scholarly journals Activity of imipenem/relebactam against Pseudomonas aeruginosa producing ESBLs and carbapenemases

2020 ◽  
Author(s):  
Shazad Mushtaq ◽  
Danièle Meunier ◽  
Anna Vickers ◽  
Neil Woodford ◽  
David M Livermore
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Latin America ◽  
Middle East ◽  
Eastern Europe ◽  
Class A ◽  
Carbapenem Resistant ◽  
Class B ◽  
Agar Dilution ◽  
Imipenem Resistance ◽  
Esbl Producers

Abstract Background ESBL- and carbapenemase-producing Pseudomonas aeruginosa are prevalent in, for example, the Middle East, Eastern Europe and Latin America, though rarer elsewhere. Because P. aeruginosa readily mutate to become carbapenem resistant via loss of OprD, isolates producing ESBLs are often as broadly resistant as those producing carbapenemases. We hypothesized that: (i) relebactam might overcome class A carbapenemases directly in P. aeruginosa; and (ii) relebactam’s inhibition of AmpC, which gives a generalized potentiation of imipenem against the species, might restore imipenem susceptibility in OprD-deficient ESBL producers. Methods MICs were determined using CLSI agar dilution for P. aeruginosa isolates producing ESBLs, principally VEB types, and for those producing GES-5, KPC and other carbapenemases. Results Relebactam potentiated imipenem by around 4–8-fold for most P. aeruginosa isolates producing VEB and other ESBLs; however, MICs were typically only reduced to 4–16 mg/L, thus mostly remaining above EUCAST’s susceptible range and only partly overlapping CLSI’s intermediate range. Strong (approx. 64-fold) potentiation was seen for isolates producing KPC carbapenemases, but only 2-fold synergy for those with GES-5. Predictably, potentiation was not seen for isolates with class B or D carbapenemase activity. Conclusions Relebactam did potentiate imipenem against ESBL-producing P. aeruginosa, which are mostly imipenem resistant via OprD loss, but this potentiation was generally insufficient to reduce imipenem MICs to the clinical range. Imipenem resistance owing to KPC carbapenemases was reversed by relebactam in P. aeruginosa, just as for Enterobacterales.

Sultanism

2021 ◽  
pp. 47-76
Author(s):  
Christopher M. Davidson
Keyword(s):  
Twentieth Century ◽  
Latin America ◽  
Middle East ◽  
Literature Review ◽  
Eastern Europe ◽  
Latin American ◽  
Max Weber ◽  
Sub Saharan Africa ◽  
Empirical Literature ◽  
Sub Saharan

To facilitate a comprehensive and up-to-date understanding of the concept of sultanism, this chapter provides a detailed theoretical and empirical literature review. Firstly, it considers the oriental origins of the concept, as applied by Max Weber and others to the Ottoman Empire and a number of South Asian examples. Secondly, it traces the emergence of ‘contemporary sultanism’, as applied by scholars to Latin American regimes from the mid-twentieth century and onwards. Thirdly, it explores the more recent concept of neo-sultanism and the development of a distinct international empirical category of autocratic-authoritarianism which includes: various Latin America regimes; some of the former communist republics of central Asia and Eastern Europe; and a number of regimes in sub-Saharan Africa and parts of Southeast Asia. Finally, it assesses the need to address the scholarly deficit in applying contemporary sultanism or neo-sultanism to the Middle East, and suggests that the present-day Saudi And UAE regimes may be strong examples.

scholarly journals Comparative Evaluation of Four Phenotypic Methods for Detection of Class A and B Carbapenemase-Producing Enterobacteriaceae in China

2018 ◽  
Vol 56 (8) ◽  
Author(s):  
Menglan Zhou ◽  
Danchen Wang ◽  
Timothy Kudinha ◽  
Qiwen Yang ◽  
Shuying Yu ◽  
...  
Keyword(s):  
Predictive Value ◽  
Comparative Evaluation ◽  
Detection Sensitivity ◽  
Detection Methods ◽  
Content Type ◽  
Class A ◽  
Carbapenem Resistant ◽  
Class B ◽  
Phenotypic Methods ◽  
Sensitivity Specificity

ABSTRACT The objective of this study was to evaluate the performance of four phenotypic methods in the detection of carbapenemase-producing Enterobacteriaceae (CPE) in China. We evaluated the performance of four carbapenemase detection methods, the modified Hodge test (MHT), the Carba NP test, the meropenem hydrolysis assay (MHA) with 1- and 2-h incubation, and the modified carbapenem inactivation method (mCIM) with meropenem, imipenem, and ertapenem, on 342 carbapenem-resistant Enterobacteriaceae isolates (CRE) in China. PCR was used as the gold standard. The 2-h-incubation MHA performed the best in carbapenemase detection (overall sensitivity, specificity, positive predictive value, and negative predictive value all 100%). Second was the Carba NP test, with a sensitivity of 99.6%. The 1-h-incubation MHA performed poorly in Klebsiella pneumoniae carbapenemase (KPC) detection (sensitivity, 71.3%). For mCIM, the best performance was observed with the meropenem disk. The MHT exhibited the worst performance, with a specificity of 88.8%. All assays except 1-h-incubation MHA, which failed to identify 68 KPC-2s, had a sensitivity of >98% in the detection of 172 KPCs. Likewise, all assays had a sensitivity of >95% in the detection of 70 class B carbapenemases, except for MHT (82.9%). The 2-h-incubation MHA significantly improved the accuracy in CPE detection compared with that for 1-h incubation and performed the best in the detection of class A and B carbapenemases. Our findings suggest that the MHA is the most practical assay for carbapenemase detection. For those who cannot afford the associated equipment, both the Carba NP test and mCIM are good alternatives with regard to the practical requirements of time and cost.

scholarly journals Characterization of clinical isolates of Pseudomonas aeruginosa heterogeneously resistant to carbapenems

2007 ◽  
Vol 56 (1) ◽  
pp. 66-70 ◽  
Author(s):  
Spyros Pournaras ◽  
Alexandros Ikonomidis ◽  
Antonios Markogiannakis ◽  
Nicholas Spanakis ◽  
Antonios N. Maniatis ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Population Analysis ◽  
Growth Curves ◽  
Clinical Isolates ◽  
Lag Phase ◽  
Carbapenem Resistant ◽  
One Step ◽  
Agar Dilution ◽  
Resistant Mutants ◽  
Selection Of

Fourteen apparently carbapenem-susceptible Pseudomonas aeruginosa clinical isolates that exhibited colonies within the inhibition zone around carbapenem discs were analysed. MICs of carbapenems were determined and the isolates were genotyped by PFGE. Population analysis, one-step selection of carbapenem-resistant mutants and growth curves of progenitors and carbapenem-resistant subpopulations were performed. Agar dilution MICs of imipenem and meropenem ranged from 0.5 to 4 mg l−1 and from 0.25 to 2 mg l−1, respectively. Population analysis confirmed subpopulations that grew in concentrations of up to 18 mg l−1 and 12 mg l−1 of imipenem and meropenem, respectively, at frequencies ranging from 6.9×10−5 to 1.1×10−7, suggesting that they might not be detected by standard agar dilution MIC testing. The minority subpopulations exhibited MICs for imipenem ranging from 10 to 20 mg l−1 and for meropenem from 4 to 14 mg l−1. The one-step 8 mg l−1 selection of imipenem-resistant mutants test showed growth in all isolates at frequencies ranging from 3.8×10−4 to 5.1×10−7. Growth curves revealed a prolonged lag phase and a short exponential phase for the heterogeneous subpopulations compared with their respective native subpopulations. These findings may be indicative that the use of carbapenems can lead to selection of P. aeruginosa resistant subpopulations that subsequently cause infections and result in treatment failure.

GPC-1, a novel class A carbapenemase detected in a clinical Pseudomonas aeruginosa isolate

2020 ◽  
Vol 75 (4) ◽  
pp. 911-916 ◽  
Author(s):  
Jennifer Schauer ◽  
Sören G Gatermann ◽  
Daniel Hoffmann ◽  
Lars Hupfeld ◽  
Niels Pfennigwerth
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Heterologous Expression ◽  
Biochemical Characterization ◽  
Resistance Mechanism ◽  
Carbapenem Resistance ◽  
Amino Acid Identity ◽  
The Novel ◽  
Bacterial Strains ◽  
Class A ◽  
Carbapenem Resistant

Abstract Objectives To investigate the carbapenem resistance mechanism of a carbapenem-resistant clinical Pseudomonas aeruginosa isolate. Methods A carbapenem-resistant P. aeruginosa isolate was recovered from a tracheal swab from a patient of a general ward in central Germany. Various phenotypic tests confirmed production of a carbapenemase that could not be identified further by PCR. A novel bla gene was identified by WGS and its carbapenemase activity was verified by heterologous expression in an Escherichia coli cloning strain. Kinetic parameters of the novel β-lactamase were determined by spectrophotometric measurements using purified enzyme. Results WGS confirmed the presence of a novel class A carbapenemase. The novel bla gene was named GPC-1 (GPC standing for German Pseudomonas Carbapenemase) and exhibited 77% amino acid identity to BKC-1. WGS also showed that blaGPC-1 was located on the chromosome surrounded by multiple ISs as part of a 26 kb genetic island. Heterologous expression of GPC-1 in E. coli TOP10 led to increased MICs of penicillins, oxyimino-cephalosporins, aztreonam and imipenem, but not of meropenem or ertapenem. Spectrophotometric measurements supported the MIC studies, but detected a slight hydrolysis of ertapenem and meropenem when using high concentrations of purified enzyme. Conclusions The biochemical characterization of GPC-1 emphasizes the ongoing emergence of novel carbapenemases. Strains expressing a weak carbapenemase like GPC-1 might go unrecognized by routine diagnostics due to low MICs for the bacterial strains producing such enzymes.

scholarly journals Characterization of Imipenem Unsusceptible Pseudomonas Aeruginosa Isolates from Inpatients without Carbapenem Treatment

2013 ◽  
Vol 2 (1) ◽  
pp. 1-5
Author(s):  
Yi-hai Gu ◽  
Xiao Zhu ◽  
Jing-yun Li ◽  
Jun Zhang ◽  
Qing-yuan Zhou ◽  
...  
Keyword(s):  
Risk Factors ◽  
Pseudomonas Aeruginosa ◽  
Wide Spectrum ◽  
Mechanism Analysis ◽  
Antimicrobial Susceptibility Test ◽  
Resistance Development ◽  
Carbapenem Resistant ◽  
Drug Classes ◽  
Imipenem Resistance

Abstract Objective To identify the risk factors for imipenem resistance development and transmission of clinical Pseudomonas aeruginosa isolates. Methods Thirty-seven imipenem unsusceptible Pseudomonas aeruginosa isolates collected from patients in absence of carbapenem treatment were characterized by antimicrobial susceptibility test, pulsed field gel electrophoresis (PFGE) and carbapenem resistant mechanism analysis. Results Before the collection of imipenem unsusceptible Pseudomonas aeruginosa isolates, the average time of patients treated with more than one antimicrobial (20.0 ± 9.5 days, n = 16) was significantly longer than those treated with only one antimicrobial (12.6 ± 4.4 days, n = 21; t-test, Welch, t = -2.9004, P < 0.01). And 32 isolates showed resistance to more than 3 classes of antimicrobials. Six PFGE clusters were identified and 26 isolates were grouped into one dominant cluster (C2). An ISpa1328 sequence insertion in oprD was detected in 33 isolates and the function of efflux was observed in all 37 isolates in the presence of a wide spectrum efflux inhibitor. Conclusions Our data demonstrated that exposure to non-carbapenem drug classes, especially fluoroquinolones and β-lactams, may be important risk factors for the spread of carbapenem resistant Pseudomonas aeruginosa.

scholarly journals Detection of blaCTX-M gene among Pseudomonas aeruginosa isolated from water samples in Baghdad

2017 ◽  
Vol 28 (1) ◽  
pp. 35
Author(s):  
Saba R. Khdair
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Tap Water ◽  
Antibiotic Sensitivity ◽  
Penicillin G ◽  
Dilution Method ◽  
Agar Dilution Method ◽  
M Gene ◽  
Antibiotic Sensitivity Test ◽  
Agar Dilution ◽  
Esbl Producers

A total of 50 environmental Pseudomonas aeruginosa isolates were collected from sewage and tap water in Baghdad, Iraq. The MICs of Cefotaxime and Ceftazidime were determined by using agar dilution method, The MIC ranged from 2 to 256 µg/ml.The results of antibiotic sensitivity test showed that among sewage P. aeruginosa isolates, resistance was observed most often to Ticarcillin (92%), Penicillin G (84%), Ceftazidime (12%), (8%) for each of Cefotaxime and Ticarcillin. On the other hand, all tap water isolates were sensitive to Ofloxacin and Levofloxacin, Except (5%) of isolates were resistant to Cefotaxime (25%) to Ceftazidime and (95%) to Ticarcillin. All isolates were tested for Extended-Spectrum β-Lactamase (ESBL) production. Ten isolates (20%) were found to be ESBL producers. All environmental P. aeruginosa isolates were screened for the presence of the blaCTX-M genes by application PCR, Only (30%) of them were positive for this test.

scholarly journals Activity of β-lactam/taniborbactam (VNRX-5133) combinations against carbapenem-resistant Gram-negative bacteria

2020 ◽  
Vol 76 (1) ◽  
pp. 160-170
Author(s):  
Shazad Mushtaq ◽  
Anna Vickers ◽  
Michel Doumith ◽  
Matthew J Ellington ◽  
Neil Woodford ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Pseudomonas Aeruginosa ◽  
Stenotrophomonas Maltophilia ◽  
Clinical Development ◽  
Published Data ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Class A ◽  
Carbapenem Resistant ◽  
Elizabethkingia Meningoseptica

Abstract Background Boronates are of growing interest as β-lactamase inhibitors. The only marketed analogue, vaborbactam, principally targets KPC carbapenemases, but taniborbactam (VNRX-5133, Venatorx) has a broader spectrum. Methods MICs of cefepime and meropenem were determined combined with taniborbactam or avibactam for carbapenem-resistant UK isolates. β-Lactamase genes and porin alterations were sought by PCR or sequencing. Results Taniborbactam potentiated partner β-lactams against: (i) Enterobacterales with KPC, other class A, OXA-48-like, VIM and NDM (not IMP) carbapenemases; and (ii) Enterobacterales inferred to have combinations of ESBL or AmpC activity and impermeability. Potentiation of cefepime (the partner for clinical development) by taniborbactam was slightly weaker than by avibactam for Enterobacterales with KPC or OXA-48-like carbapenemases, but MICs of cefepime/taniborbactam were similar to those of ceftazidime/avibactam, and the spectrum was wider. MICs of cefepime/taniborbactam nonetheless remained &gt;8 + 4 mg/L for 22%–32% of NDM-producing Enterobacterales. Correlates of raised cefepime/taniborbactam MICs among these NDM Enterobacterales were a cefepime MIC &gt;128 mg/L, particular STs and, for Escherichia coli only: (i) the particular blaNDM variant (even though published data suggest all variants are inhibited similarly); (ii) inserts in PBP3; and (iii) raised aztreonam/avibactam MICs. Little or no potentiation of cefepime or meropenem was seen for Pseudomonas aeruginosa and Acinetobacter baumannii with MBLs, probably reflecting slower uptake or stronger efflux. Potentiation of cefepime was seen for Stenotrophomonas maltophilia and Elizabethkingia meningoseptica, which have both chromosomal ESBLs and MBLs. Conclusions Taniborbactam broadly reversed cefepime or meropenem non-susceptibility in Enterobacterales and, less reliably, in non-fermenters.

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