Comparative in vitro antimicrobial susceptibilities and synergistic activities of antimicrobial combinations against carbapenem-resistant Acinetobacter species: Acinetobacter baumannii versus Acinetobacter genospecies 3 and 13TU

2011 ◽  
Vol 70 (3) ◽  
pp. 380-386 ◽  
Author(s):  
Wang-Huei Sheng ◽  
Jann-Tay Wang ◽  
Shu-Ying Li ◽  
Yu-Chi Lin ◽  
Aristine Cheng ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Acinetobacter Species ◽  
Carbapenem Resistant ◽  
Antimicrobial Susceptibilities ◽  
Antimicrobial Combinations

scholarly journals In-Vitro Evaluation of Different Antimicrobial Combinations with and without Colistin Against Carbapenem-Resistant Acinetobacter Baumannii

Molecules ◽  
2019 ◽  
Vol 24 (5) ◽  
pp. 886 ◽  
Author(s):  
Alessandra Oliva ◽  
Stefania Garzoli ◽  
Massimiliano De Angelis ◽  
Carolina Marzuillo ◽  
Vincenzo Vullo ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Bactericidal Activity ◽  
High Morbidity ◽  
Synergistic Activity ◽  
Carbapenem Resistant ◽  
Resistant Strains ◽  
High Level ◽  
University Of Rome ◽  
Antimicrobial Combinations

Carbapenem-resistant Acinetobacter baumannii (CR-Ab) infections are associated with high morbidity and mortality. The aim of the study was to evaluate the in-vitro activity of different antimicrobial combinations (with and without colistin, COL) against clinical isolates of CR-Ab collected from patients with CR-Ab infection, including unconventional combinations such as COL + VANcomycin (VAN) and COL + rifampin (RIF). CR-Ab strains were collected from hospitalized patients at Sapienza University of Rome. Antimicrobial susceptibility patterns were determined throughout MIC50/90s whereas the synergistic activity was evaluated by qualitative (i.e., checkerboard) and quantitative (i.e., killing studies) methods. All the strains were found oxacillinase (OXA) producers and tigecycline (TIG) sensitive whereas 2 strains were resistant to COL. Application of the checkerboard method indicated complete synergism in COL combinations at different extension: 21.4%, 57.1%, 42.8%, 35.7% for COL + meropenem (MEM), COL + RIF, COL + VAN and COL + TIG, respectively, with the non-conventional combinations COL + VAN and COL + RIF exhibiting the highest rate of synergism. Regarding COL-free combination, complete synergism was observed in 35.7% of the strains for MEM + TIG. Killing studies showed that the combinations COL + MEM, COL + TIG and MEM + TIG were bactericidal and synergistic against both colistin-sensitive and low colistin-resistant strains whereas only the combinations COL + VAN and COL + RIF showed an early and durable bactericidal activity against all the tested strains, with absence of growth at 24 h. This study demonstrated that COL-based combinations lead to a high level of synergic and bactericidal activity, especially COL + VAN and COL + RIF, even in the presence of high level of COL resistance.

scholarly journals In Vitro Synergistic Antimicrobial Activity of Combinations of Meropenem, Colistin, Tigecycline, Rifampin, and Ceftolozane/Tazobactam Against Carbapenem-Resistant Acinetobacter Baumannii

2021 ◽  
Author(s):  
Yong Guk Ju ◽  
Hak Joon Lee ◽  
Hong Soon Yim ◽  
Chang Kyu Lee ◽  
Mingoo Lee ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Bactericidal Effect ◽  
Drug Combinations ◽  
Synergistic Activity ◽  
Antibiotic Concentration ◽  
Carbapenem Resistant ◽  
Potential Alternative ◽  
Time Kill ◽  
Antimicrobial Combinations

Abstract The aim of this study was to investigate the in vitro activity of various antimicrobial combinations against carbapenem-resistant Acinetobacter baumannii (CRAB) isolates producing OXA-23 carbapenemases.In vitro activity of six two-drug combinations against CRAB isolates collected from patients with CRAB bacteremia was evaluated using the checkerboard method and time-kill assay [0.5 ×, 1 ×, 2 × minimum inhibitory concentrations (MIC)], to identify potential synergistic and bactericidal two-drug combinations against CRAB isolates, using meropenem, colistin, tigecycline, rifampin, and ceftolozane/tazobactam. All 10 CRAB isolates in our study carried the OXA-58-type and OXA-23-type carbapenem-hydrolyzing oxacillinase. The colistin-ceftolozane/tazobactam combination demonstrated a synergistic effect in both the time-kill assay (using an antibiotic concentration of 1 × MIC) and the checkerboard method, while simultaneously showing a bactericidal effect in the time-kill assay. For all 10 CRAB isolates, time-kill curves showed a significant synergistic bactericidal activity of the colistin-ceftolozane/tazobactam combination at 0.5 × MIC. Overall, there is substantial discordance of synergistic activity between the checkerboard microdilution and time-kill assay (with a concordance of 35%). Our study demonstrated that the two-drug combinations of colistin and ceftolozane/tazobactam can be a potential alternative for treating CRAB infections. The effect of these antibiotic combinations should be evaluated through clinical trials.

scholarly journals Investigating the in vitro synergistic activities of several antibiotic combinationsagainst carbapenem-resistant Acinetobacter baumannii isolates

2016 ◽  
Vol 46 ◽  
pp. 892-896 ◽  
Author(s):  
Sevim YAVAŞ ◽  
Meltem Arzu YETKİN ◽  
Bircan KAYAASLAN ◽  
Aliye BAŞTUĞ ◽  
Halide ASLANER ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Carbapenem Resistant

scholarly journals Semimechanistic Pharmacokinetic/Pharmacodynamic Modeling of Fosfomycin and Sulbactam Combination against Carbapenem-Resistant Acinetobacter baumannii

2021 ◽  
Vol 65 (5) ◽  
Author(s):  
Sazlyna Mohd Sazlly Lim ◽  
Aaron J. Heffernan ◽  
Jason A. Roberts ◽  
Fekade B. Sime
Keyword(s):  
Acinetobacter Baumannii ◽  
Treatment Options ◽  
Pharmacodynamic Modeling ◽  
Synergistic Activity ◽  
Bacterial Burden ◽  
Target Attainment ◽  
Content Type ◽  
Carbapenem Resistant ◽  
Time Kill

ABSTRACT Due to limited treatment options for carbapenem-resistant Acinetobacter baumannii (CR-AB) infections, antibiotic combinations are now considered potential treatments for CR-AB. This study aimed to explore the utility of fosfomycin-sulbactam combination (FOS/SUL) therapy against CR-AB isolates. Synergism of FOS/SUL against 50 clinical CR-AB isolates was screened using the checkerboard method. Thereafter, time-kill studies against two CR-AB isolates were performed. The time-kill data were described using a semimechanistic pharmacokinetic/pharmacodynamic (PK/PD) model. Monte Carlo simulations were then performed to estimate the probability of stasis, 1-log kill, and 2-log kill after 24 h of combination therapy. The FOS/SUL combination demonstrated a synergistic effect against 74% of isolates. No antagonism was observed. The MIC50 and MIC90 of FOS/SUL were decreased 4- to 8-fold, compared to the monotherapy MIC50 and MIC90. In the time-kill studies, the combination displayed bactericidal activity against both isolates and synergistic activity against one isolate at the highest clinically achievable concentrations. Our PK/PD model was able to describe the interaction between fosfomycin and sulbactam in vitro. Bacterial kill was mainly driven by sulbactam, with fosfomycin augmentation. FOS/SUL regimens that included sulbactam at 4 g every 8 h demonstrated a probability of target attainment of 1-log10 kill at 24 h of ∼69 to 76%, compared to ∼15 to 30% with monotherapy regimens at the highest doses. The reduction in the MIC values and the achievement of a moderate PTA of a 2-log10 reduction in bacterial burden demonstrated that FOS/SUL may potentially be effective against some CR-AB infections.

scholarly journals 694. In vitro Antibacterial Activity of Sulbactam–Durlobactam (ETX2514SUL) Against 121 Recent Acinetobacter baumannii Isolated from Patients in India

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S314-S314
Author(s):  
Alita Miller ◽  
Sarah McLeod ◽  
Tarun Mathur ◽  
Ian Morrissey
Keyword(s):  
Antibacterial Activity ◽  
Acinetobacter Baumannii ◽  
Package Insert ◽  
Multidrug Resistant ◽  
Antibiotic Resistant ◽  
Carbapenem Resistant ◽  
In Vitro Antibacterial Activity ◽  
Spectrum Activity ◽  
Broad Spectrum Activity

Abstract Background The incidence of infections caused by multidrug-resistant Acinetobacter baumannii is increasing at an alarming rate in Southeast Asia and other parts of the world. Sulbactam (SUL) has intrinsic antibacterial activity against A. baumannii; however, the prevalence of β-lactamases in this species has limited its therapeutic use. Durlobactam (ETX2514, DUR) is a novel β-lactamase inhibitor with broad-spectrum activity against Ambler class A, C and D β-lactamases. DUR restores SUL in vitro activity against multidrug-resistant A. baumannii. Against >3,600 globally diverse, clinical isolates from 2012–2017, addition of 4 mg/L DUR reduced the SUL MIC90 from >32 to 2 mg/L. SUL-DUR is currently in Phase 3 clinical development for the treatment of infections caused by carbapenem-resistant Acinetobacter spp.The goal of this study was to determine the activity of SUL-DUR and comparator antibiotics (amikacin (AMK), ampicillin-sulbactam (AMP-SUL), cefoperazone-sulbactam (CFP-SUL) and meropenem (MEM)) against A. baumannii isolated from hospitalized patients in India. Methods A total of 121 clinical A. baumannii isolates from multiple hospital settings and infection sources were collected between 2016–2019 from six geographically diverse hospitals in India. Species identification was performed by MALDI-TOF. Susceptibility of these isolates to SUL-DUR (10µg/10µg) and comparator antibiotics was determined by disk diffusion using CLSI methodology and interpretive criteria, except for CFP-SUL, for which resistance was defined using breakpoints from the CFP-SUL package insert. Results As shown in Table 1, resistance of this collection of isolates to marketed agents was extremely high. In contrast, based on preliminary breakpoint criteria, only 11.5% of isolates were resistant to SUL-DUR. Conclusion The in vitro antibacterial activity of SUL-DUR was significantly more potent than comparator agents against multidrug-resistant A. baumannii isolates collected from diverse sites in India. These data support the continued development of SUL-DUR for the treatment of antibiotic-resistant infections caused by A. baumannii. Disclosures All authors: No reported disclosures.

scholarly journals In vitro activities of carbapenem/sulbactam combination, colistin, colistin/rifampicin combination and tigecycline against carbapenem-resistant Acinetobacter baumannii

2007 ◽  
Vol 60 (2) ◽  
pp. 317-322 ◽  
Author(s):  
Joon Young Song ◽  
Sae Yoon Kee ◽  
In Sook Hwang ◽  
Yu Bin Seo ◽  
Hye Won Jeong ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Carbapenem Resistant

scholarly journals Distinct Mechanisms of Dissemination of NDM-1 Metallo-β-Lactamase in Acinetobacter Species in Argentina

2020 ◽  
Vol 64 (5) ◽  
Author(s):  
Mark D. Adams ◽  
Fernando Pasteran ◽  
German M. Traglia ◽  
Jasmine Martinez ◽  
Fanny Huang ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Resistance Gene ◽  
Genome Sequencing ◽  
Acinetobacter Species ◽  
Content Type ◽  
Resistance Determinants ◽  
Carbapenem Resistant ◽  
Gene Island

ABSTRACT A 4-year surveillance of carbapenem-resistant Acinetobacter spp. isolates in Argentina identified 40 strains carrying blaNDM-1. Genome sequencing revealed that most were Acinetobacter baumannii, whereas seven represented other Acinetobacter spp. The A. baumannii genomes were closely related, suggesting recent spread. blaNDM-1 was located in the chromosome of A. baumannii strains and on a plasmid in non-A. baumannii strains. A resistance gene island carrying blaPER-7 and other resistance determinants was found on a plasmid in some A. baumannii strains.

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