scholarly journals Potent Synergy and Sustained Bactericidal Activity of a Vancomycin-Colistin Combination versus Multidrug-Resistant Strains of Acinetobacter baumannii

2010 ◽  
Vol 54 (12) ◽  
pp. 5316-5322 ◽  
Author(s):  
N. C. Gordon ◽  
K. Png ◽  
D. W. Wareham
Keyword(s):  
Health Care ◽  
Acinetobacter Baumannii ◽  
Multidrug Resistant ◽  
Clinical Use ◽  
Gram Negative ◽  
Resistant Strains ◽  
Bacterial Outer Membrane ◽  
Gram Negative Organisms ◽  
Time Kill ◽  
Emergence Of Resistance

ABSTRACT Multidrug-resistant Acinetobacter baumannii (MDRAB) presents an increasing challenge to health care. Although colistin has been used as a treatment of last resort, there is concern regarding its potential for toxicity and the emergence of resistance. The mechanism of action of colistin, however, raises the possibility of synergy with compounds that are normally inactive against Gram-negative organisms by virtue of the impermeability of the bacterial outer membrane. This study evaluated the effect of colistin combined with vancomycin on 5 previously characterized epidemic strains and 34 MDRAB clinical isolates by using time-kill assay, microdilution, and Etest methods. For all the isolates, significant synergy was demonstrated by at least one method, with reductions in the MIC of vancomycin from >256 μg/ml to ≤48 μg/ml for all strains after exposure to 0.5 μg/ml colistin. This raises the possibility of the clinical use of this combination for infections due to MDRAB, with the potential for doses lower than those currently used.

scholarly journals Synergistic Activity of Colistin-Containing Combinations against Colistin-ResistantEnterobacteriaceae

2018 ◽  
Vol 62 (10) ◽  
Author(s):  
Thea Brennan-Krohn ◽  
Alejandro Pironti ◽  
James E. Kirby
Keyword(s):  
Treatment Options ◽  
Multidrug Resistant ◽  
Synergistic Activity ◽  
Gram Negative ◽  
Content Type ◽  
Carbapenem Resistant ◽  
Resistant Strains ◽  
Bacterial Outer Membrane ◽  
Time Kill ◽  
Synergistic Combinations

ABSTRACTResistance to colistin, a polypeptide drug used as an agent of last resort for the treatment of infections caused by multidrug-resistant (MDR) and extensively drug-resistant (XDR) Gram-negative bacteria, including carbapenem-resistantEnterobacteriaceae(CRE), severely limits treatment options and may even transform an XDR organism into one that is pan-resistant. We investigated the synergistic activity of colistin in combination with 19 antibiotics against a collection of 20 colistin-resistantEnterobacteriaceaeisolates, 15 of which were also CRE. All combinations were tested against all strains using an inkjet printer-assisted digital dispensing checkerboard array, and the activities of those that demonstrated synergy by this method were evaluated against a single isolate in a time-kill synergy study. Eighteen of 19 combinations demonstrated synergy against two or more isolates, and the 4 most highly synergistic combinations (colistin combined with linezolid, rifampin, azithromycin, and fusidic acid) were synergistic against ≥90% of strains. Sixteen of 18 combinations (88.9%) that were synergistic in the checkerboard array were also synergistic in a time-kill study. Our findings demonstrate that colistin in combination with a range of antibiotics, particularly protein and RNA synthesis inhibitors, exhibits synergy against colistin-resistant strains, suggesting that colistin may exert a subinhibitory permeabilizing effect on the Gram-negative bacterial outer membrane even in isolates that are resistant to it. These findings suggest that colistin combination therapy may have promise as a treatment approach for patients infected with colistin-resistant XDR Gram-negative pathogens.

scholarly journals In Vitro Activity of the Histatin Derivative P-113 against Multidrug-Resistant Pathogens Responsible for Pneumonia in Immunocompromised Patients

2005 ◽  
Vol 49 (3) ◽  
pp. 1249-1252 ◽  
Author(s):  
Andrea Giacometti ◽  
Oscar Cirioni ◽  
Wojciech Kamysz ◽  
Giuseppina D'Amato ◽  
Carmela Silvestri ◽  
...  
Keyword(s):  
Multidrug Resistant ◽  
Vitro Activity ◽  
Immunocompromised Patients ◽  
In Vitro Activity ◽  
Beta Lactams ◽  
Gram Negative ◽  
Resistant Strains ◽  
Multidrug Resistant Pathogens ◽  
Gram Negative Organisms

ABSTRACT The in vitro activity of the histatin derivative P-113, alone or combined with eight antibiotics, was investigated against multidrug-resistant strains isolated from clinical specimens of immunocompromised patients with pneumonia. The gram-negative isolates were susceptible to P-113. S. aureus showed less susceptibility. Synergy was demonstrated when P-113 was combined with beta-lactams against gram-negative organisms.

scholarly journals In Vitro Antibacterial Activity of Cefiderocol against Multidrug-Resistant Acinetobacter baumannii

2021 ◽  
Author(s):  
Jacinda C. Abdul-Mutakabbir ◽  
Logan Nguyen ◽  
Philip T. Maassen ◽  
Kyle C. Stamper ◽  
Razieh Kebriaei ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Susceptibility Testing ◽  
Inhibitory Concentration ◽  
Multidrug Resistant ◽  
Synergistic Activity ◽  
Strong Activity ◽  
Gram Negative ◽  
In Vitro Antibacterial Activity ◽  
Time Kill

Cefiderocol (CFDC), a novel siderophore cephalosporin, demonstrates strong activity against multidrug-resistant (MDR) Acinetobacter baumannii. Limited studies have evaluated CFDC alone and in combination with other Gram-negative antibiotics against MDR A. baumannii isolates. Susceptibility testing revealed lower CFDC minimum inhibitory concentration (MIC) values than the comparator Gram-negative agents (87% of MICs ≤ 4mg/L). Six isolates, with elevated CFDC MICs (16-32 mg/L), were selected for further experiments. Time-kill analyses presented with synergistic activity and beta-lactamase inhibitors increased CFDC susceptibility in each of the isolates.

scholarly journals Global Assessment of the Activity of Tigecycline against Multidrug-Resistant Gram-Negative Pathogens between 2004 and 2014 as Part of the Tigecycline Evaluation and Surveillance Trial

mSphere ◽  
2017 ◽  
Vol 2 (1) ◽  
Author(s):  
Anna Giammanco ◽  
Cinzia Calà ◽  
Teresa Fasciana ◽  
Michael J. Dowzicky
Keyword(s):  
Health Care ◽  
Pseudomonas Aeruginosa ◽  
Multidrug Resistance ◽  
Acinetobacter Baumannii ◽  
Multidrug Resistant ◽  
Current Status ◽  
Gram Negative ◽  
Content Type ◽  
Trial Test

ABSTRACT Multidrug resistance among bacterial pathogens is an ongoing global problem and renders antimicrobial agents ineffective at treating bacterial infections. In the health care setting, infections caused by multidrug-resistant (MDR) Gram-negative bacteria can cause increased mortality, longer hospital stays, and higher treatments costs. The aim of the Tigecycline Evaluation and Surveillance Trial (TEST) is to assess the in vitro antimicrobial activities of tigecycline and other contemporary agents against clinically relevant pathogens. This paper presents antimicrobial activity data from the TEST study between 2004 and 2014 and examines global rates of MDR Gram-negative isolates, including Acinetobacter baumannii, Pseudomonas aeruginosa, and members of the Enterobacteriaceae, during this time. Our results show that tigecycline retained in vitro activity against many MDR Gram-negative pathogens over the study period, while rates of MDR A. baumannii increased globally. Using these findings, we hope to highlight the current status of multidrug resistance in medical facilities worldwide. Multidrug-resistant (MDR) Gram-negative organisms are a burden on the global health care system. The Tigecycline Evaluation and Surveillance Trial (TEST) is an ongoing global study designed to monitor the in vitro activities of tigecycline and a panel of marketed antimicrobials against a range of clinically significant pathogens. In this study, in vitro data are presented for MDR Acinetobacter baumannii, Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Enterobacter aerogenes, and Enterobacter cloacae isolates collected from 2004 to 2014. In total, 13% (21,967/170,759) of isolates displayed multidrug resistance globally, with the highest rates recorded among A. baumannii (overall rate, 44% [8,294/18,741], increasing from 23% [309/1,323] in 2004 to 63% [447/712] in 2014). Other multidrug resistance rates ranged from 2.5% for K. oxytoca (203/8,000) to 12% for P. aeruginosa and K. pneumoniae (3,951/32,786 and 3,895/32,888, respectively), and rates among these pathogens remained stable during the study period. Against MDR E. coli, Klebsiella spp., and E. aerogenes, the lowest rates of resistance were to tigecycline (0.2%, 6%, and 12%, respectively), and the lowest MIC90 value against A. baumannii was observed for tigecycline (2 mg/liter; MIC range, ≤0.008 to ≥32 mg/liter). The only significant change in resistance to tigecycline during the study period was for MDR E. coli (P < 0.01), among which eight resistant isolates were identified globally from 2009 to 2013. In summary, these results show that tigecycline retained in vitro activity against the majority of MDR Gram-negative organisms presented here, but the rising rates of MDR A. baumannii highlight the need for the continued monitoring of global multidrug resistance. IMPORTANCE Multidrug resistance among bacterial pathogens is an ongoing global problem and renders antimicrobial agents ineffective at treating bacterial infections. In the health care setting, infections caused by multidrug-resistant (MDR) Gram-negative bacteria can cause increased mortality, longer hospital stays, and higher treatments costs. The aim of the Tigecycline Evaluation and Surveillance Trial (TEST) is to assess the in vitro antimicrobial activities of tigecycline and other contemporary agents against clinically relevant pathogens. This paper presents antimicrobial activity data from the TEST study between 2004 and 2014 and examines global rates of MDR Gram-negative isolates, including Acinetobacter baumannii, Pseudomonas aeruginosa, and members of the Enterobacteriaceae, during this time. Our results show that tigecycline retained in vitro activity against many MDR Gram-negative pathogens over the study period, while rates of MDR A. baumannii increased globally. Using these findings, we hope to highlight the current status of multidrug resistance in medical facilities worldwide.

scholarly journals 698. In vitro Activity of a New Generation Oxopyrazole Antibiotic Against Multidrug-Resistant Gram-Negative Bacilli

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S315-S316
Author(s):  
Joel Goldberg ◽  
Christopher Bethel ◽  
Andrea M Hujer ◽  
Kristine Hujer ◽  
Steven Marshall ◽  
...  
Keyword(s):  
Multidrug Resistant ◽  
Gram Negative ◽  
Penicillin Binding Proteins ◽  
E Coli ◽  
New Class ◽  
Resistant Strains ◽  
Gram Negative Organisms ◽  
New Generation ◽  
Hospital Acquired

Abstract Background Multidrug-resistant Gram-negative bacilli (MDRGNB) are emerging as a challenging cause of hospital-acquired infections and represent a critical need for innovative antibacterial development. New oxopyrazole agents targeting penicillin-binding proteins (PBPs) based on a non-β-lactam core and incorporating a siderophore moiety (Figure 1) which facilitates transport to the periplasm are being developed that show promise against Gram-negative organisms including multidrug-resistant strains of E. coli, K. pneumoniae and P. aeruginosa. Methods YU253434, an example of this new class of antibacterials, was investigated in vitro. Minimum inhibitory concentrations (MICs) were determined by broth microdilution against a representative panel comprising 15 strains each of E. coli, K. pneumoniae and P. aeruginosa, which contain extended-spectrum β-lactamase (ESBL) and/or carbapenemases genes.All studies were performed according to current Clinical & Laboratory Standards Institute (CLSI) guidelines using iron-depleted media. Ceftazidime breakpoints were arbitrability chosen as a reference for YU253434 (susceptibilities ≤4 μg/mL for Enterobacteriaceae and ≤8 μg/mL for P. aeruginosa). Results MIC testing (Figures 2–4) against E. coli showed 11 strains were YU253434 susceptible (compared with 6 for ceftazidime, and 3 for imipenem); against K. pneumoniae 13 strains were YU253434 susceptible (compared with 2 for ceftazidime and 6 for imipenem); against P. aeruginosa 10 strains were YU253434 susceptible (compared with 0 for both ceftazidime and imipenem). There appeared to be no correlation between YU253434 resistance and the presence of specific lactamase genes. Conclusion YU253434, a new generation oxopyrazole antibiotic, demonstrated promising in vitro potency against a panel of E. coli, K. pneumonia, and P. aeruginosa strains which contain ESBL and/or carbapenemases genes. Disclosures All authors: No reported disclosures.

scholarly journals Colistin and Fusidic Acid, a Novel Potent Synergistic Combination for Treatment of Multidrug-Resistant Acinetobacter baumannii Infections

2015 ◽  
Vol 59 (8) ◽  
pp. 4544-4550 ◽  
Author(s):  
Lynette M. Phee ◽  
Jonathan W. Betts ◽  
Binutha Bharathan ◽  
David W. Wareham
Keyword(s):  
Acinetobacter Baumannii ◽  
Fusidic Acid ◽  
Multidrug Resistant ◽  
Content Type ◽  
Low Concentrations ◽  
Resistant Strains ◽  
Time Kill ◽  
Susceptibility Breakpoint ◽  
Selection Of

ABSTRACTThe spread of multidrug-resistantAcinetobacter baumannii(MDRAB) has led to the renaissance of colistin (COL), often the only agent to which MDRAB remains susceptible. Effective therapy with COL is beset with problems due to unpredictable pharmacokinetics, toxicity, and the rapid selection of resistance. Here, we describe a potent synergistic interaction when COL was combined with fusidic acid (FD) againstA. baumannii. Synergyin vitrowas assessed against 11 MDRAB isolates using disc diffusion, checkerboard methodology (fractional inhibitory concentration index [FICI] of ≤ 0.5, susceptibility breakpoint index [SBPI] of >2), and time-kill methodology (≥2 log10CFU/ml reduction). The ability of FD to limit the emergence of COL resistance was assessed in the presence and absence of each drug alone and in combination. Synergy was demonstrated against all strains, with an average FICI and SBPI of 0.064 and 78.85, respectively. In time-kill assays, COL-FD was synergistic and rapidly bactericidal, including against COL-resistant strains. Fusidic acid prevented the emergence of COL resistance, which was readily selected with COL alone. This is the first description of a novel COL-FD regimen for the treatment of MDRAB. The combination was effective at low concentrations, which should be therapeutically achievable while limiting toxicity. Further studies are warranted to determine the mechanism underlying the interaction and the suitability of COL-FD as an unorthodox therapy for the treatment of multidrug-resistant Gram-negative infections.

scholarly journals Effects of Efflux Pump Inhibitors on Colistin Resistance in Multidrug-Resistant Gram-Negative Bacteria

2016 ◽  
Vol 60 (5) ◽  
pp. 3215-3218 ◽  
Author(s):  
Wentao Ni ◽  
Yanjun Li ◽  
Jie Guan ◽  
Jin Zhao ◽  
Junchang Cui ◽  
...  
Keyword(s):  
Stenotrophomonas Maltophilia ◽  
Efflux Pump ◽  
Multidrug Resistant ◽  
Gram Negative Bacteria ◽  
Colistin Resistance ◽  
Gram Negative ◽  
Content Type ◽  
Resistant Strains ◽  
Efflux Pump Inhibitors ◽  
Time Kill

ABSTRACTWe tested the effects of various putative efflux pump inhibitors on colistin resistance in multidrug-resistant Gram-negative bacteria. Addition of 10 mg/liter cyanide 3-chlorophenylhydrazone (CCCP) to the test medium could significantly decrease the MICs of colistin-resistant strains. Time-kill assays showed CCCP could reverse colistin resistance and inhibit the regrowth of the resistant subpopulation, especially inAcinetobacter baumanniiandStenotrophomonas maltophilia. These results suggest colistin resistance in Gram-negative bacteria can be suppressed and reversed by CCCP.

scholarly journals Evaluation of the Synergy of Ceftazidime-Avibactam in Combination with Meropenem, Amikacin, Aztreonam, Colistin, or Fosfomycin against Well-Characterized Multidrug-Resistant Klebsiella pneumoniae and Pseudomonas aeruginosa

2019 ◽  
Vol 63 (8) ◽  
Author(s):  
Sandra Mikhail ◽  
Nivedita B. Singh ◽  
Razieh Kebriaei ◽  
Seth A. Rice ◽  
Kyle C. Stamper ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Klebsiella Pneumoniae ◽  
Multidrug Resistant ◽  
Health Concern ◽  
Content Type ◽  
Carbapenem Resistant ◽  
Sds Page ◽  
Gram Negative Organisms ◽  
Time Kill ◽  
Emergence Of Resistance

ABSTRACT Multidrug-resistant (MDR) Gram-negative organisms are a major health concern due to lack of effective therapy. Emergence of resistance to newer agents like ceftazidime-avibactam (CZA) further magnifies the problem. In this context, combination therapy of CZA with other antimicrobials may have potential in treating these pathogens. Unfortunately, there are limited data regarding these combinations. Therefore, the objective of this study was to evaluate CZA in combination with amikacin (AMK), aztreonam (AZT), colistin (COL), fosfomycin (FOS), and meropenem (MEM) against 21 carbapenem-resistant Klebsiella pneumoniae and 21 MDR Pseudomonas aeruginosa strains. The potential for synergy was evaluated via MIC combination evaluation and time-kill assays. All strains were further characterized by whole-genome sequencing, quantitative real-time PCR, and SDS-PAGE analysis to determine potential mechanisms of resistance. Compared to CZA alone, we observed a 4-fold decrease in CZA MICs for a majority of K. pneumoniae strains and at least a 2-fold decrease for most P. aeruginosa isolates in the majority of combinations tested. In both P. aeruginosa and K. pneumoniae strains, CZA in combination with AMK or AZT was synergistic (≥2.15-log10 CFU/ml decrease). CZA-MEM was effective against P. aeruginosa and CZA-FOS was effective against K. pneumoniae. Time-kill analysis also revealed that the synergy of CZA with MEM or AZT may be due to the previously reported restoration of MEM or AZT activity against these organisms. Our findings show that CZA in combination with these antibiotics has potential for therapeutic options in difficult to treat pathogens. Further evaluation of these combinations is warranted.

scholarly journals In vitro antimicrobials activity against endemic Acinetobacter baumannii multiresistant clones

2010 ◽  
Vol 4 (03) ◽  
pp. 164-167 ◽  
Author(s):  
Carlos Hernan Rodriguez ◽  
Alejandra De Ambrosio ◽  
Milena Bajuk ◽  
Mariela Spinozzi ◽  
Marcela Nastro ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Buenos Aires ◽  
Multidrug Resistant ◽  
University Hospital ◽  
Pfge Type ◽  
The World ◽  
Resistant Strains ◽  
Resistant Mutants ◽  
Emergence Of Resistance

Background: Multidrug-resistant strains of Acinetobacter baumannii have been reported increasingly around the world. The administration of an association of antibiotics has been proposed to create an active combination and to prevent the emergence of resistance. Methodology: The activity of colistin, rifampicin, gentamicin, imipenem and their associations was evaluated by means of killing curves in fourteen isolates belonging to three endemic PFGE types, in a university hospital of Buenos Aires city. The 14 isolates were selected on the basis of different mechanisms responsible for resistance to carbapenems and different susceptibility to colistin. Results: The mechanism responsible for the resistance to imipenem was the production of OXA-23 and OXA-58 carbapenemases. Heteroresistance to colistin was observed in six isolates. The associations colistin-rifampicin and colistin-imipenem were synergistic in heteroresistant isolates and prevented the development of colistin-resistant mutants. The association imipenem-gentamicin was bactericidal in gentamicin susceptible isolates, whereas the association imipenem-rifampicin was always indifferent. Conclusion: The antimicrobial activity and the presence of synergy are related to the antimicrobials' susceptibilities irrespective of the PFGE type or the OXA-carbapenemase produced.

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