In Vitro Pharmacodynamic Characteristics of Nystatin Including Time-Kill and Postantifungal Effect

Gunderson, Shana M.; Hoffman, Holly; Ernst, Erika J.; Pfaller, Michael A.; Klepser, Michael E.

doi:10.1128/aac.44.10.2887-2890.2000

Cited by 36 publications

(22 citation statements)

References 11 publications

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“…Available in vitro data demonstrate that the effect of amphotericin B is concentration dependent (23,99). This pharmacodynamic pattern has also been shown for nystatin, a related polyene antifungal (85). The in vivo prediction of such a result is that the most relevant pharmacodynamic correlate should be the ratio of peak drug concentration to MIC, and precisely this in vivo result was recently shown for amphotericin B in a murine model of invasive candidiasis (5).…”

Section: Support For the Clinical Relevance Of Nccls M27 Mics In Yeastsmentioning

confidence: 99%

Antifungal Susceptibility Testing: Practical Aspects and Current Challenges

Rex¹,

et al. 2001

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Development of standardized antifungal susceptibility testing methods has been the focus of intensive research for the last 15 years. Reference methods for yeasts (NCCLS M27-A) and molds (M38-P) are now available. The development of these methods provides researchers not only with standardized methods for testing but also with an understanding of the variables that affect interlaboratory reproducibility. With this knowledge, we have now moved into the phase of (i) demonstrating the clinical value (or lack thereof) of standardized methods, (ii) developing modifications to these reference methods that address specific problems, and (iii) developing reliable commercial test kits. Clinically relevant testing is now available for selected fungi and drugs: Candida spp. against fluconazole, itraconazole, flucytosine, and (perhaps) amphotericin B; Cryptococcus neoformans against (perhaps) fluconazole and amphotericin B; and Aspergillus spp. against (perhaps) itraconazole. Expanding the range of useful testing procedures is the current focus of research in this area

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Section: Support For the Clinical Relevance Of Nccls M27 Mics In Yeastsmentioning

confidence: 99%

Antifungal Susceptibility Testing: Practical Aspects and Current Challenges

Rex¹,

et al. 2001

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“…To compare the concentration-effect relationships at 2, 4, 6, 12, and 24 h of ABT-492 and levofloxacin against S. pneumoniae, H. influenzae, and M. catarrhalis, the mean time-kill data at each time point for each bacterial isolate were combined according to bacterial species. The net change (log 10 numbers of CFU per milliliter) in bacterial density at each time point for each concentration was fitted by multivariate nonlinear-regression analysis with a four-parameter sigmoidal Hill (E max ) model by using SigmaPlot 2000 for Windows (version 6.0; SPSS Inc.) (6,8). In this model, effect (the net change in the log 10 number of CFU per milliliter) is equal to…”

Section: Methodsmentioning

confidence: 99%

In Vitro Pharmacodynamic Activities of ABT-492, a Novel Quinolone, Compared to Those of Levofloxacin against Streptococcus pneumoniae , Haemophilus influenzae , and Moraxella catarrhalis

Gunderson

Hayes

Quinn

et al. 2004

Antimicrob Agents Chemother

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ABT-492 is a novel quinolone with potent activity against gram-positive, gram-negative, and atypical pathogens, making this compound an ideal candidate for the treatment of community-acquired pneumonia. We therefore compared the in vitro pharmacodynamic activity of ABT-492 to that of levofloxacin, an antibiotic commonly used for the treatment of pneumonia, through MIC determination and time-kill kinetic analysis. ABT-492 demonstrated potent activity against penicillin-sensitive, penicillin-resistant, and levofloxacin-resistant Streptococcus pneumoniae strains (MICs ranging from 0.0078 to 0.125 g/ml); ␤-lactamase-positive and ␤-lactamase-negative Haemophilus influenzae strains (MICs ranging from 0.000313 to 0.00125 g/ml); and ␤-lactamase-positive and ␤-lactamase-negative Moraxella catarrhalis strains (MICs ranging from 0.001 to 0.0025 g/ml), with MICs being much lower than those of levofloxacin. Both ABT-492 and levofloxacin demonstrated concentration-dependent bactericidal activities in time-kill kinetics studies at four and eight times the MIC with 10 of 12 bacterial isolates exposed to ABT-492 and with 12 of 12 bacterial isolates exposed to levofloxacin. Sigmoidal maximal-effect models support concentration-dependent bactericidal activity. The model predicts that 50% of maximal activity can be achieved with concentrations ranging from one to two times the MIC for both ABT-492 and levofloxacin and that near-maximal activity (90% effective concentration) can be achieved at concentrations ranging from two to five times the MIC for ABT-492 and one to six times the MIC for levofloxacin.

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“…The method used for determining PAFE in molds was based on methods used for bacteria and yeasts, with some modifications (4,10,12). Amphotericin B and itraconazole were dissolved in DMSO at initial concentrations of 400 g/ml, and aliquots of the stock solution were stored at Ϫ70°C until used.…”

Section: Isolatesmentioning

confidence: 99%

“…Conidia were counted, and the percent germination was estimated in duplicate at 0, 4,8,12,16,24, and 36 h.…”

Section: Isolatesmentioning

confidence: 99%

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Method for Measuring Postantifungal Effect inAspergillusSpecies

Vitale

Mouton

Afeltra

et al. 2002

Antimicrob Agents Chemother

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An in vitro method for determination of postantifungal effect (PAFE) in molds was developed by using three isolates each of Aspergillus fumigatus, A. flavus, A. terreus, A. nidulans, and A. ustus. MICs of amphotericin B and itraconazole were determined by using National Committee for Clinical Laboratory Standards guidelines (M38-P). The inoculum was prepared in RPMI 1640 broth buffered with MOPS (morpholinepropanesulfonic acid) at pH 7.0, and conidia were exposed to amphotericin B and itraconazole at concentrations of 4, 1, and 0.25 times the MIC, each for 4, 2, and 1 h at 37°C. The same procedure was followed for controls with drug-free medium. Following exposure, the conidia were washed three times in saline and the numbers of CFU per milliliter were determined. Exposed and control conidia were then inoculated into microtitration plates and incubated at 37°C for 48 h in a spectrophotometer reader. The optical density (OD) was measured automatically at 10-min intervals, resulting in growth curves. PAFE was quantified by comparing three arbitrary points in the control growth curve, the first increase of OD and the points when 20 and 50% of the maximal growth were reached, with the growth curve of drug-exposed conidia. Amphotericin B induced PAFE in A. fumigatus at four times the MIC after 2 and 4 h of exposure ranging from 1.83 to 6.00 h and 9.33 to 10.80 h, respectively. Significantly shorter PAFEs or lack of PAFE was observed for A. terreus, A. ustus, and A. nidulans. Itraconazole did not induce measurable PAFE in the Aspergillus isolates at any concentration or exposure time tested. Further studies are warranted to investigate the implications of PAFE in relation to clinical efficacy and dosing frequency.Aspergillus species are documented as some of the most prevalent airborne molds, and the frequency of mycoses due to these fungi is rising worldwide, especially invasive infections that occur in immunocompromised patients, such as cancer patients, bone marrow transplant recipients, solid-organ transplant recipients (13), and human immunodeficiency virus-infected patients (18).Aspergillus fumigatus and Aspergillus flavus are encountered most frequently, although other species have been documented to cause disease. Aspergillus terreus is an increasing cause of invasive infection in neutropenic patients and Aspergillus nidulans in patients with chronic granulomatous disease (22). Although amphotericin B is considered the drug of choice for treatment of invasive aspergillosis, the clinical response is limited, especially in infections caused by the latter two species. Alternatively, itraconazole is a triazole antifungal drug with good in vitro activity against Aspergillus and has been used successfully as first-line treatment in patients with invasive disease (2, 6).Methods for in vitro susceptibility testing of molds have been proposed only recently by the National Committee for Clinical Laboratory Standards (NCCLS) (19), but the correlation between MIC and clinical response remains unclear, especially for ampho...

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In Vitro Pharmacodynamic Characteristics of Nystatin Including Time-Kill and Postantifungal Effect

Cited by 36 publications

References 11 publications

Antifungal Susceptibility Testing: Practical Aspects and Current Challenges

Antifungal Susceptibility Testing: Practical Aspects and Current Challenges

In Vitro Pharmacodynamic Activities of ABT-492, a Novel Quinolone, Compared to Those of Levofloxacin against Streptococcus pneumoniae , Haemophilus influenzae , and Moraxella catarrhalis

Method for Measuring Postantifungal Effect inAspergillusSpecies

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