scholarly journals 009.1 Standardised, quality assured time-kill curve analysis and pharmacodynamic functions of different antibiotics forin vitroevaluation of treatment regimens forneisseria gonorrhoeae

2015 ◽  
Vol 91 (Suppl 2) ◽  
pp. A44.3-A45
Author(s):  
SF Foerster ◽  
M Unemo ◽  
LJ Hathaway ◽  
N Low ◽  
CL Althaus
Keyword(s):  
Curve Analysis ◽  
Treatment Regimens ◽  
Kill Curve ◽  
Time Kill

scholarly journals In vitro antimicrobial combination testing of and evolution of resistance to the first-in-class spiropyrimidinetrione zoliflodacin combined with six therapeutically relevant antimicrobials for Neisseria gonorrhoeae

2019 ◽  
Vol 74 (12) ◽  
pp. 3521-3529 ◽  
Author(s):  
Sunniva Foerster ◽  
George Drusano ◽  
Daniel Golparian ◽  
Michael Neely ◽  
Laura J V Piddock ◽  
...  
Keyword(s):  
Neisseria Gonorrhoeae ◽  
Single Agent ◽  
Curve Analysis ◽  
Phase Iii ◽  
Transmitted Infection ◽  
Kill Curve ◽  
Time Kill ◽  
Selection Of ◽  
Selection Of Resistance

Abstract Objectives Resistance in Neisseria gonorrhoeae to all gonorrhoea therapeutic antimicrobials has emerged. Novel therapeutic antimicrobials are imperative and the first-in-class spiropyrimidinetrione zoliflodacin appears promising. Zoliflodacin could be introduced in dual antimicrobial therapies to prevent the emergence and/or spread of resistance. We investigated the in vitro activity of and selection of resistance to zoliflodacin alone and in combination with six gonorrhoea therapeutic antimicrobials against N. gonorrhoeae. Methods The international gonococcal reference strains WHO F (WT) and WHO O, WHO V and WHO X (strains with different AMR profiles) were examined. Zoliflodacin was evaluated alone or combined with ceftriaxone, cefixime, spectinomycin, gentamicin, tetracycline, cethromycin or sitafloxacin in chequerboard assays, time–kill curve analysis and selection-of-resistance studies. Results Zoliflodacin alone or in combination with all six antimicrobials showed rapid growth inhibition against all examined strains. The time–kill curve analysis indicated that tetracycline or cethromycin combined with zoliflodacin can significantly decrease the zoliflodacin kill rate in vitro. The frequency of selected zoliflodacin-resistance mutations was low when evaluated as a single agent and further reduced for all antimicrobial combinations. All resistant mutants contained the GyrB mutations D429N, K450T or K450N, resulting in zoliflodacin MICs of 0.5–4 mg/L. Conclusions Zoliflodacin, alone or in combination with sexually transmitted infection therapeutic antimicrobials, rapidly kills gonococci with infrequent resistance emergence. Zoliflodacin remains promising for gonorrhoea oral monotherapy and as part of dual antimicrobial therapy with low resistance emergence potential. A Phase III trial evaluating efficacy and safety of zoliflodacin for uncomplicated gonorrhoea treatment is planned in 2019.

scholarly journals What individual antimicrobials add to Mycobacterium avium complex therapies; an in vitro perspective

2021 ◽  
Author(s):  
Vidhisha V. Sonawane ◽  
Mike Marvin Ruth ◽  
Lian J. Pennings ◽  
Elin M Svensson ◽  
Heiman F.L. Wertheim ◽  
...  
Keyword(s):  
Mycobacterium Avium ◽  
Effect Size ◽  
Current Treatment ◽  
Treatment Regimens ◽  
Drug Regimens ◽  
Kill Curve ◽  
Cure Rates ◽  
Time Kill ◽  
Bliss Independence

Objective: For Mycobacterium avium complex pulmonary disease (MAC-PD), current treatment regimens yield low cure rates. To obtain an evidence based combination therapy we assessed the in vitro activity of six drugs - clarithromycin (CLR), rifampicin (RIF), ethambutol (EMB), amikacin (AMK), clofazimine (CFZ), and minocycline (MIN) alone and in combinations against Mycobacterium avium and studied the contributions of individual antibiotics to efficacy. Methods: The MICs of all antibiotics against M. avium ATCC 700898 were determined by broth microdilution. We performed time-kill kinetic assays (TKA) of all single drugs and clinically relevant two, three, four and five drug combinations against M. avium. Pharmacodynamic interactions of these combinations were assessed using area under the time-kill curve-derived effect size and Bliss independence. Results: Adding a second drug yielded an average increase of the effect size (E) of 18.7 ± 32.9% log10 cfu/mL*day, though antagonism was seen in some combinations. Adding a third drug showed a lower increase in effect size (+12.2 ± 11.5%). The rifampicin-clofazimine-clarithromycin (E=102 log10 cfu/mL*day), rifampicin-amikacin-clarithromycin (E=101 log10 cfu/mL*day) and amikacin-minocycline-ethambutol (E=97.8 log10 cfu/mL*day) regimens proved more active than the recommended rifampicin-ethambutol-clarithromycin regimen (E=89.1 log10 cfu/mL*day). The addition of a fourth drug had little impact on effect size (+4.54 ± 3.08%). Conclusions: In vitro, several two- and three-drug regimens are as effective as the currently recommended regimen for MAC-PD. Adding a fourth drug to any regimen had little additional effect. In vitro, the most promising regimen would be rifampicin-amikacin-macrolide or rifampicin-clofazimine-macrolide.

scholarly journals Antibacterial activity of taro [Colocasia esculenta (L.) Schott] leaves extract against foodborne pathogens and its effect on microbial population in raw chicken meat

Food Research ◽  
2021 ◽  
Vol 5 (2) ◽  
pp. 401-409
Author(s):  
A.M. Alzabt ◽  
Y. Rukayadi
Keyword(s):  
Antibacterial Activity ◽  
Foodborne Pathogens ◽  
Microbial Population ◽  
Residual Effect ◽  
Colocasia Esculenta ◽  
Chicken Meat ◽  
Curve Analysis ◽  
Chemical Preservatives ◽  
Kill Curve ◽  
Time Kill

Chicken meat is one of the most consumed animal products worldwide. It is a favourable medium for bacterial growth due to its high moisture content and nitrogenous compounds. The growth of foodborne pathogens in food products can cause food poisoning and foodborne illness. Chemical preservatives act to restrict microbial growth which causes deterioration and spoilage of chicken meat and chicken meat products. Chemical preservatives, however, are not preferred nowadays due to consumer perception and their residual effect on the human body. Therefore, the interest in the development of plantbased bio preservatives as a natural alternative to chemical preservatives is increasingly gaining attention. This study aimed to evaluate the antimicrobial activity of taro [Colocasia esculenta (L.) Schott] leaves extract against foodborne pathogens, including Escherichia coli ATCC 43895, Listeria monocytogenes ATCC 19112, Salmonella enterica serovar Typhimurium ATCC 14028, and Staphylococcus aureus ATCC 29737, as well as its effect on microbial population in chicken meat at different concentrations and exposure times. Taro leaves powder was extracted by maceration methods using ethanol as a solvent. The crude extract was tested for antibacterial activity by means of disc diffusion assay (DDA), minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and time-kill curve analysis. The effects of the extract on microbial population were evaluated at different concentrations, exposure times and storage temperatures. The results showed the inhibition zone of the extract against tested bacterial ranged from 9.5±0.3 mm to 11.6±0.2 mm. The extract can inhibit the growth and kill the tested bacteria with MIC and MBC of 2.50 and 5.00 mg/mL, respectively. The time-kill curve analysis demonstrated that the extract can completely kill the tested bacteria at 4× MIC for 0.5 hrs. Approximately, 5% of the extract could reduce all the microbial population in chicken meat samples with an exposure time of 30 mins. The result suggested that taro leaves extract (TLE) can be integrated into the food system as a natural food preservative.

scholarly journals Antimicrobial Activities of Ceragenins against Clinical Isolates of Resistant Staphylococcus aureus

2007 ◽  
Vol 51 (4) ◽  
pp. 1268-1273 ◽  
Author(s):  
Judy N. Chin ◽  
Michael J. Rybak ◽  
Chrissy M. Cheung ◽  
Paul B. Savage
Keyword(s):  
Staphylococcus Aureus ◽  
Multidrug Resistant ◽  
Antimicrobial Activities ◽  
Curve Analysis ◽  
Clinical Isolates ◽  
Resistant Bacteria ◽  
Inoculum Effect ◽  
Kill Curve ◽  
Time Required ◽  
Time Kill

ABSTRACT The rise in the rates of glycopeptide resistance among Staphylococcus aureus isolates is concerning and underscores the need for the development of novel potent compounds. Ceragenins CSA-8 and CSA-13, cationic steroid molecules that mimic endogenous antimicrobial peptides, have previously been demonstrated to possess broad-spectrum activities against multidrug-resistant bacteria. We examined the activities of CSA-8 and CSA-13 against clinical isolates of vancomycin-intermediate S. aureus (VISA), heterogeneous vancomycin-intermediate S. aureus (hVISA), as well as vancomycin-resistant S. aureus (VRSA) and compared them to those of daptomycin, linezolid, and vancomycin by susceptibility testing and killing curve analysis. We also examined CSA-13 for its concentration-dependent activity, inoculum effect, postantibiotic effect (PAE), and synergy in combination with various antimicrobials. Overall, the MICs and minimal bactericidal concentrations of CSA-13 were fourfold lower than those of CSA-8. Time-kill curve analysis of the VRSA, VISA, and hVISA clinical isolates demonstrated concentration-dependent bactericidal killing. An inoculum effect was also observed when a higher starting bacterial density was used, with the time required to achieve 99.9% killing reaching 1 h with a 6-log10-CFU/ml starting inoculum, whereas it was ≥24 h with a 8- to 9-log10-CFU/ml starting inoculum with 10× the MIC (P ≤ 0.001). A concentration-dependent PAE was demonstrated with CSA-13, nearly doubling from 2× to 4× the MIC (P = 0.03). With respect to the CSA-13 antimicrobial combinations, time-kill curve analysis showed no difference in the log10 CFU/ml at 24 h for the majority of the organisms tested. However, early synergy at 4 to 8 h was detected against the VRSA Pennsylvania strain (2002) when CSA-13 was tested in combination with gentamicin, while early additivity was demonstrated against all of the other organisms.

In vitro activity and time-kill curve analysis of sitafloxacin against a global panel of antimicrobial-resistant and multidrug-resistant Neisseria gonorrhoeae isolates

Apmis ◽  
2017 ◽  
Vol 126 (1) ◽  
pp. 29-37 ◽  
Author(s):  
Agnez Jönsson ◽  
Sunniva Foerster ◽  
Daniel Golparian ◽  
Ryoichi Hamasuna ◽  
Susanne Jacobsson ◽  
...  
Keyword(s):  
Neisseria Gonorrhoeae ◽  
Multidrug Resistant ◽  
Curve Analysis ◽  
Vitro Activity ◽  
In Vitro Activity ◽  
Kill Curve ◽  
Time Kill

scholarly journals Trans-Cinnamaldehyde Exhibits Synergy with Conventional Antibiotic against Methicillin-Resistant Staphylococcus aureus

2021 ◽  
Vol 22 (5) ◽  
pp. 2752
Author(s):  
Shu Wang ◽  
Ok-Hwa Kang ◽  
Dong-Yeul Kwon
Keyword(s):  
Staphylococcus Aureus ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Synergistic Effects ◽  
Regulatory Gene ◽  
Western Blot Assay ◽  
Methicillin Resistant ◽  
Wide Range ◽  
Kill Curve ◽  
Conventional Antibiotics ◽  
Time Kill

Methicillin-resistant Staphylococcus aureus (MRSA) is a major nosocomial pathogen worldwide and has acquired multiple resistance to a wide range of antibiotics. Hence, there is a pressing need to explore novel strategies to overcome the increase in antimicrobial resistance. The present study aims to investigate the efficacy and mechanism of plant-derived antimicrobials, trans-cinnamaldehyde (TCA) in decreasing MRSA’s resistance to eight conventional antibiotics. A checkerboard dilution test and time–kill curve assay are used to determine the synergistic effects of TCA combined with the antibiotics. The results indicated that TCA increased the antibacterial activity of the antibiotics by 2-16-fold. To study the mechanism of the synergism, we analyzed the mecA transcription gene and the penicillin-binding protein 2a level of MRSA treated with TCA by quantitative RT-PCR or Western blot assay. The gene transcription and the protein level were significantly inhibited. Additionally, it was verified that TCA can significantly inhibit the biofilm, which is highly resistant to antibiotics. The expression of the biofilm regulatory gene hld of MRSA after TCA treatment was also significantly downregulated. These findings suggest that TCA maybe is an exceptionally potent modulator of antibiotics.

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