Effect of 50% human serum on the killing activity of micafungin against eight Candida species using time–kill methodology

2012 ◽  
Vol 73 (4) ◽  
pp. 338-342 ◽  
Author(s):  
Richárd Földi ◽  
Judit Szilágyi ◽  
Gábor Kardos ◽  
Réka Berényi ◽  
Renátó Kovács ◽  
...  
Keyword(s):  
Human Serum ◽  
Candida Species ◽  
Killing Activity ◽  
Time Kill

Effect of nikkomycin Z and 50% human serum on the killing activity of high-concentration caspofungin againstCandida speciesusing time-kill methodology

2012 ◽  
Vol 24 (1) ◽  
pp. 18-25 ◽  
Author(s):  
Judit Szilágyi ◽  
Richárd Földi ◽  
Sedigh Bayegan ◽  
Gábor Kardos ◽  
László Majoros
Keyword(s):  
Human Serum ◽  
High Concentration ◽  
Killing Activity ◽  
Nikkomycin Z ◽  
Time Kill

scholarly journals Bactericidal Activity, Absence of Serum Effect, and Time-Kill Kinetics of Ceftazidime-Avibactam against β-Lactamase-Producing Enterobacteriaceae and Pseudomonas aeruginosa

2014 ◽  
Vol 58 (9) ◽  
pp. 5297-5305 ◽  
Author(s):  
Tiffany R. Keepers ◽  
Marcela Gomez ◽  
Chris Celeri ◽  
Wright W. Nichols ◽  
Kevin M. Krause
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Human Serum ◽  
Bactericidal Activity ◽  
Minimum Bactericidal Concentration ◽  
Wild Type ◽  
Content Type ◽  
Positive Isolate ◽  
New Treatment ◽  
Time Kill ◽  
Kinetics Of

ABSTRACTAvibactam, a non-β-lactam β-lactamase inhibitor with activity against extended-spectrum β-lactamases (ESBLs), KPC, AmpC, and some OXA enzymes, extends the antibacterial activity of ceftazidime against most ceftazidime-resistant organisms producing these enzymes. In this study, the bactericidal activity of ceftazidime-avibactam against 18Pseudomonas aeruginosaisolates and 15Enterobacteriaceaeisolates, including wild-type isolates and ESBL, KPC, and/or AmpC producers, was evaluated. Ceftazidime-avibactam MICs (0.016 to 32 μg/ml) were lower than those for ceftazidime alone (0.06 to ≥256 μg/ml) against all isolates except for 2P. aeruginosaisolates (1blaVIM-positive isolate and 1blaOXA-23-positive isolate). The minimum bactericidal concentration/MIC ratios of ceftazidime-avibactam were ≤4 for all isolates, indicating bactericidal activity. Human serum and human serum albumin had a minimal effect on ceftazidime-avibactam MICs. Ceftazidime-avibactam time-kill kinetics were evaluated at low MIC multiples and showed time-dependent reductions in the number of CFU/ml from 0 to 6 h for all strains tested. A ≥3-log10decrease in the number of CFU/ml was observed at 6 h for allEnterobacteriaceae, and a 2-log10reduction in the number of CFU/ml was observed at 6 h for 3 of the 6P. aeruginosaisolates. Regrowth was noted at 24 h for some of the isolates tested in time-kill assays. These data demonstrate the potent bactericidal activity of ceftazidime-avibactam and support the continued clinical development of ceftazidime-avibactam as a new treatment option for infections caused byEnterobacteriaceaeandP. aeruginosa, including isolates resistant to ceftazidime by mechanisms dependent on avibactam-sensitive β-lactamases.

scholarly journals In Vitro Time-Kill of Common Ocular Pathogens with Besifloxacin Alone and in Combination with Benzalkonium Chloride

2021 ◽  
Vol 14 (6) ◽  
pp. 517
Author(s):  
Joseph Blondeau ◽  
Heleen DeCory
Keyword(s):  
Staphylococcus Epidermidis ◽  
Benzalkonium Chloride ◽  
Bacterial Species ◽  
Drug Resistant ◽  
Resistance Development ◽  
Aureus Isolate ◽  
Killing Activity ◽  
Time Kill ◽  
Variable Impact

Background: Besifloxacin ophthalmic suspension 0.6% (w/v%) contains benzalkonium chloride (BAK) as a preservative. We evaluated the in vitro time-kill activity of besifloxacin, alone and in combination with BAK, against common bacteria implicated in ophthalmic infections. Methods: The activity of besifloxacin (100 µg/mL), BAK (10, 15, 20, and 100 µg/mL), and combinations of besifloxacin and BAK were evaluated against isolates of Staphylococcus epidermidis (n = 4), Staphylococcus aureus (n = 3), Haemophilus influenzae (n = 2), and Pseudomonas aeruginosa (n = 2) in time-kill experiments of 180 min duration. With the exception of one S. aureus isolate, all of the staphylococcal isolates were methicillin- and/or ciprofloxacin-resistant; one P. aeruginosa isolate was ciprofloxacin-resistant. The reductions in the viable colony counts (log10 CFU/mL) were plotted against time, and the differences among the time–kill curves were evaluated using an analysis of variance. Areas-under-the-killing-curve (AUKCs) were also computed. Results: Besifloxacin alone demonstrated ≥3-log killing of P. aeruginosa (<5 min) and H. influenzae (<120 min), and approached 3-log kills of S. aureus. BAK alone demonstrated concentration-dependent killing of S. epidermidis, S. aureus and H. influenzae, and at 100 µg/mL produced ≥3-log kills in <5 min against these species. The addition of BAK (10, 15, and 20 µg/mL) to besifloxacin increased the rate of killing compared to besifloxacin alone, with earlier 3-log kills of all species except P. aeruginosa and a variable impact on S. aureus. The greatest reductions in AUKC were observed among H. influenzae (8-fold) and S. epidermidis (≥5-fold). Similar results were found when the isolates were evaluated individually by their resistance phenotype. Conclusions: In addition to confirming the activity of 100 µg/mL BAK as a preservative in the bottle, these data suggest that BAK may help besifloxacin to achieve faster time-kills on-eye in the immediate timeframe post-instillation before extensive dilution against bacterial species implicated in ophthalmic infections, including drug-resistant S. epidermidis. Greater killing activity may help prevent resistance development and/or help treat resistant organisms.

scholarly journals 1723. Human Serum Albumin Regulates the Growth of Candida auris in vitro

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S631-S632
Author(s):  
Jun Sakai
Keyword(s):  
Human Serum Albumin ◽  
Serum Albumin ◽  
Human Serum ◽  
Candida Species ◽  
Blood Protein ◽  
Albumin Concentration ◽  
Blood Proteins ◽  
Candida Auris ◽  
Xtt Assay ◽  
High Albumin

Abstract Background Candida auris is commonly detected in human ear secretions. However, C. auris occasionally causes bloodstream infections even in immunocompetent patients resulting in poor prognosis. It was speculated that C. auris growth within the blood might be regulated by proteins in the bloodstream. Thus, in this study, the potential role of blood proteins in the regulation of C. auris growth was investigated. Methods Five Candida species (C. albicans, C. auris, C. glabrata, C. parapsilosis, and C. tropicalis) were incubated overnight. Colony suspensions for each species were prepared and adjusted to OD 1.0 at absorbance 0.1. Then, human serum albumin (HSA) and bovine serum albumin (BSA) were diluted (2.5 g/dL–0.002 g/dL) and mixed with the suspensions. Mixed samples were adjusted to 100 μL and incubated on MHA plates at 35°C for 2 days. Then, 50 μL of the combined sample was extracted and streaked onto Yeast extract-Peptone-Dextrose (YPD) agar. The remaining 50 μL sample was analyzed using an XTT assay. Further testing was then conducted on the effects of a specific blood protein albumin on Candida. Thereby, C. albicans and C. auris were cultured following the procedure above and stained with Annexin V and PI. Results The growth of C. auris mixed with a high albumin concentration (2.5~0.15 g/dL) was regulated compared with that of other Candida species (P < 0.01) (Figures 1 and 2); however, the growth of C. auris mixed with a lower albumin concentration was similar to that of other species. The wash-out study showed that C. auris growth and survival in the high albumin concentration was not different than that of other species. Conclusion HSA and BSA regulated C. auris growth which led to increased necrosis of C. auris. Conversely, growth of the other Candida species was not regulated. Therefore, albumin might be involved in the growth and necrosis of C. auris. As the highest concentration at which albumin regulated C. auris growth was similar to that found in human serum, it is possible that serum albumin might help prevent C. auris from entering the bloodstream via the ear or skin. Disclosures All authors: No reported disclosures.

scholarly journals Head-to-Head Comparison of Inhibitory and Fungicidal Activities of Fluconazole, Itraconazole, Voriconazole, Posaconazole, and Isavuconazole against Clinical Isolates of Trichosporon asahii

2013 ◽  
Vol 57 (10) ◽  
pp. 4841-4847 ◽  
Author(s):  
Gulsen Hazirolan ◽  
Emilia Canton ◽  
Selma Sahin ◽  
Sevtap Arikan-Akdagli
Keyword(s):  
Rank Order ◽  
Growth Control ◽  
Clinical Isolates ◽  
Content Type ◽  
Trichosporon Asahii ◽  
Killing Activity ◽  
Fungistatic Activity ◽  
Microdilution Method ◽  
Inhibition Of Growth ◽  
Time Kill

ABSTRACTTreatment of disseminatedTrichosporoninfections still remains difficult. Amphotericin B frequently displays inadequate fungicidal activity and echinocandins have no meaningful antifungal effect against this genus. Triazoles are currently the drugs of choice for the treatment ofTrichosporoninfections. This study evaluates the inhibitory and fungicidal activities of five triazoles against 90 clinical isolates ofTrichosporon asahii. MICs (μg/ml) were determined according to Clinical and Laboratory Standards Institute microdilution method M27-A3 at 24 and 48 h using two endpoints, MIC-2 and MIC-0 (the lowest concentrations that inhibited ∼50 and 100% of growth, respectively). Minimum fungicidal concentrations (MFCs; μg/ml) were determined by seeding 100 μl of all clear MIC wells (using an inoculum of 104CFU/ml) onto Sabouraud dextrose agar. Time-kill curves were assayed against four clinicalT. asahiiisolates and theT. asahiiATCC 201110 strain. The MIC-2 (∼50% reduction in turbidity compared to the growth control well)/MIC-0 (complete inhibition of growth)/MFC values that inhibited 90% of isolates at 48 h were, respectively, 8/32/64 μg/ml for fluconazole, 1/2/8 μg/ml for itraconazole, 0.12/0.5/2 μg/ml for voriconazole, 0.5/2/4 μg/ml for posaconazole, and 0.25/1/4 μg/ml for isavuconazole. The MIC-0 endpoints yielded more consistent MIC results, which remained mostly unchanged when extending the incubation to 48 h (98 to 100% agreement with 24-h values) and are easier to interpret. Based on the time-kill experiments, none of the drugs reached the fungicidal endpoint (99.9% killing), killing activity being shown but at concentrations not reached in serum. Statistical analysis revealed that killing rates are dose and antifungal dependent. The lowest concentration at which killing activity begins was for voriconazole, and the highest was for fluconazole. These results suggest that azoles display fungistatic activity and lack fungicidal effect againstT. asahii. By rank order, the most active triazole is voriconazole, followed by itraconazole ∼ posaconazole ∼ isavuconazole > fluconazole.

scholarly journals Silver diamine fluoride (SDF) used in childhood caries management has potent antifungal activity against oral Candida species

2020 ◽  
Author(s):  
Kausar Sadia Fakhruddin ◽  
Hiroshi Egusa ◽  
Hien Chi Ngo ◽  
Chamila Panduwawala ◽  
Siripen Pesee ◽  
...  
Keyword(s):  
Candida Species ◽  
Fungal Species ◽  
Silver Diamine Fluoride ◽  
Low Concentrations ◽  
Caries Management ◽  
Bacteria And Fungi ◽  
Oral Candida ◽  
Time Kill ◽  
First Time ◽  
Childhood Caries

Abstract Background: The microbiome of Severe-Early Childhood Caries (S-ECC), is characterized by an ecosystem comprising bacterial and fungal species, with a predominance of Candida species. Hence, an anti-cariogen effective against both bacteria and fungi would be valuable in the management of S-ECC. Here we evaluate the antifungal effect of silver diamine fluoride (SDF) against 35-clinical yeast isolates (Ten-each of C. albicans , C. krusei, C. tropicalis and five C. glabrata strains) from dentinal caries-lesions from S-ECC. Results: Disc-diffusion and time-kill assays as well as MIC 50 and MIC 90 evaluations against therapeutic concentrations confirmed the broad-spectrum anti-candidal potency of SDF. Ultrastructural images revealed morphologic aberrations of yeast-cell walls on exposure to SDF. All C. krusei and C. glabrata isolates were significantly more sensitive to SDF, relative to the standard antifungal fluconazole. Further, SDF appears to effectively abrogate filamentation of C. albicans even at very low concentrations. Conclusions: Our data, for the first time, elucidate the anti-candidal potency of SDF, in addition to its known antibacterial activity, in the management of S-ECC.

scholarly journals Antimicrobial Activity of Ceftriaxone Compared with Cefotaxime in the Presence of Serum Albumin

1995 ◽  
Vol 6 (1) ◽  
pp. 21-27 ◽  
Author(s):  
Swapan K Nath ◽  
Gary A Foster ◽  
Lionel A Mandell ◽  
Coleman Rotstein
Keyword(s):  
Antimicrobial Activity ◽  
Human Serum Albumin ◽  
Serum Albumin ◽  
Human Serum ◽  
Significant Interaction ◽  
Gram Negative ◽  
In Vitro Antimicrobial Activity ◽  
Bactericidal Activities ◽  
Time Kill

The effect of serum albumin on the antimicrobial activity of ceftriaxone, cefotaxime, and a 1:1 ratio of cefotaxime and its desacetyl metabolite against nonpseudomonal Gram-negative bacilli was determined. Antimicrobial activity of drugs was evaluated by measuring minimum inhibitory (mic) and bactericidal (mbc) concentrations in broth with and without human serum albumin. The analysis of logarithmically transformed meanmics andmbcs showed that there was a highly significant interaction between drug and serum albumin (P<0.0001). The inhibitory and bactericidal activities were greatest for cefotaxime followed by cefotaxime/desacetylcefotaxime and ceftriaxone (P<0.01). Time-kill kinetics demonstrated that ceftriaxone was less bactericidal than cefotaxime in broth with albumin. On the basis of these results it was concluded that the in vitro antimicrobial activity of ceftriaxone compared with that of cefotaxime was significantly diminished in the presence of serum albumin.

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