Determination of Activities of Levofloxacin, Alone and Combined with Gentamicin, Ceftazidime, Cefpirome, and Meropenem, against 124 Strains of Pseudomonas aeruginosa by Checkerboard and Time-Kill Methodology

1998 ◽  
Vol 42 (4) ◽  
pp. 953-955 ◽  
Author(s):  
Melissa A. Visalli ◽  
Michael R. Jacobs ◽  
Peter C. Appelbaum
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Inhibitory Concentration ◽  
Fractional Inhibitory Concentration ◽  
Time Kill

ABSTRACT A total of 124 Pseudomonas aeruginosa strains were tested for synergy between levofloxacin and cefpirome, ceftazidime, gentamicin, and meropenem. Checkerboards yielded synergistic fractional inhibitory concentration (FIC) indices (≤0.5) with 25 of 496 possible combinations. All other FIC indices were >0.5 to 2 (additive or indifferent), with no antagonism. Time-kill studies with 12 strains showed that levofloxacin (0.06 to 0.5 μg/ml) was synergistic with cefpirome, ceftazidime, gentamicin, and meropenem in 10, 9, 4, and 11 strains, respectively.

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.

scholarly journals Antipneumococcal activities of cefpirome and cefotaxime, alone and in combination with vancomycin and teicoplanin, determined by checkerboard and time-kill methods.

1996 ◽  
Vol 40 (9) ◽  
pp. 1973-1976 ◽  
Author(s):  
S Bajaksouzian ◽  
M A Visalli ◽  
M R Jacobs ◽  
P C Appelbaum
Keyword(s):  
Inhibitory Concentration ◽  
Fractional Inhibitory Concentration ◽  
Beta Lactams ◽  
Pneumococcal Infections ◽  
Titration Method ◽  
Resistant Strains ◽  
Time Kill ◽  
Checkerboard Titration

The checkerboard titration method was used to test the synergy of cefpirome and cefotaxime with teicoplanin or vancomycin against 35 penicillin-susceptible, 34 penicillin-intermediate, and 31 penicillin-resistant pneumococci. The MICs at which 50 and 90% of isolates are inhibited (MIC50s and MIC90s, respectively) of both cefpirome and cefotaxime were 0.016 and 0.06 microgram/ml, respectively, for penicillin-susceptible strains and 0.125 and 0.5 microgram/ml, respectively, for penicillin-intermediate strains. The MIC50s and MIC90s of cefotaxime for penicillin-resistant strains were 1.0 and 2.0 micrograms/ml, respectively, and those of cefpirome were 0.5 and 1.0 microgram/ml, respectively. All pneumococci were inhibited by cefpirome at MICs of < or = 1.0 microgram/ml. The MIC50s and MIC90s of vancomycin and teicoplanin (0.25 and 0.25 microgram/ml and 0.03 and 0.03 microgram/ml, respectively) did not differ for the three groups. Checkerboard synergy studies showed that cefpirome and vancomycin showed synergy for 31 strains (fractional inhibitory concentration [FIC] indices, < or = 0.5) cefpirome and teicoplanin showed synergy for 18 strains, cefotaxime and vancomycin showed synergy for 51 strains, and cefotaxime and teicoplanin showed synergy for 27 strains. Cefpirome and vancomycin had FIC indices indicating indifference (2.0) for two strains, and cefotaxime and vancomycin had FIC indices indicating indifference for one strain. All other FIC indices indicating indifference or additivity were > 0.5 to 1.0. No FIC indices indicating antagonism (> 4.0) were found. Synergy between beta-lactams and glycopeptides for three susceptible, three intermediate, and three resistant strains were tested by the time-kill assay, and all combinations were synergistic by this method. Synergy between cephalosporins and glycopeptides can be demonstrated and may be useful for the treatment of pneumococcal infections, especially meningitis.

scholarly journals Evaluation of Antimicrobial Activity and Synergistic Effect of Spices against Few Selected Pathogens

2019 ◽  
Vol 6 ◽  
pp. 10-18
Author(s):  
Renuka Maharjan ◽  
Saru Thapa ◽  
Amrit Acharya
Keyword(s):  
Antimicrobial Activity ◽  
Synergistic Effect ◽  
Inhibitory Concentration ◽  
Agar Plate ◽  
Ethanolic Extract ◽  
Fractional Inhibitory Concentration ◽  
Zone Of Inhibition ◽  
Soxhlet Apparatus ◽  
Mic Value

Objectives: The main objective of this study was to evaluate antimicrobial activity of ethanolic extract of spices along with determination of its synergistic effect against few selected pathogens. Methods: In this study, ethanolic extract of 5 different spices; Zingiber officinale (Ginger), Allium sativum (Garlic), Curcuma longa (Turmeric), Capsicum annum (Chili) and Allium cepa (Onion) were obtained by using Soxhlet apparatus. The ethanolic extract was concentrated by evaporation and different concentrations of extract were prepared in Dimethy Sulphoxide (DMSO) solvent. Test organisms included mainly pathogens i.e. Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumoniae. The antimicrobial activities of the extracts were determined by well diffusion technique both individually and in combination. On the other hand, Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) was determined by serial dilution technique. The result were interpreted on the basis of the fact that the growth occurs in positive control and other tubes with inadequate amount of extract whereas the lowest concentration of agent that inhibits growth of organism, detected by lack of visible turbidity by inhibition of 99% is designed as the MIC. The MBC is identified by determining the lowest concentration of extract solution that reduces the viability of the initial bacterial inoculum by a predetermined reduction such as ≥99.9%. Likewise, for determination of Fractional Inhibitory Concentration Index (FICI), two extracts were combined along with standardized inoculum of bacterial strain. Tubes without visible turbidity were streaked on agar plate and observed for 99.9% killing.   Results: All the tested extract of spices were found effective against S. aureus and K. pneumoniae only. The highest zone of inhibition (ZOI) was found in chili extract (ZOI=26 mm) against S. aureus whereas lowest zone of inhibition was found in garlic extract against K. pneumoniae (ZOI=12mm). Similarly, highest ZOI was produced by combined extract of both Turmeric and Ginger (ZOI= 26 mm). Turmeric extract was found to be effective against S. aureus (MIC value = 62.5 mg /ml and MBC value = 31.25 mg/ml) and K. pneumoniae (MIC value 125 mg/ml and MBC value = 62.5 mg/ml). The Fractional Inhibitory Concentration (FIC) values of combined extract suggested synergistic and additive effect (0.5<FIC<1). Chili and ginger were effective with FIC value of 0.25. Conclusion: To recapitulate, the extract of spices can be used to prevent the pathogenic organism.

Evaluation of the in vitro interaction of fosfomycin and meropenem against metallo-β-lactamase–producing Pseudomonas aeruginosa using Etest and time-kill assay

2020 ◽  
pp. jim-2020-001573
Author(s):  
Sanjida Jahan ◽  
Heather Davis ◽  
Deborah S Ashcraft ◽  
George A Pankey
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Inhibitory Concentration ◽  
Multidrug Resistant ◽  
Resistance Mechanisms ◽  
Microdilution Method ◽  
Broth Microdilution Method ◽  
Time Kill ◽  
In Vitro Interaction ◽  
Antimicrobial Combinations

Pseudomonas aeruginosa is a nosocomial pathogen containing various resistance mechanisms. Among them, metallo-β-lactamase (MBL)–producing Pseudomonas are difficult to treat. Fosfomycin is an older antibiotic that has recently seen increased usage due to its activity against a broad spectrum of multidrug-resistant organisms. Our aim was to evaluate the combination of fosfomycin and meropenem against 20 MBL-producing P. aeruginosa (100% meropenem-resistant and 20% fosfomycin-resistant) using both an Etest minimal inhibitory concentration (MIC): MIC method and time-kill assay. MICs for fosfomycin and meropenem were determined by Etest and by broth microdilution method for the latter. The combination demonstrated synergy by Etest in 3/20 (15%) isolates and 5/20 (25%) isolates by time-kill assay. Results from the Etest method and time-kill assay were in agreement for 14/20 (70%) of isolates. No antagonism was found. Comparing both methods, Etest MIC: MIC method may be useful to rapidly evaluate other antimicrobial combinations.

scholarly journals Activities of levofloxacin, ofloxacin, and ciprofloxacin, alone and in combination with amikacin, against acinetobacters as determined by checkerboard and time-kill studies.

1997 ◽  
Vol 41 (5) ◽  
pp. 1073-1076 ◽  
Author(s):  
S Bajaksouzian ◽  
M A Visalli ◽  
M R Jacobs ◽  
P C Appelbaum
Keyword(s):  
Acinetobacter Baumannii ◽  
Active Compound ◽  
Inhibitory Concentration ◽  
Clinical Use ◽  
Fractional Inhibitory Concentration ◽  
Time Kill ◽  
Checkerboard Titration

A total of 101 Acinetobacter genospecies (77 Acinetobacter baumannii strains and 24 non-A. baumannii strains) were tested for their susceptibilities to levofloxacin, ofloxacin, and ciprofloxacin and for synergy between the quinolones and amikacin by checkerboard titration and time-kill analyses. The MICs at which 50% of the isolates are inhibited (MIC50)/MIC90s for the 101 strains were as follows (in micrograms per milliliter): levofloxacin, 0.25/16.0; ofloxacin, 0.5/32.0; ciprofloxacin, 0.25/> 64.0; and amikacin, 1.0/> 32.0. At empiric breakpoints of < or = 2.0 microg/ml, 61% of the strains were susceptible to all three quinolones. At a breakpoint of < or = 16.0 microg/ml, 84% of the strains were susceptible to amikacin. Checkerboard titrations yielded synergistic fractional inhibitory concentration (FIC) indices (< or = 0.5) for one strain with levofloxacin and amikacin and for two strains with ofloxacin and amikacin. Indices of > 0.5 to 1.0 were seen for 57, 54, and 55 strains with levofloxacin plus amikacin, ofloxacin plus amikacin, and ciprofloxacin plus amikacin, respectively, and indices of > 1.0 in 43, 45, and 46 strains, respectively, were found with the above three combinations. No strains yielded antagonistic FIC indices (> 4.0). Most FIC results of > 1.0 occurred in strains for which the quinolone MICs were > 2.0 microg/ml and for which the amikacin MICs were > or = 32.0 microg/ml. By contrast, synergy (defined as > or = 2 log10 decrease compared to the more active compound alone by time-kill analysis) was found in all seven strains tested for which the quinolone MICs were < or = 2.0 microg/ml. For eight other strains for which the quinolone MICs were > 2.0 microg/ml as determined by time-kill analysis, quinolone and amikacin concentrations in combination were usually too high to permit clinical use. Time-kill analysis was found to be more sensitive in detecting synergy than was the checkerboard method.

scholarly journals FICI Value Determination of Combination of Aquilaria microcarpa Baill. Ethanolic Extract with Amoxicillin against Salmonella typhi

2021 ◽  
Vol 8 (1) ◽  
pp. 9
Author(s):  
Pratiwi - Apridamayanti ◽  
Robiyanto Robiyanto ◽  
Trie - Farica
Keyword(s):  
Concentration Index ◽  
Inhibitory Concentration ◽  
Ethanolic Extract ◽  
Salmonella Typhi ◽  
Fractional Inhibitory Concentration ◽  
Fractional Inhibitory Concentration Index ◽  
Value Determination

<p>Karas (<em>Aquilaria microcarpa</em> Baill.) adalah tanaman yang memiliki aktivitas antibakteri terhadap beberapa bakteri patogen. Tujuan dari penelitian ini untuk mengetahui nilai FICI dari kombinasi ekstrak etanol daun karas (<em>Aquilaria microcarpa</em> Baill.) dengan amoksisilin terhadap bakteri <em>Salmonella typhi</em>. Metode yang digunakan adalah metode difusi cakram Kirby-Bauer. Analisis data dilakukan secara deskriptif untuk mengetahui karakteristik kombinasi. Hasil penelitian menunjukkan bahwa nilai FICI kombinasi ekstrak etanol daun karas (<em>Aquilaria microcarpa</em> Baill.) dengan amoksisilin terhadap <em>Salmonella typhi</em> adalah 4. Sehingga dapat disimpulkan bahwa karakteristik kombinasi terhadap bakteri <em>Salmonella typhi</em> bersifat <em>indifferent</em> atau tak berbeda.</p><p><strong>Kata kunci :</strong> <em>Aquilaria microcarpa </em>Baill.<em>, </em>ekstrak etanol, amoksisilin, <em>Salmonella typhi</em> , <em>Fractional Inhibitory Concentration Index</em> (FICI)</p>

scholarly journals Synergistic Antibacterial and Antibiofilm Activity of the MreB Inhibitor A22 Hydrochloride in Combination with Conventional Antibiotics against Pseudomonas aeruginosa and Escherichia coli Clinical Isolates

2021 ◽  
Vol 2021 ◽  
pp. 1-17
Author(s):  
Anastasia Kotzialampou ◽  
Efthymia Protonotariou ◽  
Lemonia Skoura ◽  
Afroditi Sivropoulou
Keyword(s):  
Escherichia Coli ◽  
Pseudomonas Aeruginosa ◽  
Inhibitory Concentration ◽  
Human Cells ◽  
Laser Scanning Microscopy ◽  
Clinical Isolates ◽  
Antibiofilm Activity ◽  
Conventional Antibiotics ◽  
Time Kill ◽  
Synergistic Combinations

In the era of antibiotic resistance, the bacterial cytoskeletal protein MreB is presented as a potential target for the development of novel antimicrobials. Combined treatments of clinical antibiotics with anti-MreB compounds may be promising candidates in combating the resistance crisis, but also in preserving the potency of many conventional drugs. This study aimed to evaluate the synergistic antibacterial and antibiofilm activities of the MreB inhibitor A22 hydrochloride in combination with various antibiotics. The minimum inhibitory concentration (MIC) values of the individual compounds were determined by the broth microdilution method against 66 clinical isolates of Gram-negative bacteria. Synergy was assessed by the checkerboard assay. The fractional inhibitory concentration index was calculated for each of the A22-antibiotic combination. Bactericidal activity of the combinations was evaluated by time-kill curve assays. The antibiofilm activity of the most synergistic combinations was determined by crystal violet stain, methyl thiazol tetrazolium assay, and confocal laser scanning microscopy analysis. The combined cytotoxic and hemolytic activity was also evaluated toward human cells. According to our results, Pseudomonas aeruginosa and Escherichia coli isolates were resistant to conventional antibiotics to varying degrees. A22 inhibited the bacterial growth in a dose-dependent manner with MIC values ranging between 2 and 64 μg/mL. In combination studies, synergism occurred most frequently with A22-ceftazidime and A22-meropemen against Pseudomonas aeruginosa and A22-cefoxitin and A22-azithromycin against Escherichia coli. No antagonism was observed. In time-kill studies, synergism was observed with all expected combinations. Synergistic combinations even at the lowest tested concentrations were able to inhibit biofilm formation and eradicate mature biofilms in both strains. Cytotoxic and hemolytic effects of the same combinations toward human cells were not observed. The findings of the present study support previous research regarding the use of MreB as a novel antibiotic target. The obtained data expand the existing knowledge about the antimicrobial and antibiofilm activity of the A22 inhibitor, and they indicate that A22 can serve as a leading compound for studying potential synergism between MreB inhibitors and antibiotics in the future.

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

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