scholarly journals Activity of Eravacycline against Enterobacteriaceae and Acinetobacter baumannii, Including Multidrug-Resistant Isolates, from New York City

2014 ◽  
Vol 59 (3) ◽  
pp. 1802-1805 ◽  
Author(s):  
Marie Abdallah ◽  
Olawole Olafisoye ◽  
Christopher Cortes ◽  
Carl Urban ◽  
David Landman ◽  
...  
Keyword(s):  
New York ◽  
New York City ◽  
Acinetobacter Baumannii ◽  
York City ◽  
Enterobacter Aerogenes ◽  
Enterobacter Cloacae ◽  
Multidrug Resistant ◽  
Gram Negative ◽  
Content Type

ABSTRACTEravacycline demonstratedin vitroactivity against a contemporary collection of more than 4,000 Gram-negative pathogens from New York City hospitals, with MIC50/MIC90values, respectively, forEscherichia coliof 0.12/0.5 μg/ml,Klebsiella pneumoniaeof 0.25/1 μg/ml,Enterobacter aerogenesof 0.25/1 μg/ml,Enterobacter cloacae0.5/1 μg/ml, andAcinetobacter baumanniiof 0.5/1 μg/ml. Activity was retained against multidrug-resistant isolates, including those expressing KPC and OXA carbapenemases. ForA. baumannii, eravacycline MICs correlated with increased expression of theadeBgene.

scholarly journals Activity of Meropenem with a Novel Broader-Spectrum β-Lactamase Inhibitor, WCK 4234, against Gram-Negative Pathogens Endemic to New York City

2019 ◽  
Vol 64 (1) ◽  
Author(s):  
Alejandro Iregui ◽  
Zeb Khan ◽  
David Landman ◽  
John Quale
Keyword(s):  
New York ◽  
New York City ◽  
York City ◽  
Multidrug Resistant ◽  
Resistance Mechanisms ◽  
Gram Negative ◽  
Content Type ◽  
Carbapenem Resistant ◽  
Lactamase Inhibitor

ABSTRACT WCK 4234 is a novel diazabicyclooctane with potent inhibitory activity against class A and D carbapenemases and class C enzymes. We examined the in vitro activity of meropenem plus WCK 4234 (4 or 8 μg/ml) against Gram-negative pathogens from New York City. Three groups of isolates were analyzed: a contemporary collection of isolates, a collection of known carbapenem-resistant isolates, and a collection of isolates with defined resistance mechanisms. From the contemporary collection, we found (i) that all Enterobacteriaceae were susceptible to meropenem plus WCK 4234, (ii) that susceptibility rates for Acinetobacter baumannii were 56.5% for meropenem alone, 82.6% with 4 μg/ml WCK 4234, and 95.7% with 8 μg/ml WCK 4234, and (iii) that WCK 4234 had a modest effect on susceptibility of Pseudomonas aeruginosa. Against a collection of carbapenem-resistant isolates, the addition of WCK 4234 to meropenem (i) restored meropenem susceptibility against Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae isolates, (ii) improved susceptibility against A. baumannii, and (iii) had a negligible effect against P. aeruginosa. When tested against isolates with defined mechanisms of resistance, MICs of meropenem plus WCK 4234 were higher for K. pneumoniae with blaKPC albeit well below the susceptibility breakpoint; efflux systems or porins did not correlate with susceptibility. For A. baumannii, MICs of meropenem plus WCK 4234 did not correlate with efflux systems, outer membrane protein, blaampC, or blaoxa-51; however, MICs were higher in isolates with extended-spectrum β-lactamases (ESBLs). For P. aeruginosa, isolates with relatively higher MICs of meropenem plus WCK 4234 had increased expression of ampC. WCK 4234 is a potent β-lactamase inhibitor that, when combined with meropenem, displays promising activity against multidrug-resistant pathogens.

scholarly journals Activity of Meropenem Combined with RPX7009, a Novel β-Lactamase Inhibitor, against Gram-Negative Clinical Isolates in New York City

2015 ◽  
Vol 59 (8) ◽  
pp. 4856-4860 ◽  
Author(s):  
Amabel Lapuebla ◽  
Marie Abdallah ◽  
Olawole Olafisoye ◽  
Christopher Cortes ◽  
Carl Urban ◽  
...  
Keyword(s):  
New York ◽  
New York City ◽  
York City ◽  
Carbapenem Resistance ◽  
Multidrug Resistant ◽  
Clinical Isolates ◽  
Gram Negative ◽  
Content Type ◽  
Lactamase Inhibitor

ABSTRACTMultidrug-resistantKlebsiella pneumoniaecarbapenemase (KPC)-producingEnterobacteriaceaeare endemic to hospitals in New York City and other regions. RPX7009 is a novel β-lactamase inhibitor with activity against serine carbapenemases. We tested the activity of meropenem plus RPX7009 against 4,500 recent Gram-negative clinical isolates from 11 New York City hospitals. The meropenem-RPX7009 combination was found to have excellentin vitroactivity againstEscherichia coli,K. pneumoniae, andEnterobacterspp., including multidrug-resistant (MDR) KPC-producing strains. Overall, 131/133 (98.5%) KPC-producingEnterobacteriaceaestrains were inhibited by meropenem (≤1 μg/ml) plus RPX7009 (8 μg/ml). In a limited number of strains, the combination appeared to have reduced activity against KPC-producingK. pneumoniaeisolates with diminishedompK35andompK36expression. The addition of RPX7009 did not affect the activity of meropenem againstAcinetobacter baumanniiandPseudomonas aeruginosa. The meropenem-RPX7009 combination shows promise as a novel agent against KPC-producingEnterobacteriaceaeand deserves further study. Other approaches will be needed to address multidrug-resistantA. baumanniiandP. aeruginosa, which typically possess different mechanisms of carbapenem resistance.

scholarly journals Activity of Imipenem with Relebactam against Gram-Negative Pathogens from New York City

2015 ◽  
Vol 59 (8) ◽  
pp. 5029-5031 ◽  
Author(s):  
Amabel Lapuebla ◽  
Marie Abdallah ◽  
Olawole Olafisoye ◽  
Christopher Cortes ◽  
Carl Urban ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
New York ◽  
Pseudomonas Aeruginosa ◽  
New York City ◽  
Klebsiella Pneumoniae ◽  
York City ◽  
Multidrug Resistant ◽  
Gram Negative ◽  
Content Type ◽  
Added Benefit

ABSTRACTImipenem with relebactam was active againstEscherichia coli,Klebsiella pneumoniae, andEnterobacterspp., includingK. pneumoniaecarbapenemase (KPC)-producing isolates. Loss of OmpK36 in KPC-producingK. pneumoniaeisolates affected the susceptibility of this combination. Enhanced activity was evident againstPseudomonas aeruginosa, including isolates with depressedoprDand increasedampCexpression. However, the addition of relebactam to imipenem did not provide added benefit againstAcinetobacter baumannii. The combination of imipenem with relebactam demonstrated activity against KPC-producingEnterobacteriaceaeand multidrug-resistantP. aeruginosa.

scholarly journals In VitroActivity of RX-P873 against Enterobacteriaceae, Pseudomonas aeruginosa, and Acinetobacter baumannii

2015 ◽  
Vol 59 (4) ◽  
pp. 2280-2285 ◽  
Author(s):  
Robert K. Flamm ◽  
Paul R. Rhomberg ◽  
Ronald N. Jones ◽  
David J. Farrell
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Acinetobacter Baumannii ◽  
Active Agent ◽  
Multidrug Resistant ◽  
Surveillance Program ◽  
Gram Negative ◽  
Content Type ◽  
Highly Active ◽  
Bacterial Ribosome

ABSTRACTRX-P873 is a novel antibiotic from the pyrrolocytosine series which exhibits high binding affinity for the bacterial ribosome and broad-spectrum antibiotic properties. The pyrrolocytosines have shownin vitroactivity against multidrug-resistant Gram-negative and Gram-positive strains of bacteria known to cause complicated urinary tract, skin, and lung infections, as well as sepsis.Enterobacteriaceae(657),Pseudomonas aeruginosa(200), andAcinetobacter baumannii(202) isolates from North America and Europe collected in 2012 as part of a worldwide surveillance program were testedin vitroby broth microdilution using Clinical and Laboratory Standards Institute (CLSI) methodology. RX-P873 (MIC90, 0.5 μg/ml) was >32-fold more active than ceftazidime and inhibited 97.1% and 99.5% ofEnterobacteriaceaeisolates at MIC values of ≤1 and ≤4 μg/ml, respectively. There were only three isolates with an MIC value of >4 μg/ml (all were indole-positiveProtea). RX-P873 (MIC50/90, 2/4 μg/ml) was highly active againstPseudomonas aeruginosaisolates, including isolates which were nonsusceptible to ceftazidime or meropenem. RX-P873 was 2-fold less active againstP. aeruginosathan tobramycin (MIC90, 2 μg/ml; 91.0% susceptible) and colistin (MIC90, 2 μg/ml; 99.5% susceptible) and 2-fold more potent than amikacin (MIC90, 8 μg/ml; 93.5% susceptible) and meropenem (MIC90, 8 μg/ml; 76.0% susceptible). RX-P873, the most active agent againstAcinetobacter baumannii(MIC90, 1 μg/ml), was 2-fold more active than colistin (MIC90, 2 μg/ml; 97.0% susceptible) and 4-fold more active than tigecycline (MIC90, 4 μg/ml). This novel agent merits further exploration of its potential against multidrug-resistant Gram-negative bacteria.

scholarly journals Novel Engineered Peptides of a Phage Lysin as Effective Antimicrobials against Multidrug-Resistant Acinetobacter baumannii

2016 ◽  
Vol 60 (5) ◽  
pp. 2671-2679 ◽  
Author(s):  
Mya Thandar ◽  
Rolf Lood ◽  
Benjamin Y. Winer ◽  
Douglas R. Deutsch ◽  
Chad W. Euler ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Bacterial Pathogen ◽  
Antibacterial Activities ◽  
Polymyxin B ◽  
Multidrug Resistant ◽  
Gram Negative ◽  
Content Type ◽  
Human Red Blood Cells ◽  
Phage Lysin

ABSTRACTAcinetobacter baumanniiis a Gram-negative bacterial pathogen responsible for a range of nosocomial infections. The recent rise and spread of multidrug-resistantA. baumanniiclones has fueled a search for alternative therapies, including bacteriophage endolysins with potent antibacterial activities. A common feature of these lysins is the presence of a highly positively charged C-terminal domain with a likely role in promoting outer membrane penetration. In the present study, we show that the C-terminal amino acids 108 to 138 of phage lysin PlyF307, named P307, alone were sufficient to killA. baumannii(>3 logs). Furthermore, P307 could be engineered for improved activity, the most active derivative being P307SQ-8C(>5-log kill). Both P307 and P307SQ-8Cshowed highin vitroactivity againstA. baumanniiin biofilms. Moreover, P307SQ-8Cexhibited MICs comparable to those of levofloxacin and ceftazidime and acted synergistically with polymyxin B. Although the peptides were shown to kill by disrupting the bacterial cytoplasmic membrane, they did not lyse human red blood cells or B cells; however, serum was found to be inhibitory to lytic activity. In a murine model ofA. baumanniiskin infection, P307SQ-8Creduced the bacterial burden by ∼2 logs in 2 h. This study demonstrates the prospect of using peptide derivatives from bacteriophage lysins to treat topical infections and remove biofilms caused by Gram-negative pathogens.

scholarly journals Multidrug-Resistant Acinetobacter baumannii in New York City—10 Years Into the Epidemic

2009 ◽  
Vol 30 (2) ◽  
pp. 196-197 ◽  
Author(s):  
Daniel J. Morgan ◽  
Scott A. Weisenberg ◽  
Michael H. Augenbraun ◽  
David P. Calfee ◽  
Brian P. Currie ◽  
...  
Keyword(s):  
New York ◽  
New York City ◽  
Acinetobacter Baumannii ◽  
York City ◽  
Multidrug Resistant

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.

Activity of cefepime/zidebactam (WCK 5222) against Enterobacteriaceae, Pseudomonas aeruginosa and Acinetobacter baumannii endemic to New York City medical centres

2019 ◽  
Vol 74 (10) ◽  
pp. 2938-2942 ◽  
Author(s):  
Zeb Khan ◽  
Alejandro Iregui ◽  
David Landman ◽  
John Quale
Keyword(s):  
New York ◽  
Pseudomonas Aeruginosa ◽  
New York City ◽  
Acinetobacter Baumannii ◽  
York City ◽  
Resistance Mechanisms ◽  
Gram Negative ◽  
Carbapenem Resistant ◽  
Excellent Activity ◽  
Susceptibility Tests

Abstract Background The combination of cefepime and zidebactam (WCK5222), a novel β-lactam enhancer, has demonstrated activity against a wide variety of Gram-negative pathogens and is currently under clinical evaluation. Objectives To examine the activity of cefepime/zidebactam against: (i) a contemporary collection of Gram-negative isolates from New York City; (ii) a collection of carbapenem-resistant clinical isolates; and (iii) a collection of isolates with characterized resistance mechanisms. Methods Susceptibility tests were performed using broth microdilution for cefepime, zidebactam and cefepime/zidebactam (1:1). Results More than 99% of a contemporary collection of Escherichia coli, Klebsiella pneumoniae and Enterobacter spp. had cefepime/zidebactam MICs ≤2 mg/L, the susceptibility breakpoint for cefepime. For K. pneumoniae, the acquisition of blaKPC resulted in increased MICs, although MICs remained ≤2 mg/L for 90% of KPC-possessing isolates. Overall for Pseudomonas aeruginosa, 98% of isolates had MICs ≤8 mg/L and MICs were affected by increased expression of ampC. For carbapenem-resistant P. aeruginosa, 78% of isolates had cefepime/zidebactam MICs ≤8 mg/L. The activity of cefepime/zidebactam against Acinetobacter baumannii was lower, with 85% of all isolates and 34% of carbapenem-resistant isolates with MICs ≤8 mg/L (cefepime interpretative criteria). Conclusions Cefepime/zidebactam demonstrated excellent activity against Enterobacteriaceae and P. aeruginosa, although activity was reduced in carbapenem-non-susceptible isolates. The activity against A. baumannii was reduced and studies examining the therapeutic efficacy in strains with high cefepime/zidebactam MICs are warranted.

scholarly journals Novel Phage Lysin Capable of Killing the Multidrug-Resistant Gram-Negative Bacterium Acinetobacter baumannii in a Mouse Bacteremia Model

2015 ◽  
Vol 59 (4) ◽  
pp. 1983-1991 ◽  
Author(s):  
Rolf Lood ◽  
Benjamin Y. Winer ◽  
Adam J. Pelzek ◽  
Roberto Diez-Martinez ◽  
Mya Thandar ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Genomic Library ◽  
Multidrug Resistant ◽  
Clinical Isolates ◽  
Gram Negative ◽  
Content Type ◽  
Highly Active ◽  
Genes Encoding

ABSTRACTAcinetobacter baumannii, a Gram-negative multidrug-resistant (MDR) bacterium, is now recognized as one of the more common nosocomial pathogens. Because most clinical isolates are found to be multidrug resistant, alternative therapies need to be developed to control this pathogen. We constructed a bacteriophage genomic library based on prophages induced from 13A. baumanniistrains and screened it for genes encoding bacteriolytic activity. Using this approach, we identified 21 distinct lysins with different activities and sequence diversity that were capable of killingA. baumannii. The lysin (PlyF307) displaying the greatest activity was further characterized and was shown to efficiently kill (>5-log-unit decrease) all testedA. baumanniiclinical isolates. Treatment with PlyF307 was able to significantly reduce planktonic and biofilmA. baumanniibothin vitroandin vivo. Finally, PlyF307 rescued mice from lethalA. baumanniibacteremia and as such represents the first highly active therapeutic lysin specific for Gram-negative organisms in an array of native lysins found inAcinetobacterphage.

Sign in / Sign up

Export Citation Format

Share Document