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Natural antimicrobial systems and their potential in food preservation of the future.

The extensive literature on natural antimicrobial systems in animals, plants, and microorganisms is surveyed and particular systems are discussed, viz., the peroxidase systems in saliva and milk, singlet oxygen in the phagosome, cecropins and attacins in insects, complement, lysozyme and, to a limited extent, phytoalexins. The review draws attention to the cardinal role of targets on the cell envelopes of alien cells, especially bacteria, and emphasizes a possible approach to preservation based on the selection of specific agents for particular targets. The available evidence suggests that the perturbation of the homeostasis of all the organisms in the mixed flora of a food is unlikely to be achieved by one antimicrobial substance in isolation. Future studies need to consider therefore a tandem approach with two or more agents chosen because of their complementary action. Alternatively, natural system(s) and an established preservative method, either chemical or physical, warrant investigation. The extensive literature on the mechanisms whereby specialist pathogens overcome the defenses of plants and animals emphasizes the inherent dangers of selection leading to the persistent contamination of food processing areas with organisms tolerant of a particular antimicrobial system.

Animals↗

The effect of indigenous bacterial populations on buccal epithelial cells on subsequent microbial adhesion in vitro.

Despite the numerous investigations on the adhesion of microorganisms to buccal epithelial cells, it is difficult to correlate different results, as disparate adherence values have been reported for a given organism. As one reason for this disparity may be the indigenous or natural bacterial populations on human buccal epithelial cells, the effect of the latter on subsequent microbial adherence in vitro was examined. There was a highly significant correlation between the degree of natural bacterial colonization on pooled buccal epithelial cells from 8 healthy donors and the adhesion of a single isolate each of Streptococcus mitis, Escherichia coli and Actinomyces naeslundii. However, no such relationship could be established for Candida albicans, Streptococcus milleri and another isolate of Streptococcus mitis. As in previous studies, variation in adherence values was found, both between samples from different donors, and from the same donor over time, but to a far lesser degree in pooled samples from different donors. These results imply that natural bacterial populations on buccal epithelial cells may affect the adhesion values derived from laboratory experimentation, and hence such data should be interpreted with caution.

Actinomyces↗

In vitro inhibition of adhesion of Candida albicans clinical isolates to human buccal epithelial cells by Fuc alpha 1----2Gal beta-bearing complex carbohydrates.

The role of cell surface glycoconjugates as possible adhesion receptors for Candida albicans yeasts on human buccal epithelial cells was investigated by using a quantitative radiometric assay involving 14C-metabolically labeled microorganisms. Various structurally defined soluble glycopeptides and oligosaccharides were tested at a low concentration (1 mg/ml) for their ability to competitively inhibit yeast adhesion to such exfoliated cells. Comparisons were also made with various molecular species previously proposed to act as adhesion molecules. A preparation of glycopeptides derived from pooled human newborn meconiums inhibited the attachment (up to 55%) of all three clinical isolates examined. The mild hydrolysis of fucosyl residues from the above mixture totally abolished its inhibitory potency. By using human milk oligosaccharide probes, the minimal structural requirement for activity was found to be the Fuc alpha 1----2Gal beta determinant (the H sugar sequence found on all blood group substances of the ABO [H] system). By contrast, the fucosylated determinants of the Lewis blood group system were found to be totally inactive. Total adhesion inhibitions were never obtained in the present experiments, suggesting that H disaccharide-bearing cell surface glycoconjugates could act as host receptors for C. albicans on human buccal epithelial cells as a part of a mechanism involving multireceptor specificities.

ABO Blood-Group System↗

Mucosal and systemic immune responses to a recombinant protein expressed on the surface of the oral commensal bacterium Streptococcus gordonii after oral colonization.

To circumvent the need to engineer pathogenic microorganisms as live vaccine-delivery vehicles, a system was developed which allowed for the stable expression of a wide range of protein antigens on the surface of Gram-positive commensal bacteria. The human oral commensal Streptococcus gordonii was engineered to surface express a 204-amino acid allergen from hornet venom (Ag5.2) as a fusion with the anchor region of the M6 protein of Streptococcus pyogenes. The immunogenicity of the M6-Ag5.2 fusion protein was assessed in mice inoculated orally and intranasally with a single dose of recombinant bacteria, resulting in the colonization of the oral/pharyngeal mucosa for 10-11 weeks. A significant increase of Ag5.2-specific IgA with relation to the total IgA was detected in saliva and lung lavages when compared with mice colonized with wild-type S. gordonii. A systemic IgG response to Ag5.2 was also induced after oral colonization. Thus, recombinant Gram-positive commensal bacteria may be a safe and effective way of inducing a local and systemic immune response.

Animals↗

Suspected periodontopathic microorganisms and their oral habitats in young children.

Samples of subgingival plaque from 67 children, 5-7 years of age, were examined for the presence of certain suspected periodontal pathogenic species using the conventional technique of anaerobic sonification, dilution and spiral plating. When this technique was compared with a direct plating procedure which involved no preliminary dispersion and dilution of plaque specimens, it was found that the direct method resulted in double the frequency of children in whom black-pigmented Bacteroides (BPB) were detected and a 10-times increase in the number of subjects harbouring Actinobacillus actinomycetemcomitans. Samples from the tongue, tonsils and saliva were also plated using the direct technique. BPB were detected less commonly in the plaque specimens (61.3% of children) than in saliva (89.5%), or on the tongue (86.6%) and tonsils (97.1%). Expressed as percentages of a pooled sample of the total BPB population, the most frequently detected species in plaque were Bacteroides intermedius (44.4%) and Bacteroides melaninogenicus (48.0%). The most prevalent isolate in all other oral sites was B. melaninogenicus. Expressed as percentages of children in whom BPB were detected, the most frequently isolated species from plaque using the conventional dilution technique was B. intermedius (21.3%), whereas other BPB species were present in fewer than 5% of children. Fusobacterium nucleatum and Capnocytophaga species were isolated most frequently from plaque but were also commonly detected in the various other oral sites.

Aggregatibacter actinomycetemcomitans↗

Candida albicans, Staphylococcus aureus and Streptococcus mutans colonization in patients wearing dental prosthesis.

BACKGROUND: Denture stomatitis is associated to Candida albicans, different bacteria and other co-factors such as an acid pH, a carbohydrate ingestion increase, different systemic illnesses and pharmacological treatments. OBJECTIVE: The aim of this study was to determine Candida albicans, Staphylococcus aureus and Streptococcus mutans prevalence in the mucous membrane and prosthesis of patients with and without atrophic denture stomatitis and its relationship with other potential clinical co-factors. STUDY DESIGN: Saliva was collected from 105 patients (62 female and 43 male) wearing dental prosthesis in order to measure their pH. Oral samples of the mucous membrane and the internal surface of dental prosthesis were taken with sterile cotton to proceed with the microbiological study. The identification of the isolated microorganisms was performed using conventional microbiological methods. RESULTS: Diabetes and Hypertension were the most frequent systemic illnesses. High carbohydrate ingestion was observed in numerous patients. Atrophic denture stomatitis was reported in 50 patients and the pH average in saliva was of 5.2. The presence of C albicans, S. aureus and S. mutans in the mucous membrane and prosthesis was of 51.4%, 52.4% and 67.6%, respectively. C. albicans was isolated in 66.7% from the prosthesis, whereas S. aureus and S. mutans were isolated in 49.5% of those same prosthesis. C. albicans was isolated in 86% of the patients with atrophic denture stomatitis and S. aureus was isolated in a similar percentage (84% of patients). The isolation of S. mutans was less frequent, and it was observed in 16% of the oral samples of these patients. CONCLUSIONS: C. albicans, S. aureus and S. mutans frequently colonize the oral mucous of patients wearing dental prosthesis. This illness-bearing condition is more frequent in patients with denture stomatitis, even though dental prosthesis colonization is lower than in the oral mucous.

Aged↗

Salivary IgA response of triathletes participating in the French Iron Tour.

Athletes are susceptible to upper respiratory tract infections (URTI) during intense training and after major competitions. Secretory IgA, which is the predominant antibody of the mucosal immune system, is the major effector of host-resistance to many microorganisms causing URTI. Previous studies have shown that salivary IgA-mediated immunity decreases after a single short distance triathlon, but the effect of repeated triathlon competitions on secretory IgA levels remains unknown. The purpose of this study was to examine the salivary IgA response of elite triathletes in repeated triathlon races during the 2001 French Iron Tour (FIT). Eight triathletes participated in this study. Saliva samples were collected daily after waking up (fasting basal state), before (pre-race) and after (post-race) each day's competition. Salivary IgA, total protein, and flow rate were measured. Salivary IgA concentrations were measured by an enzyme-linked immunosorbent assay. The salivary flow rate was significantly decreased after each race compared with the fasting basal state (p < 0.01). The salivary IgA concentration of the fasting basal state decreased over the FIT and was even lower than that of the post-race values (p < 0.05). The salivary IgA secretion rate of the fasting basal state decreased by 51.9% over the FIT (p < 0.05). Our data suggest that intense exercise repeated daily has a cumulative negative effect on basal levels of salivary IgA.

Adult↗

In vitro antimicrobial activities of bakuchiol against oral microorganisms.

Bakuchiol was isolated from the seeds of Psoralea corylifolia, a tree native to China with various uses in traditional medicine, followed by extraction with ether and column chromatography combined with silica gel and octyldecyl silane. In this study, the antimicrobial activities of bakuchiol against some oral microorganisms were evaluated in vitro. The cell growth of Streptococcus mutans was inhibited in a bakuchiol concentration-dependent manner, and growth of S. mutans was completely prevented by 20 microg of bakuchiol per ml. The bactericidal effect of bakuchiol on S. mutans was dependent on temperature and stable under the following conditions: sucrose, 0 to 10% (wt/vol); pH, 3.0 to 7.0; organic acids (3% [wt/vol] citric and malic acids). Bakuchiol showed bactericidal effects against all bacteria tested, including S. mutans, Streptococcus sanguis, Streptococcus salivarius, Streptococcus sobrinus, Enterococcus faecalis, Enterococcus faecium, Lactobacillus acidophilus, Lactobacillus casei, Lactobacillus plantarum, Actinomyces viscosus, and Porphyromonas gingivalis, with MICs ranging from 1 to 4 microg/ml and the sterilizing concentration for 15 min ranging from 5 to 20 microg/ml. Furthermore, bakuchiol was also effective against adherent cells of S. mutans in water-insoluble glucan in the presence of sucrose and inhibited the reduction of pH in the broth. Thus, bakuchiol would be a useful compound for development of antibacterial agents against oral pathogens and has great potential for use in food additives and mouthwash for preventing and treating dental caries.

Anti-Bacterial Agents↗

[Characteristics of fauces microflora in children treated in intensive care units].

Characteristic features of fauces aerobic microflora in children treated in intensive care units (ICU) were analysed. For comparison fauces microflora in children outpatients and in children patients from general surgical units was investigated. A retrospective analysis of all the smears without exception for 2 years (a total of 2120) revealed a direct dependence of the changes in the fauces microflora composition on the patient condition and the antibiotic load. It was shown that the fauces indigenic microflora in ICU patients was more often replaced by enterococci, gramnegative enteric bacteria and nonfermenting bacteria which are not usual under the normal conditions. The flora in such cases was represented by monoculture. Thus, microorganisms natural for the fauces i.e. Haemophilus influenzae and Neisseria spp. were not practically detected in the fauces of the ICU patients (0.5 and 0.4 per cent, respectively). Grampositive cocci in the children of the surgical units and in the outpatients included alpha-hemolytic streptococci in association with beta-hemolytic or nonhemolytic streptococci. No such bacteria were isolated from the ICU newborns. The associations of gramnegative organisms from the ICU patients included 40 variants. Seventy-eight association variants of Pseudomonas aeruginosa were mainly represented by the combinations with Serratia spp. and Klebsiella spp. as well as with coagulase negative staphylococci or enterococci, especially in the ICU newborns. The results of the study demonstrated that the target-aimed antibiotic therapy providing eradication of P.aeruginosa in the ICU patients was not always justified because of possible superinfection practically due to any organism from the association. Massive antibiotic therapy with pressing on gramnegative flora in the ICU patients induced selective contamination of the mucosa by polyresistant enterococci thus increasing their potential role in the development of hospital infections.

Anti-Bacterial Agents↗

Calcium hypochlorite as a disinfecting additive for dental stone.

STATEMENT OF PROBLEM: Dental casts come into direct contact with impression materials and other items that are contaminated by saliva and blood from a patient's mouth, leaving the casts susceptible to cross-contamination. Topical methods of disinfecting casts are difficult to control, while immersion methods are potentially destructive. Thus, an additional method to control cross-contamination between patients and laboratory personnel is needed. PURPOSE: This study was undertaken in an attempt to develop a dental stone with disinfecting properties and adequate compressive and tensile strengths. MATERIAL AND METHODS: Calcium hypochlorite [Ca(OCl)(2)] in aqueous solution in concentrations from 0 to 1.5% was tested as a disinfecting additive to type V dental stone. The compressive and tensile strength properties of the modified stone were measured (MPa) using a universal testing machine at a consistency similar to unmodified stone. Strength data were analyzed by 1-way ANOVA and post hoc Tukey-Kramer procedure (alpha < or =.05). To measure the disinfecting ability, the effect on Bacillis subtilis bacteriophage phi29 was tested in triplicate to find the minimum concentration at which no phage was detected. Additionally, 3 impressions were disinfected with CaviCide, and 3 impressions rinsed in water served as controls. RESULTS: In general, the effect of adding the disinfectant to the stone was a decrease in strength. Exceptions were the dry compressive strength, for which there was a significant increase in strength (P=.048) at 0.5%, and the wet compressive and wet tensile strength, which showed no significant difference between the 1.5% and the control. When Ca(OCl)(2) was added at the concentration 0.5% (2765 ppm available chlorine), the gypsum had acceptable mechanical properties; dry compressive strength was 78.86 +/- 4.12 MPa, and dry tensile strength was 10.64 +/- 1.27 MPa, compared to control values of 67.85 +/- 6.28 and 13.41 +/- 1.24 MPa, respectively. At concentrations of 0.3% and higher (36 1650 ppm of available chlorine), calcium hypochlorite was able to completely inactivate phi29. CONCLUSION: It is possible to prepare a type V dental stone that contains a disinfectant, has adequate mechanical properties, and will reduce numbers of residual microorganisms. For example, stone mixed with water containing 0.5% Ca(OCl)(2) meets these criteria.

Analysis of Variance↗

Interleukin-18 and gamma interferon production by oral epithelial cells in response to exposure to Candida albicans or lipopolysaccharide stimulation.

Oral candidiasis is a collective name for a group of disorders caused by the dimorphic fungus Candida albicans. Host defenses against C. albicans essentially fall into two categories: specific immune mechanisms and local oral mucosal epithelial cell defenses. Since oral epithelial cells secrete a variety of cytokines and chemokines in response to oral microorganisms and since C. albicans is closely associated with oral epithelial cells as a commensal organism, we wanted to determine whether interleukin-18 (IL-18) and gamma interferon (IFN-gamma) were produced by oral epithelial cells in response to C. albicans infection and lipopolysaccharide (LPS) stimulation. Our results showed that IL-18 mRNA and protein were constitutively expressed by oral epithelial cells and were down-regulated by Candida infections but increased following LPS stimulation. Both C. albicans and LPS significantly decreased pro-IL-18 (24 kDa) levels and increased active IL-18 (18 kDa) levels. This effect was IL-1beta-converting-enzyme dependent. The increase in active IL-18 protein levels promoted the production of IFN-gamma by infected cells. No effect was obtained with LPS. Although produced only at an early stage, secreted IFN-gamma seemed to be a preferential response by oral epithelial cells to C. albicans growth. These results provide additional evidence for the contribution of oral epithelial cells to local (direct contact) and systemic (IL-18 and IFN-gamma production) defense against exogenous stimulation such as C. albicans infection or LPS stimulation.

Candida albicans↗

Antagonistic interactions among Fusobacterium nucleatum and Prevotella intermedia with oral lactobacilli.

Microbiota residing in oral ecosystems show great complexity because of the mutual interdependence of certain microorganisms that might influence their presence or absence at a given site. The aim of this work was to evaluate possible antagonistic interactions among Fusobacterium nucleatum and Prevotella intermedia, isolated from periodontal pockets, and Lactobacillus casei, L. salivarius, L. rhamnosus and L. plantarum isolated from saliva. Different tests were carried out using each strain as an effector as well as a sensitive strain, alternatively: (1) agar diffusion with paper disks embedded with supernatants and pellets in different culture media; (b) the well diffusion assay; (c) the double layer method; and (d) OD(560) measurements of the kinetic growth of Lactobacillus strains in LAPTg broth with different volumes of F. nucleatum supernatant. P. intermedia supernatant did not have an inhibitory effect on Lactobacillus growth, except for L. casei, when the double plaque method was used. F. nucleatum supernatant inhibited growth of all Lactobacillus strains when the well diffusion method was used. F. nucleatum inhibited L. casei growth whatever the method used. The substance responsible for inhibition was a thermoresistant extracellular protein which was hydrolyzed by trypsin-like proteases. None of the species of lactobacilli studied inhibited the growth of P. intermedia or F. nucleatum.

Antibiosis↗

The in vitro effects of cetyltrimethylammonium naproxenate on oral and pharyngeal microorganisms of various ecological niches.

The purpose of this study was to determine the in vitro susceptibility to cetyltrimethylammonium naproxenate for various aerobic and anaerobic micro-organisms responsible for oral and pharyngeal diseases by assessing the minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) or minimum fungicidal concentrations (MFCs) and by determining kill-times. The MICs of cetyltrimethylammonium naproxenate for 46 tested strains (25 reference strains and 21 clinical isolates) ranged from 8 to 500 micrograms/ml. The MIC was found to be 31.25 micrograms/ml for 36% of the reference strains. Even lower MIC values (15.63 micrograms/ml) were observed for some anaerobic strains, for Haemophilus influenzae and for Candida tropicalis. MIC and MBC values corresponded for the majority of strains tested while the MFC for C. tropicalis and C. albicans was much higher. Only 9.5% of the clinical isolates gave a MIC value of 31.25 micrograms/ml. Enterococcus faecalis, Streptococcus pyogenes and Staphylococcus aureus showed MIC at 62.5 micrograms/ml. The MIC and MBC values among the isolates were comparable, while the MFC value for the yeasts was greater. A concentration of 125 micrograms/ml of cetyltrimethylammonium naproxenate inhibited the growth of all bacteria, except Enterobacteriaceae and Pseudomonaceae, and yeasts. Cetyltrimethylammonium naproxenate shows very rapid kill-time for S. sanguis (0"), and rapid (15") for S. pyogenes, S. dysgalactiae and S. mutans and for Moraxella catarrhalis, while a longer kill-time was necessary for the other microbes tested.

Anti-Infective Agents, Local↗

In vivo binding of the salivary glycoprotein EP-GP (identical to GCDFP-15) to oral and non-oral bacteria detection and identification of EP-GP binding species.

Extra Parotid Glycoprotein (EP-GP) is a glycoprotein isolated from human saliva, having homologues in several other body fluids. The biological role of EP-GP and its homologues is unknown. Recently, EP-GP was shown to bind in vitro to the bacterium Streptococcus salivarius HB. In contrast, no binding to a number of other oral microorganisms could be demonstrated. In the present study we have determined whether binding of EP-GP to bacteria occurs in vivo in saliva and in other EP-GP containing body fluids. Therefore the presence of EP-GP on bacteria in vivo was determined by analyzing oral, skin and ear floras by confocal fluoresence microscopy using specific antibodies. About 12% of the in vivo oral flora had EP-GP present on their surface, while approximately 5% of the bacteria from ear canal or skin was positive for EP-GP. IgA was detected on approximately 65% of the salivary bacteria, whereas the high-molecular weight mucin (MG1) and cystatin C were not detectable on any oral bacterium. Using a replica-plate assay, a number of EP-GP binding strains in saliva were isolated and identified as Gemella haemolysans, Gemella morbillorium, Streptococcus acidominimus, Streptococcus oralis, Streptococcus salivarius and Streptococcus parasanguis. Bacteria from the ear canal and skin bacteria were identified as Staphylococcus hominis. It is concluded that EP-GP is selectively bound in vivo to several oral and non-oral bacterial species.

Body Fluids↗

Influence of temperature on the co-adhesion of oral microbial pairs in saliva.

Coaggregation (interactions between two planktonic microorganisms) and co-adhesion (interactions between sessile and planktonic microorganisms) are believed to be important factors in the formation of dental plaque by many investigators, although others doubt whether coaggregation and co-adhesion occur in vivo. It is known that coaggregation and co-adhesion generally occur equally well in buffer as in saliva, but the influence of temperature on the co-adhesion of coaggregating oral microbial pairs in saliva is unknown. Therefore, co-adhesion of streptococci suspended in saliva to glass with adhering actinomyces present (1.0 x 10(6) cells cm-2) was studied in a parallel plate flow chamber in the temperature range from 22 degrees C to 40 degrees C. In the range from 22 degrees C up to 35 degrees C both pairs studied, Streptococcus oralis 34 with Actinomyces naeslundii 5951 and Streptococcus oralis J22 with A. naeslundii 5951, displayed similar co-adhesion kinetics and co-adhesion in a stationary end-point, but around and above 37 degrees C co-adhesion almost disappeared. Hence, we conclude that co-adhesion of coaggregating oral microbial pairs in saliva may be critically influenced by temperature, especially around the temperatures prevailing in the oral cavity.

Actinomyces↗

Adherence of Candida species to human epidermal corneocytes and buccal mucosal cells: correlation with cutaneous pathogenicity.

Adherence of microorganisms to epidermal corneocytes may be a prerequisite for cutaneous colonization and infection. Six species of Candida were assayed in vitro for adherence to human epidermal corneocytes and buccal mucosal cells, and compared to previous studies of pathogenicity in a rodent model of cutaneous candidiasis. C. albicans and C. stellatoidea exhibited marked adherence to both epithelial cell types over time, and were cutaneous pathogens in the rodent model. The remaining species showed little or no adherence, and were nonpathogenic to skin. Adherence to corneocytes was not inhibited by ethylenediamine tetraacetic acid, mannan polysaccharide, or concanavalin A lectin. Fresh human serum, but not heat-inactivated serum, inhibited C. albicans adherence by 50%, and was associated with the deposition of complement components, C3 and factor B on blastospores. Adherence to epithelial corneocytes and mucosal cells is a property of pathogenic species of Candida, and may participate in cutaneous colonization and infection mechanisms. Adherence was time-dependent, and did not require divalent cations. Cell wall mannan may participate in the "adhesin" complex. Mannan activation of serum complement and deposition of C3 and factor B on blastospores may provide a protective action by inhibiting Candida adherence to corneocytes.

Candida↗

Infection and mucosal injury in cancer treatment.

The oral and gastrointestinal mucosa acts as an important mechanical barrier that prevents local or systemic invasion by microorganisms. Cytotoxic chemotherapy-induced mucosal injury (MI) of oral cavity and intestinal epithelium occurs in many patients treated for malignancy. Compromise of the mucosal barrier can contribute to local invasion by colonizing microorganisms and, subsequently, to systemic infection. Historically, gram-negative bacteremia has been the most problematic bacterial infection in neutropenic patients, but its incidence has reduced over time because of the use of prophylactic antibiotics. There has been a shift in the type of infecting organisms responsible for bacteremia in these patients, from predominantly gram-negative organisms to gram-positive cocci. The viridans group of streptococci is composed of the most frequent bacterial pathogens associated with MI. When speciated, oral colonizers such as Streptococcus mitis, Streptococcus oralis, and Streptococcus sangulis II are the most frequently identified pathogens. Other systemic infections caused by vancomycin-resistant enterococci, Stenotrophomonas maltophilia, and Candida species have also been associated with MI after cancer treatment. Infection can also exacerbate MI after cancer treatment. The best recognized example is herpes simplex virus type 1 (HSV-1). Latent virus is frequently reactivated in HSV-seropositive patients; this reactivation leads to stomatitis, which can be indistinguishable from MI caused by cytoreductive therapies. Antiviral prophylaxis or treatment can control the virus-induced MI and bring about overall amelioration of MI. Recognition of this infectious cause of MI is important in order for clinicians to anticipate and minimize oral toxicity and to facilitate optimal delivery of the antineoplastic regimen.

Antineoplastic Agents↗

Pharmacologic management of the patient with disorders of the cardiovascular system. Infective endocarditis.

IE, although an infrequent event, remains a serious and frequently lethal complication in patients at risk. Oral microorganisms undoubtedly play a significant role in the development of IE in such patients. For example, in a retrospective review of prosthetic cardiac valve candidates (156) at the Cleveland Clinic Foundation, 15% were found to have at least one abscessed tooth, whereas approximately 17% were found to have severe (class IV) periodontal disease. Cardiac defects in conjunction with bacteremias from such dental pathoses clearly elevate the risk, although a small but increasing number of noncardiac conditions and behavioral patterns seem also to be able to induce susceptibility. Whether dental or other medical procedures are truly direct inducers of IE, however, remains to be proven and in all probability are only minor contributors overall. Despite its ubiquitous use, antibiotic prophylaxis has not been proven in human clinical trials, and its underlying rationale is arbitrary and questionable at best; nevertheless, its efficacy in animal models has led to the current human protocols. A more profitable strategy, and certainly an adjunctive one, should be to direct one's effort at eliminating oral pathology and educating and motivating patients at risk toward meticulous oral hygiene--an exhortation published many years before the advent of antibiotics and still undoubtedly the best recommendation today.

Abscess↗