Objectives: Peri-implantitis is a destructive disease on dental implants where an inflammatory lesion induces bleeding on probing of peri-implant soft tissues, increased peri-implant probing depths, and progressive resorption of surrounding crestal alveolar bone. Treatment of peri-implantitis is controversial, with no universally accepted treatment protocol presently established. Systemic antibiotic therapy has been employed as an adjunct to mechanical implant surface debridement of peri-implantitis lesions, with conflicting outcomes reported with various antibiotics. However, recent clinical trials have found systemic administration of either azithromycin or metronidazole as an adjunct to non-surgical peri-implantitis treatment provided statistically significant additional improvements in peri-implant clinical status than placebo-treated peri-implantitis patients receiving mechanical implant debridement alone. These clinical trial findings suggest potential value of both systemic azithromycin and metronidazole in human peri- implantitis treatment.However, clinical use of azithromycin or metronidazole may be complicated by the presence of pathogenic bacteria in peri-implantitis lesions which are resistant to the antibiotics. Previous studies have reported that peri-implantitis patients in the United States frequently harbor submucosal bacteria resistant to a number of antibiotics commonly prescribed in clinical dental practice, with microbial resistance to metronidazole among major putative bacteria pathogens detected in more than one in five peri-implantitis patients. To date, no data are available on the prevalence of azithromycin resistance in peri-implantitis bacterial populations. Thus, it is not known whether antibiotic resistance of major putative bacterial pathogens in peri-implantitis is greater to metronidazole or to azithromycin. As a result, the purpose of the present study was to determine the prevalence of in vitro resistance of selected bacteria from human peri- implantitis lesions to azithromycin as compared to metronidazole.
Methods: Selected data on 65 consecutive peri-implantitis-affected adult patients with in vitro antibiotic testing on their submucosal biofilm samples with azithromycin at a concentration of 4 mg/L, and metronidazole at a concentration of 16 mg/L, were extracted from pre-existing 2021-2022 archived records in the Oral Microbiology Testing Service (OMTS) Laboratory at Temple University School of Dentistry in Philadelphia, Pennsylvania. Qualifying inclusion criteria for the study patient records were 1.) the patient’s submucosal biofilm specimen was culture-positive with one or more of the following bacteria: Porphyromonas gingivalis, Tannerella forsythia, Prevotella intermedia/nigrescens, Parvimonas micra, Fusobacterium nucleatum, Streptococcus constellatus, Campylobacter rectus, Streptococcus intermedius, or gram-negative enteric rods, 2.) the patient was aged between 35-88 years, 3.) the patient was diagnosed by a periodontist as having peri-implantitis, 4.) the patient’s birth year and gender was reported, and 5.) the total submucosal anaerobic viable count per patient, the total submucosal percent cultivable of P. gingivalis, T. forsythia, P. intermedia/ nigrescens, P. micra, F. nucleatum, S. constellatus, C. rectus, S. intermedius, or gram-negative enteric rods, if present, and whether or not the isolates were resistant in vitro to breakpoint concentrations of either azithromycin (4 mg/L) or metronidazole (16 mg/L), were reported. When a qualifying patient record was identified, the above data were extracted and directly entered into a Microsoft Excel spreadsheet contained in a password-protected and encrypted computer file. Descriptive analysis tabulated de-identified patient data on age, gender, and smoking status, mean total submucosal anaerobic viable count per patient, the prevalence and proportional cultivable recovery of the test bacteria in patients, and the prevalence and subgingival proportions of azithromycin-resistant and metronidazole-resistant test species in patients. Fisher’s exact test evaluated among patients the presence one or more azithromycin-resistant test bacteria as compared to metronidazole-resistant test species. A paired t-test examined mean total cultivable submucosal proportions of the test bacteria per patient resistant in vitro to azithromycin as compared to mean total proportions per patient resistant to metronidazole. Logistic regression statistical modeling was used to assess the relationship between peri- implantitis patients with and without azithromycin-resistant or metronidazole-resistant test submucosal species and patient age of 65 years or older, patient gender, and patient current smoking status. A 2-tailed P-value of ≤ 0.05 was required for all tests of statistical significance.
Results: The 65 peri-implantitis patients averaged 64.5 years in age, with females more frequent (52.3%) and only 10.8% with a current smoking habit. All of the peri- implantitis patients yielded one or more of the evaluated putative bacterial pathogens from submucosal biofilm samples, with P. micra, F. nucleatum and P. intermedia/ nigrescens the most frequently isolated test species. No azithromycin-resistant or metronidazole-resistant test bacterial species were found in 20 (30.8%) of the peri- implantitis study subjects. A total of 43 (66.2%) of the 65 peri-implantitis patients harbored azithromycin-resistant test species in submucosal biofilm samples, which was significantly greater than 8 (12.3%) peri-implantitis patients with metronidazole-resistant submucosal species (5.4-fold difference, P < 0.001, Fisher’s exact test). P. micra, S. constellatus, P. intermedia/nigrescens, T. forsythia, and F. nucleatum were test species most frequently resistant to 4 mg/L of azithromycin, whereas a subset of S. intermedius, F. nucleatum and S. constellatus were the only test species resistant to 16 mg/L of metronidazole. Total submucosal proportions of test bacterial species resistant to azithromycin averaged 8.8% per patient, as compared to only 1.4% resistant to metronidazole (P < 0.001, paired t-test). No statistically significant relationships were found between peri-implantitis patients with and without one or more azithromycin- resistant or metronidazole-resistant test species and older patient age (≥ 65 years), gender, or current smoking habit (all P-values > 0.05).
Conclusions: Azithromycin in vitro antibiotic resistance was frequently found among predominant cultivable bacteria in human peri-implantitis lesions at levels more than 5-fold more frequent, and at significantly higher total cultivable proportions in submucosal biofilms, than is resistance to metronidazole. The high prevalence of azithromycin microbial resistance in peri-implantitis patients highlights the potential risk of therapeutic failure with empiric prescription of azithromycin in peri-implantitis therapy without guidance from antibiotic resistance testing of putative submucosal bacterial pathogens. / Oral Biology
| Identifer | oai:union.ndltd.org:TEMPLE/oai:scholarshare.temple.edu:20.500.12613/8589 |
| Date | January 2023 |
| Creators | Stanazai, Khalida |
| Contributors | Rams, Thomas E., Page, Lawrence, Whitaker, Eugene J. |
| Publisher | Temple University. Libraries |
| Source Sets | Temple University |
| Language | English |
| Detected Language | English |
| Type | Thesis/Dissertation, Text |
| Format | 41 pages |
| Rights | IN COPYRIGHT- This Rights Statement can be used for an Item that is in copyright. Using this statement implies that the organization making this Item available has determined that the Item is in copyright and either is the rights-holder, has obtained permission from the rights-holder(s) to make their Work(s) available, or makes the Item available under an exception or limitation to copyright (including Fair Use) that entitles it to make the Item available., http://rightsstatements.org/vocab/InC/1.0/ |
| Relation | http://dx.doi.org/10.34944/dspace/8553, Theses and Dissertations |
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