Antimicrobial Resistance in the Intensive Care Unit

Bacterial infections are a frequent cause of hospitalization, and nosocomial infections are an increasingly common condition, particularly within the acute/critical care setting. Infection control practices and new antimicrobial development have primarily focused on gram-positive bacteria; however, in recent years, the incidence of infections caused by gram-negative bacteria has risen considerably in intensive care units. Infections caused by multidrug-resistant (MDR) gram-negative organisms are associated with high morbidity and mortality, with significant direct and indirect costs resulting from prolonged hospitalizations due to antibiotic treatment failures. Of particular concern is the increasing prevalence of antimicrobial resistance to β-lactam antibiotics (including carbapenems) among Pseudomonas aeruginosa and Acinetobacter baumannii and, recently, among pathogens of the Enterobacteriaceae family. Treatment options for infections caused by these pathogens are limited. Antimicrobial stewardship programs focus on optimizing the appropriate use of currently available antimicrobial agents with the goals of improving outcomes for patients with infections caused by MDR gram-negative organisms, slowing the progression of antimicrobial resistance, and reducing hospital costs. Newly approved treatment options are available, such as β-lactam/β-lactamase inhibitor combinations, which significantly extend the armamentarium against MDR gram-negative bacteria.

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Bacteriocins, Antimicrobial Peptides from Bacterial Origin: Overview of Their Biology and Their Impact against Multidrug-Resistant Bacteria

Microorganisms ◽

10.3390/microorganisms8050639 ◽

2020 ◽

Vol 8 (5) ◽

pp. 639 ◽

Cited By ~ 13

Author(s):

Alexis Simons ◽

Kamel Alhanout ◽

Raphaël E. Duval

Keyword(s):

Antimicrobial Resistance ◽

Bacterial Infections ◽

Antimicrobial Agents ◽

Multidrug Resistant ◽

Resistant Bacteria ◽

Gram Negative Bacteria ◽

Multidrug Resistant Bacteria ◽

Gram Negative ◽

Gram Positive Bacteria ◽

Further Development

Currently, the emergence and ongoing dissemination of antimicrobial resistance among bacteria are critical health and economic issue, leading to increased rates of morbidity and mortality related to bacterial infections. Research and development for new antimicrobial agents is currently needed to overcome this problem. Among the different approaches studied, bacteriocins seem to be a promising possibility. These molecules are peptides naturally synthesized by ribosomes, produced by both Gram-positive bacteria (GPB) and Gram-negative bacteria (GNB), which will allow these bacteriocin producers to survive in highly competitive polymicrobial environment. Bacteriocins exhibit antimicrobial activity with variable spectrum depending on the peptide, which may target several bacteria. Already used in some areas such as agro-food, bacteriocins may be considered as interesting candidates for further development as antimicrobial agents used in health contexts, particularly considering the issue of antimicrobial resistance. The aim of this review is to present an updated global report on the biology of bacteriocins produced by GPB and GNB, as well as their antibacterial activity against relevant bacterial pathogens, and especially against multidrug-resistant bacteria.

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Synthesis, In Vitro and In Silico Studies of Indolequinone Derivatives against Clinically Relevant Bacterial Pathogens

Current Topics in Medicinal Chemistry ◽

10.2174/1568026620666191223110518 ◽

2020 ◽

Vol 20 (3) ◽

pp. 192-208 ◽

Cited By ~ 1

Author(s):

Talita Odriane Custodio Leite ◽

Juliana Silva Novais ◽

Beatriz Lima Cosenza de Carvalho ◽

Vitor Francisco Ferreira ◽

Leonardo Alves Miceli ◽

...

Keyword(s):

In Silico ◽

Bacterial Infections ◽

Antimicrobial Agents ◽

Mass Spectrometry Analysis ◽

World Health ◽

Gram Negative Bacteria ◽

Gram Negative ◽

Dione Derivative ◽

In Silico Studies

Background: According to the World Health Organization, antimicrobial resistance is one of the most important public health threats of the 21st century. Therefore, there is an urgent need for the development of antimicrobial agents with new mechanism of action, especially those capable of evading known resistance mechanisms. Objective: We described the synthesis, in vitro antimicrobial evaluation, and in silico analysis of a series of 1H-indole-4,7-dione derivatives. Methods: The new series of 1H-indole-4,7-diones was prepared with good yield by using a copper(II)- mediated reaction between bromoquinone and β-enamino ketones bearing alkyl or phenyl groups attached to the nitrogen atom. The antimicrobial potential of indole derivatives was assessed. Molecular docking studies were also performed using AutoDock 4.2 for Windows. Characterization of all compounds was confirmed by one- and two-dimensional NMR techniques 1H and 13C NMR spectra [1H, 13C – APT, 1H x 1H – COSY, HSQC and HMBC], IR and mass spectrometry analysis. Results: Several indolequinone compounds showed effective antimicrobial profile against Grampositive (MIC = 16 µg.mL-1) and Gram-negative bacteria (MIC = 8 µg.mL-1) similar to antimicrobials current on the market. The 3-acetyl-1-(2,5-dimethylphenyl)-1H-indole-4,7-dione derivative exhibited an important effect against different biofilm stages formed by a serious hospital life-threatening resistant strain of Methicillin-Resistant Staphylococcus aureus (MRSA). A hemocompatibility profile analysis based on in vitro hemolysis assays revealed the low toxicity effects of this new series. Indeed, in silico studies showed a good pharmacokinetics and toxicological profiles for all indolequinone derivatives, reinforcing their feasibility to display a promising oral bioavailability. An elucidation of the promising indolequinone derivatives binding mode was achieved, showing interactions with important sites to biological activity of S. aureus DNA gyrase. These results highlighted 3-acetyl-1-(2-hydroxyethyl)-1Hindole- 4,7-dione derivative as broad-spectrum antimicrobial prototype to be further explored for treating bacterial infections. Conclusion: The highly substituted indolequinones were obtained in moderate to good yields. The pharmacological study indicated that these compounds should be exploited in the search for a leading substance in a project aimed at obtaining new antimicrobials effective against Gram-negative bacteria.

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Crumbling the Castle: Targeting DNABII Proteins for Collapsing Bacterial Biofilms as a Therapeutic Approach to Treat Disease and Combat Antimicrobial Resistance

Antibiotics ◽

10.3390/antibiotics11010104 ◽

2022 ◽

Vol 11 (1) ◽

pp. 104

Author(s):

James V. Rogers ◽

Veronica L. Hall ◽

Charles C. McOsker

Keyword(s):

Antimicrobial Resistance ◽

Bacterial Infections ◽

Antimicrobial Agents ◽

Defense Mechanism ◽

Treatment Options ◽

Bacterial Biofilms ◽

Host Immune System ◽

New Antibiotics ◽

Financial Burdens ◽

Global Threat

Antimicrobial resistance (AMR) is a concerning global threat that, if not addressed, could lead to increases in morbidity and mortality, coupled with societal and financial burdens. The emergence of AMR bacteria can be attributed, in part, to the decreased development of new antibiotics, increased misuse and overuse of existing antibiotics, and inadequate treatment options for biofilms formed during bacterial infections. Biofilms are complex microbiomes enshrouded in a self-produced extracellular polymeric substance (EPS) that is a primary defense mechanism of the resident microorganisms against antimicrobial agents and the host immune system. In addition to the physical protective EPS barrier, biofilm-resident bacteria exhibit tolerance mechanisms enabling persistence and the establishment of recurrent infections. As current antibiotics and therapeutics are becoming less effective in combating AMR, new innovative technologies are needed to address the growing AMR threat. This perspective article highlights such a product, CMTX-101, a humanized monoclonal antibody that targets a universal component of bacterial biofilms, leading to pathogen-agnostic rapid biofilm collapse and engaging three modes of action—the sensitization of bacteria to antibiotics, host immune enablement, and the suppression of site-specific tissue inflammation. CMTX-101 is a new tool used to enhance the effectiveness of existing, relatively inexpensive first-line antibiotics to fight infections while promoting antimicrobial stewardship.

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Treatment Options for Carbapenem-resistant Gram-negative Bacterial Infections

Clinical Infectious Diseases ◽

10.1093/cid/ciz830 ◽

2019 ◽

Vol 69 (Supplement_7) ◽

pp. S565-S575 ◽

Cited By ~ 36

Author(s):

Yohei Doi

Keyword(s):

Bacterial Infections ◽

Treatment Options ◽

Clinical Development ◽

Gram Negative Bacteria ◽

First Line ◽

Safe Alternative ◽

New Agents ◽

Gram Negative ◽

Carbapenem Resistant

AbstractAntimicrobial resistance has become one of the greatest threats to public health, with rising resistance to carbapenems being a particular concern due to the lack of effective and safe alternative treatment options. Carbapenem-resistant gram-negative bacteria of clinical relevance include the Enterobacteriaceae, Pseudomonas aeruginosa, Acinetobacter baumannii, and more recently, Stenotrophomonas maltophilia. Colistin and tigecycline have been used as first-line agents for the treatment of infections caused by these pathogens; however, there are uncertainties regarding their efficacy even when used in combination with other agents. More recently, several new agents with activity against certain carbapenem-resistant pathogens have been approved for clinical use or are reaching late-stage clinical development. They include ceftazidime-avibactam, ceftolozane-tazobactam, meropenem-vaborbactam, imipenem-cilastatin-relebactam, plazomicin, eravacycline, and cefiderocol. In addition, fosfomycin has been redeveloped in a new intravenous formulation. Data regarding the clinical efficacy of these new agents specific to infections caused by carbapenem-resistant pathogens are slowly emerging and appear to generally favor newer agents over previous best available therapy. As more treatment options become widely available for carbapenem-resistant gram-negative infections, the role of antimicrobial stewardship will become crucial in ensuring appropriate and rationale use of these new agents.

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Antimicrobial Resistance Surveillance of Gram-Negative Bacteria Isolated from Intensive Care Units of Four Different Hospitals in Turkey

Chemotherapy ◽

10.1159/000048550 ◽

2001 ◽

Vol 47 (6) ◽

pp. 396-408 ◽

Cited By ~ 4

Author(s):

Bekir Sami Kocazeybek

Keyword(s):

Intensive Care ◽

Antimicrobial Resistance ◽

Intensive Care Units ◽

Gram Negative Bacteria ◽

Gram Negative ◽

Antimicrobial Resistance Surveillance

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Extended Spectrum Beta-Lactamase (ESBL) Produced by Gram-Negative Bacteria in Trinidad and Tobago

International Journal of Microbiology ◽

10.1155/2021/5582755 ◽

2021 ◽

Vol 2021 ◽

pp. 1-16

Author(s):

Patrick Eberechi Akpaka ◽

Angel Vaillant ◽

Clyde Wilson ◽

Padman Jayaratne

Keyword(s):

Trinidad And Tobago ◽

Bacterial Infections ◽

High Morbidity ◽

Beta Lactamase ◽

Beta Lactam ◽

Esbl Production ◽

Gram Negative ◽

Extended Spectrum Beta Lactamase ◽

Extended Spectrum ◽

Gram Negative Organisms

Gram-negative bacterial infections are a global health problem. The production of beta-lactamase is still the most vital factor leading to beta-lactam resistance. In Trinidad and Tobago, extended spectrum beta-lactamase (ESBL) production has been detected and reported mainly in the isolates of Klebsiella pneumoniae and Escherichia coli and constitutes a public health emergency that causes high morbidity and mortality in some patients. In this literature review, the authors cover vast information on ESBL frequency and laboratory detection using both conventional and molecular methods from clinical data. The aim is to make the reader reflect on how the actual knowledge can be used for rapid detection and understanding of the spread of antimicrobial resistance problems stemming from ESBL production among common Gram-negative organisms in the health care system.

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Etiology and Antimicrobial Resistance of Secondary Bacterial Infections in Patients Hospitalized With COVID-19 in Wuhan, China: A Retrospective Analysis

10.21203/rs.3.rs-47870/v1 ◽

2020 ◽

Author(s):

Jie Li ◽

Junwei Wang ◽

Yi Yang ◽

Peishan Cai ◽

Jingchao Cao ◽

...

Keyword(s):

Antimicrobial Resistance ◽

Bacterial Infections ◽

Virus Disease ◽

Considerable Proportion ◽

Gram Negative Bacteria ◽

Gram Negative ◽

Carbapenem Resistant ◽

Union Hospital ◽

Critical Patients ◽

Resistance Rates

Abstract Background: A considerable proportion of patients hospitalized with corona virus disease 2019 (COVID-19) have acquired secondary bacterial infections (SBIs). We report the etiology and antimicrobial resistance of bacteria to provide theoretical basis for appropriate infection therapy.Methods: In the retrospective study, we reviewed electronic medical records of all the patients hospitalized with COVID-19 in the Wuhan Union hospital from January 27 to March 17, 2020. According to the inclusion and exclusion criteria, patients who acquired SBIs were enrolled. Demographic, clinical course, etiology and antimicrobial resistance data of the SBIs were collected. Outcomes were also compared between patients who were classified as severe on admission and those who were classified as critical.Results: 6.8% (102/1495) of the patients with COVID-19 had acquired SBIs and almost half of them (50, 49.0%) died during hospitalization. Compared with the severe patients, the critical patients had a higher chance of SBIs. 159 strains of bacteria were isolated, 85.5% of which were Gram-negative bacteria. The top three bacteria of SBIs were A. baumannii (35.8%), K. pneumoniae (30.8%) and Staphylococcus (8.8%). The isolation rate of carbapenem-resistant A. baumannii and K. pneumoniae were 91.2% and 75.5%, respectively. Meticillin resistance was in 100% of Staphylococcus, and vancomycin resistance was not found. Conclusions: SBIs may occur in patients hospitalized with COVID-19 and lead to high mortality. The incidence of SBIs was associated with the grade on admission. Gram-negative bacteria, especially A. baumannii and K. pneumoniae, were the main bacteria and the resistance rates of the major isolated bacteria were generally high.

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Incidence of Hospital-Acquired Bacterial Pneumonia and Its Resistance Profiles in Patients Admitted to Intensive Care Unit

Global Journal of Health Science ◽

10.5539/gjhs.v9n3p73 ◽

2016 ◽

Vol 9 (3) ◽

pp. 73 ◽

Cited By ~ 1

Author(s):

Vahid Boostani ◽

Farzaneh Dehghan ◽

Afsaneh Karmostaji ◽

Nader Zolghadri ◽

Afsaneh Shafii

Keyword(s):

Intensive Care Unit ◽

Intensive Care ◽

Antimicrobial Resistance ◽

Bacterial Pneumonia ◽

Clinical Signs ◽

Resistance Rate ◽

Gram Negative Bacteria ◽

Cross Sectional ◽

Gram Negative ◽

Hospital Acquired

Hospital-acquired bacterial pneumonia (HABP) is one of the most important causes of morbidity, mortality and economic problems especially for patients admitted in the intensive care unit (ICU) ward. The aim of this study was to determine the incidence of nosocomial pneumonia in ICU, identify the causative bacteria and their resistance profiles. This cross sectional study was performed on 214 patients who were admitted in the ICU ward of a general hospital requiring mechanical ventilation for at least 48 h. Identification of HABP was based on the clinical signs manifested 48 h or more after admission, new chest X-ray infiltrates and microbiologic examination of endo tracheal secretion. Data were analyzed using SPSS 21 to perform the descriptive statistics. The isolated gram negative bacteria were Klebsiella pneumoniae (50%), Staphylococcus aureus (18.7%), Acinetobacter baumannii (12.5%), Escherichia coli (12.5%) and Pseudomonas aeroginosa (6.3%). The maximum antimicrobial resistance of gram negative bacteria was to Cefazolin (100%) and Ampicillin (84.6%), while antimicrobial resistance to Clindamycin, Azithromycin, Amoxycillin+clavulanate, Trimethoprim+sulfamethoxazole and Ciprofloxacin was 33.3%. No resistance was seen towards carbapenems.The most frequent gram negative isolated bacterium was K. pneumoniae, and maximum antimicrobial resistance rate was observed for Cefazolin and Ampicillin, which is due to betalactamase production.

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