scholarly journals Epidemiology and Diagnostics of Carbapenem Resistance in Gram-negative Bacteria

2019 ◽  
Vol 69 (Supplement_7) ◽  
pp. S521-S528 ◽  
Author(s):  
Patrice Nordmann ◽  
Laurent Poirel
Keyword(s):  
Large Population ◽  
Carbapenem Resistance ◽  
Population Based ◽  
Resistance Mechanisms ◽  
Rapid Diagnostic Tests ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Global Epidemic ◽  
Carbapenem Resistant ◽  
The Impact

Abstract Carbapenem resistance in gram-negative bacteria has caused a global epidemic that continues to grow. Although carbapenemase-producing Enterobacteriaceae have received the most attention because resistance was first reported in these pathogens in the early 1990s, there is increased awareness of the impact of carbapenem-resistant nonfermenting gram-negative bacteria, such as Acinetobacter baumannii, Pseudomonas aeruginosa, and Stenotrophomonas maltophilia. Moreover, evaluating the problem of carbapenem resistance requires the consideration of both carbapenemase-producing bacteria as well as bacteria with other carbapenem resistance mechanisms. Advances in rapid diagnostic tests to improve the detection of carbapenem resistance and the use of large, population-based datasets to capture a greater proportion of carbapenem-resistant organisms can help us gain a better understanding of this urgent threat and enable physicians to select the most appropriate antibiotics.

scholarly journals Identification of blaGIM-1 in Acinetobacter variabilis isolated from the hospital environment in Tamil Nadu, India

2019 ◽  
Author(s):  
Prasanth Manohar ◽  
Murugavel Ragavi ◽  
Ashby Augustine ◽  
Hrishikesh MV ◽  
Nachimuthu Ramesh
Keyword(s):  
Tamil Nadu ◽  
Carbapenem Resistance ◽  
Resistance Mechanisms ◽  
Hospital Environment ◽  
Resistant Bacteria ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Carbapenem Resistant ◽  
Hospital Environments ◽  
Surveillance Programs

AbstractBackgroundEmergence of carbapenem resistance mechanisms among Gram-negative bacteria is a worrisome health problem. Here, we focused on to identify the presence of carbapenem-resistant bacteria among the samples collected from hospital environments in Tamil Nadu.MethodsA total of 30 hospital environmental samples were collected between August 2017 and January 2018 from hospitals located in Chennai and Vellore such as lift switches, stair rails, switchboards, nursing desks, used nursing gloves, door handles, wheelchairs, touch screens, chairs and from pillars inside the hospitals.Results and discussionA total of 22 carbapenem-resistant Gram-negative bacteria were isolated that included Escherichia coli, Klebsiella sp., Enterobacter sp., Salmonella sp., Pseudomonas aeruginosa and Acinetobacter sp. Interestingly, blaGIM-1 was detected in Acinetobacter variabilis strain isolated in samples collected from hospitals. Unlike other studies, the identified GIM-1 was not plasmid encoded, and this is the first report for the presence of GIM-1 (German imipenemase) in India.ConclusionExtensive surveillance programs are necessary to trace the uncontrolled spread of carbapenem-resistance genes in order to reduce the rapid spread of resistance.

scholarly journals Changing Epidemiology and Decreased Mortality Associated With Carbapenem-resistant Gram-negative Bacteria, 2000–2017

2020 ◽  
Author(s):  
Ahmed Babiker ◽  
Lloyd G Clarke ◽  
Melissa Saul ◽  
Julie A Gealey ◽  
Cornelius J Clancy ◽  
...  
Keyword(s):  
Patient Outcomes ◽  
Carbapenem Resistance ◽  
Bloodstream Infections ◽  
Gram Negative Bacteria ◽  
Term Care ◽  
Gram Negative ◽  
Carbapenem Resistant ◽  
Healthcare Crisis ◽  
The Impact ◽  
Over Time

Abstract Background Carbapenem-resistant gram-negative bacteria (CRGNB) continue to present a global healthcare crisis. We aimed to identify emerging trends of CRGNB over nearly 2 decades and describe the impact of CRGNB on patient outcomes. Methods Patients from whom CRGNB were isolated between 2000 and 2017 were included in the study. Carbapenem resistance was defined by the most recent breakpoints and applied across the study period. Patient demographics, clinical characteristics, and outcomes were retrieved from the electronic health record. Results A total of 94 888 isolates from 64 422 patients were identified; 9882 (10%) isolates from 4038 patients were carbapenem-resistant. Pseudomonas aeruginosa was the most common CRGNB each year. The second most common CRGNB emerged in waves over time. Carbapenem daily defined doses increased in parallel with CRGNB rates (R2 = 0.8131). The overall 30-day mortality rate was 19%, which decreased from 24% in 2000 to 17% in 2017 (P = .003; R2 = .4330). Among patients with CRGNB bloodstream infections (n = 319), overall 30- and 90-day mortality rates were 27% and 38%, respectively. Charlson score (adjusted odds ratio [aOR], 1.11 per point), intensive care unit residence (aOR, 7.32), and severe liver disease (aOR, 4.8.4) were independent predictors of 30-day mortality, while receipt of transplantation was associated with lower rates of death (aOR, 0.39). Among patients admitted between 2011 and 2017 (n = 2230), 17% died during hospitalization, 32% were transferred to long-term care facilities, and 38% were discharged home. Conclusions CRGNB emerged in waves over time, causing high rates of mortality. Despite increasing rates of CRGNB, overall patient outcomes have improved, suggesting that recognition and novel therapeutics have made a major impact.

scholarly journals An overview of carbapenem, its resistance and therapeutic options for infections caused by carbapenem resistant bacteria

2020 ◽  
Vol 9 (9) ◽  
pp. 1454
Author(s):  
Hari P. Nepal ◽  
Rama Paudel
Keyword(s):  
Bacterial Infections ◽  
Carbapenem Resistance ◽  
Therapeutic Options ◽  
Resistant Bacteria ◽  
Gram Negative Bacteria ◽  
Beta Lactam ◽  
Gram Negative ◽  
Penicillin Binding Proteins ◽  
Carbapenem Resistant ◽  
The World

Carbapenems are beta-lactam drugs that have broadest spectrum of activity. They are commonly used as the drugs of last resort to treat complicated bacterial infections. They bind to penicillin binding proteins (PBPs) and inhibit cell wall synthesis in bacteria. Important members that are in clinical use include doripenem, ertapenem, imipenem, and meropenem. Unlike other members, imipenem is hydrolyzed significantly by renal dehydropeptidase; therefore, it is administered together with an inhibitor of renal dehydropeptidase, cilastatin. Carbapenems are usually administered intravenously due to their low oral bioavailability. Most common side effects of these drugs include nausea, vomiting, diarrhea, skin rashes, and reactions at the infusion sites. Increasing resistance to these antibiotics is being reported throughout the world and is posing a threat to public health.  Primary mechanisms of carbapenem resistance include expulsion of drug and inactivation of the drug by production of carbapenemases which may not only hydrolyze carbapenem, but also cephalosporin, penicillin, and aztreonam. Resistance especially among Gram negative bacteria is of much concern since there are only limited therapeutic options available for infections caused by carbapenem resistant Gram-negative bacterial pathogens. Commonly used drugs to treat such infections include polymyxins, fosfomycin and tigecycline.

Determination of carbapenemase genes in clinical isolates using Cepheid Xpert Carba-R

2021 ◽  
pp. 16-19
Author(s):  
N. I. Gabrielyan ◽  
V. G. Kormilitsyna ◽  
V. K. Zaletaeva ◽  
A. V. Krotevich ◽  
I. A. Miloserdov ◽  
...  
Keyword(s):  
Targeted Therapy ◽  
Infection Control ◽  
Resistance Genes ◽  
Carbapenem Resistance ◽  
Critical Issue ◽  
Sensitivity Study ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Carbapenem Resistant

Detection of carbapenem resistance genes is a critical issue for hospitals due to possible recommendations for infection control and targeted therapy. The Cepheid Xpert instrument, a Carba-R test for the detection and differentiation of five common carbapenemase genes, was tested from September 2020 to February 2021. As part of the approbation, 20 tests were provided. This review presents the results of the approbation of a relatively regular sensitivity study on Siemens WalkAway‑96 plus. Cepheid Xpert Carba-R analysis has been shown to be an accurate and fast tool for detecting colonization by carbapenem-resistant gram-negative bacteria, which can help limit the spread of these organisms in hospitals.

scholarly journals In vivo studies on antibiotic combination for the treatment of carbapenem-resistant Gram-negative bacteria: a systematic review and meta-analysis protocol

2020 ◽  
Vol 4 (1) ◽  
pp. e100055
Author(s):  
Elda Righi ◽  
Luigia Scudeller ◽  
Margherita Chiamenti ◽  
Kamilia Abdelraouf ◽  
Thomas Lodise ◽  
...  
Keyword(s):  
Systematic Review ◽  
Meta Analysis ◽  
Resistant Bacteria ◽  
Gram Negative Bacteria ◽  
In Vivo Models ◽  
Gram Negative ◽  
Carbapenem Resistant ◽  
The Impact ◽  
Antibiotic Combination

ObjectiveThere is poor evidence to determine the superiority of combination regimens versus monotherapy against infections due to carbapenem-resistant (CR) Gram-negative bacteria. In vivo models can simulate the pathophysiology of infections in humans and assess antibiotic efficacy. We aim to investigate in vivo effects of antibiotic combination on mortality and disease burden for infections due to CR Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacteriaceae and provide an unbiased overview of existing knowledge. The results of the study can help prioritising future research on the most promising therapies against CR bacteria.Methods and analysisThis protocol was formulated using the Systematic Review Protocol for Animal Intervention Studies (SYRCLE) Checklist. Publications will be collected from PubMed, Scopus, Embase and Web of Science. Quality checklists adapted by Collaborative Approach to Meta-Analysis and Review of Animal Data from Experimental Studies and SYRCLE’s risk of bias tool will be used. If the meta-analysis seems feasible, the ES and the 95% CI will be analysed. The heterogeneity between studies will be assessed by I2 test. Subgroup meta-analysis will be performed when possible to assess the impact of the studies on efficacy of the treatments. Funnel plotting will be used to evaluate the risk of publication bias.DisseminationThis systematic review and meta-analysis is part of a wider research collaboration project, the COmbination tHErapy to treat sepsis due to carbapenem-Resistant bacteria in adult and paediatric population: EvideNCE and common practice (COHERENCE) study that includes also the analyses of in vitro and human studies. Data will be presented at international conferences and the results will be published in peer-reviewed journals.PROSPERO registration numberCRD42019128104(available at: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42019128104).

Diversity of Carbapenem Resistance Mechanisms in Clinical Gram-Negative Bacteria in Pakistan

2020 ◽  
Author(s):  
Linda Hadjadj ◽  
Muhammad Ali Syed ◽  
Shahid Ahmad Abbasi ◽  
Jean-Marc Rolain ◽  
Bushra Jamil
Keyword(s):  
Carbapenem Resistance ◽  
Resistance Mechanisms ◽  
Gram Negative Bacteria ◽  
Gram Negative

scholarly journals In Vitro Activity of Cefiderocol Against a Broad Range of Clinically Important Gram-negative Bacteria

2019 ◽  
Vol 69 (Supplement_7) ◽  
pp. S544-S551 ◽  
Author(s):  
Yoshinori Yamano
Keyword(s):  
Efflux Pump ◽  
Bloodstream Infections ◽  
Resistance Mechanisms ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Highly Active ◽  
Carbapenem Resistant ◽  
Surveillance Programs ◽  
Tract Infections

AbstractCarbapenem-resistant gram-negative bacteria including Enterobacteriaceae as well as nonfermenters, such as Pseudomonas aeruginosa and Acinetobacter baumannii, have emerged as significant global clinical threats. Although new agents have recently been approved, none are active across the entire range of resistance mechanisms presented by carbapenem-resistant gram-negative bacteria. Cefiderocol, a novel siderophore cephalosporin, has been shown in large surveillance programs and independent in vitro studies to be highly active against all key gram-negative causative pathogens isolated from patients with hospital-acquired or ventilator-associated pneumonia, bloodstream infections, or complicated urinary tract infections. The improved structure, the novel mode of entry into bacteria, and its stability against carbapenemases enables cefiderocol to exhibit high potency against isolates that produce carbapenemases of all classes or are resistant due to porin channel mutations and/or efflux pump overexpression. Resistance to cefiderocol is uncommon and appears to be multifactorial.

scholarly journals Performance of the BD Phoenix CPO detect assay for detection and classification of carbapenemase-producing organisms

2020 ◽  
Author(s):  
Laura Berneking ◽  
Anna Both ◽  
Benjamin Berinson ◽  
Armin Hoffmann ◽  
Marc Lütgehetmann ◽  
...  
Keyword(s):  
Susceptibility Testing ◽  
Carbapenem Resistance ◽  
Alternative Methods ◽  
Gram Negative Bacteria ◽  
Accurate Identification ◽  
Gram Negative ◽  
Carbapenem Resistant ◽  
Gradient Diffusion ◽  
Assay Performance

AbstractIncreasing worldwide, prevalence of carbapenem-resistant gram-negative bacteria demands urgent a need for rapid detection and accurate identification of carbapenemases. The BD Phoenix CPO detect (PCD) assay possesses an in-built capacity for parallel susceptibility testing and detection of carbapenemases. Here, the ability of the assay to detect and classify carbapenemase production was tested in a collection of carbapenem-resistant Enterobacterales and non-fermentative gram-negative rods. The ability of the PCD assay to detect and classify carbapenemases was investigated in a collection of 194 clinical, carbapenem-resistant isolates (Enterobacterales [n = 65]; non-fermentative gram-negative rods [n = 129]). AST results were compared to MICS determined by gradient diffusion to determine accuracy of the PCD assay. The accuracy of the PCD assay to detect carbapenemases was compared to the results of molecular isolate characterization using a LDT multiplex carbapenemase PCR assay. All 194 isolates classified as carbapenem-resistant by reference susceptibility testing were also classified correctly as CRO by the PCD assay. Performance analysis of the PCD assay to detect carbapenemase production revealed an overall sensitivity of 98.29% and specificity of 17.95% for the detection of carbapenemase production. For the classification of carbapenemases classes A, B, and D, the PCD correctly classified 79.17% Enterobacterales and 67.16% non-fermentative gram-negative rods. The PCD assay is a reliable tool for the detection of carbapenem resistance and allows for parallel analysis of carbapenemase production. However, while sensitivity is high, low specificity in carbapenemase detection and erroneous classification demands mandatory confirmation by alternative methods, especially in non-fermentative gram-negative bacteria.

scholarly journals Carbapenem Resistance in Gram-negative Bacteria in South-western Nigeria: The Role of Extended-spectrum β-lactamase CTX-M-15

2018 ◽  
pp. 344-349
Author(s):  
Do Ogbolu ◽  
Ma Webber
Keyword(s):  
Outer Membrane ◽  
Antimicrobial Agents ◽  
Random Amplified Polymorphic Dna ◽  
Outer Membrane Proteins ◽  
Carbapenem Resistance ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Carbapenem Resistant ◽  
Extended Spectrum

Objective: To determine the role of extended-spectrum β-lactamases in carbapenem-resistant Gram-negative bacteria from south-western Nigeria. Methods: Twenty-seven carbapenem-resistant isolates that were found to be non-carbapenemase producers (15 Escherichia coli, 9 Klebsiella pneumoniae and 3 Pseudomonas aeruginosa) were further studied. These isolates were subjected to analysis including phenotypic and genotypic detection of various β-lactamases, efflux activity, outer membrane protein, plasmids replicon typing, detection of transferable genes and resistances and typing using random amplified polymorphic DNA tests. Results: No isolates demonstrated de-repression of efflux, but all showed either complete loss or reduced production of outer membrane proteins. Transconjugants from these strains contained various genes including plasmid-mediated quinolone resistance and extended-spectrum beta-lactamases. All the transconjugants carried the blaCTX-M-15 gene. The transconjugants had varying minimum inhibitory concentrations of carbapenems ranging from 0.03 μg/ml to 8 μg/ml. Varying resistances to other antimicrobial agents were also transferred with the plasmids. The donor isolates were not clonally related by molecular typing. Conclusion: Resistance to carbapenem antibiotics in this sample was not mediated only by carbapenemases but also by production of extended-spectrum β-lactamases (largely CTX-M-15), accompanied by protein loss. This was an important mechanism underpinning carbapenem resistance in these clinical isolates of various species.

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