Meropenem is an ultra-broad spectrum injectable antibiotic used to treat a wide variety of infections. It is a b-lactam and belongs to the subgroup of carbapenem, similar to imipenem and ertapenem. Meropenem was originally developed by Dainippon Sumitomo Pharma [1]. It gained US FDA approval in July 1996. It penetrates well into many tissues and body fluids including the cerebrospinal fluid, bile, heart valves, lung, and peritoneal fluid.[2] It is active against Gram-positive and Gram-negative bacteria. Meropenem exerts its action by penetrating bacterial cells readily and interfering with the synthesis of vital cell wall components, which leads to cell death. Bactericidal concentrations (defined as a 3 log10 reduction in cell counts within 12 to 24 hours) are typically 1-2 times the bacteriostatic concentrations of meropenem, with the exception of Listeria monocytogenes, against which lethal activity is not observed.
Meropenem has significant stability to hydrolysis by β-lactamases of most categories, both penicillinases and cephalosporinases produced by Gram-positive and Gram-negative bacteria.
Meropenem should not be used to treat methicillin-resistant staphylococci (MRSA).
In vitro tests show meropenem to act synergistically with aminoglycoside antibiotics against some isolates of Pseudomonas aeruginosa.

Therapeutic use

For use as single agent therapy for the treatment of the following infections when caused by susceptible isolates of the designated microorganisms: complicated skin and skin structure infections due to Staphylococcus aureus (b-lactamase and non-b-lactamase producing, methicillin-susceptible isolates only), Streptococcus pyogenes, Streptococcus agalactiae, viridans group streptococci, Enterococcus faecalis (excluding vancomycin-resistant isolates), Pseudomonas aeruginosa, Escherichia coli, Proteus mirabilis, Bacteroides fragilis and Peptostreptococcus species; complicated appendicitis and peritonitis caused by viridans group streptococci, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Bacteroides fragilis, B. thetaiotaomicron, and Peptostreptococcus species. Also for use in the treatment of bacterial meningitis caused by Streptococcus pneumoniae, Haemophilus influenzae (b-lactamase and non-b-lactamase-producing isolates), and Neisseria meningitidis. Meropenem is frequently given in the treatment of febrile neutropenia. This condition frequently occurs in patients with hematological malignancies and cancer patients receiving anticancer drugs that cause bone marrow suppression.

meropenem I.V. is indicated as single agent therapy for the treatment of the following infections when caused by susceptible isolates of the designated microorganisms:

Skin and Skin Structure Infections

Complicated skin and skin structure infections due to Staphylococcus aureus (β-lactamase and non-β-lactamase producing, methicillin susceptible isolates only), Streptococcus pyogenes, Streptococcus agalactiae, viridans group streptococci, Enterococcus faecalis (excluding vancomycin-resistant isolates), Pseudomonas aeruginosa, Escherichia coli, Proteus mirabilis, Bacteroides fragilis, and Peptostreptococcus species.

Intra-abdominal Infections

Complicated appendicitis and peritonitis caused by viridans group streptococci, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Bacteroides fragilis, B. thetaiotaomicron, and Peptostreptococcus species.

Bacterial Meningitis (Pediatric patients > 3 months only)

Bacterial meningitis caused by Streptococcus pneumoniae‡, Haemophilus influenzae (β-lactamase and non-β-lactamase-producing isolates)and Neisseria meningitidis.

‡ The efficacy of meropenem as monotherapy in the treatment of meningitis caused by penicillin nonsusceptible isolates of Streptococcus pneumoniae has not been established.

Meropenem I.V. has been found to be effective in eliminating concurrent bacteremia in association with bacterial meningitis.

Dosage and Administration

Meropenem must be administered intravenously. It is supplied as a white crystalline powder to be dissolved in 5% monobasic potassium phosphate solution. Dosing must be adjusted for altered kidney function and for haemofiltration [3].


The recommended dose of meropenem I.V. is 500 mg given every 8 hours for skin and skin structure infections and 1 g given every 8 hours for intra-abdominal infections. meropenem I.V. should be administered by intravenous infusion over approximately 15 to 30 minutes. Doses of 1 g may also be administered as an intravenous bolus injection (5 to 20 mL) over approximately 3-5 minutes.

Use in Adults with Renal Impairment

Dosage should be reduced in patients with creatinine clearance less than 51 mL/min. (see dosing table below).

Recommended meropenem I.V. Dosage Schedule for Adults With Impaired Renal Function (Table 1)

Table 1. Recommended meropenem doses





(dependent on type of infection)

Dosing Interval
≥51 Recommended dose (500 mg cSSSI and 1 g Intra-abdominal) Every 8 hours
26-50 Recommended dose Every 12 hours
10-25 One-half recommended dose Every 12 hours
<10 One-half recommended dose Every 24 hours

When only serum creatinine is available, the following formula (Cockcroft and Gault equation)5 may be used to estimate creatinine clearance.

Males: Creatinine Clearance (mL/min)=

Weight (kg) x (140 - age)

72 x serum creatinine (mg/dL)

Females: 0.85 x above value

There is inadequate information regarding the use of meropenem I.V. in patients on hemodialysis.

There is no experience with peritoneal dialysis.

Use in Adults With Hepatic Insufficiency

No dosage adjustment is necessary in patients with impaired hepatic function.

Use in Elderly Patients

No dosage adjustment is required for elderly patients with creatinine clearance values above 50 mL/min.

Use in Pediatric Patients

For pediatric patients from 3 months of age and older, the meropenem I.V. dose is 10, 20 or 40 mg/kg every 8 hours (maximum dose is 2 g every 8 hours), depending on the type of infection (complicated skin and skin structure, intra-abdominal or meningitis). (See dosing table below.) Pediatric patients weighing over 50 kg should be administered meropenem I.V. at a dose of 500 mg every 8 hours for complicated skin and skin structure infections, 1 g every 8 hours for intra-abdominal infections and 2 g every 8 hours for meningitis. meropenem I.V. should be given as intravenous infusion over approximately 15 to 30 minutes or as an intravenous bolus injection (5 to 20 mL) over approximately 3-5 minutes.

Recommended meropenem I.V. Dosage Schedule for Pediatrics with Normal Renal Function (Table 2)

Table 2. Reccomended meropenem dose for pediatrics with normal renal function

Type of Infection Dose (mg/kg) Up to Maximum Dose Dosing Interval
Complicated skin and skin structure 10 500 mg Every 8 hours
Intra-abdominal 20 1 g Every 8 hours
Meningitis 40 2 g Every 8 hours

There is no experience in pediatric patients with renal impairment.



In mice and rats, large intravenous doses of meropenem (2200-4000 mg/kg) have been associated with ataxia, dyspnea, convulsions, and mortalities.




Seizures and other CNS adverse experiences have been reported during treatment with MERREM I.V.

Pseudomembranous colitis has been reported with nearly all antibacterial agents, including meropenem, and may range in severity from mild to life-threatening. Therefore, it is important to consider this diagnosis in patients who present with diarrhea subsequent to the administration of antibacterial agents.

Treatment with antibacterial agents alters the normal flora of the colon and may permit overgrowth of clostridia. Studies indicate that a toxin produced by Clostridium difficile is a primary cause of “antibiotic-associated colitis”.

After the diagnosis of pseudomembranous colitis has been established, therapeutic measures should be initiated. Mild cases of pseudomembranous colitis usually respond to drug discontinuation alone. In moderate-to-severe cases, consideration should be given to management with fluids and electrolytes, protein supplementation, and treatment with an antibacterial drug clinically effective against Clostridium difficile colitis.

Common adverse effects

The most common adverse effects are diarrhea (4.8%), nausea and vomiting (3.6%), injection-site inflammation (2.4%), headache (2.3%), rash (1.9%), and thrombophlebitis (0.9%). Many of these adverse effects were observed in the setting of severely ill individuals who were already taking many medications including Vancomycin. One study showed Clostridium difficile associated diarrhea (CDAD) happened in 3.6% of the patients on meropenem. Meropenem also has a reduced potential for causing seizures in comparison with imipenem. Several cases of severe hypokalemia have been reported.


Meropenem has an half life of approximately 1 hour in adults and children 2 years of age and older with normal renal function. Approximately 1.5 hours in children 3 months to 2 years of age.  The pharmacokinetics are linear over the dose range from 10 to 40 mg/kg.

Pharmacokinetic studies with meropenem I.V. in patients with renal insufficiency have shown that the plasma clearance of meropenem correlates with creatinine clearance. Dosage adjustments are necessary in subjects with renal impairment.

Bioavailability 0% per os
Protein binding 2%
Half-life 1 hr
Cmax (mg/ml) 45 μg/mL (500mg dose)

112 μg/mL (1 g dose)

tmax (hrs)  
Distribution volume Vd (l)  
Excretion renal


At the end of a 30-minute intravenous infusion of a single dose of meropenem I.V. in normal volunteers, mean peak plasma concentrations are approximately 23 μg/mL (range 14-26) for the 500 mg dose and 49 μg/mL (range 39-58) for the 1 g dose. A 5-minute intravenous bolus injection of meropenem I.V. in normal volunteers results in mean peak plasma concentrations of approximately 45 μg/mL (range 18-65) for the 500 mg dose and 112 μg/mL (range 83-140) for the 1 g dose. Following intravenous doses of 500 mg, mean plasma concentrations of meropenem usually decline to approximately 1 μg/mL at 6 hours after administration.


Meropenem penetrates well into most body fluids and tissues including cerebrospinal fluid, achieving concentrations matching or exceeding those required to inhibit most susceptible bacteria. After a single intravenous dose of meropenem I.V., the highest mean concentrations of meropenem were found in tissues and fluids at 1 hour (0.5 to 1.5 hours) after the start of infusion, except where indicated in the tissues and fluids listed in the Table 3 below.

Table 3. Meropenem Concentrations in Selected Tissues (Highest Concentrations Reported)

Tissue I.V. Dose (g) Number of Samples Mean [μg/mL or μg/(g)]* Range [μg/mL or μg/(g)]
*at 1 hour unless otherwise noted
**obtained from buler fluid
***in pediatric patients of age 5 months to 8 years
****in pediatric patients of age 1 month to 15 years
Endometrium 0.5 7 4.2 1.7-10.2
Myometrium 0.5 15 3.8 0.4-8.1
Ovary 0.5 8 2.8 0.8-4.8
Cervix 0.5 2 7.0 5.4-8.5
Fallopian tube 0.5 9 1.7 0.3-3.4
Skin 0.5 22 3.3 0.5-12.6
Interstitial fluid** 0.5 9 5.5 3.2-8.6
Skin 1.0 10 5.3 1.3-16.7
Interstitial fluid** 1.0 5 26.3 20.9-37.4
Colon 1.0 2 2.6 2.5-2.7
Bile 1.0 7 14.6 (3 h) 4.0-25.7
Gall bladder 1.0 1 - 3.9
Peritoneal fluid 1.0 9 30.2 7.4-54.6
Lung 1.0 2 4.8 (2 h) 1.4-8.2
Bronchial mucosa 1.0 7 4.5 1.3-11.1
Muscle 1.0 2 6.1 (2 h) 5.3-6.9
Fascia 1.0 9 8.8 1.5-20
Heart valves 1.0 7 9.7 6.4-12.1
Myocardium 1.0 10 15.5 5.2-25.5
CSF (inflamed) 20 mg/kg***

40 mg/kg****



1.1 (2 h)

3.3 (3 h)



CSF (uninflamed) 1.0 4 0.2 (2 h) 0.1-0.3


Approximately 70% of the intravenously administered dose is recovered as unchanged meropenem in the urine over 12 hours, after which little further urinary excretion is detectable.  Urinary concentrations of meropenem in excess of 10 μg/mL are maintained for up to 5 hours after a 500 mg dose. No accumulation of meropenem in plasma or urine was observed with regimens using 500 mg administered every 8 hours or 1 g administered every 6 hours in volunteers with normal renal function.


There is one metabolite which is microbiologically inactive.

Stability in biological fluids [4]

In Vitro Permeation of Meropenem across Rat Ileal Segments

The cumulative permeation of meropenem (1 mM) across rat ileal segments almost linearly increased with time both in mucosal-to-serosal and serosal-to-mucosal directions. The S- to-M permeation of meropenem across rat ileal segments was much greater than the M-to-S permeation, and the S-to-M/M-to-S ratio of permeation rate was approximately 4.9 (Table 4). Similarly to meropenem, the permeation of cefotaxime, an orally inactive cephem antibiotic, across rat ileal seg-ments was greatly secretory-oriented and the S-to-M/M-to-S ratio of permeation rate was approximately 5.9.

Table 4. Permeation rates of meropenem, cefotaxime, ceftibuten, and faropenem across rat ileum.

  M to S (mmol/min) S to M (mmol/min) S to M / M to S
Meropenem 0.042 0.209 4.9
Meropenem (3-O-methyl-D-glucose) 0.061 0.078 1.3
Cefotaxime 0.063 0.374 5.9
Cefibuten 0.043 0.058 1.3
Faropenem 0.018 0.023 1.3

 Stability of Meropenem in JP 1st and 2nd Fluids

In the JP 2nd fluid with pH of 6.8, meropenem was stable and only 10% was disappeared after 6 h at 37˚C. However, meropenem was very unstable in the JP 1st fluid with pH of 1.2 and approximately 80% of meropenem disappeared by 30 min after the start of incubation. Although cefotaxime, ceftibuten, and faropenem time-dependently disappeared in the JP 1st fluid, they are rather stable compared with meropenem. The percentage of cefotaxime, ceftibuten, and faropenem remaining in the JP 1st fluid after incubation for 1 h were 65.0%, 94.1%, and 70.2%, respectively.

Stability of Meropenem in Supernatant Fluid Obtained from Mucosal Homogenate of Rat Small Intestine

Only slight decrease (approximately 5%) in meropenem concentration was observed in the absence or pre- sence of the supernatant fluids for 60 min.



Skin and Skin Structure

Adult patients with complicated skin and skin structure infections including complicated cellulitis, complex abscesses, perirectal abscesses, and skin infections requiring intravenous antimicrobials, hospitalization, and surgical intervention were enrolled in a randomized, multi-center, international, double-blind trial. The study evaluated meropenem at doses of 500 mg administered intravenously every 8 hours and imipenem-cilastatin at doses of 500 mg administered intravenously every 8 hours. The study compared the clinical response between treatment groups in the clinically evaluable population at the follow-up visit (test-of-cure). The trial was conducted in the United States, South Africa, Canada, and Brazil. At enrollment, approximately 37% of the patients had underlying diabetes, 12% had underlying peripheral vascular disease and 67% had a surgical intervention. The study included 510 patients randomized to meropenem and 527 patients randomized to imipenem-cilastatin. Two hundred and sixty-one (261) patients randomized to meropenem and 287 patients randomized to imipenem-cilastatin were clinically evaluable. The success rates in the clinically evaluable patients at the follow-up visit were 86% (225/261) in the meropenem arm and 83% (238/287) in imipenem-cilastatin arm.

The following table provides the results for the overall as well as subgroup comparisons in clinically evaluable population.

Success Rate




n/N (%)


n/N (%)

* Percent of satisfactory clinical response at follow-up evaluation.

n=number of patients with satisfactory response.

N=number of patients in the clinically evaluable population or respective subgroup within treatment groups.


225/261 (86)

238/287 (83)

Diabetes mellitus

83/97 (86)

76/105 (72)

No diabetes mellitus

142/164 (87)

162/182 (89)

<65 years of age

190/218 (87)

205/241 (85)

≥65 years of age

35/43 (81)

33/46 (72)


130/148 (88)

137/172 (80)


95/113 (84)

101/115 (88)


The following clinical efficacy rates were obtained, per organism. The values represent the number of patients clinically cured/number of clinically evaluable patients at the post-treatment follow-up visit, with the percent cure in parentheses (Fully Evaluable analysis set).




n/N (%)


n/N (%)

aPatients may have more than one pretreatment pathogen.

%= Percent of satisfactory clinical response at follow-up evaluation.

n=number of patients with satisfactory response.

N=number of patients in the clinically evaluable population or subgroup within treatment groups.

Gram-positive aerobes



Staphylococcus aureus, methicillin susceptible

82/88 (93)

84/100 (84)

Streptococcus pyogenes (Group A)

26/29 (90)

28/32 (88)

Streptococcus agalactiae (Group B)

12/17 (71)

16/19 (84)

Enterococcus faecalis

9/12 (75)

14/20 (70)

Streptococcus viridans Group, nos

11/12 (92)

5/6 (83)

Gram-negative aerobes



Escherichia coli

12/15 (80)

15/21 (71)

Pseudomonas aeruginosa

11/15 (73)

13/15 (87)

Proteus mirabilis

11/13 (85)

6/7 (86)




Bacteroides fragilis

10/11 (91)

9/10 (90)

Peptostreptococcus species

10/13 (77)

14/16 (88)

The proportion of patients who discontinued study treatment due to an adverse event was similar for both treatment groups. (meropenem, 2.5% and imipenem-cilastatin, 2.7%).


One controlled clinical study of complicated intra-abdominal infection was performed in the United States where meropenem was compared to clindamycin/tobramycin. Three controlled clinical studies of complicated intra-abdominal infections were performed in Europe; meropenem was compared to imipenem (two trials) and cefotaxime/metronidazole (one trial).

Using strict evaluability criteria and microbiologic eradication and clinical cures at follow-up which occurred 7 or more days after completion of therapy, the following presumptive microbiologic eradication/clinical cure rates and statistical findings were obtained:

Treatment Arm No. evaluable/ No. enrolled (%) Microbiologic Eradication Rate Clinical Cure Rate Outcome
meropenem 146/516 (28%) 98/146 (67%) 101/146 (69%)  
imipenem 65/220 (30%) 40/65 (62%) 42/65 (65%) Meropenem equivalent to control
cefotaxime/ metronidazole 26/85 (30%) 22/26 (85%) 22/26 (85%) Meropenem not equivalent to control
clindamycin/ tobramycin 50/212 (24%) 38/50 (76%) 38/50 (76%) Meropenem equivalent to control

The finding that meropenem was not statistically equivalent to cefotaxime/metronidazole may have been due to uneven assignment of more seriously ill patients to the meropenem arm. Currently there is no additional information available to further interpret this observation.

Bacterial Meningitis

Four hundred forty-six patients (397 pediatric patients > 3 months to < 17 years of age) were enrolled in 4 separate clinical trials and randomized to treatment with meropenem (n=225) at a dose of 40 mg/kg q 8 hours or a comparator drug, i.e., cefotaxime (n=187) or ceftriaxone (n=34), at the approved dosing regimens. A comparable number of patients were found to be clinically evaluable (ranging from 61-68%) and with a similar distribution of pathogens isolated on initial CSF culture.

Patients were defined as clinically not cured if any one of the following three criteria were met:

  • At the 5-7 week post-completion of therapy visit, the patient had any one of the following: moderate to severe motor, behavior or development deficits, hearing loss of >60 decibels in one or both ears, or blindness.

  • During therapy the patient’s clinical status necessitated the addition of other antibiotics.

  • Either during or post-therapy, the patient developed a large subdural effusion needing surgical drainage, or a cerebral abscess, or a bacteriologic relapse.

Using the definition, the following efficacy rates were obtained, per organism. The values represent the number of patients clinically cured/number of clinically evaluable patients, with the percent cure in parentheses.

(+) β-lactamase-producing; (-/NT) non-β-lactamase-producing or not tested
S. pneumoniae 17/24 (71) 19/30 (63)
H. influenzae(+) 8/10 (80) 6/6 (100)
H. influenzae (-/NT) 44/59 (75) 44/60 (73)
N. meningitidis 30/35 (86) 35/39 (90)
Total (including others) 102/131 (78) 108/140 (77)

Sequelae were the most common reason patients were assessed as clinically not cured.

Five patients were found to be bacteriologically not cured, 3 in the comparator group (1 relapse and 2 patients with cerebral abscesses) and 2 in the meropenem group (1 relapse and 1 with continued growth of Pseudomonas aeruginosa).

The adverse events seen were comparable between the two treatment groups both in type and frequency. The meropenem group did have a statistically higher number of patients with transient elevation of liver enzymes.

Rates of seizure activity during therapy were comparable between patients with no CNS abnormalities who received meropenem and those who received comparator agents. In the meropenem I.V. treated group, 12/15 patients with seizures had late onset seizures (defined as occurring on day 3 or later) versus 7/20 in the comparator arm.

With respect to hearing loss, 263 of the 271 evaluable patients had at least one hearing test performed post-therapy. The following table shows the degree of hearing loss between the meropenem-treated patients and the comparator-treated patients.

Degree of Hearing Loss

(in one or both ears)


n = 128


n = 135

No loss 61% 56%
20-40 decibels 20% 24%
>40-60 decibels 8% 7%
>60 decibels 9% 10%


Mechanism of Action

The bactericidal activity of meropenem results from the inhibition of cell wall synthesis. Meropenem readily penetrates the cell wall of most Gram-positive and Gram-negative bacteria to reach penicillin-binding- protein (PBP) targets. Its strongest affinities are toward PBPs 2, 3 and 4 of Escherichia coli and Pseudomonas aeruginosa; and PBPs 1, 2 and 4 of Staphylococcus aureus.

Other pharmacological effects


Medicinal Chemistry

CAS number:  119478-56-7  EINECS:

Molecular Formula: C17H25N3O5S

Average mass:  383.462494 Da

Monoisotopic mass: 383.151489 Da

Systematic name: 3-[5-(dimethylcarbamoyl) pyrrolidin-2-yl] sulfanyl-6- (1-hydroxyethyl)-4-methyl-7-oxo- 1-azabicyclo[3.2.0] hept-2-ene-2-carboxylic acid

SMILES: C[C@@H]1[C@@H]2[C@H](C(=O)N2C(=C1S[C@H]3C[C@H](NC3)C(=O)N(C)C)C(=O)O)[C@@H](C)O

Std. InChI: 1S/C17H25N3O5S/c1-7-12-11(8(2)21)16(23)20(12)13(17(24)25)14(7)26-9-5-10(18-6-9)15(22)19(3)4/h7-12,18,21H,5-6H2,1-4H3,(H,24,25)/t7-,8-,9+,10+,11-,12-/m1/s1

ACD/LogP: -3.13±0.75 # of Rule of 5 Violations: 0
ACD/LogD (pH 5.5): -5.61 ACD/LogD (pH 7.4): -5.73
ACD/BCF (pH 5.5): 1.00 ACD/BCF (pH 7.4): 1.00
ACD/KOC (pH 5.5): 1.00 ACD/KOC (pH 7.4): 1.00
#H bond acceptors: 8 #H bond donors: 3
#Freely Rotating Bonds: 6 Polar Surface Area: 135.48 Ĺ2
Index of Refraction: 1.639 Molar Refractivity: 96.8±0.4 cm3
Molar Volume: 268.9±5.0 cm3 Polarizability: 38.4±0.5 10-24cm3
Surface Tension: 68.4±5.0 dyne/cm Density: 1.4±0.1 g/cm3
Flash Point: 333.2±31.5 °C Enthalpy of Vaporization: 106.4±6.0 kJ/mol
Boiling Point: 627.4±55.0 °C at 760 mmHg Vapour Pressure: 0.0±4.2 mmHg at 25°C


Major Impurities:

Appearance: White to pale yellow crystalline powder.

Melting point:

Optical rotation:

Solubility: The solution varies from colorless to yellow depending on the concentration. The pH of freshly constituted solutions is between 7.3 and 8.3. Meropenem is soluble in 5% monobasic potassium phosphate solution, sparingly soluble in water, very slightly soluble in hydrated ethanol, and practically insoluble in acetone or ether.



1. Edwards JR, Turner PJ, Wannop C, Withnell ES, Grindey AJ, Nairn K. "In vitro antibacterial activity of SM-7338, a carbapenem antibiotic with stability to dehydropeptidase I". Antimicrob. Agents Chemother. 33, (2): 215-22, 1989.

2. AHFS DRUG INFORMATION 2006 (2006 ed.). American Society of Health-System Pharmacists. 2006.

3. Bilgrami, I.; Roberts, J. A.; Wallis, S. C.; Thomas, J.; Davis, J.; Fowler, S.; Goldrick, P. B.; Lipman, J. "Meropenem Dosing in Critically Ill Patients with Sepsis Receiving High-Volume Continuous Venovenous Hemofiltration". Antimicrobial Agents and Chemotherapy 54, (7): 2974–2978, 2010.

4. Toshihide Saito, Rinako Sawazaki, Kaori Ujiie, Masako Oda, Hiroshi Saitoh "Possible Factors Involved in Oral Inactivity of Meropenem, a Carbapenem Antibiotic". Pharmacology & Pharmacy, 3, 201-206, (2012).


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