A Multi-center Study: The Impact of Dental Implants on Candida Colonization in the Oral Cavity and Their Response to Antifungal Agents

A Multi-center Study: The Impact of Dental Implants on Candida Colonization in the Oral Cavity and Their Response to Antifungal Agents | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article A Multi-center Study: The Impact of Dental Implants on Candida Colonization in the Oral Cavity and Their Response to Antifungal Agents Ahmed A. Abdulhabeb¹, Taghreed Al-Kibsi¹, Hassan Abdulwahab Al-Shamahy² This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9242873/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background : Dental implants are a cornerstone of modern restorative dentistry; however, fungal colonization, particularly by Candida species, remains a clinical concern. This multi-center study aimed to evaluate the prevalence of Candida colonization on dental implants compared to natural teeth and to assess the susceptibility of these isolates to common antifungal agents. Methods : A cross-sectional multi-center study was conducted involving five clinical settings in Sana'a, Yemen, including the Faculty of Dentistry at Sana'a University and four specialized private dental centers. A total of 66 participants (34 with dental implants and 32 with natural teeth as a control group) were enrolled. Oral swabs were collected from the buccal mucosa and tongue and cultured on Sabouraud dextrose agar. And Chromogenic Agar. Colony-forming units (CFU/ml) were quantified, Fungal identification and antifungal susceptibility testing was performed for Nystatin, Fluconazole, Clotrimazole, Ketoconazole, and Amphotericin B were performed using standardized laboratory protocols. Results : Candida colonization was detected in both groups, with a higher prevalence in implant patients (52.9%) compared to controls (31.2%). The mean CFU count was 115.6 ± 42.3 CFU/ml in implant patients and 109.6 ± 38.7 CFU/ml in controls (p = 0.42). Amphotericin B showed the highest sensitivity (70%), while Fluconazole showed the lowest (35%). Conclusion : This study highlights that dental implants are more prone to Candida colonization than natural teeth. The findings from these diverse clinical centersemphasize the need for strict oral hygiene protocols and targeted antifungal therapy to prevent peri-implant complications Dental implants Candida albicans Antifungal susceptibility Multi-center study Yemen Figures Figure 1 Figure 2 Introduction Dental implants are a reliable and widely accepted treatment modality for the replacement of missing teeth[ 1 , 2 ]. Despite their high success rates, microbial colonization around implant surfaces remains a significant concern, potentially leading to peri-implant diseases[ 3 , 4 , 5 ]. Candida species are common commensal organisms in the oral cavity but may become opportunistic pathogens under certain conditions[ 6 , 7 ]. Among these, Candida albicans is the most frequently isolated species and is known for its ability to adhere to surfaces and form biofilms, enhancing its pathogenicity and resistance to antifungal agents[ 8 , 9 , 10 ]. Implant surfaces, particularly those with micro-rough characteristics, may facilitate microbial adhesion and biofilm formation[ 11 , 12 , 13 ]. This raises concerns regarding the role of dental implants in promoting fungal colonization[ 14 , 15 ]. Therefore, this study aimed to evaluate the prevalence of Candida colonization in patients with dental implants and assess the antifungal susceptibility patterns of the isolated species. Materials and Methods Study Design and Setting This was a multi-center , comparative cross-sectional study conducted between [Insert Date] and [Insert Date]. To ensure a diverse and representative patient population, participants were recruited from five distinct clinical settings in Sana’a, Yemen. These included the specialized clinics at the Faculty of Dentistry, Sana’a University , and four major private dental implant centers across the capital city. ​ Study Population and Sampling : The study enrolled a total of 66 participants , categorized into two groups: an implant group (n = 34) consisting of patients with at least one functional dental implant, and a control group (n = 32) comprising subjects without any dental implants. ​ Inclusion and Exclusion Criteria : Participants were required to be adults (aged ≥ 18 years). For the implant group, only those with implants in function for at least six months were included. Exclusion criteria involved immunocompromised individuals, patients who had received antibiotic or antifungal therapy within the 14 days prior to sampling, and those with systemic diseases known to significantly alter oral microflora.026inger Nature Sample Collection: Oral swabs were obtained from the buccal mucosa and tongue using sterile cotton swabs and transported immediately to the microbiology laboratory. Microbiological Analysis: Samples were cultured on Sabouraud dextrose agar and incubated under appropriate conditions. Candida colonies were quantified as CFU/ml[ 16 , 17 ].". Antifungal Susceptibility Testing: Isolates were tested against Nystatin, Fluconazole, Clotrimazole, Ketoconazole, and Amphotericin B[ 18 , 19 ].". Statistical Analysis: Data were analyzed using SPSS version 25. Independent t-test and Chi-square test were used. A p-value < 0.05 was considered statistically significant. Results Candida colonization was detected in both groups, with a higher prevalence in implant patients. Table 1 Prevalence of Candida colonization in study groups Group Number of Patients Candida Positive Percentage Implant group 34 18 52.9% Control group 32 10 31.2% Table 2 Mean Candida CFU/ml in study groups Group Mean CFU/ml Standard Deviation P-value Implant 115.6 42.3 Control 109.6 38.7 0.42 Table 3 Antifungal susceptibility pattern Antifungal Sensitive Nystatin 60% Fluconazole 35% Clotrimazole 45% Ketoconazole 40% Amphotericin B 70% Discussion This study demonstrated that Candida colonization occurs in both implant and non-implant patients, with a higher prevalence among implant patients. This finding supports previous studies suggesting that implant surfaces may promote microbial adhesion and biofilm formation[ 20 , 21 ].". The lack of statistical significance in CFU counts may be attributed to the relatively small sample size and the multifactorial nature of Candida colonization, including oral hygiene and host-related factors. The higher sensitivity to Amphotericin B and Nystatin observed in this study is consistent with previous reports indicating the effectiveness of polyene antifungals against Candida species[ 22 , 23 ].. In contrast, reduced sensitivity to azole antifungals such as Fluconazole may reflect increasing antifungal resistance, particularly in biofilm-associated infections.[ 24 , 25 ]." Biofilm formation plays a critical role in antifungal resistance, as it limits drug penetration and enhances microbial survival. Conclusion ​ In conclusion, this multi-center study provides clear clinical evidence that dental implants are more susceptible to Candida colonization (52.9%) compared to natural teeth (31.2%). Although the difference in mean CFU counts was not statistically significant (p = 0.42), the higher prevalence among implant patients suggests that implant surfaces may provide favorable niches for fungal adhesion and biofilm formation. ​Crucially, our findings reveal a concerning pattern of antifungal resistance; while Amphotericin B and Nystatin remains highly effective (70% and 60% sensitivity, respectively), there is a significant reduction in sensitivity to Fluconazole (35%). These results emphasize the necessity for regular microbiological monitoring and the implementation of strict oral hygiene protocols for dental implant patients. Clinicians should consider these susceptibility patterns when managing peri-implant fungal infections to ensure effective treatment outcomes and prevent potential implant failure. Declarations Ethical Approval : The study was approved by the Ethical Committee of the Faculty of Dentistry, Sana’a University, Yemen. Consent to Participate : Written informed consent was obtained from all participants. Conflict of Interest : The authors declare no conflict of interest. Funding : This research received no external funding. Author Contributions: "AAA designed the study and wrote the manuscript. TAAMAK supervised the research and contributed to the study design. HAAS performed the microbiological analysis and reviewed the final manuscript. All authors read and approved the final manuscript." Consent to Publish: "Not applicable." Data Availability Statement: "The datasets used and analyzed during the current study are available from the corresponding author on reasonable request." References Rodrigues CF, Silva S, Henriques M (2023) Candida biofilms and oral infections. J Fungi 9(2):150 Vila T, Sultan AS, Montelongo-Jauregui D, Jabra-Rizk MA (2022) Oral Candida biofilms. J Fungi 8(4):325 Williams DW, Lewis MA (2021) Pathogenesis of oral candidosis. Oral Dis 27(3):455–467 Ramage G et al (2020) Fungal biofilms in oral health and disease. J Dent Res 99(2):123–132 Seneviratne CJ et al (2022) Oral microbial biofilms in health and disease. Clin Oral Investig 26:3531–3543 Silva S, Rodrigues CF, Araújo D (2023) Candida species and antifungal resistance. J Fungi 9:300 Nobile CJ, Johnson AD (2020) Candida albicans biofilms. Microbiol Mol Biol Rev 84:e00064–e00019 Pereira D et al (2023) Candida colonization in oral prostheses. Clin Oral Investig 27:2145–2153 Samaranayake LP (2021) Oral mycoses and fungal infections. Dent Clin North Am 65:65–75 Koo H, Allan RN, Howlin RP (2022) Biofilm formation in the oral cavity. Nat Rev Microbiol 20:94–109 Alrabiah M et al (2022) Candida colonization in implant patients. Clin Implant Dent Relat Res De Andrade D et al (2021) Candida adherence to implant surfaces. Int J Oral Maxillofac Implants Gendreau L et al (2020) Fungal infections associated with dental implants. J Prosthodont Zomorodian K et al (2023) Antifungal susceptibility of oral Candida isolates. J Mycol Med Barasch A et al (2021) Oral fungal infections and systemic health. Oral Surg Oral Med Oral Pathol Mergoni G et al (2022) Candida species distribution in oral cavity. BMC Oral Health Costa AC et al (2021) Candida biofilms on biomaterials. Biofouling Nassar HM et al (2023) Oral fungal microbiota and implants. Clin Oral Investig Xu H et al (2022) Mechanisms of antifungal resistance in Candida. Front Microbiol Sherry L et al (2021) Biofilm-mediated resistance in Candida species. J Fungi Dwivedi P et al (2023) Emerging antifungal resistance in Candida. Microorganisms Silva-Dias A et al (2022) Candida infections in oral cavity. J Oral Microbiol Akpan A, Morgan R (2020) Oral candidiasis review. Postgrad Med J Ghannoum MA et al (2021) Oral fungal microbiome. Clin Microbiol Rev Li X et al (2024) Candida biofilm and implant infections. Front Cell Infect Microbiol Additional Declarations No competing interests reported. Supplementary Files IMG20251121WA0003.jpg IMG20251121WA0004.jpg IMG20251213WA0006.jpg IMG20251213WA0005.jpg IMG20250804WA00051.jpg Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-9242873","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":615180770,"identity":"f891cb49-477a-46ca-9a6a-cf3079aa3d96","order_by":0,"name":"Ahmed A. 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Agents\u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003eDental implants are a reliable and widely accepted treatment modality for the replacement of missing teeth[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Despite their high success rates, microbial colonization around implant surfaces remains a significant concern, potentially leading to peri-implant diseases[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eCandida species are common commensal organisms in the oral cavity but may become opportunistic pathogens under certain conditions[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Among these, Candida albicans is the most frequently isolated species and is known for its ability to adhere to surfaces and form biofilms, enhancing its pathogenicity and resistance to antifungal agents[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eImplant surfaces, particularly those with micro-rough characteristics, may facilitate microbial adhesion and biofilm formation[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThis raises concerns regarding the role of dental implants in promoting fungal colonization[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eTherefore, this study aimed to evaluate the prevalence of Candida colonization in patients with dental implants and assess the antifungal susceptibility patterns of the isolated species.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eStudy Design and Setting\u003c/strong\u003e \u003cp\u003eThis was a \u003cb\u003emulti-center\u003c/b\u003e, comparative cross-sectional study conducted between [Insert Date] and [Insert Date]. To ensure a diverse and representative patient population, participants were recruited from \u003cb\u003efive distinct clinical settings\u003c/b\u003e in Sana\u0026rsquo;a, Yemen. These included the specialized clinics at the \u003cb\u003eFaculty of Dentistry, Sana\u0026rsquo;a University\u003c/b\u003e, and \u003cb\u003efour major private dental implant centers\u003c/b\u003e across the capital city.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e​\u003cb\u003eStudy Population and Sampling\u003c/b\u003e: The study enrolled a total of \u003cb\u003e66 participants\u003c/b\u003e, categorized into two groups: an \u003cb\u003eimplant group (n\u0026thinsp;=\u0026thinsp;34)\u003c/b\u003e consisting of patients with at least one functional dental implant, and a \u003cb\u003econtrol group (n\u0026thinsp;=\u0026thinsp;32)\u003c/b\u003e comprising subjects without any dental implants.\u003c/p\u003e \u003cp\u003e​\u003cb\u003eInclusion and Exclusion Criteria\u003c/b\u003e: Participants were required to be adults (aged\u0026thinsp;\u0026ge;\u0026thinsp;18 years). For the implant group, only those with implants in function for at least six months were included. Exclusion criteria involved immunocompromised individuals, patients who had received antibiotic or antifungal therapy within the 14 days prior to sampling, and those with systemic diseases known to significantly alter oral microflora.026inger Nature\u003c/p\u003e \u003cp\u003e Sample Collection: Oral swabs were obtained from the buccal mucosa and tongue using sterile cotton swabs and transported immediately to the microbiology laboratory.\u003c/p\u003e \u003cp\u003eMicrobiological Analysis: Samples were cultured on Sabouraud dextrose agar and incubated under appropriate conditions. Candida colonies were quantified as CFU/ml[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e].\".\u003c/p\u003e \u003cp\u003eAntifungal Susceptibility Testing: Isolates were tested against Nystatin, Fluconazole, Clotrimazole, Ketoconazole, and Amphotericin B[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e].\".\u003c/p\u003e \u003cp\u003eStatistical Analysis: Data were analyzed using SPSS version 25. Independent t-test and Chi-square test were used. A p-value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eCandida colonization was detected in both groups, with a higher prevalence in implant patients.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003ePrevalence of Candida colonization in study groups\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGroup\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNumber of Patients\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCandida Positive\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePercentage\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eImplant group\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e52.9%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eControl group\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e31.2%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eMean Candida CFU/ml in study groups\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGroup\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMean CFU/ml\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eStandard Deviation\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eImplant\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e115.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e42.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eControl\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e109.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e38.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.42\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eAntifungal susceptibility pattern\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAntifungal\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSensitive\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNystatin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e60%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFluconazole\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e35%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eClotrimazole\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e45%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eKetoconazole\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e40%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAmphotericin B\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e70%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis study demonstrated that Candida colonization occurs in both implant and non-implant patients, with a higher prevalence among implant patients. This finding supports previous studies suggesting that implant surfaces may promote microbial adhesion and biofilm formation[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e].\".\u003c/p\u003e \u003cp\u003eThe lack of statistical significance in CFU counts may be attributed to the relatively small sample size and the multifactorial nature of Candida colonization, including oral hygiene and host-related factors.\u003c/p\u003e \u003cp\u003eThe higher sensitivity to Amphotericin B and Nystatin observed in this study is consistent with previous reports indicating the effectiveness of polyene antifungals against Candida species[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]..\u003c/p\u003e \u003cp\u003eIn contrast, reduced sensitivity to azole antifungals such as Fluconazole may reflect increasing antifungal resistance, particularly in biofilm-associated infections.[\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e].\"\u003c/p\u003e \u003cp\u003eBiofilm formation plays a critical role in antifungal resistance, as it limits drug penetration and enhances microbial survival.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003e​ In conclusion, this \u003cb\u003emulti-center study\u003c/b\u003e provides clear clinical evidence that dental implants are more susceptible to \u003cem\u003eCandida\u003c/em\u003e colonization (52.9%) compared to natural teeth (31.2%). Although the difference in mean CFU counts was not statistically significant (p\u0026thinsp;=\u0026thinsp;0.42), the higher prevalence among implant patients suggests that implant surfaces may provide favorable niches for fungal adhesion and biofilm formation.\u003c/p\u003e \u003cp\u003e​Crucially, our findings reveal a concerning pattern of antifungal resistance; while \u003cb\u003eAmphotericin B\u003c/b\u003e and \u003cb\u003eNystatin\u003c/b\u003e remains highly effective (70% and 60% sensitivity, respectively), there is a significant reduction in sensitivity to \u003cb\u003eFluconazole\u003c/b\u003e (35%). These results emphasize the necessity for regular microbiological monitoring and the implementation of strict oral hygiene protocols for dental implant patients. Clinicians should consider these susceptibility patterns when managing peri-implant fungal infections to ensure effective treatment outcomes and prevent potential implant failure.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthical Approval\u003c/strong\u003e:\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe study was approved by the Ethical Committee of the Faculty of Dentistry, Sana\u0026rsquo;a University, Yemen.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to Participate\u003c/strong\u003e:\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eWritten informed consent was obtained from all participants.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of Interest\u003c/strong\u003e:\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe authors declare no conflict of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e:\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThis research received no external funding.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cspan lang=\"\"\u003eAuthor Contributions:\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cspan lang=\"\"\u003e\u0026quot;AAA designed the study and wrote the manuscript. TAAMAK supervised the research and contributed to the study design. HAAS performed the microbiological analysis and reviewed the final manuscript. All authors read and approved the final manuscript.\u0026quot;\u003c/span\u003e\u003c/p\u003e\n\u003cp\u003e\u003cspan lang=\"\"\u003e\u003cstrong\u003eConsent to Publish:\u003c/strong\u003e\u003c/span\u003e\u003c/p\u003e\n\u003cp\u003e\u003cspan lang=\"\"\u003e\u0026quot;Not applicable.\u0026quot;\u003c/span\u003e\u003c/p\u003e\n\u003cp\u003e\u003cspan lang=\"\"\u003e\u003cstrong\u003eData Availability Statement:\u003c/strong\u003e\u003c/span\u003e\u003c/p\u003e\n\u003cp\u003e\u003cspan lang=\"\"\u003e\u0026quot;The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.\u0026quot;\u003c/span\u003e\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eRodrigues CF, Silva S, Henriques M (2023) Candida biofilms and oral infections. J Fungi 9(2):150\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVila T, Sultan AS, Montelongo-Jauregui D, Jabra-Rizk MA (2022) Oral Candida biofilms. J Fungi 8(4):325\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWilliams DW, Lewis MA (2021) Pathogenesis of oral candidosis. Oral Dis 27(3):455\u0026ndash;467\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRamage G et al (2020) Fungal biofilms in oral health and disease. J Dent Res 99(2):123\u0026ndash;132\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSeneviratne CJ et al (2022) Oral microbial biofilms in health and disease. Clin Oral Investig 26:3531\u0026ndash;3543\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSilva S, Rodrigues CF, Ara\u0026uacute;jo D (2023) Candida species and antifungal resistance. J Fungi 9:300\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNobile CJ, Johnson AD (2020) Candida albicans biofilms. Microbiol Mol Biol Rev 84:e00064\u0026ndash;e00019\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePereira D et al (2023) Candida colonization in oral prostheses. Clin Oral Investig 27:2145\u0026ndash;2153\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSamaranayake LP (2021) Oral mycoses and fungal infections. Dent Clin North Am 65:65\u0026ndash;75\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKoo H, Allan RN, Howlin RP (2022) Biofilm formation in the oral cavity. Nat Rev Microbiol 20:94\u0026ndash;109\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAlrabiah M et al (2022) Candida colonization in implant patients. Clin Implant Dent Relat Res\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDe Andrade D et al (2021) Candida adherence to implant surfaces. Int J Oral Maxillofac Implants\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGendreau L et al (2020) Fungal infections associated with dental implants. J Prosthodont\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZomorodian K et al (2023) Antifungal susceptibility of oral Candida isolates. J Mycol Med\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBarasch A et al (2021) Oral fungal infections and systemic health. Oral Surg Oral Med Oral Pathol\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMergoni G et al (2022) Candida species distribution in oral cavity. BMC Oral Health\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCosta AC et al (2021) Candida biofilms on biomaterials. Biofouling\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNassar HM et al (2023) Oral fungal microbiota and implants. Clin Oral Investig\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eXu H et al (2022) Mechanisms of antifungal resistance in Candida. Front Microbiol\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSherry L et al (2021) Biofilm-mediated resistance in Candida species. J Fungi\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDwivedi P et al (2023) Emerging antifungal resistance in Candida. Microorganisms\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSilva-Dias A et al (2022) Candida infections in oral cavity. J Oral Microbiol\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAkpan A, Morgan R (2020) Oral candidiasis review. Postgrad Med J\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGhannoum MA et al (2021) Oral fungal microbiome. Clin Microbiol Rev\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLi X et al (2024) Candida biofilm and implant infections. Front Cell Infect Microbiol\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Dental implants, Candida albicans, Antifungal susceptibility, Multi-center study, Yemen","lastPublishedDoi":"10.21203/rs.3.rs-9242873/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9242873/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e: Dental implants are a cornerstone of modern restorative dentistry; however, fungal colonization, particularly by Candida species, remains a clinical concern. This multi-center study aimed to evaluate the prevalence of Candida colonization on dental implants compared to natural teeth and to assess the susceptibility of these isolates to common antifungal agents.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e: A cross-sectional multi-center study was conducted involving five clinical settings in Sana'a, Yemen, including the Faculty of Dentistry at Sana'a University and four specialized private dental centers.\u003c/p\u003e\n\u003cp\u003eA total of 66 participants (34 with dental implants and 32 with natural teeth as a control group) were enrolled.\u003c/p\u003e\n\u003cp\u003eOral swabs were collected from the buccal mucosa and tongue and cultured on Sabouraud dextrose agar. And Chromogenic Agar.\u003c/p\u003e\n\u003cp\u003eColony-forming units (CFU/ml) were quantified, Fungal identification and antifungal susceptibility testing was performed for Nystatin, Fluconazole, Clotrimazole, Ketoconazole, and Amphotericin B were performed using standardized laboratory protocols.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e: Candida colonization was detected in both groups, with a higher prevalence in implant patients (52.9%) compared to controls (31.2%). The mean CFU count was 115.6 ± 42.3 CFU/ml in implant patients and 109.6 ± 38.7 CFU/ml in controls (p = 0.42). Amphotericin B showed the highest sensitivity (70%), while Fluconazole showed the lowest (35%).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e: This study highlights that dental implants are more prone to \u003cem\u003eCandida\u003c/em\u003e colonization than natural teeth. The findings from these diverse clinical centersemphasize the need for strict oral hygiene protocols and targeted antifungal therapy to prevent peri-implant complications\u003c/p\u003e","manuscriptTitle":"A Multi-center Study: The Impact of Dental Implants on Candida Colonization in the Oral Cavity and Their Response to Antifungal Agents","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-04-02 07:19:00","doi":"10.21203/rs.3.rs-9242873/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"8dcb611e-588f-4f18-ad79-91c103840b97","owner":[],"postedDate":"April 2nd, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-04-07T13:27:43+00:00","versionOfRecord":[],"versionCreatedAt":"2026-04-02 07:19:00","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9242873","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9242873","identity":"rs-9242873","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}