Abstract. Husebye ES, Perheentupa J, Rautemaa R,

Objectives: Recent increases in triazole resistance in Aspergillus fumigatus have been attributed primarily to target site (cyp51A) mutations. A recent survey of resistant isolates in Manchester showed that .50% of resistant isolates had no mutation in cyp51A or its promoter. We investigated the mechanisms of resistance in clinical azole-resistant isolates without cyp51A mutations.Methods: Twelve azole-resistant isolates, 10 of which were itraconazole resistant, were studied. Bioinformatic comparisons between Candida albicans efflux genes and A. fumigatus genome data identified 20 putative azole transporter genes. Basal and azole-induced expression of these genes and cyp51A was quantified using RT-PCR with comparison with clinical azole-susceptible isolates. Function of high basal or itraconazole-induced expression transporters was tested by gene knockout in azole-susceptible and azole-resistant isolates.Results: All susceptible strains showed minimal basal expression of cdr1B compared with 8 of 10 azole-resistant strains with high basal expression of this gene (.5-fold), 3 of which showed .30-fold increased expression. Knockout of this gene resulted in a 4-fold reduction in itraconazole, posaconazole and voriconazole MICs for a susceptible clinical isolate and a 4-fold reduction in itraconazole susceptibility in a clinical resistant isolate. One strain showed a .500-fold induction of cyp51A. No increase in basal expression or expression after induction was seen for the 18 remaining putative transporters. Conclusions:The reasons behind the shift away from target site mutation in azole-resistant isolates from Manchester are unknown. The modest change in expression of cdr1B in azole-susceptible strains implies that only study of resistant isolates will lead to further understanding of resistance mechanisms in A. fumigatus.

Aerosols containing microbes from the oral cavity of the patient are created when using modern high-speed rotating instruments in restorative dentistry. How far these aerosols spread and what level of contamination they cause in the dental surgery has become a growing concern as the number of patients with oro-nasal meticillin-resistant Staphylococcus aureus colonization has increased. The present study aimed to determine how far airborne bacteria spread during dental treatment, and the level of contamination. Fall out samples were collected on blood agar plates placed in six different sectors, 0.5-2m from the patient. Restorative dentistry fallout samples (N=72) were collected from rooms (N=6) where high-speed rotating instruments were used, and control samples (N=24) were collected from rooms (N=4) used for periodontal and orthodontic treatment where rotating and ultrasonic instruments were not used. The collection times were 1.5 and 3 h. In addition, samples were taken from facial masks of personnel and from surfaces in the rooms before and after disinfection. After 48 h of incubation at 37 degrees C, colonies were counted and classified by Gram stain. The results showed significant contamination of the room at all distances sampled when high-speed instruments were used (mean 970 colony-forming units/m2/h). The bacterial density was found to be higher in the more remote sampling points. Gram-positive cocci, namely viridans streptococci and staphylococci, were the most common findings. The area that becomes contaminated during dental procedures is far larger than previously thought and practically encompasses the whole room. These results emphasize the need for developing new means for preventing microbial aerosols in dentistry and protection of all items stored temporarily on work surfaces. This is especially important when treating generally ill or immunocompromised patients at dental surgeries in hospital environments.

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.

The frequency of Candida infection in periodontal tissues of chronic periodontitis (CP) patients and the extent of candidal penetration into gingival tissues was studied. Tissue specimens collected from 25 CP patients during periodontal flap operations of initial periodontal therapy were examined by immunohistochemistry using Candida albicans-specific antibodies. Sections were also stained with periodic acid-Schiff (PAS) and subgingival plaque samples from 17 patients were cultured. Immunoreactivity for Candida was present in four of the 25 CP specimens (16%). Only one yeast-positive specimen was found when PAS-staining was used (4%) and two yeast-positive specimens were found with plaque culture (8%). Hyphal formation seemed essential and candidal hyphae were found to extend into the periodontal connective tissue. The degree and type of inflammation adjacent to the hyphae varied from a site and a patient to another. The sensitivity of specific antibodies was superior to PAS-stain or plaque culture in detection of Candida in tissues.

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The relationship between oral and general health has been increasingly recognised during the past two decades. Several epidemiological studies have linked poor oral health with cardiovascular disease, poor glycaemic control in diabetics, low birth-weight pre-term babies, and a number of other conditions, including rheumatoid arthritis and osteoporosis. Oral infections are also recognised as a problem for individuals suffering from a range of chronic conditions, including cancer and infection with human immunodeficiency virus, as well as patients with ventilator-associated pneumonia. This review considers the systemic consequences of odontogenic infections and the possible mechanisms by which oral infection and inflammation can contribute to cardiovascular disease, as well as the oral conditions associated with medically compromised patients. A large number of clinical studies have established the clinical efficacy of topical antimicrobial agents, e.g., chlorhexidine and triclosan, in the prevention and control of oral disease, especially gingivitis and dental plaque. The possible risks of antimicrobial resistance are a concern, and the benefits of long-term use of triclosan require further evaluation. Oral infections have become an increasingly common risk-factor for systemic disease, which clinicians should take into account. Clinicians should increase their knowledge of oral diseases, and dentists must strengthen their understanding of general medicine, in order to avoid unnecessary risks for infection that originate in the mouth.

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