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Meropenem

Class: Carbapenems
Chemical Name: [4R-[3(3S*,5S*),4α,5β,6β(R)]]-3-[[5- [(Dimethylamino)carbonyl]-3-pyrrolidinyl]thio]-6-(1-hydroxyethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid trihydrate
Molecular Formula: C17H25N3O5S•3H2OC17H25N3O5S
CAS Number: 119478-56-7
Brands: Merrem

Medically reviewed by Drugs.com on Jun 30, 2021. Written by ASHP.

Introduction

Antibacterial; carbapenem β-lactam antibiotic.

Uses for Meropenem

Intra-abdominal Tract Infections

Treatment of intra-abdominal infections (complicated appendicitis, peritonitis) caused by susceptible viridans streptococci, Escherichia coli, Klebsiella pneumonia, Pseudomonas aeruginosa, Bacteroides fragilis, B. thetaiotaomicron, or Peptostreptococcus.

Has a broad spectrum of antibacterial activity against both aerobes and anaerobes; may be used empirically to treat intra-abdominal infections before identification of the causative organism.

For immunosuppressed patients or those with severe intra-abdominal infections, IDSA recommends an initial empiric regimen with broad spectrum of activity such as meropenem or imipenem; a third or fourth generation cephalosporin (cefepime, cefotaxime, ceftazidime, ceftizoxime, ceftriaxone) in conjunction with metronidazole; ciprofloxacin in conjunction with metronidazole; piperacillin-tazobactam; or aztreonam in conjunction with metronidazole. For mild to moderate community-acquired intra-abdominal infections, IDSA recommends an initial empiric regimen with narrower spectrum of activity such as ampicillin-sulbactam; cefazolin or cefuroxime in conjunction with metronidazole; ticarcillin-clavulanate; ertapenem; or a fluoroquinolone (ciprofloxacin, gatifloxacin, levofloxacin, moxifloxacin) in conjunction with metronidazole.

For postoperative (nosocomial) intra-abdominal infections, IDSA recommends the empiric regimen be selected based on local nosocomial susceptibility patterns; these infections usually require treatment with multiple-drug regimens and often involve resistant organisms.

Meningitis

Treatment of bacterial meningitis caused by susceptible Streptococcus pneumoniae, Haemophilus influenzae (including β-lactamase-producing strains), or Neisseria meningitidis in children ≥3 months of age. Also has been used for treatment of meningitis in adults.

Efficacy for treatment of meningitis caused by highly penicillin- or cephalosporin-resistant S. pneumoniae has not been established.

Can be used as monotherapy for meningitis caused by susceptible bacteria. Although not usually considered initial drug of choice, recommended as an alternative in children and adults for treatment of meningitis caused by S. pneumoniae or H. influenzae. Also may be useful for meningitis caused by susceptible gram-negative bacteria (e.g., Enterobacter, Citrobacter, Serratia marcescens) resistant to usually recommended regimens.

Respiratory Tract Infections

Treatment of respiratory tract infections, including community-acquired pneumonia (CAP) and nosocomial pneumonia.

ATS, IDSA, and others consider meropenem an alternative, not a drug of first choice, for empiric treatment of CAP caused by S. pneumoniae. ATS and IDSA suggest the drug be reserved for when CAP may be caused by Ps. aeruginosa, Klebsiella, or other gram-negative bacteria. Also may be considered when anaerobes are known or suspected to be involved.

A drug of choice for empiric treatment of nosocomial pneumonia. ATS, IDSA, and others recommend an antipseudomonal cephalosporin (cefepime, ceftazidime), antipseudomonal penicillin (piperacillin-tazobactam, ticarcillin-clavulanate), or antipseudomonal carbapenem (imipenem or meropenem) for initial therapy of hospital-acquired pneumonia, ventilator-associated pneumonia, or health-care associated pneumonia because these drugs have broad spectrum of activity against gram-positive, gram-negative, and anaerobic bacteria. In severely ill patients or in those with late-onset disease or risk factors for multidrug-resistant bacteria, initial regimen should also include an aminoglycoside (amikacin, gentamicin, tobramycin) or antipseudomonal fluoroquinolone (ciprofloxacin or levofloxacin) to improve coverage against Pseudomonas. In hospitals where oxacillin-resistant (methicillin-resistant) Staphylococcus are common or if there are risk factors for these strains, the initial regimen also should include vancomycin or linezolid. In hospitals where multidrug-resistant Ps. aeruginosa are frequent causes of nosocomial pneumonia, an initial regimen of cefepime or a carbapenem (imipenem or meropenem) in conjunction with an aminoglycoside is recommended.

Septicemia

Treatment of septicemia caused by susceptible bacteria.

Skin and Skin Structure Infections

Treatment of complicated skin and skin structure infections caused by susceptible S. aureus (including β-lactamase-producing strains, but not oxacillin-resistant [methicillin-resistant] strains), S. pyogenes (group A β-hemolytic streptococci), S. agalactiae (group B streptococci), viridans streptococci, Enterococcus faecalis (not vancomycin-resistant strains), Ps. aeruginosa, E. coli, Proteus mirabilis, B. fragilis, or Peptostreptococcus.

Urinary Tract Infections

Treatment of complicated urinary tract infections caused by susceptible bacteria.

Acinetobacter Infections

Treatment of infections caused by Acinetobacter; a drug of choice used with or without an aminoglycoside.

Anthrax

Recommended as one of several anti-infectives that can be included in multiple-drug regimens used for the treatment of anthrax, including inhalational anthrax and anthrax meningitis.

Has in vitro activity against Bacillus anthracis; data not available regarding in vivo activity.

Bacillus Infections

Treatment of infections caused by Bacillus cereus. Vancomycin considered drug of choice; carbapenems (imipenem or meropenem) or clindamycin are alternatives.

Burkholderia Infections

Treatment of melioidosis caused by Burkholderia pseudomallei. Severe illness requires an initial parenteral regimen of ceftazidime, imipenem, or meropenem (with or without concomitant co-trimoxazole or doxycycline), followed by a prolonged oral maintenance regimen of co-trimoxazole in conjunction with doxycycline or amoxicillin-clavulanate.

Treatment of glanders caused by B. mallei. Experience is limited regarding treatment of human cases; optimum regimens not identified. Some clinicians suggest streptomycin used in conjunction with tetracycline or chloramphenicol or imipenem monotherapy. Others suggest that, pending results of in vitro susceptibility tests, regimens used for treatment of melioidosis can be used for initial empiric treatment of glanders.

The US Army Medical Research Institute of Infectious Diseases (USAMRIID) and European Commission’s Task Force on Biological and Chemical Agent Threats (BICHAT) state that the same treatment regimens recommended for naturally occurring melioidosis or glanders should be used if these Burkholderia infections occur in the context of biologic warfare or bioterrorism. These experts suggest that postexposure prophylaxis with doxycycline or co-trimoxazole for ≥10 days can be attempted in such situations, but is of unproven benefit.

Campylobacter Infections

Treatment of systemic infections caused by Campylobacter fetus; a drug of choice.

Capnocytophaga Infections

Treatment of infections caused by Capnocytophaga canimorsus.

Optimum regimens for treatment of Capnocytophaga infections not identified; some clinicians recommend use of penicillin G or, alternatively, a third generation cephalosporin (cefotaxime, ceftizoxime, ceftriaxone), a carbapenem (imipenem or meropenem), vancomycin, a fluoroquinolone, or clindamycin.

Clostridium Infections

Treatment of infections caused by Clostridium perfringens; alternative to penicillin G for those with penicillin hypersensitivity or for polymicrobial infections.

Nocardia Infections

Treatment of infections caused by Nocardia. Co-trimoxazole usually drug of first choice; alternatives include sulfisoxazole, a tetracycline (e.g., doxycycline, minocycline), a carbapenem (imipenem or meropenem), amikacin, ceftriaxone, amoxicillin-clavulanate, cycloserine, or linezolid.

Rhodococcus Infections

Treatment of infections caused by Rhodococcus equi. Optimum regimens not identified; combination regimens usually recommended, including vancomycin given with a fluoroquinolone, rifampin, a carbapenem (imipenem or meropenem), or amikacin.

Empiric Therapy in Febrile Neutropenic Patients

Empiric anti-infective therapy of presumed bacterial infections in febrile neutropenic patients. Used alone or in conjunction with other anti-infectives.

Consult published protocols for the treatment of infections in febrile neutropenic patients for specific recommendations regarding selection of the initial empiric regimen, when to change the initial regimen, possible subsequent regimens, and duration of therapy in these patients. Consultation with an infectious disease expert knowledgeable about infections in immunocompromised patients also is advised.

Meropenem Dosage and Administration

Administration

Administer by IV injection or infusion.

For solution and drug compatibility information, see Compatibility under Stability.

IV Injection

Reconstitution

Reconstitute single-use vials containing 500 mg or 1 g with 10 or 20 mL, respectively, of sterile water for injection to provide a solution containing approximately 50 mg/mL. The vial should be shaken until dissolution occurs and then allowed to stand until the solution is clear.

Rate of Administration

The appropriate dose of reconstituted solution should be injected over a period of 3–5 minutes.

IV Infusion

Reconstitution and Dilution

Reconstitute infusion vials containing 500 mg or 1 g with a compatible IV solution (e.g., 0.9% sodium chloride, 5% dextrose) to provide solutions containing approximately 2.5–50 mg/mL. Alternatively, reconstitute vials containing 500 mg or 1 g with 10 or 20 mL, respectively, of sterile water for injection and then further dilute in a compatible IV.

Rate of Administration

Infuse IV over 15–30 minutes.

Dosage

Available as the trihydrate; dosage expressed in terms of anhydrous meropenem.

To minimize risk of seizures, closely adhere to dosage recommendations, especially in patients with factors known to predispose to seizure activity; dosage adjustment recommended for patients with advanced age and/or renal impairment.

Anticonvulsant therapy should be continued in patients with existing seizure disorders. (See CNS Effects under Cautions.)

Pediatric Patients

Intra-abdominal Infections
IV

Children ≥3 months of age weighing ≤50 kg: 20 mg/kg (up to 1 g) every 8 hours.

Children ≥3 months weighing >50 kg: 1 g every 8 hours.

Meningitis
IV

Children ≥3 months of age weighing ≤50 kg: 40 mg/kg (up to 2 g) every 8 hours.

Children ≥3 months weighing >50 kg: 2 g every 8 hours.

Skin and Skin Structure Infections
IV

Children ≥3 months of age weighing ≤50 kg: 10 mg/kg (up to 500 mg) every 8 hours.

Children ≥3 months weighing >50 kg: 500 mg every 8 hours.

Burkholderia Infections†
Initial Treatment of Severe Disease†
IV

Children ≥3 months of age weighing ≤40 kg: 10–20 mg/kg every 8 hours.

Children ≥3 months weighing >40 kg: use adult dosage.

Initial IV regimen continued for ≥14 days and until clinical improvement occurs. When appropriate, switch to a prolonged oral maintenance regimen (e.g., co-trimoxazole with doxycycline, amoxicillin-clavulanate). Lifelong follow-up recommended for all patients to identify relapse.

Adults

Intra-abdominal Infections
IV

1 g every 8 hours.

Meningitis†
IV

6 g daily. Dosage of 40 mg/kg every 8 hours (up to 6 g daily) has been used in conjunction with ceftriaxone or cefotaxime.

Respiratory Tract Infections†
Nosocomial Pneumonia†
IV

1 g every 8 hours.

Skin and Skin Structure Infections
IV

500 mg every 8 hours.

Burkholderia Infections†
Initial Treatment of Severe Disease†
IV

25 mg/kg IV every 8 hours (up to 6 g daily) recommended by USAMRIID and others; concomitant co-trimoxazole (8 mg/kg of trimethoprim daily given IV in 4 divided doses) also may be indicated. Other clinicians recommend 0.5–1 g every 8 hours with or without co-trimoxazole.

Initial IV regimen continued for ≥14 days and until clinical improvement occurs. When appropriate, switch to a prolonged oral maintenance regimen (e.g., co-trimoxazole with doxycycline, amoxicillin-clavulanate). Lifelong follow-up recommended for all patients to identify relapse.

Prescribing Limits

Pediatric Patients

IV

2 g every 8 hours.

Special Populations

Hepatic Impairment

Dosage adjustments not required.

Renal Impairment

Dosage adjustments recommended in adults with Clcr ≤50 mL/minute. Data insufficient to make dosage recommendations for pediatric patients with renal impairment.

Dosage for Adults with Renal Impairment1

Clcr (mL/min)

Daily Dosage

26–50

usual dose every 12 hours

10–25

50% of usual dose every 12 hours

<10

50% of usual dose once every 24 hours

Manufacturer states data insufficient to make dosage recommendations in patients undergoing hemodialysis or peritoneal dialysis. Meropenem removed by hemodialysis; some clinicians suggest that supplemental doses be given after each hemodialysis session. Also removed by various forms of continuous renal replacement therapy, including continuous venovenous hemodiafiltration (CVVHDF), continuous venovenous hemofiltration (CVVHF), and continuous ambulatory peritoneal dialysis (CAPD). To avoid inadequate concentrations in anuric patients undergoing these procedures, some clinicians suggest dosage adjustments are necessary and should be based on characteristics of the specific procedure (e.g., filter or membrane type, amount of filtrate produced, dialysate flow rate).

Geriatric Patients

No dosage adjustments except those related to renal impairment. (See Renal Impairment under Dosage and Administration.)

Cautions for Meropenem

Contraindications

  • Known hypersensitivity to meropenem, other carbapenems, or any ingredient in the formulation.

  • History of anaphylactic reaction to β-lactams.

Warnings/Precautions

Warnings

Superinfection/Clostridium difficile-associated Colitis

Possible emergence and overgrowth of nonsusceptible organism. Careful observation of the patient is essential. Institute appropriate therapy if superinfection occurs.

Treatment with anti-infectives may permit overgrowth of clostridia. Consider Clostridium difficile-associated diarrhea and colitis (antibiotic-associated pseudomembranous colitis) if diarrhea develops and manage accordingly.

Some mild cases of C. difficile-associated diarrhea and colitis may respond to discontinuance alone. Manage moderate to severe cases with fluid, electrolyte, and protein supplementation; appropriate anti-infective therapy (e.g., oral metronidazole or vancomycin) recommended if colitis is severe.

CNS Effects

Seizures and other CNS effects reported, especially in those with CNS disorders (e.g., brain lesions, history of seizures) or with bacterial meningitis and/or renal impairment.

Do not exceed recommended dosage, especially in those with known factors that predispose to seizures. Anticonvulsant therapy should be continued in those with known seizure disorders.

If focal tremors, myoclonus, or seizures occur, evaluate the patient neurologically, initiate anticonvulsant therapy if necessary, and determine whether meropenem dosage should be decreased or the drug discontinued.

Sensitivity Reactions

Hypersensitivity Reactions

Serious and occasionally fatal hypersensitivity reactions (e.g., anaphylaxis) reported with β-lactams.

If hypersensitivity occurs, discontinue meropenem and institute appropriate therapy as indicated (e.g., epinephrine, corticosteroids, and maintenance of an adequate airway and oxygen).

Cross-hypersensitivity

Partial cross-allergenicity among β-lactam antibiotics, including penicillins, cephalosporins, and other β-lactams.

Prior to initiation of therapy, make careful inquiry concerning previous hypersensitivity reactions to meropenem, cephalosporins, penicillins, or other drugs.

General Precautions

Selection and Use of Anti-infectives

To reduce development of drug-resistant bacteria and maintain effectiveness of meropenem and other antibacterials, use only for treatment or prevention of infections proven or strongly suspected to be caused by susceptible bacteria.

When selecting or modifying anti-infective therapy, use results of culture and in vitro susceptibility testing. In the absence of such data, consider local epidemiology and susceptibility patterns when selecting anti-infectives for empiric therapy.

Laboratory Monitoring

Periodically assess organ system functions, including renal, hepatic, and hematopoietic, during prolonged therapy.

Sodium Content

Each g of meropenem contains 3.92 mEq (90.2 mg) of sodium as sodium carbonate.

Specific Populations

Pregnancy

Category B.

Lactation

Not known whether distributed into milk. Use with caution.

Pediatric Use

Safety and efficacy not established in children <3 months of age.

Geriatric Use

No substantial differences in safety and efficacy relative to younger adults, but increased sensitivity cannot be ruled out.

Substantially eliminated by kidneys; risk of toxicity may be greater in patients with impaired renal function. Select dosage with caution and assess renal function periodically since geriatric patients are more likely to have renal impairment.

No dosage adjustments except those related to renal function. (See Renal Impairment under Dosage and Administration.)

Hepatic Impairment

Pharmacokinetics not affected by hepatic impairment; dosage adjustments not required.

Renal Impairment

Decreased clearance. Dosage adjustments recommended in patients with Clcr ≤50 mL/minute. (See Renal Impairment under Dosage and Administration.)

Common Adverse Effects

GI effects (diarrhea, nausea, vomiting, constipation), local reactions (pain and inflammation at injection site, phlebitis/thrombophlebitis), headache, anemia, rash, pruritus, sepsis, apnea, shock, glossitis, oral candidiasis.

Interactions for Meropenem

Specific Drugs

Drug

Interaction

Comments

Aminoglycosides

In vitro evidence of synergistic antibacterial effects against Ps. aeruginosa

Probenecid

Decreased renal tubular secretion of meropenem; increased meropenem concentrations and AUC and prolonged half-life

Concomitant use not recommended

Valproic acid

Valproic serum concentrations may be decreased to subtherapeutic concentrations; possible increased risk of seizures

Use concomitantly with caution

Meropenem Pharmacokinetics

Distribution

Extent

Well distributed into body tissues and fluids, including bronchial mucosa, lung, bile, gynecologic tissue (endometrium, myometrium, ovary, cervix, fallopian tube), muscle, heart valves, skin, and interstitial and peritoneal fluid.

Distributed into CSF.

Plasma Protein Binding

Approximately 2%.

Elimination

Metabolism

Partially metabolized; at least 1 metabolite is microbiologically active.

Elimination Route

Eliminated in urine as unchanged drug. 70% of an IV dose eliminated in urine as unchanged drug.

Half-life

Adults with normal renal function: approximately 1 hour.

Children 3 months to 2 years of age: approximately 1.5 hours.

Special Populations

Pharmacokinetics not affected by hepatic impairment.

Decreased clearance in patients with renal impairment.

Stability

Storage

Parenteral

Powder for Injection

20–25°C. Do not freeze reconstituted or diluted solutions.

Solutions for IV injection containing approximately 50 mg/mL prepared using water for injection are stable for 2 hours at 15–25°C or 12 hours at 4°C.

Solutions for IV infusion containing 2.5–50 mg/mL prepared using 0.9% sodium chloride are stable for up to 2 hours at 15–25°C or 18 hours at 4°C; those prepared using 5% dextrose are stable for up to 1 hour at 15–25°C or 8 hours at 4°C.

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Solution CompatibilityHID

Incompatible (by conventional definition, but recommended for dilution with use in shorter periods of time)

Dextrose 5% with potassium chloride 0.15%

Dextrose 5% in Ringer’s injection, lactated

Dextrose 5% with sodium bicarbonate 0.02%

Dextrose 2.5% in sodium chloride 0.45%

Dextrose 5% in sodium chloride 0.2 or 0.9%

Dextrose 5 or 10% in water

Mannitol 2.5 or 10%

Normosol M with dextrose 5%

Ringer’s injection

Ringer’s injection, lactated

Sodium bicarbonate 5%

Sodium chloride 0.45%

Sodium lactate 1/6 M

Variable

Sodium chloride 0.9%

Drug Compatibility
Admixture CompatibilityHID

Compatible

Aminophylline

Atropine sulfate

Dexamethasone sodium phosphate

Dobutamine HCl

Dopamine HCl

Enalaprilat

Fluconazole

Furosemide

Gentamicin sulfate

Heparin sodium

Insulin, regular

Magnesium sulfate

Metoclopramide HCl

Morphine sulfate

Norepinephrine bitartrate

Phenobarbital sodium

Ranitidine HCl

Vancomycin HCl

Incompatible

Amphotericin B

Multivitamins

Variable

Acyclovir sodium

Doxycycline hyclate

Ondansetron HCl

Zidovudine

Y-Site CompatibilityHID

Compatible

Aminophylline

Anidulafungin

Atropine sulfate

Caspofungin acetate

Cyclosporine

Dexamethasone sodium phosphate

Digoxin

Diphenhydramine HCl

Docetaxel

Enalaprilat

Fluconazole

Furosemide

Gentamicin sulfate

Heparin sodium

Insulin, regular

Linezolid

Metoclopramide HCl

Milrinone lactate

Morphine sulfate

Norepinephrine bitartrate

Phenobarbital sodium

Potassium chloride

Telavancin HCl

Vancomycin HCl

Vasopressin

Incompatible

Amphotericin B

Diazepam

Variable

Acyclovir sodium

Calcium gluconate

Doxycycline hyclate

Ondansetron HCl

Zidovudine

Actions and Spectrum

  • Synthetic carbapenem β-lactam antibiotic; structurally and pharmacologically related to imipenem and ertapenem.

  • Usually bactericidal in action.

  • Like other β-lactam antibiotics, antibacterial activity results from inhibition of bacterial cell wall synthesis.

  • Spectrum of activity includes many gram-positive and -negative aerobic bacteria and some gram-positive and -negative anaerobic bacteria. Stable in the presence of a variety of β-lactamases (including penicillinases, cephalosporinases, and extended-spectrum β-lactamases).

  • Gram-positive aerobes: Active in vitro and in clinical infections against Streptococcus pneumoniae (penicillin-susceptible strains only) and viridans streptococci. Also active in vitro against Staphylococcus aureus and S. epidermidis. Oxacillin-resistant (methicillin-resistant) staphylococci are resistant.

  • Gram-negative aerobes: Active in vitro and in clinical infections against Escherichia coli, Haemophilus influenzae (including β-lactamase-producing strains), Klebsiella pneumoniae, Neisseria meningitidis and Pseudomonas aeruginosa. Also active in vitro against Acinetobacter, Aeromonas hydrophila, Campylobacter jejuni, Citrobacter, Enterobacter, H. influenzae (ampicillin-resistant, non-β-lactamase-producing strains; BLNAR), Havnia alvei, K. oxytoca, Moraxella catarrhalis, Morganella morganii, Pasteurella multocida, Proteus mirabilis, P. vulgaris, Salmonella, Shigella, Serratia marcescens, and Yersinia enterocolitica.

  • Anaerobes: Active in vitro and in clinical infections against Bacteroides fragilis, B. thetaiotaomicron, and Peptostreptococcus. Also active in vitro against B. distasonis, B. ovatus, B. uniformis, B. ureolyticus, B. vulgatus, Clostridium difficile, C. perfringens, Eubacterium lentum, Fusobacterium, Prevotella bivia, P. intermedia, P. melaninogenica, Porphyromonas asaccharolytica, and Propionibacterium acnes.

Advice to Patients

  • Advise patients that antibacterials (including meropenem) should only be used to treat bacterial infections and not used to treat viral infections (e.g., the common cold).

  • Importance of completing full course of therapy, even if feeling better after a few days.

  • Advise patients that skipping doses or not completing the full course of therapy may decrease effectiveness and increase the likelihood that bacteria will develop resistance and will not be treatable with meropenem or other antibacterials in the future.

  • Importance of informing clinicians of other medical conditions, including history of seizures.

  • Importance of discontinuing therapy and informing clinician if an allergic or hypersensitivity reaction occurs.

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.

  • Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Meropenem (Trihydrate)

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

For injection, for IV use only

500 mg (of anhydrous meropenem)

Merrem I.V.

AstraZeneca

1 g (of anhydrous meropenem)

Merrem I.V.

AstraZeneca

AHFS DI Essentials™. © Copyright 2022, Selected Revisions July 10, 2013. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

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