293 results match your criteria fosfomycin pharmacokinetics


Intravenous fosfomycin for the treatment of patients with bone and joint infections: a review.

Expert Rev Anti Infect Ther 2021 May 25. Epub 2021 May 25.

Alfa Institute of Biomedical Sciences, Athens, Greece.

Introduction: Fosfomycin is a wide spectrum bactericidal antibiotic with a unique mode of action, low toxicity and good penetration in tissues with deep seated infections, including bone and joint infections.

Areas Covered: Data were extracted from 19 published articles. 365 patients, with broad age range, received intravenous fosfomycin for the treatment of bone and joint infections (including arthritis, acute and chronic osteomyelitis, discitis, periprosthetic joint infection). Read More

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IV and oral fosfomycin pharmacokinetics in neonates with suspected clinical sepsis.

J Antimicrob Chemother 2021 Apr 14. Epub 2021 Apr 14.

Infection, Immunity and Inflammation, Great Ormond Street Institute of Child Health, University College London, London, UK.

Background: Fosfomycin has the potential to be re-purposed as part of a combination therapy to treat neonatal sepsis where resistance to current standard of care (SOC) is common. Limited data exist on neonatal fosfomycin pharmacokinetics and estimates of bioavailability and CSF/plasma ratio in this vulnerable population are lacking.

Objectives: To generate data informing the appropriate dosing of IV and oral fosfomycin in neonates using a population pharmacokinetic analysis of plasma and CSF data. Read More

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Optimal empiric treatment for KPC-2-producing Klebsiella pneumoniae infections in critically ill patients with normal or decreased renal function using Monte Carlo simulation.

BMC Infect Dis 2021 Mar 26;21(1):307. Epub 2021 Mar 26.

State Key Laboratory for Diagnosis and Treatment of Infectious Disease, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310003, China.

Background: Limited clinical studies describe the pharmacodynamics of fosfomycin (FOS), tigecycline (TGC) and colistin methanesulfonate (CMS) in combination against KPC-producing Klebsiella pneumoniae (KPC-Kp). Population pharmacokinetic models were used in our study. Monte Carlo simulation was conducted to calculate probability of target attainment (PTA) and cumulative fraction of response (CFR) of each agent alone and in combination against KPC-Kp in patients with normal or decreased renal function. Read More

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Population pharmacokinetics and Monte Carlo simulation for dosage optimization of fosfomycin in the treatment of osteoarticular infections in patients without renal dysfunction.

Antimicrob Agents Chemother 2021 Feb 22. Epub 2021 Feb 22.

Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna, Italy.

Fosfomycin is gaining interest in the treatment of complex osteoarticular infections (OI) due to MDR pathogens. The aims were to conduct population pharmacokinetics of fosfomycin in a cohort of OI patients receiving 16g/daily by intermittent (II) or continuous infusion (CI), and to carry out Monte Carlo simulations for dosage optimization in the treatment of these infections. Patients underwent blood sampling on day 5 of therapy (2-3 serial samples). Read More

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February 2021

Fosfomycin in continuous or prolonged infusion for systemic bacterial infections: a systematic review of its dosing regimen proposal from in vitro, in vivo and clinical studies.

Eur J Clin Microbiol Infect Dis 2021 Jun 18;40(6):1117-1126. Epub 2021 Feb 18.

Clinical Department of Medical, Surgical and Health Sciences, Trieste University, 34127, Trieste, Italy.

Fosfomycin (FOS) administered intravenously has been recently rediscovered for the treatment of systemic infections due to multidrug-resistant bacteria. Its pharmacokinetic properties suggest a time-dependent dosing schedule with more clinical benefits from prolonged (PI) or continuous infusion (CI) than from intermittent infusion. We revised literature concerning PI and CI FOS to identify the best dosing regimen based on current evidence. Read More

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Pharmacokinetics of culture-directed antibiotics for the treatment of peritonitis in automated peritoneal dialysis: A systematic narrative review.

Perit Dial Int 2021 May 9;41(3):261-272. Epub 2021 Feb 9.

522555Faculty of Medicine and Health, The University of Sydney, New South Wales, Australia.

The objectives of this study were to provide a summary of the pharmacokinetic data of some intraperitoneal (IP) antibiotics that could be used for both empirical and culture-directed therapy, as per the ISPD recommendations, and examine factors to consider when using IP antibiotics for the management of automated peritoneal dialysis (APD)-associated peritonitis. A literature search of PubMed, EMBASE, Scopus, MEDLINE and Google Scholar for articles published between 1998 and 2020 was conducted. To be eligible, articles had to describe the use of antibiotics via the IP route in adult patients ≥18 years old on APD in the context of pharmacokinetic studies or case reports/series. Read More

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Mono vs. combo regimens with novel beta-lactam/beta-lactamase inhibitor combinations for the treatment of infections due to carbapenemase-producing Enterobacterales: insights from the literature.

Infection 2021 Jun 3;49(3):411-421. Epub 2021 Feb 3.

Infectious Disease Unit, Department of Medicine, University of Udine, Udine, Italy.

Ceftazidime-avibactam (CZA), meropenem-vaborbactam (MVB) and imipenem-relebactam (I-R) are combinations of old ß-lactams with novel non-ß-lactam ß-lactamase inhibitors (BLBLIs) able to inhibit some carbapenemases, such as the KPC-type, thus are becoming the standard for difficult-to-treat carbapenemase-producing Enterobacterales (CPE); a practical question is whether these novel BLBLIs should be used as monotherapy or as part of a combination regimen with other antibiotics, and if so, with which ones, to reduce the emergence of resistant strains and to optimize their efficacy. In this short review, we assessed clinical outcomes in patients with CPE-infections treated with the novel BLBLIs as mono- or combo-regimens, and laboratory studies on the synergistic effects with other antimicrobials. Available evidence on combination therapy is scarce and mainly limited to retrospective studies involving 630 patients treated with CZA: aminoglycosides were used in 39. Read More

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Millisecond-Long Simulations of Antibiotics Transport through Outer Membrane Channels.

J Chem Theory Comput 2021 Jan 30;17(1):549-559. Epub 2020 Dec 30.

Department of Physics and Earth Sciences, Jacobs University Bremen, 28759 Bremen, Germany.

To reach their target site inside Gram-negative bacteria, almost all antibiotics need to cross the outer membrane. Computational modeling of such processes can be numerically demanding due to the size of the systems and especially due to the timescales involved. Recently, a hybrid Brownian and molecular dynamics approach, i. Read More

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January 2021

Quantitative Determination of Fosfomycin in 10 μL of Plasma and Dialysate by Hydrophilic Interaction Liquid Chromatography Electrospray Ionization Mass Spectrometry.

J Chromatogr Sci 2021 Jan;59(2):165-174

CBR Center of Breath Research, Department of Anesthesiology, Intensive Care and Pain Therapy, Saarland University Medical Center and Saarland University Faculty of Medicine, Kirrberger Straße 100, D-66424 Homburg, Germany.

Fosfomycin is an antibiotic with a broad spectrum of activity against many multidrug-resistant bacterial strains. It is mainly excreted unchanged by the kidneys, and its half-life therefore depends on kidney function which varies considerably among individuals, and within individuals over time. Proper fosfomycin dosing thus depends on assaying blood concentration of the drug. Read More

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January 2021

Clinical Pharmacokinetics of Fosfomycin after Continuous Infusion Compared with Intermittent Infusion: a Randomized Crossover Study in Healthy Volunteers.

Antimicrob Agents Chemother 2020 12 16;65(1). Epub 2020 Dec 16.

Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria

Continuous infusion (CON) of fosfomycin has been proposed as potentially advantageous in certain clinical scenarios. However, no clinical data on the pharmacokinetics (PK) of fosfomycin after CON are available to date. This study aimed to investigate the PK of fosfomycin after CON and compare it with intermittent infusion (INT) of fosfomycin. Read More

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December 2020

A Systematic Review of Studies Reporting Antibiotic Pharmacokinetic Data in the Cerebrospinal Fluid of Critically Ill Patients with Uninflamed Meninges.

Antimicrob Agents Chemother 2020 12 16;65(1). Epub 2020 Dec 16.

University of Queensland Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia

Ventriculostomy-associated infections in critically ill patients remain therapeutically challenging because of drug- and disease-related factors that contribute to suboptimal antibiotic concentrations in cerebrospinal fluid. Optimal antibiotic dosing for the treatment and prevention of such infections should be based on robust and contextually specific pharmacokinetic data. The objects of this study were to describe and critically appraise studies with reported antibiotic concentrations or pharmacokinetic data in cerebrospinal fluid of critically ill patients without meningeal inflammation. Read More

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December 2020

Evaluation of Intravenous Fosfomycin Disodium Dosing Regimens in Critically Ill Patients for Treatment of Carbapenem-Resistant Enterobacterales Infections Using Monte Carlo Simulation.

Antibiotics (Basel) 2020 Sep 18;9(9). Epub 2020 Sep 18.

Division of Clinical Pharmacy, Department of Pharmacy, Faculty of Pharmacy, Mahidol University, Bangkok 10400, Thailand.

There are limited intravenous fosfomycin disodium (IVFOS) dosing regimens to treat carbapenem-resistant Enterobacterales (CRE) infections. This study aimed to use Monte Carlo simulation (MCS) for evaluation of IVFOS dosing regimens in critically ill patients with CRE infections. The dosing regimens in critically ill patients with various creatinine clearance were evaluated with MCS using minimum inhibitory concentration (MIC) distributions of fosfomycin against CRE clinical isolates in Thailand and the 24 h area under the plasma drug concentration-time curve over the minimum inhibitory concentration (AUC/MIC) of ≥21. Read More

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September 2020

Pharmacokinetics of fosfomycin in patients with prophylactic treatment for recurrent Escherichia coli urinary tract infection.

J Antimicrob Chemother 2020 11;75(11):3278-3285

Department of Internal Medicine, Haga Teaching Hospital, The Hague, The Netherlands.

Objectives: To evaluate the pharmacokinetics and clinical effectiveness of IV and oral fosfomycin treatment in patients with recurrent urinary tract infection (rUTI) with Escherichia coli.

Patients And Methods: Patients with rUTI treated with 3 g of oral fosfomycin every 72 h for at least 14 days were included in a prospective open-label single-centre study. Serum samples were taken after oral and IV administration of fosfomycin. Read More

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November 2020

Intravenous fosfomycin for the treatment of patients with central nervous system infections: evaluation of the published evidence.

Expert Rev Anti Infect Ther 2020 07 13;18(7):657-668. Epub 2020 May 13.

Alfa Institute of Biomedical Sciences , Athens, Greece.

Introduction: Central nervous system (CNS) infections have considerable morbidity and mortality. Fosfomycin is a broad spectrum bactericidal antibiotic with favorable pharmacokinetic properties and low toxicity, satisfactory penetration in the cerebrospinal fluid and is authorized for the treatment of bacterial meningitis.

Areas Covered: The objective of this analysis was to evaluate the available data regarding the effectiveness and safety of intravenous fosfomycin for the treatment of CNS infections. Read More

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Oral Fosfomycin Treatment for Enterococcal Urinary Tract Infections in a Dynamic Model.

Antimicrob Agents Chemother 2020 05 21;64(6). Epub 2020 May 21.

Department of Infectious Diseases, The Alfred Hospital and Central Clinical School, Monash University, Melbourne, Victoria, Australia

There are limited treatment options for enterococcal urinary tract infections, especially vancomycin-resistant (VRE). Oral fosfomycin is a potential option, although limited data are available guiding dosing and susceptibility. We undertook pharmacodynamic profiling of fosfomycin against and isolates using a dynamic bladder infection model. Read More

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Evaluation of pooled human urine and synthetic alternatives in a dynamic bladder infection in vitro model simulating oral fosfomycin therapy.

J Microbiol Methods 2020 04 5;171:105861. Epub 2020 Feb 5.

Department of Infectious Diseases, The Alfred and Central Clinical School, Monash University, Melbourne, VIC, Australia; Infection and Immunity Program, Monash Biomedicine Discovery Institute, Department of Microbiology, Monash University, Clayton, VIC, Australia. Electronic address:

The impact of the bladder environment on fosfomycin activity and treatment response is uncertain. Standard laboratory media does not reflect the biomatrix of urine, where limited nutritional factors are important for growth and antimicrobial kill rates. We compared fosfomycin activity against Enterobacteriaceae in laboratory media, human urine and synthetic alternatives. Read More

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The plasma pharmacokinetics of fosfomycin and metronidazole after intraperitoneal administration in patients undergoing appendectomy for uncomplicated appendicitis.

Fundam Clin Pharmacol 2020 Aug 28;34(4):504-512. Epub 2020 Jan 28.

Department of Surgery, Centre for Perioperative Optimisation, Herlev and Gentofte Hospital, University of Copenhagen, Herlev Ringvej 75, DK-2730, Herlev, Denmark.

We aimed to investigate the pharmacokinetics of fosfomycin and metronidazole after intraperitoneal administration of the combination of fosfomycin and metronidazole in patients undergoing laparoscopic appendectomy for uncomplicated appendicitis. We included eight otherwise healthy men undergoing laparoscopic appendectomy. The trial treatment was administered at the end of the surgical procedure and left in the abdominal cavity. Read More

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Effect of drug combinations on the kinetics of antibiotic resistance emergence in Escherichia coli CFT073 using an in vitro hollow-fibre infection model.

Int J Antimicrob Agents 2020 Apr 13;55(4):105861. Epub 2019 Dec 13.

Division of Applied Regulatory Science, Office of Clinical Pharmacology, Center for Drug Evaluation and Research, US Food and Drug Administration, USA. Electronic address:

Antibiotic resistance is one of the major threats to public health today. To address this problem requires an urgent comprehensive approach. Strategic and multitargeted combination therapy has been increasingly used clinically to treat bacterial infections. Read More

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A pharmacokinetic-pharmacodynamic assessment of oral antibiotics for pyelonephritis.

Eur J Clin Microbiol Infect Dis 2019 Dec 7;38(12):2311-2321. Epub 2019 Sep 7.

University of Leeds, Leeds, LS2 9JT, UK.

Antibiotic resistance to oral antibiotics recommended for pyelonephritis is increasing. The objective was to determine if there is a pharmacological basis to consider alternative treatments/novel dosing regimens for the oral treatment of pyelonephritis. A systematic review identified pharmacokinetic models of suitable quality for a selection of antibiotics with activity against Escherichia coli. Read More

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December 2019

Epidemiology and Treatment of Multidrug-Resistant and Extensively Drug-Resistant Pseudomonas aeruginosa Infections.

Clin Microbiol Rev 2019 09 28;32(4). Epub 2019 Aug 28.

Service of Pharmacy, Hospital del Mar, Infectious Pathology and Antimicrobials Research Group, Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), Universitat Autònoma de Barcelona, Barcelona, Spain.

In recent years, the worldwide spread of the so-called high-risk clones of multidrug-resistant or extensively drug-resistant (MDR/XDR) has become a public health threat. This article reviews their mechanisms of resistance, epidemiology, and clinical impact and current and upcoming therapeutic options. and treatment studies and pharmacokinetic and pharmacodynamic (PK/PD) models are discussed. Read More

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September 2019

Relative potency of different generic brands of meropenem, colistin and fosfomycin: Implications for antimicrobial therapy and antimicrobial formulary.

Indian J Med Microbiol 2019 Jan-Mar;37(1):95-98

Department of Clinical Hematology, Tata Medical Center, Kolkata, West Bengal, India.

There is a need of a relatively simple and inexpensive method for the determination of relative potency of various generic brands of antibiotics in comparison to original products. The current study describes an agar diffusion method which can be performed in any microbiology laboratory, is cheap (costs $2 per test) and its results can be available after overnight incubation. The results show that neither all generics are reliable nor are all generic antibiotics of poor quality. Read More

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December 2019

Urinary antibacterial activity of fosfomycin and nitrofurantoin at registered dosages in healthy volunteers.

Int J Antimicrob Agents 2019 Oct 2;54(4):435-441. Epub 2019 Aug 2.

Department of Medical Microbiology and Infectious Diseases, Erasmus University Medical Center, Rotterdam, The Netherlands.

Given emerging uropathogen resistance to more recent antibiotics, old antibiotics used for uncomplicated urinary tract infection (UTI) warrant re-examination. In this study, the urinary antibacterial activities of fosfomycin and nitrofurantoin were investigated by determining the urinary inhibitory titre and urinary bactericidal titre against uropathogens in urine samples from female volunteers following administration of single-dose fosfomycin (3 g) or nitrofurantoin (50 mg q6h or 100 mg q8h). Urine samples were collected over 48 h (fosfomycin) or 6 or 8 h (nitrofurantoin), with drug levels quantified with every void. Read More

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October 2019

What Antibiotic Exposures Are Required to Suppress the Emergence of Resistance for Gram-Negative Bacteria? A Systematic Review.

Clin Pharmacokinet 2019 11;58(11):1407-1443

Centre for Translational Anti-Infective Pharmacodynamics, School of Pharmacy, The University of Queensland, Brisbane, QLD, Australia.

Background: The rates of antibiotic resistance in Gram-negative bacteria are increasing. One method to minimize resistance emergence may be optimization of antibiotic dosing regimens to achieve drug exposure that suppress the emergence of resistance.

Objective: The aim of this systematic review was to describe the antibiotic exposures associated with suppression of the emergence of resistance for Gram-negative bacteria. Read More

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November 2019

Treatment Options for Colistin Resistant : Present and Future.

J Clin Med 2019 Jun 28;8(7). Epub 2019 Jun 28.

Systemic and Immunocompromised Host Infection Unit, National Institute for Infectious Diseases "L. Spallanzani", IRCCS-Via Portuense, 292 00149 Rome, Italy.

Multidrug-resistant (MDR) represents an increasing threat to human health, causing difficult-to-treat infections with a high mortality rate. Since colistin is one of the few treatment options for carbapenem-resistant , colistin resistance represents a challenge due to the limited range of potentially available effective antimicrobials, including tigecycline, gentamicin, fosfomycin and ceftazidime/avibactam. Moreover, the choice of these antimicrobials depends on their pharmacokinetics/pharmacodynamics properties, the site of infection and the susceptibility profile of the isolated strain, and is sometimes hampered by side effects. Read More

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The "Old" and the "New" Antibiotics for MDR Gram-Negative Pathogens: For Whom, When, and How.

Front Public Health 2019 11;7:151. Epub 2019 Jun 11.

Third Department of Medicine, School of Medicine, Sotiria General Hospital, National and Kapodistrian University of Athens, Athens, Greece.

The recent expansion of multidrug resistant and pan-drug-resistant pathogens poses significant challenges in the treatment of healthcare associated infections. An important advancement, is a handful of recently launched new antibiotics targeting some of the current most problematic Gram-negative pathogens, namely carbapenem-producing Enterobacteriaceae (CRE) and carbapenem-resistant (CRPA). Less options are available against carbapenem-resistant (CRAB) and strains producing metallo-beta lactamases (MBL). Read More

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Oral and intravenous fosfomycin in complicated urinary tract infections.

Rev Esp Quimioter 2019 May;32 Suppl 1:37-44

Juan Pablo Horcajada, Servicio de Enfermedades Infecciosas, Hospital del Mar, Barcelona, Spain.

Urinary tract infections are one of the most common health problems and entail a high consumption of health system resources. Due to the increase in global antibiotic resistances in recent years, it is increasingly common to find uropathogens with multiple resistance mechanisms, including quinolone-resistant bacteria, broad-spectrum β-lactamase producers and carbapenemase producers. In this scenario, the role of fosfomycin has gained considerable importance, given its spectrum of activity against multidrug resistant microorganisms (Gram-positive and Gram-negative), becoming an attractive alternative therapy. Read More

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The role of fosfomycin in osteoarticular infection.

Authors:
L Morata A Soriano

Rev Esp Quimioter 2019 May;32 Suppl 1:30-36

Alex Soriano, Hospital Clínic de Barcelona. IDIBAPS. Universidad de Barcelona, Spain.

Osteoarticular infections include septic arthritis and osteomyelitis, with Gram-positive microorganisms isolated most frequently. In recent years, there has been an increase in the number of resistant strains in this type of infection, which complicates the treatment. Fosfomycin is active against a large percentage of Gram-positive and Gram-negative pathogens, including multidrug-resistant strains, and its properties include low protein binding, low molecular weight and good bone dissemination. Read More

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Deciphering pharmacokinetics and pharmacodynamics of fosfomycin.

Rev Esp Quimioter 2019 May;32 Suppl 1:19-24

Andrés Canut-Blasco. Microbiology Service, Edificio Consultas Externas, Hospital Universitario de Álava. c/Francisco Leandro de Viana, s/n. 01009. Vitoria-Gasteiz, Spain.

Fosfomycin, a low molecular weight and hydrophilic drug with negligible protein binding, is eliminated almost exclusively by glomerular filtration, whose clearance is subject to patient renal function. The volume of distribution approximates to the extracellular body water (about 0.3 L/Kg) in healthy volunteers, but it is increased in critically ill patients with bacterial infections. Read More

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New perspectives for reassessing fosfomycin: applicability in current clinical practice.

Rev Esp Quimioter 2019 May;32 Suppl 1:1-7

Francisco Javier Candel González. Enfermedades Infecciosas. Microbiología Clínica. Instituto de Investigación sanitaria San Carlos (IdIISC). Instituto de Medicina de Laboratorio (IML). Hospital Clínico San Carlos. Universidad Complutense de Madrid, Spain.

Fosfomycin is a bactericidal antibiotic that interferes with cell wall synthesis. The drug therefore has a broad spectrum of activity against a wide range of Gram-positive and Gram-negative bacteria. Both the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA) have started review processes of the accumulated information on the use of fosfomycin and on information from new clinical trials. Read More

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