Fungal peritonitis complicating continuous ambulatory peritoneal dialysis: Successful treatment with fluconazole, a new orally active antifungal agent

Levine, Jerrold S.; Bernard, David B.; Idelson, Beldon A.; Farnham, H.; Saunders, Charles; Sugar, Alan M.

doi:10.1016/0002-9343(89)90481-6

Cited by 70 publications

(26 citation statements)

References 11 publications

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“…Of note, the fluconazole MIC end points obtained for susceptible organisms (0.25 ,ug/ml) by using this method correspond to achievable levels of fluconazole in blood and tissue of humans and experimental animals and are in agreement with the known in vivo activity of the drug in the setting of human and experimental candidiasis (7,17,18,20,25). Additional experiments are currently ongoing to correlate our in vitro findings with in vivo results of treatment in a murine model of systemic candidiasis.…”

Section: Resultssupporting

confidence: 61%

“…MICs of fluconazole obtained by direct visual reading without agitation, however, were difficult to read and were in the resistant range (MIC for 50% of the isolates tested [MIC50], >64 ,ug/ml; range, 16 to >64 ,ug/ml) (Table 1), not in keeping with the known activity of this drug in experimental and human candidiasis (7,13,17,18,20). Before agitation, the visible growth for the susceptible strains was noted at 64 ,ug/ml, gradually increasing as the drug concentration fell to 0.125 ,ug/ml but without any significant differences between consecutive wells, which would have allowed end point determination (Fig.…”

Section: Resultsmentioning

confidence: 99%

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Fluconazole susceptibility testing of Candida albicans: microtiter method that is independent of inoculum size, temperature, and time of reading

Anaissie

Paetznick

Bodey

1991

Antimicrob Agents Chemother

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In vitro antifungal susceptibility testing generally remains unstandardized and unreliable for directing therapy. When azoles are tested, this problem is further compounded by the lack of definite reading end points. We determined the in vitro susceptibility of 50 Candida albicans isolates (including 10 reference strains) to fluconazole by using a microbroth dilution method in which microtiter plates were agitated immediately before reading. Six fungal inoculum sizes (ranging from 2 x 102 to 4 x 105 CFU/ml), three different times of reading (24, 48, and 72 h) Over the past several years, we have witnessed an increasing number of opportunistic fungal infections in immunocompromised patients (1,5,14,28). In addition, fungi previously considered harmless colonizers have now emerged as significant pathogens, and many of them are resistant to available drugs (4,19,24). At the same time, several new antifungal agents have become available, resulting in a great demand for in vitro susceptibility testing (9,13,20,23,25,26). Although major advances in antifungal susceptibility testing have been achieved, particularly through the efforts of the National Committee for Clinical Laboratory Standards (NCCLS) (2, 6, 8-10, 21, 22), currently available methods remain difficult to duplicate and cannot be relied upon for directing therapy (6,9,10,26). This problem is particularly relevant to tests of susceptibility to azoles because of the lack of definite reading end points due to the "trailing effect." In this report, we present results of our determination of the in vitro susceptibility of 50 Candida albicans isolates to fluconazole by using a microbroth dilution method with agitation of the plates immediately before reading. This method resulted in clear-cut visual end points that were reproducible; that were independent of inoculum size, time of reading, and incubation temperature; and that correlated with the degree of fungal inhibition as determined by turbidity studies. MATERIALS AND METHODSAntifungal agent. Fluconazole (Pfizer, Sandwich, United Kingdom) was rendered soluble in 100% dimethyl sulfoxide (Sigma Chemical Co., St. Louis, Mo.) at a starting concentration of 6,400 ,ug/ml. Fluconazole was diluted with assay medium to the highest drug concentration of 64 pg/ml (4% dimethyl sulfoxide). Twofold dilutions were made for the remaining wells according to the NCCLS's modification of Ericsson and Sherris' method of dilution (8).Assay medium. RPMI 1640 medium powder with L-glu-* Corresponding author. tamine and without phosphate buffer (Sigma Chemical Co.) was used as the assay medium. Preweighed aliquots of 10.4 g of medium were mixed with 1,000 ml of deionized water buffered with morpholinepropanesulfonic acid (MOPS; Sigma Chemical Co.). The buffer solution was prepared with 34.53 g of MOPS (0.165 M) per 1,000 ml of water. Clear solutions of both the buffer powder-water and medium powder-buffered water combinations were obtained by using magnetic spin bars at room temperature. The solutions were titrated by using 10 N sod...

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Section: Resultssupporting

confidence: 61%

Section: Resultsmentioning

confidence: 99%

Fluconazole susceptibility testing of Candida albicans: microtiter method that is independent of inoculum size, temperature, and time of reading

Anaissie

Paetznick

Bodey

1991

Antimicrob Agents Chemother

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“…Temporary or even permanent cessation of PD is indeed often necessary in cases of FP; thus, 17 of our patients had to undergo tem porary hemodialysis which in particular involved the problem of vascular access and also of the availability of emergency hemodialysis facilities. Ten of these patients permanently switched from PD to hemodialysis, a pro portion that varied in different series [23,24], The rea sons for this transfer were very different: they included the patient's choice, a medical decision due in particular to repeated episodes of bacterial peritonitis, and failure of PD catheter replacement due to peritoneal adhesions caused by FP and/or by certain antifungal drugs [3,5,8,23], Priority aims for an optimal treatment strategy are the maintenance of peritoneal permeability and the pre vention of peritoneal adhesion formation, concomitantly 117 with fast and permanent sterilization of the peritoneal cavity. At the present time, such a strategy is hard to determine for FP.…”

Section: Discussionmentioning

confidence: 99%

“…Nevertheless, the recent commerciali zation of fluconazole seems likely to make it the preferred drug for use during PD, because of its excellent bioavail ability when given orally and because of its high concen trations in the peritoneal dialysate, whether it is adminis tered orally or intravenously [31], Fluconazole also seems to be less toxic than kétoconazole. In addition, Sugar [7] and Levine et al [24] suggested that with fluconazole the formation of peritoneal adhesions could be prevented, at least in peritonitis due to Candida organisms, by continu ing PD in cases displaying favorable clinical and bacterio logical responses or in other cases by rapid replacement of a new PD catheter. Although prospective clinical trials of PD-related FP comparing amphotericin B to the triazolefluorocytosine combination had not be performed, a ret rospective analysis of published data leads The ad hoc Advisory Committee on Peritonitis Management [25] to consider the latter combination as efficious as amphoteri cin B and to modify their recommendations in 1993: instead of removing systematically the peritoneal catheter as soon as the diagnosis of FP is made, they recommend to initiate lluconazole-fluorocytosine therapy while con tinuing CAPD.…”

Section: Discussionmentioning

confidence: 99%

“…Reported cases of FP treated with fluconazole-fluorocytosine are still few at present [24,29,[32][33][34][35][36][37][38][39] (table 4). In our opinion, unduly hopes should not be placed in this combination, and the clinical course should be cautiously monitored in order to enable catheter removal in time, if clinical or bacteriological responses are not rapidly seen with this treatment and in cases of filamentous fungi.…”

Section: Discussionmentioning

confidence: 99%

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Fungal Peritonitis in Patients on Peritoneal Dialysis

et al. 1994

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Fungal peritonitis (FP) is a serious complication of peritoneal dialysis, both in terms of morbidity and mortality. Available data on the effectiveness of fluconazole in eradicating FP without catheter removal are still controversial. We reviewed 20 FP cases that occurred among 325 patients who underwent peritoneal dialysis in our center between January 1984 and January 1992, in order to establish whether a profile of patients at risk of developing FP could be identified and to evaluate the effectiveness of fluconazole in treating FP (7 cases). Age, sex, a particular cause of end-stage renal disease, and the presence of diabetes did not correlate significantly with the development of FP. The risk of FP increased in patients on immunosuppressive treatment. Sixteen of our 20 patients had bacterial peritonitis during the month before they developed FP. Nineteen were treated with antibiotics. Neither the type of bacterial organism isolated during the bacterial peritonitis preceding FP nor modality and duration of antibiotic treatment correlated significantly with the development of FP. Patients who subsequently developed FP were more frequently treated with antibiotics while in hospital (p < 0.001). Candida species accounted for 15 of our 20 FP cases (75 %), with Candida albicans being by far the most common isolate. Treatment strategies varied among the 20 patients. The combination of intravenous or intraperitoneal administration of 5-fluoro-cytosine and oral administration of fluconazole was used in 7 cases: only 1 patient was cured without catheter removal, 1 patient died within the first 4 days of treatment, removal of peritoneal catheter was necessary in the other 5 patients. The main risk factors for the development of FP are a recent episode of bacterial peritonitis and recent exposure to antibiotics, especially when antibiotics were administered while in hospital. Under these circumstances, prophylactic administration of fluconazole should be considered. Despite initially favorable reports, fluconazole does not avoid the need for catheter removal to eradicate FP in most cases.

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Induction of Fluconazole Metabolism by Rifampin: In Vivo Study in Humans

Apseloff

Hilligoss

Gardner

et al. 1991

The Journal of Clinical Pharma

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The effects of rifampin on the pharmacokinetics of fluconazole were analyzed in an open-label, placebo-controlled, parallel study. Sixteen healthy male volunteers, randomized into two groups, received 200 mg of oral fluconazole on days 1 and 22. On days 8 through 27, group I received oral rifampin, 600 mg/d, and group II received placebo. Fluconazole in serum was analyzed by HPLC. On days 1 and 22, respectively, the AUC (micrograms.hr/mL) (mean +/- SD) was 160.5 +/- 19.5 and 124 +/- 22.2 in group I, 152 +/- 25 and 152.8 +/- 33.9 in group II; the Kel (hr-1) was .0211 +/- .0030 and .0264 +/- .0040 in group I, .0219 +/- .0036 and .0216 +/- .0053 in group II. Cmax and Tmax did not change significantly in either group. Urinary 6 beta-hydroxycortisol/cortisol increased from 3.47 +/- 1.04 to 15.2 +/- 5.07 in group I, but was unchanged (3.54 +/- 1.33-4.26 +/- 2.36) in group II on days 1 and 22, respectively. The findings in this study indicate that rifampin induces the metabolism of fluconazole.

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Fungal peritonitis complicating continuous ambulatory peritoneal dialysis: Successful treatment with fluconazole, a new orally active antifungal agent

Cited by 70 publications

References 11 publications

Fluconazole susceptibility testing of Candida albicans: microtiter method that is independent of inoculum size, temperature, and time of reading

Fluconazole susceptibility testing of Candida albicans: microtiter method that is independent of inoculum size, temperature, and time of reading

Fungal Peritonitis in Patients on Peritoneal Dialysis

Induction of Fluconazole Metabolism by Rifampin: In Vivo Study in Humans

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