Cefiderocol as Rescue Therapy for Acinetobacter baumannii and Other Carbapenem-resistant Gram-negative Infections in Intensive Care Unit Patients

2020 ◽  
Author(s):  
Marco Falcone ◽  
Giusy Tiseo ◽  
Manuela Nicastro ◽  
Alessandro Leonildi ◽  
Alessandra Vecchione ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Stenotrophomonas Maltophilia ◽  
Inhibitory Concentration ◽  
Clinical Success ◽  
Rescue Therapy ◽  
Survival Rates ◽  
New Delhi ◽  
Ventilator Associated Pneumonia ◽  
Gram Negative ◽  
Carbapenem Resistant

Abstract Ten critically ill patients with either bacteremia or ventilator-associated pneumonia caused by carbapenem-resistant Acinetobacter baumannii, Stenotrophomonas maltophilia, or New Delhi metallo-β-lactamase–producing Klebsiella pneumoniae received cefiderocol. All strains had minimum inhibitory concentration ≤2 μg/mL. Thirty-day clinical success and survival rates were 70% and 90%, respectively. Two patients had a microbiological failure. Future prospective studies are warranted.

scholarly journals ARGONAUT-I: Activity of Cefiderocol (S-649266), a Siderophore Cephalosporin, against Gram-Negative Bacteria, Including Carbapenem-Resistant Nonfermenters and Enterobacteriaceae with Defined Extended-Spectrum β-Lactamases and Carbapenemases

2018 ◽  
Vol 63 (1) ◽  
Author(s):  
Michael R. Jacobs ◽  
Ayman M. Abdelhamed ◽  
Caryn E. Good ◽  
Daniel D. Rhoads ◽  
Kristine M. Hujer ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Acinetobacter Baumannii ◽  
Stenotrophomonas Maltophilia ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Content Type ◽  
Carbapenem Resistant ◽  
Extended Spectrum ◽  
Mueller Hinton ◽  
Mueller Hinton Broth

ABSTRACT The activity of the siderophore cephalosporin cefiderocol is targeted against carbapenem-resistant Gram-negative bacteria. In this study, the activity of cefiderocol against characterized carbapenem-resistant Acinetobacter baumannii complex, Stenotrophomonas maltophilia, Pseudomonas aeruginosa, and Enterobacteriaceae strains was determined by microdilution in iron-depleted Mueller-Hinton broth. The MIC90s against A. baumannii, S. maltophilia, and P. aeruginosa were 1, 0.25, and 0.5 mg/liter, respectively. Against Enterobacteriaceae, the MIC90 was 1 mg/liter for the group harboring OXA-48-like, 2 mg/liter for the group harboring KPC-3, and 8 mg/liter for the group harboring TEM/SHV ESBL, NDM, and KPC-2.

scholarly journals Infections in patients colonized with carbapenem-resistant Gram-negative bacteria in a medium Spanish city

2021 ◽  
Author(s):  
Carmen Soria-Segarra ◽  
Mercedes Delgado-Valverde ◽  
María Luisa Serrano-García ◽  
Inmaculada López-Hernández ◽  
José María Navarro-Marí ◽  
...  
Keyword(s):  
Predictive Value ◽  
Stenotrophomonas Maltophilia ◽  
Sanger Sequencing ◽  
Clinical Samples ◽  
Clinical Implications ◽  
Gram Negative Bacteria ◽  
Cross Sectional ◽  
Gram Negative ◽  
Carbapenem Resistant ◽  
Pulsed Field Electrophoresis

Objective. Because there are few studies on the clinical implications of colonization by carbapenem-resistant gram-negative bacteria (CRB) this was analyzed in rectal smears (RS) and pharyngeals (PS) and its ability to predict infection/colonization. Methodology. A cross-sectional, retrospective study from adult inpatients between January 2016 and December 2019 was conducted. The isolates were characterized by MicroScan and spectrometry of masses applying EUCAST 2018 cutoff points. The detection of carbapenemases was performed by PCR and Sanger sequencing; sequencies was assigned by MLST. The genetic relationship between the clinical isolates was made by pulsed field electrophoresis using the enzymes Xbal, Spel or Apal. Results. A total of 308 (86.03%) RS and 50 (13.97%) positive PS were detected, the RS had a 85% sensibility, 100% specificity, 100% positive predictive value and 97% negative predictive value. In RS, the following were isolated: 44% (n=135) Acinetobacter baumannii, 26% (n =80) Enterobacterales (20 KPC, 29 OXA-48, 22 VIM, 2 IMP, 7 NDM), 17% (n=53) Pseudomonas aeruginosa and 13% (n=40) Stenotrophomonas maltophilia. In the PS were isolated 44% (n=22) S. maltophilia, 40% (n = 20) A. baumannii, 8% (n=4) P. aeruginosa and 8% (n=4) Enterobacterales (3 VIM, 1 OXA). From the patients with simultaneous RS and PS, 41 (40.6%) had positivity in both smears, 45 (44.6%) only in RS and 15 (14.9%) only in PS. Colonization preceded infection in 81.3% (n=13) of the isolates; association between infection and colonization was found (p<0.001; χ2); and the episodes where the information was found all the isolates from the clinical samples and from the smears were similar. Conclusions. The probability of predicting infection through the CRB colonized in different clinical samples is feasible. The RS has a major sensibility to detect colonization.

scholarly journals Therapeutic Effects of Inhibitor of ompA Expression against Carbapenem-Resistant Acinetobacter baumannii Strains

2021 ◽  
Vol 22 (22) ◽  
pp. 12257
Author(s):  
Seok-Hyeon Na ◽  
Hyejin Jeon ◽  
Man-Hwan Oh ◽  
Yoo-Jeong Kim ◽  
Mingi Chu ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Survival Rates ◽  
Clinical Settings ◽  
Therapeutic Effects ◽  
Dependent Manner ◽  
Bacteriostatic Activity ◽  
Carbapenem Resistant ◽  
Eskape Pathogens

The widespread of carbapenem-resistant Acinetobacter baumannii (CRAB) is of great concern in clinical settings worldwide. It is urgent to develop new therapeutic agents against this pathogen. This study aimed to evaluate the therapeutic potentials of compound 62520, which has been previously identified as an inhibitor of the ompA promoter activity of A. baumannii, against CRAB isolates, both in vitro and in vivo. Compound 62520 was found to inhibit the ompA expression and biofilm formation in A. baumannii ATCC 17978 at sub-inhibitory concentrations in a dose-dependent manner. These inhibitory properties were also observed in clinical CRAB isolates belonging to sequence type (ST) 191. Additionally, compound 62520 exhibited a bacteriostatic activity against clinical clonal complex (CC) 208 CRAB isolates, including ST191, and ESKAPE pathogens. This bacteriostatic activity was not different between STs of CRAB isolates. Bacterial clearance was observed in mice infected with bioimaging A. baumannii strain 24 h after treatment with compound 62520. Compound 62520 was shown to significantly increase the survival rates of both immunocompetent and neutropenic mice infected with A. baumannii ATCC 17978. This compound also increased the survival rates of mice infected with clinical CRAB isolate. These results suggest that compound 62520 is a promising scaffold to develop a novel therapeutic agent against CRAB infections.

scholarly journals Emerging resistance to carbapenem among Gram-negative bacteria in a tertiary care hospital

2020 ◽  
Vol 11 (SPL2) ◽  
pp. 153-156
Author(s):  
Pooja Nair ◽  
Renu Mathews ◽  
Kalyani M
Keyword(s):  
Minimum Inhibitory Concentration ◽  
Inhibitory Concentration ◽  
Tertiary Care Hospital ◽  
Tertiary Care ◽  
Carbapenem Resistance ◽  
Clinical Samples ◽  
Care Hospital ◽  
Gram Negative ◽  
Carbapenem Resistant ◽  
Diffusion Technique

The emergence of bacterial antibiotic resistance is a cardinal concern in the health care system. The spread of resistance in Enterobacteriaceae and non-fermenters to the currently available drugs make the treatment of serious nosocomial infections troublesome.  The purpose of the study is to find out the carbapenem resistance among Gram-negative bacilli in a tertiary care hospital. Antibiotic susceptibility pattern of 1913 aerobic Gram-negative bacilli isolated from clinical samples was made for a period of 6 months. All the isolates were tested for susceptibility to antibiotics by the Kirby-Bauer disc diffusion technique according to CLSI guidelines. Carbapenemase production was confirmed by the Modified Hodge Test (MHT). Minimum Inhibitory Concentration (MIC) by Epsilometer (E) test was performed (for Imipenem and Meropenem) for carbapenem-resistant strains. A total of 1731 clinical samples, 1913 Gram-negative bacilli were isolated. 1476 (77.1%) were Enterobacteriaceae and 433 (22.6%) were non-fermenters. 54 were carbapenemase-producing Gram-negative bacilli. Meropenem E test was done for carbapenemase-producing Gram-negative bacilli. The minimum inhibitory concentration for Meropenem ranged from 0.002μg/ml to 32μg/ml. To overcome the problem of emerging resistance, combined interaction and cooperation of microbiologists, clinicians and the infection control team is needed.

scholarly journals Biocide susceptibilities and biofilm-forming capacities of Acinetobacter baumannii clinical isolates from Malaysia

2019 ◽  
Vol 13 (07) ◽  
pp. 626-633
Author(s):  
Muhammad Harith Nor A'shimi ◽  
Ahmed Ghazi Alattraqchi ◽  
Farahiyah Mohd Rani ◽  
Nor Iza A Rahman ◽  
Salwani Ismail ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Benzalkonium Chloride ◽  
Inhibitory Concentration ◽  
Antimicrobial Compounds ◽  
Nosocomial Pathogen ◽  
Chain Reaction ◽  
Gram Negative ◽  
Biocide Resistance ◽  
Benzethonium Chloride ◽  
Polymerase Chain

Introduction. Acinetobacter baumannii is a Gram-negative nosocomial pathogen that has the capacity to develop resistance to all classes of antimicrobial compounds. However, very little is known regarding its susceptibility to biocides (antiseptics and disinfectants) and capacity to form biofilms, particularly for Malaysian isolates. Aim. To determine the susceptibility of A. baumannii isolates to commonly-used biocides, investigate their biofilm-forming capacities and the prevalence of biocide resistance and biofilm-associated genes. Methodology. The minimum inhibitory concentration (MIC) values of 100 A. baumannii hospital isolates from Terengganu, Malaysia, towards the biocides benzalkonium chloride (BZK), benzethonium chloride (BZT) and chlorhexidine digluconate (CLX), were determined by broth microdilution. The isolates were also examined for their ability to form biofilms in 96-well microplates. The prevalence of biocide resistance genes qacA, qacE and qacDE1 and the biofilm-associated genes bap and abaI were determined by polymerase chain reaction (PCR). Results. Majority of the A. baumannii isolates (43%) showed higher MIC values (> 50 µg/mL) for CLX than for BZK (5% for MIC > 50 µg/mL) and BZT (9% for MIC > 50 µg/mL). The qacDE1 gene was predominant (63%) followed by qacE (28%) whereas no isolate was found harbouring qacA. All isolates were positive for the bap and abaI genes although the biofilm-forming capacity varied among the isolates. Conclusion. The Terengganu A. baumannii isolates showed higher prevalence of qacDE1 compared to qacE although no correlation was found with the biocides’ MIC values. No correlation was also observed between the isolates’ biofilm-forming capacity and the MIC values for the biocides.

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