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 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 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 1597. Ceftolozane-Tazobactam and Meropenem Synergy Testing Against Multi-Drug and Extensively-Drug Resistant Pseudomonas aeruginosa

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S794-S795
Author(s):  
Mary Francine P Chua ◽  
Syeda Sara Nida ◽  
Jerry Lawhorn ◽  
Janak Koirala
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Synergistic Effect ◽  
Inhibitory Concentration ◽  
Multidrug Resistant ◽  
Additive Effect ◽  
Teaching Hospitals ◽  
Drug Resistant ◽  
Extensively Drug Resistant ◽  
Synergy Testing ◽  
Concentration Indices

Abstract Background Multidrug-resistant (MDR) and extensively drug-resistant (XDR) Pseudomonas aeruginosa (PA) have limited therapeutic options for treatment. Ceftolozane/tazobactam is a newer anti-pseudomonal drug effective against resistant PA infections, however resistance against this drug has now also developed and is increasing. In this study, we explored the combination of ceftolozane/tazobactam (CT) and meropenem (MP) as a possible effective regimen against MDR and XDR PA. Methods We obtained 33 non-duplicate isolates of MDR and XDR PA grown from blood, urine and respiratory samples collected from patients admitted between 2015 and 2019 at our two affiliate teaching hospitals. MDR PA was defined as resistance to 3 or more classes of anti-pseudomonal antibiotics, and XDR PA as resistance to all but two or less classes of anti-pseudomonal antibiotics. Antimicrobial preparations of both MP and CT were made according to manufacturer instructions. Susceptibility testing was performed using the checkerboard method in accordance to CLSI guidelines (CLSI M100, 2017). The ATCC 27853 strain of PA used as control. Synergy, additive effect, indifference and antagonism were defined as FIC (fractional inhibitory concentration) indices of ≤0.5, &gt;0.5 to &lt;1, &gt;1 to &lt;4, and &gt;4, respectively. Results Thirteen (39%) of 33 PA isolates were classified as XDR, while 20 (61%) PA isolates were MDR. All isolates were resistant to MP (MIC50 &gt;32 ug/mL), while only 2 (6%) isolates were susceptible to CT (MIC50 64 ug/mL). A synergistic effect was seen in 9 (27.3%) of PA isolates (FIC index range 0.28 to 0.5)— 2 of which were XDR PA, and 7 were MDR PA. An additive effect was seen in 12 (36.4%), with indifference seen in 12 (36.4%) of isolates. In this study, no antagonism was seen when CT and MP were combined. Conclusion When used in combination, CT and MP can exert a synergistic effect against MDR and XDR PA. Additive effect and indifference can also be seen when both antibiotics were used. Moreover, there was no antagonism seen when both antibiotics were combined. This study shows that the use of CT and MP in combination may be an option against XDR and MDR PA infections. Disclosures All Authors: No reported disclosures

Comparative activity of trovafloxacin, alone and in combination with other agents, against gram-negative nonfermentative rods.

1997 ◽  
Vol 41 (7) ◽  
pp. 1475-1481 ◽  
Author(s):  
M A Visalli ◽  
S Bajaksouzian ◽  
M R Jacobs ◽  
P C Appelbaum
Keyword(s):  
Burkholderia Cepacia ◽  
Inhibitory Concentration ◽  
Pseudomonas Stutzeri ◽  
Alcaligenes Faecalis ◽  
Gram Negative ◽  
Agar Dilution ◽  
Flavobacterium Odoratum ◽  
Time Kill ◽  
Synergy Testing ◽  
Comparative Activity

In the first part of this study, agar dilution MICs were used to test the activities of trovafloxacin, ciprofloxacin, ofloxacin, levofloxacin, sparfloxacin, clinafloxacin, ceftazidime, and imipenem against 458 gram-negative nonfermenters. The overall respective MICs at which 50% of isolates are inhibited (MIC50s) and MIC90s were as follows: trovafloxacin, 1.0 and 16.0 microg/ml; ciprofloxacin, 2.0 and 16.0 microg/ml; ofloxacin, 2.0 and 32.0 microg/ml; levofloxacin, 1.0 and 16.0 microg/ml; sparfloxacin, 1.0 and 16.0 microg/ml; clinafloxacin, 0.5 and 4.0 microg/ml; ceftazidime, 8.0 and 128.0 microg/ml; imipenem, 2.0 and 256.0 microg/ml. Clinafloxacin was the most active of all the quinolones tested. The MIC90s of trovafloxacin were < or = 4.0 microg/ml for Pseudomonas aeruginosa, Stenotrophomonas maltophilia, Flavobacterium odoratum, and Chryseobacterium meningosepticum; trovafloxacin MIC90s were < or = 2.0 microg/ml for Moraxella spp., Pseudomonas stutzeri, and Chryseobacterium indologenes-C. gleum. Of the other quinolones tested, the MICs of sparfloxacin and levofloxacin were lower than those of ciprofloxacin and ofloxacin. High ceftazidime MICs (> or = 32.0 microg/ml) were observed for all nonfermentative species tested. Although for the majority of strains tested imipenem MICs were < or = 8.0 microg/ml, high imipenem MICs were observed for many species, especially S. maltophilia, Burkholderia cepacia, F. odoratum, and Chryseobacterium meningosepticum. For Alcaligenes xylosoxidans strains, the MICs of all compounds were generally a few dilutions lower than those for Alcaligenes faecalis-A. odorans. Time-kill studies with five strains revealed that trovafloxacin and all quinolones yielded more rapid time-kill kinetics than ceftazidime and imipenem. Synergy testing by checkerboard titrations of 286 strains with trovafloxacin combined with ceftazidime, amikacin, and imipenem revealed fractional inhibitory concentration (FIC) indices in the range indicating synergism (< or = 0.5) for 81, 41, and 40 strains, respectively, and FIC indices indicating additivity or indifference (> 0.5 to 4.0) for 205, 245, and 246 strains, respectively. No FIC indices indicating antagonism (> 4.0) were observed. Synergy between trovafloxacin and ceftazidime was found for 32 of 36 S. maltophilia strains. Time-kill studies with 20 strains showed that for most strains for which FIC indices were in the range indicating additivity or indifference, FIC indices indicated synergy by the time-kill method. Synergy was particularly noticeable for S. maltophilia strains with combinations of ceftazidime and trovafloxacin.

scholarly journals Combinations of Lysostaphin with β-Lactams Are Synergistic against Oxacillin-Resistant Staphylococcus epidermidis

2002 ◽  
Vol 46 (6) ◽  
pp. 2017-2020 ◽  
Author(s):  
Nandini Kiri ◽  
Gordon Archer ◽  
Michael W. Climo
Keyword(s):  
Staphylococcus Aureus ◽  
Aortic Valve ◽  
Staphylococcus Epidermidis ◽  
Concentration Index ◽  
Inhibitory Concentration ◽  
Rabbit Model ◽  
Fractional Inhibitory Concentration ◽  
Fractional Inhibitory Concentration Index ◽  
Synergy Testing ◽  
Better Than

ABSTRACT Oxacillin-resistant Staphylococcus aureus is rapidly killed by the endopeptidase lysostaphin, and the addition of β-lactam antibiotics provides synergistic killing. We investigated the possibility that β-lactams given in combination with lysostaphin would improve the activity of lysostaphin against oxacillin-resistant Staphylococcus epidermidis (ORSE), which is normally less susceptible to lysostaphin. Checkerboard synergy testing was performed for lysostaphin given in combination with oxacillin against 10 ORSE isolates for which the lysostaphin MICs were ≥ 8 μg/ml. The fractional inhibitory concentration index ranged from 0.0234 to 0.2656, indicating synergy, which was confirmed in growth curve experiments. In the rabbit model of experimental aortic valve endocarditis using an ORSE strain, the combination of lysostaphin and nafcillin was as effective as vancomycin alone and significantly better than lysostaphin or nafcillin alone. We conclude that β-lactam antibiotics given in combination with lysostaphin are synergistic against many strains of ORSE.

scholarly journals Multilaboratory Testing of Antifungal Drug Combinations against Candida Species and Aspergillus fumigatus: Utility of 100 Percent Inhibition as the Endpoint

2014 ◽  
Vol 59 (3) ◽  
pp. 1759-1766 ◽  
Author(s):  
Ping Ren ◽  
Ming Luo ◽  
Shao Lin ◽  
Mahmoud A. Ghannoum ◽  
Nancy Isham ◽  
...  
Keyword(s):  
Confidence Interval ◽  
Drug Interactions ◽  
Aspergillus Fumigatus ◽  
Amphotericin B ◽  
Candida Species ◽  
Inhibitory Concentration ◽  
Fractional Inhibitory Concentration ◽  
Content Type ◽  
Drug Antagonism ◽  
Concentration Indices

ABSTRACTFour laboratories tested three isolates ofCandidaspecies and two isolates ofAspergillus fumigatususing 96-well plates containing combinations of amphotericin B, anidulafungin, caspofungin, micafungin, fluconazole, itraconazole, posaconazole, and voriconazole. The majority of summation fractional inhibitory concentration indices (ΣFICI) based on the Lowe additivity formula suggested indifferent drug interactions (ΣFICI > 0.5 and ≤4.0) and no instance of drug antagonism (ΣFICI > 4.0). The intra- and interlaboratory agreement rates were superior when MIC100readings were used as endpoints (at a 99% confidence interval [CI]).

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 Evaluation of Combination Effects of Ethanolic Extract ofZiziphus mucronataWilld. subsp.mucronataWilld. and Antibiotics against Clinically Important Bacteria

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Olufunmiso Olusola Olajuyigbe ◽  
Anthony Jide Afolayan
Keyword(s):  
Nalidixic Acid ◽  
Antimicrobial Agents ◽  
Inhibitory Concentration ◽  
Synergistic Effects ◽  
Ethanolic Extract ◽  
Herbal Remedies ◽  
Bark Extract ◽  
Resistant Bacteria ◽  
Fractional Inhibitory Concentration ◽  
Concentration Indices

A pragmatic approach to the treatment of infectious diseases with multicausal agents and prevention of the development of resistant isolates is the combination of herbal remedies with the first-line antimicrobial agents to which most of them have become resistant. This study evaluated the interactions between the ethanolic bark extract ofZiziphus mucronatawith known antimicrobial agentsin vitro. In this study, the results showed that varied zones of inhibitions (ZME—chloramphenicol (17–42 mm), ZME—amoxicillin (17–35 mm), ZME—tetracycline (17–36 mm), ZME—ciprofloxacin (20–41 mm), ZME—nalidixic acid (17–34 mm), and ZME—kanamycin (17–38 mm)) were produced by the antibacterial combinations. At the highest combined concentrations, 12 isolates (ZME—ciprofloxacin) > 10 isolates (ZME—chloramphenicol) = (ZME—kanamycin) > 6 isolates (ZME—amoxicillin) = (ZME—nalidixic acid) and 5 isolates (ZME—tetracycline) were inhibited with zones of inhibition greater than20±1.0 mm. Although the agar diffusion assay suggested that the interactions between the ethanolic extract ofZ. mucronataand the antibiotics were both synergistic and additive in nature, the fractional inhibitory concentration indices (FICI) showed that the interactions were synergistic (54.17%), additive (27.78%), indifferent (16.67%), and antagonistic (1.39%). While the fractional inhibitory concentration indices (FICIs) for synergism ranged between 0.00391 and 0.5, that of additivity ranged between 0.516 and 1.0, indifferences ranged between 1.062 and 3.0 and antagonistic interaction was 5.0. The synergistic effects implied that the antibacterial combinations would be more effective and useful in the treatment of multicausal and multidrug-resistant bacteria than a single monotherapy of either antibacterial agent.

scholarly journals Functional Synergy between Antimicrobial Peptoids and Peptides against Gram-Negative Bacteria

2011 ◽  
Vol 55 (11) ◽  
pp. 5399-5402 ◽  
Author(s):  
Nathaniel P. Chongsiriwatana ◽  
Modi Wetzler ◽  
Annelise E. Barron
Keyword(s):  
Antimicrobial Activity ◽  
Innate Immunity ◽  
Antimicrobial Peptides ◽  
Inhibitory Concentration ◽  
Gram Negative Bacteria ◽  
Fractional Inhibitory Concentration ◽  
Gram Negative ◽  
Peptoid Mimics ◽  
Selective Antimicrobial Activity ◽  
Concentration Indices

ABSTRACTAntimicrobial peptides (AMPs) are integral components of innate immunity and are typically found in combinations in which they can synergize for broader-spectrum or more potent activity. Previously, we reported peptoid mimics of AMPs with potent and selective antimicrobial activity. Using checkerboard assays, we demonstrate that peptoids and AMPs can interact synergistically, with fractional inhibitory concentration indices as low as 0.16. These results strongly suggest that antimicrobial peptoids and peptides are functionally and mechanistically analogous.

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