# | Rank | Similarity | Title + Abs. | Year | PMID |
|---|---|---|---|---|---|
| 0 | 1 | 2 | 3 | 4 | 5 |
| 3745 | 0 | 0.9806 | Antimicrobial resistance in methicillin-resistant staphylococcus aureus. In the medical community, antibiotics are revered as a miracle because they stop diseases brought on by pathogenic bacteria. Antibiotics have become the cornerstone of contemporary medical advancements ever since penicillin was discovered. Antibiotic resistance developed among germs quickly, placing a strain in the medical field. Methicillin-resistant Staphylococcus aureus (MRSA), Since 1961, has emerged as the major general antimicrobial resistant bacteria (AMR) worldwide. MRSA can easily transmit across the hospital system and has mostly gained resistance to medications called beta-lactamases. This enzyme destroys the cell wall of beta-lactam antibiotics resulting in resistance against that respective antibiotic. Daptomycin, linezolid and vancomycin were previously used to treat MRSA infections. However, due to mutations and Single nucleotide polymorphisms (SNPs) in Open reading frames (ORFs) and SCCmec machinery of respective antibody, MRSA developed resistance against those antibiotics. The MRSA strains (USA300, CC398, CC130 etc.), when their pan-genomes were analyzed were found the genes involved in invoking resistance against the antibiotics as well as the epidemiology of that respective strain. PENC (penicillin plus potassium clavulanate) is the new antibiotic showing potential in treatment of MRSA though it is itself resistant against penicillin alone. In this review, our main focus is on mechanism of development of AMR in MRSA, how different ORFs are involved in evoking resistance in MRSA and what is the core-genome of different antimicrobial resistant MRSA. | 2023 | 36936699 |
| 3746 | 1 | 0.9800 | Severe Disseminated Infection with Emerging Lineage of Methicillin-Sensitive Staphylococcus aureus. We report a case of severe disseminated infection in an immunocompetent man caused by an emerging lineage of methicillin-sensitive Staphylococcus aureus clonal complex 398. Genes encoding classic virulence factors were absent. The patient made a slow recovery after multiple surgical interventions and a protracted course of intravenous flucloxacillin. | 2019 | 30561304 |
| 3656 | 2 | 0.9799 | Surveillance of antimicrobial resistance in bacteria isolated from food animals to antimicrobial growth promoters and related therapeutic agents in Denmark. This study was conducted to describe the occurrence of acquired resistance to antimicrobials used for growth promotion among bacteria isolated from swine, cattle and poultry in Denmark. Resistance to structurally related therapeutic agents was also examined. Three categories of bacteria were tested: 1) indicator bacteria (Escherichia coli, Enterococcus faecalis, Enterococcus faecium), 2) zoonotic bacteria (Campylobacter, Salmonella, Yersinia enterocolitica), and 3) animal pathogens (E. coli, Staphylococcus aureus, coagulase-negative staphylococci (CNS), Staphylococcus hyicus, Actinobacillus pleuropneumoniae). All antimicrobials used as growth promoters in Denmark and some structurally related therapeutic agents (in brackets) were included: Avilamycin, avoparcin (vancomycin), bacitracin, carbadox, flavomycin, monensin, olaquindox, salinomycin, spiramycin (erythromycin, lincomycin), tylosin (erythromycin, lincomycin), and virginiamycin (pristinamycin). Bacterial species intrinsically resistant to an antimicrobial were not tested towards that antimicrobial. Breakpoints for growth promoters were established by population distribution of the bacteria tested. A total of 2,372 bacterial isolates collected during October 1995 to September 1996 were included in the study. Acquired resistance to all currently used growth promoting antimicrobials was found. A frequent occurrence of resistance were observed to avilamycin, avoparcin, bacitracin, flavomycin, spiramycin, tylosin and virginiamycin, whereas resistance to carbadox, monensin, olaquindox and salinomycin was less frequent. The occurrence of resistance varied by animal origin and bacterial species. The highest levels of resistance was observed among enterococci, whereas less resistance was observed among zoonotic bacteria and bacteria pathogenic to animals. The association between the occurrence of resistance and the consumption of the antimicrobial is discussed. The results show the present level of resistance to growth promoters in bacteria from food animals in Denmark. They will form the baseline for comparison with future prospective studies, thereby enabling the determination of trends over time. | 1998 | 9725794 |
| 5436 | 3 | 0.9797 | Plasmid-Encoded Transferable mecB-Mediated Methicillin Resistance in Staphylococcus aureus. During cefoxitin-based nasal screening, phenotypically categorized methicillin-resistant Staphylococcus aureus (MRSA) was isolated and tested negative for the presence of the mecA and mecC genes as well as for the SCCmec-orfX junction region. The isolate was found to carry a mecB gene previously described for Macrococcus caseolyticus but not for staphylococcal species. The gene is flanked by β-lactam regulatory genes similar to mecR, mecI, and blaZ and is part of an 84.6-kb multidrug-resistance plasmid that harbors genes encoding additional resistances to aminoglycosides (aacA-aphD, aphA, and aadK) as well as macrolides (ermB) and tetracyclines (tetS). This further plasmidborne β-lactam resistance mechanism harbors the putative risk of acceleration or reacceleration of MRSA spread, resulting in broad ineffectiveness of β-lactams as a main therapeutic application against staphylococcal infections. | 2018 | 29350135 |
| 1750 | 4 | 0.9797 | The European Union Summary Report on Antimicrobial Resistance in zoonotic and indicator bacteria from humans, animals and food in 2020/2021. Antimicrobial resistance (AMR) data on zoonotic and indicator bacteria from humans, animals and food are collected annually by the EU Member States (MSs) and reporting countries, jointly analysed by EFSA and ECDC and presented in a yearly EU Summary Report. This report provides an overview of the main findings of the 2020-2021 harmonised AMR monitoring in Salmonella spp., Campylobacter jejuni and C. coli in humans and food-producing animals (broilers, laying hens and turkeys, fattening pigs and bovines under 1 year of age) and relevant meat thereof. For animals and meat thereof, indicator E. coli data on the occurrence of AMR and presumptive Extended spectrum β-lactamases (ESBL)-/AmpC β-lactamases (AmpC)-/carbapenemases (CP)-producers, as well as the occurrence of methicillin-resistant Staphylococcus aureus are also analysed. In 2021, MSs submitted for the first time AMR data on E. coli isolates from meat sampled at border control posts. Where available, monitoring data from humans, food-producing animals and meat thereof were combined and compared at the EU level, with emphasis on multidrug resistance, complete susceptibility and combined resistance patterns to selected and critically important antimicrobials, as well as Salmonella and E. coli isolates exhibiting ESBL-/AmpC-/carbapenemase phenotypes. Resistance was frequently found to commonly used antimicrobials in Salmonella spp. and Campylobacter isolates from humans and animals. Combined resistance to critically important antimicrobials was mainly observed at low levels except in some Salmonella serotypes and in C. coli in some countries. The reporting of a number of CP-producing E. coli isolates (harbouring bla (OXA-48), bla (OXA-181), and bla (NDM-5) genes) in pigs, bovines and meat thereof by a limited number of MSs (4) in 2021, requests a thorough follow-up. The temporal trend analyses in both key outcome indicators (rate of complete susceptibility and prevalence of ESBL-/AmpC- producers) showed that encouraging progress have been registered in reducing AMR in food-producing animals in several EU MSs over the last years. | 2023 | 36891283 |
| 3748 | 5 | 0.9797 | Vancomycin resistance in Gram-positive bacteria other than Enterococcus spp. This is a review article on vancomycin resistance on gram positive bacteria other than enterococci. Epidemiology of varying resistance, its clinical relevance and therapeutic options in infections caused by vancomycin resistant Listeria spp., Corynebacteria, streptococci and staphylocci are discussed. | 2000 | 10720798 |
| 3658 | 6 | 0.9795 | Antibiotics for gram-positive bacterial infections. Vancomycin, teicoplanin, quinupristin/dalfopristin, and linezolid. Vancomycin is a safe, effective antibiotic for a variety of serious gram-positive infections. Because of emerging resistance in enterococci and staphylococci and the emerging threat of spread of vancomycin-resistant genes to other gram-positive organisms, judicious use of vancomycin should be promoted. Quinupristin/dalfopristin, a streptogramin antibiotic, and linezolid, an oxazolidinone, show promise against some strains of gram-positive bacteria that are resistant to vancomycin. | 2000 | 10829266 |
| 2519 | 7 | 0.9795 | Clinical Perspective of Antimicrobial Resistance in Bacteria. Antimicrobial resistance (AMR) has become a global clinical problem in recent years. With the discovery of antibiotics, infections were not a deadly problem for clinicians as they used to be. However, worldwide AMR comes with the overuse/misuse of antibiotics and the spread of resistance is deteriorated by a multitude of mobile genetic elements and relevant resistant genes. This review provides an overview of the current situation, mechanism, epidemiology, detection methods and clinical treatment for antimicrobial resistant genes in clinical important bacteria including methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus (VRE), penicillin-resistant Streptococcus pneumoniae (PRSP), extended-spectrum β-lactamase-producing Enterobacteriaceae, acquired AmpC β-lactamase-producing Enterobacteriaceae, carbapenemase-producing Enterobacteriaceae (CPE), multidrug-resistant (MDR) Acinetobacter baumannii and Pseudomonas aeruginosa. | 2022 | 35264857 |
| 2258 | 8 | 0.9794 | Antimicrobial-Resistant Bacteria in Infected Wounds, Ghana, 2014(1). Wound infections are an emerging medical problem worldwide, frequently neglected in under-resourced countries. Bacterial culture and antimicrobial drug resistance testing of infected wounds in patients in a rural hospital in Ghana identified no methicillin-resistant Staphylococcus aureus or carbapenem-resistant Enterobacteriaceae but identified high combined resistance of Enterobacteriaceae against third-generation cephalosporins and fluoroquinolones. | 2018 | 29664368 |
| 1749 | 9 | 0.9794 | The European Union summary report on antimicrobial resistance in zoonotic and indicator bacteria from humans, animals and food in 2021-2022. This report by the European Food Safety Authority and the European Centre for Disease prevention and Control, provides an overview of the main findings of the 2021-2022 harmonised Antimicrobial Resistance (AMR) monitoring in Salmonella spp., Campylobacter jejuni and C. coli from humans and food-producing animals (broilers, laying hens and fattening turkeys, fattening pigs and cattle under one year of age) and relevant meat thereof. For animals and meat thereof, AMR data on indicator commensal Escherichia coli, presumptive extended-spectrum beta-lactamases (ESBL)-/AmpC beta-lactamases (AmpC)-/carbapenemase (CP)-producing E. coli, and the occurrence of methicillin-resistant Staphylococcus aureus (MRSA) are also analysed. Generally, resistance levels differed greatly between reporting countries and antimicrobials. Resistance to commonly used antimicrobials was frequently found in Salmonella and Campylobacter isolates from humans and animals. In humans, increasing trends in resistance to one of two critically antimicrobials (CIA) for treatment was observed in poultry-associated Salmonella serovars and Campylobacter, in at least half of the reporting countries. Combined resistance to CIA was however observed at low levels except in some Salmonella serovars and in C. coli from humans and animals in some countries. While CP-producing Salmonella isolates were not detected in animals in 2021-2022, nor in 2021 for human cases, in 2022 five human cases of CP-producing Salmonella were reported (four harbouring bla (OXA-48) or bla (OXA-48-like) genes). The reporting of a number of CP-producing E. coli isolates (harbouring bla (OXA-48), bla (OXA-181), bla (NDM-5) and bla (VIM-1) genes) in fattening pigs, cattle under 1 year of age, poultry and meat thereof by a limited number of MSs (5) in 2021 and 2022, requires a thorough follow-up. The temporal trend analyses in both key outcome indicators (rate of complete susceptibility and prevalence of ESBL-/AmpC-producers in E. coli) showed an encouraging progress in reducing AMR in food-producing animals in several EU MSs over the last 7 years. | 2024 | 38419967 |
| 5566 | 10 | 0.9794 | Resistance to antimicrobial agents used for animal therapy in pathogenic-, zoonotic- and indicator bacteria isolated from different food animals in Denmark: a baseline study for the Danish Integrated Antimicrobial Resistance Monitoring Programme (DANMAP). This study describes the establishment and first results of a continuous surveillance system of antimicrobial resistance among bacteria isolated from pigs, cattle and broilers in Denmark. The three categories of bacteria tested were: 1) indicator bacteria (Escherichia coli, Enterococcus faecalis, Enterococcus faecium), 2) zoonotic bacteria (Campylobacter coli/jejuni, Salmonella enterica, Yersinia enterocolitica), and 3) animal pathogens (E. coli, Staphylococcus aureus, coagulase-negative staphylococci (CNS), Staphylococcus hyicus, Actinobacillus pleuropneumoniae). A total of 3304 bacterial isolates collected from October 1995 through December 1996 were tested for susceptibility to all major classes of antimicrobial agents used for therapy in Denmark. Bacterial species intrinsically resistant to an antimicrobial were not tested towards that antimicrobial. Acquired resistance to all antimicrobials was found. The occurrence of resistance varied by animal origin and bacterial species. In general, resistance was observed more frequently among isolates from pigs than from cattle and broilers. The association between the occurrence of resistance and the consumption of the antimicrobial is discussed, as is the occurrence of resistance in other countries. The results of this study show the present level of resistance to antimicrobial agents among a number of bacterial species isolated from food animals in Denmark. Thus, the baseline for comparison with future prospective studies has been established, enabling the determination of trends over time. | 1998 | 9744762 |
| 2259 | 11 | 0.9794 | Gram-Negative Bacteria Harboring Multiple Carbapenemase Genes, United States, 2012-2019. Reports of organisms harboring multiple carbapenemase genes have increased since 2010. During October 2012-April 2019, the Centers for Disease Control and Prevention documented 151 of these isolates from 100 patients in the United States. Possible risk factors included recent history of international travel, international inpatient healthcare, and solid organ or bone marrow transplantation. | 2021 | 34424168 |
| 2270 | 12 | 0.9794 | Antibiotic resistant bacteria and resistance genes in biofilms in clinical wastewater networks. Increasing isolation rates of resistant bacteria in the last years require identification of potential infection reservoirs in healthcare facilities. Especially the clinical wastewater network represents a potential source of antibiotic resistant bacteria. In this work, the siphons of the sanitary installations from 18 hospital rooms of two German hospitals were examined for antibiotic resistant bacteria and antibiotic residues including siphons of showers and washbasins and toilets in sanitary units of psychosomatic, haemato-oncological, and rehabilitation wards. In addition, in seven rooms of the haemato-oncological ward, the effect of 24 h of stagnation on the antibiotic concentrations and MDR (multi-drug-resistant) bacteria in biofilms was evaluated. Whereas no antibiotic residues were found in the psychosomatic ward, potential selective concentrations of piperacillin, meropenem and ciprofloxacin were detected at a rehabilitation ward and ciprofloxacin and trimethoprim were present at a haemato-oncology ward. Antibiotic resistant bacteria were isolated from the siphons of all wards, however in the psychosomatic ward, only one MDR strain with resistance to piperacillin, third generation cephalosporins and quinolones (3MRGN) was detected. In contrast, the other two wards yielded 11 carbapenemase producing MDR isolates and 15 3MRGN strains. The isolates from the haemato-oncological ward belonged mostly to two specific rare sequence types (ST) (P. aeruginosa ST823 and Enterobacter cloacae complex ST167). In conclusion, clinical wastewater systems represent a reservoir for multi-drug-resistant bacteria. Consequently, preventive and intervention measures should not start at the wastewater treatment in the treatment plant, but already in the immediate surroundings of the patient, in order to minimize the infection potential. | 2019 | 30905579 |
| 2518 | 13 | 0.9794 | Plasmids Carrying Antimicrobial Resistance Genes in Gram-Negative Bacteria. Gram-negative bacteria are prevalent pathogens associated with hospital-acquired infections (HAI) that are a major challenge for patient safety, especially in intensive care units [...]. | 2022 | 36014095 |
| 1850 | 14 | 0.9794 | One Health Spread of 16S Ribosomal RNA Methyltransferase-Harboring Gram-Negative Bacterial Genomes: An Overview of the Americas. Aminoglycoside antimicrobials remain valuable therapeutic options, but their effectiveness has been threatened by the production of bacterial 16S ribosomal RNA methyltransferases (16S-RMTases). In this study, we evaluated the genomic epidemiology of 16S-RMTase genes among Gram-negative bacteria circulating in the American continent. A total of 4877 16S-RMTase sequences were identified mainly in Enterobacterales and nonfermenting Gram-negative bacilli isolated from humans, animals, foods, and the environment during 1931-2023. Most of the sequences identified were found in the United States, Brazil, Canada, and Mexico, and the prevalence of 16S-RMTase genes have increased in the last five years (2018-2022). The three species most frequently carrying 16S-RMTase genes were Acinetobacter baummannii, Klebsiella pneumoniae, and Escherichia coli. The armA gene was the most prevalent, but other 16S-RMTase genes (e.g., rmtB, rmtE, and rmtF) could be emerging backstage. More than 90% of 16S-RMTase sequences in the Americas were found in North American countries, and although the 16S-RMTase genes were less prevalent in Central and South American countries, these findings may be underestimations due to limited genomic data. Therefore, whole-genome sequence-based studies focusing on aminoglycoside resistance using a One Health approach in low- and middle-income countries should be encouraged. | 2023 | 37764972 |
| 2264 | 15 | 0.9793 | Assessment of three antibiotic combination regimens against Gram-negative bacteria causing neonatal sepsis in low- and middle-income countries. Gram-negative bacteria (GNB) are a major cause of neonatal sepsis in low- and middle-income countries (LMICs). Although the World Health Organization (WHO) reports that over 80% of these sepsis deaths could be prevented through improved treatment, the efficacy of the currently recommended first- and second-line treatment regimens for this condition is increasingly affected by high rates of drug resistance. Here we assess three well known antibiotics, fosfomycin, flomoxef and amikacin, in combination as potential antibiotic treatment regimens by investigating the drug resistance and genetic profiles of commonly isolated GNB causing neonatal sepsis in LMICs. The five most prevalent bacterial isolates in the NeoOBS study (NCT03721302) are Klebsiella pneumoniae, Acinetobacter baumannii, E. coli, Serratia marcescens and Enterobacter cloacae complex. Among these isolates, high levels of ESBL and carbapenemase encoding genes are detected along with resistance to ampicillin, gentamicin and cefotaxime, the current WHO recommended empiric regimens. The three new combinations show excellent in vitro activity against ESBL-producing K. pneumoniae and E. coli isolates. Our data should further inform and support the clinical evaluation of these three antibiotic combinations for the treatment of neonatal sepsis in areas with high rates of multidrug-resistant Gram-negative bacteria. | 2024 | 38729951 |
| 2495 | 16 | 0.9793 | Transmission of Mobile Colistin Resistance (mcr-1) by Duodenoscope. BACKGROUND: Clinicians increasingly utilize polymyxins for treatment of serious infections caused by multidrug-resistant gram-negative bacteria. Emergence of plasmid-mediated, mobile colistin resistance genes creates potential for rapid spread of polymyxin resistance. We investigated the possible transmission of Klebsiella pneumoniae carrying mcr-1 via duodenoscope and report the first documented healthcare transmission of mcr-1-harboring bacteria in the United States. METHODS: A field investigation, including screening targeted high-risk groups, evaluation of the duodenoscope, and genome sequencing of isolated organisms, was conducted. The study site included a tertiary care academic health center in Boston, Massachusetts, and extended to community locations in New England. RESULTS: Two patients had highly related mcr-1-positive K. pneumoniae isolated from clinical cultures; a duodenoscope was the only identified epidemiological link. Screening tests for mcr-1 in 20 healthcare contacts and 2 household contacts were negative. Klebsiella pneumoniae and Escherichia coli were recovered from the duodenoscope; neither carried mcr-1. Evaluation of the duodenoscope identified intrusion of biomaterial under the sealed distal cap; devices were recalled to repair this defect. CONCLUSIONS: We identified transmission of mcr-1 in a United States acute care hospital that likely occurred via duodenoscope despite no identifiable breaches in reprocessing or infection control practices. Duodenoscope design flaws leading to transmission of multidrug-resistant organsisms persist despite recent initiatives to improve device safety. Reliable detection of colistin resistance is currently challenging for clinical laboratories, particularly given the absence of a US Food and Drug Administration-cleared test; improved clinical laboratory capacity for colistin susceptibility testing is needed to prevent the spread of mcr-carrying bacteria in healthcare settings. | 2019 | 30204838 |
| 2105 | 17 | 0.9793 | Infections Caused by Antimicrobial Drug-Resistant Saprophytic Gram-Negative Bacteria in the Environment. BACKGROUND: Drug-resistance genes found in human bacterial pathogens are increasingly recognized in saprophytic Gram-negative bacteria (GNB) from environmental sources. The clinical implication of such environmental GNBs is unknown. OBJECTIVES: We conducted a systematic review to determine how often such saprophytic GNBs cause human infections. METHODS: We queried PubMed for articles published in English, Spanish, and French between January 2006 and July 2014 for 20 common environmental saprophytic GNB species, using search terms "infections," "human infections," "hospital infection." We analyzed 251 of 1,275 non-duplicate publications that satisfied our selection criteria. Saprophytes implicated in blood stream infection (BSI), urinary tract infection (UTI), skin and soft tissue infection (SSTI), post-surgical infection (PSI), osteomyelitis (Osteo), and pneumonia (PNA) were quantitatively assessed. RESULTS: Thirteen of the 20 queried GNB saprophytic species were implicated in 674 distinct infection episodes from 45 countries. The most common species included Enterobacter aerogenes, Pantoea agglomerans, and Pseudomonas putida. Of these infections, 443 (66%) had BSI, 48 (7%) had SSTI, 36 (5%) had UTI, 28 (4%) had PSI, 21 (3%) had PNA, 16 (3%) had Osteo, and 82 (12%) had other infections. Nearly all infections occurred in subjects with comorbidities. Resistant strains harbored extended-spectrum beta-lactamase (ESBL), carbapenemase, and metallo-β-lactamase genes recognized in human pathogens. CONCLUSION: These observations show that saprophytic GNB organisms that harbor recognized drug-resistance genes cause a wide spectrum of infections, especially as opportunistic pathogens. Such GNB saprophytes may become increasingly more common in healthcare settings, as has already been observed with other environmental GNBs such as Acinetobacter baumannii and Pseudomonas aeruginosa. | 2017 | 29164118 |
| 4753 | 18 | 0.9793 | Vancomycin-resistant enterococci. Enterococci, a part of normal gut flora, are not particularly pathogenic organisms in humans. For example, they do not cause respiratory tract infections. The most frequent enterococcal infections are urinary tract infections. Despite their lack of pathogenicity, enterococci have emerged as significant nosocomial pathogens in the United States and elsewhere. Enterococci are formidable pathogens because of their resistance to antimicrobial agents. Enterococci are intrinsically resistant to beta-lactam agents and aminoglycosides and were the first bacteria to acquire vancomycin resistance. Infection control measures have been far from effective at preventing the dissemination of vancomycin-resistant enterococci in the hospital. Therapy for infections due to vancomycin-resistant enterococci presents real challenges. Most isolates remain susceptible to nitrofurantoin, but this agent is useful only for urinary tract infections. The greatest threat posed by vancomycin-resistant enterococci is the potential to transfer their resistance genes to more pathogenic gram-positive bacteria, which could produce truly frightening pathogens. | 1998 | 9597252 |
| 4852 | 19 | 0.9793 | Recent trends in antibiotic resistance in European ICUs. PURPOSE OF REVIEW: Antimicrobial resistance is an emerging problem in ICUs worldwide. As numbers of published results from national/international surveillance studies rise rapidly, the amount of new information may be overwhelming. Therefore, we reviewed recent trends in antibiotic resistance in ICUs across Europe in the past 18 months. RECENT FINDINGS: In this period, infections caused by methicillin-resistant Staphylococcus aureus appeared to stabilize (and even decrease) in some countries, and infection rates due to Gram-positive bacteria resistant to vancomycin, linezolid or daptomycin have remained low. In contrast, we are witnessing a continent-wide emergence of infections caused by multiresistant Gram-negative bacteria, especially Escherichia coli and Klebsiella pneumoniae, with easily exchangeable resistance genes located on plasmids, producing enzymes such as extended spectrum β-lactamases and carbapenamases. In the absence of new antibiotics, prevention of infections, reducing unnecessary antibiotic use, optimizing adherence to universal hygienic and infection control measures, and improving implementation of diagnostic tests are our only tools to combat this threat. SUMMARY: As the epidemiology of antibiotic resistance in ICUs is rapidly changing toward more frequently occurring epidemics and endemicity of multi and panresistant Gram-negative pathogens, better infection control and improved diagnostics will become even more important than before. | 2011 | 21986462 |