Antifungal Activity of Amphotericin B, Fluconazole, and Voriconazole in an In Vitro Model of Candida Catheter-Related Bloodstream Infection

ABSTRACT The activity of five simulated antifungal regimens for eradication of catheter-related bloodstream Candida infection was evaluated with an in vitro pharmacodynamic model. Single-lumen central venous catheters were colonized with Candida species by sequentially incubating central venous catheters in plasma and then in growth medium (RPMI plus morpholinepropanesulfonic acid) containing a standardized suspension (105 CFU/ml) of Candida albicans, Candida glabrata, or slime-producing Candida parapsilosis. Colonized central venous catheters were then placed in a one-compartment pharmacodynamic model where five antifungal regimens (plus control) were simulated: amphotericin B, 1.0 mg/kg every 24 h; amphotericin B, 0.5 mg/kg every 24 h; fluconazole, 400 mg every 24 h; fluconazole, 800 mg every 24 h; and voriconazole, 4 mg/kg every 12 h. During exposure to the simulated clinical regimens, samples were serially removed from the model over 48 h for quantitation of viable organisms. All antifungal regimens suppressed fungal counts by both peripheral and catheter sampling versus control (P = 0.001). Overall, antifungal activity ranked amphotericin B (1 mg/kg) > amphotericin B (0.5 mg/kg) ≥ voriconazole > fluconazole (800 mg) ≥ fluconazole (400 mg). No regimen, however, completely eradicated (by culture and electron microscopy) central venous catheter colonization. Regrowth was noted in the model during therapy against C. glabrata and C. parapsilosis but was not associated with an increase in the MICs for the isolates. Lack of in vitro antifungal activity against biofilm-encased organisms appeared to be the primary reason for mycological failure of antifungal regimens in the model.

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Antifungal Activity of Flocculosin, a Novel Glycolipid Isolated from Pseudozyma flocculosa

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.49.4.1597-1599.2005 ◽

2005 ◽

Vol 49 (4) ◽

pp. 1597-1599 ◽

Cited By ~ 61

Author(s):

Benjamin Mimee ◽

Caroline Labbé ◽

René Pelletier ◽

Richard R. Bélanger

Keyword(s):

Antifungal Activity ◽

Amphotericin B ◽

Cell Lines ◽

Human Cell ◽

Synergistic Activity ◽

Human Cell Lines ◽

Antifungal Properties ◽

Pseudozyma Flocculosa ◽

In Vitro Antifungal Activity

ABSTRACT Flocculosin, a glycolipid isolated from the yeast-like fungus Pseudozyma flocculosa, was investigated for in vitro antifungal activity. The compound displayed antifungal properties against several pathogenic yeasts. Synergistic activity was observed between flocculosin and amphotericin B, and no significant cytotoxicity was demonstrated when tested against human cell lines.

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Amphotericin B in Lipid Emulsion: Stability, Compatibility, and In Vitro Antifungal Activity

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.42.4.762 ◽

1998 ◽

Vol 42 (4) ◽

pp. 762-766 ◽

Cited By ~ 18

Author(s):

Scott Walker ◽

Sandra A. N. Tailor ◽

Mark Lee ◽

Lisa Louie ◽

Marie Louie ◽

...

Keyword(s):

Antifungal Activity ◽

Amphotericin B ◽

Clinical Laboratory ◽

National Committee ◽

Compatibility Study ◽

The Stability ◽

Few Data ◽

Reference Strains ◽

In Vitro Antifungal Activity

ABSTRACT Newer formulations of amphotericin B (AmB) complexed with liposomes or lipid suspensions have been developed. Preliminary studies have suggested that AmB in Intralipid (IL) may be as effective as, but less toxic than, conventional formulations of AmB, but few data are available regarding its stability, compatibility, or in vitro antifungal activity. A compatibility study was done to evaluate the effects of AmB concentrations in IL containing either 10 or 20% soybean oil. The effects of temperature, shaking, and AmB and IL concentrations on the stability of AmB-IL suspensions were analyzed by visual inspection and liquid chromatography. The in vitro antifungal activity of AmB-IL, compared to that of AmB alone against reference strains of Candida species was determined by using a broth macrodilution method in accordance with National Committee for Clinical Laboratory Standards guidelines (M27-T). Samples of AmB-IL which were lightly shaken retained more than 90% of the AmB concentration over 21 days when stored at either 4 or 23°C. Varying the AmB concentration did not appear to affect the stability of AmB-IL. However, a precipitate was formed when mixtures with more than 30% lipid as a proportion of the total volume were centrifuged. AmB-IL and AmB alone had similar in vitro antifungal activities against reference strains of yeasts. Further pharmacologic and clinical studies with AmB-IL are warranted, although AmB should not be combined with IL in concentrations capable of producing a precipitate.

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Intravascular Ultrasonographic Assessment of Thrombus Formation on Central Venous Catheters

Acta Radiologica ◽

10.1177/028418519303400212 ◽

1993 ◽

Vol 34 (2) ◽

pp. 162-167 ◽

Cited By ~ 5

Author(s):

K.-D. Bolz ◽

P. Aadahl ◽

J. Mangersnes ◽

J. Å. Rødsjø ◽

S. Jørstad ◽

...

Keyword(s):

Thrombus Formation ◽

Venous Catheter ◽

Central Venous Catheters ◽

Brachiocephalic Vein ◽

Intravascular Ultrasonography ◽

Central Venous ◽

Vein Thrombosis ◽

Clinical Investigations ◽

Ultrasonographic Assessment

In vitro experiments were performed in order to investigate the appearance of different types of central venous catheters at intravascular ultrasonography. The experiments were repeated with artificially produced thrombi which were made adherent to the catheter wall. All thrombi larger than 1 mm could be identified. In a clinical study including 12 patients who had a central venous catheter, transfemoral intravascular ultrasonography was performed. The catheters had been in place for an average period of 54 days (range 1–360 days). In 3 patients a catheter thrombus, mural thrombus, or occlusive vein thrombosis was found. In 2 of these patients the catheter was occluded, in the 3rd patient it was malpositioned into the contralateral brachiocephalic vein. There were no complications following the ultrasonographic procedures. Mean catheterization time was 7.5 min (range 3–20 min). The advantages of this new method compared with conventional phlebographic studies and its impact on further clinical investigations are discussed.

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Comparison of the in vitro antifungal activity of free and liposome-encapsulated amphotericin B

European Journal of Clinical Microbiology & Infectious Diseases ◽

10.1007/bf01975823 ◽

1991 ◽

Vol 10 (8) ◽

pp. 665-668 ◽

Cited By ~ 65

Author(s):

E. Anaissie ◽

V. Paetznick ◽

R. Proffitt ◽

J. Adler-Moore ◽

G. P. Bodey

Keyword(s):

Antifungal Activity ◽

Amphotericin B ◽

In Vitro Antifungal Activity

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Characterization of the colloidal properties, in vitro antifungal activity, antileishmanial activity and toxicity in mice of a distigmasterylhemisuccinoyl-glycero-phosphocholine liposome-intercalated amphotericin B

International Journal of Pharmaceutics ◽

10.1016/j.ijpharm.2011.01.044 ◽

2011 ◽

Vol 408 (1-2) ◽

pp. 163-172 ◽

Cited By ~ 33

Author(s):

Maryam Iman ◽

Zhaohua Huang ◽

Francis C. Szoka ◽

Mahmoud R. Jaafari

Keyword(s):

Antifungal Activity ◽

Amphotericin B ◽

Antileishmanial Activity ◽

Colloidal Properties ◽

In Vitro Antifungal Activity

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Linezolid Compared with Eperezolid, Vancomycin, and Gentamicin in an In Vitro Model of Antimicrobial Lock Therapy for Staphylococcus epidermidis Central Venous Catheter-Related Biofilm Infections

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.47.10.3145-3148.2003 ◽

2003 ◽

Vol 47 (10) ◽

pp. 3145-3148 ◽

Cited By ~ 76

Author(s):

John Curtin ◽

Martin Cormican ◽

Gerard Fleming ◽

John Keelehan ◽

Emer Colleran

Keyword(s):

Central Venous Catheter ◽

Staphylococcus Epidermidis ◽

In Vitro Model ◽

Physiological Saline ◽

Venous Catheter ◽

Saline Control ◽

Central Venous ◽

The Mean ◽

Vitro Model

ABSTRACT Central venous catheter (CVC)-related infection (CVC-RI) is a common complication of CVC use. The most common etiological agents of CVC-RI are gram-positive organisms, in particular, staphylococci. An in vitro model for the formation of biofilms by Staphylococcus epidermidis ATCC 35984 on polyurethane coupons in a modified Robbins device was established. Biofilm formation was confirmed by electron microscopy and was quantified by determination of viable counts. Mueller-Hinton broth was replaced with sterile physiological saline (control) or a solution of vancomycin (10 mg/ml), gentamicin (10 mg/ml), linezolid (2 mg/ml), or eperezolid (4 mg/ml). Viable counts were performed with the coupons after exposure to antimicrobials for periods of 24, 72, 168, and 240 h. The mean viable count per coupon following establishment of the biofilm was 4.6 × 108 CFU/coupon, and that after 14 days of exposure to physiological saline was 2.5 × 107 CFU/coupon. On exposure to vancomycin (10 mg/ml), the mean counts were 2.5 × 107 CFU/coupon at 24 h, 4.3 × 106 CFU/coupon at 72 h, 1.4 × 105 CFU/coupon at 168 h, and undetectable at 240 h. With gentamicin (10 mg/ml) the mean counts were 2.7 × 107 CFU/coupon at 24 h, 3.7 × 106 CFU/coupon at 72 h, 8.4 × 106 CFU/coupon at 168 h, and 6.5 × 106 CFU/coupon at 240 h. With linezolid at 2 mg/ml the mean counts were 7.1 × 105 CFU/coupon at 24 h and not detectable at 72, 168, and 240 h. With eperezolid (4 mg/ml) no viable cells were recovered after 168 h. These data suggest that linezolid (2 mg/ml) and eperezolid (4 mg/ml) achieve eradication of S. epidermidis biofilms more rapidly than vancomycin (10 mg/ml) and gentamicin (10 mg/ml).

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