scholarly journals Diversity and Distribution of Resistance Markers in Pseudomonas aeruginosa International High-Risk Clones

2021 ◽  
Vol 9 (2) ◽  
pp. 359
Author(s):  
Béla Kocsis ◽  
Dániel Gulyás ◽  
Dóra Szabó
Keyword(s):  
Pseudomonas Aeruginosa ◽  
High Risk ◽  
Sequence Data ◽  
Resistance Mechanisms ◽  
Whole Genome Sequence ◽  
Beta Lactamases ◽  
Resistance Determinants ◽  
Causative Agents ◽  
Surveillance Programs ◽  
Hospital Acquired

Pseudomonas aeruginosa high-risk clones are disseminated worldwide and they are common causative agents of hospital-acquired infections. In this review, we will summarize available data of high-risk P. aeruginosa clones from confirmed outbreaks and based on whole-genome sequence data. Common feature of high-risk clones is the production of beta-lactamases and among metallo-beta-lactamases NDM, VIM and IMP types are widely disseminated in different sequence types (STs), by contrast FIM type has been reported in ST235 in Italy, whereas GIM type in ST111 in Germany. In the case of ST277, it is most frequently detected in Brazil and it carries a resistome linked to blaSPM. Colistin resistance develops among P. aeruginosa clones in a lesser extent compared to other resistance mechanisms, as ST235 strains remain mainly susceptible to colistin however, some reports described mcr positive P. aeurigonsa ST235. Transferable quinolone resistance determinants are detected in P. aeruginosa high-risk clones and aac(6′)-Ib-cr variant is the most frequently reported as this determinant is incorporated in integrons. Additionally, qnrVC1 was recently detected in ST773 in Hungary and in ST175 in Spain. Continuous monitoring and surveillance programs are mandatory to track high-risk clones and to analyze emergence of novel clones as well as novel resistance determinants.

scholarly journals Genomic Insights into Drug Resistance Determinants in Cedecea neteri, A Rare Opportunistic Pathogen

2021 ◽  
Vol 9 (8) ◽  
pp. 1741
Author(s):  
Dorothea K. Thompson ◽  
Stephen M. Sharkady
Keyword(s):  
Drug Resistance ◽  
Sequence Data ◽  
Opportunistic Pathogen ◽  
Resistance Mechanisms ◽  
Whole Genome Sequence ◽  
Multidrug Efflux ◽  
Resistance Determinants ◽  
Multidrug Efflux Pumps ◽  
Novel Variant ◽  
Immunocompromised Hosts

Cedecea, a genus in the Enterobacteriaceae family, includes several opportunistic pathogens reported to cause an array of sporadic acute infections, most notably of the lung and bloodstream. One species, Cedecea neteri, is associated with cases of bacteremia in immunocompromised hosts and has documented resistance to different antibiotics, including β-lactams and colistin. Despite the potential to inflict serious infections, knowledge about drug resistance determinants in Cedecea is limited. In this study, we utilized whole-genome sequence data available for three environmental strains (SSMD04, M006, ND14a) of C. neteri and various bioinformatics tools to analyze drug resistance genes in this bacterium. All three genomes harbor multiple chromosome-encoded β-lactamase genes. A deeper analysis of β-lactamase genes in SSMD04 revealed four metallo-β-lactamases, a novel variant, and a CMY/ACT-type AmpC putatively regulated by a divergently transcribed AmpR. Homologs of known resistance-nodulation-cell division (RND)-type multidrug efflux pumps such as OqxB, AcrB, AcrD, and MdtBC were also identified. Genomic island prediction for SSMD04 indicated that tolC, involved in drug and toxin export across the outer membrane of Gram-negative bacteria, was acquired by a transposase-mediated genetic transfer mechanism. Our study provides new insights into drug resistance mechanisms of an environmental microorganism capable of behaving as a clinically relevant opportunistic pathogen.

scholarly journals Resistance Mechanisms of Multiresistant Pseudomonas aeruginosa Strains from Germany and Correlation with Hypermutation

2007 ◽  
Vol 51 (11) ◽  
pp. 4062-4070 ◽  
Author(s):  
B. Henrichfreise ◽  
I. Wiegand ◽  
W. Pfister ◽  
B. Wiedemann
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Efflux Pump ◽  
Acquired Resistance ◽  
Resistance Mechanisms ◽  
Type Ii ◽  
Mechanisms Of Resistance ◽  
Resistance Determinants ◽  
Class 1 ◽  
Mutator Strains ◽  
Multiresistant Strains

ABSTRACT In this study, we analyzed the mechanisms of multiresistance for 22 clinical multiresistant and clonally different Pseudomonas aeruginosa strains from Germany. Twelve and 10 strains originated from cystic fibrosis (CF) and non-CF patients, respectively. Overproduction of the efflux systems MexAB-OprM, MexCD-OprJ, MexEF-OprN, and MexXY-OprM was studied. Furthermore, loss of OprD, alterations in type II topoisomerases, AmpC overproduction, and the presence of 25 acquired resistance determinants were investigated. The presence of a hypermutation phenotype was also taken into account. Besides modifications in GyrA (91%), the most frequent mechanisms of resistance were MexXY-OprM overproduction (82%), OprD loss (82%), and AmpC overproduction (73%). Clear differences between strains from CF and non-CF patients were found: numerous genes coding for aminoglycoside-modifying enzymes and located, partially in combination with β-lactamase genes, in class 1 integrons were found only in strains from non-CF patients. Furthermore, multiple modifications in type II topoisomerases conferring high quinolone resistance levels and overexpression of MexAB-OprM were exclusively detected in multiresistant strains from non-CF patients. Correlations of the detected phenotypes and resistance mechanisms revealed a great impact of efflux pump overproduction on multiresistance in P. aeruginosa. Confirming previous studies, we found that additional, unknown chromosomally mediated resistance mechanisms remain to be determined. In our study, 11 out of 12 strains and 3 out of 10 strains from CF patients and non-CF patients, respectively, were hypermutable. This extremely high proportion of mutator strains should be taken into consideration for the treatment of multiresistant P. aeruginosa.

scholarly journals Bridging the TB data gap: in silico extraction of rifampicin-resistant tuberculosis diagnostic test results from whole genome sequence data

2019 ◽  
Author(s):  
Kamela Charmaine S. Ng ◽  
Jean Claude S. Ngabonziza ◽  
Pauline Lempens ◽  
Bouke Catherine de Jong ◽  
Frank van Leth ◽  
...  
Keyword(s):  
Sequence Data ◽  
Whole Genome Sequence ◽  
Whole Genome ◽  
Data Generation ◽  
Continuous Analysis ◽  
Middle Income ◽  
Tb Control ◽  
Sequencing Technologies ◽  
Surveillance Programs ◽  
Low And Middle Income

AbstractBackgroundMycobacterium tuberculosis rapid diagnostic tests (RDTs) are widely employed in routine laboratories and national surveys for detection of rifampicin-resistant (RR)-TB. However, as next generation sequencing technologies have become more commonplace in research and surveillance programs, RDTs are being increasingly complemented by whole genome sequencing (WGS). While comparison between RDTs is difficult, all RDT results can be derived from WGS data. This can facilitate continuous analysis of RR-TB burden regardless of the data generation technology employed. By converting WGS to RDT results, we enable comparison of data with different formats and sources particularly for low and middle income high TB burden countries that employ different diagnostic algorithms for drug resistance surveys. This allows national TB control programs (NTPs) and epidemiologists to utilize all available data in the setting for improved RR-TB surveillance.MethodsWe developed the Python-based MTB Genome to Test (MTBGT) tool that transforms WGS-derived data into laboratory-validated results of the primary RDTs – Xpert MTB/RIF, XpertMTB/RIF Ultra, GenoType MDRTBplus v2.0, and GenoscholarNTM+MDRTB II. The tool was validated through RDT results of RR-TB strains with diverse resistance patterns and geographic origins and applied on routine-derived WGS data.ResultsThe MTBGT tool correctly transformed the SNP data into the RDT results and generated tabulated frequencies of the RDT probes as well as rifampicin susceptible cases. The tool supplemented the RDT probe reactions output with the RR-conferring mutation based on identified SNPs. The MTBGT tool facilitated continuous analysis of RR-TB and Xpert probe reactions from different platforms and collection periods in Rwanda.ConclusionOverall, the MTBGT tool allows low and middle income countries to make sense of the increasingly generated WGS in light of the readily available RDT results, and assess whether currently implemented RDTs adequately detect RR-TB in their setting. With its feature to transform WGS to RDT results and facilitate continuous RR-TB data analysis, the MTBGT tool may bridge the gap between and among data from periodic surveys, continuous surveillance, research, and routine tests, and may be integrated within the existing national connectivity platform for use by the NTP and epidemiologists to improve setting-specific RR-TB control. The MTBGT source code and accompanying documentation is available at https://github.com/KamelaNg/MTBGT.

Detection of resistance genes from Pseudomonas aeruginosa using immunomagnetic isolation and chemiluminescence

2020 ◽  
Vol 10 (3) ◽  
pp. 412-418
Author(s):  
Fei Xu ◽  
Cheng Chen ◽  
Xing Li ◽  
Bo Zhang
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Resistance Genes ◽  
High Efficiency ◽  
Bacterial Pathogen ◽  
Resistance Mechanisms ◽  
Clinical Samples ◽  
Specific Gene ◽  
Beta Lactamases ◽  
Immunomagnetic Isolation ◽  
Encoding Gene

Pseudomonas aeruginosa (P. aeruginosa) is a common opportunistic and nosocomial bacterial pathogen. Various multi-resistance mechanisms present across numerous P. aeruginosa strains counteract conventional antimicrobial therapy, thereby becoming a great challenge. This study aimed to establish the application of immunomagnetic isolation and chemiluminescence to detect the presence of extended spectra of β-lactamases encoding genes: blaTEM and blaVEB; metallo-beta-lactamases encoding gene: blaVIM; aminoglycoside modifying enzymes encoding gene: aac(6)II, ant(3)I; and the specific gene for P. aeruginosa, gyrB. P. aeruginosa was specifically selected using the immunomagnetic nanoparticles (IMNPs) in the six parallel bacterial plates counting, proving that they are reliable. Then, the high efficiency of IMNPs@Probes in targeting the resistance genes of P. aeruginosa was demonstrated using the results of chemiluminescent intensities of blaTEM, blaVEB, blaVIM aac(6)II, ant(3)I, and gyrB (more than 10 times higher than that of the control). Sixty-eight in situ clinical samples were tested for the presence of these resistance genes, and one more blaTEM and three more blaVIM individuals were detected using this method compared to the traditional PCR. Thus, the application of our method in clinical screening is specific, accurate, and reliable, and it could be useful in the administration of appropriate treatment.

scholarly journals Nosocomial Spread of Colistin-Only-Sensitive Sequence Type 235 Pseudomonas aeruginosa Isolates Producing the Extended-Spectrum β-Lactamases GES-1 and GES-5 in Spain

2009 ◽  
Vol 53 (11) ◽  
pp. 4930-4933 ◽  
Author(s):  
Esther Viedma ◽  
Carlos Juan ◽  
Joshi Acosta ◽  
Laura Zamorano ◽  
Joaquín R. Otero ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Gel Electrophoresis ◽  
Multilocus Sequence Typing ◽  
Resistance Mechanisms ◽  
Pulsed Field Gel Electrophoresis ◽  
Sequence Type ◽  
Pulsed Field ◽  
Resistance Determinants ◽  
Extended Spectrum ◽  
Spanish Hospital

ABSTRACT The mechanisms responsible for the increasing prevalence of colistin-only-sensitive (COS) Pseudomonas aeruginosa isolates in a Spanish hospital were investigated. Pulsed-field gel electrophoresis revealed that 24 (50%) of the studied isolates belonged to the same clone, identified as the internationally spread sequence type 235 (ST235) through multilocus sequence typing. In addition to several mutational resistance mechanisms, an integron containing seven resistance determinants was detected. Remarkably, the extended-spectrum β-lactamase GES-1 and its Gly170Ser carbapenem-hydrolyzing derivative GES-5 were first documented to be encoded in a single integron. This work is the first to describe GES enzymes in Spain and adds them to the growing list of β-lactamases of concern (PER, VIM, and OXA) detected in ST235 clone isolates.

scholarly journals In Vitro Activity of the Ultra-Broad-Spectrum Beta-lactamase Inhibitor QPX7728 in Combination with Multiple Beta-Lactam Antibiotics against Pseudomonas aeruginosa

2021 ◽  
Author(s):  
Olga Lomovskaya ◽  
Debora Rubio-Aparicio ◽  
Kirk Nelson ◽  
Dongxu Sun ◽  
Ruslan Tsivkovski ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Resistance Mechanisms ◽  
Clinical Isolates ◽  
Beta Lactamase ◽  
In Vitro Activity ◽  
Beta Lactam ◽  
Beta Lactams ◽  
Beta Lactamases ◽  
Lactamase Inhibitor

QPX7728 is an ultra-broad-spectrum beta-lactamase inhibitor with potent inhibition of key serine and metallo beta-lactamases. QPX7728 enhances the potency of multiple beta-lactams in beta-lactamase producing Enterobacterales and Acinetobacter spp. In this study we evaluated the in vitro activity of QPX7728 (8 μg/ml) combined with multiple beta-lactams against clinical isolates of Pseudomonas aeruginosa with varying beta-lactam resistance mechanisms. Seven-hundred-ninety clinical isolates were included in this study; 500 isolates, termed a “representative panel”, were selected to be representative the MIC distribution of meropenem (MEM), ceftazidime-avibactam (CAZ-AVI), and ceftolozane-tazobactam (TOL-TAZ) resistance for clinical isolates according to 2017 SENTRY surveillance data (representative panel). An additional 290 selected isolates (“challenge panel”), that were either non-susceptible to MEM or were resistant to TOL-TAZ or CAZ-AVI were also tested; 61 strains carried metallo beta-lactamases (MBLs), 211 strains were defective in the carbapenem porin OprD and 185 strains had the MexAB-OprM efflux pump overproduced based on a phenotypic test. Against the representative panel, susceptibility for all QPX7728/beta-lactam combinations was >90%. For the challenge panel, QPX-ceftolozane (TOL) was the most active combination (78.6% susceptible) followed by equipotent QPX-piperacillin (PIP) and QPX-cefepime (FEP), restoring susceptibility in 70.3% of strains (CLSI breakpoints for the beta-lactam compound alone). For MBL-negative strains, QPX-TOL and QPX-FEP restored the MIC values to susceptibility rates in ∼90% and ∼80% of strains, respectively, vs 68-70% for QPX-MEM and QPX-PIP and 63-65% for TOL-TAZ and CAZ-AVI. For MBL-positive strains, QPX-PIP restored the MIC to susceptibility values for ∼70% of strains vs 2-40% for other combinations. Increased efflux and impaired OprD had varying effect on QPX7728 combination depending on the partner beta-lactam tested. QPX7728 enhanced the potency of multiple beta-lactams against P. aeruginosa, with varying results according to the beta-lactamase production and other intrinsic resistance mechanisms.

scholarly journals Review of Ceftazidime-Avibactam for the Treatment of Infections Caused by Pseudomonas aeruginosa

Antibiotics ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 1126
Author(s):  
George L. Daikos ◽  
Clóvis Arns da da Cunha ◽  
Gian Maria Rossolini ◽  
Gregory G. Stone ◽  
Nathalie Baillon-Plot ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Multidrug Resistant ◽  
Resistance Mechanisms ◽  
Real World Data ◽  
Serious Infections ◽  
Tract Infections ◽  
Abdominal Infections ◽  
Hospital Acquired

Pseudomonas aeruginosa is an opportunistic Gram-negative pathogen that causes a range of serious infections that are often challenging to treat, as this pathogen can express multiple resistance mechanisms, including multidrug-resistant (MDR) and extensively drug-resistant (XDR) phenotypes. Ceftazidime–avibactam is a combination antimicrobial agent comprising ceftazidime, a third-generation semisynthetic cephalosporin, and avibactam, a novel non-β-lactam β-lactamase inhibitor. This review explores the potential role of ceftazidime–avibactam for the treatment of P. aeruginosa infections. Ceftazidime–avibactam has good in vitro activity against P. aeruginosa relative to comparator β-lactam agents and fluoroquinolones, comparable to amikacin and ceftolozane–tazobactam. In Phase 3 clinical trials, ceftazidime–avibactam has generally demonstrated similar clinical and microbiological outcomes to comparators in patients with complicated intra-abdominal infections, complicated urinary tract infections or hospital-acquired/ventilator-associated pneumonia caused by P. aeruginosa. Although real-world data are limited, favourable outcomes with ceftazidime–avibactam treatment have been reported in some patients with MDR and XDR P. aeruginosa infections. Thus, ceftazidime–avibactam may have a potentially important role in the management of serious and complicated P. aeruginosa infections, including those caused by MDR and XDR strains.

scholarly journals International High-Risk Clones Among Extended-Spectrum β-Lactamase–Producing Escherichia coli in Dhaka, Bangladesh

2021 ◽  
Vol 12 ◽  
Author(s):  
Razib Mazumder ◽  
Arif Hussain ◽  
Ahmed Abdullah ◽  
Md. Nazrul Islam ◽  
Md. Tuhin Sadique ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
High Risk ◽  
Sequence Data ◽  
Diarrhoeal Disease ◽  
Resistance Mechanisms ◽  
Genome Comparison ◽  
E Coli ◽  
Extended Spectrum ◽  
Genome Phylogeny ◽  
Cephalosporin Resistance

Background:Escherichia coli is a major extended-spectrum β-lactamase (ESBL)–producing organism responsible for the rapid spread of antimicrobial resistance (AMR) that has compromised our ability to treat infections. Baseline data on population structure, virulence, and resistance mechanisms in E. coli lineages from developing countries such as Bangladesh are lacking.Methods: Whole-genome sequencing was performed for 46 ESBL–E. coli isolates cultured from patient samples at the International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b)-Dhaka. Sequence data were analyzed to glean details of AMR, virulence, and phylogenetic and molecular markers of E. coli lineages.Results: Genome comparison revealed presence of all major high-risk clones including sequence type 131 (ST131) (46%), ST405 (13%), ST648 (7%), ST410 (4.3%), ST38 (2%), ST73 (2%), and ST1193 (2%). The predominant ESBL gene and plasmid combination were blaCTX–M–15 and FII-FIA-FIB detected in diverse E. coli phylogroups and STs. The blaNDM–5 (9%) gene was present in prominent E. coli STs. One (2%) mcr-1–positive ST1011 E. coli, coharboring blaCTXM–55 gene, was detected. The extraintestinal pathogenic E. coli genotype was associated with specific E. coli lineages. The single nucleotide polymorphism (SNP)-based genome phylogeny largely showed correlation with phylogroups, serogroups, and fimH types. Majority of these isolates were susceptible to amikacin (93%), imipenem (93%), and nitrofurantoin (83%).Conclusion: Our study reveals a high diversity of E. coli lineages among ESBL-producing E. coli from Dhaka. This study suggests ongoing circulation of ST131 and all major non-ST131 high-risk clones that are strongly associated with cephalosporin resistance and virulence genes. These findings warrant prospective monitoring of high-risk clones, which would otherwise worsen the AMR crises.

scholarly journals Mechanisms of Resistance in Gram-Negative Urinary Pathogens: From Country-Specific Molecular Insights to Global Clinical Relevance

Diagnostics ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 800
Author(s):  
Branka Bedenić ◽  
Tomislav Meštrović
Keyword(s):  
Clinical Importance ◽  
Resistance Mechanisms ◽  
Bacterial Strains ◽  
Mechanisms Of Resistance ◽  
Gram Negative ◽  
Beta Lactamases ◽  
Resistance Determinants ◽  
Genes Encoding ◽  
Extended Spectrum Beta Lactamases ◽  
Tract Infections

Urinary tract infections (UTIs) are the most frequent hospital infections and among the most commonly observed community acquired infections. Alongside their clinical importance, they are notorious because the pathogens that cause them are prone to acquiring various resistance determinants, including extended-spectrum beta-lactamases (ESBL); plasmid-encoded AmpC β-lactamases (p-AmpC); carbapenemases belonging to class A, B, and D; qnr genes encoding reduced susceptibility to fluoroquinolones; as well as genes encoding enzymes that hydrolyse aminoglycosides. In Escherichia coli and Klebsiella pneumoniae, the dominant resistance mechanisms are ESBLs belonging to the CTX-M, TEM, and SHV families; p-AmpC; and (more recently) carbapenemases belonging to classes A, B, and D. Urinary Pseudomonas aeruginosa isolates harbour metallo-beta-lactamases (MBLs) and ESBLs belonging to PER and GES families, while carbapenemases of class D are found in urinary Acinetobacter baumannii isolates. The identification of resistance mechanisms in routine diagnostic practice is primarily based on phenotypic tests for the detection of beta-lactamases, such as the double-disk synergy test or Hodge test, while polymerase chain reaction (PCR) for the detection of resistance genes is mostly pursued in reference laboratories for research purposes. As the emergence of drug-resistant bacterial strains poses serious challenges in the management of UTIs, this review aimed to appraise mechanisms of resistance in relevant Gram-negative urinary pathogens, to provide a detailed map of resistance determinants in Croatia and the world, and to discuss the implications of these resistance traits on diagnostic approaches. We summarized a sundry of different resistance mechanisms among urinary isolates and showed how their prevalence highly depends on the local epidemiological context, highlighting the need for tailored interventions in the field of antimicrobial stewardship.

Sign in / Sign up

Export Citation Format

Share Document