scholarly journals Comparative analysis of the pathogenicity between multidrug-resistant Acinetobacter baumannii clinical isolates: isolation of highly pathogenic multidrug-resistant A. baumannii and experimental therapeutics with fourth-generation cephalosporin cefozopran

2018 ◽  
Vol Volume 11 ◽  
pp. 1715-1722 ◽  
Author(s):  
Satoshi Nishida ◽  
Yasuo Ono
Keyword(s):  
Comparative Analysis ◽  
Acinetobacter Baumannii ◽  
Generation Cephalosporin ◽  
Multidrug Resistant ◽  
Clinical Isolates ◽  
Fourth Generation ◽  
Experimental Therapeutics ◽  
Highly Pathogenic

scholarly journals 1293. Sulbactam-durlobactam is active against recent, multi-drug resistant Acinetobacter baumannii clinical isolates from the Middle East

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S662-S662
Author(s):  
Alita Miller ◽  
Sarah McLeod ◽  
Samir Moussa ◽  
Meredith Hackel
Keyword(s):  
Antibacterial Activity ◽  
Middle East ◽  
Acinetobacter Baumannii ◽  
United Arab Emirates ◽  
Blood Stream ◽  
Multidrug Resistant ◽  
Clinical Isolates ◽  
Surveillance Systems ◽  
Spectrum Activity

Abstract Background The incidence of infections caused by multidrug-resistant (MDR) Acinetobacter baumannii (Ab) is increasing at an alarming rate in certain regions of the world, including the Middle East. Sulbactam (SUL) has intrinsic antibacterial activity against Ab; however, the prevalence of β-lactamases in Ab has limited its therapeutic utility. Durlobactam (DUR, formerly ETX2514) is a diazabicyclooctenone β-lactamase inhibitor with broad-spectrum activity against Ambler class A, C and D β-lactamases that restores SUL activity in vitro against MDR Ab. SUL-DUR is an antibiotic designed to treat serious infections caused by Acinetobacter, including multidrug-resistant strains, that is currently in Phase 3 clinical development. In global surveillance studies of >3600 isolates from 2012-2017, the MIC90 of SUL-DUR was 2 mg/L. Although surveillance systems to monitor MDR infections in the Middle East are currently being established, quantitative, prevalence-based data are not yet available. Therefore, the potency of SUL-DUR was determined against 190 recent, diverse Ab clinical isolates from this region. Methods 190 Ab isolates were collected between 2016 - 2018 from medical centers located in Israel (N = 47), Jordan (N = 36), Qatar (N = 13), Kuwait (N = 42), Lebanon (N = 8), Saudi Arabia (N = 24) and United Arab Emirates (N = 20). Seventy-five percent and 20.5% of these isolates were from respiratory and blood stream infections, respectively. Susceptibility to SUL-DUR and comparator agents was performed according to CLSI guidelines, and data analysis was performed using CLSI and EUCAST breakpoint criteria where available. Results This collection of isolates was 86% carbapenem-resistant and 90% sulbactam-resistant (based on a breakpoint of 4 mg/L). The addition of SUL-DUR (fixed at 4 mg/L) decreased the sulbactam MIC90 from 64 mg/L to 4 mg/L. Only 3 isolates (1.6%) had SUL-DUR MIC values of > 4 mg/L. This potency was consistent across countries, sources of infection and subsets of resistance phenotypes. Conclusion SUL-DUR demonstrated potent antibacterial activity against recent clinical isolates of Ab from the Middle East, including MDR isolates. These data support the global development of SUL-DUR for the treatment of MDR Ab infections. Disclosures Alita Miller, PhD, Entasis Therapeutics (Employee) Sarah McLeod, PhD, Entasis Therapeutics (Employee) Samir Moussa, PhD, Entasis Therapeutics (Employee)

scholarly journals In Vitro Activity of Sulbactam-Durlobactam against Acinetobacter baumannii-calcoaceticus Complex Isolates Collected Globally in 2016 and 2017

2020 ◽  
Vol 64 (4) ◽  
Author(s):  
Sarah M. McLeod ◽  
Samir H. Moussa ◽  
Meredith A. Hackel ◽  
Alita A. Miller
Keyword(s):  
Acinetobacter Baumannii ◽  
Antibacterial Activities ◽  
Multidrug Resistant ◽  
Clinical Isolates ◽  
Single Amino Acid ◽  
Content Type ◽  
Level Of Activity ◽  
Severe Infections ◽  
Sources Of Infection

ABSTRACT Acinetobacter baumannii-calcoaceticus complex (ABC) organisms cause severe infections that are difficult to treat due to preexisting antibiotic resistance. Sulbactam-durlobactam (formerly sulbactam-ETX2514) (SUL-DUR) is a β-lactam–β-lactamase inhibitor combination antibiotic designed to treat serious infections caused by ABC organisms, including multidrug-resistant (MDR) strains. The in vitro antibacterial activities of SUL-DUR and comparator agents were determined by broth microdilution against 1,722 clinical isolates of ABC organisms collected in 2016 and 2017 from 31 countries across Asia/South Pacific, Europe, Latin America, the Middle East, and North America. Over 50% of these isolates were resistant to carbapenems. Against this collection of global isolates, SUL-DUR had a MIC50/MIC90 of 1/2 μg/ml compared to a MIC50/MIC90 of 8/64 μg/ml for sulbactam alone. This level of activity was found to be consistent across organisms, regions, sources of infection, and subsets of resistance phenotypes, including MDR and extensively drug-resistant isolates. The SUL-DUR activity was superior to those of the tested comparators, with only colistin having similar potency. Whole-genome sequencing of the 39 isolates (2.3%) with a SUL-DUR MIC of >4 μg/ml revealed that these strains encoded either the metallo-β-lactamase NDM-1, which durlobactam does not inhibit, or single amino acid substitutions near the active site of penicillin binding protein 3 (PBP3), the primary target of sulbactam. In summary, SUL-DUR demonstrated potent antibacterial activity against recent, geographically diverse clinical isolates of ABC organisms, including MDR isolates.

Efflux pump inhibitory activity of biologically synthesized silver nanoparticles against multidrug-resistant Acinetobacter baumannii clinical isolates

2020 ◽  
Vol 60 (6) ◽  
pp. 494-507 ◽  
Author(s):  
Reyhaneh Behdad ◽  
Minoo Pargol ◽  
Amir Mirzaie ◽  
Shohreh Zare Karizi ◽  
Hassan Noorbazargan ◽  
...  
Keyword(s):  
Silver Nanoparticles ◽  
Acinetobacter Baumannii ◽  
Inhibitory Activity ◽  
Efflux Pump ◽  
Multidrug Resistant ◽  
Clinical Isolates

scholarly journals Multidrug-resistant Acinetobacter baumannii resists reactive oxygen species and survives in macrophages

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Yoshinori Sato ◽  
Yuka Unno ◽  
Chizuru Miyazaki ◽  
Tsuneyuki Ubagai ◽  
Yasuo Ono
Keyword(s):  
Reactive Oxygen Species ◽  
Acinetobacter Baumannii ◽  
Reactive Oxygen ◽  
Bacterial Count ◽  
Multidrug Resistant ◽  
Intracellular Reactive Oxygen Species ◽  
Clinical Isolates ◽  
Oxygen Species ◽  
Tnf Α ◽  
Mouse Macrophages

AbstractWe investigated the intracellular survival of multidrug-resistant Acinetobacter baumannii (MDRAB) clinical isolates in macrophages, after phagocytosis, to determine their virulence characteristics. After ATCC 19606 and 5 clinical isolates of MDRAB were phagocytosed by mouse and human macrophages, the bacterial count of MDRAB strains, R4 and R5, increased in the mouse macrophages, 24 hours after phagocytosis. Bacterial count of the strains, R1 and R2, was almost equal 4 and 24 hours after phagocytosis. Intracellular reactive oxygen species was detected in the macrophages after phagocytosis of these bacteria. Further, the strains R1, R2, R4, and R5 showed higher catalase activity than ATCC 19606. Additionally, strains R1, R4, and R5 grew more efficiently than ATCC 19606 in the presence of H2O2, whereas growth of strains R2 and R3 was marginally more than that of ATCC 19606 in the presence of H2O2. The MDRAB clinical isolates altered the expression of TNF-α, IL-1β, IL-6, and MIP-2 mRNA induced in J774A.1 cells, 24 hours after phagocytosis. These results provide insights into the renewed virulence characteristics of MDRAB clinical isolates. Finally, tigecycline killed MDRAB phagocytosed by the macrophages more effectively than colistin, although colistin and tigecycline are both considered effective antibiotics for the treatment of MDRAB.

scholarly journals Genetic Basis of Multidrug Resistance in Acinetobacter baumannii Clinical Isolates at a Tertiary Medical Center in Pennsylvania

2008 ◽  
Vol 52 (11) ◽  
pp. 3837-3843 ◽  
Author(s):  
Jennifer M. Adams-Haduch ◽  
David L. Paterson ◽  
Hanna E. Sidjabat ◽  
Anthony W. Pasculle ◽  
Brian A. Potoski ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Genetic Basis ◽  
Medical Center ◽  
Multidrug Resistant ◽  
Quinolone Resistance ◽  
Clinical Isolates ◽  
Clinical Microbiology Laboratory ◽  
Carbapenemase Gene ◽  
Methylase Gene ◽  
High Level

ABSTRACT A total of 49 unique clinical isolates of multidrug-resistant (MDR) Acinetobacter baumannii identified at a tertiary medical center in Pittsburgh, Pennsylvania, between August 2006 and September 2007 were studied for the genetic basis of their MDR phenotype. Approximately half of all A. baumannii clinical isolates identified during this period qualified as MDR, defined by nonsusceptibility to three or more of the antimicrobials routinely tested in the clinical microbiology laboratory. Among the MDR isolates, 18.4% were resistant to imipenem. The frequencies of resistance to amikacin and ciprofloxacin were high at 36.7% and 95.9%, respectively. None of the isolates was resistant to colistin or tigecycline. The presence of the carbapenemase gene bla OXA-23 and the 16S rRNA methylase gene armA predicted high-level resistance to imipenem and amikacin, respectively. bla OXA-23 was preceded by insertion sequence ISAba1, which likely provided a potent promoter activity for the expression of the carbapenemase gene. The structure of the transposon defined by ISAba1 differed from those reported in Europe, suggesting that ISAba1-mediated acquisition of bla OXA-23 may occur as an independent event. Typical substitutions in the quinolone resistance-determining regions of the gyrA and parC genes were observed in the ciprofloxacin-resistant isolates. Plasmid-mediated quinolone resistance genes, including the qnr genes, were not identified. Fifty-nine percent of the MDR isolates belonged to a single clonal group over the course of the study period, as demonstrated by pulsed-field gel electrophoresis.

scholarly journals Draft Genome Sequences of 11 Clinical Isolates of Acinetobacter baumannii

2016 ◽  
Vol 4 (2) ◽  
Author(s):  
P. G. Higgins ◽  
J. Z.-M. Chan ◽  
H. Seifert ◽  
M. J. Pallen ◽  
A. D. Millard
Keyword(s):  
Antimicrobial Resistance ◽  
Acinetobacter Baumannii ◽  
Draft Genome ◽  
Hospital Setting ◽  
Multidrug Resistant ◽  
Clinical Isolates ◽  
Single Patient ◽  
Genome Sequences

The development of multidrug-resistant Acinetobacter baumannii is of serious concern in the hospital setting. Here, we report draft genome sequences of 11 A. baumannii isolates that were isolated from a single patient over a 65-day period, during which time the isolates exhibited increased antimicrobial resistance.

scholarly journals Draft Genome Sequences of Clinical Isolates of Multidrug-Resistant Acinetobacter baumannii

2017 ◽  
Vol 5 (5) ◽  
Author(s):  
Keesha E. Erickson ◽  
Nancy E. Madinger ◽  
Anushree Chatterjee
Keyword(s):  
Acinetobacter Baumannii ◽  
Resistance Genes ◽  
Draft Genome ◽  
Multidrug Resistant ◽  
Clinical Isolates ◽  
Genome Sequences ◽  
Content Type ◽  
University Of Colorado ◽  
The University

ABSTRACT We report here the draft genome sequences of two clinically isolated Acinetobacter baumannii strains. These samples were obtained from patients at the University of Colorado Hospital in 2007 and 2013 and encode an estimated 20 and 13 resistance genes, respectively.

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