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 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 A Pilot Study of the Synergy between Two Antimicrobial Peptides and Two Common Antibiotics

Antibiotics ◽  
2019 ◽  
Vol 8 (2) ◽  
pp. 60 ◽  
Author(s):  
Franziska Kampshoff ◽  
Mark D. P. Willcox ◽  
Debarun Dutta
Keyword(s):  
Staphylococcus Aureus ◽  
Antibacterial Agents ◽  
Inhibitory Concentration ◽  
Synergistic Activity ◽  
Fractional Inhibitory Concentration ◽  
First Line ◽  
Checkerboard Assay ◽  
Resistant Strains ◽  
And Staphylococcus Aureus ◽  
Broth Dilution

Background: Frequent and unrestricted use of antibiotics has been associated with the development of antibiotic resistance by microorganisms. Thus, there is a need to find novel antibacterial agents or a combination of agents as the first line of treatment for various infections. This study aimed to investigate the synergy between antimicrobial peptide (AMP) combinations or between AMP-antibiotics combinations using two common pathogens, Pseudomonas aeruginosa and Staphylococcus aureus. Methods: The AMPs melimine, Mel4 and protamine, and antibiotics cefepime and ciprofloxacin were used in this study. The minimum inhibitory concentration (MIC) of each were evaluated against P. aeruginosa and S. aureus strains by a microtiter broth dilution. Based on the MIC of each antimicrobial agent, a checkerboard assay was performed to investigate the synergy between them, which was expressed as the fractional inhibitory concentration (FIC). Results: The combination of melimine and ciprofloxacin showed synergistic activity against antibiotic sensitive or resistant strains of P. aeruginosa and with FIC values ≤0.5. Conclusion: Combinations of AMPs and the fluoroquinolone ciprofloxacin is a promising method for reducing resistance to the fluoroquinolone of P. aeruginosa.

scholarly journals MIC and time-kill studies of antipneumococcal activity of GV 118819X (sanfetrinem) compared with those of other agents.

1997 ◽  
Vol 41 (1) ◽  
pp. 148-155 ◽  
Author(s):  
S K Spangler ◽  
M R Jacobs ◽  
P C Appelbaum
Keyword(s):  
United States ◽  
The United States ◽  
Broth Microdilution ◽  
Beta Lactam ◽  
Beta Lactams ◽  
Amoxicillin Clavulanate ◽  
Agar Dilution ◽  
Resistant Strains ◽  
Time Kill

Agar dilution MIC methodology was used to test the activities of GV 118819X (sanfetrinem), ampicillin, amoxicillin, amoxicillin-clavulanate, cefpodoxime, loracarbef, levofloxacin, clarithromycin, ceftriaxone, imipenem, and vancomycin against 53 penicillin-susceptible, 84 penicillin-intermediate and 74 penicillin-resistant pneumococci isolated in the United States. GV 118819X was the most active oral beta-lactam, with MIC at which 50% of the isolates were inhibited (MIC50)/MIC90 values of 0.008/0.03, 0.06/0.5, and 0.5/1.0 micrograms/ml against penicillin-susceptible, -intermediate, and -resistant stains, respectively. Amoxicillin and amoxicillin in the presence of clavulanate (2:1) were the second most-active oral beta-lactams, followed by ampicillin and cefpodoxime; loracarbef was not active against penicillin-intermediate and -resistant strains. Clarithromycin was most active against penicillin-susceptible strains but was less active against intermediate and resistant stains. All pneumococcal stains were inhibited by ceftriaxone and imipenem at MICs of < or = 4.0 and < or = 1.0 micrograms/ml, respectively. The activities of levofloxacin and vancomycin were unaffected by penicillin susceptibility. Time-kill studies of three penicillin-susceptible, three penicillin-intermediate, and three penicillin-resistant pneumococci showed that all compounds, at the broth microdilution MIC, yielded 99.9% killing of all strains after 24 h. Kinetic patterns of all oral beta-lactams, ceftriaxone, and vancomycin were similar relative to the MIC, with 90% killing of all strains first observed after 12 h. However, killing by amoxicillin-clavulanate, imipenem, and levofloxacin was slightly faster and that by clarithromycin was slower than that by the above-described drugs. At 2 x the MIC, more strains were killed earlier than was the case at the MIC, but the pattern seen at the MIC prevailed. When MICs and kill kinetics were combined, sanfetrinem was the most active oral antipneumococcal agent in this study.

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 Comparative Activities of Telavancin Combined with Nafcillin, Imipenem, and Gentamicin against Staphylococcus aureus

2013 ◽  
Vol 57 (6) ◽  
pp. 2678-2683 ◽  
Author(s):  
Steven N. Leonard ◽  
Megan E. Supple ◽  
Ronak G. Gandhi ◽  
Meghna D. Patel
Keyword(s):  
Staphylococcus Aureus ◽  
Clinical Utility ◽  
Beta Lactam ◽  
Beta Lactams ◽  
Once Daily ◽  
Content Type ◽  
Resistant Strains ◽  
Synergy Test ◽  
Time Kill

ABSTRACTBeta-lactams enhance the killing activity of vancomycin. Due to structural and mechanistic similarities between vancomycin and telavancin, we investigated the activity of telavancin combined with nafcillin and imipenem compared to the known synergistic combination of telavancin and gentamicin. Thirty strains ofStaphylococcus aureus, 10 methicillin-susceptibleS. aureus(MSSA), 10 methicillin-resistantS. aureus(MRSA), and 10 heterogeneously vancomycin-intermediateS. aureus(hVISA), were tested for synergy by time-kill methodology. Six strains (2 each of MSSA, MRSA, and hVISA) were further evaluated in anin vitropharmacokinetic/pharmacodynamic (PK/PD) model with simulated regimens of 10 mg/kg of body weight of telavancin once daily alone and combined with 2 g nafcillin every 4 h, 500 mg imipenem every 6 h, or 5 mg/kg gentamicin once daily over 72 h. In the synergy test, 67% of strains displayed synergy with the combination of telavancin and gentamicin, 70% with telavancin and nafcillin, and 63% with telavancin and imipenem. In the PK/PD model, the activities of all three combinations against MRSA and hVISA were superior to all individual drugs alone (P≤ 0.002) and were similar to each other (P≥ 0.187). The activities of all three combinations against MSSA were generally similar to each other except for one strain where the combination of telavancin and imipenem was superior to all other regimens (P≤ 0.011). The activity of the combination of telavancin and beta-lactam agents was similar to that of telavancin and gentamicin againstS. aureus, including resistant strains. Because beta-lactam combinations are less likely to be nephrotoxic than telavancin plus gentamicin, these beta-lactam combinations may have clinical utility.

scholarly journals Antifungal Combinations against Candida albicans Biofilms In Vitro

2003 ◽  
Vol 47 (11) ◽  
pp. 3657-3659 ◽  
Author(s):  
Stefano P. Bachmann ◽  
Gordon Ramage ◽  
Kacy VandeWalle ◽  
Thomas F. Patterson ◽  
Brian L. Wickes ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Amphotericin B ◽  
Antifungal Agents ◽  
Antagonistic Effect ◽  
Titration Method ◽  
Time Kill ◽  
Candida Albicans Biofilms ◽  
Checkerboard Titration

ABSTRACT Candida biofilms display increased resistance to most antifungal agents. We have evaluated the efficacy of combinations of fluconazole (FLC), amphotericin B, and caspofungin (CSP) against Candida albicans biofilms in vitro. Indifference was observed for all the combinations of paired antifungal agents when a checkerboard titration method was used. Time-kill experiments revealed an antagonistic effect of high FLC doses with CSP.

In Vitro Synergism of Sulbactam- Cefoperazone and Fosfomycin Against Escherichia Coli and Klebsiella Aeromobilis from Indonesia

2021 ◽  
Vol 71 (5) ◽  
pp. 209-214
Author(s):  
Agus Syahrurachman ◽  
Atna Permana
Keyword(s):  
Inhibitory Concentration ◽  
Clinical Laboratory ◽  
Independent Effect ◽  
E Coli ◽  
Susceptibility Data ◽  
Antibiotic Effect ◽  
Time Kill ◽  
Checkerboard Titration ◽  
Post Antibiotic Effect

Introduction: There is no susceptibility data of E. coli and K. aeromobilis in Indonesia, even data regarding minimal inhibitory concentration (MIC)-based susceptibility of E. coli and K. aeromobilis towards single antibiotic or combination of fosfomycin (FOS) and sulbactam-cepoferazone (SUL-CPZ) is very scarce, even though the data is required by clinicians. Methods: A descriptive observational study was carried out at the Microbiology Clinical Laboratory of the Faculty of Medicine, Universitas Indonesia. Thirty strains each of clinical isolates of E. coli and K. aeromobilis were subjected to MIC determination against FOS and SUL-CPZ. For susceptibility criteria, we adopted the Eucast guideline. The synergism of the combined antibiotics was determined by checkerboard titration. One strain of E. coli and K. aeromobilis showing a synergistic and independent effect against the combined antibiotics was subjected to a time-kill assay. The post-antibiotic effect (PAE) was determined on a strain of E. coli showing synergism against the combined antibiotics. Results: The MIC level of all strains decreased when the bacteria were exposed to the combined antibiotics. Synergism was observed in 53.3% of E. coli and 56.8% of K. aeromobilis. No antagonism was observed. Higher bacterial death during the first four hours occurred with the isolate, showing synergism compared to the isolate showing an independent effect. The PAE of E. coli was longer when exposed to combined antibiotics. Conclusion: In vitro synergism of FOS and SUL-CPZ was observed in the majority of isolates and could be used as the basis for further research on empirical treatment

scholarly journals In vitro efficacy of gentamicin against multidrug-resistant Neisseria gonorrhoeae: synergy of three gentamicin antimicrobial combinations

2021 ◽  
Author(s):  
Xuechun Li ◽  
Wenjing Le ◽  
Xiangdi Lou ◽  
Biwei Wang ◽  
Caroline A. Genco ◽  
...  
Keyword(s):  
Inhibitory Concentration ◽  
Geometric Mean ◽  
Multidrug Resistant ◽  
Dilution Method ◽  
Agar Dilution Method ◽  
Fractional Inhibitory Concentration ◽  
Agar Dilution ◽  
Resistant Strains ◽  
Antimicrobial Combinations

ABSTRACTObjectivesTo determine in vitro activities of gentamicin alone and in combination with ceftriaxone, ertapenem and azithromycin against multidrug-resistant (MDR) N. gonorrhoeae isolates.Methods407 isolates from Nanjing, China, obtained in 2016 and 2017, had minimum inhibitory concentrations (MICs) determined for gentamicin using the agar dilution method. Antimicrobial combinations were also tested in 97 MDR strains using the antimicrobial gradient epsilometer test (Etest); results ranging from synergy to antagonism were interpreted using the fractional inhibitory concentration (FICI).ResultsAll 407 gonococcal isolates were susceptible to gentamicin. MICs ranged from 2 mg/L to 16 mg/L. Synergy was demonstrated in 16.5%(16/97), 27.8%(27/97) and 8.2%(8/97) MDR strains when gentamicin was combined with ceftriaxone [geometric mean (GM) FICI; 0.747], ertapenem (GM FICI; 0.662) and azithromycin (GM FICI; 1.021), respectively. No antimicrobial antagonism was observed with any combination. The three antimicrobial combinations were indifferent overall. The overall GM MICs of gentamicin were reduced by 2.63-, 3.80- and 1.98-fold when tested in combination with ceftriaxone, ertapenem and azithromycin, respectively. The GM MICs of the three antimicrobials by themselves were reduced by 3-, 2.57- and 1.98-fold respectively, when each was tested in combination with gentamicin. No antimicrobial antagonism was observed with any combination.ConclusionsGentamicin alone was effective in vitro against MDR N. gonorrhoeae and in combination with ceftriaxone, ertapenem or azithromycin. Combination testing of resistant strains, overall, showed lower effective MICs against gentamicin itself and each of the three antimicrobials when used in combination with gentamicin.

Comparison of methodologies for synergism testing of drug combinations against resistant strains of Pseudomonas aeruginosa.

1996 ◽  
Vol 40 (3) ◽  
pp. 677-683 ◽  
Author(s):  
D M Cappelletty ◽  
M J Rybak
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Clinical Isolate ◽  
Inhibitory Concentration ◽  
Laboratory Strain ◽  
Fractional Inhibitory Concentration ◽  
Beta Lactam ◽  
Beta Lactams ◽  
Drug Concentrations ◽  
Concentration Indices

The purpose of this study was to determine if synergism was maintained for various combinations of beta-lactams with an aminoglycoside against four clinical strains and one laboratory strain of Pseudomonas aeruginosa which were resistant, according to the MICs, to the beta-lactams and/or aminoglycoside. The results from both the checkerboard and killing curve methodologies were compared. The laboratory strain (ATCC 27853) was manipulated in vitro by serial passage onto agar containing increasing concentrations of each antibiotic to select for resistance. One clinical isolate (R61) was also serially passed to raise the MIC of piperacillin from 128 to 1,024 micrograms/ml. The fractional inhibitory concentration indices for all isolates indicated indifference for all combination therapies, with values ranging from 0.6 to 3. In contrast, killing curve results for all isolates demonstrated synergism with drug concentrations at either one-fourth or one-half the MIC for each organism. The MIC of piperacillin for the laboratory-manipulated clinical isolate R61 was 1,024 micrograms/ml, and synergism was still observed with concentrations of one-half the MIC of piperacillin and amikacin. For clinical isolate R166, which was beta-lactam and tobramycin resistant, synergism continued to be demonstrated with concentrations of tobramycin (1/16 MIC) in combination with piperacillin and cefepime at 1/2 the MIC. The results of this study indicate that against P. aeruginosa, synergism is observed in spite of resistance to beta-lactams and/or aminoglycosides. Synergism appears to be maintained even at very high MICs (piperacillin, 1,024 micrograms/ml; tobramycin, 128 micrograms/ml) with drug concentrations within achievable therapeutic ranges. With current definitions of synergism there was a complete lack of correlation between the results obtained by the checkerboard and killing curve methodologies, with the fractional inhibitory concentration indices showing indifference and killing curves resulting in synergism. The methodologies and definitions of synergism or antagonism are variable and not standardized and should be reevaluated.

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