scholarly journals Review of therapeutic options for infections with carbapenem-resistant Klebsiella pneumoniae

2020 ◽  
Vol 10 (3) ◽  
pp. 115-124
Author(s):  
Rasmus G. Bandick ◽  
Soraya Mousavi ◽  
Stefan Bereswill ◽  
Markus M. Heimesaat
Keyword(s):  
Clinical Trials ◽  
Klebsiella Pneumoniae ◽  
Control Treatment ◽  
Drug Resistant ◽  
Treatment Regimens ◽  
Combined Application ◽  
Carbapenem Resistant ◽  
Antibiotic Compounds ◽  
Life Threatening

AbstractInfections with multi-drug resistant (MDR) bacteria including carbapenem-resistant Klebsiella pneumoniae are emerging worldwide but are difficult to treat with the currently available antibiotic compounds and therefore constitute serious threats to human health. This prompted us to perform a literature survey applying the MEDLINE database and Cochrane Register of Controlled Trials including clinical trials comparing different treatment regimens for infections caused by carbapenem-resistant K. pneumoniae. Our survey revealed that a combined application of antibiotic compounds such as meropenem plus vaborbactam, meropenem plus colistin and carbapenem plus carbapenem, resulted in significantly increased clinical cure and decreased mortality rates as compared to respective control treatment. However, further research on novel antibiotic compounds, but also on antibiotic-independent molecules providing synergistic or at least resistance-modifying properties needs to be undertaken in vitro as well as in large clinical trials to provide future options in the combat of emerging life-threatening infections caused by MDR bacteria.

scholarly journals Combination Therapy of Phage vB_KpnM_P-KP2 and Gentamicin Combats Acute Pneumonia Caused by K47 Serotype Klebsiella pneumoniae

2021 ◽  
Vol 12 ◽  
Author(s):  
Zijing Wang ◽  
Ruopeng Cai ◽  
Gang Wang ◽  
Zhimin Guo ◽  
Xiao Liu ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Klebsiella Pneumoniae ◽  
Therapeutic Effect ◽  
Combined Treatment ◽  
Animal Experiments ◽  
Opportunistic Pathogen ◽  
Drug Resistant ◽  
Carbapenem Resistant ◽  
Acute Pneumonia

Klebsiella pneumoniae (K. pneumoniae) is an important nosocomial and community acquired opportunistic pathogen which causes various infections. The emergence of multi-drug resistant (MDR) K. pneumoniae and carbapenem-resistant hypervirulent K. pneumoniae (CR-hvKP) has brought more severe challenge to the treatment of K. pneumoniae infection. In this study, a novel bacteriophage that specifically infects K. pneumoniae was isolated and named as vB_KpnM_P-KP2 (abbreviated as P-KP2). The biological characteristics of P-KP2 and the bioinformatics of its genome were analyzed, and then the therapeutic effect of P-KP2 was tested by animal experiments. P-KP2 presents high lysis efficiency in vitro. The genome of P-KP2 shows homology with nine phages which belong to “KP15 virus” family and its genome comprises 172,138 bp and 264 ORFs. Besides, P-KP2 was comparable to gentamicin in the treatment of lethal pneumonia caused by K. pneumoniae W-KP2 (K47 serotype). Furthermore, the combined treatment of P-KP2 and gentamicin completely rescued the infected mice. Therefore, this study not only introduces a new member to the phage therapeutic library, but also serves as a reference for other phage-antibiotic combinations to combat MDR pathogens.

scholarly journals Biosynthesis of Zinc Oxide Nanoparticles from Acacia nilotica (L.) Extract to Overcome Carbapenem-Resistant Klebsiella Pneumoniae

Molecules ◽  
2021 ◽  
Vol 26 (7) ◽  
pp. 1919
Author(s):  
Elsayim Rasha ◽  
AlOthman Monerah ◽  
Alkhulaifi Manal ◽  
Ali Rehab ◽  
Doud Mohammed ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Zinc Oxide ◽  
Klebsiella Pneumoniae ◽  
Zinc Oxide Nanoparticles ◽  
Acacia Nilotica ◽  
Oxide Nanoparticles ◽  
Zno Nps ◽  
X Ray ◽  
Carbapenem Resistant

Recently, concerns have been raised globally about antimicrobial resistance, the prevalence of which has increased significantly. Carbapenem-resistant Klebsiella pneumoniae (KPC) is considered one of the most common resistant bacteria, which has spread to ICUs in Saudi Arabia. This study was established to investigate the antibacterial activity of biosynthesized zinc oxide nanoparticles (ZnO-NPs) against KPC in vitro and in vivo. In this study, we used the aqueous extract of Acacia nilotica (L.) fruits to mediate the synthesis of ZnO-NPs. The nanoparticles produced were characterized by UV-vis spectroscopy, zetasizer and zeta potential analyses, X-ray diffraction (XRD) spectroscopy, Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), and transmission electron microscopy (TEM). The antimicrobial activity of ZnO-NPs against KPC was determined via the well diffusion method, and determining minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC), the results showed low MIC and MBC when compared with the MIC and MBC of Imipenem and Meropenem antibiotics. The results of in vitro analysis were supported by the results upon applying ZnO-NP ointment to promote wound closure of rats, which showed better wound healing than the results with imipenem ointment. The biosynthesized ZnO-NPs showed good potential for use against bacteria due to their small size, applicability, and low toxicity to human cells.

scholarly journals Enterobacteriaceae isolates carrying the New Delhi metallo-β-lactamase gene in Yemen

2014 ◽  
Vol 63 (10) ◽  
pp. 1316-1323 ◽  
Author(s):  
Alima Gharout-Sait ◽  
Samer-Ahmed Alsharapy ◽  
Lucien Brasme ◽  
Abdelaziz Touati ◽  
Rachida Kermas ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Susceptibility Testing ◽  
Enterobacter Cloacae ◽  
New Delhi ◽  
Carbapenem Resistant ◽  
Genes Encoding ◽  
Phenotypic Tests ◽  
Lactamase Gene ◽  
Sequence Types

Ten carbapenem-resistant Enterobacteriaceae (eight Klebsiella pneumoniae isolates and two Enterobacter cloacae) isolates from Yemen were investigated using in vitro antimicrobial susceptibility testing, phenotypic carbapenemase detection, multilocus sequence typing (MLST) and replicon typing. Carbapenemase, extended-spectrum β-lactamase (ESBL) and plasmid-mediated quinolone resistance determinant genes were identified using PCR and sequencing. All of the 10 carbapenem-resistant Enterobacteriaceae were resistant to β-lactams, tobramycin, ciprofloxacin and cotrimoxazole. Imipenem, doripenem and meropenem MICs ranged from 2 to >32 mg l−1 and ertapenem MICs ranged from 6 to >32 mg l−1. All of the K. pneumoniae isolates showed ESBL activity in phenotypic tests. Genes encoding bla NDM were detected in all strains. All K. pneumoniae strains produced CTX-M-15 ESBL and SHV β-lactamases. TEM-1 β-lactamase was detected in seven isolates. Nine isolates were qnr positive including QnrB1, QnrA1 and QnrS1, and six isolates produced AAC-6′-Ib-cr. MLST identified five different sequence types (STs): ST1399, ST147, ST29, ST405 and ST340. Replicon typing showed the presence of IncFII1K plasmids in four transformants. To the best of our knowledge, this is the first report of NDM-1-producing Enterobacteriaceae isolates in Yemen.

scholarly journals 1348. In vitro Activity of Plazomicin, a Next-Generation Aminoglycoside, Against Carbapenemase-Producing Klebsiella pneumoniae

2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S412-S413
Author(s):  
Michael R Jacobs ◽  
Caryn E Good ◽  
Ayman M Abdelhamed ◽  
Daniel D Rhoads ◽  
Kristine M Hujer ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Carbapenem Resistance ◽  
Vitro Activity ◽  
In Vitro Activity ◽  
Next Generation ◽  
Aminoglycoside Resistance ◽  
Carbapenem Resistant ◽  
Carbapenemase Gene ◽  
Research Grant

Abstract Background Plazomicin is a next-generation aminoglycoside with in vitro activity against multidrug-resistant Gram-negative species, including carbapenem-resistant isolates. The Consortium on Resistance Against Carbapenems in Klebsiella and other Enterobacteriaceae (CRACKLE) is a federally funded, prospective multicenter consortium of 20 hospitals from nine US healthcare systems to track carbapenem-resistant Enterobacteriaceae. Methods Minimum inhibitory concentrations (MICs) of plazomicin were determined by broth microdilution according to current CLSI guidelines against a collection of 697 carbapenem-resistant Klebsiella pneumoniae with defined carbapenem resistance mechanisms, including KPC and OXA carbapenemases. Isolates were submitted by participating CRACKLE centers. Results Carbapenemases present in study isolates included KPC-2 (n = 323), KPC-3 (n = 364), KPC-4 (n = 2), OXA-48 like (n = 7), and NDM (n = 1). Plazomicin MICs ranged from ≤0.12 to >32 mg/L, with MIC50 and MIC90 values of 0.25 and 1 mg/L, respectively (figure). MICs of 689 (98.8%) isolates were ≤4 mg/L, while MICs of the remaining eight isolates were >32 mg/L. Plazomicin MICs were related to specific carbapenemases present in isolates: of eight isolates with MICs >32 mg/L, seven contained OXA-48 like and one contained KPC-3, suggesting that these isolates possess an aminoglycoside-resistance mechanism on the same plasmid as their carbapenemase gene, such as a 16S ribosomal RNA methyltransferase, against which plazomicin is not active. Conclusion Plazomicin has good in vitro potency against a collection of carbapenemase-producing K. pneumoniae, with MIC90 value of 1 mg/L and MICs of ≤4 mg/L for 98.9% of isolates. Disclosures M. R. Jacobs, Achaogen: Investigator, Research grant. Shionogi: Investigator, Research grant. L. Connolly, Achaogen, Inc.: Consultant, Consulting fee. K. M. Krause, Achaogen: Employee, Salary. S. S. Richter, bioMerieux: Grant Investigator, Research grant. BD Diagnostics: Grant Investigator, Research grant. Roche: Grant Investigator, Research grant. Hologic: Grant Investigator, Research grant. Diasorin: Grant Investigator, Research grant. Accelerate: Grant Investigator, Research grant. Biofire: Grant Investigator, Research grant. D. Van Duin, achaogen: Scientific Advisor, Consulting fee. shionogi: Scientific Advisor, Consulting fee. Allergan: Scientific Advisor, Consulting fee. Astellas: Scientific Advisor, Consulting fee. Neumedicine: Scientific Advisor, Consulting fee. Roche: Scientific Advisor, Consulting fee. T2 Biosystems: Scientific Advisor, Consulting fee.

scholarly journals Klebsiella virus UPM2146 lyses multiple drug-resistant Klebsiella pneumoniae in vitro and in vivo

PLoS ONE ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. e0245354
Author(s):  
Omar Assafiri ◽  
Adelene Ai-Lian Song ◽  
Geok Hun Tan ◽  
Irwan Hanish ◽  
Amalia Mohd Hashim ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Multiple Drug ◽  
Drug Resistant ◽  
Zebrafish Model ◽  
Whole Genome Analysis ◽  
Narrow Host Range ◽  
Opportunistic Bacteria ◽  
Multiple Drug Resistant

Klebsiella pneumoniae are opportunistic bacteria found in the gut. In recent years they have been associated with nosocomial infections. The increased incidence of multiple drug-resistant K. pneumoniae makes it necessary to find new alternatives to treat the disease. In this study, phage UPM2146 was isolated from a polluted lake which can lyse its host K. pneumoniae ATCC BAA-2146. Observation from TEM shows that UPM2146 belongs to Caudoviriales (Order) based on morphological appearance. Whole genome analysis of UPM2146 showed that its genome comprises 160,795 bp encoding for 214 putative open reading frames (ORFs). Phylogenetic analysis revealed that the phage belongs to Ackermannviridae (Family) under the Caudoviriales. UPM2146 produces clear plaques with high titers of 1010 PFU/ml. The phage has an adsorption period of 4 min, latent period of 20 min, rise period of 5 min, and releases approximately 20 PFU/ bacteria at Multiplicity of Infection (MOI) of 0.001. UPM2146 has a narrow host-range and can lyse 5 out of 22 K. pneumoniae isolates (22.72%) based on spot test and efficiency of plating (EOP). The zebrafish larvae model was used to test the efficacy of UPM2146 in lysing its host. Based on colony forming unit counts, UPM2146 was able to completely lyse its host at 10 hours onwards. Moreover, we show that the phage is safe to be used in the treatment against K. pneumoniae infections in the zebrafish model.

In silico Repurposing of Anticancer Drug (5-Fluorouracil) as an Antibacterial Agent against Klebsiella pneumoniae

2021 ◽  
Vol 18 ◽  
Author(s):  
Amey Sharma ◽  
Apoorva Rana ◽  
Lakshya Mangtani ◽  
Aakanksha Kalra ◽  
Ravi Ranjan Kumar Niraj
Keyword(s):  
Molecular Docking ◽  
Klebsiella Pneumoniae ◽  
Thymidylate Synthase ◽  
In Silico ◽  
Homology Modelling ◽  
Klebsiella Pneumonia ◽  
Drug Resistant ◽  
Vitro Analysis ◽  
In Vitro Analysis

Background: Infections caused by drug resistant microorganisms have been increasing worldwide thereby being one of the major causes of morbidity in the 21st century. Klebsiella pneumoniae is one such bacteria causing lung inflammation, lung injury and death. Emergence of hyper-virulent and drug resistant species such as ESBL and CRKP has made this microbe a serious and urgent threat. The pace of emergence of these species is outgrowing the development of novel drug and vaccine candidates thereby focusing on drug repurposing approach. Objective: 1. Homology Modelling of Thymidylate Synthase. 2. Verification of Modelled Structure. 3. Molecular Docking. 4. Molecular Dynamic Simulation of Docked Complex. 5. In vitro analysis of 5-FU activity against Klebsiella pneumonia. Method: The 3-D structure of Thymidylate Synthase was predicted using Swiss-Model server and validated by in silico approaches. - Determination protein-protein interactions using STRING database. - Molecular docking. - MD simulations of 5-FU with predicted structure of thymidylate synthase. - In vitro antimicrobial drug sensitivity assay at different concentrations. Result: Hydrogen bond was observed in Molecular Docking - Protein-ligand complex remains stable during simulation. - 5-FU shows antimicrobial activity against Klebsiella pneumonia during In vitro study. Conclusion: Both In silico as well as in vitro analysis have indicated that 5-FU can potentially be developed as an antimicrobial agent towards Klebsiella pneumonia

Detection of extensively drug-resistant and hypervirulent Klebsiella pneumoniae ST15, ST147, ST377 and ST442 in Iran

2021 ◽  
Author(s):  
Sara Davoudabadi ◽  
Hossein Goudarzi ◽  
Mehdi Goudarzi ◽  
Abdollah Ardebili ◽  
Ebrahim Faghihloo ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Pcr Amplification ◽  
Multidrug Resistant ◽  
Diffusion Method ◽  
Drug Resistant ◽  
Carbapenem Resistant ◽  
Extensively Drug Resistant ◽  
String Test ◽  
Pcr Method ◽  
Extensively Drug Resistance

Abstract In this study, we focused on the emergence of extensively drug-resistant (XDR), pandrug-resistant (PDR), and hypervirulent Klebsiella pneumoniae (hvKP) in Iran. During 2018 to 2020 a total of 52 K. pneumoniae isolates were collected from different clinical specimens. The hvKP isolates were identified by PCR amplification of virulence and capsular serotype-specific genes. Hypermucoviscous K. pneumoniae (hmKP) were identified by string test. Carbapenem-resistant hvKP (CR-hvKP), multidrug-resistant hvKP (MDR-hvKP), extensively drug-resistant hvKP (XDR-hvKP), and pandrug-resistant hvKP (PDR-hvKP) were determined by disc diffusion method, Carba-NP test and PCR method. XDR-hvKP isolates were typed by multilocus sequence typing (MLST). Among all K. pneumoniae isolates 14 (26.9%) were identified as hvKP and 78.6% (11/14) of them were hmKP however, none of the classic K. pneumoniae (cKP) isolates were hmKP. The predominant capsular serotype of hvKP was K2 (42.85%) followed by K1 (35.71%). The prevalence of MDR-hvKP, XDR-hvKP and PDR-hvKP isolates were 6 (42.9%), 5 (35.7%) and 1 (7.1%), respectively. ESBL production was found in 85.7% of hvKP isolates and most of them carried bla TEM gene (78.6%) and 6 isolates (42.9%) were CR-hvKP. Among hvKP isolates, 1 (7.1%), 2 (14.3%), 3 (21.4%), 8 (28.6%), and 11 (78.6%) carried bla NDM-6, bla OXA-48, bla CTX-M, bla SHV, and bla TEM genes, respectively. According to MLST analysis, 2, 1, 1, and 1 XDR-hvKP isolates belonged to ST15, ST377, ST442, and ST147, respectively. The occurrence of such isolates is deeply concerning due to the combination of hypervirulence and extensively drug-resistance or pandrug-resistance.

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