We investigated the in vitro activity of nystatin and liposomal nystatin against 103 Candida isolates to determine the effect of both time and medium on MICs. We also compared the nystatin MICs with those of amphotericin B and fluconazole. Testing was performed in accordance with the National Committee for Clinical Laboratory Standards M27-A microdilution methodology with RPMI 1640, RPMI 1640 supplemented with glucose to 2% (RPMI-2), and antibiotic medium 3 supplemented with glucose to 2% (AM3). While nystatin MICs were similar to or slightly lower than liposomal nystatin MICs in RPMI 1640 and RPMI-2, they were markedly higher than liposomal nystatin MICs in AM3. Use of AM3 and determination of the MIC after 24 h of incubation provided a slightly wider range of liposomal nystatin MICs (0.06 to >16 g/ml). Under these conditions, the MICs at which 90% of isolates were inhibited of nystatin and liposomal nystatin were 2 and 1 g/ml, respectively. Nystatin and liposomal nystatin in general showed good activity against all Candida spp. tested. Although the MICs of nystatin and liposomal nystatin tended to rise in parallel with the amphotericin B MICs, nystatin and liposomal nystatin MICs of 1 to 2 and 0.5 to 1 g/ml, respectively, were obtained for seven and six, respectively, of nine isolates for which amphotericin B MICs were >0.25 g/ml. No correlation between fluconazole and nystatin or liposomal nystatin MICs was observed. As amphotericin B MICs of >0.25 g/ml correlate with in vitro resistance, these results suggest that liposomal nystatin might have activity against some amphotericin B-resistant isolates. In vivo testing in animal models is required for clarification of this issue.As acquired resistance has been described for both amphotericin B and the current azoles (4,10,30,31,34), there is interest in developing new antifungal agents. Nystatin, a polyene antibiotic derived from Streptomyces noursei, is known to be effective against a variety of fungal infections in humans. Although the drug has been widely used as oral and topical therapy for superficial mycoses (16), intravenous use has been limited by its toxic side effects. To overcome these problems, nystatin has been reformulated in a lipid complex that has demonstrated reduced side effects while maintaining antifungal activity in vitro and in vivo 6, 9, 11, 17, 18, 32; C. J. Jessup, T. J. Wallace, and M. A. Ghannoum, Abstr. 37th Intersci. Conf. Antimicrob. Agents Chemother., abstr. F-88, 1997).The relevance, if any, of in vitro testing with lipid-based preparations of polyenes such as amphotericin B and nystatin (rather than the parent drug) is unclear. Some feel that the role of a lipid formulation is solely to alter in vivo drug delivery and that testing the in vitro activity of lipid formulations is of little relevance. On the other hand, use of a lipid-based polyene preparation could be viewed as simply being an alternative way to dissolve the polyene, as opposed to the use of the dimethyl sulfoxide (DMSO) specified by the National Committee for Clin...
abnormal colposcopic findings. Six of the seven were reported to have had complete excision and would therefore not have been selected for more detailed follow up under the authors' revised policy. N. Mahadevan D. H. Horwell Department of Obstetrics and Gynaecology Luton and Dunstable Hospital NHS TrustLuton LU40DZ The recommendations made in the flow chart are the result of continuing evolutionary review using a variety of treatment methods during the last 18 years. The systems that we have recommended depend on high quality cytology and histopathology services which we are fortunate to have available. Our recommendations are made on the basis of extremely careful audit and analysis of information. The experience of Mahadevan and Horwell in in finding that among their own patients six of the 11 patients with histologically proven residual disease detected at four months, had had apparently normal cytology may be a reflection of smear taking technique or reporting, rather than an inadequacy of the system. Similarly in their letter where five of the six of their cases were reported to have had complete excision, this may warrant a careful review of the histopathology techniques used. C O R R E S P O N D E N C E 795 ReferencesWe have no doubt that this paper which is one of many generated from this department's very large long term data base will almost certainly not be the last word on this subject. It is currently our view that this flow chart is the most sophisticated and accurate way of dealing with the problem of CIN enabling us to deal efficiently and rapidly with those patients who have significant lesions and also to deal more conservatively with those patients who have low grade lesions and to reduce the number of stressful colposcopy clinic visits that these patients have to submit to. J. M. Monaghan Prostaglandin prophylaxis and bladder function after vaginal hysterectomy: a prospective randomised studySir, We read the paper by Bergman et al. (1993) and were surprised that a direct comparison was being made between two prostaglandin compounds administered differently. Whilst the molecular weights of the compounds are similar (PGE2-352.5 and PGFza-3545) there are no data regarding the absorption of PGF2, which is not normally administered intravesically and therefore a comparison with the rapid and complete absorption of PGE;? is not possible. As no figures are given for the systemic concentrations of these substances it seems hard to draw the conclusion that one drug is more efficacious than the other when the effect may be dose related, due to differential absorption through the stratified squamous epithelium of the vagina and the transitional epithelium of the bladder.May we also point out that the conclusion in the abstract is erroneous in stating that either intravesical or intravaginal prostaglandins is beneficial in enhancing bladder function after vaginal hysterectomy when the article concludes that vaginal PGE;? is superior. ). Blood concentration was not compared since we studied only the clin...
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