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Sigurdur Gudmundsson - One of the best experts on this subject based on the ideXlab platform.
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different patterns of bacterial dna synthesis during postantibiotic effect
Antimicrobial Agents and Chemotherapy, 1995Co-Authors: Magnus Gottfredsson, Helga Erlendsdottir, Agust Gudmundsson, Sigurdur GudmundssonAbstract:Studies on bacterial metabolism during the postantibiotic effect (PAE) period are limited but might provide insight into the nature of the PAE. We evaluated the rate of DNA synthesis in bacteria during the PAE period after a 1-h exposure of organisms in the logarithmic growth phase to various antibiotics. Staphylococcus aureus ATCC 25923 was exposed to vancomycin, Dicloxacillin, rifampin, and ciprofloxacin ; Escherichia coli ATCC 25922 was exposed to gentamicin, tobramycin, rifampin, imipenem, and ciprofloxacin ; and Pseudomonas aeruginosa ATCC 25783 was exposed to imipenem, tobramycin, and ciprofloxacin. DNA synthesis was determined by measuring the rate of [ 3 H]thymidine incorporation in S. aureus and E. coli and [ 3 H]adenine incorporation in P. aeruginosa. DNA synthesis in S. aureus was suppressed during the PAE phase with vancomycin, Dicloxacillin, and rifampin, it was suppressed in E. coli with rifampin, and it was suppressed in P. aeruginosa after exposure to tobramycin. Conversely, DNA synthesis was relatively enhanced in the gram-negative bacilli after exposure to imipenem and in all three species after exposure to ciprofloxacin. However, DNA synthesis in E. coli was only minimally affected after exposure to tobramycin and gentamicin. The differences in DNA synthesis observed after exposure to various antimicrobial agents suggest multiple mechanisms for the PAE.
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different patterns of bacterial dna synthesis during postantibiotic effect
Antimicrobial Agents and Chemotherapy, 1995Co-Authors: Magnus Gottfredsson, Helga Erlendsdottir, Agust Gudmundsson, Sigurdur GudmundssonAbstract:Studies on bacterial metabolism during the postantibiotic effect (PAE) period are limited but might provide insight into the nature of the PAE. We evaluated the rate of DNA synthesis in bacteria during the PAE period after a 1-h exposure of organisms in the logarithmic growth phase to various antibiotics. Staphylococcus aureus ATCC 25923 was exposed to vancomycin, Dicloxacillin, rifampin, and ciprofloxacin ; Escherichia coli ATCC 25922 was exposed to gentamicin, tobramycin, rifampin, imipenem, and ciprofloxacin ; and Pseudomonas aeruginosa ATCC 25783 was exposed to imipenem, tobramycin, and ciprofloxacin. DNA synthesis was determined by measuring the rate of [ 3 H]thymidine incorporation in S. aureus and E. coli and [ 3 H]adenine incorporation in P. aeruginosa. DNA synthesis in S. aureus was suppressed during the PAE phase with vancomycin, Dicloxacillin, and rifampin, it was suppressed in E. coli with rifampin, and it was suppressed in P. aeruginosa after exposure to tobramycin. Conversely, DNA synthesis was relatively enhanced in the gram-negative bacilli after exposure to imipenem and in all three species after exposure to ciprofloxacin. However, DNA synthesis in E. coli was only minimally affected after exposure to tobramycin and gentamicin. The differences in DNA synthesis observed after exposure to various antimicrobial agents suggest multiple mechanisms for the PAE.
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ultrastructural alterations of bacteria during the postantibiotic effect
Chemotherapy, 1993Co-Authors: Magnus Gottfredsson, Helga Erlendsdottir, Ragnhildur Kolka, Agust Gudmundsson, Sigurdur GudmundssonAbstract:Ultrastructural alterations of Staphylococcus aureus and Pseudomonas aeruginosa were examined during the postantibiotic effect (PAE) with transmission electron microscopy. After exposure to Dicloxacillin the staphylococci were characterized by an increase in the number of crosswalls, rifampin produced thickening of the cell wall, but only minimal changes were induced by gentamicin. Intracellular electrondense aggregates were observed in P. aeruginosa after exposure to imipenem, tobramycin and ciprofloxacin, and imipenem caused globoid cell formations. These alterations were not uniform in every organism, but they correlated well with the duration of the PAE determined by viable counts.
Janne Kudsk Klitgaard - One of the best experts on this subject based on the ideXlab platform.
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molecular mechanisms of thioridazine resistance in staphylococcus aureus
PLOS ONE, 2018Co-Authors: Claes Sondergaard Wassmann, Birgitte H. Kallipolitis, Hans Jørn Kolmos, Lars Christian Lund, Mette Thorsing, Sabrina Prehn Lauritzen, Janne Kudsk KlitgaardAbstract:Staphylococcus aureus has developed resistance towards the most commonly used anti-staphylococcal antibiotics. Therefore, there is an urgent need to find new treatment opportunities. A new approach relies on the use of helper compounds, which are able to potentiate the effect of antibiotics. A well-studied helper compound is thioridazine, which potentiates the effect of the β-lactam antibiotic Dicloxacillin against Methicillin-resistant Staphylococcus aureus (MRSA). In order to identify thioridazine’s mechanism of action and how it potentiates the effect of Dicloxacillin, we generated thioridazine resistant strains of MRSA USA300 by serial passage experiments. Selected strains were whole-genome sequenced to find mutations causing thioridazine resistance. Genes observed to be mutated were attempted deleted in MRSA USA300. The cls gene encoding a cardiolipin synthase important for synthesis of the membrane lipid cardiolipin was found to be mutated in thioridazine resistant strains. Deletion of this gene resulted in a two-fold increased Minimum inhibitory concentrations (MIC) value for thioridazine compared to the wild type and decreased susceptibility similar to the thioridazine resistant strains. Since cardiolipin likely plays a role in resistance towards thioridazine, it might also be important for the mechanism of action behind the potentiating effect of thioridazine. TDZ is known to intercalate into the membrane and we show here that TDZ can depolarize the plasma membrane. However, our results indicate that the membrane potential reducing effect of TDZ is independent of the resistance mechanism.
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Systemic thioridazine in combination with Dicloxacillin against early aortic graft infections caused by Staphylococcus aureus in a porcine model: In vivo results do not reproduce the in vitro synergistic activity - Fig 2
2017Co-Authors: Michael Stenger, Janne Kudsk Klitgaard, Hans Jørn Kolmos, Carsten Behr-rasmussen, Kasper Klein, Rasmus B. Grønnemose, Thomas Emil Andersen, Jes S. LindholtAbstract:Changes in weight (A), temperature (B), white blood cell count (WBC) (C), haemoglobin (HGB) (D), and haptoglobin (E) of each treatment group during the experimental period are displayed as mean values with standard deviation bars at predefined time points. Graft implantation and inoculation was at day -7 and the dotted grey line indicates treatment initiation at day 0. Dicloxacillin (DCX); Thioridazine (TDZ)
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A-D: Main trial: Box-whisker plots of bacterial quantities displayed as ln(CFU/mL) in all treatments groups sorted by bacteriological endpoints–(A) P-flush, (B) Spleen, (C) Kidney, and (D) Total.
2015Co-Authors: Michael Stenger, Hans Jørn Kolmos, Kristoffer Hendel, Peter Bollen, Peter B. Licht, Janne Kudsk KlitgaardAbstract:The filled dots indicate outliers. DCX: Dicloxacillin; TDZ: Thioridazine; VAN: Vancomycin; SALINE: Isotonic saline.
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IP trial: Box-whisker plot of pooled bacteriological endpoints related to treatment groups in the IP-trial.
2015Co-Authors: Michael Stenger, Hans Jørn Kolmos, Kristoffer Hendel, Peter Bollen, Peter B. Licht, Janne Kudsk KlitgaardAbstract:The filled dots indicate outliers. DCX_ip: Dicloxacillin administered IP; TDZ_ip: Thioridazine administered IP; VAN_ip: Vancomycin administered IP.
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thioridazine potentiates the effect of a beta lactam antibiotic against staphylococcus aureus independently of meca expression
Research in Microbiology, 2013Co-Authors: Marianne Nielsine Skov, Birgitte H. Kallipolitis, Hans Jørn Kolmos, Mette Thorsing, Marianne Ostergaard Poulsen, Kirstine Jacobsen, Nadia R D Kristensen, Julie Clasen, Eva Maria Sternkopf Lillebaek, Janne Kudsk KlitgaardAbstract:The neuroleptic antipsychotic derivate thioridazine has been shown to increase the susceptibility of a methicillin-resistant Staphylococcus aureus (MRSA) isolate towards Dicloxacillin. The aim of this study was to investigate the combinatorial effect of the two drugs on a broad selection of staphylococcal strains by analyzing a large collection of MRSA strains carrying different types of SCCmec, as well as MSSA strains. Transcription and translation of the resistance marker PBP2a encoded by mecA within the SCCmec cassette were analyzed by primer extension and western blotting. We observed increased susceptibility to Dicloxacillin in the presence of thioridazine in all tested MRSA isolates. In contrast to previously published results, the synergistic effect was also applicable to methicillin-susceptible S. aureus (MSSA). We conclude that the combination of Dicloxacillin and thioridazine potentiates the killing effect against S. aureus in a broad selection of clinical isolates. Additionally, the study indicates that the killing effect by the combinatorial treatment is independent of PBP2a-mediated resistance mechanisms.
Magnus Gottfredsson - One of the best experts on this subject based on the ideXlab platform.
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different patterns of bacterial dna synthesis during postantibiotic effect
Antimicrobial Agents and Chemotherapy, 1995Co-Authors: Magnus Gottfredsson, Helga Erlendsdottir, Agust Gudmundsson, Sigurdur GudmundssonAbstract:Studies on bacterial metabolism during the postantibiotic effect (PAE) period are limited but might provide insight into the nature of the PAE. We evaluated the rate of DNA synthesis in bacteria during the PAE period after a 1-h exposure of organisms in the logarithmic growth phase to various antibiotics. Staphylococcus aureus ATCC 25923 was exposed to vancomycin, Dicloxacillin, rifampin, and ciprofloxacin ; Escherichia coli ATCC 25922 was exposed to gentamicin, tobramycin, rifampin, imipenem, and ciprofloxacin ; and Pseudomonas aeruginosa ATCC 25783 was exposed to imipenem, tobramycin, and ciprofloxacin. DNA synthesis was determined by measuring the rate of [ 3 H]thymidine incorporation in S. aureus and E. coli and [ 3 H]adenine incorporation in P. aeruginosa. DNA synthesis in S. aureus was suppressed during the PAE phase with vancomycin, Dicloxacillin, and rifampin, it was suppressed in E. coli with rifampin, and it was suppressed in P. aeruginosa after exposure to tobramycin. Conversely, DNA synthesis was relatively enhanced in the gram-negative bacilli after exposure to imipenem and in all three species after exposure to ciprofloxacin. However, DNA synthesis in E. coli was only minimally affected after exposure to tobramycin and gentamicin. The differences in DNA synthesis observed after exposure to various antimicrobial agents suggest multiple mechanisms for the PAE.
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different patterns of bacterial dna synthesis during postantibiotic effect
Antimicrobial Agents and Chemotherapy, 1995Co-Authors: Magnus Gottfredsson, Helga Erlendsdottir, Agust Gudmundsson, Sigurdur GudmundssonAbstract:Studies on bacterial metabolism during the postantibiotic effect (PAE) period are limited but might provide insight into the nature of the PAE. We evaluated the rate of DNA synthesis in bacteria during the PAE period after a 1-h exposure of organisms in the logarithmic growth phase to various antibiotics. Staphylococcus aureus ATCC 25923 was exposed to vancomycin, Dicloxacillin, rifampin, and ciprofloxacin ; Escherichia coli ATCC 25922 was exposed to gentamicin, tobramycin, rifampin, imipenem, and ciprofloxacin ; and Pseudomonas aeruginosa ATCC 25783 was exposed to imipenem, tobramycin, and ciprofloxacin. DNA synthesis was determined by measuring the rate of [ 3 H]thymidine incorporation in S. aureus and E. coli and [ 3 H]adenine incorporation in P. aeruginosa. DNA synthesis in S. aureus was suppressed during the PAE phase with vancomycin, Dicloxacillin, and rifampin, it was suppressed in E. coli with rifampin, and it was suppressed in P. aeruginosa after exposure to tobramycin. Conversely, DNA synthesis was relatively enhanced in the gram-negative bacilli after exposure to imipenem and in all three species after exposure to ciprofloxacin. However, DNA synthesis in E. coli was only minimally affected after exposure to tobramycin and gentamicin. The differences in DNA synthesis observed after exposure to various antimicrobial agents suggest multiple mechanisms for the PAE.
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ultrastructural alterations of bacteria during the postantibiotic effect
Chemotherapy, 1993Co-Authors: Magnus Gottfredsson, Helga Erlendsdottir, Ragnhildur Kolka, Agust Gudmundsson, Sigurdur GudmundssonAbstract:Ultrastructural alterations of Staphylococcus aureus and Pseudomonas aeruginosa were examined during the postantibiotic effect (PAE) with transmission electron microscopy. After exposure to Dicloxacillin the staphylococci were characterized by an increase in the number of crosswalls, rifampin produced thickening of the cell wall, but only minimal changes were induced by gentamicin. Intracellular electrondense aggregates were observed in P. aeruginosa after exposure to imipenem, tobramycin and ciprofloxacin, and imipenem caused globoid cell formations. These alterations were not uniform in every organism, but they correlated well with the duration of the PAE determined by viable counts.
Thomas Benfield - One of the best experts on this subject based on the ideXlab platform.
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propensity-score-adjusted case–control and
2016Co-Authors: Jette Lindbjerg Nissen, Robert Skov, Jenny Dahl Knudsen, Christian Ostergaard, Henrik Carl Schonheyder, Niels Frimodt-møller, Thomas BenfieldAbstract:Effectiveness of penicillin, Dicloxacillin and cefuroxime for penicillin-susceptible Staphylococcus aureus bacteraemia: a retrospective
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relative efficacy of cefuroxime versus Dicloxacillin as definitive antimicrobial therapy in methicillin susceptible staphylococcus aureus bacteraemia a propensity score adjusted retrospective cohort study
Journal of Antimicrobial Chemotherapy, 2014Co-Authors: Jon Rasmussen, Jenny Dahl Knudsen, Henrik Carl Schonheyder, Thomas Benfield, Magnus Arpi, Christian OstergaardAbstract:OBJECTIVES The objective of the present study was to compare the efficacy of cefuroxime with that of Dicloxacillin as definitive antimicrobial therapy in methicillin-susceptible Staphylococcus aureus bacteraemia (MS-SAB) using a Danish bacteraemia database, information on the indication for antimicrobial therapy, multivariate adjustment and propensity score (PS) matching. METHODS This was a retrospective cohort study. MS-SAB cases from 1 January 2006 to 31 December 2008 were included from a total of seven hospitals in the greater Copenhagen area and seven hospitals in the North Denmark Region. Information including demographics, antimicrobial therapy and clinical condition was obtained. The physician's note detailing the indication for starting empirical antimicrobial therapy was given special attention. Hazard ratios (HRs) and 95% CIs for 30 day and 90 day mortality were calculated using PS-adjusted Cox proportional hazards regression analyses. In addition, PS matching was performed. RESULTS A total of 691 patients with MS-SAB received either Dicloxacillin (n = 368) or cefuroxime (n = 323) as definitive antimicrobial therapy. Twenty-eight different indications for empirical antimicrobial therapy were identified and grouped into eight categories. There was no statistically significant difference in 30 day mortality between the two groups (HR 1.02, 95% CI 0.68-1.52). Definitive antimicrobial therapy with cefuroxime was associated with increased 90 day mortality in a PS-adjusted multivariate analysis (HR 1.43, 95% CI 1.03-1.98) and in the PS matching (OR 1.65, 95% CI 1.06-2.56). Antimicrobial therapy for an indication of 'severe infection' was independently associated with 90 day mortality (HR 1.97, 95% CI 1.19-3.28). CONCLUSIONS Definitive antimicrobial therapy with cefuroxime was associated with significantly higher 90 day mortality than was Dicloxacillin therapy in patients with MS-SAB.
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effectiveness of penicillin Dicloxacillin and cefuroxime for penicillin susceptible staphylococcus aureus bacteraemia a retrospective propensity score adjusted case control and cohort analysis
Journal of Antimicrobial Chemotherapy, 2013Co-Authors: Jette Nissen, Robert Skov, Jenny Dahl Knudsen, Christian Ostergaard, Henrik Carl Schonheyder, Niels Frimodtmoller, Thomas BenfieldAbstract:Results: Definitive therapy with cefuroxime was associated with an increased risk of 30 day mortality compared with penicillin (adjusted HR 2.54, 95% CI 1.49‐4.32). Other variables that were statistically significantly associated with 30 day mortality included increasing age, disease severity and a primary respiratory focus. Osteomyelitis/arthritis was associated with a lower risk of death than were other secondary manifestations. Propensity-score-matched case‐control studies confirmed an increased risk of 30 day mortality: cefuroxime treatment (39%) versus penicillin treatment (20%), P ¼0.037; and cefuroxime treatment (38%) versus Dicloxacillin treatment (10%), P ¼0.004. Conclusions: Definitive therapy for penicillin-susceptible SAB with cefuroxime was associated with a significantly higher mortality than was seen with therapy with penicillin or Dicloxacillin.
Yauli Ñaupas Emmanuel - One of the best experts on this subject based on the ideXlab platform.
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Eficacia Antibacteriana del Extracto Hidroalcohólico de Oenothera Rosea “Yawar Soqo”, sobre Staphylococcus Aureus Atcc 25923 Comparado con Dicloxacilina, In Vitro
'Universidad Cesar Vallejo', 2019Co-Authors: Yauli Ñaupas EmmanuelAbstract:The antibacterial efficacy of hydroalcoholic extract of Oenothera rosea on strains of Staphylococcus aureus ATCC 25923 was evaluated as compared with Dicloxacillin in-vitro. An experimental scheme was designed consisting of 4 dilutions (40%-60%-80%-100%), 1 positive control (Dicloxacillin 3µg) and 1 negative control. The study showed that dilutions at 40% and 60% have no inhibitory effect; at 80%, the diameter of the zone of inhibition was 7.5 mm (SD 0.1±0.13 95% CI: 7.4 to 7.5) between the intervals of 7.4 to 7.6 mm; but it is also evident that at 100% concentration the maximum zone of inhibition value reached 11.6 mm (SD 0.0±0.03 95%CI: 11.5 to 11.6) between the intervals of 11.5 to 11.6 mm. In relation to Dicloxacillin, it had an inhibition zone of 16.6 mm (SD 0.1±0.05 CI 95%: 16.6 to 16.6) between the intervals 16.5 to 16.7 mm. It was concluded that there was no antibacterial efficacy in any of the concentrations of Oenothera rosea.TesisTrujilloEscuela Académico Profesional de MedicinaEnfermedades Infecciosas Y TransmisiblesSe evaluó la eficacia antibacteriana del extracto hidroalcohólico de la Oenothera rosea sobre cepas de Staphylococcus aureus ATCC 25923 comparado con la Dicloxacilina in vitro. Se diseñó un esquema experimental compuesto por 4 diluciones (40%-60%-80%-100%), 1 control positivo (dicloxacilina 3µg) y 1 control negativo; El estudio demostró que las diluciones al 40% y 60% no presentan efecto inhibitorio; al 80%, el diámetro del halo de inhibición fue de 7.5 mm (DS 0.1±0.13 IC95%: 7.4 a 7.5) entre los intervalos de 7.4 a 7.6 mm; pero también se logra evidenciar que a la concentración de 100% el valor máximo de halo inhibitorio llegó a 11.6 mm (DS 0.0±0.03 IC95%: 11.5 a 11.6) entre los intervalos de 11.5 a 11.6 mm. En relación a la Dicloxacilina tuvo una zona de inhibición de 16,6 mm (DS 0.1±0.05 IC 95%: 16.6 a 16.6) entre los intervalos 16.5 a 16.7mm. Concluyéndose que no presenta eficacia antibacteriana en ninguna de las concentraciones de la Oenothera rosea
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Eficacia Antibacteriana del Extracto Hidroalcohólico de Oenothera Rosea “Yawar Soqo”, sobre Staphylococcus Aureus Atcc 25923 Comparado con Dicloxacilina, In Vitro
'Universidad Cesar Vallejo', 2019Co-Authors: Yauli Ñaupas EmmanuelAbstract:The antibacterial efficacy of hydroalcoholic extract of Oenothera rosea on strains of Staphylococcus aureus ATCC 25923 was evaluated as compared with Dicloxacillin in-vitro. An experimental scheme was designed consisting of 4 dilutions (40%-60%-80%-100%), 1 positive control (Dicloxacillin 3µg) and 1 negative control. The study showed that dilutions at 40% and 60% have no inhibitory effect; at 80%, the diameter of the zone of inhibition was 7.5 mm (SD 0.1±0.13 95% CI: 7.4 to 7.5) between the intervals of 7.4 to 7.6 mm; but it is also evident that at 100% concentration the maximum zone of inhibition value reached 11.6 mm (SD 0.0±0.03 95%CI: 11.5 to 11.6) between the intervals of 11.5 to 11.6 mm. In relation to Dicloxacillin, it had an inhibition zone of 16.6 mm (SD 0.1±0.05 CI 95%: 16.6 to 16.6) between the intervals 16.5 to 16.7 mm. It was concluded that there was no antibacterial efficacy in any of the concentrations of Oenothera rosea.Se evaluó la eficacia antibacteriana del extracto hidroalcohólico de la Oenothera rosea sobre cepas de Staphylococcus aureus ATCC 25923 comparado con la Dicloxacilina in vitro. Se diseñó un esquema experimental compuesto por 4 diluciones (40%-60%-80%-100%), 1 control positivo (dicloxacilina 3µg) y 1 control negativo; El estudio demostró que las diluciones al 40% y 60% no presentan efecto inhibitorio; al 80%, el diámetro del halo de inhibición fue de 7.5 mm (DS 0.1±0.13 IC95%: 7.4 a 7.5) entre los intervalos de 7.4 a 7.6 mm; pero también se logra evidenciar que a la concentración de 100% el valor máximo de halo inhibitorio llegó a 11.6 mm (DS 0.0±0.03 IC95%: 11.5 a 11.6) entre los intervalos de 11.5 a 11.6 mm. En relación a la Dicloxacilina tuvo una zona de inhibición de 16,6 mm (DS 0.1±0.05 IC 95%: 16.6 a 16.6) entre los intervalos 16.5 a 16.7mm. Concluyéndose que no presenta eficacia antibacteriana en ninguna de las concentraciones de la Oenothera rosea