scholarly journals Treatment Options for Carbapenem-resistant Gram-negative Bacterial Infections

2019 ◽  
Vol 69 (Supplement_7) ◽  
pp. S565-S575 ◽  
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.

scholarly journals Flavonoids as Inhibitors of Bacterial Efflux Pumps

Molecules ◽  
2021 ◽  
Vol 26 (22) ◽  
pp. 6904
Author(s):  
Martin Waditzer ◽  
Franz Bucar
Keyword(s):  
Bacterial Infections ◽  
Treatment Options ◽  
Plant Secondary Metabolites ◽  
Herbal Medicines ◽  
Efflux Pumps ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Plant Constituents ◽  
Kaempferol Glycosides

Flavonoids are widely occurring secondary plant constituents, and are abundant in vegetable and fruit diets as well as herbal medicines. Therapeutic treatment options for bacterial infections are limited due to the spread of antimicrobial resistances. Hence, in a number of studies during the last few years, different classes of plant secondary metabolites as resistance-modifying agents have been carried out. In this review, we present the role of flavonoids as inhibitors of bacterial efflux pumps. Active compounds could be identified in the subclasses of chalcones, flavan-3-ols, flavanones, flavones, flavonols, flavonolignans and isoflavones; by far the majority of compounds were aglycones, although some glycosides like kaempferol glycosides with p-coumaroyl acylation showed remarkable results. Staphylococcus aureus NorA pump was the focus of many studies, followed by mycobacteria, whereas Gram-negative bacteria are still under-investigated.

scholarly journals Clinical Treatment Options for Carbapenem-resistant Gram-negative Infections in China: a Single Centre Real-world Experience

2021 ◽  
Author(s):  
Ruanmei Sheng ◽  
Xuemin Wang ◽  
Yanqiang Hou ◽  
Jun Liu ◽  
Zhiwen Yang
Keyword(s):  
Success Rate ◽  
Bacterial Infections ◽  
Clinical Success ◽  
Treatment Options ◽  
Clinical Success Rate ◽  
Gram Negative Bacteria ◽  
Single Centre ◽  
Gram Negative ◽  
Carbapenem Resistant ◽  
Clinical Strategies

Abstract Carbapenem-resistant gram-negative bacteria constitute a serious threat to public health worldwide. However, as a result of the complexities of clinical therapy, antibiotic options against carbapenem-resistant pathogens have not yet been fully standardized. Here, we conducted a retrospective study in 65,000 inpatients over a 2-year period that involved a total of 86 patients from whom carbapenem-resistant gram-negative bacteria were isolated. Monotherapy using trimethoprim/ sulfamethoxazole, amikacin, meropenem, and/or doxycycline in our hospital exhibited a clinical success rate of 83.3% for carbapenem-resistant Klebsiella pneumoniae, monotherapy using moxifloxacin, piperacillin/tazobactam, cefepime, and/or ceftazidime for carbapenem-resistant Pseudomonas aeruginosa exhibited a clinical success rate of 77.7%, and monotherapy using cefoperazone/sulbactam or combination therapy with tigecycline and cefoperazone/sulbactam for carbapenem-resistant Acinetobacter baumannii exhibited a clinical success rate of 62.1%. Our findings highlight the clinical strategies used in our hospital to successfully treat carbapenem-resistant gram-negative bacterial infections.

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.

scholarly journals Dissemination of Carbapenem-resistance and Plasmids-encoding Carbapenemases in Gram-negative Bacteria Isolated from India

2020 ◽  
Author(s):  
Prasanth Manohar ◽  
Sebastian Leptihn ◽  
Bruno S. Lopes ◽  
Nachimuthu Ramesh
Keyword(s):  
Tamil Nadu ◽  
Treatment Options ◽  
Public Health Problem ◽  
Carbapenem Resistance ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
E Coli ◽  
Diagnostic Center ◽  
Lactamase Gene

AbstractCarbapenem resistance in Gram-negative bacteria is an ongoing public-health problem of global dimensions leaving very few treatment options for severely infected patients. This study focuses on the dissemination of plasmid-borne carbapenemase genes in Gram-negative bacteria in Tamil Nadu, India. A total of 151 non-repetitive isolates belonging to 11 genera were collected from a diagnostic center in Tamil Nadu. E. coli (n=57) isolates were classified as, Enteropathogenic (n=12), Enteroaggregative (n=9), Enterohemorrhagic (n=8), Enterotoxigenic (n=3), Enteroinvasive (n=1) and unclassified E. coli (n=24). Of the 45 Klebsiella species, 14 were K1 whereas 11 were K2 serotype and in 20 Klebsiella serotype could not be determined. Other isolates (n=49) consisted of P. aeruginosa, S. typhi, E. cloacae, A. baumannii, S. marcescens, A. xylosoxidans, P. mirabilis and E. meningoseptica. Of the 151 isolates, 71% (n=107) and 68% (n=103) were found to be resistant to meropenem and imipenem respectively. The most prevalent beta-lactamase gene was blaNDM-1 (21%, 12/57) followed by blaOXA-181 (16%, 9/57), blaGES-9 (n=8), blaOXA-23 (n=7), blaIMP-1 (n=3), blaGES-1 (n=11) and blaOXA-51 (n=9). The unusual presence of blaOXA-23 was seen in E. coli (n=4), and blaOXA-23 and blaOXA-51 (IncA/C) in K. pneumoniae (n=3). Plasmid incompatibility (inc/rep) typing results showed that the plasmids carrying resistance genes (n=11) belonged to IncX, IncA/C, IncFIA-FIB and IncFIIA groups. E. coli and K. pneumoniae were able to transfer plasmid-borne carbapenemase via conjugation. This study highlights the prevalence of carbapenem resistance and the acquisition of plasmid-borne carbapenemase genes in Gram-negative bacteria highlighting the role of plasmid transfer in disseminating resistance.

scholarly journals Investigating colistin drug resistance: The role of high-throughput sequencing and bioinformatics

F1000Research ◽  
2019 ◽  
Vol 8 ◽  
pp. 150 ◽  
Author(s):  
Dickson Aruhomukama ◽  
Ivan Sserwadda ◽  
Gerald Mboowa
Keyword(s):  
Antibiotic Resistance ◽  
High Throughput ◽  
Bacterial Infections ◽  
High Throughput Sequencing ◽  
Health Concern ◽  
Gram Negative Bacteria ◽  
Drug Resistant ◽  
Colistin Resistance ◽  
Gram Negative

Bacterial infections involving antibiotic resistant gram-negative bacteria continue to increase and represent a major global public health concern. Resistance to antibiotics in these bacteria is mediated by chromosomal and/or acquired resistance mechanisms, these give rise to multi-drug resistant (MDR) or extensive drug resistant (XDR) bacterial strains. Most recently, a novel acquired plasmid mediated resistance mechanism to colistin, an antibiotic that had been set apart as the last resort antibiotic in the treatment of infections involving MDR and XDR gram-negative bacteria, has been reported. Plasmid mediated colistin resistant gram-negative bacteria have been described to be pan-drug resistant, implying a state devoid of alternative antibiotic therapeutic options. This review describes the evolution of antibiotic resistance to plasmid mediated colistin resistance, and discusses the potential role of high-throughput sequencing technologies, genomics and bioinformatics towards improving antibiotic resistance surveillance, the search for novel drug targets and precision antibiotic therapy focused at combating colistin resistance, and antimicrobial resistance as a whole.

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

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.

scholarly journals Infections with Carbapenem-Resistant Gram-Negative Bacteria are a Serious Problem Among Critically Ill Children: A Single-Centre Retrospective Study

Pathogens ◽  
2019 ◽  
Vol 8 (2) ◽  
pp. 69 ◽  
Author(s):  
Fatih Aygun ◽  
Fatma Deniz Aygun ◽  
Fatih Varol ◽  
Cansu Durak ◽  
Haluk Çokuğraş ◽  
...  
Keyword(s):  
Retrospective Study ◽  
Critically Ill ◽  
Bacterial Infections ◽  
Invasive Mechanical Ventilation ◽  
Critically Ill Children ◽  
Resistant Bacteria ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Carbapenem Resistant ◽  
Culture Positive

Children in paediatric intensive care units (PICUs) are vulnerable to infections because invasive devices are frequently used during their admission. We aimed to determine the prevalence, associated factors, and prognosis of infections in our PICU. This retrospective study evaluated culture results from 477 paediatric patients who were treated in the PICU between January 2014 and March 2019. Ninety patients (18.9%) had bacterial infections, with gram-negative bacteria being the predominant infectious agents. Culture-positive patients were younger than culture-negative patients, and age was related to mortality and various clinical factors. Culture-positive bacterial infections in the PICU were associated with increased use of invasive mechanical ventilation (odds ratio(OR); 2.254), red blood cell (RBC) transfusions (OR:2.624), and inotropic drugs (OR:2.262). Carbapenem resistance was found in approximately one-third of gram-negative bacteria, and was most common in tracheal aspirate specimens and cases involving Klebsiella spp. Total parenteral nutrition was a significant risk factor (OR:5.870). Positive blood culture results were associated with poorer patient survival than other culture results. These findings indicate that infections, especially those involving carbapenem-resistant bacteria, are an important issue when treating critically ill children.

Antimicrobial Resistance in the Intensive Care Unit

2016 ◽  
Vol 32 (1) ◽  
pp. 25-37 ◽  
Author(s):  
Shawn H. MacVane
Keyword(s):  
Intensive Care ◽  
Antimicrobial Resistance ◽  
Bacterial Infections ◽  
Antimicrobial Agents ◽  
Treatment Options ◽  
Hospital Costs ◽  
High Morbidity ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Gram Negative Organisms

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.

scholarly journals Cefiderocol for Extensively Drug-Resistant Gram-Negative Bacterial Infections: Real-world Experience From a Case Series and Review of the Literature

2020 ◽  
Vol 7 (6) ◽  
Author(s):  
Sandra Zingg ◽  
G Jacopo Nicoletti ◽  
Sabine Kuster ◽  
Milena Junker ◽  
Andreas Widmer ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Case Reports ◽  
Case Series ◽  
Gram Negative Bacteria ◽  
Drug Resistant ◽  
Gram Negative ◽  
Carbapenem Resistant ◽  
Extensively Drug Resistant ◽  
Health Care Associated Infections ◽  
Tract Infections

Abstract Cefiderocol is a new siderophore cephalosporin with activity against carbapenem-resistant gram-negative bacteria. Data on its clinical efficacy are limited to complicated urinary tract infections. We present a series of 3 patients successfully treated with cefiderocol for complicated health care–associated infections and review published case reports.

scholarly journals Resistance to colistin in Klebsiella pneumoniae: a 4.0 strain?

2017 ◽  
Vol 9 (2) ◽  
Author(s):  
Guido Granata ◽  
Nicola Petrosillo
Keyword(s):  
Infection Prevention ◽  
Antimicrobial Agents ◽  
Treatment Options ◽  
Multidrug Resistant ◽  
New Agents ◽  
Gram Negative ◽  
Beta Lactamases ◽  
Carbapenem Resistant ◽  
Chromosomal Genes ◽  
Global Spread

The global rise of multidrug-resistant gram-negative bacteria represents an increasing threat to patient safety. From the first observation of a carbapenem-resistant gramnegative bacteria a global spread of extendedspectrum beta-lactamases and carbapenemases producing <em>Klebsiella</em> <em>pneumoniae</em> has been observed. Treatment options for multidrug-resistant <em>K. pneumoniae</em> are actually limited to combination therapy with some aminoglycosides, tigecycline and to older antimicrobial agents. Unfortunately, the prevalence of colistin-resistant and tigecycline- resistant <em>K. pneumoniae</em> is increasing globally. Infection due to colistin-resistant <em>K. pneumoniae</em> represents an independent risk factor for mortality. Resistance to colistin in <em>K. pneumoniae</em> may be multifactorial, as it is mediated by chromosomal genes or plasmids. The emergence of transmissible, plasmidmediated colistin resistance is an alarming finding. The absence of new agents effective against resistant Gram-negative pathogens means that enhanced surveillance, compliance with infection prevention procedures, and antimicrobial stewardship programs will be required to limit the spread of colistinresistant <em>K. pneumoniae</em>.

Sign in / Sign up

Export Citation Format

Share Document