cellular Biochemistry, College of Medicine and Public Health, The Ohio State University Health Sciences Center
- *Address correspondence and reprint requests to: John D. Walters, College of Dentistry, The Ohio State University, 305 West 12th Avenue, P.O. Box 182357, Columbus, OH 43218-2357, Telephone: (614) 292-1169, Fax: (614) 292-2438, e-mail:
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Rare Actinobacillus Infection of the Cavernous Sinus Causing Painful Ophthalmoplegia: Case Report. Neurosurgery 2002. [DOI: 10.1097/00006123-200209000-00037] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
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Müller HP, Holderrieth S, Burkhardt U, Höffler U. In vitro antimicrobial susceptibility of oral strains of Actinobacillus actinomycetemcomitans to seven antibiotics. J Clin Periodontol 2002; 29:736-42. [PMID: 12390570 DOI: 10.1034/j.1600-051x.2002.290810.x] [Citation(s) in RCA: 43] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
BACKGROUND/AIMS Periodontal infections with Actinobacillus actinomycetemcomitans seem to be refractory to conventional therapy. The aim of the present study was to test the in vitro susceptibilities of A. actinomycetemcomitans strains to a panel of seven orally administrable antibiotics. METHODS A total of 60 isolates of A. actinomycetemcomitans recovered from 43 individuals with gingivitis or periodontitis were tested. In addition, laboratory strains UP-6 and JP2 were analysed. The E-test was employed in order to determine minimal inhibitory concentrations (MIC) of antibiotics ampicillin/sulbactam, roxithromycin, azithromycin, doxycycline, metronidazole, ciprofloxacin, and moxifloxacin. RESULTS A. actinomycetemcomitans was highly susceptible to both fluoro-quinolones (MIC90 of 0.006 microgram/mL of ciprofloxacin and 0.032 microgram/mL of moxifloxacin). Good susceptibilities were found for ampicillin/sulbactam and doxycycline (MIC90 of 0.75 microgram/mL and 1 microgram/mL, respectively), and moderate susceptibilities for azithromycin (MIC90 of 3 microgram/mL). Most strains were resistant to metronidazole and roxithromycin. Cluster analysis revealed two larger clusters of A. actinomycetemcomitans strains with the smaller cluster assembling isolates with significantly higher MICs of most antibiotics. CONCLUSIONS Due to reported favourable pharmacokinetics, the fluoro-quinolone moxifloxacin appeared to be a promising candidate for adjunctive systemic antibiotic therapy in periodontal infections with A. actinomycetemcomitans.
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Affiliation(s)
- H-P Müller
- School of Dental Medicine, Ruprecht-Karls-University, Heidelberg, Germany.
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36
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Cacchillo DA, Walters JD. Effect of ciprofloxacin on killing of Actinobacillus actinomycetemcomitans by polymorphonuclear leukocytes. Antimicrob Agents Chemother 2002; 46:1980-4. [PMID: 12019120 PMCID: PMC127222 DOI: 10.1128/aac.46.6.1980-1984.2002] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Actinobacillus actinomycetemcomitans, a pathogen associated with aggressive periodontitis, resists phagocytic killing by polymorphonuclear leukocytes (PMNs). It is susceptible to ciprofloxacin, which PMNs actively accumulate. This study tested the hypothesis that ciprofloxacin-loaded PMNs are more effective at killing A. actinomycetemcomitans than control PMNs. Isolated human PMNs were loaded by brief incubation with 0.5 microg of ciprofloxacin/ml. Opsonized bacteria (ATCC 43718) were incubated at 37 degrees C with control and ciprofloxacin-loaded PMNs and in the presence and absence of 0.5 microg of ciprofloxacin/ml. When assayed at bacteria-to-PMN ratios of 30:1 and 90:1, ciprofloxacin-loaded PMNs killed significantly more bacteria and achieved significantly shorter half times for killing than control PMNs (P < 0.05; Tukey's test). At ratios of 3:1 and 10:1, these differences were not significant.
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Affiliation(s)
- David A Cacchillo
- Section of Periodontology, College of Dentistry, The Ohio State University Health Sciences Center, Columbus, Ohio 43218-2357, USA
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37
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Conway TB, Beck FM, Walters JD. Gingival fluid ciprofloxacin levels at healthy and inflamed human periodontal sites. J Periodontol 2000; 71:1448-52. [PMID: 11022774 PMCID: PMC2483303 DOI: 10.1902/jop.2000.71.9.1448] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
BACKGROUND Polymorphonuclear leukocytes (PMNs) take up and accumulate ciprofloxacin. This may allow them to enhance the delivery of this agent to the inflamed periodontium. METHODS Cross-sectional and longitudinal approaches were used to test the hypothesis. In the cross-sectional study, 7 periodontally healthy adults and 8 adults with untreated periodontitis were administered three doses of ciprofloxacin (500 mg bid). Gingival fluid (GF) and serum samples were obtained after 28 hours and analyzed by high-performance liquid chromatography (HPLC). In the longitudinal study, 8 adult periodontitis subjects were administered 500 mg ciprofloxacin bid for 8 days. After 28 hours, GF from 4 sites with 5 to 8 mm probing depths was sampled in each subject, serum samples were obtained, and 2 of the 4 sites were root planed. GF and serum were sampled again 7 days later (196 hours after the initial dose). RESULTS The mean ciprofloxacin levels in the GF and serum of periodontally healthy subjects were 2.52 +/- 0.22 microg/ml and 0.47 +/- 0.05 microg/ml, respectively. In subjects with periodontitis, these levels were 2.69 +/- 0.44 microg/ml and 0.61 +/- 0.13 microg/ml, respectively. GF ciprofloxacin levels were significantly higher than corresponding serum levels in healthy and diseased subjects (P<0.01), but there were no significant differences in GF or serum levels between the 2 subject groups. Since GF flow was significantly higher at diseased sites, however, more ciprofloxacin was distributed to these sites than to healthy sites. In the longitudinal study, GF flow at 196 hours was 16% lower at root planed sites than at untreated control sites (P = 0.412). The minor decrease in this index of inflammation was accompanied by a small (9%), but statistically significant (P= 0.007), decrease in GF ciprofloxacin levels. CONCLUSIONS GF ciprofloxacin levels decreased slightly at inflamed periodontal sites after root planing, but were significantly higher than serum levels even at healthy periodontal sites. Inflammation may enhance the distribution of ciprofloxacin to diseased sites, but it is not a major determinant of GF ciprofloxacin levels.
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Affiliation(s)
- Theresa B. Conway
- Sections of Periodontology, The Ohio State University Health Sciences Center
| | - Frank M. Beck
- Sections of Health Services Research, College of Dentistry, The Ohio State University Health Sciences Center
| | - John D. Walters
- Sections of Periodontology, The Ohio State University Health Sciences Center
- Department of Molecular and Cellular Biochemistry, College of Medicine and Public Health, The Ohio State University Health Sciences Center
- *Address correspondence and reprint requests to: John D. Walters, College of Dentistry, The Ohio State University, 305 West 12th Avenue, Columbus, OH 43210, Telephone: (614) 292-1322, Fax: (614) 292-2438,
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38
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Loesche WJ. The antimicrobial treatment of periodontal disease: changing the treatment paradigm. CRITICAL REVIEWS IN ORAL BIOLOGY AND MEDICINE : AN OFFICIAL PUBLICATION OF THE AMERICAN ASSOCIATION OF ORAL BIOLOGISTS 2000; 10:245-75. [PMID: 10759408 DOI: 10.1177/10454411990100030101] [Citation(s) in RCA: 53] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Over the last 100 years, methods of surgical periodontal treatment have enjoyed a history of success in improving oral health. The paradigm of care is based on the "non-specific plaque hypothesis"--that is, the overgrowth of bacterial plaques cause periodontal disease, and the suppression of this overgrowth reduces disease risk. The central feature of this approach to care is the removal of inflamed gingival tissue around the teeth to reduce periodontal pocket depth, thereby facilitating plaque removal by the dentist and by the patient at home. Over the last 30 years, with the recognition that periodontal disease(s) is caused by specific bacteria and that specific antimicrobial agents can reduce or eliminate the infection, a second paradigm has developed. This new paradigm, the "specific plaque hypothesis", focuses on reducing the specific bacteria that cause periodontal attachment loss. The contrast between the two paradigms can be succinctly stated as follows: The antimicrobial therapy reduces the cause, while the surgical therapy reduces the result of the periodontal infection. The specific plaque hypothesis has two important implications. First, with the increasing attention to evidence-based models for prevention, treatment, outcome assessment, and reimbursement of care, increasing attention and financial effort will be channeled into effective preventive and treatment methods. Second, the recent observations that periodontal infections increase the risk of specific systemic health problems, such as cardiovascular disease, argue for the prevention and elimination of these periodontal infections. This review highlights some of the evidence for the specific plaque hypothesis, and the questions that should be addressed if antimicrobial agents are to be used responsively and effectively.
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Affiliation(s)
- W J Loesche
- University of Michigan School of Dentistry, Ann Arbor 48109, USA
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39
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Eick S, Pfister W, Straube E. Antimicrobial susceptibility of anaerobic and capnophilic bacteria isolated from odontogenic abscesses and rapidly progressive periodontitis. Int J Antimicrob Agents 1999; 12:41-6. [PMID: 10389646 DOI: 10.1016/s0924-8579(99)00056-4] [Citation(s) in RCA: 40] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/17/2022]
Abstract
In dentistry antimicrobials are used in the treatment of progressive periodontitis and odontogenic abscesses, therefore the susceptibility to commonly used antibiotics of capnophilic and anaerobic species causing these diseases should be investigated. The activity of penicillin, amoxycillin, cefoxitin, clindamycin, doxycycline, metronidazole and ciprofloxacin was investigated. One hundred and sixty four isolates from subgingival plaque samples of 66 patients with progressive periodontitis and 192 bacterial strains from pus of 74 patients with odontogenic abscesses were included in this study. The majority of species tested were gram-negative anaerobes (Prevotella spp., Porphyromonas spp., Fusobacterium spp.), and were highly susceptible to clindamycin and metronidazole. Nearly 6% of the periodontal isolates and 22% of the bacteria obtained from pus samples produced beta-lactamases. With the exception of the periodontopathogenic species Actinobacillus actinomycetemcomitans and Eikenella corrodens, clindamycin seemed to be a useful antibiotic and could be recommended for empirical antimicrobial treatment.
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Affiliation(s)
- S Eick
- Department of Medical Microbiology, University Hospital of Jena, Germany.
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40
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41
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Piccolomini R, Di Bonaventura G, Catamo G, Picciani C, Paolantonio M. In vitro antimicrobial susceptibility of periodontopathic Actinobacillus actinomycetemcomitans to roxithromycin and erythromycin. ORAL MICROBIOLOGY AND IMMUNOLOGY 1997; 12:366-71. [PMID: 9573812 DOI: 10.1111/j.1399-302x.1997.tb00740.x] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
The in vitro minimal inhibitory concentrations (MIC) and minimal bactericidal concentration (MBC) of roxithromycin and erythromycin against Actinobacillus actinomycetemcomitans were evaluated. Sixty-seven different A. actinomycetemcomitans isolated from periodontal pockets of 101 subjects with different forms of early-onset and adult periodontitis and three reference strains of A. actinomycetemcomitans (ATCC 29522, ATCC 29523, and NCTC 9710) were included in this study. Erythromycin showed poor in vitro activity against A. actinomycetemcomitans; roxithromycin, on the contrary, exhibited good in vitro activity. Moreover, roxithromycin showed the best in vitro antimicrobial activity against 17 serotype a and 12 serotype c subpopulations of A. actinomycetemcomitans; against 38 serotype b subpopulation of A. actinomycetemcomitans, roxithromycin was consistently active. Roxithromycin exhibited MBC values usually equal to, or one-fold higher than MIC values. All the MBC values of erythromycin were three- to four-fold higher than the respective MIC result. Since roxithromycin is characterized by high concentrations in serum and good penetration and diffusion into gingival tissue, it could be expected to pass into the gingival crevicular fluid at levels sufficiently high to inhibit A. actinomycetemcomitans in vivo. These data indicate that roxithromycin might be a potential candidate for therapeutic trials in patients with A. actinomycetemcomitans-associated periodontitis.
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Affiliation(s)
- R Piccolomini
- Department of Biomedical Sciences, G. D'Annunzio University, Chieti, Italy
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42
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Abstract
The nitroimidazole antibiotic metronidazole has a limited spectrum of activity that encompasses various protozoans and most Gram-negative and Gram-positive anaerobic bacteria. Metronidazole has activity against protozoans like Entamoeba histolytica, Giardia lamblia and Trichomonas vaginalis, for which the drug was first approved as an effective treatment. Anaerobic bacteria which are typically sensitive are primarily Gram-negative anaerobes belonging to the Bacteroides and Fusobacterium spp. Gram-positive anaerobes such as peptostreptococci and Clostridia spp. are likely to test sensitive to metronidazole, but resistant isolates are probably encountered with greater frequency than with the Gram-negative anaerobes. Gardnerella vaginalis is a pleomorphic Gram-variable bacterial bacillus that is also susceptible to metronidazole. Helicobacter pylori has been strongly associated with gastritis and duodenal ulcers. Classic regimens for eradicating this pathogen have included metronidazole, usually with acid suppression medication plus bismuth and amoxicillin. The activity of metronidazole against anaerobic bowel flora has been used for prophylaxis and treatment of patients with Crohn's disease who might develop an infectious complication. Treatment of Clostridium difficile-induced pseudomembraneous colitis has usually been with oral metronidazole or vancomycin, but the lower cost and similar efficacy of metronidazole, coupled with the increased concern about imprudent use of vancomycin leading to increased resistance in enterococci, have made metronidazole the preferred agent here. Metronidazole has played an important role in anaerobic-related infections. Advantages to using metronidazole are the percentage of sensitive Gram-negative anaerobes, its availability as oral and intravenous dosage forms, its rapid bacterial killing, its good tissue penetration, its considerably lower chance of inducing C. difficile colitis, and expense. Metronidazole has notable effectiveness in treating anaerobic brain abscesses. Metronidazole is a cost-effective agent due to its low acquisition cost, its pharmacokinetics and pharmacodynamics, an acceptable adverse effect profile, and its undiminished antimicrobial activity. While its role as part of a therapeutic regimen for treating mixed aerobic/anaerobic infections has been reduced by newer, more expensive combination therapies, these new combinations have not been shown to have any therapeutic advantage over metronidazole. Although the use of metronidazole on a global scale has been curtailed by newer agents for various infections, metronidazole still has a role for these and other therapeutic uses. Many clinicians still consider metronidazole to be the 'gold standard' antibiotic against which all other antibiotics with anaerobic activity should be compared.
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Affiliation(s)
- C D Freeman
- Department of Medicine, University of Missouri-Kansas City School of Medicine, USA.
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43
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Edlund C, Hedberg M, Nord CE. Antimicrobial treatment of periodontal diseases disturbs the human ecology: a review. J Chemother 1996; 8:331-41. [PMID: 8957712 DOI: 10.1179/joc.1996.8.5.331] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
Periodontal diseases are associated with specific pathogenic microorganisms and therefore antimicrobial agents are often used in the treatment of patients with periodontitis refractory to conventional mechanical therapy. Perorally administered antimicrobial agents often lead to ecological disturbances in the normal oral and intestinal microflora with overgrowth of potentially pathogenic microorganisms, which may spread within the host or from patient to patient, causing infections. The use of antimicrobial agents also promotes the emergence of bacterial drug resistance, both in the periodontal pocket and in the normal oral and intestinal microflora. Topical administration of antimicrobial agents in the periodontal pockets causes restricted disturbances in the intestinal microflora, although there is a substantial risk of development of resistance at the site of application. A number of clinical studies imply that correct use of antimicrobial agents might be beneficial for a subset of patients with adult or juvenile periodontitis. The choice of antimicrobial agent should always be based on accurate microbial analyses of the subgingival microflora and in vitro antimicrobial susceptibility tests of the most important periodontal pathogens. Preferably, agents with low potential of causing ecological disturbances should be used.
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Affiliation(s)
- C Edlund
- Department of Immunology, Microbiology, Pathology and Infectious Diseases, Karolinska Institute, Huddinge University Hospital, Stockholm, Sweden
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44
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Callahan C, DeMassi R, Vila I, Greene JN, Sandin RL. Pulmonary Pseudotumors: Infections and Other Causes. Cancer Control 1996; 3:158-163. [PMID: 10792876 DOI: 10.1177/107327489600300210] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Affiliation(s)
- C Callahan
- Department of Infectious Diseases, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida 33612, USA
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45
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Affiliation(s)
- A J van Winkelhoff
- Department of Oral Microbiology, Academic Centre for Dentistry Amsterdam, The Netherlands
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46
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Avila-Campos MJ, Carvalho MA, Zelante F. Distribution of biotypes and antimicrobial susceptibility of Actinobacillus actinomycetemcomitans. ORAL MICROBIOLOGY AND IMMUNOLOGY 1995; 10:382-4. [PMID: 8602348 DOI: 10.1111/j.1399-302x.1995.tb00171.x] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Eighty isolates of Actinobacillus actinomycetemcomitans from 30 Brazilian periodontitis patients were examined to determine the distribution of biotypes and in vitro antimicrobial susceptibility. Seventy-seven percent of the isolates belonged to biotype X. All A. actinomycetemcomitans isolates were susceptible to cefoxitin, imipenem and tetracycline.
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Affiliation(s)
- M J Avila-Campos
- Department of Microbiology, Instituto de Ciências Biomédicas, Universidade de São Paulo, Brazil
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47
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Stelzel M, Flores-de-Jacoby L. [The GTR technic within the framework of combined periodontal-orthodontic treatments. A case report]. FORTSCHRITTE DER KIEFERORTHOPADIE 1995; 56:347-52. [PMID: 8655107 DOI: 10.1007/bf02173161] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
Periodontal defects in adolescents or young adults are often an incidental finding within the framework of orthodontic treatment. Often these patients are suffering from a special form of periodontal disease, juvenile periodontitis. Guided tissue regeneration (GTR) offers a technique for long-term therapy in such cases. In the case presented here, the periodontal problems were aggravated by malpositioning of the affected teeth. Orthodontic and periodontal treatment enabled the malpositioning to be corrected and the osseous defects to be largely regenerated. Controls on regular bases up to now revealed a stable status over 2 years.
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Affiliation(s)
- M Stelzel
- Abteilung für Parodontologie, Philipps-Universität Marburg
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48
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Roe DE, Braham PH, Weinberg A, Roberts MC. Characterization of tetracycline resistance in Actinobacillus actinomycetemcomitans. ORAL MICROBIOLOGY AND IMMUNOLOGY 1995; 10:227-32. [PMID: 8602335 DOI: 10.1111/j.1399-302x.1995.tb00147.x] [Citation(s) in RCA: 31] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Comparison of susceptibility data for Actinobacillus actinomycetemcomitans has been difficult because of the lack of standard susceptibility testing conditions. In this study, minimum inhibitory concentration to tetracycline was evaluated by comparing different media, air conditions and incubation times. Ten of 22 (45%) A. actinomycetemcomitans isolated from periodontally diseased sites grew on media supplemented with 4 micrograms per ml of tetracycline, but minimum inhibitory concentrations ranged from 0.125 to 8 micrograms/ml depending on the media and condition used. The best results were obtained with brain heart infusion agar (Difco Laboratories, Detroit MI) incubated in 5% CO2 for 48 h. Eighteen (82%) of the A. actinomycetemcomitans isolates hybridized with the Tet B determinant. The Tet B determinant was transferable between A. actinomycetemcomitans isolates as well as a Haemophilus influenzae recipient and appears to be associated with conjugative plasmids.
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Affiliation(s)
- D E Roe
- Department of Pathobiology, University of Washington, Seattle, USA
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49
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Miyake Y, Tsuruda K, Okuda K, Iwamoto Y, Suginaka H. In vitro activity of tetracyclines, macrolides, quinolones, clindamycin and metronidazole against periodontopathic bacteria. J Periodontal Res 1995; 30:290-3. [PMID: 7562327 DOI: 10.1111/j.1600-0765.1995.tb02136.x] [Citation(s) in RCA: 36] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/26/2023]
Abstract
We re-evaluated several antibiotics including newer ones, for their in vitro killing activity, as well as their inhibitory activity, against clinical isolates of periodontopathic bacteria. Tetracyclines were active against Porphyromonas gingivalis, and were highly active against Prevotella intermedia, but demonstrated only a low killing activity against Actinobacillus actinomycetemcomitans. Rokitamycin, a new macrolide, and clindamycin were highly active against P. gingivalis and P. intermedia, but showed very weak killing activity against A. actinomycetemcomitans. Quinolones demonstrated excellent bactericidal activity against A. actinomycetemcomitans, and good inhibitory and bactericidal activity against P. gingivalis and P. intermedia. Metronidazole had an activity almost equivalent to quinolones against P. gingivalis and P. intermedia; but it was the least active against A. actinomycetemcomitans.
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Affiliation(s)
- Y Miyake
- Department of Microbiology, Hiroshima University School of Dentistry, Japan
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