scholarly journals Investigation of Carbapenemase Genes in Carbapenem Resistant Enterobacterales Isolates: First KPC Report From Dokuz Eylul University Hospital

2021 ◽  
Author(s):  
Şeyda Şilan Okalin ◽  
Ayşe Nur Sarı Kaygısız ◽  
Mahmut Cem Ergon ◽  
İbrahim Mehmet Ali Öktem
Keyword(s):  
Treatment Options ◽  
Carbapenem Resistance ◽  
Tracheal Aspirate ◽  
University Hospital ◽  
Chain Reaction ◽  
Specific Primers ◽  
E Coli ◽  
Carbapenem Resistant ◽  
Carbapenemase Gene ◽  
Polymerase Chain

Objective: In recent years, increasing carbapenem resistance of Enterobacterales bacteria limits treatment options, considerably. The main mechanism of this resistance is the production of carbapenemase enzymes. The aim of this study is to determine carbapenemase gene types in Enterobacterales isolates from our hospitalized patients and assess the clonal associations of the isolates with KPC gene. Method: A total of 48 clinical Enterobacterales isolates resistant to at least one carbapeneme and received between January 2019 and March 2019 were included in the study. Sample types were consisted of urine, blood, tracheal aspirate, wound and sputum. Of these isolates, three were Escherichia coli while 45 were Klebsiella pneumoniae. Types of carbapenemases were investigated by polymerase chain reaction, using specific primers for VIM, IMP, NDM, KPC and OXA-48 genes. PFGE was performed to determine the clonal associations between blaKPC positive K. pnemoniae isolates. Results: According to the results, blaOXA-48 (n=2) and blaKPC (n=1) were found to be present among E. coli isolates. Regarding 45 K. pneumoniae isolates; only blaOXA-48 and only blaNDM were present in 30 and two isolates, respectively. Seven K. pneumoniae isolates were found positive for both blaOXA-48 and blaNDM. Remaining K. pneumoniae isolates (n=6) harboured only blaKPC. None of the isolates were positive for blaIMP and blaVIM. PFGE analysis showed four isolates had the same pulsotype (A), while two had different pulsotypes (B-C). Conclusion: To our knowledge, this is the first report of KPC gene isolated in Dokuz Eylul University Hospital.

scholarly journals Prevalence and molecular detection of shiga toxin producing Escherichia coli from diarrheic cattle

2016 ◽  
Vol 14 (1) ◽  
pp. 63-68 ◽  
Author(s):  
MM Akter ◽  
S Majumder ◽  
KH MNH Nazir ◽  
M Rahman
Keyword(s):  
Escherichia Coli ◽  
Shiga Toxin ◽  
Molecular Detection ◽  
Chain Reaction ◽  
Specific Primers ◽  
Fecal Samples ◽  
E Coli ◽  
Uremic Syndrome ◽  
Polymerase Chain ◽  
Positive Isolate

Shiga toxin-producing Escherichia coli (STEC) are zoonotically important pathogen which causes hemorrhagic colitis, diarrhea, and hemolytic uremic syndrome in animals and humans. The present study was designed to isolate and identify the STEC from fecal samples of diarrheic cattle. A total of 35 diarrheic fecal samples were collected from Bangladesh Agricultural University (BAU) Veterinary Teaching Hospital. The samples were primarily examined for the detection of E. coli by cultural, morphological and biochemical characteristics, followed by confirmation of the isolates by Polymerase Chain Reaction (PCR) using gene specific primers. Later, the STEC were identified among the isolated E. coli through detection of Stx-1 and Stx-2 genes using duplex PCR. Out of 35 samples, 25 (71.43%) isolates were confirmed to be associated with E. coli, of which only 7 (28%) isolates were shiga toxin producers, and all of them were positive for Stx-1. However, no Stx-2 positive isolate could be detected. From this study, it may be concluded that cattle can act as a reservoir of STEC which may transmit to human or other animals.J. Bangladesh Agril. Univ. 14(1): 63-68, June 2016

scholarly journals The Inc FII Plasmid and its Contribution in the Transmission of blaNDM-1 and blaKPC-2 in Klebsiella pneumoniae in Egypt

Antibiotics ◽  
2019 ◽  
Vol 8 (4) ◽  
pp. 266 ◽  
Author(s):  
Eman Ramadan Mohamed ◽  
Mamdouh Yones Ali ◽  
Nancy G F M Waly ◽  
Hamada Mohamed Halby ◽  
Rehab Mahmoud Abd El-Baky
Keyword(s):  
Polymerase Chain Reaction ◽  
Klebsiella Pneumoniae ◽  
Molecular Typing ◽  
University Hospital ◽  
Chain Reaction ◽  
Great Problem ◽  
E Coli ◽  
String Test ◽  
Resistance Patterns ◽  
Polymerase Chain

The emergence of blaKPC-2 and blaNDM-1 producing Klebsiella pneumoniae represents a great problem in many Egyptian hospitals. One hundred and twenty-six K. pneumoniae isolates from patients admitted to Assiut University Hospital were identified by an API20E kit. Carbapenemase-producing K. pneumoniae (CPKP) was detected by the modified carbapenem inactivation method (mCIM), the EDTA-modified carbapenem inactivation method (eCIM), and an E-test. Based on the polymerase chain reaction, all isolates were negative for bla-VIM-1 and bla-IMP-1, fifteen of these isolates were positive for both blaKPC-2 and blaNDM-1, two isolates were positive for blaKPC-2 only, and twenty-eight isolates were positive for bla-NDM-1 only. Although one isolate was positive for the string test, all CPKP isolates were negative for capsular genes. Only 71.1% of CPKP transferred their plasmids to their corresponding transconjugants (E. coli J53). The resistance patterns of the clinical isolates and their transconjugates were similar, except for 12 isolates, which showed differences with their transconjugates in the resistance profile of four antibiotics. Molecular typing of the plasmids based on replicon typing showed that Inc FIIK and FII plasmids predominated in isolates and their transconjugants carrying blaKPC-2 and/or blaNDM-1. Conjugative Inc FII plasmids play an important role in the spread of CPKP, and their recognition is essential to limit their spread.

scholarly journals Detection and Characterization of Carbapenem resistant Gram-negative bacilli isolates recovered from hospitalized patients at Soba University Hospital, Sudan

2020 ◽  
Author(s):  
Hana S. Elbadawi ◽  
Kamal M. Elhag ◽  
Elsheikh Mahgoub ◽  
Hisham N Altayb ◽  
Francine Ntoumi ◽  
...  
Keyword(s):  
Resistance Genes ◽  
Nosocomial Infections ◽  
Carbapenem Resistance ◽  
Clinical Isolates ◽  
University Hospital ◽  
P Value ◽  
Relative Distribution ◽  
Gram Negative ◽  
Carbapenem Resistant ◽  
Carbapenemase Gene

Abstract Background:Antimicrobial resistance (AMR) poses a threat to global health security. Whilst over the past decade, there has been an increase in reports of nosocomial infections globally caused by carbapenem resistant Gram-negative bacilli (GNB), data from Africa have been scanty. We performed a study of carbapenem resistance genes among GNB isolated from patients treated in hospitals in Khartoum state, Sudan.Methods:A cross-sectional study was conducted at Soba University Hospital (SUH) and Institute of Endemic Diseases, University of Khartoum for the period October 2016 to February 2017. A total of 206 GNB isolates from different clinical specimens were analyzed for carbapenem resistance genes using phenotypic tests and affirmed by genes detection. Multiplex PCR was performed for each strain to detect the carbapenemase genes, including the blaNDM, blaVIM, blaIMP, blaKPC, and blaOXA-48. In addition to blaCTXM, blaTEM and blaSHV. DNA sequencing and bioinformatics analysis were used to detect genes subtypes.Findings:Of 206 isolates, 171 (83%) were confirmed resistant phenotypically and 121 (58.7%) isolates were positive for the presence of one or more carbapenemase gene. New Delhi metallo-β-lactamase (NDM) types were the most predominant genes, blaNDM 107(88.4%). Others included blaIMP 7 (5.7%), blaOXA-48 5(4.1%), blaVIM 2 (1.6%) and blaKPC 0 (0%). Co- resistance genes with NDM producing GNB were detected in 87 (81.3%) of all blaNDM positive isolates. A significant association between phenotypic and genotypic resistance was observed (P- value < 0.001). NDM-1 was the most sub type was observed in 75 isolates (70 %), other subtypes were NDM- 5 and NDM-6. Infections due to Carbapenem resistant GNB are increasing at SUH, with the blaNDM being the prevalent genes among clinical isolates and belong to the Indian lineage.Conclusions:The frequency of carbapenemase producing bacilli was found to be improperly high in Khartoum hospitals. NDM was found to be the most prevalent carbapenemase gene among clinical isolates. Close surveillance across all hospitals in Sudan is required. The relative distribution of Carbapenemase genes among GNB in nosocomial infections in Africa needs to be defined.

scholarly journals 548. Carbapenem-Resistant Acinetobacter baumannii Antibiotic Susceptibility Testing and Antibiogram Formation, Connecticut 2017–2019

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S261-S261
Author(s):  
Anu Paranandi ◽  
Meghan Maloney ◽  
Erin Grogan ◽  
Bobbie Macierowski ◽  
Diane Noel ◽  
...  
Keyword(s):  
Susceptibility Testing ◽  
Inhibitory Concentration ◽  
Treatment Options ◽  
Carbapenem Resistance ◽  
Acinetobacter Baumanii ◽  
Antibiotic Development ◽  
Carbapenem Resistant ◽  
Testing Susceptibility ◽  
Polymerase Chain ◽  
Infectious Disease Threat

Abstract Background Carbapenem-resistant Acinetobacter baumanii (CRAB) is an infectious disease threat with limited treatment options. Statewide CRAB reporting and isolate submission has been mandated in Connecticut (CT) since 2017, which allowed the creation of a statewide CRAB antibiogram to assist with empiric treatment options for CRAB. Methods Clinical CRAB isolates from 2017 through the first quarter of 2019 underwent carbapenemase and expanded susceptibility testing at the CT State Public Health Laboratory or the Antibiotic Resistance Laboratory Network regional lab for carbapenemase and expanded susceptibility testing. Susceptibility testing was done by broth microdilution and disk diffusion, and interpreted using Clinical and Laboratory Standards Institute breakpoints. Carbapenemase producers were detected by the modified carbapenem inactivation method. Polymerase chain reaction testing identified carbapenemase genes. Results Of the 64 CRAB isolates submitted, 40 remained after confirmation of carbapenem resistance, i.e., resistance to at least one carbapenem, and deduplication of patients. Of these, 19 were carbapenemase producers (CP), and 21 were non-carpabenemase producers (Non-CP). All isolates were non-susceptible to cefepime, ceftazidime, levofloxacin and all carbapenems. Colistin susceptibilities were available for 33 isolates, 32 (97%) of which were susceptible. Tobramycin susceptibilities were available for 31 isolates, only 10 (32%) of which were susceptible. Of the CP, all 15 were susceptible to colistin, but only 2 (14%) were susceptible to tobramycin. Of the Non-CP, 16 (89%) were susceptible to colistin, and 8 (47%) were susceptible to tobramycin. Most CRABs had a tigecycline minimum inhibitory concentration (MIC) of ≤2 μg/mL, with a higher proportion of Non-CP with lower MIC values than CP. Conclusion CRAB shows resistance to all carbapenems, and most non-carbapenem antibiotics except colistin and in rare circumstances tobramycin. Most CRAB isolates had tigecycline MICs of ≤2 μg/mL. The statewide antibiogram illustrates the lack of approved antibiotics for the treatment of CRAB, underscoring the importance of further antibiotic development for CRAB treatment. Disclosures All authors: No reported disclosures.

scholarly journals High frequency of simultaneous presence of ESBL and carbapenemase producers among nosocomial  coliform isolates in Faisalabad, Pakistan

2020 ◽  
Vol 37 (1) ◽  
Author(s):  
Sofia Irfan ◽  
Aysha Azhar ◽  
Asad Bashir Awan ◽  
Salman Ahmad ◽  
Abdul Haque
Keyword(s):  
High Frequency ◽  
Original Work ◽  
Carbapenem Resistance ◽  
Simultaneous Presence ◽  
Chain Reaction ◽  
E Coli ◽  
Creative Commons ◽  
Polymerase Chain ◽  
Open Access Article ◽  
Phenotypic Susceptibility

Objectives: The objective of the current study was to find prevalence of relevant ESBL and carbapenemase producing genes in nosocomial E. coli and K. pneumoniae isolates and to check phenotypic susceptibility of all ESBL positive isolates to carbapenems. Methods: Forty ESBL producing clinical isolates of Escherichia coli (n=33) and Klebsiella pneumoniae (n=7) were examined for the presence of β-lactamase genes (CTX-M, CTX-M-1, 2, 3, 4 and TEM). Carbapenem resistance was checked phenotypically and by presence of blaNDM-1 gene. Results: Nine (27%) were positive for CTX-M genes, and 10 (30%) for TEM among E. coli isolates. Importantly, six isolates showed co-existence of CTX-M and TEM genes. In K. pneumoniae, two (28%) isolates were positive for CTX-M and one (14%) for TEM genes. Eight (24%) E. coli and one (14%) K. pneumoniae isolates were positive for CTX-M-1. Respective figures for CTX-M-4 were three (10%) and one (14%). CTX-M-2 and CTX-M-3 groups were not represented. Twenty (50%) isolates were resistant to both imipenem and meropenem out of which only four isolates expressed blaNDM-1 gene. Conclusions: The significant presence of both ESBL and carbapenemase producers and co-existence of ESBL and carbapenemases in the same isolates is worrisome. Abbreviations: ESBL: Extended spectrum β-lactamase. MBL: Metallo-betlactamase. PCR: Polymerase chain reaction. doi: https://doi.org/10.12669/pjms.37.1.3192 How to cite this:Irfan S, Azhar A, Bashir A, Ahmed S, Haque A. High frequency of simultaneous presence of ESBL and carbapenemase producers among nosocomial coliform isolates in Faisalabad, Pakistan. Pak J Med Sci. 2021;37(1):34-39.  doi: https://doi.org/10.12669/pjms.37.1.3192 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

scholarly journals Genetic Characterization Among Carbapenem-resistant Escherichia coli Strains Using Enterobacterial Repetitive Intergenic Consensus Polymerase Chain Reaction (ERIC-PCR) Fingerprinting in South Africa

2020 ◽  
Author(s):  
Kingsley Ehi Ebomah ◽  
Anthony Ifeanyi Okoh
Keyword(s):  
Escherichia Coli ◽  
Polymerase Chain Reaction ◽  
Antimicrobial Agents ◽  
Genetic Relatedness ◽  
Carbapenem Resistance ◽  
Beta Lactam ◽  
Enterobacterial Repetitive Intergenic Consensus ◽  
Chain Reaction ◽  
E Coli ◽  
Polymerase Chain

Abstract Background Carbapenems belong to beta-lactam class of antibiotics usually considered as the last line of defense because they can be effective against severe infections caused by prevalent multidrug-resistant (MDR) pathogens. However, carbapenems can be deactivated by bacteria that produce carbapenemase (beta-lactamase). This study was conducted to screen for carbapenem-resistance genes (CRGs) harbored by pathogenic strains of Escherichia coli recovered from different environmental samples. We also assessed the genetic relatedness among selected E. coli pathotypes using enterobacterial repetitive intergenic consensus-polymerase chain reaction (ERIC-PCR).Method: Molecular identification and characterization of the presumptive isolates were performed using PCR and isolates that exhibited antimicrobial resistance (AMR) phenotypically were further screened for some relevant CRGs (blaNDM−1, blaKPC and blaOXA−48−like). Furthermore, ERIC-PCR was used to determine the similarity and diversity of 31 E. coli strains which were randomly selected from the different sources analyzed in this study.Result Our findings revealed a total of 238 presumptive E. coli isolates, out of which 192 were confirmed positive for uidA gene. Further screening revealed 77 (40%) isolates belong to six key E. coli pathotypes and 70 of them exhibited phenotypic AMR. Additionally, twenty-nine (41%) of the 70 MDR pathogenic E. coli strains harbored CRGs; with 24 strains harboring blaNDM−1, 8 harboring blaKPC and 2 harboring blaOXA−48−like genes.Conclusion Findings also suggest that the selected E. coli pathotypes belonged to different genomic clusters, while the cluster analysis showed a possible genetic diversity among aquatic and farm isolates. Proper treatment of final effluents before discharge as well as the development of more effective strategies to control and manage the use of antimicrobial agents were strongly recommended.

scholarly journals Detection and characterization of Carbapenem resistant Gram-negative bacilli isolates recovered from hospitalized patients at Soba University Hospital, Sudan

2021 ◽  
Author(s):  
Hana S. Elbadawi ◽  
Kamal M. Elhag ◽  
Elsheikh Mahgoub ◽  
Hisham N Altayb ◽  
Ayman Ahmed ◽  
...  
Keyword(s):  
Nosocomial Infections ◽  
Carbapenem Resistance ◽  
Hospitalized Patients ◽  
University Hospital ◽  
Relative Distribution ◽  
Health Coverage ◽  
Health Security ◽  
Gram Negative ◽  
Carbapenem Resistant ◽  
Carbapenemase Gene

Abstract Background: Antimicrobial resistance (AMR) poses a complex threat to global health security and universal health coverage. Over recent decades, there has been an increase globally in reports of nosocomial infections caused by carbapenem-resistant Gram-negative bacilli (GNB). We aimed to explore the molecular characterization and detection of genes associated with carbapenem producing Gram negative bacteria isolated from hospitalized patients in Soba University Hospital (SUH) in Khartoum State, Sudan. Results: A total of 206 GNB clinical specimens were collected between October 2016 and February 2017 from hospitalized patients in SUH. Of 206 carbapenem resistance isolates, 171 (83%) were confirmed as phenotypically resistant and 121 (58.7%) isolates harboured one or more carbapenemase genes. New Delhi metallo-β-lactamase (NDM) types were the most predominant genes, blaNDM 107(52%). Others included blaIMP 7 (3.4%), blaOXA-48 5(2.4%) and blaVIM 2 (0.9%) Co-resistance genes with NDM producing GNB were detected in 87 (81.3%) of all blaNDM producing isolates. NDM1 was the most frequent subtype observed in 75 (70 %) blaNDM producing isolates.Conclusions: The frequency of carbapenemase producing bacilli was found to be high in SUH. NDM was found to be the most prevalent carbapenemase gene among clinical isolates. Close surveillance across all hospitals in Sudan is required. The relative distribution of carbapenemase genes among GNB in nosocomial infections in Africa needs to be defined.

scholarly journals Verification of the performance of the BD MAX Check-Points CPO Assay on clinical isolates

2020 ◽  
Vol 44 (3) ◽  
pp. 165-168
Author(s):  
Hae-Sun Chung ◽  
Miae Lee
Keyword(s):  
Rapid Detection ◽  
Clinical Laboratory ◽  
New Delhi ◽  
Bacterial Isolates ◽  
Chain Reaction ◽  
Clinical Specimens ◽  
Carbapenem Resistant ◽  
Carbapenemase Gene ◽  
Check Points ◽  
Polymerase Chain

Abstract Objectives The BD MAX Check-Points CPO Assay (BD MAX CPO Assay; BD, The Netherlands) is a diagnostic test designed for the rapid detection and differentiation of the bla KPC, bla NDM, bla VIM/bla IMP-1, and bla OXA-48 genes. We verified the performance of the BD MAX CPO Assay to implement it in the clinical laboratory. Methods A total of 113 bacterial isolates collected from various clinical specimens harboring carbapenemase genes as confirmed by polymerase chain reaction (PCR) and sequencing were evaluated. The results of the BD MAX CPO Assay were compared to previously confirmed results. Results All results of the BD MAX CPO Assay were concordant with previous results; 61 Klebsiella pneumoniae carbapenemase (KPC), 40 New Delhi metallo-β-lactamase (NDM), three oxacillinase-48 (OXA-48)-like, two imipenem (IMP), and four multiple carbapenemase genes (one KPC/NDM, three NDM/OXA) were detected by the BD MAX CPO Assay. Three non-carbapenemase-producing carbapenem-resistant Enterobacteriaceae isolates were negative. Conclusions The BD MAX CPO Assay can be used to identify carbapenemase gene in bacterial isolates cultured from clinical specimens in the clinical laboratory.

scholarly journals Investigation of NDM, VIM, KPC and OXA-48 genes, blue-carba and CIM in carbapenem resistant Enterobacterales isolates

2021 ◽  
Vol 15 (05) ◽  
pp. 696-703
Author(s):  
Yeliz Tanriverdi Cayci ◽  
Ilknur Biyik ◽  
Ferhan Korkmaz ◽  
Asuman Birinci
Keyword(s):  
Polymerase Chain Reaction ◽  
Carbapenem Resistance ◽  
Chain Reaction ◽  
Carbapenem Resistant ◽  
Pcr Method ◽  
Polymerase Chain

Introduction: Carbapenem resistance is an emerging problem in Enterobactarales. We aimed to investigate the presence of carbapenemase genes blaNDM, blaKPC, blaVIM and blaOXA-48 and evaluate the phenotypic blue-carba method and carbapenem inactivation method (CIM) in Enterobacterales isolates. Methodology: Total of 153 Enterobacterales isolates were tested in the study. Presence of blaNDM, blaKPC, blaVIM and blaOXA-48 genes was investigated by polymerase chain reaction (PCR) method. Carbapenemase production of the isolates was also tested by blue-carba method and CIM. Results: The presence of blaOXA-48 gene was detected in 110 (71.4%) and blaNDM gene was detected in 2 (1.3%) of the Enterobacterales isolates by PCR method. None of the isolates were positive for blaKPC and blaVIM genes. The 121 (78.54%) of the isolates were found to be positive by blue-carba method and CIM. And 105 (68.18%) of the isolates were determined as positive by both PCR, blue-carba and CIM. Conclusions: In our study, 112 (72.7%) of the Enterobacterales isolates were found to be positive for carbapenemase genes (blaoxa-48 and blaNDM), and 121 (78.57%) of different isolates were found to be positive for blue-carba and CIM. However, 105 (68.18%) of the carbapenem resistance isolates found to be positive for all three methods.

scholarly journals Molecular characterization and antibiotic resistance of Acinetobacter baumannii in cerebrospinal fluid and blood

PLoS ONE ◽  
2021 ◽  
Vol 16 (2) ◽  
pp. e0247418
Author(s):  
Xiaohong Shi ◽  
Hong Wang ◽  
Xin Wang ◽  
Huaiqi Jing ◽  
Ran Duan ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Infection Control ◽  
Acinetobacter Baumannii ◽  
Detection Rate ◽  
Genetic Relatedness ◽  
Treatment Options ◽  
Carbapenem Resistance ◽  
Control Measures ◽  
Carbapenem Resistant ◽  
Carbapenemase Gene

The increasing prevalence of carbapenem-resistant Acinetobacter baumannii (CRAB) caused nosocomial infections generate significant comorbidity and can cause death among patients. Current treatment options are limited. These infections pose great difficulties for infection control and clinical treatment. To identify the antimicrobial resistance, carbapenemases and genetic relatedness of Acinetobacter baumannii isolates from cerebrospinal fluid (CSF) and blood, a total of 50 nonrepetitive CSF isolates and 44 blood isolates were collected. The resistance phenotypes were determined, and polymerase chain reaction (PCR) was performed to examine the mechanisms of carbapenem resistance. Finally, multilocus sequence typing (MLST) was conducted to determine the genetic relatedness of these isolates. It was observed that 88 of the 94 collected isolates were resistant to imipenem or meropenem. Among them, the blaOXA-23 gene was the most prevalent carbapenemase gene, with an observed detection rate of 91.5% (86/94), followed by the blaOXA-24 gene with a 2.1% detection rate (2/94). Among all carbapenem-resistant Acinetobacter baumannii (CRAB) observations, isolates with the blaOXA-23 gene were resistant to both imipenem and meropenem. Interestingly, isolates positive for the blaOXA-24 gene but negative for the blaOXA-23 gene showed an imipenem-sensitive but meropenem-resistant phenotype. The MLST analysis identified 21 different sequence types (STs), with ST195, ST540 and ST208 most frequently detected (25.5%, 12.8% and 11.7%, respectively). 80 of the 94 isolates (85.1%) were clustered into CC92 which showed a carbapenem resistance phenotype (except AB13). Five novel STs were detected, and most of them belong to CRAB. In conclusion, these findings provide additional observations and epidemiological data of CSF and blood A. baumannii strains, which may improve future infection-control measures and aid in potential clinical treatments in hospitals and other clinical settings.

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