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.

In vitro activity of ceftolozane/tazobactam alone and in combination with amikacin against MDR/XDR Pseudomonas aeruginosa isolates from Greece

2020 ◽  
Author(s):  
Irene Galani ◽  
Vassiliki Papoutsaki ◽  
Irene Karantani ◽  
Ilias Karaiskos ◽  
Lamprini Galani ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Peak Plasma ◽  
Peak Plasma Concentration ◽  
Active Agent ◽  
Synergistic Interaction ◽  
Vitro Activity ◽  
In Vitro Activity ◽  
Time Kill ◽  
Synergy Testing

Abstract Objectives We evaluated the in vitro activity of ceftolozane/tazobactam and comparator agents against MDR non-MBL Pseudomonas aeruginosa isolates collected from nine Greek hospitals and we assessed the potential synergistic interaction between ceftolozane/tazobactam and amikacin. Methods A total of 160 non-MBL P. aeruginosa isolates collected in 2016 were tested for susceptibility to ceftolozane/tazobactam and seven comparator agents including ceftazidime/avibactam. Time–kill assays were performed for synergy testing using ceftolozane/tazobactam 60 or 7.5 mg/L, corresponding to the peak and trough concentrations of a 1.5 g q8h dose, respectively, in combination with 69 mg/L amikacin, corresponding to the free peak plasma concentration. Synergy was defined as a ≥2 log10 cfu/mL reduction compared with the most active agent. Results Overall, ceftolozane/tazobactam inhibited 64.4% of the P. aeruginosa strains at ≤4 mg/L. Colistin was the most active agent (MIC50/90, 0.5/2 mg/L; 96.3% susceptible) followed by ceftazidime/avibactam (MIC50/90, 4/16 mg/L; 80.6% susceptible). GES-type enzymes were predominantly responsible for ceftolozane/tazobactam resistance; 81.6% of the non-producers were susceptible. MICs for the P. aeruginosa isolates selected for synergy testing were 2–32 mg/L ceftolozane/tazobactam and 2–128 mg/L amikacin. The combination of ceftolozane/tazobactam with amikacin was synergistic against 85.0% of all the isolates tested and against 75.0% of the GES producers. No antagonistic interactions were observed. Conclusions Ceftolozane/tazobactam demonstrated good in vitro activity against MDR/XDR P. aeruginosa clinical isolates, including strains with co-resistance to other antipseudomonal drugs. In combination with amikacin, a synergistic interaction at 24 h was observed against 85.0% of P. aeruginosa strains tested, including isolates with ceftolozane/tazobactam MICs of 32 mg/L or GES producers.

scholarly journals In Vitro Synergy of Ciprofloxacin and Gatifloxacin against Ciprofloxacin-Resistant Pseudomonas aeruginosa

2005 ◽  
Vol 49 (7) ◽  
pp. 2959-2964 ◽  
Author(s):  
George A. Pankey ◽  
Deborah S. Ashcraft
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Efflux Pump ◽  
In Vitro Study ◽  
Multidrug Resistant ◽  
Efflux Pump Inhibition ◽  
Pump Mechanism ◽  
Time Kill ◽  
Synergy Testing ◽  
Unique Plasmid

ABSTRACT Multidrug-resistant Pseudomonas aeruginosa with combined decreased susceptibility to ceftazidime, ciprofloxacin, imipenem, and piperacillin is increasingly being found as a cause of nosocomial infections. It is important to look for combinations of drugs that might be synergistic. Ciprofloxacin resistance by P. aeruginosa is mediated in part by an efflux pump mechanism. Gatifloxacin, an 8-methoxyfluoroquinolone, inhibits a staphylococcal efflux pump. An earlier in vitro study using an Etest synergy method and time-kill assay suggested synergy of ciprofloxacin and gatifloxacin against P. aeruginosa. Synergy testing was performed by Etest and time-kill assay for 31 clinically unique, plasmid DNA distinct, U.S. P. aeruginosa isolates. Etest MICs for ciprofloxacin were 4 to >32 μg/ml, and for gatifloxacin they were >32 μg/ml. Ciprofloxacin plus gatifloxacin showed synergy by the Etest method for 6 (19%) of the 31 P. aeruginosa isolates using a summation fractional inhibitory concentration of ≤0.5 for synergy. Synergy was demonstrated for 13/31 (42%) of isolates by time-kill assay. No antagonism was detected. The remaining isolates were indifferent to the combination. The Etest method and time-kill assay were 65% (20/31) concordant. The mechanism of the in vitro synergy may include P. aeruginosa ciprofloxacin efflux pump inhibition by gatifloxacin.

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 Correlation of Checkerboard Synergy Testing with Time-Kill Analysis and Clinical Outcomes of Extensively Drug-Resistant Acinetobacter baumannii Respiratory Infections

2016 ◽  
Vol 60 (11) ◽  
pp. 6892-6895 ◽  
Author(s):  
Derek N. Bremmer ◽  
Karri A. Bauer ◽  
Stephanie M. Pouch ◽  
Keelie Thomas ◽  
Debra Smith ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Clinical Outcomes ◽  
Clinical Utility ◽  
Respiratory Infections ◽  
Drug Resistant ◽  
Content Type ◽  
Extensively Drug Resistant ◽  
Time Kill ◽  
Synergy Testing

ABSTRACTWe tested 76 extensively drug-resistant (XDR)Acinetobacter baumanniiisolates by the checkerboard method using only wells containing serum-achievable concentrations (SACs) of drugs. Checkerboard results were correlated by time-kill assay and clinical outcomes. Minocycline-colistin was the best combinationin vitro, as it inhibited growth in one or more SAC wells in all isolates. Patients who received a combination that inhibited growth in one or more SAC wells demonstrated better microbiological clearance than those who did not (88% versus 30%;P= 0.025). The checkerboard platform may have clinical utility for XDRA. baumanniiinfections.

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 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 In Vitro Synergy of Daptomycin plus Rifampin against Enterococcus faecium Resistant to both Linezolid and Vancomycin

2005 ◽  
Vol 49 (12) ◽  
pp. 5166-5168 ◽  
Author(s):  
George Pankey ◽  
Deborah Ashcraft ◽  
Nalini Patel
Keyword(s):  
Enterococcus Faecium ◽  
Time Kill ◽  
Synergy Testing

ABSTRACT In vitro synergy testing of daptomycin plus rifampin was performed against 24 unique isolates of Enterococcus faecium resistant to both linezolid and vancomycin. Synergy testing showed that 21/24 (88%) were synergistic and 3/24 (12%) were indifferent by the Etest method. Time-kill assays revealed synergy for 18/24 (75%) and indifference for 6/24 (25%).

Sign in / Sign up

Export Citation Format

Share Document