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Emergence of K. pneumoniae, P. mirabilis and Enterobacter spp. clinical isolates carrying blaOXA-48-like genes on the period from 01.01.2013 to 01.11.2014: square no gene, filled triangleblaOXA-48 gene, filled circleblaOXA-244 gene; A, B, C, D, E, F, G, H, I, J, K, L, M, N and O patients
Source publication
Background
The spread of carbapenemase-producing Enterobacteriaceae (CPE) is a great problem of healthcare worldwide. Study of the spread for blaOXA-48-like genes coding epidemically significant carbapenemases among hospital pathogens is important for the regional and global epidemiology of antimicrobial resistance.
Methods
Antibacterial resistant...
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1Ural State Medical University, Ekaterinburg, Russian Federation
2Regional Children’s Clinical Hospital, Ekaterinburg, Russian Federation
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Background:
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Background: The prompt and accurate detection of carbapenemase-producing Enterobacteriaceae is essential for patient care and infection control procedures. Therefore, the introduction of a standardised method for routine carbapenemase detection in clinical diagnostic laboratories seems to be mandatory. The aim of the present study was to compare th...
Citations
... OXA-48 was originally described in K. pneumoniae in Turkey in 2004 [52] and, thereafter, has spread among different genera of Enterobacterales via highly conjugative IncL plasmids [53]. The first report of this widespread CHDL in P. mirabilis originated in 2015 from Russia [54], as shown in Table 3. Recently, OXA-48 with a very unusual resistance phenotype was described in nine P. mirabilis in Germany [55]. ...
The management of infectious diseases has proven to be a daunting task for clinicians worldwide, and the rapid development of antibiotic resistance among Gram-negative bacteria is making it even more challenging. The first-line therapy is empirical, and it most often comprises β-lactam antibiotics. Among Gram-negative bacteria, Proteus mirabilis, an important community and hospital pathogen associated primarily with urinary tract and wound infection, holds a special place. This review’s aim was to collate and examine recent studies investigating β-lactam resistance phenotypes and mechanisms of Proteus species and the global significance of its β-lactam resistance evolution. Moreover, the genetic background of resistance traits and the role of mobile genetic elements in the dissemination of resistance genes were evaluated. P. mirabilis as the dominant pathogen develops resistance to expanded-spectrum cephalosporins (ESC) by producing extended-spectrum β-lactamases (ESBL) and plasmid-mediated AmpC β-lactamases (p-AmpC). β-lactamase-mediated resistance to carbapenems in Enterobacterales, including Proteus spp., is mostly due to expression of carbapenemases of class A (KPC); class B (metallo-β-lactamases or MBLs of IMP, VIM, or NDM series); or class D or carbapenem-hydrolyzing oxacillinases (CHDL). Previously, a dominant ESBL type in P. mirabilis was TEM-52; yet, lately, it has been replaced by CTX-M variants, particularly CTX-M-14. ESC resistance can also be mediated by p-AmpC, with CMY-16 as the dominant variant. Carbapenem resistance in Proteus spp. is a challenge due to its intrinsic resistance to colistin and tigecyclin. The first carbapenemases reported belonged to class B, most frequently VIM-1 and NDM-5. In Europe, predominantly France and Belgium, a clonal lineage positive for OXA-23 CHDL spreads rapidly undetected, due to its low-level resistance to carbapenems. The amazing capacity of Proteus spp. to accumulate a plethora of various resistance traits is leading to multidrug or extensively drug-resistant phenotypes.
... Sequencing analysis of their variable region revealed that they mainly carried distinctive cassettes encoding aminoglycosides and trimethoprim resistance determinants. Previous reports have also indicated that most integronscarrying genes for aminoglycosides and trimethoprim resistance (Fursova et al., 2015). Variable insights into the diversity and relatedness of strains are obtained by comparing the genetic sequences obtained from P. mirabilis isolates from various sources. ...
Proteus mirabilis has become a prevalent opportunistic pathogenic agent in clinical infections globally. The objective of this study was to analyze and discover some of genes responsible for antibiotic resistance in clinical isolates of P. mirabilis that exhibit resistance to multiple drugs, including IntI1, IntI2 and to assess the relationship in the phylogenetic tree among these genes in Iraq, comparing to world-wide strains in National Center for Biotechnology Information (NCBI ). A total of 250 samples from different sources were isolated in some Diyala province hospitals from August 2023 to January 2024 to be identified for the presence of P. mirabilis by biochemical and genetics test. The study demonstrated that 75 isolates were P. mirabilis 35 isolates (46.7%) from urine, (10.7%) from wounds, (13.3%) from burns and diabetic foot and 12 isolates (16%) from vaginal swabs and tested against 15 antibiotics for susceptibility. The prevalence of multi drug- resistance ( MDR) in this study was high (97%) while only 2 isolates was tended to be extensively drug -resistance (XDR) (3%) no pan-drug –resistance(PDR) was detected. From 12 isolates of p.mirabilis 9 Intl1 and 6 Intl2 genes were detectable. homology between the sequenced sample of P. mirabilis reference target sequences. These genes were sequenced and phylogenetic relationships among these genes and global genes were documented in NCBI. The study suggests that some Iraqi isolates contain genetic variation compared to global strains and demonstrated the utility of IntI1, IntI2 sequencing in investigating the genetic diversity of P. mirabilis strains and offering insights into the evolutionary history of these crucial bacterial pathogens.
... The majority of carbapenemases were identified in two clusters: IncHI1B(pNDM-MAR)/IncFIB(pNDM-Mar)-like (cluster 2) and IncL-like (cluster 7). Medium-sized (median length 65,474 bp) IncL-like plasmids have been globally reported to be associated with bla OXA-48 [13], although this gene was also detected on IncFIA(HI1) plasmids in our dataset. Large IncHI1B(pNDM-MAR)/IncFIB(pNDM-Mar) -like plasmids carried mostly the bla NDM-1 gene, but bla OXA-48 carbapenemase was also found. ...
Background/Objectives: Carbapenem-resistant Enterobacterales (CRE) are a global health threat due to their high morbidity and mortality rates and limited treatment options. This study examines the plasmid-mediated transmission of virulence and antibiotic resistance determinants in carbapenem-resistant Klebsiella pneumoniae (Kpn) and Escherichia coli (E. coli) isolated from Russian hospitals. Methods: We performed short- and long-read whole-genome sequencing of 53 clinical isolates (48 Kpn and 5 E. coli) attributed to 15 genetic lineages and collected from 21 hospitals across nine Russian cities between 2016 and 2022. Results: The plasmid analysis identified 18 clusters that showed high concordance with replicon typing, with all clusters having a major replicon type. The majority of plasmids in the IncHI1B(pNDM-MAR)/IncFIB(pNDM-Mar)-like cluster (79.16%) carried both antibiotic resistance genes (e.g., blaNDM-1 and blaOXA-48) and virulence factors (VFs) such as siderophore genes. We hypothesized that hybrid plasmids could play a critical role in the dissemination of antibiotic resistance genes and VFs. Comparative analyses with global plasmid databases revealed high-risk lineages of hybrid plasmids that are predominantly spread throughout Russia at present. Conclusions: Our findings underscore the importance of monitoring plasmid backbones for clinical management, surveillance, and infection control activities.
... Carbapenemase-encoding plasmids in Enterobacteriaceae not only carry resistance determinants but also assist in the development and spread of ESBLs [144]. Additionally, various other plasmids carrying ARGs have been identified, including mcr (colistin resistance) [6], blaOXA-48, blaVIM, blaKPC, blaNDM (carbapenem resistance) [145][146][147][148], and blaCMY-2 (cephamycinase) [149], blaDHA-1 (cephalosporin resistance) [150]. ...
Multidrug resistance (MDR) in bacteria poses a serious global health threat, compromising the effectiveness of antibiotics. MDR causes approximately 700,000 deaths annually, with MDR tuberculosis alone claiming 230,000 lives. While bacteria inherently possess intrinsic resistance, acquired resistance stands out as the primary culprit in MDR development. Acquired resistance mechanisms mediated by the bacterial cell wall, nucleic acids, and proteins play a pivotal role in the genesis of MDR. Bacteria can modify their cell wall structure, produce resistant enzymes, exhibit mutations in antibiotic-targeted genes, and acquire resistant genes through horizontal gene transfer. Bacteria can produce proteins that act as enzymes, chemically modifying or directly degrading the antibiotic molecules, leading to the loss of their functionality. Apart from these mechanisms, biofilms also play a pivotal role in MDR expansion. Despite the development of several antibiotics since the discovery of penicillin, continuous structural and molecular modifications in bacteria render these antibiotics ineffective against MDR. The most recent approaches such as clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated proteins (CRISPR-Cas), nanotechnology, a combination of CRISPR-Cas, and nanoparticles, show promise in treating MDR. Thus, this review delves deep into the molecular mechanisms of MDR, emphasizing the limitations of current antibiotics due to bacterial evolution and highlighting current strategies in the fight against MDR bacteria. This will drive comprehensive research to uncover additional resistance mechanisms and develop innovative strategies to combat resistant bacteria effectively.
... The presence of Cluster A suggests continuous exchange of K. pneumoniae strains not only within single hospital wards but also between different hospital wards. This emphasizes the role of widespread dissemination within a hospital setting [37]. ...
Background
Carbapenemase-producing Klebsiella pneumoniae (CRKP) presents a significant challenge to antimicrobial therapy, especially when compounded by resistance to colistin. The objective of this study was to explore molecular epidemiological insights into strains of clinical K. pneumoniae that produce carbapenemases and exhibit resistance to colistin. Eighty clinical isolates of CRKP were obtained from Milad Hospital in Tehran, Iran. Antimicrobial susceptibility and colistin broth disk elution were determined. PCR assays were conducted to examine the prevalence of resistance-associated genes, including blaKPC, blaIMP, blaVIM, blaOXA−48, blaNDM and mcr-1 to -10. Molecular typing (PFGE) was used to assess their spread.
Results
Colistin resistance was observed in 27 isolates (33.7%) using the Broth Disk Elution method. Among positive isolates for carbapenemase genes, the most frequent gene was blaOXA−48, identified in 36 strains (45%). The mcr-1 gene was detected in 3.7% of the obtained isolates, with none of the other of the other mcr genes detected in the studied isolates.
Conclusion
To stop the spread of resistant K. pneumoniae and prevent the evolution of mcr genes, it is imperative to enhance surveillance, adhere rigorously to infection prevention protocols, and implement antibiotic stewardship practices.
... Integrons are not self-transferable elements, however they are frequently located on transposons or plasmids, allowing efficient gene transfer. More than 100 gene cassettes bearing resistance to different classes of antibiotics have been reported [51,52,69,70]. Class I and II integrons were detected in 86.4% of the tested isolates. ...
... Sequencing analysis of their variable region revealed that they carried distinctive cassettes encoding aminoglycosides and trimethoprim resistance determinants mainly. Previous reports have also indicated that most integrons-carrying genes are coding for aminoglycosides and trimethoprim resistance [52,[69][70][71]. ...
... The high rate of MDR and emergence of XDR among the tested isolates along with their enormous diversity (ERIC-PCR genotyping) could be explained by horizontal transfer of resistance determinants among bacterial isolates in hospitals. Variable rates of MDR (14.5-100%) were reported worldwide among P. mirabilis clinical isolates [3,52,69]. Previous studies in Egypt reported MDR (29.3-87.2%) among P. mirabilis clinical isolates [9,10,67]. ...
Background
Proteus mirabilis is an opportunistic pathogen that has been held responsible for numerous nosocomial and community-acquired infections which are difficult to be controlled because of its diverse antimicrobial resistance mechanisms.
Methods
Antimicrobial susceptibility patterns of P. mirabilis isolates collected from different clinical sources in Mansoura University Hospitals, Egypt was determined. Moreover, the underlying resistance mechanisms and genetic relatedness between isolates were investigated.
Results
Antimicrobial susceptibility testing indicated elevated levels of resistance to different classes of antimicrobials among the tested P. mirabilis clinical isolates (n = 66). ERIC-PCR showed great diversity among the tested isolates. Six isolates (9.1%) were XDR while all the remaining isolates were MDR. ESBLs and AmpCs were detected in 57.6% and 21.2% of the isolates, respectively, where blaTEM, blaSHV, blaCTX−M, blaCIT−M and blaAmpC were detected. Carbapenemases and MBLs were detected in 10.6 and 9.1% of the isolates, respectively, where blaOXA−48 and blaNDM−1 genes were detected. Quinolone resistant isolates (75.8%) harbored acc(6')-Ib-cr, qnrD, qnrA, and qnrS genes. Resistance to aminoglycosides, trimethoprim-sulfamethoxazole and chloramphenicol exceeded 80%. Fosfomycin was the most active drug against the tested isolates as only 22.7% were resistant. Class I or II integrons were detected in 86.4% of the isolates. Among class I integron positive isolates, four different gene cassette arrays (dfrA17- aadA5, aadB-aadA2, aadA2-lnuF, and dfrA14-arr-3-blaOXA−10-aadA15) and two gene cassettes (dfrA7 and aadA1) were detected. While class II integron positive isolates carried four different gene cassette arrays (dfrA1-sat1-aadA1, estXVr-sat2-aadA1, lnuF- dfrA1-aadA1, and dfrA1-sat2).
Conclusion
P. Mirabilis ability to acquire resistance determinants via integrons may be held responsible for the elevated rates of antimicrobial resistance and emergence of XDR or even PDR strains limiting the available therapeutic options for management of infections caused by those strains.
... Only in one isolate, bla OXA-48 had the typical genomic location within a Tn1999-like transposon on an IncL plasmid, which is usually present in K. pneumoniae or E. coli. From the scarce available data on bla OXA-48 in P. mirabilis, two studies found bla OXA-48 located on IncL/M plasmids [12,34], while a third study detected bla OXA-48 on the chromosome of a P. mirabilis outbreak clone in Spain [4]. ...
... The genetic environment of bla OXA-48 -like in P. mirabilis seems to be diverse, and the genetic background of the included isolates differs from the isolates published so far from other countries. Furthermore, other OXA-48like subtypes have been described in P. mirabilis from other countries, such as OXA-204 in France [52] and OXA-244 in Russia [34]. Therefore, it is likely that in other geographic regions, different genetic environments of bla OXA-48 -like are present, which should be further studied. ...
OXA-48-like enzymes represent the most frequently detected carbapenemases in Enterobacterales in Western Europe, North Africa and the Middle East. In contrast to other species, the presence of OXA-48-like in Proteus mirabilis leads to an unusually susceptible phenotype with low MICs for carbapenems and piperacillin-tazobactam, which is easily missed in the diagnostic laboratory. So far, there is little data available on the genetic environments of the corresponding genes, blaOXA-48-like, in P. mirabilis. In this study susceptibility phenotypes and genomic data of 13 OXA-48-like-producing P. mirabilis were investigated (OXA-48, n = 9; OXA-181, n = 3; OXA-162, n = 1). Ten isolates were susceptible to meropenem and ertapenem and three isolates were susceptible to piperacillin-tazobactam. The gene blaOXA-48 was chromosomally located in 7/9 isolates. Thereof, in three isolates blaOXA-48 was inserted into a P. mirabilis genomic island. Of the three isolates harbouring blaOXA-181 one was located on an IncX3 plasmid and two were located on a novel MOBF plasmid, pOXA-P12, within the new transposon Tn7713. In 5/6 isolates with plasmidic location of blaOXA-48-like, the plasmids could conjugate to E. coli recipients in vitro. Vice versa, blaOXA-48-carrying plasmids could conjugate from other Enterobacterales into a P. mirabilis recipient. These data show a high diversity of blaOXA-48-like genetic environments compared to other Enterobacterales, where genetic environments are quite homogenous. Given the difficult-to-detect phenotype of OXA-48-like-producing P. mirabilis and the location of blaOXA-48-like on mobile genetic elements, it is likely that OXA-48-like-producing P. mirabilis can disseminate, escape most surveillance systems, and contribute to a hidden spread of OXA-48-like.
... from India, France, and China [7,15,19,20]. Previous studies reported a significant prevalence of blaCTX-M among Proteus spp from Egypt, China, Europe, and Russia [8,21,22], which contradicts the findings of our study. ...
Background
Emerging antibiotic resistance (ABR) in Proteus spp., especially to third-generation cephalosporins (3GCc), carbapenems, and fluoroquinolones, challenges the treatment outcome and infection prevention. Limited studies pose a knowledge gap between them and ABR.
Methods
We investigated the in vitro efficacy of therapeutic options and prevalence of β-lac-tamase and plasmid-mediated quinolone resistance (PMQR) traits in 3GC- and/or fluoroquino-lone-nonsusceptible Proteus (P.) spp. (n=27) in Kolkata, India, during 2021–2022. P. mirabilis was commonly isolated (>80%) from superficial and urine samples. The majority of the isolates (48-78%) remained susceptible to piperacillin-tazobactam, meropenem, amikacin, cefoperazone-sulbactam, and cefepime.
Results
All isolates showed >0.2 multiple-antibiotic resistance index, with >65% being multi-drug and >30% being extensively drug-resistant. blaTEM (n=9), blaNDM (n=9), and qnrA (n=6) were commonly noted with the co-production of β-lactamases and PMQR in ten (37%) isolates. More than 50% of the isolates were devoid of the tested acquired genes.
Conclusion
The study concludes that superbugs dominate, with limited occurrence of plasmid-borne markers in this geographic location.
... Среди множества известных карбапенемаз глобальное распространение и, соответственно, значение получили плазмидные ферменты KPC-, NDM-, OXA-48-типов [4]. В Российской Федерации доминируют карбапенемазы NDM-OXA-48-типов [5][6][7]. Благоприятным фактором, ограничивающим бремя клебсиеллёзных инфекций, можно считать то, что большинство клебсиелл -возбудителей нозокомиальных инфекций различной локализации, при высокой частоте множественной устойчивости характеризуются невысокой вирулентностью. ...
Background . Currently, it is customary to distinguish two pathotypes of Klebsiella pneumoniae — classical and hypervirulent, which have the ability to cause community-acquired infections in healthy people. It has been shown that an increase in virulence is associated with the acquisition of additional genetic material — a plasmid carrying a cluster of aerobactin genes. Aim. To assess the prevalence of the aforementioned virulent plasmids around the globe and in Russia in particular, as well as to identify their key genetic features. Materials and methods . Plasmid sequences were downloaded from PLSDB and BV-BRC databases, annotated with the Abricate and Kleborate programs; cluster analysis was performed using the mge-cluster program, and phylogenetic analysis was performed using the Parsnp program. Results. 296 plasmid sequences isolated from 23 countries from clinical isolates of K.pneumoniae between 2006 and 2021 with a peak in 2019 were analyzed, with more than half of the plasmids coming from China. More than 30 sequence types were identified, among which ST11 and ST23 were predominant. Replicon genes of the IncFIB group were identified in almost all plasmids studied. The pre dominant type of aerobactin in the studied sequences was the first type (iuc1); sequences with iuc3 and iuc5 were also identified. Salmochelin synthesis genes were identified in only 37.1% of sequences; the yersiniabactin cluster was identified in two plasmids from China. 32.1% of plasmids carried resistance genes, of which 7.4% carried extended-spectrum beta-lactase genes and 5% contained carbapenemase genes. Nine clusters of sequences were obtained; almost all plasmids from Russia were assigned to one cluster and were NDM-positive. Together with plasmids from other European countries (Great Britain, Norway, Czech Republic), they formed a separate branch on the phylogenetic tree. Conclusion . Virulent plasmids carrying the aerobactin synthesis gene cluster are distributed globaly, and almost a third of them also carry antibiotic resistance genes.
... A variant of the latter is OXA-244, which differs from OXA-48 by a single amino-acid substitution showing reduced activity against carbapenems, thus making its detection particularly challenging (Oteo et al., 2013, Hoyos-Mallecot et al., 2017. It was first described in 2013 in a Klebsiella pneumoniae isolate from Spain and has also been identified in K. aerogenes and Proteus mirabilis from Russia as well as in sporadic cases of Escherichia coli from Germany, France and the Netherlands (Oteo et al., 2013, Fursova et al., 2015, van Hattem et al., 2016, Hoyos-Mallecot et al., 2017. However, unlike its plasmid localization in the Enterobacterales species, OXA-244 has predominantly been found to be integrated into the chromosome in E. coli, including isolates belonging to the sequence type (ST)38 (Oteo et al., 2013, Fursova et al., 2015, Hoyos-Mallecot et al., 2017, Potron et al., 2016. ...
... It was first described in 2013 in a Klebsiella pneumoniae isolate from Spain and has also been identified in K. aerogenes and Proteus mirabilis from Russia as well as in sporadic cases of Escherichia coli from Germany, France and the Netherlands (Oteo et al., 2013, Fursova et al., 2015, van Hattem et al., 2016, Hoyos-Mallecot et al., 2017. However, unlike its plasmid localization in the Enterobacterales species, OXA-244 has predominantly been found to be integrated into the chromosome in E. coli, including isolates belonging to the sequence type (ST)38 (Oteo et al., 2013, Fursova et al., 2015, Hoyos-Mallecot et al., 2017, Potron et al., 2016. Indeed, besides other global lineages of extraintestinal pathogenic E. coli (ExPEC) carrying bla , such as ST10, ST69, ST131, ST167 and ST361, the emergence and rapid dissemination of OXA-244-producing E. coli in Europe was predominantly due to genetically clustered isolates of ST38, as revealed by a rapid risk assessment coordinated and published by the European Centre for Disease Prevention and Control (ECDC) (ECDC, 2020, Hammerum et al., 2020, Welker et al., 2020. ...
