scholarly journals Synergistic activity of azoles with amiodarone against clinically resistant Candida albicans tested by chequerboard and time–kill methods

2008 ◽  
Vol 57 (4) ◽  
pp. 457-462 ◽  
Author(s):  
Qiongjie Guo ◽  
Shujuan Sun ◽  
Jinlong Yu ◽  
Yan Li ◽  
Lili Cao
Keyword(s):  
Candida Albicans ◽  
Inhibitory Concentration ◽  
Systemic Disease ◽  
Synergistic Activity ◽  
Synergistic Interactions ◽  
Colony Counting ◽  
Reduction Assay ◽  
Time Kill ◽  
Concentration Indices

Candida albicans is the most common candidal pathogen, causing serious systemic disease in immunocompromised patients. Azoles are widely applied and largely effective; however, they are generally fungistatic and clinically resistant isolates are emerging increasingly. The present study provided in vitro evidence using a chequerboard technique that amiodarone is strongly synergistic with azoles against resistant C. albicans, with mean fractional inhibitory concentration indices of 0.01 and high-percentage synergistic interactions of 1250 %. A time–kill study performed by both colony counting and a colorimetric reduction assay confirmed the synergistic interaction, with a ≥2 log10 decrease in c.f.u. ml−1 compared with the corresponding azoles alone. These results suggest the possibility of supplementing azoles with amiodarone to treat resistant C. albicans infections.

scholarly journals Synergistic anticryptosporidial potential of the combination alpha-1-antitrypsin and paromomycin.

1997 ◽  
Vol 41 (9) ◽  
pp. 2006-2008 ◽  
Author(s):  
J R Forney ◽  
S Yang ◽  
M C Healey
Keyword(s):  
Inhibitory Concentration ◽  
Combined Treatment ◽  
Serine Protease Inhibitor ◽  
Synergistic Activity ◽  
Combined Treatments ◽  
Treatment Groups ◽  
The Mean ◽  
Alpha 1 Antitrypsin ◽  
Concentration Indices

The combined effect of the serine protease inhibitor alpha-1-antitrypsin (AAT) and the aminoglycoside paromomycin on Cryptosporidium parvum infection in vitro was investigated. AAT and paromomycin were mixed with C. parvum oocysts as either single or combined treatments and used to inoculate epithelial cell cultures. Single- and combined-treatment groups had significantly lower (P < 0.01) parasite numbers than untreated controls. The mean fractional inhibitory concentration indices suggested significant synergistic activity.

scholarly journals Thidiazuron, a phenyl-urea cytokinin, inhibits ergosterol synthesis and attenuates biofilm formation of Candida albicans

2021 ◽  
Author(s):  
Harikrishnan Pandurangan ◽  
Balamani Arayambath ◽  
Vijay Karthik Jayaraman ◽  
Kanimozhi Ekambaram ◽  
Emad A Ahmed ◽  
...  
Keyword(s):  
Gene Expression ◽  
Candida Albicans ◽  
Crystal Violet ◽  
Biofilm Formation ◽  
Reduction Assay ◽  
Ergosterol Synthesis ◽  
Inhibitory Potential ◽  
Anti Fungal ◽  
Time Kill

Abstract Candida albicans is a commensal human fungal pathogen that colonizes and develops dental biofilm which cause Oral candidiosis. This study investigates the effects of a new molecule Thidiazuron against the growth and biofilm formation properties of C. albicans. This study applied computational and in vitro approaches such as broth microdilution, SEM, time-kill dynamics, crystal violet assay, XTT reduction assay, ergosterol quantification and quantitative RT PCR analysis of gene expression to validate the growth and biofilm inhibitory potential of thidiazuron against C. albicans. Preliminary molecular docking study revealed potential interaction between thidiazuron and amino acids residues of CYP51. Further in vitro anti-fungal susceptibility test, SEM and time kill analysis revealed anti-fungal potency of thidiazuron in dose and time dependent passion. Crystal violet staining, XTT reduction assay and Acridine Orange staining visually confirmed biofilm inhibitory potential of thidiazuron. Gene expression study shows that thidiazuron treatment down regulated the expression of genes involved in ergosterol synthesis, cell adhesion and hyphae development in C. albicans. This study identified thidiazuron as CYP51 inhibitor and a new antibiofilm agent against C. albicans.

scholarly journals In Vitro Antibacterial Activity of Cefiderocol against Multidrug-Resistant Acinetobacter baumannii

2021 ◽  
Author(s):  
Jacinda C. Abdul-Mutakabbir ◽  
Logan Nguyen ◽  
Philip T. Maassen ◽  
Kyle C. Stamper ◽  
Razieh Kebriaei ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Susceptibility Testing ◽  
Inhibitory Concentration ◽  
Multidrug Resistant ◽  
Synergistic Activity ◽  
Strong Activity ◽  
Gram Negative ◽  
In Vitro Antibacterial Activity ◽  
Time Kill

Cefiderocol (CFDC), a novel siderophore cephalosporin, demonstrates strong activity against multidrug-resistant (MDR) Acinetobacter baumannii. Limited studies have evaluated CFDC alone and in combination with other Gram-negative antibiotics against MDR A. baumannii isolates. Susceptibility testing revealed lower CFDC minimum inhibitory concentration (MIC) values than the comparator Gram-negative agents (87% of MICs ≤ 4mg/L). Six isolates, with elevated CFDC MICs (16-32 mg/L), were selected for further experiments. Time-kill analyses presented with synergistic activity and beta-lactamase inhibitors increased CFDC susceptibility in each of the isolates.

scholarly journals In Vitro Activities of Retigeric Acid B Alone and in Combination with Azole Antifungal Agents against Candida albicans

2009 ◽  
Vol 53 (4) ◽  
pp. 1586-1591 ◽  
Author(s):  
Lingmei Sun ◽  
Shujuan Sun ◽  
Aixia Cheng ◽  
Xiuzhen Wu ◽  
Yu Zhang ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Inhibitory Concentration ◽  
Colorimetric Assay ◽  
Fungal Growth ◽  
Synergistic Interactions ◽  
Pentacyclic Triterpenoid ◽  
Antifungal Effects ◽  
Resistant Strains ◽  
The Difference

ABSTRACT The vitro antifungal activity of retigeric acid B (RAB), a pentacyclic triterpenoid from the lichen species Lobaria kurokawae, was evaluated alone and in combination with fluconazole, ketoconazole, and itraconazole against Candida albicans using checkerboard microdilution and time-killing tests. The MICs for RAB against 10 different C. albicans isolates ranged from 8 to 16 μg/ml. A synergistic action of RAB and azole was observed in azole-resistant strains, whereas synergistic or indifferent effects were observed in azole-sensitive strains when interpreted by a separate approach of the fractional inhibitory concentration index and ΔE model (the difference between the predicted and measured fungal growth percentages). In time-killing tests, we used both colony counts and a colorimetric assay to evaluate the combinational antifungal effects of RAB and azoles, which further confirmed their synergistic interactions. These findings suggest that the natural product RAB may play a certain role in increasing the susceptibilities of azole-resistant C. albicans strains.

scholarly journals In VitroActivities of Combinations of Rifampin with Other Antimicrobials against Multidrug-Resistant Acinetobacter baumannii

2014 ◽  
Vol 59 (3) ◽  
pp. 1466-1471 ◽  
Author(s):  
Yan Bai ◽  
Bin Liu ◽  
Tianlin Wang ◽  
Yun Cai ◽  
Beibei Liang ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Inhibitory Concentration ◽  
Multidrug Resistant ◽  
Antimicrobial Treatment ◽  
Clinical Isolates ◽  
Content Type ◽  
Synergistic Interactions ◽  
Therapeutic Alternatives ◽  
Concentration Indices

ABSTRACTThe antimicrobial treatment of multidrug-resistant (MDR)Acinetobacter baumanniiinfections has become a great challenge for medical staff all over the world. Increasing numbers of MDRA. baumanniiinfections have been identified and reported, but effective clinical treatments for them are decreasing. The objective of this study was to investigate thein vitroactivities of combinations of rifampin (an established antimicrobial) and other antimicrobials, including biapenem, colistin, and tigecycline, against 73 clinical isolates of MDRA. baumannii. In total, 73 clinical isolates of MDRA. baumanniiwere collected from two A-level general hospitals in Beijing, and the MICs of rifampin, biapenem, colistin, and tigecycline were determined. The checkerboard method was used to determine the fractional inhibitory concentration indices (FICIs), that is, whether the combinations acted synergistically against these isolates. The MIC50, MIC90, and MICrangeof rifampin combined with biapenem, colistin, and tigecycline against the isolates were clearly lower than those for four antimicrobials (rifampin, biapenem, colistin, and tigecycline) that were used alone. Combinations of rifampin with biapenem, colistin, and tigecycline individually demonstrated the following interactions: synergistic interactions (FICI ≤ 0.5) for 31.51%, 34.25%, and 31.51% of the isolates, partially synergistic interactions (0.5 < FICI < 1) for 49.31%, 43.83%, and 47.94% of the isolates, and additive interactions (FICI = 1) for 19.18%, 21.92%, and 20.55% of the isolates, respectively. There were no indifferent (1 < FICI < 4) or antagonistic (FICI ≥ 4) interactions. Therefore, combinations of rifampin with biapenem, colistin, or tigecycline may be future therapeutic alternatives for the treatment of MDRA. baumanniiinfections.

scholarly journals Synergistic interactions of quercetin with antibiotics against biofilm associated clinical isolates of Pseudomonas aeruginosa in vitro

2019 ◽  
Author(s):  
C. Vipin ◽  
M. Mujeeburahiman ◽  
K. Saptami ◽  
A.B. Arun ◽  
P.D. Rekha
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Synergistic Effect ◽  
Cell Viability ◽  
Inhibitory Concentration ◽  
Extreme Resistance ◽  
Antibiotic Overuse ◽  
Synergistic Interactions ◽  
Time Kill ◽  
Multiple Antibiotics

AbstractDevelopment of extreme resistance to multiple antibiotics is the major concern in infections due to biofilm forming Pseudomonas aeruginosa. The existing antibiotics have become ineffective against biofilm associated infections and hence, in this study, the combinatorial efficacy of antibiotics with a quorum sensing inhibitor (quercetin) was tested against biofilm forming P. aeruginosa isolates. The effect of drug combinations was studied by the checkerboard method. The fractional inhibitory concentration index (FICI) was calculated for determining the synergistic effect. Additionally, biofilm cell viability, time-kill and live-dead assays were performed to study the combinatorial effect. MIC of quercetin against all the P. aeruginosa strains was 500 μg/mL. However, quercetin at 125 μg/mL showed synergistic effect with ½ × MIC or ¼ × MIC of all the antibiotics against all the strains. Quercetin (125 μg/mL) with ½ MIC of levofloxacin and tobramycin combinations were highly effective with ≥80% killing of biofilm associated cells. Increasing the concentration to 250 μg/mL with ½ × MIC antibiotics could completely inhibit the biofilm cell viability in quercetin combination with amikacin and tobramycin. The findings show that quercetin combinations can enhance the treatment outcome against P. aeruginosa infection and this approach may reduce antibiotic overuse and selection pressure.Graphical abstract

scholarly journals Synergy of Nitric Oxide and Azoles againstCandida Species In Vitro

1998 ◽  
Vol 42 (9) ◽  
pp. 2342-2346 ◽  
Author(s):  
Gail E. McElhaney-Feser ◽  
Robert E. Raulli ◽  
Ronald L. Cihlar
Keyword(s):  
Nitric Oxide ◽  
Candida Albicans ◽  
Half Life ◽  
Inhibitory Concentration ◽  
Therapeutic Strategies ◽  
Fractional Inhibitory Concentration ◽  
Concentration Indices

ABSTRACT The candidacidal activity of nitric oxide (NO) as delivered by a class of compounds termed diazeniumdiolates has been investigated. Diazeniumdiolates are stable agents capable of releasing NO in a biologically usable form at a predicted rate, and three such compounds were examined for activity. One compound, (Z)-1-[N-(2-aminoethyl)-N-(2-ammonioethyl)amino]diazen-1-ium-1,2-diolate (DETA-NO), proved to be most suitable for examining NO activity due to its relatively long half-life (20 h) and because of limited candidacidal activity of the uncomplexed DETA nucleophile. DETA-NO was active against six species of Candida for which the MICs necessary to inhibit 50% growth (MIC50s) ranged from 0.25 to 1.0 mg/ml. C. parapsilosis and C. kruseiwere the most susceptible to the compound. In addition to a determination of NO effects alone, the complex was utilized to investigate the synergistic potential of released NO in combination with ketoconazole, fluconazole, and miconazole. Activity was investigated in vitro against representative strains of Candida albicans, C. krusei, C. parapsilosis,C. tropicalis, C. glabrata, and C. dubliniensis. Determination of MIC50, MIC80 and MICs indicated that DETA-NO inhibits all strains tested, with strains of C. parapsilosis and C. krusei being consistently the most sensitive. The combination of DETA-NO with each azole was synergistic against all strains tested as measured by fractional inhibitory concentration indices that ranged from 0.1222 to 0.4583. The data suggest that DETA-NO or compounds with similar properties may be useful in the development of new therapeutic strategies for treatment of Candida infections.

scholarly journals Semimechanistic Pharmacokinetic/Pharmacodynamic Modeling of Fosfomycin and Sulbactam Combination against Carbapenem-Resistant Acinetobacter baumannii

2021 ◽  
Vol 65 (5) ◽  
Author(s):  
Sazlyna Mohd Sazlly Lim ◽  
Aaron J. Heffernan ◽  
Jason A. Roberts ◽  
Fekade B. Sime
Keyword(s):  
Acinetobacter Baumannii ◽  
Treatment Options ◽  
Pharmacodynamic Modeling ◽  
Synergistic Activity ◽  
Bacterial Burden ◽  
Target Attainment ◽  
Content Type ◽  
Carbapenem Resistant ◽  
Time Kill

ABSTRACT Due to limited treatment options for carbapenem-resistant Acinetobacter baumannii (CR-AB) infections, antibiotic combinations are now considered potential treatments for CR-AB. This study aimed to explore the utility of fosfomycin-sulbactam combination (FOS/SUL) therapy against CR-AB isolates. Synergism of FOS/SUL against 50 clinical CR-AB isolates was screened using the checkerboard method. Thereafter, time-kill studies against two CR-AB isolates were performed. The time-kill data were described using a semimechanistic pharmacokinetic/pharmacodynamic (PK/PD) model. Monte Carlo simulations were then performed to estimate the probability of stasis, 1-log kill, and 2-log kill after 24 h of combination therapy. The FOS/SUL combination demonstrated a synergistic effect against 74% of isolates. No antagonism was observed. The MIC50 and MIC90 of FOS/SUL were decreased 4- to 8-fold, compared to the monotherapy MIC50 and MIC90. In the time-kill studies, the combination displayed bactericidal activity against both isolates and synergistic activity against one isolate at the highest clinically achievable concentrations. Our PK/PD model was able to describe the interaction between fosfomycin and sulbactam in vitro. Bacterial kill was mainly driven by sulbactam, with fosfomycin augmentation. FOS/SUL regimens that included sulbactam at 4 g every 8 h demonstrated a probability of target attainment of 1-log10 kill at 24 h of ∼69 to 76%, compared to ∼15 to 30% with monotherapy regimens at the highest doses. The reduction in the MIC values and the achievement of a moderate PTA of a 2-log10 reduction in bacterial burden demonstrated that FOS/SUL may potentially be effective against some CR-AB infections.

scholarly journals In vitro activities of Traganum nudatum and Mentha pulegium extracts combined with amphotericin B against Candida albicans in production of hydrolytic enzymes

2020 ◽  
Author(s):  
Ikram Tefiani ◽  
Sidi Mohammed Lahbib Seddiki ◽  
Moustafa Yassine Mahdad
Keyword(s):  
Candida Albicans ◽  
Minimum Inhibitory Concentration ◽  
Amphotericin B ◽  
Inhibitory Concentration ◽  
Culture Media ◽  
Hydrolytic Enzymes ◽  
Normal Flora ◽  
Mentha Pulegium ◽  
Hydrolytic Activities

Background and Purpose: Candida albicans is an important microorganism in the normal flora of a healthy subject; however, it has an expedient pathogenic character that induces hydrolytic virulence. Regarding this, the present study aimed to find an in vitro alternative that could reduce the virulence of this yeast. Materials and Methods: For the purpose of the study, the effect of amphotericin B (AmB) combined with the extract of Traganum nudatum (E1) or Mentha pulegium (E2) was evaluated against the hydrolytic activities of esterase, protease, and phospholipase. This effect was determined by calculating the minimum inhibitory concentration (MIC), used to adjust the extract/AmB mixtures in culture media. Results: The evaluated Pz values, which corresponded to the different enzymatic activities, showed a decrease in the hydrolytic activities of C. albicans strains after the addition of E1/AmB and E2/AmB combinations at descending concentrations (lower than the obtained MICs). Conclusion: Based on the findings, it would be possible to reduce the pathogenesis of this species without destabilizing the balance of the flora.

scholarly journals Activities of Three Quinolones, Alone and in Combination with Extended-Spectrum Cephalosporins or Gentamicin, against Stenotrophomonas maltophilia

1998 ◽  
Vol 42 (8) ◽  
pp. 2002-2005 ◽  
Author(s):  
Melissa A. Visalli ◽  
Michael R. Jacobs ◽  
Peter C. Appelbaum
Keyword(s):  
Active Compound ◽  
Stenotrophomonas Maltophilia ◽  
Inhibitory Concentration ◽  
Fractional Inhibitory Concentration ◽  
Determination Method ◽  
Extended Spectrum ◽  
Time Kill ◽  
Synergy Testing ◽  
Checkerboard Titration ◽  
Concentration Indices

The present study examined the activities of trovafloxacin, levofloxacin, and ciprofloxacin, alone and in combination with cefoperazone, ceftazidime, cefpirome, and gentamicin, against 100 strains of Stenotrophomonas maltophilia by the MIC determination method and by synergy testing of the combinations by the time-kill and checkerboard titration methods for 20 strains. The respective MICs at which 50% and 90% of isolates were inhibited for the drugs used alone were as follows: trovafloxacin, 0.5 and 2.0 μg/ml; levofloxacin, 2.0 and 4.0 μg/ml; ciprofloxacin, 4.0 and 16.0 μg/ml; cefoperazone, >128.0 and >128.0 μg/ml; ceftazidime, 32.0 and >128.0 μg/ml; cefpirome, >128.0 and >128.0 μg/ml; and gentamicin, 128.0 and >128.0 μg/ml. Synergistic fractional inhibitory concentration indices (≤0.5) were found for ≥50% of strains for trovafloxacin-cefoperazone, trovafloxacin-ceftazidime, levofloxacin-cefoperazone, levofloxacin-ceftazidime, ciprofloxacin-cefoperazone, and ciprofloxacin-ceftazidime, with other combinations affecting fewer strains. For 20 strains tested by the checkerboard titration and time-kill methods, synergy (≥100-fold drop in count compared to the count achieved with the more active compound) was more pronounced after 12 h due to regrowth after 24 h. At 12 h, trovafloxacin at 0.004 to 0.5 μg/ml showed synergy with cefoperazone for 90% of strains, with ceftazidime for 95% of strains with cefpirome for 95% of strains, and with gentamicin for 65% of strains. Levofloxacin at 0.03 to 0.5 μg/ml and ciprofloxacin at 0.5 to 2.0 μg/ml showed synergy with cefoperazone for 80% of strains, with ceftazidime for 90 and 85% of strains, respectively, with cefpirome for 85 and 75% of strains, respectively, and with gentamicin for 65 and 75% of strains, respectively. Time-kill assays were more discriminatory than checkerboard titration assays in demonstrating synergy for all combinations.

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