The challenge of growing oral spirochaetes.

Research in periodontal disease has shown the presence of oral spirochaetes repeatedly in subgingival plaque. There is uncertainty as to whether these spirochaetes are involved in the actual disease process; however, it has been shown that their presence is a definite marker for disease occurrence. An understanding of their role in periodontal disease requires further characterisation of these organisms. Diagnostic tests would be useful for the clinician and enable treatment for the patient to be planned. Studies on characterising the different treponemal species have been limited by difficulties in culturing these organisms. Moreover, there is a need to obtain pure cultures of these organisms and to identify them in order to associate particular species with disease and, ultimately, to make probes for their easy detection directly from dental plaque. This review examines the methods used, and reports our own experience, in obtaining pure cultures of oral spirochaetes. The techniques available and the problems that occur when identifying these organisms are also considered.

Phospholipid profiles of Clostridium difficile.

Phospholipid molecular species present in 32 isolates of Clostridium difficile were examined by fast atom bombardment-mass spectrometry in negative-ion mode. This revealed major anions consistent with the expected presence of the following phosphatidylglycerol (PG) analogs: PG(31:2), PG(32:1), PG(33:2), PG(33:1), PG(34:2), and PG(34:1). The major phospholipid molecular species are distinct from those of other bacterial groups examined.

In vitro activity of BMS-181184 compared with those of fluconazole and amphotericin B against various candida spp.

We compared the in vitro activity of BMS-181184, the first compound of a new class of antifungal agents, the pradimicins, with those of fluconazole and amphotericin B against 64 clinical isolates of Candida species. MICs were determined by a microdilution method with high resolution medium for BMS-181184 and fluconazole and antibiotic medium no. 3 with 2% glucose for amphotericin B. MICs of BMS-181184 for all yeasts were in the range of 0.78 to 12.5 micrograms/ml. BMS-181184 was active against isolates resistant to other antifungal agents, consistent with a novel mode of action. Minimum fungicidal concentrations for 16 isolates showed that BMS-181184 was fungicidal. Clinical studies are now required to confirm its activity.

In vitro activity of D0870 compared with those of other azoles against fluconazole-resistant Candida spp.

We compared the in vitro activity of a new triazole, D0870, with those of fluconazole, itraconazole, and ketoconazole against 41 clinical isolates of fluconazole-resistant Candida belonging to nine different species. The 50% inhibitory concentrations (IC50s) were determined by a microdilution method with morpholinopropanesulfonic acid (MOPS)-buffered RPMI medium and an inoculum of approximately 10(4) yeasts per ml. After incubation for 48 h at 37 degrees C the optical density at 550 nm was measured. The IC50 was the lowest drug concentration which reduced the optical density at 550 nm by > or = 50% compared with that for a drug-free control. D0870 had significant activity against many of the isolates. Its activity was comparable to that of ketoconazole, slightly superior to that of itraconazole, and markedly superior to that of fluconazole against Candida albicans. Against Candida glabrata, Candida krusei, and Candida inconspicua, it had activity similar to those of itraconazole and ketoconazole but had activity superior to that of fluconazole. D0870 IC50s for some isolates were increased. This may be due to cross-resistance mechanisms because the IC50s of both itraconazole and ketoconazole for these isolates were often high. When IC50s and IC80s were compared there was a marked organism and drug variation. With C. glabrata much higher endpoints for itraconazole were observed when an IC80 endpoint was used. For C. albicans there was also a significant shift upward in endpoints for itraconazole and ketoconazole. Values were changed little when IC50 and IC80 endpoints of D0870 were compared. For 35 of 41 isolates tested the D0870 IC50 was less than the 2.5-mg/liter breakpoint threshold proposed previously. Therefore, D0870 may be a useful agent for the therapy of infections caused by fluconazole-resistant Candida spp.

High prevalence of antifungal resistance in Candida spp. from patients with AIDS.

Three hundred and forty-eight isolates of Candida spp. from patients treated at a regional infectious diseases unit for AIDS, immunocompromised patients admitted to the Hope Hospital and isolates referred from around the North West of England were tested for their in-vitro susceptibility to amphotericin B, fluconazole and flucytosine using standardized methods. Candida albicans comprised 73% of isolates, Candida glabrata 10% and Candida parapsilosis 7%. Ninety-six percent of isolates were susceptible to amphotericin B and resistance to > or = 12.5 mg/L fluconazole was found in 61 (17.5%) of the 348 isolates tested. Among isolates from patients with AIDS the incidence of fluconazole resistance was 33% whereas in other patients the incidence was only 11%. Flucytosine resistance was seen in only 12 (3.4%) isolates, 11 of which were C. albicans and in 6.5% of isolates from patients with AIDS. Resistance to fluconazole and flucytosine is now sufficiently prevalent among Candida spp. isolated from patients with AIDS to warrant routine susceptibility testing of yeast isolates.

Influence of site of drug delivery on the systemic availability of metoprolol: comparison of intragastric infusion and 14/190 Oros administration.

The influence of the site of drug delivery on the systemic availability of metoprolol has been evaluated by measuring plasma drug concentrations in six healthy volunteers after administration of a continuous 13.5 h intragastric infusion and a 14/190 Oros controlled-release dosage form, on two separate occasions. The same total amount of drug was administered at the same rate on both occasions but the Oros system moved through the gut whereas the site of the infusion was constant. The differences between treatments were confined largely to the period 6-15 h after dosing when lower plasma concentrations were obtained after administration of the Oros system. The levels after 20 h were higher for Oros, however, reflecting its longer duration of drug release. The amount of drug reaching the circulation was 19.8% less for the Oros preparation compared with intragastric infusion but this was not due to incomplete release since the residual amounts of drug in three systems recovered from faeces corresponded to less than 12% of the administered dose. Analysis of the plasma profiles by the Wagner-Nelson method indicated a reasonable agreement between in vitro release and in vivo absorption. The appearance of drug in plasma was delayed for both treatments, and for Oros the apparent absorption rate slowed 6 h after dosing. Plasma profiles after 14/190 metoprolol Oros were consistent with prolonged in vivo delivery and absorption from the gut. The absorption process, however, was associated with some reduction both in the rate, after 6 h, and in the total amount reaching the circulation.