Genomic analysis of carbapenem resistant Pseudomonas aeruginosa ST143 clone showing susceptibility to broad spectrum cephalosporins

ABSTRACT As shifts in the epidemiology of β-lactamase-mediated resistance continue, carbapenem-resistant Enterobacterales (CRE) and carbapenem-resistant Pseudomonas aeruginosa (CRPA) are the most urgent threats. Although approved β-lactam (BL)–β-lactamase inhibitor (BLI) combinations address widespread serine β-lactamases (SBLs), such as CTX-M-15, none provide broad coverage against either clinically important serine-β-lactamases (KPC, OXA-48) or clinically important metallo-β-lactamases (MBLs; e.g., NDM-1). VNRX-5133 (taniborbactam) is a new cyclic boronate BLI that is in clinical development combined with cefepime for the treatment of infections caused by β-lactamase-producing CRE and CRPA. Taniborbactam is the first BLI with direct inhibitory activity against Ambler class A, B, C, and D enzymes. From biochemical and structural analyses, taniborbactam exploits substrate mimicry while employing distinct mechanisms to inhibit both SBLs and MBLs. It is a reversible covalent inhibitor of SBLs with slow dissociation and a prolonged active-site residence time (half-life, 30 to 105 min), while in MBLs, it behaves as a competitive inhibitor, with inhibitor constant (Ki) values ranging from 0.019 to 0.081 μM. Inhibition is achieved by mimicking the transition state structure and exploiting interactions with highly conserved active-site residues. In microbiological testing, taniborbactam restored cefepime activity in 33/34 engineered Escherichia coli strains overproducing individual enzymes covering Ambler classes A, B, C, and D, providing up to a 1,024-fold shift in the MIC. Addition of taniborbactam restored the antibacterial activity of cefepime against all 102 Enterobacterales clinical isolates tested and 38/41 P. aeruginosa clinical isolates tested with MIC90s of 1 and 4 μg/ml, respectively, representing ≥256- and ≥32-fold improvements, respectively, in antibacterial activity over that of cefepime alone. The data demonstrate the potent, broad-spectrum rescue of cefepime activity by taniborbactam against clinical isolates of CRE and CRPA.

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The Study of Bacillus Subtils Antimicrobial Activity on Some of the Pathological Isolates

International Journal of Drug Delivery Technology ◽

10.25258/ijddt.9.2.12 ◽

2019 ◽

Vol 9 (02) ◽

Author(s):

Hussein A Kadhum ◽

Thualfakar H Hasan2

Keyword(s):

Staphylococcus Aureus ◽

Pseudomonas Aeruginosa ◽

Antimicrobial Activity ◽

Bacillus Subtilis ◽

Bacterial Growth ◽

Broad Spectrum ◽

Inhibitory Activity ◽

Bacterial Pathogens ◽

Inhibitory Ability ◽

Selection Of

The study involved the selection of two isolates from Bacillus subtilis to investigate their inhibitory activity against some bacterial pathogens. B sub-bacteria were found to have a broad spectrum against test bacteria such as Staphylococcus aureus and Pseudomonas aeruginosa. They were about 23-30 mm and less against Klebsiella sp. The sensitivity of some antibodies was tested on the test samples. The results showed that the inhibitory ability of bacterial growth in the test samples using B. subtilis extract was more effective than the antibiotics used.

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Ceftolozane/Tazobactam-Induced Leukocytosis and Clinical Failure in a Patient Being Treated for Ventilator-Associated Pneumonia Caused by Carbapenem-Resistant Pseudomonas aeruginosa: a Case Report

SN Comprehensive Clinical Medicine ◽

10.1007/s42399-021-00750-5 ◽

2021 ◽

Vol 3 (2) ◽

pp. 701-704

Author(s):

Bejoy P. Maniara ◽

Ian Wells

Keyword(s):

Pseudomonas Aeruginosa ◽

Case Report ◽

Ventilator Associated Pneumonia ◽

Clinical Failure ◽

Carbapenem Resistant

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Prevalence of metallo-β-lactamase genes among Pseudomonas aeruginosa isolated from various clinical samples in China

Journal of Laboratory Medicine ◽

10.1515/labmed-2019-0162 ◽

2020 ◽

Vol 0 (0) ◽

Author(s):

Wei Wang ◽

Xiaoya Wang

Keyword(s):

Pseudomonas Aeruginosa ◽

Antibiotic Susceptibility ◽

Ethylenediaminetetraacetic Acid ◽

Carbapenem Resistance ◽

Opportunistic Pathogen ◽

Detection Methods ◽

Clinical Samples ◽

Routine Practice ◽

Carbapenem Resistant ◽

High Prevalence

AbstractBackgroundPseudomonas aeruginosa is an opportunistic pathogen which is associated with nosocomial infections and causes various diseases including urinary tract infection, pneumonia, soft-tissue infection and sepsis. The emergence of P. aeruginosa-acquired metallo-β-lactamase (MBL) is most worrisome and poses a serious threat during treatment and infection control. The objective of this study was to identify antibiotic susceptibility, phenotypic detection of MBL production and to determine the prevalence of MBL genes in carbapenem-resistant P. aeruginosa isolated from different clinical samples.MethodsA total of 329 non-duplicate P. aeruginosa isolated from various clinical samples from two hospitals in China between September 2017 and March 2019 were included in this study. Phenotypic detection of MBL was performed by the combined detection method using imipenem and imipenem-ethylenediaminetetraacetic acid (EDTA) discs. MBL-encoding genes including blaVIM-1, blaVIM-2, blaIMP-1, blaIMP-2, blaSPM-1, blaSIM, blaNDM-1 and blaGIM were detected by polymerase chain reaction (PCR).ResultsOf the 329 P. aeruginosa, majority of the isolates were resistant to imipenem (77.5%) followed by meropenem (64.7%). Of the 270 P. aeruginosa isolates tested, 149 (55.2%) isolates were found to be positive for MBL detection. Of the different samples, 57.8% (n = 26) of P. aeruginosa isolated from blood were found to be positive for MBL production. Of the various MBL genes, blaIMP-1 (28.2%) was the most predominant gene detected followed by blaVIM-2 (18.8%), blaVIM-1 (16.1%), blaNDM-1 (9.4%), blaIMP-2 (6.7%), blaSIM (6.0%), blaSPM-1 (4.0%) and blaGIM (1.3%) genes.ConclusionsThe high resistance of P. aeruginosa toward imipenem and meropenem and the high prevalence of blaIMP-1 and blaVIM-2 set the alarm on the increasing, perhaps the increased, carbapenem resistance. In addition to routine antibiotic susceptibility testings, our results emphasize the importance of both the phenotypic and genotypic MBL detection methods in routine practice for early detection of carbapenem resistance and to prevent further dissemination of this resistant pathogen.

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834. Clinical Outcomes with Carbapenem-Resistant Pseudomonas aeruginosa that Retain Susceptibility to Traditional Antipseudomonal β-lactams: Atlanta, 2016-2018

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1023 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S457-S458

Author(s):

Jessica Howard-Anderson ◽

Chris W Bower ◽

Gillian Smith ◽

Sarah W Satola ◽

Jesse T Jacob

Keyword(s):

Pseudomonas Aeruginosa ◽

Research Training ◽

Multivariable Analysis ◽

Care Facility ◽

Hospitalized Patients ◽

First Episode ◽

Common Source ◽

Unexpected Finding ◽

Term Care ◽

Carbapenem Resistant

Abstract Background Carbapenem-resistant Pseudomonas aeruginosa (CRPA) often results from multiple mechanisms, creating unique phenotypic patterns of resistance including retaining susceptibility to traditional antipseudomonal β-lactams: cefepime (FEP), ceftazidime (CAZ) and piperacillin-tazobactam (TZP). Outcomes of patients with CRPA susceptible to FEP, CAZ and TZP are unclear. Methods The Georgia Emerging Infections Programed performs active, population-based surveillance for CRPA (minimum inhibitory concentration [MIC] ≥ 8 µg/mL for doripenem, imipenem or meropenem) isolated from sterile sites, urine, lower respiratory tracts and wounds in metropolitan Atlanta. We created a retrospective cohort of adults without cystic fibrosis with their first episode of CRPA while hospitalized or hospitalized within 1 week, from 8/2016 – 7/2018. We compared patients with CRPA that remained susceptible to FEP, CAZ and TZP (“susceptible CRPA”) to those that were not (“resistant CRPA”) including multivariable logistic regression for 30-day mortality. Results Among 643 patients, 638 had susceptibility results available for FEP, CAZ or TZP. 60% were male, median age was 65 years, and median Charlson comorbidity index was 2 (Table 1). Most (66%) resided in a hospital or long-term care facility 4 days prior to culture. The most common source was urine (38%). Non-susceptibility to multiple antibiotic classes was common: 523 (81%) for 3 classes and 214 (33%) for 5 classes (Table 2). 220 (34%) patients had susceptible CRPA and compared to patients with resistant CRPA, were more likely to have lived in a private residence, have a community-associated infection, and less likely to be in the ICU previously (Table 1). Patients with susceptible CRPA had a similar crude 30-day mortality (16% vs 12%, p = 0.15) to those with resistant CRPA, but in a multivariable analysis had an increased 30-day mortality (OR 1.9; 95% CI 1.1–3.2). Table 1 (Part 1/2): Characteristics and outcomes of hospitalized patients with carbapenem-resistant Pseudomonas aeruginosa (CRPA) in metropolitan Atlanta, stratified by antipseudomonal β-lactam susceptibility Table 1 (Part 2/2): Characteristics and outcomes of hospitalized patients with carbapenem-resistant Pseudomonas aeruginosa (CRPA) in metropolitan Atlanta, stratified by antipseudomonal β-lactam susceptibility Table 2: Antibacterial susceptibility results for hospitalized patients with carbapenem-resistant Pseudomonas aeruginosa in metropolitan Atlanta Conclusion Over 1/3 of hospitalized patients with CRPA retained susceptibility to other antipseudomonal β-lactams, but had an increased mortality compared to CRPA resistant to other β-lactams. Further research into mechanisms of resistance or antibiotics received might help explain this unexpected finding. Disclosures Jessica Howard-Anderson, MD, Antibacterial Resistance Leadership Group (ARLG) (Other Financial or Material Support, The ARLG fellowship provides salary support for ID fellowship and mentored research training)

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Carbapenem-Resistant Pseudomonas aeruginosa Strains-Distribution of the Essential Enzymatic Virulence Factors Genes

Antibiotics ◽

10.3390/antibiotics10010008 ◽

2020 ◽

Vol 10 (1) ◽

pp. 8

Author(s):

Tomasz Bogiel ◽

Małgorzata Prażyńska ◽

Joanna Kwiecińska-Piróg ◽

Agnieszka Mikucka ◽

Eugenia Gospodarek-Komkowska

Keyword(s):

Pseudomonas Aeruginosa ◽

Alkaline Protease ◽

Virulence Genes ◽

Virulence Gene ◽

Hospital Environment ◽

Gene Encoding ◽

Virulence Gene Expression ◽

Carbapenem Resistant ◽

Antimicrobial Resistance Genes ◽

The Difference

Pseudomonas aeruginosa is one of the most commonly isolated bacteria from clinical specimens, with increasing isolation frequency in nosocomial infections. Herein, we investigated whether antimicrobial-resistant P. aeruginosa strains, e.g., metallo-beta-lactamase (MBL)-producing isolates, may possess a reduced number of virulence genes, resulting from appropriate genome management to adapt to a changing hospital environment. Hospital conditions, such as selective pressure, may lead to the replacement of virulence genes by antimicrobial resistance genes that are crucial to survive under current conditions. The study aimed to compare, using PCR, the frequency of the chosen enzymatic virulence factor genes (alkaline protease-aprA, elastase B-lasB, neuraminidases-nan1 and nan2, and both variants of phospholipase C-plcH and plcN) to MBL distribution among 107 non-duplicated carbapenem-resistant P. aeruginosa isolates. The gene encoding alkaline protease was noted with the highest frequency (100%), while the neuraminidase-1 gene was observed in 37.4% of the examined strains. The difference in lasB and nan1 prevalence amongst the MBL-positive and MBL-negative strains, was statistically significant. Although P. aeruginosa virulence is generally more likely determined by the complex regulation of the virulence gene expression, herein, we found differences in the prevalence of various virulence genes in MBL-producers.

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Genomic analysis of an extensively drug-resistant Pseudomonas aeruginosa ST312 harbouring IncU plasmid-mediated blaKPC-2 isolated from ascitic fluid

Journal of Global Antimicrobial Resistance ◽

10.1016/j.jgar.2021.03.012 ◽

2021 ◽

Vol 25 ◽

pp. 151-153

Author(s):

Daniela Cristina Tartari ◽

Caetana Paes Zamparette ◽

Graciele Martini ◽

Sandra Christakis ◽

Luiz Henrique Costa ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Ascitic Fluid ◽

Genomic Analysis ◽

Drug Resistant ◽

Extensively Drug Resistant

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157. A Multidisciplinary Approach to Carbapenem Stewardship at a Large Community Hospital in Brooklyn, New York

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.202 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S88-S88

Author(s):

Samuel Simon ◽

Rosanna Li ◽

Yu Shia Lin ◽

Suri Mayer ◽

Edward Chapnick ◽

...

Keyword(s):

New York ◽

Pseudomonas Aeruginosa ◽

Klebsiella Pneumoniae ◽

Infectious Diseases ◽

Antimicrobial Stewardship ◽

Audit And Feedback ◽

Chi Square ◽

Carbapenem Resistant ◽

Days Of Therapy ◽

Prospective Audit And Feedback

Abstract Background Carbapenem-resistant gram-negative organisms are a continuously mounting threat, underscoring the need for effective antimicrobial stewardship interventions to improve the use of carbapenems. We sought to implement several multidisciplinary antimicrobial stewardship interventions beginning in January 2019 in an effort to reduce unnecessary meropenem use and the incidence of carbapenem-resistant gram-negatives. Methods Prospective audit and feedback was utilized daily in combination with weekly stewardship rounds between an Infectious Diseases pharmacist and physician in the Intensive Care Units. A second Infectious Diseases physician attended weekly interdisciplinary rounds on meropenem high-use units. Meropenem Days of Therapy (DOT) per 1,000 patient days and the incidence of meropenem resistant Pseudomonas aeruginosa and Klebsiella pneumoniae were compared by the chi-square test of proportions. Results Between 2018 and 2019 the institution’s meropenem DOT per 1,000 patient days decreased 33%, from 57 to 38 days per 1,000 patient days (difference, 19 days per 1,000 patient days; p< 0.001). In the hospital antibiogram, the meropenem susceptibility of Pseudomonas aeruginosa over the same time period increased from 71% to 77% of isolates (difference, 6%; p = 0.009). A non-significant decrease in the susceptibility of meropenem to Klebsiella pneumoniae was also observed from 92 to 90% (difference, 2%: p = 0.1658). Conclusion These data support the need for antimicrobial stewardship efforts targeting broad-spectrum antimicrobials such as meropenem. In the setting of a sustained decrease in meropenem use over 12 months, we observed a significant improvement in the percent susceptibility rate of Pseudomonas aeruginosa to meropenem for the first time in five years. Disclosures All Authors: No reported disclosures

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Antimicrobial and antibiofilm activities of meropenem loaded-mesoporous silica nanoparticles against carbapenem-resistant Pseudomonas aeruginosa

Journal of Biomaterials Applications ◽

10.1177/08853282211003848 ◽

2021 ◽

pp. 088532822110038

Author(s):

Mohammad Yousef Memar ◽

Mina Yekani ◽

Hadi Ghanbari ◽

Edris Nabizadeh ◽

Sepideh Zununi Vahed ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Mesoporous Silica ◽

Silica Nanoparticles ◽

Mesoporous Silica Nanoparticles ◽

Carbapenem Resistant ◽

Toxicity In Vitro ◽

Different Levels

The aims of the present study were the determination of antimicrobial and antibiofilm effects of meropenem-loaded mesoporous silica nanoparticles (MSNs) on carbapenem resistant Pseudomonas aeruginosa ( P. aeruginosa) and cytotoxicity properties in vitro. The meropenem-loaded MSNs had shown antibacterial and biofilm inhibitory activities on all isolates at different levels lower than MICs and BICs of meropenem. The viability of HC-04 cells treated with serial concentrations as MICs and BICs of meropenem-loaded MSNs was 92–100%. According to the obtained results, meropenem-loaded MSNs display the significant antibacterial and antibiofilm effects against carbapenem resistant and biofilm forming P. aeruginosa and low cell toxicity in vitro. Then, the prepared system can be an appropriate option for the delivery of carbapenem for further evaluation in vivo assays.

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