Research

11 pages, 1707 KiB

Open AccessArticle

In Vitro Growth-Inhibitory Synergistic Effect of Zinc Pyrithione in Combination with Gentamicin against Bacterial Skin Pathogens of Livestock

by Lucie Mala, Klara Lalouckova, Eva Skrivanova, Marketa Houdkova, Marie Strakova and Ladislav Kokoska

Antibiotics 2022, 11(7), 960; https://doi.org/10.3390/antibiotics11070960 - 17 Jul 2022

Viewed by 2030

Abstract

Bacterial skin diseases of livestock could be a serious global threat, especially in association with overcoming bacterial resistance. Combinatory action of antimicrobial agents proves to be an effective strategy to overcome the problem of increasing antibiotic resistance of microorganisms. In this study, the [...] Read more.

Bacterial skin diseases of livestock could be a serious global threat, especially in association with overcoming bacterial resistance. Combinatory action of antimicrobial agents proves to be an effective strategy to overcome the problem of increasing antibiotic resistance of microorganisms. In this study, the in vitro combined effect of zinc pyrithione with gentamicin against bacterial skin pathogens of livestock (Staphylococcus aureus, Streptococcus agalactiae, and Streptococcus dysgalactiae) was evaluated according to the sum of fractional inhibitory concentration indices (FICI) obtained by checkerboard method. The results showed that a combination of zinc pyrithione with gentamicin produced a strong synergistic effect (p < 0.001) against all tested streptococcal strains (with FICI values ranging from 0.20 to 0.42). Compared to that, only three out of eight S. aureus strains were highly susceptible to the combination of antimicrobial agents at single concentration (0.25 µg/mL) of zinc pyrithione with range of FICI 0.35–0.43. These findings suggest that interference between agents tested in this study can be used for the development of future veterinary pharmaceutical preparations for the treatment of bacterial skin infections of livestock. Full article

(This article belongs to the Special Issue Optimization and Improvement of Veterinary Antimicrobial Treatment to Reduce Antimicrobial Resistance)

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15 pages, 1255 KiB

Open AccessArticle

Qualitative Risk Assessment for Antimicrobial Resistance among Humans from Salmon Fillet Consumption Due to the High Use of Antibiotics against Bacterial Infections in Farmed Salmon

by Marília Salgado-Caxito, Natalia Zimin-Veselkoff, Aiko D. Adell, Jorge Olivares-Pacheco and Fernando O. Mardones

Antibiotics 2022, 11(5), 662; https://doi.org/10.3390/antibiotics11050662 - 15 May 2022

Cited by 3 | Viewed by 2794

Abstract

Background: Worldwide, aquaculture is considered as a hotspot environment for antimicrobial resistance (AMR) due to the intense use of antibiotics in its productive systems. Chile is the second largest producer of farmed salmon worldwide, and tons of antibiotics are used to control bacterial [...] Read more.

Background: Worldwide, aquaculture is considered as a hotspot environment for antimicrobial resistance (AMR) due to the intense use of antibiotics in its productive systems. Chile is the second largest producer of farmed salmon worldwide, and tons of antibiotics are used to control bacterial diseases, such as Salmon Rickettsial Syndrome (SRS) and Bacterial Kidney Disease (BKD). However, studies determining the risk of consuming salmon fillets that have been treated with antibiotics during the salmon production are limited. Consulting leading experts in the field could provide a knowledge base to identify and address this question and research gaps. Methods: Multisectoral risk perception of AMR through salmon fillet consumption was evaluated by eliciting expert data obtained through discussions during a workshop and from questionnaires given to experts from academia (n = 15, 63%), the public sector (n = 5, 21%), and the salmon industry (n = 4, 17%). Results: The qualitative risk analysis suggested an overall ‘low’ probability of AMR acquisition by consumption of salmon fillet that had been treated during the production cycle. The risk perception varied slightly between production stages in freshwater and seawater. In consensus with all sectors, this overall ‘low’, but existing, risk was probably associated with bacterial infections and the use of antibiotics. Conclusions: As it is essential to reduce the use of antibiotics in the Chilean salmon industry, this intersectoral approach and consensual results could favor effective implementation of targeted initiatives for the control and prevention of major bacterial diseases. Full article

(This article belongs to the Special Issue Optimization and Improvement of Veterinary Antimicrobial Treatment to Reduce Antimicrobial Resistance)

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14 pages, 5309 KiB

Open AccessArticle

Discovery of MurA Inhibitors as Novel Antimicrobials through an Integrated Computational and Experimental Approach

by Fangyuan Zhang, Joshua Graham, Tianhua Zhai, Yanhong Liu and Zuyi Huang

Antibiotics 2022, 11(4), 528; https://doi.org/10.3390/antibiotics11040528 - 14 Apr 2022

Cited by 9 | Viewed by 2274

Abstract

The bacterial cell wall is essential for protecting bacteria from the surrounding environment and maintaining the integrity of bacteria cells. The MurA enzyme, which is an essential enzyme involved in bacterial cell wall synthesis, could be a good drug target for antibiotics. Although [...] Read more.

The bacterial cell wall is essential for protecting bacteria from the surrounding environment and maintaining the integrity of bacteria cells. The MurA enzyme, which is an essential enzyme involved in bacterial cell wall synthesis, could be a good drug target for antibiotics. Although fosfomycin is used clinically as a MurA inhibitor, resistance to this antibiotic is a concern. Here we used molecular docking-based virtual screening approaches to identify potential MurA inhibitors from 1.412 million compounds from three databases. Thirty-three top compounds from virtual screening were experimentally tested in Listeria innocua (Gram-positive bacterium) and Escherichia coli (Gram-negative bacterium). Compound 2-Amino-5-bromobenzimidazole (S17) showed growth inhibition effect in both L. innocua and E. coli, with the same Minimum Inhibitory Concentration (MIC) value of 0.5 mg/mL. Compound 2-[4-(dimethylamino)benzylidene]-n-nitrohydrazinecarboximidamide (C1) had growth inhibition effect only in L. innocua, with a MIC value of 0.5 mg/mL. Two FDA-approved drugs, albendazole (S4) and diflunisal (S8), had a growth inhibition effect only in E. coli, with a MIC value of 0.0625 mg/mL. The identified MurA inhibitors could be potential novel antibiotics. Furthermore, they could be potential fosfomycin substitutes for the fosfomycin-resistant strains. Full article

(This article belongs to the Special Issue Optimization and Improvement of Veterinary Antimicrobial Treatment to Reduce Antimicrobial Resistance)

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14 pages, 2724 KiB

Open AccessArticle

Effects of Tylosin, a Direct-Fed Microbial and Feedlot Pen Environment on Phenotypic Resistance among Enterococci Isolated from Beef Cattle Feces

by Sarah A. Murray, Ashlyn C. Holbert, Keri N. Norman, Sara D. Lawhon, Jason E. Sawyer and Harvey M. Scott

Antibiotics 2022, 11(1), 106; https://doi.org/10.3390/antibiotics11010106 - 14 Jan 2022

Cited by 4 | Viewed by 2116

Abstract

In two sequential replicates (n = 90 and n = 96 feedlot finisher cattle, respectively) we measured the impact of an Enterococcus faecium-based probiotic (DFM) and an altered feedlot pen environment on antimicrobial resistance among fecal enterococci in cattle fed (or, [...] Read more.

In two sequential replicates (n = 90 and n = 96 feedlot finisher cattle, respectively) we measured the impact of an Enterococcus faecium-based probiotic (DFM) and an altered feedlot pen environment on antimicrobial resistance among fecal enterococci in cattle fed (or, not fed) the macrolide tylosin. Diluted fecal samples were spiral-plated on plain and antibiotic-supplemented m-Enterococcus agar. In the first replicate, tylosin significantly (p < 0.05) increased the relative quantity of erythromycin-resistant enterococci. This effect was diminished in cattle fed the DFM in conjunction with tylosin, indicating a macrolide susceptible probiotic may help mitigate resistance. A similar observed effect was not statistically significant (p > 0.05) in the second replicate. Isolates were speciated and resistance phenotypes were obtained for E. faecium and E. hirae. Susceptible strains of bacteria fed as DFM may prove useful for mitigating the selective effects of antibiotic use; however, the longer-term sustainability of such an approach remains unclear. Full article

(This article belongs to the Special Issue Optimization and Improvement of Veterinary Antimicrobial Treatment to Reduce Antimicrobial Resistance)

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19 pages, 1107 KiB

Open AccessArticle

Farm Animal Veterinarians’ Knowledge and Attitudes toward Antimicrobial Resistance and Antimicrobial Use in the Republic of Serbia

by Jovana Vidović, Dragica Stojanović, Petra Cagnardi, Nebojša Kladar, Olga Horvat, Ivana Ćirković, Katarina Bijelić, Nenad Stojanac and Zorana Kovačević

Antibiotics 2022, 11(1), 64; https://doi.org/10.3390/antibiotics11010064 - 05 Jan 2022

Cited by 10 | Viewed by 2172

Abstract

Antimicrobial resistance (AMR) is considered one of the most prevalent global health issues in both veterinarian and human medicine. This complex problem requires a “One Health” approach with the cooperation of all healthcare sectors, as well as agriculture, finance, and consumers. We conducted [...] Read more.

Antimicrobial resistance (AMR) is considered one of the most prevalent global health issues in both veterinarian and human medicine. This complex problem requires a “One Health” approach with the cooperation of all healthcare sectors, as well as agriculture, finance, and consumers. We conducted a survey with the objective to assess the knowledge and attitudes of farm animal veterinarians toward AMR and antimicrobial use in the Republic of Serbia with a small focus on mastitis therapy. A total of 110 respondents completed the questionnaire, which represents a response rate of 27.3%. The majority of our respondents (n = 102, 92.7%) completely agreed that AMR currently represents severe concern in the health sector. Unfortunately, less than one-third (n = 34, 30.9%) of the respondents had only heard about antimicrobial stewardship. Participants showed a positive attitude toward prudent antimicrobial use and were open to solutions to the AMR crisis. We noticed a certain gap between farm veterinarians’ desire to improve and perform better in daily practice, while at the same time feeling like they did not have enough guidance, help, and resources. Full article

(This article belongs to the Special Issue Optimization and Improvement of Veterinary Antimicrobial Treatment to Reduce Antimicrobial Resistance)

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11 pages, 566 KiB

Open AccessArticle

Tylosin Dosage Adjustment Based on Allometric Scaling in Male Turkeys

by Błażej Poźniak, Marta Tikhomirov, Kamila Bobrek, Paweł Jajor and Marcin Świtała

Antibiotics 2021, 10(9), 1057; https://doi.org/10.3390/antibiotics10091057 - 31 Aug 2021

Cited by 1 | Viewed by 4526

Abstract

Turkeys’ body weight (BW) increases 10-fold within only 2.5 months, leading to a change in the pharmacokinetics (PK) of drugs according to allometric principles. Thus, the same dosage may lead to age-dependent variability in efficacy, in particular, to treatment failure and/or selection for [...] Read more.

Turkeys’ body weight (BW) increases 10-fold within only 2.5 months, leading to a change in the pharmacokinetics (PK) of drugs according to allometric principles. Thus, the same dosage may lead to age-dependent variability in efficacy, in particular, to treatment failure and/or selection for resistance. The study aimed to investigate whether a non-linear dosage based on a published allometric model for tylosin clearance, may optimize the internal exposure in growing turkeys. The single dose PK study was performed on turkeys aged 6, 9.5, 13 and 17 weeks (BW from 1.75 kg to 15.75 kg). Tylosin was administered intravenously (i.v.) or orally (p.o.) according to following protocols: Dose = 31.6 × BW^0.58 or Dose = 158 × BW^0.58, respectively. Plasma tylosin was measured using high-performance liquid chromatography and non-compartmental PK analysis was performed. The area under the curve (AUC_last) after i.v. administration was 8.90 ± 1.01; 7.51 ± 1.11; 6.54 ± 1.20 and 8.01 ± 1.75 mg × h/L in 6-; 9.5-; 13- and 17-week-old turkeys, respectively. After p.o. administration AUC_last was 4.80 ± 2.92; 4.60 ± 2.45; 3.00 ± 1.49 and 3.24 ± 2.00 mg × h/L in respective age groups indicating high variability. For i.v. administration, the non-linear dosage allowed to minimize the age-dependent variability in AUC. However, due to low oral bioavailability (8–12%) and resulting interindividual variability, the proposed approach may not improve tylosin efficacy in turkeys under farm conditions. Full article

(This article belongs to the Special Issue Optimization and Improvement of Veterinary Antimicrobial Treatment to Reduce Antimicrobial Resistance)

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16 pages, 3024 KiB

Open AccessArticle

Enrofloxacin Dose Optimization for the Treatment of Colibacillosis in Broiler Chickens Using a Drinking Behaviour Pharmacokinetic Model

by Robin Temmerman, Ludovic Pelligand, Wim Schelstraete, Gunther Antonissen, An Garmyn and Mathias Devreese

Antibiotics 2021, 10(5), 604; https://doi.org/10.3390/antibiotics10050604 - 19 May 2021

Cited by 11 | Viewed by 4202

Abstract

Enrofloxacin is frequently administered via drinking water for the treatment of colibacillosis in broiler chickens. However, the EMA/CVMP has urged to re-evaluate historically approved doses, especially for antimicrobials administered via drinking water. In response, the objectives of this study were two-fold. First, to [...] Read more.

Enrofloxacin is frequently administered via drinking water for the treatment of colibacillosis in broiler chickens. However, the EMA/CVMP has urged to re-evaluate historically approved doses, especially for antimicrobials administered via drinking water. In response, the objectives of this study were two-fold. First, to evaluate the pharmacokinetics (PK) of enrofloxacin following IV, PO and drinking water administration. Second, to predict the efficacy of a range of doses in the drinking water for the treatment of APEC infections. For the first objective, PK parameters were estimated by fitting a one-compartmental model with a zero-order IV infusion and an oral absorption lag function to the simultaneously modelled IV and PO data. After fixing these parameter values, a drinking behaviour pharmacokinetic (DBPK) model was developed for the description and prediction of drinking water PK profiles by adding three model improvements (different diurnal and nocturnal drinking rates, inter-animal variability in water consumption and taking account of dose non-proportionality). The subsequent simulations and probability of target attainment (PTA) analysis predicted that a dose of 12.5 mg/kg/24 h is efficacious in treating colibacillosis with an MIC up to 0.125 μg/mL (ECOFF), whereas the currently registered dose (10 mg/kg/24 h) reaches a PTA of 66% at ECOFF. Full article

(This article belongs to the Special Issue Optimization and Improvement of Veterinary Antimicrobial Treatment to Reduce Antimicrobial Resistance)

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14 pages, 526 KiB

Open AccessArticle

A Pilot Randomised Clinical Trial Comparing a Short-Term Perioperative Prophylaxis Regimen to a Long-Term Standard Protocol in Equine Colic Surgery

by Sabita Diana Stöckle, Dania A. Kannapin, Anne M. L. Kauter, Antina Lübke-Becker, Birgit Walther, Roswitha Merle and Heidrun Gehlen

Antibiotics 2021, 10(5), 587; https://doi.org/10.3390/antibiotics10050587 - 16 May 2021

Cited by 10 | Viewed by 3215

Abstract

Background: For surgical interventions classified as clean or clean-contaminated, including laparotomy, guidelines in human and veterinary medicine recommend a short-term perioperative antibiotic prophylaxis (PAP). In equine colic surgery, however, PAP commonly exceeds 24 h. Objectives: The aim of this study was to compare [...] Read more.

Background: For surgical interventions classified as clean or clean-contaminated, including laparotomy, guidelines in human and veterinary medicine recommend a short-term perioperative antibiotic prophylaxis (PAP). In equine colic surgery, however, PAP commonly exceeds 24 h. Objectives: The aim of this study was to compare a single-shot to a 5-day lasting PAP considering surgical site infections (SSI) and other adverse effects probably associated with the particular antimicrobial regimen. Study design: The study was designed as a randomised non-inferiority pilot study including horses subjected to colic surgery while receiving one of two distinct PAP regimens. Methods: All horses (n = 67) included in the study received the standard physical examination before and after surgery. Colic surgery was performed according to the current standard of the clinic. Horses were randomly assigned to two groups, receiving either the “single-shot” or the “5-day lasting” antibiotic prophylaxis. The “single-shot” group (n = 30) received penicillin and gentamicin only once before and, if needed, during surgery, whereas the “5-day lasting” group (n = 37) received antibiotics for five days. In addition to the standard laboratory examinations, serum amyloid A and fibrinogen were determined preoperatively and during five days after surgery. SSI, postoperative colitis and haemolytic anaemia were classified as postoperative complications potentially related to antibiotic use. Results: The outcome of this preliminary non-inferiority clinical trial showed that the occurrence of postoperative adverse events (i.e., SSI, postoperative colitis and haemolytic anaemia) lacked significant differences between the study groups. Main limitations: The main limitations of this study are the limited group sizes and our inability to blind the study. Conclusions: Single-shot PAP seems to be an alternative approach considering the 5-day lasting protocol commonly used in equine abdominal surgery. However, a proper hygiene management together with a close clinical and laboratory monitoring of the equine patient is indispensable. Full article

(This article belongs to the Special Issue Optimization and Improvement of Veterinary Antimicrobial Treatment to Reduce Antimicrobial Resistance)

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11 pages, 1346 KiB

Open AccessArticle

Antibiotic Stewardship for Canine and Feline Acute Urinary Tract Infection: An Observational Study in a Small Animal Hospital in Northwest Italy

by Cristina Vercelli, Massimiliano Della Ricca, Mariachiara Re, Graziana Gambino and Giovanni Re

Antibiotics 2021, 10(5), 562; https://doi.org/10.3390/antibiotics10050562 - 11 May 2021

Cited by 11 | Viewed by 3093

Abstract

Antimicrobial stewardship programs (ASPs) have been suggested to reduce antimicrobial resistance phenomena in veterinary medicine, as antibiotics are commonly used without microbiological confirmation. The aim of the present study is to design a specific working flow for a tailored antimicrobial treatment in the [...] Read more.

Antimicrobial stewardship programs (ASPs) have been suggested to reduce antimicrobial resistance phenomena in veterinary medicine, as antibiotics are commonly used without microbiological confirmation. The aim of the present study is to design a specific working flow for a tailored antimicrobial treatment in the case of canine and feline urinary tract infections (UTIs). Urine samples were collected by cystocentesis from 16 dogs and 12 cats presenting acute signs of UTI. The therapy was decided according to the minimal inhibitory concentration, and it was possible to monitor 14 dogs and 11 cats. Rescue therapy (amoxicillin and clavulanic acid) was included in emergency cases. Escherichia coli, Proteus mirabilis, and Streptococcus canis were isolated in dogs, and Escherichia coli, Staphylococcus pseudintermedius, and Staphylococcus aureus were isolated in cats. No multidrug-resistant strains were detected, but all Staphylococci were methicillin resistant. Only one cat received rescue therapy, and only one dog was recruited. Dogs were treated with tetracycline (1/14), fluoroquinolones (6/14), beta-lactams (6/14), and gentamicin (1/14), while cats received fluoroquinolones (3/11), nitrofurans (1/11), clindamycin (1/11), and beta-lactams (6/11). The success rate was very high. Our findings are interesting because this is the first ASP in Italy, and it may be used as a model to develop ASPs for other pathologies. Full article

(This article belongs to the Special Issue Optimization and Improvement of Veterinary Antimicrobial Treatment to Reduce Antimicrobial Resistance)

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10 pages, 982 KiB

Open AccessArticle

Population Pharmacokinetic Modelling of Orally Administered Doxycycline to Rabbits at Different Ages

by Rositsa Mileva, Anton Rusenov and Aneliya Milanova

Antibiotics 2021, 10(3), 310; https://doi.org/10.3390/antibiotics10030310 - 17 Mar 2021

Cited by 4 | Viewed by 2719

Abstract

Doxycycline is a well-tolerated tetracycline antibiotic, registered for use in rabbits and administered for treatment of bacterial infections in this animal species. Nevertheless, the available pharmacokinetic data are limited and this study aimed to investigate the pharmacokinetics of orally administered doxycycline in mature [...] Read more.

Doxycycline is a well-tolerated tetracycline antibiotic, registered for use in rabbits and administered for treatment of bacterial infections in this animal species. Nevertheless, the available pharmacokinetic data are limited and this study aimed to investigate the pharmacokinetics of orally administered doxycycline in mature and immature rabbits by application of the population approach. The rabbits were treated orally with doxycycline hyclate (5 mg/kg bw) in the form of a solid gelatin capsules. Free plasma concentrations were determined with HPLC analysis with Photodiode array detection. The estimated typical value of volume of distribution (tvV), total body clearance, and absorption rate constant were 4.429 L/kg, 1.473 L/kg/h, and 0.257 h⁻¹, respectively. The highest between-subject variability (BSV) of 69.30% was observed for tvV. Co-variates such as body weight, age, and biochemical parameters did not improve the tested model and did not contribute to explanation of the BSV. The population pharmacokinetic model of the orally administered doxycycline in rabbits should be further developed by addition of data from more animals treated with higher doses. An oral dose of 5 mg/kg could ensure percentage of the time from the dosing interval during which the concentration is above minimum inhibitory concentration (MIC) %fT > MIC of 35% if MIC of 0.18 μg·mL⁻¹ and a dosing interval of 12 h is assumed which does not cover criteria for rational use of antibiotics. Full article

(This article belongs to the Special Issue Optimization and Improvement of Veterinary Antimicrobial Treatment to Reduce Antimicrobial Resistance)

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18 pages, 3387 KiB

Open AccessArticle

Use of Local Antibiogram Data and Antimicrobial Importance Ratings to Select Optimal Empirical Therapies for Urinary Tract Infections in Dogs and Cats

by Ri Scarborough, Kirsten Bailey, Bradley Galgut, Adam Williamson, Laura Hardefeldt, James Gilkerson and Glenn Browning

Antibiotics 2020, 9(12), 924; https://doi.org/10.3390/antibiotics9120924 - 18 Dec 2020

Cited by 15 | Viewed by 5535

Abstract

International and Australian veterinary antimicrobial use guidelines recommend amoxicillin or trimethoprim-sulfonamide (TMS) for the empirical treatment of sporadic urinary tract infections (UTIs) in dogs and cats. However, in practice, these antibiotics are rarely used, and no large-scale analyses have examined the antibiograms of [...] Read more.

International and Australian veterinary antimicrobial use guidelines recommend amoxicillin or trimethoprim-sulfonamide (TMS) for the empirical treatment of sporadic urinary tract infections (UTIs) in dogs and cats. However, in practice, these antibiotics are rarely used, and no large-scale analyses have examined the antibiograms of bacteria isolated from UTIs to validate these recommendations in Australia. We analyzed five years of urine culture and antimicrobial susceptibility data from an Australian veterinary laboratory. The analysis included 6196 urinary isolates from dogs and cats, 78% of which were from samples submitted by first-opinion veterinary clinics. Escherichia coli, Enterococcus faecalis, Staphylococcus pseudintermedius and Proteus spp. were the most prevalent organisms. More than 80% of all isolated cocci were susceptible to amoxicillin, and more than 80% of bacilli were susceptible to TMS. A total of 94% of isolates were susceptible to at least one antimicrobial drug categorized as low-importance in Australia. The prevalence of multi-drug resistance (MDR) was highest in E. coli, at 9.7%; 84% of these MDR isolates were susceptible to amoxicillin-clavulanate. We performed population-level antimicrobial treatment simulations and proposed a novel method for integrating antimicrobial importance ratings with antibiogram data to optimize the selection of empirical therapy. Our findings support current guideline recommendations to use amoxicillin or TMS. We also found that bacterial morphology assisted with selection; amoxicillin was a better choice for cocci and TMS for bacilli. Full article

(This article belongs to the Special Issue Optimization and Improvement of Veterinary Antimicrobial Treatment to Reduce Antimicrobial Resistance)

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