scholarly journals AB569, a non-toxic combination of acidified nitrite and EDTA, is effective at killing the notorious Iraq/Afghanistan combat wound pathogens, multi-drug resistant Acinetobacter baumannii and Acinetobacter spp.

PLoS ONE ◽  
2021 ◽  
Vol 16 (3) ◽  
pp. e0247513
Author(s):  
Amy L. Bogue ◽  
Warunya Panmanee ◽  
Cameron T. McDaniel ◽  
Joel E. Mortensen ◽  
Edwin Kamau ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Bactericidal Activity ◽  
Ethylenediaminetetraacetic Acid ◽  
Toxicity Testing ◽  
Dermal Fibroblasts ◽  
Pcr Analysis ◽  
Drug Resistant ◽  
Siderophore Biosynthesis ◽  
Peptide Synthetase ◽  
Acinetobacter Spp

Multi-drug resistant (MDR) Acinetobacter baumannii (Ab) and Acinetobacter spp. present monumental global health challenges. These organisms represent model Gram-negative pathogens with known antibiotic resistance and biofilm-forming properties. Herein, a novel, nontoxic biocide, AB569, consisting of acidified nitrite (A-NO2-) and ethylenediaminetetraacetic acid (EDTA), demonstrated bactericidal activity against all Ab and Acinetobacter spp. strains, respectively. Average fractional inhibitory concentrations (FICs) of 0.25 mM EDTA plus 4 mM A-NO2- were observed across several clinical reference and multiple combat wound isolates from the Iraq/Afghanistan wars. Importantly, toxicity testing on human dermal fibroblasts (HDFa) revealed an upper toxicity limit of 3 mM EDTA plus 64 mM A-NO2-, and thus are in the therapeutic range for effective Ab and Acinetobacter spp. treatment. Following treatment of Ab strain ATCC 19606 with AB569, quantitative PCR analysis of selected genes products to be responsive to AB569 revealed up-regulation of iron regulated genes involved in siderophore production, siderophore biosynthesis non-ribosomal peptide synthetase module (SBNRPSM), and siderophore biosynthesis protein monooxygenase (SBPM) when compared to untreated organisms. Taken together, treating Ab infections with AB569 at inhibitory concentrations reveals the potential clinical application of preventing Ab from gaining an early growth advantage during infection followed by extensive bactericidal activity upon subsequent exposures.

scholarly journals A New Twist: The Combination of Sulbactam/Avibactam Enhances Sulbactam Activity against Carbapenem-Resistant Acinetobacter baumannii (CRAB) Isolates

Antibiotics ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 577
Author(s):  
Fernando Pasteran ◽  
Jose Cedano ◽  
Michelle Baez ◽  
Ezequiel Albornoz ◽  
Melina Rapoport ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Target Genes ◽  
Susceptibility Testing ◽  
Clinical Isolates ◽  
Drug Resistant ◽  
Carbapenem Resistant ◽  
Acinetobacter Spp

An increasing number of untreatable infections are recorded every year. Many studies have focused their efforts on developing new β-lactamase inhibitors to treat multi-drug resistant (MDR) isolates. In the present study, sulbactam/avibactam and sulbactam/relebactam combination were tested against 187 multi-drug resistant (MDR) Acinetobacter clinical isolates; both sulbactam/avibactam and sulbactam/relebactam restored sulbactam activity. A decrease ≥2 dilutions in sulbactam MICs was observed in 89% of the isolates when tested in combination with avibactam. Sulbactam/relebactam was able to restore sulbactam susceptibility in 40% of the isolates. In addition, the susceptibility testing using twenty-three A. baumannii AB5075 knockout strains revealed potential sulbactam and/or sulbactam/avibactam target genes. We observed that diazabicyclooctanes (DBOs) β-lactamase inhibitors combined with sulbactam restore sulbactam susceptibility against carbapenem-resistant Acinetobacter clinical isolates. However, relebactam was not as effective as avibactam when combined with sulbactam. Exploring novel combinations may offer new options to treat Acinetobacter spp. infections, especially for widespread oxacillinases and metallo-β-lactamases (MBLs) producers.

scholarly journals 1542. The Evaluation of the In Vitro Synergy of Colistin in Combination with Meropenem and Tigecycline against 50 Multi-Drug-resistant Acinetobacter baumannii strains

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S562-S563
Author(s):  
Jacinda Abdul-Mutakabbir ◽  
Juwom Yim ◽  
Logan Nguyen ◽  
Razieh Kebriaei ◽  
Kyle Stamper ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Bactericidal Activity ◽  
Single Agent ◽  
Resistance Mechanisms ◽  
Drug Resistant ◽  
Initial Inoculum ◽  
Log Reduction ◽  
Carbapenem Resistant ◽  
Time Kill

Abstract Background Acinetobacter baumannii possess inherent and acquired antibiotic resistance mechanisms that have rendered most antibiotics, including carbapenems, inactive. Colistin (COL) has risen as salvage therapy against these organisms due to its retained activity against A. baumannii. However, COL monotherapy is often met with suboptimal outcomes. Recently, combination therapy with COL and meropenem (MEM) or tigecycline (TGC) has been shown to be effective in eradicating multi-drug-resistant A. baumannii infections. The objective of this study was to further evaluate the efficacy of COL in combination with MEM or TGC against 50 multi-drug-resistant A. baumannii strains. Methods Fifty carbapenem-resistant A. baumannii strains were evaluated using combination minimum inhibitory concentration (MIC) testing and time-kill analysis (TKA). Single-drug MIC testing was performed for each strain by broth microdilution. Combination MIC testing was performed for COL+MEM and COL+TGC. Each strain was evaluated via 24-hour TKA to assess the synergistic capabilities of COL+MEM, and COL+TGC. Synergy was defined as a ≥ 2-log reduction CFU/mL in either combination from the most active single agent, while bactericidal activity was defined as a ≥ 3-log reduction CFU/mL of either combination from the initial inoculum. Results All 50 strains were resistant to MEM and TGC with MICs ≥ 64 µg/mL and ≥ 4 µg/mL respectively; while 3 strains were resistant to COL, MICs ≥ 2 µg/mL. MEM and TGC MIC values were reduced as much as 128-fold (median 2-fold) and 32-fold (median 2-fold),, respectively, in the presence of subinhibitory COL. COL MIC values were reduced as much as 512-fold (median 4-fold) from baseline in the presence of subinhibitory MEM, and as high as 16-fold (median 2-fold) in the presence of TGC. In TKAs, COL+MEM was synergistic in 45/50 (90%) strains and bactericidal against 43/50 (86%) strains. COL+TGC TKAs revealed synergy in 32/50 (64%) strains, and bactericidal activity against 28/50 (56%) strains. Conclusion The combinations of COL+MEM and COL+TGC demonstrate promise in combating highly resistant A. baumannii. Further research is mandated to explore other combinations that are capable of eradicating multi-drug-resistant A. baumannii. Disclosures All authors: No reported disclosures.

scholarly journals Potentiation of antimicrobial activity of colistin with antibiotics of different groups against multidrug- and extensively drug-resistant strains of Klebsiella pneumoniae, Acinetobacter baumannii and Pseudomonas aeruginosa

2020 ◽  
Vol 22 (2) ◽  
pp. 128-136
Author(s):  
Dmitry V. Tapalskiy ◽  
T.A. Petrovskaya ◽  
A.I. Kozlova ◽  
Mikhail V. Edelstein
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Antimicrobial Activity ◽  
Klebsiella Pneumoniae ◽  
Acinetobacter Baumannii ◽  
Bactericidal Activity ◽  
Drug Resistant ◽  
Extensively Drug Resistant ◽  
Potentiation Effect ◽  
Resistant Strains ◽  
Drug Resistant Strains

Objective. To reveal antibiotics being capable of potentiating the antimicrobial activity of colistin against multidrug- and extensively drug-resistant strains of Klebsiella pneumoniae, Acinetobacter baumannii and Pseudomonas aeruginosa. Materials and Methods. The minimum inhibitory concentrations (MIC) of colistin alone and in combination with fixed concentrations of antibiotics of different groups were determined for 272 multidrug- and extensively drug-resistant strains of K. pneumoniae, A. baumannii and P. aeruginosa. Bactericidal activity of colistin, carbapenems, clarithromycin and their combinations were also determined at fixed PK/PD breakpoint concentrations of antibiotics. Results. Potentiation of colistin antibacterial activity in the presence of fixed concentration of rifampicin (0.5 mg/L) was observed as a 4–16-fold MIC decrease for K. pneumoniae and A. baumannii. In the presence of fixed concentrations of azithromycin (2 mg/L) or clarithromycin (1 mg/L), the colistin MICs decreased 64–512 times for K. pneumoniae, 4–32 times for A. baumannii, 16–64 times for P. aeruginosa. Two- or more-fold reduction of MIC of colistin in the presence of 1 mg/L clarithromycin was observed for 85.2% of K. pneumoniae, 86.3% of A. baumannii and 60.2% of P. aeruginosa strains. In the presence of 1 mg/L clarithromycin and 8 mg/L meropenem, the potentiation effect was enhanced and was observed for an even larger percent of isolates: 96.1% K. pneumoniae, 98.0% A. baumannii and 61.3% P. aeruginosa. Colistin-based combinations with clarithromycin-meropenem and clarithromycin-doripenem were bactericidal against most isolates of A. baumannii and P. aeruginosa (91.4–100%), and against colistin-sensitive K. pneumoniae (95.3%) and colistin-resistant K. pneumoniae (79.1%). Conclusions. The ability of macrolides to significantly potentiate the colistin antimicrobial activity against both colistin-sensitive and colistin-resistant strains of K. pneumoniae, A. baumannii and P. aeruginosa was shown. This potentiation effect was enhanced in the presence of carbapenems. The most potent bactericidal activity was revealed with dual and triple combinations of colistin-clarithromycin and colistinclarithromycin-carbapenems.

scholarly journals Nosocomial Outbreak of Extensively Drug-Resistant Acinetobacter baumannii Isolates Containing blaOXA-237 Carried on a Plasmid

2017 ◽  
Vol 61 (11) ◽  
Author(s):  
Andrea M. Hujer ◽  
Paul G. Higgins ◽  
Susan D. Rudin ◽  
Genevieve L. Buser ◽  
Steven H. Marshall ◽  
...  
Keyword(s):  
United States ◽  
Acinetobacter Baumannii ◽  
Health Care Facilities ◽  
Pcr Analysis ◽  
Drug Resistant ◽  
Content Type ◽  
Carbapenem Resistant ◽  
Extensively Drug Resistant ◽  
Separate Branch ◽  
Carbapenemase Gene

ABSTRACT Carbapenem antibiotics are among the mainstays for treating infections caused by Acinetobacter baumannii, especially in the Northwest United States, where carbapenem-resistant A. baumannii remains relatively rare. However, between June 2012 and October 2014, an outbreak of carbapenem-resistant A. baumannii occurred in 16 patients from five health care facilities in the state of Oregon. All isolates were defined as extensively drug resistant. Multilocus sequence typing revealed that the isolates belonged to sequence type 2 (international clone 2 [IC2]) and were >95% similar as determined by repetitive-sequence-based PCR analysis. Multiplex PCR revealed the presence of a bla OXA carbapenemase gene, later identified as bla OXA-237. Whole-genome sequencing of all isolates revealed a well-supported separate branch within a global A. baumannii phylogeny. Pacific Biosciences (PacBio) SMRT sequencing was also performed on one isolate to gain insight into the genetic location of the carbapenem resistance gene. We discovered that bla OXA-237, flanked on either side by ISAba1 elements in opposite orientations, was carried on a 15,198-bp plasmid designated pORAB01-3 and was present in all 16 isolates. The plasmid also contained genes encoding a TonB-dependent receptor, septicolysin, a type IV secretory pathway (VirD4 component, TraG/TraD family) ATPase, an integrase, a RepB family plasmid DNA replication initiator protein, an alpha/beta hydrolase, and a BrnT/BrnA type II toxin-antitoxin system. This is the first reported outbreak in the northwestern United States associated with this carbapenemase. Particularly worrisome is that bla OXA-237 was carried on a plasmid and found in the most prominent worldwide clonal group IC2, potentially giving pORAB01-3 great capacity for future widespread dissemination.

Decreased carO gene expression and OXA-type carbapenemases among extensively drug-resistant Acinetobacter baumannii strains isolated from burn patients in Tehran, Iran

2020 ◽  
Author(s):  
Elham Abbasi ◽  
Hossein Goudarzi ◽  
Ali Hashemi ◽  
Alireza Salimi Chirani ◽  
Abdollah Ardebili ◽  
...  
Keyword(s):  
Gene Expression ◽  
Acinetobacter Baumannii ◽  
High Rate ◽  
Burn Patients ◽  
Drug Resistant ◽  
Disc Diffusion ◽  
Carbapenem Resistant ◽  
Extensively Drug Resistant ◽  
Sds Page ◽  
Extensively Drug Resistance

AbstractA major challenge in the treatment of infections has been the rise of extensively drug resistance (XDR) and multidrug resistance (MDR) in Acinetobacter baumannii. The goals of this study were to determine the pattern of antimicrobial susceptibility, blaOXA and carO genes among burn-isolated A. baumannii strains. In this study, 100 A. baumannii strains were isolated from burn patients and their susceptibilities to different antibiotics were determined using disc diffusion testing and broth microdilution. Presence of carO gene and OXA-type carbapenemase genes was tested by PCR and sequencing. SDS-PAGE was done to survey CarO porin and the expression level of carO gene was evaluated by Real-Time PCR. A high rate of resistance to meropenem (98%), imipenem (98%) and doripenem (98%) was detected. All tested A. baumannii strains were susceptible to colistin. The results indicated that 84.9% were XDR and 97.9% of strains were MDR. In addition, all strains bore blaOXA-51 like and blaOXA-23 like and carO genes. Nonetheless, blaOXA-58 like and blaOXA-24 like genes were harbored by 0 percent and 76 percent of strains, respectively. The relative expression levels of the carO gene ranged from 0.06 to 35.01 fold lower than that of carbapenem-susceptible A. baumannii ATCC19606 and SDS – PAGE analysis of the outer membrane protein showed that all 100 isolates produced CarO. The results of current study revealed prevalence of blaOXA genes and changes in carO gene expression in carbapenem resistant A.baumannii.

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