Assessment of activity and resistance mechanisms to cefepime in combination with the novel β-lactamase inhibitors zidebactam, taniborbactam and enmetazobactam against a multicenter collection of carbapenemase-producing Enterobacterales.

2021 ◽  
Author(s):  
Juan Carlos Vázquez-Ucha ◽  
Cristina Lasarte-Monterrubio ◽  
Paula Guijarro-Sánchez ◽  
Marina Oviaño ◽  
Laura Álvarez-Fraga ◽  
...  
Keyword(s):  
Amino Acid ◽  
Therapeutic Potential ◽  
Multidrug Resistant ◽  
Resistance Mechanisms ◽  
Resistant Bacteria ◽  
The Novel ◽  
Current Development ◽  
Mechanisms Of Resistance ◽  
Multidrug Resistant Bacteria ◽  
Excellent Activity

The global distribution of carbapenemases such as KPC, MBLs and OXA-48 gives cause for concern, as these enzymes are not inhibited by classical β-lactamase inhibitors (BLIs). The current development of new inhibitors is one of the most promising highlights for the treatment of multidrug-resistant bacteria. The activity of cefepime in combination with the novel BLIs zidebactam, taniborbactam and enmetazobactam was studied in a collection of 400 carbapenemase-producing Enterobacterales (CPE). The genomes were fully sequenced and potential mechanisms of resistance to cefepime/BLI combinations were characterized. Cefepime resistance in the whole set of isolates was 79.5% (MIC 50/90 64/≥128mg/L). The cefepime/zidebactam and cefepime/taniborbactam combinations showed the highest activity (MIC 50/90 ≤0.5/1 and ≤0.5/2 mg/L, respectively). Cefepime/zidebactam displayed high activity, regardless of the carbapenemase or ESBL considered (99% MIC ≤2 mg/L). Cefepime/taniborbactam displayed excellent activity against OXA-48- and KPC-producing Enterobacterales and lower activity against MBL-producing isolates (4 strains yielded MICs ≥16 mg/L:2 NDM producers with an insertion in PBP3, 1 VIM-1 producer with non-functional OmpK35 and 1 IMP-8 producer). Cefepime/enmetazobactam displayed the lowest activity (MIC 50/90 1/≥128 mg/L), with MICs ≥16 mg/L for 49 MBL producers, 40 OXA-48 producers (13 with amino acid changes in OmpK35/36, 4 in PBPs and 11 in RamR) and 25 KPC producers (most with an insertion in OmpK36). These results confirm the therapeutic potential of the new β-lactamase inhibitors, shedding light on the activity of cefepime and BLIs against CPE and resistance mechanisms. The cefepime/zidebactam and cefepime/taniborbactam combinations are particularly highlighted as promising alternatives to penicillin-based inhibitors for the treatment of CPE.

scholarly journals Post-antibiotic era in hemodialysis? Two case reports of simultaneous colonization and bacteremia by multidrug-resistant bacteria

2020 ◽  
Author(s):  
Johanna M. Vanegas ◽  
Lorena Salazar-Ospina ◽  
Gustavo A. Roncancio ◽  
Julián Builes ◽  
Judy Natalia Jiménez
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Bacterial Infections ◽  
Case Reports ◽  
Multidrug Resistant ◽  
Resistance Mechanisms ◽  
Control Measures ◽  
Resistant Bacteria ◽  
Multidrug Resistant Bacteria ◽  
E Coli ◽  
Carbapenem Resistant

ABSTRACT The emergence of resistance mechanisms not only limits the therapeutic options for common bacterial infections but also worsens the prognosis in patients who have conditions that increase the risk of bacterial infections. Thus, the effectiveness of important medical advances that seek to improve the quality of life of patients with chronic diseases is threatened. We report the simultaneous colonization and bacteremia by multidrug-resistant bacteria in two hemodialysis patients. The first patient was colonized by carbapenem- and colistin-resistant Klebsiella pneumoniae, carbapenem-resistant Pseudomonas aeruginosa, and methicillin-resistant Staphylococcus aureus (MRSA). The patient had a bacteremia by MRSA, and molecular typing methods confirmed the colonizing isolate was the same strain that caused infection. The second case is of a patient colonized by extended-spectrum beta-lactamases (ESBL)-producing Escherichia coli and carbapenem-resistant Pseudomonas aeruginosa. During the follow-up period, the patient presented three episodes of bacteremia, one of these caused by ESBL-producing E. coli. Molecular methods confirmed colonization by the same clone of ESBL-producing E. coli at two time points, but with a different genetic pattern to the strain isolated from the blood culture. Colonization by multidrug-resistant bacteria allows not only the spread of these microorganisms, but also increases the subsequent risk of infections with limited treatments options. In addition to infection control measures, it is important to establish policies for the prudent use of antibiotics in dialysis units.

scholarly journals Molecular Mechanisms of Bacterial Resistance to Metal and Metal Oxide Nanoparticles

2019 ◽  
Vol 20 (11) ◽  
pp. 2808 ◽  
Author(s):  
Nereyda Niño-Martínez ◽  
Marco Felipe Salas Orozco ◽  
Gabriel-Alejandro Martínez-Castañón ◽  
Fernando Torres Méndez ◽  
Facundo Ruiz
Keyword(s):  
Metal Oxide ◽  
Molecular Mechanisms ◽  
Bacterial Resistance ◽  
Bacterial Species ◽  
Metal Oxide Nanoparticles ◽  
Multidrug Resistant ◽  
Resistance Mechanisms ◽  
Resistant Bacteria ◽  
Oxide Nanoparticles ◽  
Multidrug Resistant Bacteria

The increase in bacterial resistance to one or several antibiotics has become a global health problem. Recently, nanomaterials have become a tool against multidrug-resistant bacteria. The metal and metal oxide nanoparticles are one of the most studied nanomaterials against multidrug-resistant bacteria. Several in vitro studies report that metal nanoparticles have antimicrobial properties against a broad spectrum of bacterial species. However, until recently, the bacterial resistance mechanisms to the bactericidal action of the nanoparticles had not been investigated. Some of the recently reported resistance mechanisms include electrostatic repulsion, ion efflux pumps, expression of extracellular matrices, and the adaptation of biofilms and mutations. The objective of this review is to summarize the recent findings regarding the mechanisms used by bacteria to counteract the antimicrobial effects of nanoparticles.

scholarly journals Detection of Carbapenemase Production in a Collection of Enterobacteriaceae with Characterized Resistance Mechanisms from Clinical and Environmental Origins by Use of Both Carba NP and Blue-Carba Tests: TABLE 1

2015 ◽  
Vol 54 (2) ◽  
pp. 464-466 ◽  
Author(s):  
Sergio García-Fernández ◽  
María-Isabel Morosini ◽  
Desirèe Gijón ◽  
Lorena Beatobe ◽  
Patricia Ruiz-Garbajosa ◽  
...  
Keyword(s):  
High Sensitivity ◽  
Cost Effective ◽  
Multidrug Resistant ◽  
Resistance Mechanisms ◽  
Rapid Screening ◽  
Resistant Bacteria ◽  
Screening Methods ◽  
Routine Laboratory ◽  
Multidrug Resistant Bacteria ◽  
Content Type

Rapid-screening methods to confirm the presence of resistance mechanisms in multidrug-resistant bacteria are currently recommended. Carba NP and Blue-Carba tests were evaluated in carbapenemase-producingEnterobacteriaceaefrom hospital (n= 102) and environmental (n= 57) origins for detecting the different molecular classes among them. Both methods showed to be fast and cost-effective, with high sensitivity (98% to 100%) and specificity (100%), and may be easily introduced in the routine laboratory.

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