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.

scholarly journals In VitroAntibiotic Synergy in Extensively Drug-ResistantAcinetobacter baumannii: the Effect of Testing by Time-Kill, Checkerboard, and Etest Methods

2010 ◽  
Vol 55 (1) ◽  
pp. 436-438 ◽  
Author(s):  
Thean Yen Tan ◽  
Tze Peng Lim ◽  
Winnie Hui Ling Lee ◽  
Suranthran Sasikala ◽  
Li Yang Hsu ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Polymyxin B ◽  
Drug Resistant ◽  
Extensively Drug Resistant ◽  
Resistant Strains ◽  
Time Kill

ABSTRACTThis study examined thein vitroeffects of polymyxin B, tigecycline, and rifampin combinations on 16 isolates of extensively drug-resistantAcinetobacter baumannii, including four polymyxin-resistant strains.In vitrosynergy was demonstrated in 19 (40%) of a possible 48 isolate-antibiotic combinations by time-kill methods, 8 (17%) by checkerboard methods, and only 1 (2%) by Etest methods. There was only slight agreement between Etest and checkerboard methods and no agreement between results obtained by other methods.

scholarly journals In VitroActivity of Polymyxin B in Combination with Various Antibiotics against Extensively Drug-Resistant Enterobacter cloacae with Decreased Susceptibility to Polymyxin B

2016 ◽  
Vol 60 (9) ◽  
pp. 5238-5246 ◽  
Author(s):  
Yiying Cai ◽  
Tze-Peng Lim ◽  
Jocelyn Teo ◽  
Suranthran Sasikala ◽  
Winnie Lee ◽  
...  
Keyword(s):  
Enterobacter Cloacae ◽  
Polymyxin B ◽  
Infection Model ◽  
Drug Resistant ◽  
Content Type ◽  
Extensively Drug Resistant ◽  
Dosing Regimens ◽  
Time Kill ◽  
Emergence Of Resistance

ABSTRACTAgainst extensively drug-resistant (XDR)Enterobacter cloacae, combination antibiotic therapy may be the only option. We investigated the activity of various antibiotics in combination with polymyxin B using time-kill studies (TKS). TKS were conducted with four nonclonal XDRE. cloacaeisolates with 5 log10CFU/ml bacteria against maximum, clinically achievable concentrations of polymyxin B alone and in two-drug combinations with 10 different antibiotics. A hollow-fiber infection model (HFIM) simulating clinically relevant polymyxin B and tigecycline dosing regimens was conducted for two isolates over 240 h. Emergence of resistance was quantified using antibiotic-containing (3× MIC) media. Biofitness and stability of resistant phenotypes were determined. All XDRE. cloacaeisolates were resistant to all antibiotics except for polymyxin B (polymyxin B MIC, 1 to 4 mg/liter). All isolates harbored metallo-β-lactamases (two with NDM-1, two with IMP-1). In single TKS, all antibiotics alone demonstrated regrowth at 24 h, except amikacin against two strains and polymyxin B and meropenem against one strain each. In combination TKS, only polymyxin B plus tigecycline was bactericidal against all four XDRE. cloacaeisolates at 24 h. In HFIM, tigecycline and polymyxin B alone did not exhibit any killing activity. Bactericidal kill was observed at 24 h for both isolates for polymyxin B plus tigecycline; killing was sustained for one isolate but regrowth was observed for the second. Phenotypically stable resistant mutants with reducedin vitrogrowth rates were observed. Polymyxin B plus tigecycline is a promising combination against XDRE. cloacae. However, prolonged and indiscriminate use can result in resistance emergence.

scholarly journals In VitroActivities of Novel Antimicrobial Combinations against Extensively Drug-Resistant Acinetobacter baumannii

2015 ◽  
Vol 59 (12) ◽  
pp. 7316-7319 ◽  
Author(s):  
J. Córdoba ◽  
N. M. Coronado-Álvarez ◽  
D. Parra ◽  
J. Parra-Ruiz
Keyword(s):  
Acinetobacter Baumannii ◽  
Limit Of Detection ◽  
Single Agent ◽  
Drug Resistant ◽  
Content Type ◽  
Development Of Resistance ◽  
Extensively Drug Resistant ◽  
Combination Regimens ◽  
Emergence Of Resistance

ABSTRACTExtensively drug-resistant (XDR)Acinetobacterspp. have emerged as a cause of nosocomial infections, especially under conditions of intensive care. Unfortunately, resistance to colistin is increasing and there is a need for new therapeutic options. We aimed to study the effect of some novel combinations against XDRAcinetobacter baumanniiin anin vitropharmacokinetics-pharmacodynamics (PK/PD) model. Three nonrelated clinical strains of XDRA. baumanniiwere investigated. Antibiotic-simulated regimens were colistin at 3 MU every 8 h (q8h) (first dose, 6 MU), daptomycin at 10 mg/kg of body weight q24h, imipenem at 1 g q8h, and ertapenem at 1 g q24h. Combination regimens included colistin plus daptomycin, colistin plus imipenem, and imipenem plus ertapenem. Samples were obtained at 0, 1, 2, 4, 8, and 24 h. Among the single-agent regimens, only the colistin regimen resulted in significant reductions in log10CFU per milliliter compared to the control for all the strains tested. Although colistin achieved bactericidal activity at 4 h, it was not able to reach the limit of detection (1 log10CFU/ml). One strain had significant regrowth at 24 h without the emergence of resistance. Daptomycin-colistin combinations led to a significant reduction in levels of log10CFU per milliliter that were better than those achieved with colistin as a single-agent regimen, reaching the limit of detection at 24 h against all the strains. The combination of imipenem plus ertapenem outperformed the colistin regimen, although the results did not reach the limit of detection, with significant regrowth at 24 h. Similarly, colistin-plus-imipenem combinations reduced the levels of log10CFU per milliliter at 8 h, with significant regrowth at 24 h but with development of resistance to colistin. We have shown some potentially useful alternatives for the treatment of extensively drug-resistantA. baumannii. Among them, the daptomycin-colistin combination was the most effective and should be investigated in future studies.

scholarly journals Correlation of In Vitro Combination Antimicrobial Drug Therapy With Clinical Outcomes Among Extensively Drug-Resistant Acinetobacter baumannii and Pseudomonas aeruginosa

2015 ◽  
Vol 2 (suppl_1) ◽  
Author(s):  
Derek Bremmer ◽  
Karri A. Bauer ◽  
Stephanie Pouch ◽  
Keelie Thomas (n/a) ◽  
Preeti Pancholi ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Drug Therapy ◽  
Acinetobacter Baumannii ◽  
Clinical Outcomes ◽  
Antimicrobial Drug ◽  
Drug Resistant ◽  
Extensively Drug Resistant

scholarly journals Efficacy of Ceftolozane-Tazobactam in Combination with Colistin against Extensively Drug-Resistant Pseudomonas aeruginosa, Including High-Risk Clones, in an In Vitro Pharmacodynamic Model

2020 ◽  
Vol 64 (4) ◽  
Author(s):  
María Montero ◽  
Sandra Domene Ochoa ◽  
Carla López-Causapé ◽  
Brian VanScoy ◽  
Sonia Luque ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
High Risk ◽  
Therapeutic Option ◽  
Drug Resistant ◽  
Chemostat Model ◽  
Content Type ◽  
Extensively Drug Resistant ◽  
Spanish Study ◽  
Time Kill

ABSTRACT Combination therapy is an attractive therapeutic option for extensively drug-resistant (XDR) Pseudomonas aeruginosa infections. Colistin has been the only treatment available for these infections for many years, but its results are suboptimal. Ceftolozane-tazobactam (C/T) is a newly available therapeutic option that has shown good antipseudomonal activity, even against a number of XDR P. aeruginosa strains. However, data about combinations containing C/T are scarce. The aim of this study was to analyze the activity of C/T and colistin alone and in combination against a collection of XDR P. aeruginosa strains containing 24 representative clinical isolates from a multicentre Spanish study. Twenty-four time-kill experiments performed over 24 h were conducted in duplicate to determine the effects of colistin and C/T alone and combined. An in vitro pharmacodynamic chemostat model then was used to validate this combination against three selected XDR P. aeruginosa ST175 isolates with different susceptibility levels to C/T. Static time-kill assays demonstrated superior synergistic or additive effect for C/T plus colistin against 21 of the 24 isolates studied. In the in vitro dynamic pharmacokinetic/pharmacodynamic (PK/PD) model, the C/T regimen of 2/1 g every 8 h with a steady-state concentration of 2 mg/liter colistin effectively suppressed the bacterial growth at 24 h. Additive or synergistic interactions were observed for C/T plus colistin against XDR P. aeruginosa strains and particularly against C/T-resistant strains. C/T plus colistin may be a useful treatment for XDR P. aeruginosa infections, including those caused by high risk-clones resistant to C/T.

scholarly journals Synergy Testing by Etest, Microdilution Checkerboard, and Time-Kill Methods for Pan-Drug-Resistant Acinetobacter baumannii

2010 ◽  
Vol 54 (11) ◽  
pp. 4678-4683 ◽  
Author(s):  
Madhuri M. Sopirala ◽  
Julie E. Mangino ◽  
Wondwossen A. Gebreyes ◽  
Beth Biller ◽  
Tammy Bannerman ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Drug Combination ◽  
Active Drug ◽  
Fixed Ratio ◽  
Ratio Method ◽  
Drug Resistant ◽  
Time Kill ◽  
Synergy Testing ◽  
Medium Method

ABSTRACT Pan-drug-resistant (PDR) Acinetobacter baumannii is an important nosocomial pathogen that poses therapeutic challenges. Tigecycline alone or in combination with agents such as colestimethate, imipenem, and/or amikacin is being used clinically to treat PDR A. baumannii infections. The purpose of this study was to compare in vitro susceptibility testing by epsilometric (Etest) methods and the checkerboard (CB) method with testing by time-kill analysis. PDR A. baumannii clinical strains representing eight unique pulsed-field gel electrophoresis clones selected from a total of 32 isolates were tested in vitro with tigecycline, colestimethate, imipenem, and amikacin in single- and two-drug combinations by using two different methods of Etest (with a fixed ratio method [method 1] and with the incorporation of the active drug in medium [method 2]) and by using CB. The three-drug combination of imipenem, tigecycline, and amikacin was also tested by CB. These results were compared to time-kill results. Synergy was consistently detected with the imipenem plus colestimethate and tigecycline plus imipenem combinations. The Etest method with active drug incorporated into the agar allowed us to detect synergy even in the presence of the active drug and was more comparable to CB and time-kill tests. Synergy was detected with the three-drug combination of imipenem, tigecycline, and amikacin by both CB and time-kill methods among several tested clones. These findings indicate the utility of synergy testing to predict activity of specific antibiotic combinations against PDR A. baumannii.

scholarly journals SPR741, an Antibiotic Adjuvant, Potentiates the In Vitro and In Vivo Activity of Rifampin against Clinically Relevant Extensively Drug-Resistant Acinetobacter baumannii

2017 ◽  
Vol 61 (12) ◽  
Author(s):  
Daniel V. Zurawski ◽  
Alexandria A. Reinhart ◽  
Yonas A. Alamneh ◽  
Michael J. Pucci ◽  
Yuanzheng Si ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Ventilator Associated Pneumonia ◽  
Drug Resistant ◽  
Proof Of Concept ◽  
Bacterial Burden ◽  
Content Type ◽  
Extensively Drug Resistant ◽  
Animal Survival

ABSTRACT Acinetobacter baumannii is responsible for 10% of all nosocomial infections and has >50% mortality rates when causing ventilator-associated pneumonia. In this proof-of-concept study, we evaluated SPR741, an antibiotic adjuvant that permeabilizes the Gram-negative membrane, in combination with rifampin against AB5075, an extensively drug-resistant (XDR) A. baumannii strain. In standard in vitro assays and in a murine pulmonary model, we found that this drug combination can significantly reduce bacterial burden and promote animal survival despite an aggressive infection.

scholarly journals In vitro synergistic activity of the sulbactam/avibactam combination against extensively drug-resistant Acinetobacter baumannii

2020 ◽  
Vol 69 (7) ◽  
pp. 928-931 ◽  
Author(s):  
Carlos Hernán Rodriguez ◽  
Adriana Brune ◽  
Marcela Nastro ◽  
Carlos Vay ◽  
Angela Famiglietti
Keyword(s):  
Acinetobacter Baumannii ◽  
Type Species ◽  
Synergistic Activity ◽  
Drug Resistant ◽  
Disc Diffusion ◽  
Content Type ◽  
Link Type ◽  
Extensively Drug Resistant ◽  
Synergy Test ◽  
Time Kill

Introduction. The therapeutic options to treat Acinetobacter baumannii infections are very limited. Aim. Our aim was to evaluate the activity of sulbactam combined directly with avibactam or the ampicillin-sulbactam/ceftazidime-avibactam combination against extensively drug-resistant A. baumannii isolates. Methodology. Extensively drug-resistant A. baumannii isolates (n=127) collected at several South American hospitals were studied. Synergy with the sulbactam/avibactam combination was assessed in all isolates using the agar dilution method. Avibactam was used at a fixed concentration of 4 mg l−1. A disc diffusion synergy test was also performed. Synergy by a time-kill experiment was performed in a selected isolate. Results. Synergy with sulbactam/avibactam was demonstrated in 124 isolates and it showed MIC values ≤4 mg l−1. This synergy was not detected in the three New Delhi metallo-β-lactamase-harbouring isolates. Similar results were observed with the disc diffusion synergy test of ampicillin-sulbactam/ceftazidime-avibactam. In the time-kill experiments, sulbactam/avibactam showed a rapid synergistic and bactericidal activity in ampicillin-sulbactam-resistant isolates. Conclusions. This study demonstrated that the sulbactam/avibactam combination displayed synergistic activity against A. baumannii isolates. This synergy was observed when both inhibitors were also used as part of the commercially available combinations: ampicillin-sulbactam and ceftazidime-avibactam.

scholarly journals In VitroActivity of the Novel Antimicrobial Peptide Dendrimer G3KL against Multidrug-Resistant Acinetobacter baumannii and Pseudomonas aeruginosa

2015 ◽  
Vol 59 (12) ◽  
pp. 7915-7918 ◽  
Author(s):  
João Pires ◽  
Thissa N. Siriwardena ◽  
Michaela Stach ◽  
Regula Tinguely ◽  
Sara Kasraian ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Antimicrobial Peptide ◽  
Acinetobacter Baumannii ◽  
Multidrug Resistant ◽  
Drug Resistant ◽  
The Novel ◽  
Content Type ◽  
Extensively Drug Resistant ◽  
Peptide Dendrimer

ABSTRACTThein vitroactivity of the novel antimicrobial peptide dendrimer G3KL was evaluated against 32Acinetobacter baumannii(including 10 OXA-23, 7 OXA-24, and 11 OXA-58 carbapenemase producers) and 35Pseudomonas aeruginosa(including 18 VIM and 3 IMP carbapenemase producers) strains and compared to the activities of standard antibiotics. Overall, both species collections showed MIC50/90values of 8/8 μg/ml and minimum bactericidal concentrations at which 50% or 90% of strains tested are killed (MBC50/90) of 8/8 μg/ml. G3KL is a promising molecule with antibacterial activity against multidrug-resistant and extensively drug-resistantA. baumanniiandP. aeruginosaisolates.

scholarly journals Complete Genome Sequences of Four Extensively Drug-Resistant Acinetobacter baumannii Isolates from Thailand

2020 ◽  
Vol 9 (40) ◽  
Author(s):  
Peechanika Chopjitt ◽  
Thidathip Wongsurawat ◽  
Piroon Jenjaroenpun ◽  
Parichart Boueroy ◽  
Rujirat Hatrongjit ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Complete Genome ◽  
Sequence Type ◽  
Clinical Isolates ◽  
Drug Resistant ◽  
Genome Sequences ◽  
Content Type ◽  
Type Isolate ◽  
Resistant Genes ◽  
Extensively Drug Resistant

ABSTRACT Here, we report the complete genome sequences of four clinical isolates of extensively drug-resistant Acinetobacter baumannii (XDRAB), isolated in Thailand. These results revealed multiple antimicrobial-resistant genes, each involving two sequence type 16 (ST16) isolates, ST2, and a novel sequence type isolate, ST1479.

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