scholarly journals Success of ceftazidime–avibactam and aztreonam in combination for a refractory biliary infection with recurrent bacteraemia due to blaIMP-4 carbapenemase-producing Enterobacter hormaechei subsp. oharae

2021 ◽  
Vol 3 (8) ◽  
Author(s):  
Genevieve McKew ◽  
John Merlino ◽  
Alicia Beukers ◽  
Sebastian van Hal ◽  
Thomas Gottlieb
Keyword(s):  
Treatment Options ◽  
Beta Lactamase ◽  
Therapeutic Success ◽  
Content Type ◽  
Beta Lactamases ◽  
Link Type ◽  
Carbapenem Resistant ◽  
Enterobacter Hormaechei ◽  
Miseq Platform ◽  
Alternative Antibiotic

Background. Infections due to metallo-beta-lactamase (MBL)-producing organisms are becoming a significant problem, and antibiotic treatment options are limited. Aztreonam inhibits MBLs, and its use in combination with ceftazidime–avibactam (CAZ–AVI–AZT) to inhibit other beta-lactamases shows promise. Methods. A 45-year-old woman suffered from recurrent and sustained MBL (blaIMP-4)+ Enterobacter cloacae complex bacteraemia from an undrainable biliary source, and had failed nine alternative antibiotic regimens over a 5-month period. The 10th episode was successfully treated with CAZ–AVI–AZT, and she has had no further relapses. Three of the isolates underwent whole-genome sequencing (WGS) on the MiSeq platform and were analysed with the Nullarbor pipeline. Results. A layered Etest method for synergy between CAZ–AVI and aztreonam demonstrated an MIC of 2 mg l−1 for the combination. Isolates were identified by WGS as Enterobacter hormaechei subsp. oharae . All three of the isolates had blaTEM-4 ESBL, blaOXA-1 and blaACT-25. Two of the carbapenem-resistant isolates contained blaIMP-4. Conclusion. While aztreonam inhibits MBLs, MBL-positive isolates often express other beta-lactamase enzymes. Avibactam inhibits ESBLs and other beta-lactamases, and its use in this case possibly contributed to therapeutic success due to inhibition of the concomitant blaTEM-4 in the isolates. This case demonstrates that phenotypic antimicrobial susceptibility testing (layered Etests for synergy), backed up by WGS, can produce results that allow tailored antimicrobial therapy in difficult infections. This case adds to the evidence for using CAZ–AVI–AZT in serious MBL infections.

scholarly journals Detection of New Delhi metallo-beta-lactamase enzyme gene bla NDM-1 associated with the Int-1 gene in Gram-negative bacteria collected from the effluent treatment plant of a tuberculosis care hospital in Delhi, India

2020 ◽  
Vol 2 (6) ◽  
Author(s):  
Amit Aggarwal ◽  
Manpreet Bhalla ◽  
Khan Hena Fatima
Keyword(s):  
Treatment Plant ◽  
Effluent Treatment ◽  
Diffusion Method ◽  
Care Hospital ◽  
Beta Lactamase ◽  
Genotypic Resistance ◽  
Content Type ◽  
Link Type ◽  
Carbapenem Resistant ◽  
Effluent Treatment Plant

Background. Organisms possessing the bla NDM-1 gene (responsible for carbapenem resistance) with a class-1 integron can acquire many other antibiotic resistance genes from the community sewage pool and become multidrug-resistant superbugs. In this regard, hospital sewage, which contains a large quantity of residual antibiotics, metals and disinfectants, is being recognized as a significant cause of antimicrobial resistance (AMR) origination and spread across the major centres of the world and is thus routinely investigated as a marker for tracing the origin of drug resistance. Therefore, in this study, an attempt has been made to identify and characterize the carbapenem-resistant microbes associated with integron genes amongst the organisms isolated from the effluent treatment plant (ETP) installed in a tertiary respiratory care hospital in Delhi, India. Methods. One hundred and thirty-eight organisms belonging to Escherichia , Klebsiella , Pseudomonas and Acinetobacter spp. were collected from the incoming and outgoing sewage lines of the ETP. Carbapenem sensitivity and characterization was performed by the imipenem and imipenem-EDTA disc diffusion method. Later DNA extraction and PCR steps were performed for the Int-1 and bla NDM-1 genes. Results. Of the 138 organisms, 86 (62.3 %) were imipenem-resistant (P<0.05). One hundred and twenty-four (89.9 %) organisms had one or both of the genes. Overall, the bla NDM-1 gene (genotypic resistance) was present in 71 % (98/138) of organisms. 53.6 % (74/138) organisms were double gene-positive (bla NDM-1 + Int-1), of which 40 were producing the metallo-beta-lactamase enzyme, making up almost 28.9 % (40/138) of the collected organisms. Conclusion. The current study strengthens the hypothesis that Carbapenem resistant organisms are in a high-circulation burden through the human gut and hospital ETPs are providing an environment for resistance origination and amplification.

A pentaplex real-time PCR assay for rapid identification of major beta-lactamase genes KPC, NDM, CTX, CMY, and OXA-48 directly from bacteria in blood

2021 ◽  
Vol 70 (12) ◽  
Author(s):  
Taalin R. Hoj ◽  
Bradley McNeely ◽  
Kylie Webber ◽  
Evelyn Welling ◽  
William G. Pitt ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Klebsiella Pneumoniae ◽  
Real Time ◽  
Real Time Pcr ◽  
Type Species ◽  
New Delhi ◽  
Beta Lactamase ◽  
Content Type ◽  
Link Type ◽  
Carbapenem Resistant

Introduction. Antibiotic resistance, particularly in cases of sepsis, has emerged as a growing global public health concern and economic burden. Current methods of blood culture and antimicrobial susceptibility testing of agents involved in sepsis can take as long as 3–5 days. It is vital to rapidly identify which antimicrobials can be used to effectively treat sepsis cases on an individual basis. Here, we present a pentaplex, real-time PCR-based assay that can quickly identify the most common beta-lactamase genes ( Klebsiella pneumoniae carbapenemase (KPC); New Delhi metallo-beta-lactamase (NDM); cefotaximase-Munich (CTX-M); cephamycin AmpC beta-lactamases (CMY); and Oxacillinase-48 (OXA-48)) from pathogens derived directly from the blood of patients presenting with bacterial septicemia. Aim. To develop an assay which can rapidly identify the most common beta-lactamase genes in Carbapenem-resistant Enterobacteriaceae bacteria (CREs) from the United States. Hypothesis/Gap Statement. Septicemia caused by carbapenem-resistant bacteria has a death rate of 40–60 %. Rapid diagnosis of antibiotic susceptibility directly from bacteria in blood by identification of beta-lactamase genes will greatly improve survival rates. In this work, we develop an assay capable of concurrently identifying the five most common beta-lactamase and carbapenemase genes. Methodology. Primers and probes were created which can identify all subtypes of Klebsiella pneumoniae carbapenemase (KPC); New Delhi metallo-beta-lactamase (NDM); cefotaximase-Munich (CTX); cephamycin AmpC beta-lactamase (CMY); and oxacillinase-48 (OXA-48). The assay was validated using 13 isolates containing various PCR targets from the Centre for Disease Control Antimicrobial Resistance Isolate Bank Enterobacterales Carbapenemase Diversity Panel. Blood obtained from volunteers was spiked with CREs and bacteria were separated, lysed, and subjected to analysis via the pentaplex assay. Results. This pentaplex assay successfully identified beta-lactamase genes derived from bacteria separated from blood at concentrations of 4–8 c.f.u. ml−1. Conclusion. This assay will improve patient outcomes by supplying physicians with critical drug resistance information within 2 h of septicemia onset, allowing them to prescribe effective antimicrobials corresponding to the resistance gene(s) present in the pathogen. In addition, information supplied by this assay will lessen the inappropriate use of broad-spectrum antimicrobials and prevent the evolution of further antibiotic resistance.

scholarly journals Activity of Cefiderocol, Ceftazidime-Avibactam, and Eravacycline against Carbapenem-Resistant Escherichia coli Isolates from the United States and International Sites in Relation to Clonal Background, Resistance Genes, Coresistance, and Region

2020 ◽  
Vol 64 (10) ◽  
Author(s):  
Brian D. Johnston ◽  
Paul Thuras ◽  
Stephen B. Porter ◽  
Melissa Anacker ◽  
Brittany VonBank ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Carbapenem Resistance ◽  
The United States ◽  
Asia Pacific ◽  
Beta Lactamase ◽  
Content Type ◽  
Beta Lactamases ◽  
E Coli ◽  
Carbapenem Resistant ◽  
Primary Agent

ABSTRACT Emerging carbapenem resistance in Escherichia coli, including sequence type 131 (ST131), the leading cause of extraintestinal E. coli infections globally, threatens therapeutic efficacy. Accordingly, we determined broth microdilution MICs for three distinctive newer agents, i.e., cefiderocol (CFDC), ceftazidime-avibactam (CZA), and eravacycline (ERV), plus 11 comparators, against 343 carbapenem-resistant (CR) clinical E. coli isolates, then compared susceptibility results with bacterial characteristics and region. The collection comprised 203 U.S. isolates (2002 to 2017) and 141 isolates from 17 countries in Europe, Latin America, and the Asia-West Pacific region (2003 to 2017). Isolates were characterized for phylogenetic group, resistance-associated sequence types (STs) and subsets thereof, and relevant beta-lactamase-encoding genes. CFDC, CZA, and ERV exhibited the highest percent susceptible (82% to 98%) after tigecycline (TGC) (99%); avibactam improved CZA's activity over that of CAZ (11% susceptible). Percent susceptible varied by phylogroup and ST for CFDC and CZA (greatest in phylogroups B2, D, and F, and in ST131, ST405, and ST648). Susceptibility also varied by resistance genotype, being higher with the Klebsiella pneumoniae carbapenemase (KPC) for CZA, lower with metallo-beta-lactamases for CFDC and CZA, and higher with the beta-lactamase CTX-M for ERV. Percent susceptible also varied by global region for CZA (lower in Asia-Pacific) and by U.S. region for ERV (lower in the South and Southeast). Although resistance to comparators often predicted reduced susceptibility to a primary agent (especially CFDC and CZA), even among comparator-resistant isolates the primary-agent-susceptible fraction usually exceeded 50%. These findings clarify the likely utility of CFDC, CZA, and ERV against CR E. coli in relation to multiple bacterial characteristics and geographical region.

scholarly journals Epidemiology of Enterobacter cloacae strains producing a carbapenemase or metallo-beta-lactamase in Vietnamese clinical settings in 2014–2017

2020 ◽  
Vol 69 (4) ◽  
pp. 530-536
Author(s):  
Tohru Miyoshi-Akiyama ◽  
Norio Ohmagari ◽  
Truong Thai Phuong ◽  
Nguyen Quang Huy ◽  
Nguyen Quoc Anh ◽  
...  
Keyword(s):  
Phylogenetic Analysis ◽  
Type Species ◽  
Enterobacter Cloacae ◽  
Clinical Settings ◽  
Whole Genome ◽  
Beta Lactamase ◽  
Content Type ◽  
Link Type ◽  
Bayesian Phylogenetic Analysis ◽  
Carbapenem Resistant

Introduction. Little is known about the epidemiology of Enterobacter cloacae strains producing a carbapenemase or metallo-beta-lactamase in Vietnamese hospitals. Aim. This study analysed E. cloacae strains resistant to imipenem or meropenem that had been isolated from patients admitted to one of the largest hospitals in Vietnam in 2014–2017. Methodology. Eighteen Vietnamese (VN) strains were subjected to whole-genome sequencing and their sequences compared with those of 17 E. cloacae strains carrying a carbapenemase or metallo-beta-lactamase in the database (db strains). Results. Although the distribution of virulence factors did not differ significantly between VN and db strains, all 18 VN isolates harboured blaNDM-1, phylogenetic analysis revealed a high clonality of the VN strains. Bayesian phylogenetic analysis suggested that the VN strains speciated relatively recently. Conclusions. Several prevalent clones of carbapenem-resistant E. cloacae have circulated within Vietnamese hospitals. Adequate measures are needed to prevent their further spread.

scholarly journals Acquisition of Beta-Lactamase by Neisseria meningitidis through Possible Horizontal Gene Transfer

2018 ◽  
Vol 62 (9) ◽  
Author(s):  
Eva Hong ◽  
Ala-Eddine Deghmane ◽  
Muhamed-Kheir Taha
Keyword(s):  
Gene Transfer ◽  
Horizontal Gene Transfer ◽  
Genome Sequencing ◽  
Meningococcal Disease ◽  
Bacterial Species ◽  
Whole Genome ◽  
Beta Lactamase ◽  
Content Type ◽  
Beta Lactamases ◽  
Lactamase Gene

ABSTRACT We report the detection in France of a beta-lactamase-producing invasive meningococcal isolate. Whole-genome sequencing of the isolate revealed a ROB-1-type beta-lactamase gene that is frequently encountered in Haemophilus influenzae, suggesting horizontal transfer between isolates of these bacterial species. Beta-lactamases are exceptional in meningococci, with no reports for more than 2 decades. This report is worrying, as the expansion of such isolates may jeopardize the effective treatment against invasive meningococcal disease.

Resistance to nitrofurantoin is an indicator of extensive drug-resistant (XDR) Enterobacteriaceae

2021 ◽  
Vol 70 (4) ◽  
Author(s):  
Balaram Khamari ◽  
Prakash Kumar ◽  
Bulagonda Eswarappa Pradeep
Keyword(s):  
Antimicrobial Agents ◽  
Efflux Pump ◽  
Treatment Options ◽  
Strong Association ◽  
Multidrug Resistant ◽  
Resistance Mechanisms ◽  
Resistant Bacteria ◽  
Drug Resistant ◽  
Content Type ◽  
Link Type

Introduction. Nitrofurantoin is one of the preferred antibiotics in the treatment of uropathogenic multidrug-resistant (MDR) infections. However, resistance to nitrofurantoin in extensively drug-resistant (XDR) bacteria has severely limited the treatment options. Gap statement. Information related to co-resistance or collateral sensitivity (CS) with reference to nitrofurantoin resistant bacteria is limited. Aim. To study the potential of nitrofurantoin resistance as an indicator of the XDR phenotype in Enterobacteriaceae . Methods. One hundred (45 nitrofurantoin-resistant, 21 intermediately resistant and 34 nitrofurantoin-susceptible) Enterobacteriaceae were analysed in this study. Antibiotic susceptibility testing (AST) against nitrofurantoin and 17 other antimicrobial agents across eight different classes was performed by using the Vitek 2.0 system. The isolates were screened for the prevalence of acquired antimicrobial resistance (AMR) and efflux pump genes by PCR. Results. In total, 51 % of nitrofurantoin-resistant and 28 % of intermediately nitrofurantoin resistant isolates exhibited XDR characteristics, while only 3 % of nitrofurantoin-sensitive isolates were XDR (P=0.0001). Significant co-resistance was observed between nitrofurantoin and other tested antibiotics (β-lactam, cephalosporin, carbapenem, aminoglycoside and tetracycline). Further, the prevalence of AMR and efflux pump genes was higher in the nitrofurantoin-resistant strains compared to the susceptible isolates. A strong association was observed between nitrofurantoin resistance and the presence of bla PER-1, bla NDM-1, bla OXA-48, ant(2) and oqxA-oqxB genes. Tigecycline (84 %) and colistin (95 %) were the only antibiotics to which the majority of the isolates were susceptible. Conclusion. Nitrofurantoin resistance could be an indicator of the XDR phenotype among Enterobacteriaceae , harbouring multiple AMR and efflux pump genes. Tigecycline and colistin are the only antibiotics that could be used in the treatment of such XDR infections. A deeper understanding of the co-resistance mechanisms in XDR pathogens and prescription of AST-based appropriate combination therapy may help mitigate this problem.

scholarly journals Genomic evolution and local epidemiology of Klebsiella pneumoniae from a major hospital in Beijing, China, over a 15 year period: dissemination of known and novel high-risk clones

2021 ◽  
Author(s):  
Mattia Palmieri ◽  
Kelly L. Wyres ◽  
Caroline Mirande ◽  
Zhao Qiang ◽  
Ye Liyan ◽  
...  
Keyword(s):  
High Risk ◽  
Klebsiella Pneumoniae ◽  
Type Species ◽  
Treatment Options ◽  
Multidrug Resistant ◽  
Virulence Plasmid ◽  
Content Type ◽  
Origin And Evolution ◽  
Link Type ◽  
Beijing China

Klebsiella pneumoniae is a frequent cause of nosocomial and severe community-acquired infections. Multidrug-resistant (MDR) and hypervirulent (hv) strains represent major threats, and tracking their emergence, evolution and the emerging convergence of MDR and hv traits is of major importance. We employed whole-genome sequencing (WGS) to study the evolution and epidemiology of a large longitudinal collection of clinical K. pneumoniae isolates from the H301 hospital in Beijing, China. Overall, the population was highly diverse, although some clones were predominant. Strains belonging to clonal group (CG) 258 were dominant, and represented the majority of carbapenemase-producers. While CG258 strains showed high diversity, one clone, ST11-KL47, represented the majority of isolates, and was highly associated with the KPC-2 carbapenemase and several virulence factors, including a virulence plasmid. The second dominant clone was CG23, which is the major hv clone globally. While it is usually susceptible to multiple antibiotics, we found some isolates harbouring MDR plasmids encoding for ESBLs and carbapenemases. We also reported the local emergence of a recently described high-risk clone, ST383. Conversely to strains belonging to CG258, which are usually associated to KPC-2, ST383 strains seem to readily acquire carbapenemases of different types. Moreover, we found several ST383 strains carrying the hypervirulence plasmid. Overall, we detected about 5 % of simultaneous carriage of AMR genes (ESBLs or carbapenemases) and hypervirulence genes. Tracking the emergence and evolution of such strains, causing severe infections with limited treatment options, is fundamental in order to understand their origin and evolution and to limit their spread. This article contains data hosted by Microreact.

scholarly journals Investigation of Metallo-Beta-Lactamases in Carbapenem Resistant Pseudomonas aeruginosa Strains by Phenotypic and Genotypic Methods

2020 ◽  
Vol 25 (3) ◽  
pp. 301-307
Author(s):  
M. Duygu Aksoy ◽  
H. Murat Tuğrul
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Ethylenediaminetetraacetic Acid ◽  
Carbapenem Resistance ◽  
Beta Lactamase ◽  
Bacterial Strains ◽  
Beta Lactamases ◽  
Carbapenem Resistant ◽  
Synergy Test ◽  
Phenotypic Tests ◽  
Positive Controls

Introduction: Carbapenem resistant Pseudomonas aeruginosa strains cause serious problems in treatment. A large number of identified metallo-beta-lactamase (MBL) enzymes produced by P. aeruginosa are one of the most important mechanisms in resistance to carbapenems. MBL genes are located on the chromosome or plasmid, and they can easily spread between different bacterial strains. The activities of these enzymes are zinc-dependent, and they are inhibited by ethylenediaminetetraacetic acid (EDTA). Therefore, this advantage is used in MBL identification tests. In this study, it was aimed to determine MBL among P. aeruginosa strains. Materials and Methods: MBL existence was investigated in 35 P. aeruginosa strains accepted to be mildly susceptible/resistant to any of the carbapenem group of antibiotics through phenotypic and genotypic methods. Phenotypic tests were performed as double disk synergy test (DDST), combined disk diffusion tests (CDDT) by using 0.1 M and 0.5 M EDTA, MBL E-test, and modified Hodge test (MHT). blaIMP, blaVIM, blaGIM, blaSIM, blaSPM genes and blaNDM gene were investigated by multiplex polimerase chain reaction (PCR) and PCR, respectively. Escherichia coli ATCC 25922 and P. aeruginosa ATCC 27853 standard bacteria were used in tests. VIM-1, VIM-2, IMP-13, SPM-1, NDM-1 type MBL-producing P. aeruginosa strains were used as positive controls. Results: Among the carbapenems resistant P. aeruginosa isolates, positivity of MBL was found as 54.2% by MBL E-test, 42.8% by DDST, 94.2% and 37.1% by CDDT method using 0.5 M and 0.1 M EDTA, respectively. Modified Hodge test and genotypic method did not detect MBL. Conclusion: In order to correctly evaluate the results of the phenotypic method, the investigation of resistance genes by molecular methods is also required. The most common metallo-beta-lactamase enzymes responsible for resistance to carbapenem in Pseudomonas were not observed. It was thought that different mechanisms might be responsible for the identified carbapenem resistance.

scholarly journals Semimechanistic Pharmacokinetic/Pharmacodynamic Modeling of Fosfomycin and Sulbactam Combination against Carbapenem-Resistant Acinetobacter baumannii

2021 ◽  
Vol 65 (5) ◽  
Author(s):  
Sazlyna Mohd Sazlly Lim ◽  
Aaron J. Heffernan ◽  
Jason A. Roberts ◽  
Fekade B. Sime
Keyword(s):  
Acinetobacter Baumannii ◽  
Treatment Options ◽  
Pharmacodynamic Modeling ◽  
Synergistic Activity ◽  
Bacterial Burden ◽  
Target Attainment ◽  
Content Type ◽  
Carbapenem Resistant ◽  
Time Kill

ABSTRACT Due to limited treatment options for carbapenem-resistant Acinetobacter baumannii (CR-AB) infections, antibiotic combinations are now considered potential treatments for CR-AB. This study aimed to explore the utility of fosfomycin-sulbactam combination (FOS/SUL) therapy against CR-AB isolates. Synergism of FOS/SUL against 50 clinical CR-AB isolates was screened using the checkerboard method. Thereafter, time-kill studies against two CR-AB isolates were performed. The time-kill data were described using a semimechanistic pharmacokinetic/pharmacodynamic (PK/PD) model. Monte Carlo simulations were then performed to estimate the probability of stasis, 1-log kill, and 2-log kill after 24 h of combination therapy. The FOS/SUL combination demonstrated a synergistic effect against 74% of isolates. No antagonism was observed. The MIC50 and MIC90 of FOS/SUL were decreased 4- to 8-fold, compared to the monotherapy MIC50 and MIC90. In the time-kill studies, the combination displayed bactericidal activity against both isolates and synergistic activity against one isolate at the highest clinically achievable concentrations. Our PK/PD model was able to describe the interaction between fosfomycin and sulbactam in vitro. Bacterial kill was mainly driven by sulbactam, with fosfomycin augmentation. FOS/SUL regimens that included sulbactam at 4 g every 8 h demonstrated a probability of target attainment of 1-log10 kill at 24 h of ∼69 to 76%, compared to ∼15 to 30% with monotherapy regimens at the highest doses. The reduction in the MIC values and the achievement of a moderate PTA of a 2-log10 reduction in bacterial burden demonstrated that FOS/SUL may potentially be effective against some CR-AB infections.

scholarly journals Mutations in the two component regulator systems PmrAB and PhoPQ give rise to increased colistin resistance in Citrobacter and Enterobacter spp.

2020 ◽  
Vol 69 (4) ◽  
pp. 521-529 ◽  
Author(s):  
Matthew E. Wand ◽  
J. Mark Sutton
Keyword(s):  
Growth Rate ◽  
Type Species ◽  
Galleria Mellonella ◽  
Strain Differences ◽  
Fold Increase ◽  
Colistin Resistance ◽  
Content Type ◽  
Link Type ◽  
Carbapenem Resistant ◽  
Individual Strain

Introduction. Colistin is a last resort antibiotic for treating infections caused by carbapenem-resistant isolates. Mechanisms of resistance to colistin have been widely described in Klebsiella pneumoniae and Escherichia coli but have yet to be characterized in Citrobacter and Enterobacter species. Aim. To identify the causative mutations leading to generation of colistin resistance in Citrobacter and Enterobacter spp. Methodology. Colistin resistance was generated by culturing in increasing concentrations of colistin or by direct culture in a lethal (above MIC) concentration. Whole-genome sequencing was used to identify mutations. Fitness of resistant strains was determined by changes in growth rate, and virulence in Galleria mellonella. Results. We were able to generate colistin resistance upon exposure to sub-MIC levels of colistin, in several but not all strains of Citrobacter and Enterobacter resulting in a 16-fold increase in colistin MIC values for both species. The same individual strains also developed resistance to colistin after a single exposure at 10× MIC, with a similar increase in MIC. Genetic analysis revealed that this increased resistance was attributed to mutations in PmrB for Citrobacter and PhoP in Enterobacter , although we were not able to identify causative mutations in all strains. Colistin-resistant mutants showed little difference in growth rate, and virulence in G. mellonella, although there were strain-to-strain differences. Conclusions. Stable colistin resistance may be acquired with no loss of fitness in these species. However, only select strains were able to adapt suggesting that acquisition of colistin resistance is dependent upon individual strain characteristics.

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