No full-text available
To read the full-text of this research,
you can request a copy directly from the authors.
Oral candidosis – Clinical challenges of a biofilm disease
Critical Reviews in Microbiology
Abstract
This review summarizes the impact of biofilms in oral candidosis with special emphasis on medically compromised patients. The concept of oral candidosis as a mixed candidal-bacterial biofilm infection has changed our understanding of its epidemiology and diagnosis as well as approach to its treatment. Candida albicans is the most common causative agent of oral candidosis although Candida species other than C. albicans are often seen in medically compromised patients with a history of multiple courses of azole antifungals. Although C. albicans is usually susceptible to all commonly used antifungals when tested in vitro, their biofilm form are highly resistant to most antifungals. Therefore, treatment consists of mechanical destruction of the biofilm in combination with topical drugs. Azole antifungals should be avoided for patients suffering from recurrent oral yeast infections due to a risk of selection and enrichment of resistant strains within the biofilm. Oral candidosis can also be a symptom of an undiagnosed or poorly controlled systemic disease such as HIV infection or diabetes. If the response to appropriate treatment is poor, other causes of oral mucositis should be excluded. Oral candidosis arises from the patient's mixed candidal-bacterial biofilm, i.e., dental plaque, whereby good self-care is important for successful therapy.
... Candida spp. infection only arises when an opportunity occurs, thus being known as an opportunistic infection [3,4]. Table 1 shows the various clinical forms of candidiasis. ...
... In general, there are specific and non-specific defense mechanisms present in saliva and oral mucosa, in addition to the presence of the competitive oral microbiota itself, formed by other microorganisms that restrict the growth of Candida spp. [3,5]. There are several factors that can cause oral candidiasis, and this pathology is closely linked to other disorders or conditions that are considered risk factors for its emergence [3,6], as depicted in Table 2. Therefore, oral candidiasis may be an indication of problems that affect defense mechanisms, whether local or systemic alteration of the oral microbiota or even neglected oral hygiene [5,6]. ...
... [3,5]. There are several factors that can cause oral candidiasis, and this pathology is closely linked to other disorders or conditions that are considered risk factors for its emergence [3,6], as depicted in Table 2. Therefore, oral candidiasis may be an indication of problems that affect defense mechanisms, whether local or systemic alteration of the oral microbiota or even neglected oral hygiene [5,6]. ...
Oral candidiasis is an opportunistic infection usually related to predisposing factors. Oral manifestations in patients affected by COVID-19 have been reported, as the oral mucosa is the gateway to this viral infection. Xerostomia, as well as other oral symptoms, are predisposing factors for the emergence of oral candidiasis after the COVID-19 pandemic. It is a common pathology, but fatal if left untreated. Nystatin (NYS) is the drug of first choice in the treatment of oral candidiasis. Herein, we reviewed the epidemiology of oral candidiasis and its treatments, focusing on the mechanism of action, dosage forms, and NYS efficacy. NYS is an effective drug against oral candidiasis and belongs to Class IV of the biopharmaceutical classification system; however, its low solubility and low permeability may compromise its availability in the oral cavity and, consequently, its pharmacological action. Future perspectives to overcome drug limitations were also addressed and discussed in our review.
... Irrespective of these interkingdom relationships, Candida spp. have been shown within the most accessible of these clinical sites (i.e. the oral cavity and vagina) to have the capacity to form biofilms that have the clinical appearance of white patches, or pseudomembranes (24,25). Beyond this they have the capacity to hijack wounds, catheter lines and indwelling devices to gain systemic access, and to cause debilitating and life-threatening infections (13,26), some of which are now discussed. ...
... Diagnosis of oral candidiasis is usually first based on a clinical presentation, followed up if necessary with histopathological examinations of the infected tissue (24). Routinely, oral swabs and rinses are used for microbiological analysis, with microscopy being particularly useful for detecting the presence of C. albicans hyphae, a useful biomarker for differentiating against azole-insensitive yeast such as C. krusei and C. glabrata. ...
... Routinely, oral swabs and rinses are used for microbiological analysis, with microscopy being particularly useful for detecting the presence of C. albicans hyphae, a useful biomarker for differentiating against azole-insensitive yeast such as C. krusei and C. glabrata. This is an important factor in empirical treatment of these diseases (24). These procedures can diagnose Candida species in pseudomembranous candidosis, angular chelitis and denture-induced stomatitis (DIS). ...
Clinically we have been aware of the concept of Candida biofilms for many decades, though perhaps without the formal designation. Just over twenty years ago the subject emerged on the back of progress made from the bacterial biofilms, and academic progress pace has continued to mirror the bacterial biofilm community, albeit at a decreased volume. It is apparent that Candida species have a considerable capacity to colonise surfaces and interfaces and form tenacious biofilm structures, either alone or in mixed species communities. From the oral cavity, to the respiratory and genitourinary tracts, wounds, or in and around a plethora of biomedical devices, the scope of these infections is vast. These are highly tolerant to antifungal therapies that has a measurable impact on clinical management. This review aims to provide a comprehensive overight of our current clinical understanding of where these biofilms cause infections, and we discuss existing and emerging antifungal therapies and strategies.
... Some factors associated with candidemia in intensive care units (ICU) are long durations of central venous catheterization, urinary tract catheterization and mechanical ventilation [2,3]. At low levels, Candida albicans colonizes oral mucosal surfaces [4] as a normal inhabitant, but, under certain circumstances, it can cause a superficial candidiasis characterized by the appearance of white plaques on inflamed and red mucosa and by pain when eating or swallowing [4,5]. If C. albicans infection becomes invasive, it can cause septicemia [6]. ...
... Some factors associated with candidemia in intensive care units (ICU) are long durations of central venous catheterization, urinary tract catheterization and mechanical ventilation [2,3]. At low levels, Candida albicans colonizes oral mucosal surfaces [4] as a normal inhabitant, but, under certain circumstances, it can cause a superficial candidiasis characterized by the appearance of white plaques on inflamed and red mucosa and by pain when eating or swallowing [4,5]. If C. albicans infection becomes invasive, it can cause septicemia [6]. ...
... C. albicans infections are related to several virulence factors, including biofilm formation (BF) on implanted medical devices and oral mucosa (biotic and abiotic surfaces) [4][5][6], which allow the initial adhesion to epithelial cells with subsequent tissue invasion, damage and antimicrobial resistance increased risks [5,11,12]. Further, C. albicans virulence factors include its ability to switch from the yeast form to an invasive hyphae morphotype, and to secrete proteolytic and lipolytic enzymes [13]. ...
Candida albicans infections are related to biofilm formation. The increase in antifungal resistance and their adverse effects have led to the search for therapeutic options as plant derivatives. This scoping review aims to identify the current status of in vitro research on the cytotoxicity and inhibitory effects of plant derivatives on C. albicans biofilms. In this study, PRISMA items were followed. After recognition of the inclusion criteria, full texts were read and disagreements were resolved with a third party. A risk of bias assessment was performed, and information was summarized using Microsoft Office Excel. Thirty-nine papers fulfilling the selection criteria were included. The risk of bias analysis identified most of the studies as low risk. Studies evaluated plant derivatives such as extracts, essential oils, terpenes, alkaloids, flavonoids and polyphenols. Some studies evaluated the inhibition of C. albicans biofilm formation, inhibition on preformed biofilms or both. The derivatives at concentrations greater than or equal to those that have an inhibitory effect on C. albicans biofilms, without showing cytotoxicity, include magnoflorin, ellagic acid, myricetin and eucarobustol from Eucalyptus robusta and, as the works in which these derivatives were studied are of good quality, it is desirable to carry out study in other experimental phases, with methodologies that generate comparable information.
... The proper antifungal treatment is based on the clinical presentation, severity of symptoms, and if the underlying immunologic disease is present [4]. Several factors affect the likelihood of developing oral candidiasis: immunologic and endocrine disorders, dietary factors, age, malignant and chronic diseases, hospitalization, smoking history, and hyposalivation [5,6]. The likelihood of a patient developing oral candidiasis without one of the predisposing risk factors is extremely low. ...
... Other local risk factors include denture-wearing, topical corticosteroid therapy, and smoking. Systemic risk factors, which may lead to the disseminated disease include neutropenia, age-related immunosenescence, broad-spectrum IV antibiotics, AIDS-stage HIV, systemic immunocompromise, and nutritional deficiencies [6,15]. ...
... There are many different clinical manifestations of oral candidiasis which can be simply classified as acute manifestations, chronic manifestations, or chronic mucocutaneous candidiasis syndromes [6,15]. Our patient presented with acute pseudomembranous candidiasis also known as "thrush." ...
Post-tonsillectomy complications can include bleeding, dehydration, edema, airway obstruction, and infection. Oral candidiasis or thrush is a rare complication that can occur post-operatively. We describe a case of a 10-year-old female with oral candidiasis as a postoperative complication of bilateral adenotonsillectomy, presenting on postoperative day (POD) 7 for poor oral intake secondary to worsening odynophagia. A physical exam revealed an easily scrapable, white plaque located mainly over her surgical sites, tongue, and hard palate. Microscopic examination of tissue scrapings revealed pseudohyphae confirming the diagnosis of oral candidiasis. She was treated with seven days of topical nystatin therapy, including topical and systemic pain control with significant improvement of symptoms by POD 13 and complete resolution on POD 21.
... Oral fungal infections are predominantly caused by Candida species (62). C. albicans is most common, but several other species, including C. glabrata, C. krusei, C. tropicalis, and C. parapsilosis are also frequently isolated (63). In addition to growing on mucosal surfaces, Candida is effectively forming biofilms on teeth and artificial materials, such as dentures. ...
... A rare manifestation of oral yeast infection is chronic mucocutaneous candidiasis. Chronic Candida infec-tions have been associated with malignant transformation, which may be at least partly attributed to production of carcinogenic acetaldehyde by yeasts (62,63). Furthermore, in infections, such as angular cheilitis, median rhomboid glossitis, and denture stomatitis, Candida often plays a role together with bacteria, especially staphylococci (47,49,50). ...
... A culture sample for the identification of Candida species and, possibly, for the sensitivity testing is strongly recommended in the cases of treatment failure, severely immunosuppressed patients, and if the patient needs antifungal treatment frequently. Swab or imprint samples are taken from the mucosal lesion suspected to represent Candida infection, whereas saliva and oral rinse samples can be used as a sampling method for diagnosis of more generalized oral infection (63). By culture, an approximate amount of Candida in the sample can be counted, and the identification of isolates to the species level is performed by further testing, e.g. using chromogenic media for culture. ...
... The purpose is to promote healing of the inflamed tissues. If the problem still persists, slight grinding of the tissue surface followed by an application of denture liner is advised [53]. It is known that intraoral antifungal therapy has a number of disadvantages, including the cleansing effect of saliva and muscle in the oral cavity, which reduces the drug's potency below the appropriate therapeutic concentration. ...
... Ionic liquids have been used to alter inorganic materials. They have a unique property that allows them to be utilized as templating or morphologycontrolling agents, allowing them to control the nucleation and growth of nanostructures [52][53][54]. The desirable chemical and physical properties of ILs, such as high polarity and low toxicity, make them the preferred materials for this application. ...
Recently, the use of ionic liquids (ILs) as potential solvents in dentistry has increased. Dental polymers use ionic liquids as solvents, plasticizers, surfactants, and disinfectants. Additionally, they possess antibacterial and antifungal properties. This review aimed to evaluate the potential of task‐specific liquids in dental applications. Methodology: The Scopus, PubMed, and Web of Science databases were searched electronically for studies published between May 2013 and May 2022. Relevant publications were retrieved, evaluated, and organized for data compilation. Results and conclusion: The inclusion of ILs in dental cement, resin composites, or surface modifiers on dental implants could lead to the development of novel procedures in dentistry. The influence on the durability, structural rigidity, and other physical and mechanical properties of dental materials is profound. Additionally, they have attracted the attention of dental researchers worldwide as potent antimicrobial agent. However, further research is required to determine the effects of ILs on biosafety of host cells and mechanical properties of dental materials.
... Other non-albicans species, Candida parapsilosis, Candida krusei, Candida stellatoidea, Candida tropicalis, Candida glabrata, Candida guilliermondii, and Candida dubliniensis, have also contributed to oral candidiasis to a lesser extent. The diagnosis of oral candidiasis is usually based on the cytological/histopathological examinations and clinical presentation of the infection (Rautemaa and Ramage 2011). As C. albicans is a natural habitant of the oral microbiome in the majority of healthy individuals, oral samples with a positive culture for Candida species with absence of clinical manifestation are diagnostically inconclusive. ...
... Refractory and recurrent infections usually require the use of systemic antifungals such as ketoconazole, fluconazole, and itraconazole and amphotericin in conjunction with topical agents to control the infection (Epstein and Polsky 1998). Despite treatment with antifungal, recurrence of oral candidiasis is not uncommon (Rautemaa and Ramage 2011). Recurrent infection can be due to incorrect diagnosis, inability to identify or treat underlying factors or inappropriate drug selection, or simply that the infection is biofilm-based and therefore intrinsically tolerant (Darwazeh and Darwazeh 2014). ...
Fungal biofilms are highly resilient to antifungal therapies, of which there are relatively few licensed options available in clinical medicine. Nonetheless, there is a vibrant research culture aimed at enhancing and expanding the arsenal of antifungals capable of inhibiting, killing, and disrupting fungal biofilms. This chapter aims to explore the wide variety of fungal biofilms affecting human health and to discuss the clinical options for existing and novel chemotherapeutics.KeywordsBiofilmAntifungalCandidaAzolePolyene
... Diagnosis of oral candidiasis is fundamentally clinical. Local or systemic immunosuppressive conditions and disturbances of the commensal bacterial microbiome favours Candida overgrowth and establishment of clinical infection (30). C. albicans is the predominant species detected both by culture and molecular methods in oral samples (31,32). ...
... Candida are generally susceptible to chlorhexidine, and polyene and azole antifungals. Importantly, however, species such as C. glabrata and C. krusei are commonly resistant to azoles (30,31). ...
... Medication resistance has been attributed to long-term exposure to antifungal medications [3,5,21,22] and biofilm formation [23]. Sessile cells (within the biofilm) differ from planktonic (freeliving) populations [24] in showing higher antifungal resistance levels [25]. Candida biofilms are enclosed in an extracellular matrix (ECM) of carbohydrates (e.g., polysaccharides), proteins, and DNA [26,27]. ...
Background and Purpose: Yeasts of the Candida genus are responsible for localized and disseminated infections, especially in immunocompromised populations. These infections are exacerbated by the rapid increase in drug-resistant strains, which limits treatment options and increases patient morbidity and mortality. Therefore, the utilization of easily accessible natural products as alternatives to conventional medicines has gained interest. South Africa is home to a rich biodiverse natural flora of which many are known for their antimicrobial activity, including the antifungal effects of their plant extracts. Galenia africana (kraalbos) is a local indigenous plant found to have various traditional uses, including the treatment and prevention of various human infections.
Materials and Methods: In this study, the activity of G. africana against Candida albicans and Candida glabrata preformed biofilm formation and its antibiofilm activity were tested using the xCELLigence system, which monitors biofilm formation in real time using impedance.
Results: Presence of G. africana resulted in a dose-dependent decrease in Candida biofilms and was found to be effective in the prevention of Candida biofilm formation and disruption of the existing Candida biofilms.
Conclusion: The xCELLigence impedance-based system proved to be an effective tool for medication screening. To the best of our knowledge, this is the first reported study to use real-time monitoring of a medicinal plant on microbial biofilm formation.
... In conclusion, study demonstrates that Econazole and Lactoferrin exhibit significant inhibitory effects on biofilm formation in representative fungal cultures under different tested conditions. Precoating with Econazole and Lactoferrin proved to be highly effective in reducing the formation of biofilms caused by Candida albicans, Candida tropicalis, and Candida krusei after a 24-hour incubation period [19][20][21]. Furthermore, it demonstrated superior control over Candida krusei biofilms compared to Econazole alone, particularly after a 48-hour incubation period [22]. ...
Fungal infections caused by Candida species, such as Candida albicans, Candida tropicalis, and Candida krusei, are a major concern in healthcare settings worldwide due to their ability to form biofilms. Biofilms provide protection and resistance to antifungal treatments, leading to persistent infections. In this study, we aimed to assess the antifungal effect of Lactoferrin in combination with Econazole or Econazole alone in reducing biofilms formed by these Candida species. Lactoferrin is a glycoprotein with broad-spectrum antimicrobial properties, while Econazole is an antifungal agent commonly used to treat superficial fungal infections. We conducted in vitro experiments using well-established biofilm models to evaluate the viability and metabolic activity of biofilm cells and the integrity of the biofilm matrix. Our results showed that the combination of Lactoferrin and Econazole significantly reduced biofilm formation compared to Econazole alone, particularly in Candida krusei biofilms. Confocal scanning laser microscopy confirmed the disruption of preformed biofilms by the combination treatment. These findings suggest that the synergistic effect of Lactoferrin and Econazole enhances their antifungal activity and holds promise for combating Candida biofilm-associated infections. Further preclinical and clinical investigations are needed to explore the full therapeutic potential of this combination in managing recurrent or persistent Candida infections. This research contributes to the development of innovative strategies to improve patient outcomes and reduce the burden of fungal-related morbidity and mortality.
... Dry mouth often results in dysgeusia or taste disorders, affecting the perception of flavors and altered taste sensations. Reduced saliva flow predisposes individuals to fungal infections in the mouth, such as oral thrush, which can manifest as white patches or lesions on the tongue, inner cheeks, or palate [15]. Glossodynia may also occur due to dryness and irritation of the oral mucosa. ...
Xerostomia, commonly known as dry mouth, presents a significant challenge for individuals wearing complete dentures, affecting their oral health and quality of life. This review explores the relationship between saliva and complete dentures, highlighting the varied management strategies for xerostomia. Saliva plays a critical role in denture retention, lubrication, and oral environment buffering. Complete denture wearers often experience reduced salivary flow, aggravating symptoms of xerostomia. Various management approaches are discussed, including general measures such as hydration and salivary stimulation techniques which aim to boost saliva production naturally. The use of salivary substitutes provides artificial lubrication and moisture to alleviate dry mouth discomfort. Oral lubricating devices, such as sprays, gels, and lozenges, offer relief by mimicking saliva's lubricating properties, thereby improving denture stability and comfort. This review addresses the etiology of xerostomia in complete denture wearers and explores preventive measures to reduce its impact. A comprehensive approach has been discussed for the management of xerostomia which will help to improve the oral health and well-being of complete denture wearers experiencing dry mouth.
... In the end, a tissue biopsy evaluation or culture evaluation of the lesion is frequently necessary for the diagnosis. [3,4,5] The purpose of the present study was to evaluate type, nature, and prevalence of common oral pathology lesions involving periodontium and implant in patients of tertiary level dental hospital in Hazaribagh City, Jharkhand. ...
A BSTRACT
Background
Evaluation of type, nature, and prevalence of common oral pathology lesions involving periodontium and implant in patients of tertiary level dental hospital in Hazaribagh City, Jharkhand.
Materials and Methods
A total of 2467 people were requested to take part in the oral examination. The current study cohort was made up of the 62.4% of the initial subgroup who participated in the clinical oral examination and granted their agreement for the use of the data. Between January 2023 and June 2023, the clinical oral examination was completed.
Results
No changes were observed in 89.6% of study participants. 88.2% males had no changes while 90.4% females had no changes. Normal variations were observed in 3.4% of study participants. 4.3% males had normal variations while 2.7% females had normal variations. Infectious oral pathology was observed in 3.3% of study participants. 2.4% males had infectious oral pathology while 3.2% females had infectious oral pathology Ulcerative lesions were observed in 4.1% of study participants. 3.6% males had ulcerative lesions while 2.4% females had ulcerative lesions. White lesions were observed in 6.7% of study participants. 8.2% males had white lesions while 5.6% females had white lesions.
Conclusion
This study provided a detailed evaluation of type, nature, and prevalence of different oral pathology lesions focusing on periodontium and implant.
... Previous research also portrayed the similar results. 28 We speculate that these results are due to presence of comorbidity and risk factors in the elderly. Aging causes physiological and/or pathological health problems that can disrupt the balance in the oral microbial environment or preservation of the oral health leading to higher prevalence of oral candidiasis in the aging group. ...
... Beside adjusting and managing the aforementioned predisposing factors, topical and systemic antifungal medications are still the mainstay treatment of DS [12]. However, these medications are not always effective in eradicating the fungal colonies from the dentures, and may be associated with a high risk of recurrence after antifungal therapies [12][13][14][15]. Another significant limitation of antifungal therapies is that fungal species may develop resistance against these medications especially in patients with long-term use [16]. ...
Background
Photodynamic therapy (PDT) has been recently proposed as a promising alternative therapy for Denture Stomatitis (DS). The present systematic review and meta-analysis investigated the current available evidence regarding the efficacy of PDT in the management of DS.
Materials and methods
PubMed, Scopus, Web of Science, Google Scholar, and ProQuest were searched up to June 7, 2023. All relevant clinical trials were included. RevMan software was used for the statistical analyses.
Results
Elven randomized clinical trials (460 DS patients) were included. Eight studies assessed the efficacy of PDT vs. topical antifungal therapy, while three studies assessed the adjunctive use of PDT (PDT + antifungal therapy) vs. topical antifungal therapy alone. The results revealed comparable efficacy of PDT and conventional antifungal therapy on candida colonization at 15 days (MD: 0.95, 95% CI: -0.28, 2.19, p = 0.13) and at the end of follow-up (MD: -0.17, 95% CI: -1.33, 0.98, p = 0.77). The pooled two studies revealed relatively better efficacy of adjunctive use of PDT with antifungal therapy on candida colonization compared to antifungal therapy alone at 15 days (MD: -6.67, 95% CI: -15.15, 1.82, p = 0.12), and at the end of follow-up (MD: -7.14, 95% CI: -19.78, 5.50, p = 0.27). Additionally, the results revealed comparable efficacy of PDT and topical antifungal therapy on the clinical outcomes.
Conclusions
PDT might be considered a viable option for DS either as an adjunct or as an alternative to the topical antifungal medications. Further studies with adequate sample sizes and standardized PDT parameters are warranted.
... Algunos factores de riesgo incluyen negligencia, higiene oral deficiente, disfunción salival, etapas extremas de la vida, uso prolongado de antimicrobianos, alteraciones inmunológicas, estados de inmunosupresión y emaciación [15,16,17,18]. El tratamiento farmacológico depende de la extensión, naturaleza de la lesión y estado inmunológico del paciente [19,16]. Respecto a las acciones preventivas, se ha informado que una buena higiene bucal, acompañada de revisiones periódicas puede ser suficiente, por lo que es necesario que los pacientes y cuidadores conozcan y apliquen correctamente las instrucciones de higiene bucal [20]. ...
La teleodontología (TO) se refiere a la atención odontológica en línea que evita el contacto físico entre paciente y clínico, su uso fue imprescindible durante la pandemia CoViD-19. Presentamos el caso de una paciente que vía WhatsApp solicitó atención odontológica. Se realizó el examen intraoral a través de fotografías y videos recibidos, se observó placa blanquecina en lengua que se desprendió al raspaje, inflamación gingival y lesiones erosivas en semimucosa labial. Mediante las imágenes recibidas se confirmó el diagnóstico de candidiasis pseudomembranosa oral (CPO). Se realizó tratamiento, seguimiento y se reforzaron los hábitos de higiene bucal. Las fotografías de seguimiento mostraron una respuesta satisfactoria al tratamiento. Destacamos que según el caso, la TO es una herramienta útil y eficiente para brindar atención primaria en salud de manera remota.
... Due to the widespread use of antifungal drugs such as nystatin and drug resistance in some patients, the clinical effectiveness of their treatment of oral candidiasis still needs to be improved [42]. PDT has a wide antibacterial spectrum, short therapeutic course and strong targeting, and can cause death of Candida by changing the permeability of Candida [43]. ...
Objective
To evaluate the clinical efficacy of photodynamic therapy (PDT) as an adjunct or alternative to traditional antifungal drugs in the treatment of oral candidiasis, and to provide evidence-based medical evidence for its use in the treatment of oral candidiasis.
Methods
Computer combined with manual retrieval of China Academic Journals Full-text Database (CNKI), China Biomedical Literature Database (CBM), Chinese Science and Technology Journal Database (VIP), Wanfang Database, PubMed, Web of Science, Cochrane Library, Embase, Scopus retrieval for articles published before January 2023, basic information and required data were extracted according to the inclusion and exclusion criteria, and the Revman V5.4 software was used to conduct Meta-analysis of the included literature.
Results
A total of 11 articles were included, 7 of which used nystatin as an antifungal drug, 2 of which were combined treatment of PDT and nystatin, 2 of the remaining 4 articles were treated with fluconazole, and 2 were treated with miconazole. Meta results showed that PDT was superior to nystatin in reducing the number of oral candida colonies in the palate of patients MD = -0.87, 95%CI = (-1.52,-0.23), P = 0.008 , the difference was statistically significant, and the denture site MD = -1.03, 95%CI = (-2.21, -0.15), P = 0.09 , the difference was not statistically significant; compared with the efficacy of fluconazole, RR = 1.01, 95%CI = (0.56,1.83), P = 0.96 ; compared with miconazole RR = 0.55, 95%CI = (0.38, 0.81), P = 0.002 ; PDT combined with nystatin RR = 1.27, 95%CI = (1.06, 1.52), P = 0.01 ; recurrence rate RR = 0.28, 95%CI = (0.09, 0.88), P = 0.03 .
Conclusions
PDT was effective in the treatment of oral candidiasis; PDT was more effective than nystatin for the treatment of denture stomatitis in the palate, while there was no significant difference between the two for the denture site; The efficacy of PDT for oral candidiasis was similar to that of fluconazole; PDT was less effective than miconazole for oral candidiasis; Compared with nystatin alone, the combination of PDT and nystatin is more effective in treating oral candidiasis with less risk of recurrence.
... For oral candidiasis management, topical or systemic antifungals may be used [16]. Treatment with these medicines is aimed at curing oral lesions but may lead to side effects such as gastrointestinal and liver disorders [13]. ...
... Beside adjusting and managing the aforementioned predisposing factors, topical and systemic antifungal medications are still the mainstay treatment of DS [12]. However, these medications are not always effective in eradicating the fungal colonies from the dentures, and may be associated with a high risk of recurrence after antifungal therapies [12][13][14][15]. Another signi cant limitation of antifungal therapies is that fungal species may develop resistance against these medications especially in patients with long-term use [16]. ...
Background: Photodynamic therapy (PDT) has recently been proposed as a promising therapeutic option for Denture Stomatitis (DS). This updated systematic review and meta-analysis investigated the current evidence regarding the efficacy of PDT for DS.
Materials and methods: PubMed, Scopus, Web of Science, Google Scholar, and ProQuest were searched up to June 7, 2023. All relevant clinical trials were included. RevMan software was used for meta-analysis.
Results: Elven randomized clinical trials (460 DS patients) were included. Eight studies assessed the efficacy of PDT vs. topical antifungal, while three studies assessed the adjunctive use of PDT (PDT+antifungal therapy) vs. topical antifungal therapy alone. The results revealed insignificant less efficacy of PDT in comparison to topical antifungal therapy on candida colonization at 15 days (MD: 0.95, 95% CI: -0.28, 2.19, p = 0.13), but comparable results at the end of follow-up (MD: -0.17, 95% CI: -1.33, 0.98, p = 0.77). The pooled two studies revealed relative better efficacy of adjunctive use of PDT with antifungal therapy on candida colonization compared to antifungal therapy alone at 15 days (MD: -6.67, 95% CI: -15.15, 1.82, p = 0.12), and at the end of follow-up (MD: -7.14, 95% CI: -19.78, 5.50, p = 0.27). Additionally, the results revealed comparable efficacy of PDT and topical antifungal therapy in improvement of the clinical signs.
Conclusions: PDT might be a viable option for DS as an adjunct or an alternative to the topical antifungal medications. Further studies with large sample sizes and standardized PDT parameters are warranted.
... Microbial production of carcinogenic acetaldehyde has been associated with oral cancer. The oral cavity can also act as a source of deep or systemic candidiasis in severely immunocompromised patients, such as AIDS, or immunocompromised patients, such as neutropenic patients [4][5][6]. ...
Abstract Microbiota is considered an organ that affects the health of the human body and includes many microorganisms such as bacteria, yeast, mold, viruses, protozoa, and archaea. Microorganism such as Candida sp., a part of the microbiota, is known to cause diseases in the case of opportunistic pathogens under various conditions. Yeast loads and species in the oral mycobiota of young individuals aged 18-25 were determined in our study. Two methods, centrifugation and dilution, were used to determine the oral yeast load. Samples were taken from 31 individuals for the centrifugation method, including 29 for the dilution method and five of these individuals. The samples were inoculated on Sabouraud 2% Dextrose Agar (SDA) and SDA containing chloramphenicol (SCAF). As a result, in young individuals aged 18-25, the oral yeast load was 0.01±0.01 and 1.87±0.01 log CFU in SCAF, and it was 0.01±0.01 and >3.00±0.01 log CFU in SDA. A total of 400 isolates were taken from the counting plates, and 140 were determined to be yeast by gram staining. Germ tube test of the isolates determined to be yeasts determined that 108 were probably Candida albicans or Candida dubliniensis. 140 isolates were also identified by MALDI-TOF MS. Isolates were identified as C. albicans (38.58%), C. albicans or C. africana (3.57%), C. dubliniensis (32.86%), C. parapsilosis (20%), C. inconspicua (2.14%), Pichia manshurica (2.14%), and Wickerhamomyces subpelliculosus (0.71%). It has been determined that young individuals between the ages of 18-25 carry Candida species in their oral mycobiota.
... Previous research also portrayed the similar results. 28 We speculate that these results are due to presence of comorbidity and risk factors in the elderly. Aging causes physiological and/or pathological health problems that can disrupt the balance in the oral microbial environment or preservation of the oral health leading to higher prevalence of oral candidiasis in the aging group. ...
Introduction:
Oral candidiasis is one of the most common fungal infections that has been widely reported around the world. In Malaysia, the available studies for this infection are scarce.
Materials and methods:
This is a 20-year retrospective study aimed to investigate the prevalence, demographic characteristics, clinical presentations, and the association of oral candidiasis with clinical parameters in oral candidiasis cases reported in the Faculty of Dentistry, Universiti Malaya from 1999 until 2019. A total of 12,964 histopathological records from the Oral Pathology Diagnostic and Research Laboratory (OPDRL) between 1999 to 2019 were retrieved. Oral candidiasis cases were selected according to the inclusion and exclusion criteria. Information of interest was obtained and analysed.
Results:
From the total records retrieved, 378 oral candidiasis cases were recorded and 82.8% were diagnosed from smear test. This study showed that oral candidiasis was predominantly reported in female (64.2%) and Indian population (64.2%). The peak incidence was in the sixth decades of life (27.0%). The most commonly affected site was tongue and coated tongue was the most common clinical presentation. More than 50% of the cases had comorbidity and 10.6% were associated with dentures. Ethnicity and site of occurrence were significantly associated (p<0.05) with oral candidiasis.
Conclusion:
This is the first large-scale study of oral candidiasis cases in Malaysia. The findings of this study are useful for clinical assessment of patients suspected of oral candidiasis.
... HIV/AIDS patients are usually treated topically as well as systemically. Patients with relapsing candidiasis are treated with antifungals that have the least risk of resistance development or selection of resistant strains (22). The widespread use of these antifungal agents has led to an increase in antifungal resistance. ...
Background: Oral candidiasis is an infection that follows colonization of oral cavity by Candida species mostly Candida albicans. About 90% of HIV-infected persons develop this disease during the course of HIV infection and could serve as early sign of HIV-related immunodeficiency. Treatment involves the use of antifungal drugs. The objectives of this study are to determine the prevalence of oral candidiasis and the susceptibility of isolated Candida species to available antifungal agents among selected HIV-infected patients in a mission hospital, southeast Nigeria. Methodology: This was a descriptive cross-sectional study of 150 consecutively selected HIV-infected patients attending the Heart-to-Heart clinic of Iyi-Enu mission hospital Ogidi, Anambra State, Nigeria, between December 2022 and February 2023. Demographic information of each participant was obtained using structured questionnaire. Five milliliters of whole blood were drawn from the antecubital vein of each participant for CD4+ estimation. Mouth specimens were collected using two sterile cotton swabs for microscopy and culture on Sabouraud Dextrose Agar, and Candida species were identified after subculture on CHROMAgar. Antifungal susceptibility testing was performed by Kirby-Bauer disk diffusion method using fluconazole, clotrimazole, ketoconazole, and nystatin disks, and results interpreted according to the guidelines of the Clinical and Laboratory Standards Institute. Results: A total of 98 (65.3%) HIV-infected participants were positive for oral candidiasis, with 4 species of Candida isolated; Candida albicans (62.2%), Candida glabrata (18.4%), Candida tropicalis (12.2%) and Candida krusei (7.1%). Fifty-nine (60.2%) of the 98 participants had CD4+ cell count ˂ 200, 33 (33.7%) had counts in the range of 200-399, and 6 (6.1%) had counts in the range of 400-499 cells/μL (p=0.001). The prevalence of candi- diasis was not significantly different between the female (67.0%, 65/97) and male (62.3%, 33/53) participants (p=0.6598), but the prevalence was significantly higher (p<0.05) in participants age group 21-30 years (80.7%, 42/52), divorced (100%, 1/1) and married (75%, 45/60), those with primary school level education (73.7%, 42/57), civil servants (85.7%, 18/21), and those who performed mouth hygiene once daily (71.9%, 69/96). Nystatin (77.6%, 76/98) showed the highest while fluconazole and ketoconazole (68.4%, 62/98) showed the lowest in vitro antifungal activity Conclusion: Oral candidiasis is prevalent among HIV-infected patients in the study population, with evidence of in vitro resistance of the Candida isolates to available antifungal drugs. Proper diagnosis, susceptibility testing and treatment of infection will be helpful in managing oral candidiasis infection among HIV infected patients.
... C. albicans is the main opportunistic pathogen associated with denture stomatitis. 6 Moreover, the ability C. albicans to adhere and form structured biofilms on the resin of the denture base have been considered one of the main factors responsible for the development of the disease. 7 That can evolve into a systemic infection and result in candidemia, a nosocomial infection with a high mortality rate. ...
Background:
The formation of biofilm on denture bases is a recurrent clinical problem that favors the development of denture stomatitis. The effectiveness of a hygiene protocol in a 3D-printed denture base resin is still uncertain.
Objective:
To evaluate of the effectiveness of immersion, associated or not with brushing in a soap solution, on the biofilm control of a 3D-printed denture base resin.
Methodology:
Specimens of denture base resins [Cosmos Denture (COS) and Classico (CLA/control)] were contaminated in vitro with Candida albicans and immersed in sodium hypochlorite 0.25% (SH, alkaline peroxide) AP, chlorhexidine digluconate 2% (CD or PBS-Control), associated or not with brushing with 0.78% Lifebuoy soap. Roughness was evaluated before and after brushing and immersion. The effectiveness of the protocols was assessed by CFU/mL, cellular metabolism (XTT), scanning electron microscopy (SEM), and confocal scanning laser microscopy. Data were analyzed by T student, ANOVA/Welch, and Tukey/Gomes-Howell pos-hoc tests (α = 0.05).
Results:
CLA showed greater roughness than COS. CFU/mL and XTT were higher in COS resin with a higher hyphae formation. Immersion in SH and CD eliminated CFU/mL and reduced XTT for both resins, associated or not with brushing. AP reduced CFU/mL only when associated with brushing.
Conclusions:
The biofilm on the 3D-printed resin was thicker and presumably more pathogenic, regardless of its smoother surface. Immersions in SH 0.25% and CD 2% are effective hygiene protocols for both resins, associated or not with brushing. AP should be recommended when associated with brushing with a Lifebuoy 0.78% solution.
... Local factors such as impaired local defense mechanisms, smoking, poor oral hygiene, mucosal diseases, and reduced saliva production also contribute to the development of oral candidiasis. 15 . ...
Background: Candida species biofilms commonly infect the oral cavity of cancer patients undergoing chemotherapy, leading to oral infections. These biofilms, composed of Candida organisms, pose challenges in terms of diagnosis and treatment due to their increased resistance and ability to persist in the oral environment. This study aimed to determine the frequency of Candida species biofilm colonization in the oral cavity of pediatric cancer patients receiving chemotherapy. By examining the incidence of Candida sp. biofilms, this research provides valuable insights into the oral health challenges specific to children with cancer, emphasizing the need for targeted preventive and management strategies to address these infections effectively. Materials and methods: A total of 100 oral cavity swabs were collected, with 50 swabs obtained from cancer patients undergoing chemotherapy and suspected to have oral candidiasis, and the other 50 swabs collected from non-cancer healthy individuals serving as control. All swabs were cultured on Sabouraud Dextrose agar (SDA) media, followed by microscopic examination of positive samples. The API identification candida system was utilized for the identification of Candida species, along with the implementation of biochemical tests to further study the characteristics of the identified species. Results: Our findings demonstrated that out of the 50 cancer patients, approximately 47% (23 patients) exhibited positive yeast growth on SDA agar. Among the 50 non-cancer control cases, approximately 30% (15 cases) showed positive growth on SDA agar. Furthermore, using the API candida system, we confirmed the presence of candida species in 25 cases. Candida albicans was identified as the most prevalent species, followed by Candida parapsilosis, Candida krusei, and Saccharomyces cerevisiae, which were detected less frequently. Conclusion: Our analysis reveals a significant increase in Candida species among cancer patients undergoing chemotherapy treatment in comparison to non-cancer control individuals. This finding highlights the impact of chemotherapy on the prevalence of Candida infections in cancer patients, emphasizing the need for heightened attention and appropriate management strategies in this vulnerable population
... Local and systemic factors predisposing to candidiasis.4 ...
Candida albicans is present as a normal commensal fungus of the oral cavity in 35-69% of the healthy adult population. Infection is caused by an overgrowth of these normal fungi, which can be precipitated by systemic or local host factors. Thrush is a well-known and recognisable presentation of oral candidiasis; however, it is prudent that clinicians be aware of other less common presentations.
Here we describe a case involving soft tissue changes in the oral cavity that proved to be a diagnostic challenge for clinicians across various disciplines. This case aims to highlight the diagnostic dilemma that can face clinicians when diagnosing oral lesions and the benefits of a multidisciplinary approach. Candidiasis may not always present as a white coating on the mucosa, but can also cause soft tissue changes of the tongue. The patient’s medical history should be thoroughly inspected to identify any potential contributing factors.
... Moreover, new therapeutic methods for the prevention and treatment of fungal diseases have been stimulated [18][19][20], as conventional treatments such as nystatin and azole-derived drugs result in adverse effects, including nausea and vomiting following topical use, and hepatotoxicity and gastrointestinal disorders following systemic use [12,21]. ...
Objective:
To evaluate the antimicrobial potential of silver nanoparticles (Ag NPs) synthesized using three different routes (ultraviolet light, Turkevich, and green chemistry method using Glycine max extract) associated with COREGA® denture powder adhesive.
Methods:
Heat-cured acrylic resin specimens were treated with different Ag NPs associated with the adhesive (AD + Ag UV, AD + Ag Turk, and AD + Ag Gm groups). As controls, the specimens were treated with a combination of adhesive and nystatin (AD + Nyst group), only adhesive (AD group), or submerged in (PBS group). After the treatments, biofilms of C. albicans developed for 3, 6, and 12 h on the specimen surfaces. The biofilm was quantified using colony-forming units per milliliter, colorimetric assay, and confocal laser scanning microscopy.
Results:
Regardless of the period, we observed an inhibition of fungal load and a reduction in metabolic activity and biofilm mass in the resin specimens treated with the combinations AD/Ag NPs, compared to AD and PBS. The antimicrobial action of the AD + Turk and AD + Ag Gm groups was similar than that for the AD + Nyst group in all periods and viability tests, except for the biofilm mass (12 h).
Conclusions:
The COREGA® adhesive with Ag NPs, mainly those synthesized using the Turkevich and Glycine max methods, showed excellent antimicrobial activity against C. albicans biofilms, maintained for up to 12 h.
Clinical significance:
The association of Ag NPs to the adhesive can add preventive or therapeutic effects against denture stomatitis, to this prosthetic material.
... However, the incidence of Candida albicans is around 45-90% owing to various etiological factors. 2 Some of the local and systemic factors, such as salivary gland dysfunction, dental prostheses, use of topical or inhalation corticosteroids, smoking habits, use of systemic drugs, an association of endocrine disorders, immunodeficiency conditions, and malignant diseases, have been associated with the predisposing factors for oral candidiasis. 3 Oral Candida infection is generally present in acute or chronic forms. The main variants are pseudomembranous, erythematous, hyperplastic types, Candidaassociated lesions, and keratinized lesions, which are superimposed with Candida. 4 There are various mechanisms involved with the causative factors of oral candidiasis. ...
Oral lichen planus (OLP) is a chronic inflammatory disease that commonly affects the skin and mucous membranes. There is a difference of opinion among clinicians about whether OLP has been associated with oral candidiasis. Nonetheless, in OLP patients, the oral candidiasis prevalence rate ranges from 7.7 to 16.6%, as established through biopsy findings, whereas 37-50% of the prevalence rate has been noticed in culture findings. Oral candidiasis has been linked to several local and systemic factors, including salivary gland dysfunction, dental prostheses, topical or inhaled corticosteroids, smoking, and the use of systemic medications. The aim was to highlight the association of Candida in patients diagnosed with OLP, correlate the use of steroid therapy, and enumerate the factors of using steroid therapy as implicated causes for oral candidiasis. A search was made using search engines such as PubMed, Scopus, Cochrane Database of Systematic Reviews, Science Citation Index, NIH Public Access, and Clarivate Analytics (Figure 1). The keywords using the research option for this field were "Oral Candidiasis" AND "Oral Lichen planus" or "Candidiasis" AND "Corticosteroids" or "Topical Corticosteroids" AND Oral Lichen planus or "Inhalation Corticosteroids" AND "Candidiasis" or "Oral Lichen planus" AND "Corticosteroids." The database search was made for the duration of 1991 to -2021 (Table 1). Additional articles were obtained regarding the literature on OLP and oral candidiasis and were considered background material. The incidence of oral candidiasis and associated lichen planus following steroid therapy enlisted by various authors has been addressed. According to the results of this study, there is a positive correlation between the presence of oral candidiasis in the OLP's patients treated with corticosteroids. Finally, this meta-analysis concluded that there is a positive correlation between the presence of Candida species in OLP and steroid medication.
... Kandida enfeksiyonu sigara içen, protez takan, glisemik kontrolü zayıf olan, geniş spektrumlu antibiyotik ve kortikosteroid kullanan diyabet hastalarında daha yaygın olarak görülür. Teşhisin doğrulanmasından sonra, topikal veya sistemik antifungal ajanlar reçete edilebilir (Rautemaa & Ramage, 2011;Balan et al., 2015;Nazir et al., 2018;Rohani, 2019). ...
... isolates that were identified in a single clinical sample; one of the species was C. glabrata, which was resistant to both Fluconazole and Amphotericin, and the other was C. krusei, which was resistant to Fluconazole. This finding is relevant because Fluconazole is the drug of choice for candidiasis treatment in AIDS patients although it has a fungistatic action (35,36), and both Fluconazole and Amphotericin were being used by some of the patients who participated in the research. Four patients had double colonization, and one of them had colonization by C. krusei resistant to Fluconazole. ...
Candidiasis is the most common fungal infection in hospitalized patients with acquired immune deficiency syndrome resulting to morbidity and mortality. This study aimed at characterizing, incidence, susceptibility, resistance genes, antibiofilm activity, and virulence traits of Candida species isolated from HIV-Infected patients. One hundred and eighty-one samples were collected and cultured on Sabouraud Dextrose Agar, biochemical tests and confirmed using automated Vitek-2® Compact bioMérieux followed by susceptibility tests. were done by use of various conventional antifungals against the isolates using standard procedures. Virulence factors, biofilm formations and resistance genes of Candida strains were determined. Out of the 181 samples, 46 were identified as Candida spp., 20 C. albicans (43.5%), 6 C. tropicalis (13.0%), 8 C. krusei (17.4%), 4 C. glabrata (8.7%), 3 C. famata (6.5%), 3 C. parapsilosis (6.5%), and 2 C. guilliermondii (4.3%). All the Candida albicans isolated were both Gram positive and Germ test tube test positive. Eighteen (90%) of the isolates were susceptible to Clotrimazole at a concentration of 5 μg/mL – 10μg/mL followed by 17 (85%) isolates to Panosoconazole at a concentration of 0.002 μg/mL – 5μg/mL. Eight (40.0 %) of the Candida albicans isolates possessed the gene (cdr1) that was observed at 286 bp. Virulence enzymes was determined in which 100% produced Haemolysin, followed by proteinase (75.0%), phospholipase (50%), coagulase at (50%) and lastly capsulase (25.0%). Fluconazole and Clotrimazole did not inhibit growth of C. albicans at high concentrations but from our study, it was deduced that they inhibit biofilm formation at lower concentrations. C. albicans isolates were resistant to multiple antifungal including those commonly used in the management on HIV/AIDs patient. This attributed to resistant genes and produced various virulence factors that were found to be present in the isolates. Therefore, there is a need to carry out regular surveillance on antifungal drug resistance.
... isolated from diabetic patients, the highest frequency was seen in the pH 6 group with 23 cases followed by pH 5 and pH 7 groups with each 14 cases. This study confirms prior findings that an acidic pH in the mouth favors candidal growth over normal bacterial microbiota growth [22]. Three Candida species tested in this study, found to have varying levels of susceptibility to the antifungal drugs used. ...
Oral candidiasis is a type of fungal infection that mostly affects the oral mucosa. Candida sp., the primary causative agent, is a highly adaptable commensal organism that is well adapted to its host. Contemporary knowledge of pathogens and their antibiotic susceptibility patterns is critical for keeping antibiotic policies up to date. This study was undertaken by collecting and analyzing samples from rural areas of Sirajganj, Bangladesh to determine the prevalence of Candida species that cause oral candidiasis and to determine their susceptibility pattern to antifungal drugs. SPSS analysis was done for quantitative data, i.e., the positive sample numbers and the different ages, sex, and medical conditions of carriers. A total of 304 clinical samples were collected aseptically from patients with oral candidiasis, with 64 showing positive growth with Candida sp. Further analysis revealed that the oral prevalence of Candida sp. among diabetic people was higher than that of non-diabetics, where Candida albicans (80.8%) was the most prevalent species, followed by Candida glabrata (9.6%) and Candida krusei (9.6%). We also found that Candida sp. grow best in acidic conditions (pH level 7 or less). Finally, varying levels of susceptibility to antifungal drugs were also evaluated. Nystatin and Amphotericin B had the highest sensitivity for Candida glabrata, each at 100.0%, and Fluconazole had 100% sensitivity for Candida krusei. Itraconazole and Voriconazole were highly resistant to all examined isolates (50-62%) except for Itraconazole, which exhibited 80% susceptibility to Candida krusei. These findings are crucial to identifying causative pathogens and determining the sensitivity patterns of drugs, as well as improving clinicians' knowledge of how to select the best medicine and, as a result, contributing to patient diagnosis and treatment.
... 24,31,33e37 Empirically, the treatment duration of nystatin can vary from 1 or 2e4 weeks. 24,31,32,37,38 Clinically, the symptoms of morphologically normal symptomatic candidiasis are similar to the symptoms of BMS, and if the patients have no visible oral mucosal lesions, they are easy to be diagnosed as primary BMS and treated with antidepressants or anticonvulsants, such as clonazepam. 12,15,16 However, for part of these patients, the effect of antidepressant or anticonvulsant treatment is limited. ...
Background/purpose
Previous studies have shown that some of the patients with oral mucosal dysesthesia but without objective oral mucosal manifestations (so-called oral dysesthesia patients in this study) may have good responses to oral nystatin treatment. This study evaluated the efficacy of oral nystatin treatment for oral dysesthesia patients and the necessity of Candida culture test before oral nystatin treatment.
Materials and methods
The 147 oral dysesthesia patients were divided into 3 groups: Candida culture (+) group (n = 29), Candida culture (−) group (n = 34), and without Candida culture test group (n = 84), and treated with oral nystatin. The pain improvement was evaluated by the reduction of numeric pain rating scale (NRS) and global perceived effects (GPE). We defined the GPE score ≥4 points as a great improvement.
Results
We found that 44.8% of 29 patients in the Candida culture (+) group, 47.1% of 34 patients in the Candida culture (−) group, and 47.6% of 84 patients in the without Candida culture test group showed a significant reduction in the NRS score and achieved a great improvement after oral nystatin treatment for 1–4 weeks. Moreover, 72.4% of our 29 patients with Candida culture test achieved a great improvement within one week, and all the 29 patients achieved a great improvement within 4 weeks of oral nystatin treatment.
Conclusion
A portion of our oral dysesthesia patients are infected by Candida and it is beneficial to our patients to use oral nystatin treatment before the Candida culture test.
... As a typical representative of oral fungi, Candida albicans is quite common in the oral cavity and known as a polymorphic fungus that can grow in either yeast or filamentous form, which usually inhabits the skin, the oral cavity, the gastrointestinal tract, and the lower female reproductive tract [16,17]. Under normal circumstances, C. albicans shows a form of yeast and presents as non-pathogenic. ...
In this study, the corrosion behavior and mechanism of Ti-6Al-4V in artificial saliva with Candida albicans were investigated using electrochemical and surface analysis techniques. Fluorescence microscopy (FM) and confocal laser scanning microscopy (CLSM) showed that C. albicans could easily adsorb on the surface of Ti-6Al-4V alloy to form non-dense biofilm. The non-compact biofilm provided necessary conditions for pitting corrosion on Ti-6Al-4V alloys by scanning electron microscopy (SEM) observation. The potentiodynamic polarization (PDP) curves and electrochemical impedance spectroscopy (EIS) revealed that C. albicans significantly reduced the corrosion resistance of Ti-6Al-4V alloys. The cyclic voltammetry (CV) and differential pulse voltammetry (DPV) results indicated that C. albicans biofilm promoted electron transfer from the anodic sites to cathodic depolarizer during the corrosion process, showing that the role of oral fungi must be considered when evaluating the performance of oral materials. This study may provide a new clue for evaluating the corrosion resistance of dental implant materials in the oral environment.
... OC is a fungal infection of the human oral mucosal epithelium, caused mainly by the pathogenic fungus, C. albicans [1]. C. albicans is an opportunist fungus in oral mucosa, that under specific conditions could invade tissues by either endocytosis or direct penetration, and stimulate damage of the epithelium tissue [2]. ...
Oral candidiasis (OC) is a fungal infection caused by an opportunistic fungi Candida albicans, which is found in the normal flora of healthy people. In this study, we examined the anti-candidal effect of green synthesized silver nanoparticles using leaf extract of Erodium glaucophyllum (EG-AgNPs) against C. albicans in vitro and in vivo. EG-AgNPs were synthesized for the first time using E. glaucophyllum extract and characterized by imaging (transmission electron microscopy (TEM), UV-VIS spectroscopy, zeta potential, X-ray diffraction (XRD), Energy dispersive x-ray analysis (EDX), and Fourier transform infrared spectroscopy (FTIR). A mouse model of OC was used for in vivo study. The agar well diffusion method showed the anti-candidal activity of EG-AgNPs against C. albicans with MIC 50 µg/mL. EG-AgNPs inhibited the dimorphic transition of C. albicans and suppressed the formation of biofilm by 56.36% and 52%, respectively. Additionally, EG-AgNPs significantly inhibited the production of phospholipases and proteinases by 30% and 45%, respectively. EG-AgNPs cause cytoplasm disintegration and deterioration of cell wall as imaged by SEM and TEM. Interestingly, EG-AgNPs did not display any cytotoxicity on the human gingival fibroblast-1 HGF-1 cell line at MIC concentrations. Topical treatment of the tongue of the OC mouse model with EG-AgNPs showed significant reduction in candidal tissue invasion, less inflammatory changes, and no tissue modification, in association with marked low scare and hyphal counts as compared to control group. In conclusion, our data demonstrated the potent inhibitory action of EG-AgNPs on the growth and morphogenesis of C. albicans in vitro and in vivo. Thus, EG-AgNPs represent a novel plausible therapeutic approach for treatment of OC.
Antimicrobial resistance and oral dysbiosis often reduce the efficacy of conventional antimicrobial treatments. In addition, poor permeability and insufficient accumulation of therapeutic agents in biofilms are the main causes of failure in the treatment of oral infections. Antimicrobial photodynamic therapy (PDT) is a versatile therapeutic approach that uses light-activated photosensitizers to fight bacterial infections. When irradiated with light of a specific wavelength, photosensitizers generate reactive oxygen species that selectively damage microbial cells. However, most photosensitizers are poorly soluble in water, which limits their clinical application. Nanotechnology offers a promising solution by incorporating nanocarriers into PDT. Nanocarriers can play a crucial role in improving PDT by overcoming the limitations of conventional photosensitizers. They can encapsulate photosensitizers, protect them from premature degradation, and improve their penetration and delivery to target sites. In this review, different drug delivery systems based on nanocarriers are investigated to improve the efficacy of PDT in dental applications.
Human beings are indwelled by a wide array of cellular microbes, building up their core microbiome. Amongst these, bacterial constituents comprise about 99% of the population. The remaining small, yet diverse population of microbes are termed the ‘rare-biosphere’. The eukaryotic yeasts contribute a substantial population within the rare biosphere. Despite the reduced abundance, yeasts/fungi cause a wide range of infections ranging from superficial to deep-seated, invasive, and life-threatening infections. This chapter provides an in-depth view of the role of fungi, specifically Candida albicans, in oral health and disease. We highlight the interactive profiles between the mycobiome and host oral tissues including study models for future state-of-the-art research in this important area.
The therapy of invasive candidiasis has evolved significantly over the last decade and must continue to adapt if we are to improve outcomes in this deadly infection. The treatment choices for this illness are numerous. The right technique must be selected based on the circumstances and the patient profile; occasionally, a combination of strategies is advised. Azoles, polyenes, and echinocandins are the three main therapeutic classes that are widely utilized. The success of those innovations is threatened by the rise in antibiotic resistance, though, which is encouraging researchers to keep looking for alternatives. Future changes to the management of invasive candidiasis may be influenced by these advancements as well as the continuous research underway on dose, toxicity, and resistance development.
Candida albicans, a significant human pathogenic fungus, employs hydrolytic proteases for host invasion. Conventional antifungal agents are reported with resistance issues from around the world. This study investigates the role of Bacillus licheniformis extracellular proteins (ECP) as effective antifungal peptides (AFPs). The aim was to identify and characterize the ECP of B. licheniformis through LC-MS/MS and bioinformatics analysis. LC-MS/MS analysis identified 326 proteins with 69 putative ECP, further analyzed in silico. Of these, 21 peptides exhibited antifungal properties revealed by classAMP tool and are predominantly anionic. Peptide-protein docking revealed interactions between AFPs like Peptide chain release factor 1 (Q65DV1_Seq1: SASEQLSDAK) and Putative carboxy peptidase (Q65IF0_Seq7: SDSSLEDQDFILESK) with C. albicans virulent SAP5 proteins (PDB ID 2QZX), forming hydrogen bonds and significant Pi-Pi interactions. The identification of B. licheniformis ECP is the novelty of the study that sheds light on their antifungal potential. The identified AFPs, particularly those interacting with bonafide pharmaceutical targets SAP5 of C. albicans represent promising avenues for the development of antifungal treatments with AFPs that could be the pursuit of a novel therapeutic strategy against C. albicans.
Introduction: The COVID-19 pandemic has underscored the critical importance of robust public health infrastructure in addressing infectious diseases. This chapter investigates Ghana's demographic effects and public health infrastructure challenges amidst the COVID-19 crisis. Purpose and Objectives: This study aims to analyze the impact of COVID-19 on demographic trends and public health infrastructure in Ghana. Specifically, it seeks to examine the mortality rates, healthcare accessibility, and infrastructure deficits exacerbated by the pandemic. Literature Review: Previous research highlights the significant demographic disruptions caused by pandemics, leading to elevated mortality rates and exacerbation of existing health disparities. Additionally, studies have identified underfunding and underproduction of global health resources as critical challenges in the pandemic response. System thinking concepts emphasize understanding the interplay of factors within the health system, while the theory of health and development underscores the importance of a healthy population for economic growth. Methodology: This study employs a qualitative research approach utilizing corpus construction and secondary data analysis. The selection of materials for analysis is functionally equivalent to sampling, allowing for a comprehensive examination of demographic effects and health infrastructure deficits. Results: The findings reveal the profound demographic disruptions caused by COVID-19, including increased mortality rates and challenges in accessing healthcare services. Moreover, the study highlights the underfunding and underproduction of global health resources, as evidenced by findings from the World Health Organization. Conclusions: The study underscores the need for international cooperation and strategic alliances to address the multifaceted challenges posed by pandemics. Recommendations include prioritizing vaccine distribution, strengthening international health systems, improving service quality, and increasing financial investments in public health infrastructure.
Compared with antibiotics for treating bacterial infections, there are a limited number of antifungal agents. This is due to several factors, including the difficulties of identifying suitable antifungals that target the fungal cell without damaging host cells, and the reduced rates of diagnosis of fungal infections compared with those caused by bacteria. The problem of treating fungal infections is exacerbated by an increasing incidence of antifungal resistance among human fungal pathogens. Three XF drugs (XF-73, XF-70, and DPD-207) have previously displayed innate bactericidal effects and a low propensity for microbial resistance, with XF-73 and XF-70 having a second, light-activated mechanism of action [known as photodynamic therapy (PDT)]. In an effort to expand the repertoire of antifungal agents, this research assessed the in vitro activity of XF drugs via both mechanisms of action against six strains of the fungal pathogen Candida albicans in both planktonic and biofilm cultures. In addition, this research examined the effects of XF drug treatment on biofilms of C. albicans in a reconstituted human oral epithelium model. All C . albicans strains tested were susceptible to XF-73 and XF-70, with minimum inhibitory concentrations (MICs) between 0.25 µg/mL and 2 µg/mL; DPD-207 was less potent, with MICs between 4 µg/mL and 16 µg/mL, and light activation did not enhance these MICs. Complete biofilm eradication was not reported at the tested XF drug concentrations. However, live and dead staining of C. albicans cells in biofilms after XF drug treatment demonstrated that XF-73 and XF-70 were active against most Candida biofilms tested from 64 µg/mL; again, light activation did not enhance anti-biofilm activity. Candida biofilms were more resistant to DPD-207, with fungicidal effects occurring from 256 µg/mL. XF-73 and XF-70 reduced penetration of C. albicans biofilm into reconstituted human oral epithelium (RHOE) and resulted in less damage (as determined by reduced lactate dehydrogenase release) than untreated biofilms. Overall, the results highlight the potential of XF drugs as new drugs for the management of topical infections caused by C. albicans . Further studies are warranted on the development of XF drugs as antifungals, particularly for XF-73 and XF-70.
Oral thrush is candidal infection of mouth called candidiasis. It is an ubiquitous infectious disease and its incidence has been increasing over the last few years, not only in children but also in immunocompromised patients, thus becoming a public health problem. Lysozyme, a natural component of saliva has been reported for its anticandidal activity thus hyposalivation causes candidasis. The aim of this study is to formulate and investigate the synergistic anticandidal effect of mouth paint containing lysozyme and fruit extract of Coccinia indica against Candida albicans. In combination with C. indica fruit extract, the concentration of lysozyme for inhibiting the growth of the tested Candida species could be reduced by 50%. The minimum inhibitory concentration (MIC) of lysozyme and fruit extract of C. indica against Candida species is 160 µg/ml of each. These results support the potential use of lysozyme and C. indica fruit extract as an anticandidal agent in treatment of oral thrush.
Candidiasis is the most common fungal infection in hospitalized patients with acquired immune deficiency syndrome resulting to morbidity and mortality. This study is aimed at characterizing, incidence, susceptibility, resistance genes, antibiofilm activity, and virulence traits of Candida species isolated from HIV-Infected patients. One hundred and eighty-one samples were collected and cultured on Sabouraud Dextrose Agar, biochemical tests and confirmed using automated Vitek-2 ® Compact bioMérieux followed by susceptibility tests, done by use of various conventional antifungals against the isolates using standard procedures. Virulence factors, biofilm formations and resistance genes of Candida strains were determined. Out of the 181 samples, 46 were identified as Candida spp., 20 C. albicans (43.5%), 6 C. tropicalis (13.0%), 8 C. krusei (17.4%), 4 C. glabrata (8.7%), 3 C. famata (6.5%), 3 C. parapsilosis (6.5%), and 2 C. guilliermondii (4.3%). All the Candida albicans isolated were both Gram positive and Germ test tube test positive. Eighteen (90%) of the isolates were susceptible to Clotrimazole at a concentration of 5 μg/mL – 10μg/mL followed by 17 (85%) isolates to Panosoconazole at a concentration of 0.002 μg/mL – 5μg/mL. Eight (40.0%) of the Candida albicans isolates possessed the gene (cdr1) that was observed at 286 bp. Virulence enzymes was determined in which 100% produced Haemolysin, followed by proteinase (75.0%), phospholipase (50%), coagulase at (50%) and lastly capsulase (25.0%). Fluconazole and Clotrimazole did not inhibit growth of C. albicans at high concentrations but from our study, it was deduced that they inhibit biofilm formation at lower concentrations. C. albicans isolates were resistant to multiple antifungal including those commonly used in the management on HIV/AIDs patient. This attributed to resistant genes and produced various virulence factors that were found to be present in the isolates. Therefore, there is a need to carry out regular surveillance on antifungal drug resistance.
The United Nations suggests the global population of denture wearers (an artificial device that acts as a replacement for teeth) is likely to rise significantly by 2050. Dentures become colonised by microbial biofilms, the composition of which is influenced by complex factors such as patient age and health, and the nature of the denture material. Since colonisation (and subsequence biofilm formation) by some microorganisms can significantly impact the health of the denture wearer, the study of denture microbiology has long been of interest to researchers. The specific local and systemic health risks of denture plaque are different from those of dental plaque, particularly with respect to the presence of the opportunist pathogen Candida albicans and various other non‐oral opportunists. Here, we reflect on advancements in our understanding of the relationship between microorganisms, dentures and the host, and highlight how our growing knowledge of the microbiome, biofilms and novel antimicrobial technologies may better inform diagnosis, treatment and prevention of denture‐associated infections, thereby enhancing the quality and longevity of denture wearers.
This chapter discusses the antifungal properties of various extracts of propolis collected from southern Brazil and other locations around the world. Antifungal action from propolis extract has been reported against several fungi (e.g., Candida sp., Fusarium sp., and Trichophyton sp.) responsible for causing skin and mucosal infections. Propolis has been shown to prevent invasive fungal infections. It is also used for medical device coating. This chapter examines the use of propolis (and derivatives), possible mechanisms of action, and development with new drug delivery systems.
Objective:
This study investigated the antifungal and antibiofilm activity of Cymbopogon nardus essential oil (EO) and its major compound, citronellal, in association with miconazole and chlorhexidine on clinical strains of Candida albicans. The likely mechanism(s) of action of C. nardus EO and citronellal was further determined.
Materials and methods:
The EO was chemically characterized by gas chromatography coupled with mass spectrometry (GC-MS). The antifungal activity (MIC/MFC) and antibiofilm effects of C. nardus EO and citronellal were determined by the microdilution method, and their likely mechanism(s) of action was determined by the sorbitol and ergosterol assays. Then, the samples were tested for a potential association with standard drugs through the checkerboard technique. Miconazole and chlorhexidine were used as positive controls and the assays were performed in triplicate.
Results:
The GC-MS analysis tentatively identified citronellal as the major compound in C. nardus EO. Both samples showed antifungal activity, with MIC of 256 µg/mL, as compared to 128 µg/mL and 8 µg/mL of miconazole and chlorhexidine, respectively. C. nardus EO and citronellal effectively inhibited biofilm formation (p < 0.05) and disrupted preformed biofilms (p < 0.0001). They most likely interact with the cell membrane, but not the cell wall, and did not present any synergistic activity when associated with standard drugs.
Conclusion:
C. nardus EO and citronellal showed strong in vitro antifungal and antibiofilm activity on C. albicans.
Clinical relevance:
Natural products have been historically bioprospected for novel solutions to control fungal biofilms. Our data provide relevant insights into the potential of C. nardus EO and citronellal for further clinical testing. However, additional bioavailability and toxicity studies must be carried out before these products can be used for the chemical control of oral biofilms.
Patients with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED, APS-I) suffer from chronic candidosis caused mainly by Candida albicans, and repeated courses of azole antifungals have led to the development of resistance in the APECED patient population in Finland. The aim of our study was to address whether the patients are persistently colonized with the same or genetically closely related strains, whether epidemic strains are present and which molecular mechanisms account for azole resistance.
Sets of C. albicans (n = 19) isolates from nine APECED patients reported with decreased susceptibility to fluconazole isolated up to 9 years apart were included. The strains were typed by multilocus sequence typing. CDR1/2, MDR1 and ERG11 mRNA expression was analysed by northern blotting and Cdr1, Cdr2 and Mdr1 protein expression by western blotting, and TAC1 and ERG11 genes were sequenced.
All seven patients with multiple C. albicans isolates analysed were persistently colonized with the same or a genetically closely related strain for a mean of 5 years. All patients were colonized with different strains and no epidemic strains were found. The major molecular mechanisms behind the azole resistance were mutations in TAC1 contributing to overexpression of CDR1 and CDR2. Six new TAC1 mutations were found, one of which (N740S) is likely to be a gain-of-function mutation. Most isolates were found to have gained multiple TAC1 and ERG11 point mutations.
Despite clinically successful treatment leading to relief of symptoms, colonization by C. albicans strains is persistent within APECED patients. Microevolution and point mutations occur within strains, leading to the development of azole-resistant isolates.
Candida albicans can form biofilms that exhibit elevated intrinsic resistance to various antifungal agents, in particular azoles and polyenes. The molecular mechanisms involved in the antifungal resistance of biofilms remain poorly understood. We have used transcript profiling to explore the early transcriptional responses of mature C. albicans biofilms exposed to various antifungal agents. Mature C. albicans biofilms grown under continuous flow were exposed for as long as 2 h to concentrations of fluconazole (FLU), amphotericin B (AMB), and caspofungin (CAS) that, while lethal for planktonic cells, were not lethal for biofilms. Interestingly, FLU-exposed biofilms showed no significant changes in gene expression over the course of the experiment. In AMB-exposed biofilms, 2.7% of the genes showed altered expression, while in CAS-exposed biofilms, 13.0% of the genes had their expression modified. In particular, exposure to CAS resulted in the upregulation of hypha-specific genes known to play a role in biofilm formation, such as ALS3 and HWP1. There was little overlap between AMB- or CAS-responsive genes in biofilms and those that have been identified as AMB, FLU, or CAS responsive in C. albicans planktonic cultures. These results suggested that the resistance of C. albicans biofilms to azoles or polyenes was due not to the activation of specific mechanisms in response to exposure to these antifungals but rather to the intrinsic properties of the mature biofilms. In this regard, our study led us to observe that AMB physically bound C. albicans biofilms and beta-glucans, which have been proposed to be major constituents of the biofilm extracellular matrix and to prevent azoles from reaching biofilm cells. Thus, enhanced extracellular matrix or beta-glucan synthesis during biofilm growth might prevent antifungals, such as azoles and polyenes, from reaching biofilm cells, thus limiting their toxicity to these cells and the associated transcriptional responses.
The oral microbiome-organisms residing in the oral cavity and their collective genome-are critical components of health and disease. The fungal component of the oral microbiota has not been characterized. In this study, we used a novel multitag pyrosequencing approach to characterize fungi present in the oral cavity of 20 healthy individuals, using the pan-fungal internal transcribed spacer (ITS) primers. Our results revealed the "basal" oral mycobiome profile of the enrolled individuals, and showed that across all the samples studied, the oral cavity contained 74 culturable and 11 non-culturable fungal genera. Among these genera, 39 were present in only one person, 16 genera were present in two participants, and 5 genera were present in three people, while 15 genera (including non-culturable organisms) were present in >/=4 (20%) participants. Candida species were the most frequent (isolated from 75% of participants), followed by Cladosporium (65%), Aureobasidium, Saccharomycetales (50% for both), Aspergillus (35%), Fusarium (30%), and Cryptococcus (20%). Four of these predominant genera are known to be pathogenic in humans. The low-abundance genera may represent environmental fungi present in the oral cavity and could simply be spores inhaled from the air or material ingested with food. Among the culturable genera, 61 were represented by one species each, while 13 genera comprised between 2 and 6 different species; the total number of species identified were 101. The number of species in the oral cavity of each individual ranged between 9 and 23. Principal component (PCO) analysis of the obtained data set followed by sample clustering and UniFrac analysis revealed that White males and Asian males clustered differently from each other, whereas both Asian and White females clustered together. This is the first study that identified the "basal mycobiome" of healthy individuals, and provides the basis for a detailed characterization of the oral mycobiome in health and disease.
Recovery of Candida from the respiratory tract is common. Large series on the incidence of histologically proven Candida pneumonia in intensive care unit (ICU) patients are lacking.
A two-year prospective study of all autopsies performed on patients who died in the ICU was conducted. For autopsy-proven cases of Candida pneumonia, we required microscopic demonstration of yeast invasion in lung autopsy specimens that showed inflammation. We looked for differences in incidence in patients with and without respiratory samples positive for Candida species pre-mortem.
Of 1,587 patients admitted to the ICU, 301 (19%) died of whom 232 (77%) were autopsied. Of those, 135 patients (58%) had histopathological evidence of pneumonia. A total of 77 cases (57%) with pneumonia at autopsy had positive tracheal aspirate and/or BAL cultures for Candida spp. performed during the preceding two weeks. No cases of Candida pneumonia were identified amongst those 77 cases. In the other 58 patients with autopsy-proven pneumonia and no Candida isolation pre-mortem, no Candida pneumonia was observed either.
Despite frequent isolation of Candida spp. from the airways, over a two-year period no single case of Candida pneumonia was found among the patients with evidence of pneumonia on autopsy. This study indicates that Candida pneumonia is an extremely rare occurrence in ICU patients and provides further evidence against the common use of antifungal therapy triggered by a microbiology report of Candida isolation from the respiratory tract.
A quantitative real-time RT-PCR system was established to identify which secreted aspartyl proteinase (SAP) genes are most highly expressed and potentially contribute to Candida albicans infection of human epithelium in vitro and in vivo. C. albicans SC5314 SAP1-10 gene expression was monitored in organotypic reconstituted human epithelium (RHE) models, monolayers of oral epithelial cells, and patients with oral (n=17) or vaginal (n=17) candidiasis. SAP gene expression was also analysed in Deltasap1-3, Deltasap4-6, Deltaefg1 and Deltaefg1/cph1 mutants to determine whether compensatory SAP gene regulation occurs in the absence of distinct proteinase gene subfamilies. In monolayers, RHE models and patient samples SAP9 was consistently the most highly expressed gene in wild-type cells. SAP5 was the only gene significantly upregulated as infection progressed in both RHE models and was also highly expressed in patient samples. Interestingly, the SAP4-6 subfamily was generally more highly expressed in oral monolayers than in RHE models. SAP1 and SAP2 expression was largely unchanged in all model systems, and SAP3, SAP7 and SAP8 were expressed at low levels throughout. In Deltasap1-3, expression was compensated for by increased expression of SAP5, and in Deltasap4-6, expression was compensated for by SAP2: both were observed only in the oral RHE. Both Deltasap1-3 and Deltasap4-6 mutants caused RHE tissue damage comparable to the wild-type. However, addition of pepstatin A reduced tissue damage, indicating a role for the Sap family as a whole in inducing epithelial damage. With the hypha-deficient mutants, RHE tissue damage was significantly reduced in both Deltaefg1/cph1 and Deltaefg1, but SAP5 expression was only dramatically reduced in Deltaefg1/cph1 despite the absence of hyphal growth in both mutants. This indicates that hypha formation is the predominant cause of tissue damage, and that SAP5 expression can be hypha-independent and is not solely controlled by the Efg1 pathway but also by the Cph1 pathway. This is believed to be the first study to fully quantify SAP gene expression levels during human mucosal infections; the results suggest that SAP5 and SAP9 are the most highly expressed proteinase genes in vivo. However, the overall contribution of the Sap1-3 and Sap4-6 subfamilies individually in inducing epithelial damage in the RHE models appears to be low.
The purpose of this study was to develop a site-specific sampling method that could give representative and quantitative results for defined areas of the oral mucosa and would be easy to use. Two site-specific sampling methods (swab and filter paper imprint) were compared. The filter paper sampling method was developed for this study. Samples were collected from 14 volunteers. All samples were cultured under aerobic and anaerobic conditions. The number of viable bacteria and yeasts was determined and expressed per unit area. The filter paper recovered a significantly higher number of colony types of bacteria compared to the swab sample. Both collected a large number and variety of different oral microbes. The filter paper sampling method could be the optimal technique for quantitative site-specific oral mucosal samples and is highly suitable for both culture-based and non-culture-based identification of oral microbes.
The incidence of fungal infections has increased significantly over the past decades. Very often these infections are associated with biofilm formation on implanted biomaterials and/or host surfaces. This has important clinical implications, as fungal biofilms display properties that are dramatically different from planktonic (free-living) populations, including increased resistance to antifungal agents. Here we describe a rapid and highly reproducible 96-well microtiter-based method for the formation of fungal biofilms, which is easily adaptable for antifungal susceptibility testing. This model is based on the ability of metabolically active sessile cells to reduce a tetrazolium salt (2,3-bis(2-methoxy-4-nitro-5-sulfo-phenyl)-2H-tetrazolium-5-carboxanilide) to water-soluble orange formazan compounds, the intensity of which can then be determined using a microtiter-plate reader. The entire procedure takes approximately 2 d to complete. This technique simplifies biofilm formation and quantification, making it more reliable and comparable among different laboratories, a necessary step toward the standardization of antifungal susceptibility testing of biofilms.
Direct observations have clearly shown that biofilm bacteria predominate, numerically and metabolically, in virtually all nutrient-sufficient ecosystems. Therefore, these sessile organisms predominate in most of the environmental, industrial, and medical problems and processes of interest to microbiologists. If biofilm bacteria were simply planktonic cells that had adhered to a surface, this revelation would be unimportant, but they are demonstrably and profoundly different. We first noted that biofilm cells are at least 500 times more resistant to antibacterial agents. Now we have discovered that adhesion triggers the expression of a sigma factor that derepresses a large number of genes so that biofilm cells are clearly phenotypically distinct from their planktonic counterparts. Each biofilm bacterium lives in a customized microniche in a complex microbial community that has primitive homeostasis, a primitive circulatory system, and metabolic cooperativity, and each of these sessile cells reacts to its special environment so that it differs fundamentally from a planktonic cell of the same species.
Denture biofilms represent a protective reservoir for oral microbes. The study of the biology of Candida in these biofilms requires a reliable model. A reproducible model of C. albicans denture biofilm was developed and used to determine the susceptibility of two clinically relevant C. albicans isolates against 4 antifungals. C. albicans, growing as a biofilm, exhibited resistance to amphotericin B, nystatin, chlorhexidine, and fluconazole, with 50% reduction in metabolic activity (50% RMA) at concentrations of 8, 16, 128, and > 64 microg/mL, respectively. In contrast, planktonically cultured C. albicans were susceptible (50% RMA for the same antifungals was obtained at 0.25, 1.0, 4.0, and 0.5 microg/mL, respectively). In conclusion, results obtained by means of our biofilm model show that biofilm-associated C. albicans cells, compared with cells grown in planktonic form, are resistant to antifungals used to treat denture stomatitis.
Candida albicans is implicated in many biomaterial-related infections. Typically, these infections are associated with biofilm formation.
Cells in biofilms display phenotypic traits that are dramatically different from those of their free-floating planktonic counterparts
and are notoriously resistant to antimicrobial agents. Consequently, biofilm-related infections are inherently difficult to
treat and to fully eradicate with normal treatment regimens. Here, we report a rapid and highly reproducible microtiter-based
colorimetric assay for the susceptibility testing of fungal biofilms, based on the measurement of metabolic activities of
the sessile cells by using a formazan salt reduction assay. The assay was used for in vitro antifungal susceptibility testing
of severalC. albicans strains grown as biofilms against amphotericin B and fluconazole and the increased resistance of C. albicans biofilms against these antifungal agents was demonstrated. Because of its simplicity, compatibility with a widely available
96-well microplate platform, high throughput, and automation potential, we believe this assay represents a promising tool
for the standardization of in vitro antifungal susceptibility testing of fungal biofilms.
Biofilms, likely the predominant mode of device-related microbial infection, exhibit resistance to antimicrobial agents. Evidence
suggests that Candida biofilms have dramatically reduced susceptibility to antifungal drugs. We examined antifungal susceptibilities of Candida albicans and Candida parapsilosis biofilms grown on a bioprosthetic model. In addition to conventional agents, we determined if new antifungal agents (triazoles,
amphotericin B lipid formulations, and echinocandins) have activities against Candida biofilms. We also explored effects of preincubation of C. albicans cells with subinhibitory concentrations (sub-MICs) of drugs to see if they could modify subsequent biofilm formation. Finally,
we used confocal scanning laser microscopy (CSLM) to image planktonic- and biofilm-exposed blastospores to examine drug effects
on cell structure. Candida biofilms were formed on silicone elastomer and quantified by tetrazolium and dry weight (DW) assays. Susceptibility testing
of fluconazole, nystatin, chlorhexidine, terbenafine, amphotericin B (AMB), and the triazoles voriconazole (VRC) and ravuconazole
revealed resistance in all Candida isolates examined when grown as biofilms, compared to planktonic forms. In contrast, lipid formulations of AMB (liposomal
AMB and AMB lipid complex [ABLC]) and echinocandins (caspofungin [Casp] and micafungin) showed activity against Candida biofilms. Preincubation of C. albicans cells with sub-MIC levels of antifungals decreased the ability of cells to subsequently form biofilm (measured by DW; P < 0.0005). CSLM analysis of planktonic and biofilm-associated blastospores showed treatment with VRC, Casp, and ABLC resulted
in morphological alterations, which differed with each agent. In conclusion, our data show that Candida biofilms show unique susceptibilities to echinocandins and AMB lipid formulations.
Candida albicans is the most common fungal pathogen of humans and has developed an extensive repertoire of putative virulence mechanisms that allows successful colonization and infection of the host under suitable predisposing conditions. Extracellular proteolytic activity plays a central role in Candida pathogenicity and is produced by a family of 10 secreted aspartyl proteinases (Sap proteins). Although the consequences of proteinase secretion during human infections is not precisely known, in vitro, animal, and human studies have implicated the proteinases in C. albicans virulence in one of the following seven ways: (i) correlation between Sap production in vitro and Candida virulence, (ii) degradation of human proteins and structural analysis in determining Sap substrate specificity, (iii) association of Sap production with other virulence processes of C. albicans, (iv) Sap protein production and Sap immune responses in animal and human infections, (v) SAP gene expression during Candida infections, (vi) modulation of C. albicans virulence by aspartyl proteinase inhibitors, and (vii) the use of SAP-disrupted mutants to analyze C. albicans virulence. Sap proteins fulfill a number of specialized functions during the infective process, which include the simple role of digesting molecules for nutrient acquisition, digesting or distorting host cell membranes to facilitate adhesion and tissue invasion, and digesting cells and molecules of the host immune system to avoid or resist antimicrobial attack by the host. We have critically discussed the data relevant to each of these seven criteria, with specific emphasis on how this proteinase family could contribute to Candida virulence and pathogenesis.
Candida biofilms display increased resistance to most antifungal agents. We have evaluated the efficacy of combinations of fluconazole
(FLC), amphotericin B, and caspofungin (CSP) against Candida albicans biofilms in vitro. Indifference was observed for all the combinations of paired antifungal agents when a checkerboard titration
method was used. Time-kill experiments revealed an antagonistic effect of high FLC doses with CSP.
Candida species are the most common cause of fungal infections. Candida species produce infections that range from non-life-threatening mucocutaneous illnesses to invasive processes that may involve virtually any organ. Such a broad range of infections requires an equally broad range of diagnostic and therapeutic strategies. These guidelines summarize current knowledge about treatment of multiple forms of candidiasis for the Infectious Diseases Society of America (IDSA). Throughout this document, treatment recommendations are rated according to the standard scoring scheme used in other IDSA guidelines to illustrate the strength of the supporting evidence and quality of the underlying data ( table 1). This document covers the following 4 major topical areas.
One of the most comprehensive illustrated coverages available of the oral and maxillofacial manifestations of diseases has now been revised and further extended to include problems with newer classes of drugs and systemic diseases.
Bacteria that adhere to implanted medical devices or damaged tissue can encase themselves in a hydrated matrix of polysaccharide and protein, and form a slimy layer known as a biofilm. Antibiotic resistance of bacteria in the biofilm mode of growth contributes to the chronicity of infections such as those associated with implanted medical devices. The mechanisms of resistance in biofilms are different from the now familiar plasmids, transposons, and mutations that confer innate resistance to individual bacterial cells. In biofilms, resistance seems to depend on multicellular strategies. We summarise the features of biofilm infections, review emerging mechanisms of resistance, and discuss potential therapies.
Bacteria that attach to surfaces aggregate in a hydrated polymeric matrix of their own synthesis to form biofilms. Formation of these sessile communities and their inherent resistance to antimicrobial agents are at the root of many persistent and chronic bacterial infections. Studies of biofilms have revealed differentiated, structured groups of cells with community properties. Recent advances in our understanding of the genetic and molecular basis of bacterial community behavior point to therapeutic targets that may provide a means for the control of biofilm infections.
Fungal Infection: Diagnosis and Management, 4th Edition is a concise and up-to-date guide to the clinical manifestations, laboratory diagnosis and management of superficial, subcutaneous and systemic fungal infections. This highly acclaimed book has been extensively revised and updated throughout to ensure all drug and dosage recommendations are accurate and in agreement with current guidelines. A new chapter on infections caused by Pneumocystis jirovecii has been added. The book has been designed to enable rapid information retrieval and to help clinicians make informed decisions about diagnosis and patient management. Each chapter concludes with a list of recent key publications which have been carefully selected to facilitate efficient access to further information on specific aspects of fungal infections. Clinical microbiologists, infectious disease specialists, as well as dermatologists, hematologists and oncologists, can depend on this contemporary text for authoritative information and the background necessary to understand fungal infections.
We have analysed further the y of usage of antifungals in autoimmune polyendocrinopathy - candidiasis - ectodermal dystrophy (APECED) patients and its impact on the susceptibility to fluconazole in Candida albicans. Data were obtained from patient records up to 30 y earlier. Analysing the use of azoles preceding isolation of each isolate showed that significantly more y of azole usage preceded isolation of C. albicans with decreased susceptibility to fluconazole than isolation of susceptible isolates. This was found to be mainly due to the usage of azoles other than fluconazole. Significantly more y of usage of ketoconazole and miconazole preceded the isolation of strains with decreased susceptibility to fluconazole than susceptible isolates (p=0.0241 and 0.0012, respectively). These results highlight that also topical compounds, in particular miconazole, may influence fluconazole susceptibility. Our data indicate that discretion should be used in the long-term use of all azoles, including topical miconazole. At the same time topical amphotericin B appears to be a safe choice as resistance is very rare despite y of usage.
The aim of this study was to evaluate and compare the activity of prescription and over-the-counter antimicrobial compounds against planktonic and biofilm forms of Candida albicans isolated from cases of oral candidiasis in vitro.
The efficacy of azoles, polyenes, an echinocandin, and 4 over-the-counter mouthwashes were tested against C. albicans-derived planktonic and biofilm cells.
Planktonic cells were shown to be highly sensitive to all of the antifungal agents tested. Sessile cells were highly resistant to azoles (≥128 mg/L) but equally sensitive to caspofungin and short treatments with Corsodyl, Listerine, and Oraldene.
Although C. albicans is sensitive to azole antifungal agents in planktonic form, it is highly resistant within the biofilm. The good efficacy of the over-the-counter mouthwashes against candidal biofilms in vitro suggests that clinical trials should now be designed to establish their role in the clinical management of oral candidal infections.
Oral candidosis is common in patients with diabetes mellitus, as yeasts, particularly Candida albicans, have the propensity to colonise, form biofilms and release hydrolytic enzymes which cause inflammation. This study aimed to investigate these characteristics in isolates from three groups of patients with type 1 diabetes: individuals with better controlled diabetes (BCD; >or=6 <8%), individuals with poorly controlled diabetes (PCD; >or=8%) and non-diabetics (ND; HbA(1c) <5.9%). The biomass (Bm), phospholipase (P(z)), haemolysin (H(z)) and proteinase (Pr(z)) were assessed using a microtitre biofilm assay and agar-based hydrolytic enzyme assays. Biofilm formation was significantly increased in the PCD group compared to ND and BCD groups (P < 0.05). No significant differences in P(z) levels were observed between groups, whereas both H(z) and Pr(z) were significantly greater in the diabetes groups than in the healthy control group (P < 0.05). Statistically significant correlations were found to exist between the HbA(1c) levels of the patients and the Bm (R = 0.384; P = 0.033), haemolysin activity (R = -0.455; P = 0.010) and proteinase activity (R = -0.531; P = 0.002). There was no apparent correlation between the Bm and P(z) activity (R = -0.305; P = 0.053) or H(z) activity (R = -0.100; P = 0.296). However, a negative correlation was found between Bm and Pr(z) values (R = -0.343; P = 0.030). These data suggest that biofilm formation is likely to play a role in the pathogenicity of oral candidosis, and in patients with diabetes, this may be due to the ability of C. albicans to adapt to the altered physiological environment. The production of hydrolytic enzymes is independently associated with this growth modality.
Oral candidosis is a mixed yeast-bacterial biofilm infection. Candida albicans is the most common causative agent although other Candida species are seen in medically compromised patients with a history of liberal azole usage. C. albicans is usually susceptible to all commonly used antifungals when tested in vitro. However, candida biofilms are highly resistant to most antifungals. Therefore, treatment of oral candidosis requires mechanical breakage of the biofilm in combination with topical polyenes. Azoles should be avoided in cases of recurrent infections due to risk of selection of resistant strains. Occasionally oral thrush is a symptom of an undiagnosed systemic disease.
Oropharyngeal candidiasis (OPC) remains a common problem in the HIV-infected population despite the availability of antiretroviral therapy (ART). Although Candida albicans is the most frequently implicated pathogen, other Candida species also may cause infection. The emergence of antifungal resistance within these causative yeasts, especially in patients with recurrent oropharyngeal infection or with long-term use of antifungal therapies, requires a working knowledge of alternative antifungal agents. Identification of the infecting organism and antifungal susceptibility testing enhances the ability of clinicians to prescribe appropriate antifungal therapy. Characterization of the responsible mechanisms has improved our understanding of the development of antifungal resistance and could enhance the management of these infections. Immune reconstitution has been shown to reduce rates of OPC, but few studies have evaluated the current impact of ART on the epidemiology of OPC and antifungal resistance in these patients. Preliminary results from an ongoing clinical study showed that in patients with advanced AIDS, oral yeast colonization was extensive, occurring in 81.1% of the 122 patients studied, and symptomatic infection occurred in one-third. In addition, resistant yeasts were still common, occurring in 25.3% of patients colonized with yeasts or with symptomatic infection. Thus, OPC remains a significant infection in advanced AIDS, even with ART. Current knowledge of the epidemiology, pathogenesis, clinical presentation, treatment, and mechanisms of antifungal resistance observed in OPC are important in managing patients with this infection and are the focus of this review.
Candida albicans is the predominant oral yeast associated with denture stomatitis. With an increasing population of denture wearers, the incidence of denture stomatitis is increasing. Effective management of these patients will alleviate the morbidity associated with this disease. The aim of this study was to examine the capacity of four denture cleansers to efficiently decontaminate and sterilize surfaces covered by C. albicans biofilms.
Sixteen C. albicans strains isolated from denture stomatitis patients and strain ATCC 90028 were grown as mature confluent biofilms on a 96-well format and immersed in Dentural, Medical Interporous, Steradent Active Plus, and Boots Smile denture cleansers according to the manufacturers' instructions or overnight. The metabolic activity and biomass of the biofilms were then quantified, and scanning electron microscopy (SEM) used to examine treated biofilms.
Dentural was the most effective denture cleanser, reducing the biomass by greater than 90% after 20 minutes. Steradent Active plus was significantly more effective following 10-minute immersion than overnight (p < 0.001). All cleansers reduced the metabolic activity by greater than 80% following overnight immersion; however, Boots Smile exhibited significantly reduced metabolic activity following only a 15-minute immersion (p < 0.001). SEM revealed residual C. albicans material following Dentural treatment.
This study showed that denture cleansers exhibit effective anti-C. albicans biofilm activity, both in terms of removal and disinfection; however, residual biofilm retention that could lead to regrowth and denture colonization was observed. Therefore, alternative mechanical disruptive methods are required to enhance biofilm removal.
Fungal biofilms are an escalating clinical problem associated with significant rates of mortality. Candida albicans is the most notorious of all fungal biofilm formers. However, non-Candida species, yeasts such as Cryptococcus neoformans, and filamentous moulds such as Aspergillus fumigatus, have been shown to be implicated in biofilm-associated infections. Fungal biofilms have distinct developmental phases, including adhesion, colonisation, maturation and dispersal, which are governed by complex molecular events. Recalcitrance to antifungal therapy remains the greatest threat to patients with fungal biofilms. This review discusses our current understanding of the basic biology and clinical implications associated with fungal biofilms.
The polyphenols catechins and theaflavins in black tea have been shown to possess many medicinal properties, including anticancer activity and some antifungal characteristics, but there have been few studies of their anti-Candida activity. In this paper we report the results of our study of the anti-Candida activity of tea polyphenols.
The effects of 4 different concentrations of catechins and theaflavins were evaluated on 5 isolates each of 5 Candida species employing an agar diffusion growth inhibition assay. The minimum inhibitory concentration (MIC) of the polyphenols against C. albicans was determined. The post-antifungal effect (PAFE) of the polyphenols for C. albicans was investigated. C. albicans cells exposed to polyphenols were studied using a scanning electron microscope (SEM).
Both polyphenols showed anti-Candida activity against all tested Candida species and demonstrated a MIC of 6.25 mg/ml for C. albicans. C. glabrata was found to be the most sensitive species followed by C. parapsilosis, C. albicans, C. krusei and C. tropicalis (p < 0.05 for all). Significant intraspecies variations in sensitivity were noted among C. parapsilosis and C. tropicalis (p < 0.001) for both polyphenols. Theaflavins displayed standard PAFE while catechins showed a paradoxical PAFE with all isolates of C. albicans. SEM revealed considerable cell wall damage of C. albicans cells exposed to the polyphenols.
The study reveals for the first time the anti-Candida properties of black tea polyphenols that may find therapeutic applications in future.
This review has provided an overview of variants of oral mucosal candidiasis and current therapeutic techniques followed by an outline of the rare oral mycoses and their management. The advent of the HIV infection and the increasing prevalence of compromised individuals in the community as a consequence of surgical and medical advances have resulted in a resurgence of opportunistic infections, including oral candidiasis and other rare mycoses that were once considered exotic. It is now recognized that oral candidiasis may present in many clinical guises, including the classic white lesion of thrush as well in as nondescript, red mucosal lesions that may confound the unwary clinician. Other mycotic diseases, such as aspergillosis, cryptococcosis, histoplasmosis and mucormycosis, may manifest intra-orally, both as primary lesions and as secondary manifestations of systemic disease. Periodontal manifestations of mycotic diseases are rare. If at all, such lesions may present as erythematous areas as in linear gingival erythema and rarely as ulcerations in exotic mycoses. Most of the oral mycoses respond well to either topical or systemic therapy with the polyenes or azoles. In general, the management of oral fungal infections has been revolutionized by the triazole group of drugs, fluconazole and itraconazole, although recent reports indicate an alarming increase of resistant organisms, in particular to fluconazole.
According to our results all C. albicans isolates analysed were capable of producing carcinogenic levels of ACH from EtOH. The isolates from cancer and control subjects produced significantly higher amounts of ACH than those from APECED patients but the clinical relevance of this difference is questionable since all isolates produced very high amounts. The 11 mM EtOH concentration used can be found in saliva for hours after social alcohol consumption or naturally in many products produced by fermentation.17The main finding of this study is that C. albicans may play a role in metabolizing glucose to carcinogenic ACH in the mouth and could participate in the pathogenesis of oral cancer in non-alcohol drinkers. The observation supports the concept of a novel microbially mediated mechanism in the pathogenesis of oral cancer and could partly explain why chronic oral candidosis is carcinogenic in APECED patients and why they have a high risk for oral cancer at an early age.
Chronic mucocutaneous candidiasis (CMC) is a rare disease associated with immunodeficiency and characterized by persistent and refractory infections of the skin, appendages and mucous membranes caused by members of the genus Candida. Several different disorders are classified under this common denominator, including chronic and recurrent mucocutaneous infections due to Candida spp., which are sometimes linked to autoimmune endocrinopathies. These fungal infections are usually confined to the mucocutaneous surface, with little propensity for systemic disease or septicemia. We describe a patient with CMC who had an esophageal candidiasis refractory to treatment for decades and who developed an epidermoid esophageal cancer. No risk factors such as familiar susceptibility, smoking, alcohol drinking, or living in an endemic area were verified. This case report suggests the participation of nitrosamine compounds produced by chronic Candida infections as a risk factor for esophageal cancer in a patient with autosomal-dominant chronic mucocutaneous candidiasis.
Oral yeasts are an important component of the resident microbial ecology of the oral cavity, but they are also associated with various forms of oral candidosis, such as denture stomatitis. Although Candida albicans is the predominant oral fungal pathogen, other species may also play an integral role in pathogenesis. The aim of this study was to examine the mycological ecology in patients with denture stomatitis, using an improved sampling technique, to determine whether species diversity and species quantity were related to oral pathology.
Thirty-seven patients attending the Glasgow Dental Hospital were enrolled in this study following informed consent. A full clinical history was obtained, including details of their oral hygiene practices and the levels of erythema based on Newton's classification scale. Oral rinse, denture sonicate, and swab samples were taken, which were processed for quantitative and qualitative analysis of oral yeasts.
The proportion of patients with no inflammation or Newton's Types I, II, and III were 31, 33, 25, and 14%, respectively. Denture sonication was a superior sampling procedure, with statistically greater quantities of yeasts isolated using this methodology (P < 0.01). The predominant oral yeasts isolated were C. albicans (75%) and Candida glabrata (30%), which were isolated in higher proportions in patients with the highest grades of inflammation (100 and 80%), and in combination from 80% of these patients.
This study has demonstrated that mixed C. albicans and C. glabrata biofilms may play an important role in the pathogenesis associated with severe inflammation in denture wearers.
The sensitivity of the impression culture, the neat rinse culture (NRC) and the concentrated rinse culture (CRC) methods in detecting the oral carriage of yeasts, coliforms and Staphylococcus aureus was estimated in 75 individuals. The recovery of organisms from the imprint cultures of the tongue and the CRC was similar and there was highly significant positive correlation between the two techniques. The CRC was simple to perform, equally sensitive and superior in quantifying yeast, coliform and S. aureus carriage than the imprint culture technique. Hence, it is suggested that the CRC technique be preferentially employed in future investigations to obtain comparable data from different centres.
Bacteria that attach to surfaces aggregate in a hydrated polymeric matrix of their own synthesis to form biofilms. Formation
of these sessile communities and their inherent resistance to antimicrobial agents are at the root of many persistent and
chronic bacterial infections. Studies of biofilms have revealed differentiated, structured groups of cells with community
properties. Recent advances in our understanding of the genetic and molecular basis of bacterial community behavior point
to therapeutic targets that may provide a means for the control of biofilm infections.
Adhesion to epithelial surfaces is considered as a critical step in the pathogenesis of oral candidosis. Therefore, the effects of the most commonly consumed dietary carbohydrates on the adhesion of Candida albicans, Candida tropicalis, and Candida krusei to monolayered HeLa cells were investigated. Adherence of C. albicans and C. tropicalis appeared significantly promoted by incubation in defined medium containing a high concentration (500 mM) of fructose, glucose, maltose, and sucrose (p < 0.001). C. albicans organisms grown in sucrose elicited maximal increase in adhesion, whereas adhesion of C. tropicalis and C. krusei was enhanced to the greatest extent when cultured in glucose. Maltose and fructose also promoted adherence of C. albicans and C. tropicalis (p < 0.001), but to a lesser extent than sucrose and glucose. On the other hand, sorbitol-grown yeasts demonstrated a marginal increase in adhesion (p > 0.01). Xylitol only significantly reduced adherence of C. albicans (p < 0.001). These results suggest that the frequent consumption of carbohydrates, such as sucrose, glucose, maltose, or fructose, might represent a risk factor for oral candidosis. The limitation of their consumption by substituting xylitol or sorbitol could be of value in the control of oral Candida colonization and infection.
Oral candidosis is by far the commonest human fungal infection and manifests in a variety of clinical guises. The main reason for its high incidence appears to be the multiplicity of predisposing factors, which facilitate the conversion of oral commensal Candida to a parasitic existence. Despite the availability of a number of effective antimycotics for the treatment of oral candidoses, failure of therapy is not uncommon owing to the unique environment of the oral cavity where the flushing effect of saliva and the cleansing action of the oral musculature tend to reduce the drug concentration to sub-therapeutic levels. For these and other reasons chlorhexidine is widely prescribed in dentistry both as an antiseptic mouthwash and a denture disinfectant in order to supplement other antifungals. Chlorhexidine has a broad spectrum of antimicrobial activity including Candida albicans and other common non-albicans yeast species. In this review we outline the utility of chlorhexidine as an adjunct to conventional antimycotic therapy in the management of oral Candida infections.
Bacteria that adhere to implanted medical devices or damaged tissue can encase themselves in a hydrated matrix of polysaccharide and protein, and form a slimy layer known as a biofilm. Antibiotic resistance of bacteria in the biofilm mode of growth contributes to the chronicity of infections such as those associated with implanted medical devices. The mechanisms of resistance in biofilms are different from the now familiar plasmids, transposons, and mutations that confer innate resistance to individual bacterial cells. In biofilms, resistance seems to depend on multicellular strategies. We summarise the features of biofilm infections, review emerging mechanisms of resistance, and discuss potential therapies.
Though biofilms were first described by Antonie van Leeuwenhoek, the theory describing the biofilm process was not developed until 1978. We now understand that biofilms are universal, occurring in aquatic and industrial water systems as well as a large number of environments and medical devices relevant for public health. Using tools such as the scanning electron microscope and, more recently, the confocal laser scanning microscope, biofilm researchers now understand that biofilms are not unstructured, homogeneous deposits of cells and accumulated slime, but complex communities of surface-associated cells enclosed in a polymer matrix containing open water channels. Further studies have shown that the biofilm phenotype can be described in terms of the genes expressed by biofilm-associated cells. Microorganisms growing in a biofilm are highly resistant to antimicrobial agents by one or more mechanisms. Biofilm-associated microorganisms have been shown to be associated with several human diseases, such as native valve endocarditis and cystic fibrosis, and to colonize a wide variety of medical devices. Though epidemiologic evidence points to biofilms as a source of several infectious diseases, the exact mechanisms by which biofilm-associated microorganisms elicit disease are poorly understood. Detachment of cells or cell aggregates, production of endotoxin, increased resistance to the host immune system, and provision of a niche for the generation of resistant organisms are all biofilm processes which could initiate the disease process. Effective strategies to prevent or control biofilms on medical devices must take into consideration the unique and tenacious nature of biofilms. Current intervention strategies are designed to prevent initial device colonization, minimize microbial cell attachment to the device, penetrate the biofilm matrix and kill the associated cells, or remove the device from the patient. In the future, treatments may be based on inhibition of genes involved in cell attachment and biofilm formation.
Lactobacillus bacteremia is a rare entity, and its clinical significance is poorly defined. We have reviewed the risk factors and outcome
for 89 case patients with Lactobacillus bacteremia. Species characterization was done in 53% of the cases, revealing 25 L. rhamnosus strains and 22 other Lactobacillus species. In 11 cases, the strain was identical with the probiotic L. rhamnosus GG. In 82% of the cases, the patients had severe or fatal comorbidities. Predisposing factors to bacteremia were immunosuppression,
prior prolonged hospitalization, and prior surgical interventions. No significant differences were observed in these predisposing
factors or clinical features between patients with cases associated with the various Lactobacillus species, other than higher C-reactive protein values in patients with L. rhamnosus bacteremia. Mortality was 26% at 1 month and was 48% at 1 year. In multivariate analysis, severe underlying diseases were
a significant predictor for mortality (odds ratio [OR], 15.8), whereas treatment with antimicrobials effective in vitro was
associated with lower mortality (OR, 0.22). We conclude that lactobacilli in blood cultures are of clinical significance and
that their susceptibility should guide decisions about antimicrobial treatment.