In vitro activities of ceftobiprole combined with amikacin or levofloxacin against Pseudomonas aeruginosa: evidence of a synergistic effect using time–kill methodology

2011 ◽  
Vol 38 (1) ◽  
pp. 70-75 ◽  
Author(s):  
Michael Kresken ◽  
Barbara Körber-Irrgang ◽  
Jörg Läuffer ◽  
Sabine Decker-Burgard ◽  
Todd Davies
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Synergistic Effect ◽  
Time Kill

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

scholarly journals Pseudomonas aeruginosa PAO 1 In Vitro Time–Kill Kinetics Using Single Phages and Phage Formulations—Modulating Death, Adaptation, and Resistance

Antibiotics ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 877
Author(s):  
Ana Mafalda Pinto ◽  
Alberta Faustino ◽  
Lorenzo M. Pastrana ◽  
Manuel Bañobre-López ◽  
Sanna Sillankorva
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Phage Therapy ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Chronic Infections ◽  
Swarming Motility ◽  
Resistance Development ◽  
Healthcare Settings ◽  
Time Kill

Pseudomonas aeruginosa is responsible for nosocomial and chronic infections in healthcare settings. The major challenge in treating P. aeruginosa-related diseases is its remarkable capacity for antibiotic resistance development. Bacteriophage (phage) therapy is regarded as a possible alternative that has, for years, attracted attention for fighting multidrug-resistant infections. In this work, we characterized five phages showing different lytic spectrums towards clinical isolates. Two of these phages were isolated from the Russian Microgen Sextaphage formulation and belong to the Phikmvviruses, while three Pbunaviruses were isolated from sewage. Different phage formulations for the treatment of P. aeruginosa PAO1 resulted in diversified time–kill outcomes. The best result was obtained with a formulation with all phages, prompting a lower frequency of resistant variants and considerable alterations in cell motility, resulting in a loss of 73.7% in swimming motility and a 79% change in swarming motility. These alterations diminished the virulence of the phage-resisting phenotypes but promoted their growth since most became insensitive to a single or even all phages. However, not all combinations drove to enhanced cell killings due to the competition and loss of receptors. This study highlights that more caution is needed when developing cocktail formulations to maximize phage therapy efficacy. Selecting phages for formulations should consider the emergence of phage-resistant bacteria and whether the formulations are intended for short-term or extended antibacterial application.

scholarly journals In VitroSynergistic Effect of Curcumin in Combination with Third Generation Cephalosporins against Bacteria Associated with Infectious Diarrhea

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Nishanth Kumar Sasidharan ◽  
Sreerag Ravikumar Sreekala ◽  
Jubi Jacob ◽  
Bala Nambisan
Keyword(s):  
Synergistic Effect ◽  
New Combination ◽  
Normal Fibroblast ◽  
Infectious Diarrhea ◽  
Combination Drug ◽  
Microdilution Method ◽  
Broth Microdilution Method ◽  
Time Kill ◽  
Third Generation Cephalosporins

Diarrhea is one of the leading causes of morbidity and mortality in humans in developed and developing countries. Furthermore, increased resistance to antibiotics has resulted in serious challenges in the treatment of this infectious disease worldwide. Therefore, there exists a need to develop alternative natural or combination drug therapies. The aim of the present study was to investigate the synergistic effect of curcumin-1 in combination with three antibiotics against five diarrhea causing bacteria. The antibacterial activity of curcumin-1 and antibiotics was assessed by the broth microdilution method, checkerboard dilution test, and time-kill assay. Antimicrobial activity of curcumin-1 was observed against all tested strains. The MICs of curcumin-1 against test bacteria ranged from 125 to 1000 μg/mL. In the checkerboard test, curcumin-1 markedly reduced the MICs of the antibiotics cefaclor, cefodizime, and cefotaxime. Significant synergistic effect was recorded by curcumin-1 in combination with cefotaxime. The toxicity of curcumin-1 with and without antibiotics was tested against foreskin (FS) normal fibroblast and no significant cytotoxicity was observed. From our result it is evident that curcumin-1 enhances the antibiotic potentials against diarrhea causing bacteria inin vitrocondition. This study suggested that curcumin-1 in combination with antibiotics could lead to the development of new combination of antibiotics against diarrhea causing bacteria.

Serratia marcescans Contamination of Antiseptic Soap Containing Triclosan: Implications for Nosocomial Infection

1984 ◽  
Vol 5 (9) ◽  
pp. 427-430 ◽  
Author(s):  
M. Anita Barry ◽  
Donald E. Craven ◽  
Theresa A. Goularte ◽  
Deborah A. Lichtenberg
Keyword(s):  
Intensive Care Unit ◽  
Pseudomonas Aeruginosa ◽  
Intensive Care ◽  
Nosocomial Infection ◽  
Surgical Intensive Care Unit ◽  
Minimal Bactericidal Concentration ◽  
Surgical Intensive Care ◽  
Time Kill ◽  
The Impact

Abstract During a recent investigation in our surgical intensive care unit, we found that several bottles of the antiseptic handwashing soap, OR Scrub®, were contaminated with Serratia marcescens. OR Scrub® contains 1% triclosan, lanolin, and detergents. The antimicrobial efficacy of OR Scrub® was examined in vitro using serial two-fold dilutions of soap inoculated with various concentrations of different nosocomial pathogens. The minimal bactericidal concentration (MBC) of OR Scrub® against Pseudomonas aeruginosa and several strains of S. marcescens was ≤1:2 By comparison, a non-antiseptic soap from the same manufacturer (Wash®) and 4% chlorhexidine (Hibiclens®) had MBCs for all strains tested of at least 1:64. Time-kill curves confirmed the findings of the initial experiments.This is the first report of extrinsic contamination of antiseptic soap containing triclosan. No infections could be attributed to the contaminated soap, but sporadic outbreaks of Serratia have occurred in the intensive care unit with no identifiable source. Although there have been few studies on the impact of antiseptic soap in reducing nosocomial infection, we question whether a soap with the limitations of OR Scrub® should be used in intensive care units or operating rooms.

In vitro synergy of ceftolozane/tazobactam in combination with fosfomycin or aztreonam against MDR Pseudomonas aeruginosa

2020 ◽  
Vol 75 (7) ◽  
pp. 1874-1878 ◽  
Author(s):  
Gabriel T Cuba ◽  
Gerlan Rocha-Santos ◽  
Rodrigo Cayô ◽  
Ana Paula Streling ◽  
Carolina S Nodari ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Resistance Mechanisms ◽  
Density Reduction ◽  
Carbapenem Resistant ◽  
Gradient Diffusion ◽  
Fold Reduction ◽  
The Face ◽  
Antimicrobial Synergy ◽  
Time Kill

Abstract Objectives Carbapenem-resistant Pseudomonas aeruginosa (CR-PSA) imposes great limitations on empirical therapeutic choices, which are further complicated by metallo-β-lactamase production. This study evaluated in vitro antimicrobial synergy of ceftolozane/tazobactam in combination with aztreonam and fosfomycin against MDR PSA. Methods MICs were determined by broth microdilution and gradient strips. The effect of ceftolozane/tazobactam+aztreonam and ceftolozane/tazobactam+fosfomycin combinations were tested against 27 MDR PSA isolates carrying blaSPM-1 (n = 13), blaIMP (n = 4), blaVIM (n = 3), blaGES-1 (n = 2) and blaCTX-M-like (n = 2), and 3 isolates with no acquired β-lactamase production detected by gradient diffusion strip crossing (GDSC). Six genetically unrelated SPM-1-producing isolates were also evaluated by time–kill analysis (TKA). Results All CR-PSA isolates harbouring blaSPM-1, blaGES-1 and blaIMP-1 were categorized as resistant to ceftolozane/tazobactam, meropenem and fosfomycin, with 70% being susceptible to aztreonam. Synergism for ceftolozane/tazobactam+fosfomycin and ceftolozane/tazobactam+aztreonam combinations was observed for 88.9% (24/27) and 18.5% (5/27) of the isolates by GDSC, respectively. A 3- to 9-fold reduction in ceftolozane/tazobactam MICs was observed, depending on the combination. Ceftolozane/tazobactam+fosfomycin was synergistic by TKA against one of six SPM-1-producing isolates, with additional non-synergistic bacterial density reduction for another isolate. Aztreonam peak concentrations alone demonstrated a ≥3 log10 cfu/mL reduction against all six isolates, but all strains were within the susceptible range for the drug. No antagonism was observed. Conclusions In the context of increasing CR-PSA and the genetic diversity of resistance mechanisms, new combinations and stewardship strategies may need to be explored in the face of increasingly difficult to treat pathogens.

scholarly journals In Vitro Activity of Pentamidine Alone and in Combination with Antibiotics against Multidrug-Resistant Clinical Pseudomonas aeruginosa Strains

Antibiotics ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 885
Author(s):  
Soraya Herrera-Espejo ◽  
Tania Cebrero-Cangueiro ◽  
Gema Labrador-Herrera ◽  
Jerónimo Pachón ◽  
María Eugenia Pachón-Ibáñez ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Public Health Problem ◽  
Multidrug Resistant ◽  
Vitro Activity ◽  
Synergistic Activity ◽  
In Vitro Activity ◽  
Hospital Acquired Infections ◽  
Time Kill ◽  
Hospital Acquired

Multidrug-resistant (MDR) Pseudomonas aeruginosa is a public health problem causing both community and hospital-acquired infections, and thus the development of new therapies for these infections is critical. The objective of this study was to analyze in vitro the activity of pentamidine as adjuvant in combinations to antibiotics against seven clinical P. aeruginosa strains. The Minimum Inhibitory Concentration (MIC) was determined following standard protocols, and the results were interpreted according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints; however, the gentamicin activity was interpreted according to the Clinical and Laboratory Standards Institute (CLSI) recommendations. The bactericidal in vitro activity was studied at 1×MIC concentrations by time–kill curves, and also performed in three selected strains at 1/2×MIC of pentamidine. All studies were performed in triplicate. The pentamidine MIC range was 400–1600 μg/mL. Four of the strains were MDR, and the other three were resistant to two antibiotic families. The combinations of pentamidine at 1×MIC showed synergistic activity against all the tested strains, except for pentamidine plus colistin. Pentamidine plus imipenem and meropenem were the combinations that showed synergistic activity against the most strains. At 1/2×MIC, pentamidine plus antibiotics were synergistic with all three analyzed strains. In summary, pentamidine in combination with antibiotics showed in vitro synergy against multidrug-resistant P. aeruginosa clinical strains, which suggests its possible use as adjuvant to antibiotics for the therapy of infections from MDR P. aeruginosa.

scholarly journals In Vitro Synergy of Levofloxacin Plus Piperacillin/Tazobactam againstPseudomonas aeruginosa

2009 ◽  
Vol 2009 ◽  
pp. 1-5 ◽  
Author(s):  
Vladimir Chachanidze ◽  
Aixa Curbelo-Irizarry ◽  
Deborah Ashcraft ◽  
George Pankey
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Time Kill ◽  
Synergy Testing

In vitro synergy testing using levofloxacin (LVX) plus piperacillin/tazobactam (TZP) was performed by Etest and time-kill assay (TKA) for 31 unique fluoroquinolone-resistantPseudomonas aeruginosaisolates. The Etest method showed synergy for 9/31 (29%) of isolates, while TKA showed synergy with 14/31 (45%) of isolates. When comparing the Etest method and TKA, concordant results for synergy, antagonism, and indifference were obtained for 24/31 (77%) of the isolates tested.

scholarly journals Development and Qualification of a Pharmacodynamic Model for the Pronounced Inoculum Effect of Ceftazidime against Pseudomonas aeruginosa

2008 ◽  
Vol 53 (1) ◽  
pp. 46-56 ◽  
Author(s):  
Jürgen B. Bulitta ◽  
Neang S. Ly ◽  
Jenny C. Yang ◽  
Alan Forrest ◽  
William J. Jusko ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Predictive Performance ◽  
Pkpd Model ◽  
Infection Models ◽  
The Mean ◽  
Inoculum Effect ◽  
Successful Replication ◽  
Time Kill ◽  
The Impact

ABSTRACT Evidence is mounting in support of the inoculum effect (i.e., slow killing at large initial inocula [CFUo]) for numerous antimicrobials against a variety of pathogens. Our objectives were to (i) determine the impact of the CFUo of Pseudomonas aeruginosa on ceftazidime activity and (ii) to develop and validate a pharmacokinetic/pharmacodynamic (PKPD) mathematical model accommodating a range of CFUo. Time-kill experiments using ceftazidime at seven concentrations up to 128 mg/liter (MIC, 2 mg/liter) were performed in duplicate against P. aeruginosa PAO1 at five CFUo from 105 to 109 CFU/ml. Samples were collected over 24 h and fit by candidate models in NONMEM VI and S-ADAPT 1.55 (all data were comodeled). External model qualification integrated data from eight previously published studies. Ceftazidime displayed approximately 3 to 4 log10 CFU/ml net killing at 106.2 CFUo and concentrations of 4 mg/liter (or higher), less than 1.6 log10 CFU/ml killing at 107.3 CFUo, and no killing at 108.0 CFUo for concentrations up to 128 mg/liter. The proposed mechanism-based model successfully described the inoculum effect and the concentration-independent lag time of killing. The mean generation time was 28.3 min. The effect of an autolysin was assumed to inhibit successful replication. Ceftazidime concentrations of 0.294 mg/liter stimulated the autolysin effect by 50%. The model was predictive in the internal cross-validation and had excellent in silico predictive performance for published studies of P. aeruginosa ATCC 27853 for various CFUo. The proposed PKPD model successfully described and predicted the pronounced inoculum effect of ceftazidime in vitro and integrated data from eight literature studies to support translation from time-kill experiments to in vitro infection models.

scholarly journals Clinically Relevant Plasma Concentrations of Colistin in Combination with Imipenem Enhance Pharmacodynamic Activity against Multidrug-Resistant Pseudomonas aeruginosa at Multiple Inocula

2011 ◽  
Vol 55 (11) ◽  
pp. 5134-5142 ◽  
Author(s):  
Phillip J. Bergen ◽  
Alan Forrest ◽  
Jürgen B. Bulitta ◽  
Brian T. Tsuji ◽  
Hanna E. Sidjabat ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Antibiotic Therapy ◽  
Systematic Study ◽  
Plasma Concentrations ◽  
Multidrug Resistant ◽  
Bacterial Killing ◽  
Content Type ◽  
Resistant Strains ◽  
Time Kill

ABSTRACTThe use of combination antibiotic therapy may be beneficial against rapidly emerging resistance inPseudomonas aeruginosa. The aim of this study was to systematically investigatein vitrobacterial killing and resistance emergence with colistin alone and in combination with imipenem against multidrug-resistant (MDR)P. aeruginosa. Time-kill studies were conducted over 48 h using 5 clinical isolates and ATCC 27853 at two inocula (∼106and ∼108CFU/ml); MDR, non-MDR, and colistin-heteroresistant and -resistant strains were included. Nine colistin-imipenem combinations were investigated. Microbiological response was examined by log changes at 6, 24, and 48 h. Colistin combined with imipenem at clinically relevant concentrations increased the levels of killing of MDR and colistin-heteroresistant isolates at both inocula. Substantial improvements in activity with combinations were observed across 48 h with all colistin concentrations at the low inoculum and with colistin at 4× and 16× MIC (or 4 and 32 mg/liter) at the high inoculum. Combinations were additive or synergistic against imipenem-resistant isolates (MICs, 16 and 32 mg/liter) at the 106-CFU inoculum in 9, 11, and 12 of 18 cases (i.e., 9 combinations across 2 isolates) at 6, 24, and 48 h, respectively, and against the same isolates at the 108-CFU inoculum in 11, 7, and 8 cases, respectively. Against a colistin-resistant strain (MIC, 128 mg/liter), combinations were additive or synergistic in 9 and 8 of 9 cases at 24 h at the 106- and 108-CFU inocula, respectively, and in 5 and 7 cases at 48 h. This systematic study provides important information for optimization of colistin-imipenem combinations targeting both colistin-susceptible and colistin-resistant subpopulations.

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