scholarly journals Cefiderocol, a new antibiotic against multidrug-resistant Gram-negative bacteria

2021 ◽  
Vol 34 (Suppl 1) ◽  
pp. 41-43
Author(s):  
José Tiago Silva ◽  
Francisco López-Medrano
Keyword(s):  
Bacterial Pneumonia ◽  
Treatment Options ◽  
Multidrug Resistant ◽  
Resistance Mechanisms ◽  
Phase Iii ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Tract Infections ◽  
Transport Channels ◽  
Hospital Acquired

Cefiderocol is a novel catechol-substituted siderophore cephalosporin that binds to the extracellular free iron, and uses the bacterial active iron transport channels to penetrate in the periplasmic space of Gram-negative bacteria (GNB). Cefiderocol overcomes many resistance mechanisms of these bacteria. Cefiderocol is approved for the treatment of complicated urinary tract infections, hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia in the case of adults with limited treatment options, based on the clinical data from the APEKS-cUTI, APEKS-NP and CREDIBLE-CR trials. In the CREDIBLE-CR trial, a higher all-cause mortality was observed in the group of patients who received cefiderocol, especially those with severe infections due to Acinetobacter spp. Further phase III clinical studies are necessary in order to evaluate cefiderocol´s efficacy in the treatment of serious infections.

Cefiderocol: A new cephalosporin stratagem against multidrug resistant gram-negative bacteria

2021 ◽  
Author(s):  
Sharon Ong’uti ◽  
Mary Czech ◽  
Elizabeth Robilotti ◽  
Marisa Holubar
Keyword(s):  
Clinical Trials ◽  
Multidrug Resistant ◽  
Cell Entry ◽  
Phase Iii ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Phase Iii Clinical Trials ◽  
Carbapenem Resistant ◽  
Tract Infections

Abstract Cefiderocol is a novel injectable siderophore cephalosporin which hijacks the bacterial iron transport machinery to facilitate cell entry and achieve high periplasmic concentrations. It has broad in vitro activity against gram-negative bacteria, including multidrug resistant (MDR) organisms like carbapenem resistant Enterobacterales (CRE), carbapenem resistant Pseudomonas aeruginosa and Acinetobacter baumannii. It was approved by the Food and Drug Administration (FDA) for the treatment of complicated urinary tract infections and nosocomial pneumonia based on clinical trials demonstrating noninferiority to comparators. In this review, we summarize the available in vitro and clinical data, including recent evidence from 2 phase III clinical trials (APEKS-NP and CREDIBLE-CR), and discuss the place of cefiderocol in the clinician’s armamentarium against MDR gram-negative infections.

scholarly journals Ceftazidimeavibactam use in children and adolescents

2021 ◽  
Vol 23 (2) ◽  
pp. 173-183
Author(s):  
Оlga U. Stetsiouk ◽  
Irina V. Andreeva ◽  
А.U. Lekmanov ◽  
Еlena V. Haykina
Keyword(s):  
Multidrug Resistant ◽  
Gram Negative Bacteria ◽  
Pediatric Practice ◽  
Gram Negative ◽  
Hospital Acquired Pneumonia ◽  
Tract Infections ◽  
Hospital Acquired ◽  
Limited Choice ◽  
Intraabdominal Infections

Abstract The increasing number of infections caused by multidrug-resistant gram-negative bacteria in children is a serious problem all over the world. Ceftazidim-avibactam is a promising antimicrobial drug recently approved in Russia for use in pediatric practice. This review provides information on the possible use of ceftazidime-avibactam in children with complicated intraabdominal infections (in combination with metronidazole); complicated urinary tract infections, including pyelonephritis; hospital-acquired pneumonia, including ventilator-associated pneumonia; infections caused by aerobic gram-negative microorganisms in patients with limited choice of antibacterial therapy. Based on the data on the in vitro activity of the drug, the results of clinical studies of pharmacokinetics, safety and efficacy of ceftazidimeavibactam for the treatment of infections in children the main clinical cases in which the use of ceftazidimeavibactam in pediatric practice is most justified and appropriate are identified.

scholarly journals Case Commentary: the Need for Cefiderocol Is Clear, but Are the Supporting Clinical Data?

2020 ◽  
Vol 64 (4) ◽  
Author(s):  
Ryan K. Shields
Keyword(s):  
Clinical Trials ◽  
Clinical Practice ◽  
Salvage Therapy ◽  
Randomized Clinical Trials ◽  
Treatment Options ◽  
Multidrug Resistant ◽  
Gram Negative Bacteria ◽  
Potential Utility ◽  
Gram Negative

ABSTRACT Cefiderocol is a newly approved siderophore cephalosporin that demonstrates expanded in vitro activity against multidrug-resistant Gram-negative bacteria. In two challenging cases reported here, cefiderocol shows potential utility as salvage therapy against difficult-to-treat pathogens with limited or no treatment options; however, two multicenter, randomized clinical trials have yielded mixed results among cefiderocol-treated patients. Taken together, clinicians must balance a clear need for cefiderocol in clinical practice with the uncertainties that have stemmed from the available data.

scholarly journals Trends of 9,416 multidrug-resistant Gram-negative bacteria

2015 ◽  
Vol 61 (3) ◽  
pp. 244-249 ◽  
Author(s):  
Viviane Decicera Colombo Oliveira ◽  
Fernando Góngora Rubio ◽  
Margarete Teresa Gottardo Almeida ◽  
Mara Corrêa Lelles Nogueira ◽  
Antonio Carlos Campos Pignatari
Keyword(s):  
Gradual Increase ◽  
Carbapenem Resistance ◽  
Tertiary Hospital ◽  
Multidrug Resistant ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Clinical Specimens ◽  
Bacterial Sensitivity ◽  
Hospital Acquired ◽  
Multiple Antibiotics

Summary Objective: a resistance of hospital-acquired bacteria to multiple antibiotics is a major concern worldwide. The objective of this study was to investigate multidrugresistant (MDR) bacteria, clinical specimens, origin of specimen and trends, and correlate these with bacterial sensitivity and consumption of antimicrobials. Methods: 9,416 bacteria of nosocomial origin were evaluated in a tertiary hospital, from 1999 to 2008. MDR was defined for Gram-negative bacteria (GNB) as resistance to two or more classes/groups of antibiotics. Results: GNB MDR increased by 3.7 times over the study period (p<0.001). Acinetobacter baumannii was the most prevalent (36.2%). Over the study period, there were significant 4.8-fold and 14.6-fold increases for A. baumannii and K. pneumoniae (p<0.001), respectively. Sixty-seven percent of isolates of MDR GNB were isolated in intensive care units. The resistance of A. baumannii to carbapenems increased from 7.4 to 57.5% during the study period and concomitant with an increased consumption. Conclusion: that decade showed prevalence of GNB and a gradual increase in MDR GNB. There was an increase in carbapenem resistance of 50.1% during the study.

scholarly journals Clinical Status of Efflux Resistance Mechanisms in Gram-Negative Bacteria

Antibiotics ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 1117
Author(s):  
Anne Davin-Regli ◽  
Jean-Marie Pages ◽  
Aurélie Ferrand
Keyword(s):  
Clinical Status ◽  
Efflux Pumps ◽  
Multidrug Resistant ◽  
Resistance Mechanisms ◽  
Gram Negative Bacteria ◽  
Easy Method ◽  
Gram Negative ◽  
Healthcare Associated ◽  
Rational Use Of Antibiotics ◽  
Antibiotic Efflux

Antibiotic efflux is a mechanism that is well-documented in the phenotype of multidrug resistance in bacteria. Efflux is considered as an early facilitating mechanism in the bacterial adaptation face to the concentration of antibiotics at the infectious site, which is involved in the acquirement of complementary efficient mechanisms, such as enzymatic resistance or target mutation. Various efflux pumps have been described in the Gram-negative bacteria most often encountered in infectious diseases and, in healthcare-associated infections. Some are more often involved than others and expel virtually all families of antibiotics and antibacterials. Numerous studies report the contribution of these pumps in resistant strains previously identified from their phenotypes. The authors characterize the pumps involved, the facilitating antibiotics and those mainly concerned by the efflux. However, today no study describes a process for the real-time quantification of efflux in resistant clinical strains. It is currently necessary to have at hospital level a reliable and easy method to quantify the efflux in routine and contribute to a rational choice of antibiotics. This review provides a recent overview of the prevalence of the main efflux pumps observed in clinical practice and provides an idea of the prevalence of this mechanism in the multidrug resistant Gram-negative bacteria. The development of a routine diagnostic tool is now an emergency need for the proper application of current recommendations regarding a rational use of antibiotics.

scholarly journals Assessment of Ceftazidime-Avibactam 30/20-μg Disk, Etest versus Broth Microdilution Results When Tested against Enterobacterales Clinical Isolates

2022 ◽  
Author(s):  
Renru Han ◽  
Xuelin Yang ◽  
Yang Yang ◽  
Yan Guo ◽  
Dandan Yin ◽  
...  
Keyword(s):  
Treatment Options ◽  
Multidrug Resistant ◽  
Clinical Isolates ◽  
Gram Negative Bacteria ◽  
Broth Microdilution ◽  
Gram Negative ◽  
Extended Spectrum ◽  
The World ◽  
Multidrug Resistant Pathogens ◽  
Combinational Therapies

Multidrug-resistant Gram-negative bacteria, especially for extended-spectrum β-lactamases-producing and carbapenemase-producing Enterobacterales , are disseminating rapidly around the world. Treatment options for these infections are limited, which prompt the development of novel or combinational therapies to combat the infections caused by multidrug-resistant pathogens.

scholarly journals Review of Ceftazidime-Avibactam for the Treatment of Infections Caused by Pseudomonas aeruginosa

Antibiotics ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 1126
Author(s):  
George L. Daikos ◽  
Clóvis Arns da da Cunha ◽  
Gian Maria Rossolini ◽  
Gregory G. Stone ◽  
Nathalie Baillon-Plot ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Multidrug Resistant ◽  
Resistance Mechanisms ◽  
Real World Data ◽  
Serious Infections ◽  
Tract Infections ◽  
Abdominal Infections ◽  
Hospital Acquired

Pseudomonas aeruginosa is an opportunistic Gram-negative pathogen that causes a range of serious infections that are often challenging to treat, as this pathogen can express multiple resistance mechanisms, including multidrug-resistant (MDR) and extensively drug-resistant (XDR) phenotypes. Ceftazidime–avibactam is a combination antimicrobial agent comprising ceftazidime, a third-generation semisynthetic cephalosporin, and avibactam, a novel non-β-lactam β-lactamase inhibitor. This review explores the potential role of ceftazidime–avibactam for the treatment of P. aeruginosa infections. Ceftazidime–avibactam has good in vitro activity against P. aeruginosa relative to comparator β-lactam agents and fluoroquinolones, comparable to amikacin and ceftolozane–tazobactam. In Phase 3 clinical trials, ceftazidime–avibactam has generally demonstrated similar clinical and microbiological outcomes to comparators in patients with complicated intra-abdominal infections, complicated urinary tract infections or hospital-acquired/ventilator-associated pneumonia caused by P. aeruginosa. Although real-world data are limited, favourable outcomes with ceftazidime–avibactam treatment have been reported in some patients with MDR and XDR P. aeruginosa infections. Thus, ceftazidime–avibactam may have a potentially important role in the management of serious and complicated P. aeruginosa infections, including those caused by MDR and XDR strains.

scholarly journals Pathogenicity Genomic Island-Associated CrpP-Like Fluoroquinolone-Modifying Enzymes among Pseudomonas aeruginosa Clinical Isolates in Europe

2020 ◽  
Vol 64 (7) ◽  
Author(s):  
José Manuel Ortiz de la Rosa ◽  
Patrice Nordmann ◽  
Laurent Poirel
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Genomic Island ◽  
Multidrug Resistant ◽  
Resistance Mechanisms ◽  
Genomic Islands ◽  
Clinical Isolates ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Content Type ◽  
Genes Encoding

ABSTRACT Many transferable quinolone resistance mechanisms have been identified in Gram-negative bacteria. The plasmid-encoded 65-amino-acid-long ciprofloxacin-modifying enzyme CrpP was recently identified in Pseudomonas aeruginosa isolates. We analyzed a collection of 100 clonally unrelated and multidrug-resistant P. aeruginosa clinical isolates, among which 46 were positive for crpP-like genes, encoding five CrpP variants conferring variable levels of reduced susceptibility to fluoroquinolones. These crpP-like genes were chromosomally located as part of pathogenicity genomic islands.

Sign in / Sign up

Export Citation Format

Share Document