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>.

scholarly journals Synergistic Activity of Colistin-Containing Combinations against Colistin-ResistantEnterobacteriaceae

2018 ◽  
Vol 62 (10) ◽  
Author(s):  
Thea Brennan-Krohn ◽  
Alejandro Pironti ◽  
James E. Kirby
Keyword(s):  
Treatment Options ◽  
Multidrug Resistant ◽  
Synergistic Activity ◽  
Gram Negative ◽  
Content Type ◽  
Carbapenem Resistant ◽  
Resistant Strains ◽  
Bacterial Outer Membrane ◽  
Time Kill ◽  
Synergistic Combinations

ABSTRACTResistance to colistin, a polypeptide drug used as an agent of last resort for the treatment of infections caused by multidrug-resistant (MDR) and extensively drug-resistant (XDR) Gram-negative bacteria, including carbapenem-resistantEnterobacteriaceae(CRE), severely limits treatment options and may even transform an XDR organism into one that is pan-resistant. We investigated the synergistic activity of colistin in combination with 19 antibiotics against a collection of 20 colistin-resistantEnterobacteriaceaeisolates, 15 of which were also CRE. All combinations were tested against all strains using an inkjet printer-assisted digital dispensing checkerboard array, and the activities of those that demonstrated synergy by this method were evaluated against a single isolate in a time-kill synergy study. Eighteen of 19 combinations demonstrated synergy against two or more isolates, and the 4 most highly synergistic combinations (colistin combined with linezolid, rifampin, azithromycin, and fusidic acid) were synergistic against ≥90% of strains. Sixteen of 18 combinations (88.9%) that were synergistic in the checkerboard array were also synergistic in a time-kill study. Our findings demonstrate that colistin in combination with a range of antibiotics, particularly protein and RNA synthesis inhibitors, exhibits synergy against colistin-resistant strains, suggesting that colistin may exert a subinhibitory permeabilizing effect on the Gram-negative bacterial outer membrane even in isolates that are resistant to it. These findings suggest that colistin combination therapy may have promise as a treatment approach for patients infected with colistin-resistant XDR Gram-negative pathogens.

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 A review on bacterial resistance to carbapenems: epidemiology, detection and treatment options

2020 ◽  
Vol 6 (3) ◽  
pp. FSO438 ◽  
Author(s):  
Ann A Elshamy ◽  
Khaled M Aboshanab
Keyword(s):  
Public Health ◽  
Bacterial Resistance ◽  
Antimicrobial Agents ◽  
Treatment Options ◽  
Carbapenem Resistance ◽  
Multidrug Resistant ◽  
Mechanisms Of Resistance ◽  
Carbapenem Resistant ◽  
Public Health Threat ◽  
Carbapenem Resistant Enterobacteriaceae

Carbapenems are a class of antimicrobial agents reserved for infections caused by multidrug-resistant microorganisms. The emergence of carbapenem resistance has become a serious public health threat. This type of antimicrobial resistance is spreading at an alarming rate, resulting in major outbreaks and treatment failure of community-acquired and nosocomial infections caused by the clinically relevant carbapenem-producing Enterobacteriaceae or carbapenem-resistant Enterobacteriaceae. This review is focused on carbapenem resistance, including mechanisms of resistance, history and epidemiology, phenotypic and genotypic detection in the clinically relevant bacterial pathogens and the possible treatment options available.

scholarly journals Infections Due to Acinetobacter baumannii in the ICU: Treatment Options

2017 ◽  
Vol 38 (03) ◽  
pp. 311-325 ◽  
Author(s):  
George Zhanel ◽  
Nina Clark ◽  
Joseph Lynch
Keyword(s):  
Antimicrobial Agents ◽  
Treatment Options ◽  
Multidrug Resistant ◽  
Ventilator Associated Pneumonia ◽  
Resistance Determinants ◽  
Global Spread ◽  
Polymyxin E ◽  
Acinetobacter Spp ◽  
Geographic Regions ◽  
Icu Treatment

AbstractBacteria within the genus Acinetobacter (principally A. baumannii-calcoaceticus complex [ABC]) are gram-negative coccobacilli that may cause nosocomial infections in critically ill or debilitated patients (particularly ventilator-associated pneumonia and infections of the bloodstream, urinary tract, and wounds). Treatment of Acinetobacter infections is difficult, as Acinetobacter spp. are intrinsically resistant to multiple antimicrobial agents, and have a remarkable ability to acquire new resistance determinants via mechanisms that include plasmids, transposons, integrons, and resistance islands. Since the 1990s, global resistance to antimicrobials has escalated dramatically among ABC. Global spread of multidrug-resistant (MDR)-A. baumannii strains reflects dissemination of a few clones between hospitals, geographic regions, and continents; excessive use of antibiotics amplifies this spread. Many isolates are resistant to all antimicrobials except colistin (polymyxin E) and tigecycline, and some infections are untreatable with existing antimicrobial agents. Antimicrobial resistance poses a serious threat to treat or prevent infections due to ABC. Strategies to curtail environmental colonization with MDR-ABD will require aggressive infection control efforts and cohorting of infected patients. Thoughtful antibiotic strategies are essential to limit the spread of MDR-ABC. Optimal therapy will likely require combination antimicrobial therapy of existing antibiotics as well as development of novel antibiotic classes.

scholarly journals Metallo-beta-lactamase producing Pseudomonas aeruginosa in neonatal septicemia

2010 ◽  
Vol 2 (01) ◽  
pp. 014-016 ◽  
Author(s):  
Madhu Sharma ◽  
Sarita Yadav ◽  
Uma Chaudhary
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Neonatal Sepsis ◽  
Antimicrobial Agents ◽  
Multidrug Resistant ◽  
Beta Lactamase ◽  
Neonatal Septicemia ◽  
Gram Negative ◽  
Beta Lactamases ◽  
Gram Negative Organisms

ABSTRACTGram-negative bacilli are important agents causing neonatal sepsis. The organisms isolated are often resistant to multiple antimicrobials specially which are metallo-beta-lactamases (MβL) producers. Therefore, the present study was conducted with the objective to examine the incidence of MβL producing strains in multidrug resistant (MDR) Pseudomonas aeruginosa from cases of neonatal sepsis. Between January-December 2006, 1994 cases of neonatal sepsis were investigated. The isolates obtained were identified and tested for susceptibility to various antimicrobial agents. The multidrug resistant P. aeruginosa isolates were screened for the presence of MβL by imipenem-EDTA disc method. Five hundred and ninety three (29.73%) isolates were obtained from culture of neonates. Most frequent offender was P. aeruginosa (48.2%). There was an overall predominance of gram-negative organisms. MβL production was seen in 69.5% of imipenem-resistant P. aeruginosa isolates. MβL producing P. aeruginosa is an emerging threat in neonatal septicemia and a cause of concern for physicians treating such infections.

scholarly journals In Vitro Activity of WCK 5222 (Cefepime-Zidebactam) against Worldwide Collected Gram-Negative Bacilli Not Susceptible to Carbapenems

2020 ◽  
Vol 64 (12) ◽  
Author(s):  
James A. Karlowsky ◽  
Meredith A. Hackel ◽  
Samuel K. Bouchillon ◽  
Daniel F. Sahm
Keyword(s):  
Antimicrobial Agents ◽  
Multidrug Resistant ◽  
Limiting Factor ◽  
Gram Negative ◽  
Content Type ◽  
Microdilution Method ◽  
Carbapenem Resistant ◽  
Broth Microdilution Method ◽  
Universal Stability

ABSTRACT WCK 5222 (cefepime-zidebactam, 2 g + 1g, every 8 h [q8h]) is in clinical development for the treatment of infections caused by carbapenem-resistant and multidrug-resistant (MDR) Gram-negative bacilli. We determined the in vitro susceptibility of 1,385 clinical isolates of non-carbapenem-susceptible Enterobacterales, MDR Pseudomonas aeruginosa (also non-carbapenem susceptible), Stenotrophomonas maltophilia, and Burkholderia spp. collected worldwide (49 countries) from 2014 to 2016 to cefepime-zidebactam (1:1 ratio), ceftazidime-avibactam, imipenem-relebactam, ceftolozane-tazobactam, and colistin using the CLSI broth microdilution method. Cefepime-zidebactam inhibited 98.5% of non-carbapenem-susceptible Enterobacterales (n = 1,018) at ≤8 μg/ml (provisional cefepime-zidebactam-susceptible MIC breakpoint). Against the subset of metallo-β-lactamase (MBL)-positive Enterobacterales (n = 214), cefepime-zidebactam inhibited 94.9% of isolates at ≤8 μg/ml. Further, it inhibited 99.6% of MDR P. aeruginosa (n = 262) isolates at ≤32 μg/ml (proposed cefepime-zidebactam-susceptible pharmacokinetic/pharmacodynamic MIC breakpoint), including all MBL-positive isolates (n = 94). Moreover, cefepime-zidebactam was active against the majority of isolates of Enterobacterales (≥95%) and P. aeruginosa (99%) that were not susceptible to ceftazidime-avibactam, ceftolozane-tazobactam, imipenem-relebactam, and colistin. Most isolates (99%) of S. maltophilia (n = 101; MIC50, 8 μg/ml; MIC90, 32 μg/ml) and Burkholderia spp. (n = 4; MIC range, 16 to 32 μg/ml) were also inhibited by cefepime-zidebactam at ≤32 μg/ml. The activity of cefepime-zidebactam against carbapenem-resistant Gram-negative bacteria is ascribed to its β-lactam enhancer mechanism of action (i.e., zidebactam binding to penicillin binding protein 2 [PBP2] and its universal stability to both serine β-lactamases and MBLs). The results from this study support the continued development of cefepime-zidebactam as a potential therapy for infections caused by Enterobacterales, P. aeruginosa, and other nonfermentative Gram-negative bacilli where resistance to marketed antimicrobial agents is a limiting factor.

scholarly journals Current treatment options for infections caused by carbapenem-resistant Enterobacteriaceae in patients with hematological malignancies

2020 ◽  
Vol 15 (2) ◽  
pp. 92-107
Author(s):  
G. A. Klyasova
Keyword(s):  
Hematological Malignancies ◽  
Treatment Options ◽  
Multidrug Resistant ◽  
Current Treatment ◽  
Infectious Complications ◽  
Common Complication ◽  
Gram Negative ◽  
Carbapenem Resistant ◽  
Lactamase Inhibitor ◽  
Carbapenem Resistant Enterobacteriaceae

Infections are a common complication in patients with hematological malignancies, especially during neutropenia. Recently, an increase in multidrug-resistant gram-negative pathogens has been observed in the etiology of infectious complications, including carbapenem-resistant Enterobacteriaceae. However, therapeutic options for treatment of these infections are limited. The review represents treatment options for infections caused by carbapenem-resistant Enterobacteriaceae, including the use of reserve drugs such as polymyxin, carbapenems, tigecycline, as well as a new antibiotic – ceftazidime-avibactam, which contains a new β-lactamase inhibitor with unique properties.

scholarly journals Phenotypic and genotypic detection of carbapenemase enzymes producing gram-negative bacilli isolated from patients in Khartoum State

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 1656
Author(s):  
R.A. Dahab ◽  
Alamin Mohamed Ibrahim ◽  
Hisham N. Altayb
Keyword(s):  
Treatment Options ◽  
Multidrug Resistant ◽  
Cross Sectional Study ◽  
Biochemical Tests ◽  
Isolation And Identification ◽  
Cross Sectional ◽  
Gram Negative ◽  
Clinical Specimens ◽  
Carbapenem Resistant ◽  
Life Threatening

Background: Carbapenems are used as antibiotics of last resort for treating infections due to multidrug-resistant Gram-negative bacilli, but emergence of Carbapenem resistant Gram-negative bacilli have been reported due to the production of Carbapenemase enzymes that significantly limits treatment options for life-threatening infections. Objective: This study aimed to detect Carbapenem resistant Gram-negative bacilli from patients attended to different hospitals in Khartoum state and to detect Carbapenemase enzymes production by phenotypic and genotypic methods. Methods: A hospital based cross sectional study was conducted in Khartoum state in the period from February to August 2016. Hundred and forty nine Gram-negative bacilli bacteria were isolated from different clinical specimens. Blood agar, Chromogenic agar media, MacConkey agar, XLD mediaandstandard biochemical tests were used for isolation and identification of Gram-negative bacilli from different samples. Standard antimicrobial susceptibility testing to Carbapenem antibiotic was performed for all isolates, then detection of Carbapenemase enzymes production for the resistant isolates was performed using Modified Hodge Test and PCR. Results: Hundred and forty nine Gram-negative bacilli were isolated from 147 different clinical specimens. The most predominant Gram-negative bacilli isolates was E.coli (54.4%), followed by Klebsiella species (29.5%). More than fifty percent of the isolates were Carbapenem resistant. Fifty six percent of the resistant isolates were positive by Modified Hodge Test. By using PCR, 17.3% of resistant organisms were harbored blaOXA48 gene, and 6.7% harbored blaIMP gene. E.coli was the most bacteria that harbored the blaoxa48 followed by Klebsiella species. blaIMP gene was harbored only by E.coli. Conclusion: The percentage of resistance to Carbapenems due to production of Carbapenemase enzymes is very high in Sudan.BlaOXA48 gene is more predominant than blaIMP in this study.

scholarly journals Genomic Insights Into Last-Line Antimicrobial Resistance in Multidrug-Resistant Staphylococcus and Vancomycin-Resistant Enterococcus

2021 ◽  
Vol 12 ◽  
Author(s):  
Adrianna M. Turner ◽  
Jean Y. H. Lee ◽  
Claire L. Gorrie ◽  
Benjamin P. Howden ◽  
Glen P. Carter
Keyword(s):  
Molecular Mechanisms ◽  
Antimicrobial Agents ◽  
Treatment Options ◽  
Multidrug Resistant ◽  
Vancomycin Resistant Enterococcus ◽  
Human Pathogens ◽  
Mechanisms Of Resistance ◽  
Global Spread ◽  
Vancomycin Resistant ◽  
Emergence Of Resistance

Multidrug-resistant Staphylococcus and vancomycin-resistant Enterococcus (VRE) are important human pathogens that are resistant to most clinical antibiotics. Treatment options are limited and often require the use of ‘last-line’ antimicrobials such as linezolid, daptomycin, and in the case of Staphylococcus, also vancomycin. The emergence of resistance to these last-line antimicrobial agents is therefore of considerable clinical concern. This mini-review provides an overview of resistance to last-line antimicrobial agents in Staphylococcus and VRE, with a particular focus on how genomics has provided critical insights into the emergence of resistant clones, the molecular mechanisms of resistance, and the importance of mobile genetic elements in the global spread of resistance to linezolid.

scholarly journals Intra-pleural colistin methanesulfonate therapy for pleural infection caused by carbapenem-resistant Acinetobacter baumannii: a successful case report

2014 ◽  
Vol 6 (3) ◽  
Author(s):  
Muhammad Asim Rana ◽  
Basheer Abd El Rahaman ◽  
Ahmed Fouad Mady ◽  
Mohammed Al Odat ◽  
Abdurehman Al Harthy ◽  
...  
Keyword(s):  
Treatment Options ◽  
Multidrug Resistant ◽  
Antimicrobial Treatment ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Carbapenem Resistant ◽  
Unsuccessful Treatment ◽  
Successful Case ◽  
Pleural Infection ◽  
Colistin Methanesulfonate

Infections caused by carbapenem-resistant, Gram-negative bacteria are an increasing clinical challenge, since the antimicrobial treatment options are often limited to colistin methanesulfonate. No data are available regarding the pharmacokinetics of colistin in pleural fluid. We report the case of a 92-year old man with ventilator-associated pneumonia and pleurisy caused by <em>Acinetobacter</em> <em>baumannii</em> and <em>Escherichia coli</em>, which were both multidrug-resistant. After an unsuccessful treatment with intravenous colistin methanesulfonate and imipenem-cilastatin, the addition of intra-pleural colistin methanesulfonate to the intravenous treatment led to a prompt clinical, radiological and microbiological resolution. This is the first report of a successful use of intra-pleural colistin in the literature. The intra-pleural colistin therapy should be considered in selected cases of pleurisy caused by multi-resistant Gram-negative bacteria.

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