MEROPENEM

General Administration Information
For storage information, see the specific product information within the How Supplied section.

Tuberculosis patients*
-Directly observed therapy (DOT) is recommended for all children as well as adolescents living with HIV.

Route-Specific Administration

Injectable Administration
-Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
Intravenous Administration
Intravenous (IV) Infusion
Powder Vials for Injection
Reconstitution
-Reconstitute 500 mg or 1 g vials with 10 or 20 mL of Sterile Water for Injection, respectively, for a resultant concentration of approximately 50 mg/mL. Shake to dissolve and let stand until clear.
-Alternatively, vials may be directly reconstituted with 0.9% Sodium Chloride Injection or 5% Dextrose Injection to a concentration ranging from 1 to 20 mg/mL.
-Storage: Storage requirements for reconstituted solutions are dependent on the diluent used. Do not freeze.
-Sterile Water for Injection: Stable up to 3 hours at controlled room temperature 25 degrees C (77 degrees F) or up to 13 hours at 5 degrees C (41 degrees F).
-0.9% Sodium Chloride Injection: Stable up to 1 hour at controlled room temperature 25 degrees C (77 degrees F) or up to 15 hours at 5 degrees C (41 degrees F).
-5% Dextrose Injection: Use immediately.


Dilution
-If reconstituted with Sterile Water for Injection, further dilute the reconstituted solution 0.9% Sodium Chloride Injection or 5% Dextrose Injection to a concentration ranging from 1 to 20 mg/mL.
-Storage: Storage requirements for reconstituted solutions are dependent on the diluent used. Do not freeze.
-0.9% Sodium Chloride Injection: Stable up to 1 hour at controlled room temperature 25 degrees C (77 degrees F) or up to 15 hours at 5 degrees C (41 degrees F).
-5% Dextrose Injection: Use immediately.


Duplex Drug Delivery System
-For administration in patients who require the entire 500 mg or 1 g dose and not any fraction of the dose.
-Use only if container and seals are intact.
-To inspect the drug powder for foreign matter or discoloration, peel the foil strip from the drug chamber. Protect from light after removal of foil strip.
-Allow the product to reach room temperature before patient use.
-Unfold Duplex container and point the set port downward. Starting at the hanger tab end, fold the Duplex container just below the diluent meniscus trapping all air above the fold.
-To activate, squeeze the folded diluent chamber until the seal between the diluent and powder opens, releasing diluent into the drug powder chamber.
-Agitate the liquid-powder mixture until the drug powder completely dissolves.
-Storage: If the foil strip is removed and the container will not be used immediately, refold container and latch the side tab until ready to activate; use within 7 days at room temperature. After reconstitution (activation), use within 1 hour if stored at room temperature or within 15 hours if stored under refrigeration.

Intermittent IV Infusion
-Infuse IV over 15 to 30 minutes.
-Do not use in series connections.

Intermittent Extended IV Infusion*
NOTE: Administration by extended infusion is not FDA-approved.
-Administering as an extended infusion (3- to 4-hour infusion) may increase the likelihood of pharmacodynamic target achievement in difficult to treat infections.

Intravenous (IV) Push
Powder Vials for Injection
Reconstitution
-Reconstitute 500 mg or 1 g vials with 10 or 20 mL of Sterile Water for Injection, respectively, for a resultant concentration of approximately 50 mg/mL.
-Shake to dissolve and let stand until clear.
-Storage: Stable for up to 3 hours at controlled room temperature 25 degrees C (77 degrees F) or up to 13 hours at 5 degrees C (41 degrees F).

Intermittent IV Push
-Inject doses up to 1 g (Max concentration: 50 mg/mL) IV over 3 to 5 minutes.

In clinical studies of pediatric patients receiving meropenem, adverse events (including laboratory changes) that were reported were similar to those reported in adult studies.

In a retrospective cohort study of 5566 infants < 3 months old, the rates of overall laboratory adverse events (increased creatinine, hyperbilirubinemia, and increased liver enzymes) were higher with meropenem compared with imipenem; cilastatin (odds ratio (OR) 1.41; 95% CI: 1.28-1.55); however, the probability of severe adverse events such as death or the combined outcome of death or seizure was significantly lower in infants treated with meropenem compared with those treated with imipenem; cilastatin (OR 0.68; 95% CI: 0.5-0.88 and OR 0.77; 95% CI: 0.62-0.95, respectively).

Gastrointestinal-related adverse reactions are some of the most common adverse events reported in pediatric patients in meropenem clinical trials. Diarrhea (3.5% to 6%) and nausea (0.8% to 4%) are the 2 most common effects. Vomiting was reported in 0.8% of patients older than 3 months of age in clinical trials, but in a trial of 200 neonates and infants younger than 91 days of age with suspected or confirmed complicated intra-abdominal infections, vomiting was reported in 3% of patients who received meropenem. Constipation appears to be less common in pediatric patients (0.2%) compared to adults (1.4% to 7%). Other GI-related events occurring in up to 1% of adults in clinical trials were abdominal pain, abdominal enlargement, anorexia, flatulence, ileus, dyspepsia, and GI obstruction. Unspecified gastrointestinal disorder was reported in more than 1% of adults.

Nervous system and psychiatric adverse events have been reported with meropenem therapy. Headache has been reported in up to 4% of pediatric patients in clinical trials ; headache was also relatively common in adult clinical trials (2.3-7.8%). Other nervous system events occurring in > 0.1 % to <= 1% of adults in clinical trials include insomnia, agitation, delirium, confusion, dizziness, convulsion, nervousness, paresthesias, hallucinations, drowsiness (somnolence), anxiety, depression, and asthenia.

An injection site reaction may occur with meropenem administration; monitor the site of administration for irritation and phlebitis. During clinical trials of immunocompetent adults treated for infections outside the CNS, the following local adverse reactions were reported: inflammation at the injection site (2.4%), injection site reaction (0.9%), phlebitis/thrombophlebitis (0.8%), pain at the injection site (0.4%), and edema at the injection site (0.2%).

Hematologic adverse events have been reported with meropenem use in both pediatric and adult patients. In a trial of 53 pediatric patients, 2 (3.8%) patients developed thrombocytosis and 1 (1.9%) developed eosinophilia. In other clinical trials in pediatric patients, these adverse events were not reported ; therefore the true incidence of these effects in pediatric patients is not known. In adults being treated with meropenem, anemia occurred in 0.1-5.5% of patients. Other hematologic adverse events occurring in > 0.1% to <= 1% of adults in clinical trials include epistaxis (0.2%), GI bleeding (0.5%), hemoperitoneum (0.2%), melena (0.3%), and hypochromic anemia. Eosinophilia, leukocytosis, increased or decreased platelets, decreased white blood cells, decreased hemoglobin and hematocrit, shortened prothrombin time, and shortened partial thromboplastin time were all reported in > 0.2% of patients. Agranulocytosis, positive direct or indirect Coombs test, hemolytic anemia, neutropenia, and leukopenia were reported in worldwide post-marketing surveillance reports. Thrombocytopenia has been reported in patients with renal impairment, but no clinical bleeding has been reported.

Elevated hepatic enzymes is one of the more common laboratory adverse effects reported with meropenem use in pediatric patients. In a clinical study of 200 neonates and infants < 91 days of age with suspected or confirmed complicated intra-abdominal infections, elevated hepatic enzymes (increased AST) were reported in 3% of patients who received meropenem. Hyperbilirubinemia was noted in 5% of patients. In another retrospective cohort study of 5566 infants < 3 months old, elevated hepatic enzymes (increased AST or ALT) were reported in 6.9% of the 3479 infants who received meropenem. Hyperbilirubinemia was also reported (30.2/1000 infant days), and was the most commonly observed laboratory adverse event with meropenem. In a study in children with cystic fibrosis (n = 102), increased AST and ALT were reported in 14% and 12% of patients who received meropenem/tobramycin, respectively, and increased alkaline phosphatase was reported in 8% of patients. The contribution of the patients' cystic fibrosis to these elevations is unclear. In another trial of 53 pediatric patients with serious bacterial infections, elevated hepatic enzymes occurred in 3.8-7.5% of patients. During adult clinical trials, hepatic adverse events that were reported in > 0.1% to <= 1% of patients include cholestasis with jaundice and hepatic failure.

During clinical trials with meropenem, rash (unspecified) was reported in 1.9% of adults and 1.6% to 6% of pediatric patients, and pruritus was reported in 1.2% of adults. Diaper dermatitis (moniliasis) is the most common type of rash in young patients. Other hypersensitivity or skin adverse events occurring in up to 1% of adults in clinical trials include urticaria, sweating/diaphoresis, and skin ulcer. Severe cutaneous adverse reactions such as Stevens-Johnson syndrome, toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), erythema multiforme, and acute generalized exanthematous pustulosis (AGEP) have occurred in patients receiving meropenem. Discontinue meropenem immediately and consider alternative therapy if signs and symptoms suggestive of these reactions occur. Angioedema has also been reported in postmarketing experience with meropenem. Anaphylactoid reactions have been reported in patients receiving beta-lactam therapy.

Microbial overgrowth and superinfection can occur with antibiotic use. C. difficile-associated diarrhea (CDAD) or pseudomembranous colitis has been reported with meropenem. If pseudomembranous colitis is suspected or confirmed, ongoing antibacterial therapy not directed against C. difficile may need to be discontinued. Institute appropriate fluid and electrolyte management, protein supplementation, C. difficile-directed antibacterial therapy, and surgical evaluation as clinically appropriate. During adult clinical trials, sepsis was reported in 1.6% of patients. Other infection-related adverse events that were reported in up to 1% of adult patients include chills and fever. Pharyngitis and pneumonia were noted in more 1% of adult patients. Candidiasis (oral and vaginal) was reported in up to 1% of adults, diaper area candidiasis was noted in 3.1% of pediatric patients, and oral candidiasis occurred in 1.9% of pediatric patients. Glossitis was reported in 1% of pediatric patients. In a trial of 200 neonates and infants younger than 91 days of age with suspected or confirmed complicated intra-abdominal infections, 6% of patients who received meropenem developed sepsis. Pharyngitis was reported in 6% of children with cystic fibrosis who received meropenem/tobramycin in a clinical study (n = 102).

Seizures and other CNS adverse events have been reported during treatment with meropenem; however, the risk appears to be lower than that associated with imipenem; cilastin. In a retrospective cohort study of 5566 infants < 3 months old, the rate of seizures was 5.4% (187/3479) in patients who received meropenem compared with 7.8% (180/2310) in those who received imipenem; cilastin (p < 0.001); however, on multivariate analysis, the probability of seizure occurrence was similar between the 2 treatment groups (odds ratio 0.96; 95% CI: 0.68-1.32). When seizures have occurred, they have most commonly been in patients with CNS disorders (e.g., brain lesions or history of seizures) or with bacterial meningitis and/or compromised renal function. According to the manufacturer, in pediatric patients with meningitis, the rates of seizure activity during meropenem therapy in patients with no CNS abnormalities were comparable to those who received comparator agents (ceftriaxone or cefotaxime). In a pediatric bacterial meningitis study involving 129 children who received meropenem, there were also no reports of seizures that were considered treatment-related. In a clinical study of 200 neonates and infants < 91 days of age with suspected or confirmed complicated intra-abdominal infections, seizures were reported in 5% of patients who received meropenem; however, none were considered treatment-related. In a safety review of over 6000 patients treated with meropenem, one seizure was reported in patients with infections other than meningitis, which was determined by investigators not to be treatment-related. In patients with known predisposing factors for seizure activity, do not exceed recommended doses and monitor patients carefully. Adjust dosages for patients with reduced renal function. Continue anticonvulsant therapy in patients with known seizure disorders. If focal tremor, myoclonus, or seizures occur, patients should be evaluated neurologically, placed on anticonvulsant therapy if not already instituted, and the dosage of meropenem should be evaluated to determine whether a dosage reduction or discontinuation of therapy is warranted.

In a clinical trial of 200 neonates and infants < 91 days of age with suspected or confirmed complicated intra-abdominal infections, hyperglycemia and hypoglycemia were each reported in 3% of patients who received meropenem; hypokalemia was reported in 5%. Hypoglycemia and hypokalemia have also been reported in meropenem clinical trials in adults.

In general, cardiovascular adverse events are not common with meropenem therapy. In a clinical study of 200 neonates and infants < 91 days of age with suspected or confirmed complicated intra-abdominal infections, hypotension was noted in 3% of patients who received meropenem. During adult clinical trials, shock was reported in 1.2% of patients. Other cardiovascular adverse events that were reported in > 0.1% to <= 1% of adult patients include bradycardia, chest pain (unspecified), heart failure, cardiac arrest, hypertension, hypervolemia, myocardial infarction, peripheral edema, sinus tachycardia, and syncope. Peripheral vascular disorder was reported in > 1% of adult patients in trials.

Although not commonly reported in pediatric patients, respiratory adverse events have been associated with meropenem therapy. During clinical trials of immunocompetent adults treated for infections outside the CNS, apnea was reported in 1.3% of patients. Respiratory adverse events that were reported in > 0.1% to <= 1% of adult patients include asthma, increased cough, dyspnea, hypoxia, pulmonary edema, pulmonary embolism, pleural effusion, and respiratory disorder (unspecified).

Increased creatinine (> 1.7 mg/dL) was commonly reported (24/1000 infant days) in patients who received meropenem (n = 3479; 38,705 infant days) in a retrospective cohort study of 5566 infants < 3 months old. In other studies with meropenem in pediatric patients, renal adverse events have not been commonly observed; however, they have been reported in adults. Because dosage adjustments are necessary in patients with renal impairment, renal function should be periodically monitored during therapy to avoid toxicity. Renal adverse events reported in > 0.1% to <= 1% of adult patients in clinical trials with meropenem therapy include dysuria, renal failure (unspecified), and urinary incontinence. An increase in creatinine and BUN (azotemia) was reported in > 0.2% of adults patients in trials.

During clinical trials of meropenem in adults, pain (unspecified) was reported in 5.1% of patients and back pain and pelvic pain were reported in <= 1% but > 0.1% of patients. Accidental injury was noted in > 1% of patients. These events were not reported in pediatric patients.

Positive Coombs' tests have been reported in patients receiving meropenem. In patients receiving meropenem and undergoing hematologic testing, a positive Coombs' test should be considered as possibly being caused by the antibiotic.

A false-positive reaction for glucose in the urine has been observed in patients receiving beta-lactam antibiotics, including carbapenems, and using copper-reduction tests (e.g., Benedict's solution, Fehling's solution, and Clinitest tablets). This reaction, however, has not been observed with glucose oxidase tests (e.g., Tes-tape, Clinistix, Diastix).

Meropenem is contraindicated in patients with known meropenem hypersensitivity, a history of carbapenem hypersensitivity, or a previous anaphylactic reaction to beta-lactams. Because of the potential for cross-sensitivity, caution is advised in patients with cephalosporin hypersensitivity, penicillin hypersensitivity, or hypersensitivity to any beta-lactam antibiotic. Serious and occasionally fatal hypersensitivity reactions have been reported in patients receiving therapy with beta-lactams and are more likely to occur in persons with a history of sensitivity to multiple allergens.

Use meropenem cautiously in patients with brain lesions, a history of seizure disorder, or other neurological disease or condition that may lower the seizure threshold, such as head trauma or bacterial meningitis. Seizures have been reported with meropenem use and have occurred most commonly in patients with these types of conditions; however, the risk of seizures appears to be low and is thought to be less than the risk associated with imipenem; cilastatin. The risk of seizures increases in patients given meropenem doses higher than recommended (e.g., patients with compromised renal function) or patients receiving concomitant medications with seizure potential.

Use meropenem cautiously in patients with renal impairment or renal failure because the drug is primarily eliminated by the kidneys. These patients are at higher risk for developing seizures while receiving meropenem. Thrombocytopenia has also been reported in patients with renal function impairment, although clinical bleeding has not been reported. Dosage adjustments are required in patients with renal impairment.

Consider pseudomembranous colitis in patients presenting with diarrhea after antibacterial use. Careful medical history is necessary as pseudomembranous colitis has been reported to occur over 2 months after the administration of antibacterial agents. Almost all antibacterial agents, including meropenem, have been associated with pseudomembranous colitis or C. difficile-associated diarrhea (CDAD) which may range in severity from mild to life-threatening. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile.

Neuromotor impairment, including seizures, delirium, headache, and/or paresthesias may occur in patients receiving meropenem. Patients should use caution with activities requiring coordination and concentration (e.g., riding a bike, getting out of bed) until they are aware of the effects of the drug.

Avoid sodium-containing meropenem formulations in patients who are particularly sensitive to sodium intake (e.g., elderly, patients with heart failure) or who may require sodium restriction.

Description: Meropenem is an intravenous semisynthetic carbapenem antibiotic. Although similar to imipenem, meropenem does not require concomitant administration of a renal enzyme inhibitor (e.g., cilastatin). The spectrum of activity of meropenem is very similar to imipenem although meropenem is more active against Enterobacteriaceae, Haemophilus influenzae, gonococcus, and Pseudomonas aeruginosa. Meropenem is primarily used in children for the treatment of complicated intra-abdominal and skin and skin structure infections and for bacterial meningitis. It is also used for the treatment of febrile neutropenia and is considered a first-line agent for empiric therapy in high-risk patients requiring hospitalization. In neonates, meropenem has also been used for nosocomial pneumonia and gram-negative sepsis. Meropenem has been associated with lower seizure rates compared with imipenem. Meropenem is FDA-approved for use in pediatric patients as young as neonates.

Per the manufacturer, this drug has been shown to be active against most strains of the following microorganisms either in vitro and/or in clinical infections: Aeromonas hydrophila, Bacteroides fragilis, Bacteroides ovatus, Bacteroides thetaiotaomicron, Bacteroides uniformis, Bacteroides ureolyticus, Bacteroides vulgatus, Campylobacter jejuni, Citrobacter freundii, Citrobacter koseri, Clostridioides difficile, Clostridium perfringens, Cutibacterium acnes, Eggerthella lenta, Enterobacter cloacae, Enterococcus faecalis, Escherichia coli, Fusobacterium sp., Haemophilus influenzae (beta-lactamase negative), Haemophilus influenzae (beta-lactamase positive), Hafnia alvei, Klebsiella oxytoca, Klebsiella pneumoniae, Moraxella catarrhalis, Morganella morganii, Neisseria meningitidis, Parabacteroides distasonis, Pasteurella multocida, Peptostreptococcus sp., Porphyromonas asaccharolytica, Prevotella bivia, Prevotella intermedia, Prevotella melaninogenica, Proteus mirabilis, Proteus vulgaris, Pseudomonas aeruginosa, Serratia marcescens, Staphylococcus aureus (MSSA), Staphylococcus epidermidis, Streptococcus agalactiae (group B streptococci), Streptococcus pneumoniae, Streptococcus pyogenes (group A beta-hemolytic streptococci), Viridans streptococci
NOTE: The safety and effectiveness in treating clinical infections due to organisms with in vitro data only have not been established in adequate and well-controlled clinical trials.

For the treatment of intraabdominal infections, including peritonitis, appendicitis, intraabdominal abscess, and neonatal necrotizing enterocolitis:
-for the treatment of complicated community-acquired, healthcare-acquired, or hospital-acquired intraabdominal infections with adequate source control:
Intravenous dosage:
Neonates younger than 32 weeks gestation and 0 to 13 days: 20 mg/kg/dose IV every 12 hours for 7 to 10 days. Meropenem is an option for necrotizing enterocolitis.
Neonates younger than 32 weeks gestation and 14 days and older: 20 mg/kg/dose IV every 8 hours for 7 to 10 days. Meropenem is an option for necrotizing enterocolitis.
Neonates 32 weeks gestation and older and 0 to 13 days: 20 mg/kg/dose IV every 8 hours for 7 to 10 days. Meropenem is an option for necrotizing enterocolitis.
Neonates 32 weeks gestation and older and 14 days and older: 30 mg/kg/dose IV every 8 hours for 7 to 10 days. Meropenem is an option for necrotizing enterocolitis.
Infants, Children, and Adolescents: 20 mg/kg/dose (Max: 2 g/dose) IV every 8 hours for 3 to 7 days. Higher doses (40 mg/kg/dose IV every 8 hours) have been used in patients with severe infections. Complicated infections include peritonitis and appendicitis complicated by rupture, and intraabdominal abscess.
-for the treatment of complicated community-acquired, healthcare-acquired, or hospital-acquired intraabdominal infections with adequate source control due to resistant gram-negative organisms using extended infusion dosing*:
Intravenous dosage:
Infants, Children, and Adolescents: 20 to 40 mg/kg/dose (Max: 2 g/dose) IV administered over 3 to 4 hours every 8 hours for 3 to 7 days. Complicated infections include peritonitis and appendicitis complicated by rupture, and intraabdominal abscess.
-for the treatment of uncomplicated intraabdominal infections*:
Intravenous dosage:
Infants, Children, and Adolescents: 20 mg/kg/dose (Max: 2 g/dose) IV every 8 hours. Antibiotics should be discontinued within 24 hours. Uncomplicated infections include acute appendicitis without perforation, abscess, or local peritonitis; traumatic bowel perforations repaired within 12 hours; acute cholecystitis without perforation; and ischemic, non-perforated bowel.

For the treatment of meningitis and ventriculitis*, including infections due to resistant gram-negative organisms*:
-for the treatment of meningococcal meningitis as well as meningitis due to H. influenzae:
Intravenous dosage:
Neonates younger than 32 weeks gestation and 0 to 13 days*: 40 mg/kg/dose IV every 12 hours for 7 days.
Neonates younger than 32 weeks gestation and 14 days and older*: 40 mg/kg/dose IV every 8 hours for 7 days.
Neonates 32 weeks gestation and older*: 40 mg/kg/dose IV every 8 hours for 7 days.
Infants 1 to 2 months*: 40 mg/kg/dose IV every 8 hours for 7 days.
Infants, Children, and Adolescents 3 months to 17 years: 40 mg/kg/dose (Max: 2 g/dose) IV every 8 hours for 7 days.
-for the treatment of pneumococcal meningitis or ventriculitis*:
Intravenous dosage:
Neonates younger than 32 weeks gestation and 0 to 13 days*: 40 mg/kg/dose IV every 12 hours for 10 to 14 days.
Neonates younger than 32 weeks gestation and 14 days and older*: 40 mg/kg/dose IV every 8 hours for 10 to 14 days.
Neonates 32 weeks gestation and older*: 40 mg/kg/dose IV every 8 hours for 10 to 14 days.
Infants 1 to 2 months*: 40 mg/kg/dose IV every 8 hours for 10 to 14 days.
Infants, Children, and Adolescents 3 months to 17 years: 40 mg/kg/dose (Max: 2 g/dose) IV every 8 hours for 10 to 14 days.
-for the treatment of meningitis due to L. monocytogenes*:
Intravenous dosage:
Neonates younger than 32 weeks gestation and 0 to 13 days: 40 mg/kg/dose IV every 12 hours for at least 21 days.
Neonates younger than 32 weeks gestation and 14 days and older: 40 mg/kg/dose IV every 8 hours for at least 21 days.
Neonates 32 weeks gestation and older: 40 mg/kg/dose IV every 8 hours for at least 21 days.
Infants, Children, and Adolescents: 40 mg/kg/dose (Max: 2 g/dose) IV every 8 hours for at least 21 days.
-for the treatment of meningitis or ventriculitis due to methicillin-sensitive S. aureus (MSSA)*:
Intravenous dosage:
Neonates younger than 32 weeks gestation and 0 to 13 days: 40 mg/kg/dose IV every 12 hours for 10 to 14 days.
Neonates younger than 32 weeks gestation and 14 days and older: 40 mg/kg/dose IV every 8 hours for 10 to 14 days.
Neonates 32 weeks gestation and older: 40 mg/kg/dose IV every 8 hours for 10 to 14 days.
Infants, Children, and Adolescents: 40 mg/kg/dose (Max: 2 g/dose) IV every 8 hours for 10 to 14 days.
-for the treatment of meningitis or ventriculitis due to susceptible gram-negative organisms*:
Intravenous dosage:
Neonates younger than 32 weeks gestation and 0 to 13 days: 40 mg/kg/dose IV every 12 hours for 2 weeks beyond the first sterile CSF culture or at least 21 days, whichever is longer.
Neonates younger than 32 weeks gestation and 14 days and older: 40 mg/kg/dose IV every 8 hours for 2 weeks beyond the first sterile CSF culture or at least 21 days, whichever is longer.
Neonates 32 weeks gestation and older: 40 mg/kg/dose IV every 8 hours for 2 weeks beyond the first sterile CSF culture or at least 21 days, whichever is longer.
Infants, Children, and Adolescents: 40 mg/kg/dose (Max: 2 g/dose) IV every 8 hours for 10 to 21 days.
-for the treatment of meningitis or ventriculitis due to resistant gram-negative organisms*:
Intravenous dosage:
Neonates younger than 32 weeks gestation and 0 to 13 days: 40 mg/kg/dose IV administered over 3 hours every 12 hours for 2 weeks beyond the first sterile CSF culture or at least 21 days, whichever is longer.
Neonates younger than 32 weeks gestation and 14 days and older: 40 mg/kg/dose IV administered over 3 hours every 8 hours for 2 weeks beyond the first sterile CSF culture or at least 21 days, whichever is longer.
Neonates 32 weeks gestation and older: 40 mg/kg/dose IV administered over 3 hours every 8 hours for 2 weeks beyond the first sterile CSF culture or at least 21 days, whichever is longer.
Infants, Children, and Adolescents: 40 mg/kg/dose (Max: 2 g/dose) IV administered over 3 hours every 8 hours for 10 to 21 days.

For the treatment of complicated skin and skin structure infections, including cellulitis, erysipelas, necrotizing infections, and pyomyositis:
-for the treatment of severe complicated skin and skin structure infections, such as cellulitis and erysipelas:
Intravenous dosage:
Neonates younger than 32 weeks gestation and 0 to 13 days*: 20 mg/kg/dose IV every 12 hours for 5 to 14 days.
Neonates younger than 32 weeks gestation and 14 days and older*: 20 mg/kg/dose IV every 8 hours for 5 to 14 days.
Neonates 32 weeks gestation and older and 0 to 13 days*: 20 mg/kg/dose IV every 8 hours for 5 to 14 days.
Neonates 32 weeks gestation and older and 14 days and older*: 30 mg/kg/dose IV every 8 hours for 5 to 14 days.
Infants 1 to 2 months*: 10 to 20 mg/kg/dose IV every 8 hours for 5 to 14 days.
Infants, Children, and Adolescents 3 months to 17 years: 10 to 20 mg/kg/dose (Max: 1 g/dose) IV every 8 hours for 5 to 14 days.
-for the treatment of necrotizing infections of the skin, fascia, and muscle:
Intravenous dosage:
Neonates younger than 32 weeks gestation and 0 to 13 days*: 20 mg/kg/dose IV every 12 hours until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours for mixed necrotizing infections.
Neonates younger than 32 weeks gestation and 14 days and older*: 20 mg/kg/dose IV every 8 hours until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours for mixed necrotizing infections.
Neonates 32 weeks gestation and older and 0 to 13 days*: 20 mg/kg/dose IV every 8 hours until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours for mixed necrotizing infections.
Neonates 32 weeks gestation and older and 14 days and older*: 30 mg/kg/dose IV every 8 hours until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours for mixed necrotizing infections.
Infants 1 to 2 months*: 20 mg/kg/dose IV every 8 hours until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours for mixed necrotizing infections.
Infants, Children, and Adolescents 3 months to 17 years: 20 mg/kg/dose (Max: 1 g/dose) IV every 8 hours until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours for mixed necrotizing infections.
-for the treatment of pyomyositis:
Intravenous dosage:
Infants 1 to 2 months*: 10 to 20 mg/kg/dose IV every 8 hours for 14 to 21 days plus vancomycin in patients with underlying conditions.
Infants, Children, and Adolescents 3 months to 17 years: 10 to 20 mg/kg/dose (Max: 1 g/dose) IV every 8 hours for 14 to 21 days plus vancomycin in patients with underlying conditions.

For the treatment of bacteremia* and sepsis*:
-for the treatment of bacteremia*:
Intravenous dosage:
Neonates younger than 32 weeks gestation and 0 to 13 days: 20 mg/kg/dose IV every 12 hours. Consider 40 mg/kg/dose IV every 12 hours for severe infections due to Pseudomonas sp. or other more resistant organisms; pharmacokinetic data in neonates (including premature neonates) have suggested the need for the higher dose to achieve optimal pharmacodynamic targets for these infections.
Neonates younger than 32 weeks gestation and 14 days and older: 20 mg/kg/dose IV every 8 hours. Consider 40 mg/kg/dose IV every 8 hours for severe infections due to Pseudomonas sp. or other more resistant organisms; pharmacokinetic data in neonates (including premature neonates) have suggested the need for the higher dose to achieve optimal pharmacodynamic targets for these infections.
Neonates 32 weeks gestation and older and 0 to 13 days: 20 mg/kg/dose IV every 8 hours. Consider 40 mg/kg/dose IV every 8 hours for severe infections due to Pseudomonas sp. or other more resistant organisms; pharmacokinetic data in neonates (including premature neonates) have suggested the need for the higher dose to achieve optimal pharmacodynamic targets for these infections.
Neonates 32 weeks gestation and older and 14 days and older: 30 mg/kg/dose IV every 8 hours. Consider 40 mg/kg/dose IV every 8 hours for severe infections due to Pseudomonas sp. or other more resistant organisms; pharmacokinetic data in neonates (including premature neonates) have suggested the need for the higher dose to achieve optimal pharmacodynamic targets for these infections.
Infants, Children, and Adolescents: 20 to 40 mg/kg/dose (Max: 2 g/dose) IV every 8 hours.
-for the treatment of of sepsis*:
Intravenous dosage:
Neonates younger than 32 weeks gestation and 0 to 13 days: 20 mg/kg/dose IV every 12 hours. Consider 40 mg/kg/dose IV every 12 hours for severe infections due to Pseudomonas sp. or other more resistant organisms; pharmacokinetic data in neonates (including premature neonates) have suggested the need for the higher dose to achieve optimal pharmacodynamic targets for these infections.
Neonates younger than 32 weeks gestation and 14 days and older: 20 mg/kg/dose IV every 8 hours. Consider 40 mg/kg/dose IV every 8 hours for severe infections due to Pseudomonas sp. or other more resistant organisms; pharmacokinetic data in neonates (including premature neonates) have suggested the need for the higher dose to achieve optimal pharmacodynamic targets for these infections.
Neonates 32 weeks gestation and older and 0 to 13 days: 20 mg/kg/dose IV every 8 hours. Consider 40 mg/kg/dose IV every 8 hours for severe infections due to Pseudomonas sp. or other more resistant organisms; pharmacokinetic data in neonates (including premature neonates) have suggested the need for the higher dose to achieve optimal pharmacodynamic targets for these infections. Start within 1 hour for septic shock or within 3 hours for sepsis-associated organ dysfunction without shock. Duration of therapy is not well-defined and dependent on patient- and infection-specific factors. Assess patient daily for deescalation of antimicrobial therapy based on pathogen identification and/or adequate clinical response. Neonates younger than 37 weeks gestational age were excluded from the scope of the Surviving Sepsis Campaign guidelines.
Neonates 32 weeks gestation and older and 14 days and older: 30 mg/kg/dose IV every 8 hours. Consider 40 mg/kg/dose IV every 8 hours for severe infections due to Pseudomonas sp. or other more resistant organisms; pharmacokinetic data in neonates (including premature neonates) have suggested the need for the higher dose to achieve optimal pharmacodynamic targets for these infections. Start within 1 hour for septic shock or within 3 hours for sepsis-associated organ dysfunction without shock. Duration of therapy is not well-defined and dependent on patient- and infection-specific factors. Assess patient daily for deescalation of antimicrobial therapy based on pathogen identification and/or adequate clinical response. Neonates younger than 37 weeks gestational age were excluded from the scope of the Surviving Sepsis Campaign guidelines.
Infants, Children, and Adolescents: 20 to 40 mg/kg/dose (Max: 2 g/dose) IV every 8 hours. Start within 1 hour for septic shock or within 3 hours for sepsis-associated organ dysfunction without shock. Duration of therapy is not well-defined and dependent on patient- and infection-specific factors. Assess patient daily for deescalation of antimicrobial therapy based on pathogen identification and/or adequate clinical response.
-for the treatment of bacteremia* or sepsis* using extended infusion dosing*:
Intravenous dosage:
Infants, Children, and Adolescents: 40 mg/kg/dose (Max: 2 g/dose) IV administered over 3 to 4 hours every 8 hours. Start within 1 hour for septic shock or within 3 hours for sepsis-associated organ dysfunction without shock. Duration of therapy is not well-defined and dependent on patient- and infection-specific factors. Assess patient daily for deescalation of antimicrobial therapy based on pathogen identification and/or adequate clinical response.

For the empiric treatment of febrile neutropenia*:
Intravenous dosage:
Infants, Children, and Adolescents: 20 mg/kg/dose (Max: 1 g/dose) IV every 8 hours. Meropenem has been successfully used for the empiric treatment of febrile neutropenia in pediatric patients. Guidelines for the management of fever and neutropenia in cancer patients recommend monotherapy with an antipseudomonal beta-lactam or a carbapenem as empiric treatment in high-risk patients; addition of a second gram-negative antimicrobial agent (i.e., aminoglycoside, aztreonam) is recommended for patients who are clinically unstable, when a resistant infection is suspected, or for centers with high rates of resistant pathogens.

For the treatment of pulmonary exacerbations in patients with cystic fibrosis*:
Intravenous dosage:
Children and Adolescents: 40 mg/kg/dose (Max: 2 g/dose) IV every 8 hours. In clinical studies in patients with cystic fibrosis, meropenem alone and in combination with tobramycin has shown similar efficacy as ceftazidime for the treatment of acute pulmonary exacerbations due to Pseudomonas aeruginosa.
Intravenous dosage - Extended (3 to 4 hour) infusion:
Children and Adolescents: 40 mg/kg/dose (Max: 2 g/dose) IV administered over 3 to 4 hours every 8 hours. Extending the infusion duration to 3 to 4 hours has been shown to increase the likelihood of pharmacodynamic target achievement (%T above MIC), particularly for bacteria with higher MICs (2 mcg/mL or more), such as Pseudomonas. In clinical studies in patients with cystic fibrosis, meropenem alone and in combination with tobramycin has shown similar efficacy as ceftazidime for the treatment of acute pulmonary exacerbations due to Pseudomonas aeruginosa.

For the treatment of anthrax*:
-for the treatment of cutaneous anthrax* without aerosol exposure or signs and symptoms of meningitis:
Intravenous dosage:
Neonates 32 to 33 weeks gestation and 0 to 6 days: 13.3 mg/kg/dose IV every 8 hours for 7 to 10 days or until clinical criteria for stability are met; may consider step-down to oral therapy.
Neonates 32 to 33 weeks gestation and 7 days and older: 20 mg/kg/dose IV every 8 hours for 7 to 10 days or until clinical criteria for stability are met; may consider step-down to oral therapy.
Neonates 34 weeks gestation and older: 20 mg/kg/dose IV every 8 hours for 7 to 10 days or until clinical criteria for stability are met; may consider step-down to oral therapy.
Infants, Children, and Adolescents: 20 mg/kg/dose (Max: 2 g/dose) IV every 8 hours for 7 to 10 days or until clinical criteria for stability are met; may consider step-down to oral therapy.
-for the treatment of cutaneous anthrax* with aerosol exposure and without signs and symptoms of meningitis:
Intravenous dosage:
Neonates 32 to 33 weeks gestation and 0 to 6 days: 13.3 mg/kg/dose IV every 8 hours for 7 to 10 days or until clinical criteria for stability are met; may consider step-down to oral therapy. Transition to a postexposure prophylaxis regimen to complete a 60-day total treatment course.
Neonates 32 to 33 weeks gestation and 7 days and older: 20 mg/kg/dose IV every 8 hours for 7 to 10 days or until clinical criteria for stability are met; may consider step-down to oral therapy. Transition to a postexposure prophylaxis regimen to complete a 60-day total treatment course.
Neonates 34 weeks gestation and older: 20 mg/kg/dose IV every 8 hours for 7 to 10 days or until clinical criteria for stability are met; may consider step-down to oral therapy. Transition to a postexposure prophylaxis regimen to complete a 60-day total treatment course.
Infants, Children, and Adolescents: 20 mg/kg/dose (Max: 2 g/dose) IV every 8 hours for 7 to 10 days or until clinical criteria for stability are met; may consider step-down to oral therapy. Transition to a postexposure prophylaxis regimen to complete a 60-day total treatment course.
-for the treatment of systemic anthrax* without aerosol exposure, including those with signs and symptoms of meningitis, as part of combination therapy:
Intravenous dosage:
Neonates 32 to 33 weeks gestation and 0 to 6 days: 13.3 mg/kg/dose IV every 8 hours for at least 14 days; may consider step-down to oral therapy.
Neonates 32 to 33 weeks gestation and 7 days and older: 20 mg/kg/dose IV every 8 hours for at least 14 days; may consider step-down to oral therapy.
Neonates 34 weeks gestation and older: 20 mg/kg/dose IV every 8 hours for at least 14 days; may consider step-down to oral therapy.
Infants, Children, and Adolescents: 40 mg/kg/dose (Max: 2 g/dose) IV every 8 hours for at least 14 days; may consider step-down to oral therapy.
-for the treatment of systemic anthrax* with aerosol exposure, including those with signs and symptoms of meningitis, as part of combination therapy:
Intravenous dosage:
Neonates 32 to 33 weeks gestation and 0 to 6 days: 13.3 mg/kg/dose IV every 8 hours for at least 14 days; may consider step-down to oral therapy. Transition to a postexposure prophylaxis regimen to complete a 60-day total treatment course from illness onset.
Neonates 32 to 33 weeks gestation and 7 days and older: 20 mg/kg/dose IV every 8 hours for at least 14 days; may consider step-down to oral therapy. Transition to a postexposure prophylaxis regimen to complete a 60-day total treatment course from illness onset.
Neonates 34 weeks gestation and older: 20 mg/kg/dose IV every 8 hours for at least 14 days; may consider step-down to oral therapy. Transition to a postexposure prophylaxis regimen to complete a 60-day total treatment course from illness onset.
Infants, Children, and Adolescents: 40 mg/kg/dose (Max: 2 g/dose) IV every 8 hours for at least 14 days; may consider step-down to oral therapy.
Immunocompromised Infants, Children, and Adolescents: 40 mg/kg/dose (Max: 2 g/dose) IV every 8 hours for at least 14 days; may consider step-down to oral therapy. Transition to a postexposure prophylaxis regimen to complete a 60-day total treatment course from illness onset.

For the treatment of community-acquired pneumonia* (CAP), nosocomial pneumonia*, and pleural empyema*:
-for the treatment of community-acquired pneumonia (CAP)*:
Intravenous dosage:
Adolescents: 20 to 40 mg/kg/dose (Max: 2 g/dose) IV every 8 hours for 5 to 7 days.
-for the treatment of nosocomial pneumonia*:
Intravenous dosage:
Neonates younger than 32 weeks gestation and 0 to 13 days: 20 mg/kg/dose IV every 12 hours. Consider 40 mg/kg/dose IV every 12 hours for severe infections due to Pseudomonas sp. or other more resistant organisms; pharmacokinetic data in neonates (including premature neonates) have suggested the need for the higher dose to achieve optimal pharmacodynamic targets for these infections.
Neonates younger than 32 weeks gestation and 14 days and older: 20 mg/kg/dose IV every 8 hours. Consider 40 mg/kg/dose IV every 8 hours for severe infections due to Pseudomonas sp. or other more resistant organisms; pharmacokinetic data in neonates (including premature neonates) have suggested the need for the higher dose to achieve optimal pharmacodynamic targets for these infections.
Neonates 32 weeks gestation and older and 0 to 13 days: 20 mg/kg/dose IV every 8 hours. Consider 40 mg/kg/dose IV every 8 hours for severe infections due to Pseudomonas sp. or other more resistant organisms; pharmacokinetic data in neonates (including premature neonates) have suggested the need for the higher dose to achieve optimal pharmacodynamic targets for these infections.
Neonates 32 weeks gestation and older and 14 days and older: 30 mg/kg/dose IV every 8 hours. Consider 40 mg/kg/dose IV every 8 hours for severe infections due to Pseudomonas sp. or other more resistant organisms; pharmacokinetic data in neonates (including premature neonates) have suggested the need for the higher dose to achieve optimal pharmacodynamic targets for these infections.
Infants, Children, and Adolescents: 20 to 40 mg/kg/dose (Max: 2 g/dose) IV every 8 hours.
-for the treatment of hospital-acquired or postprocedural pleural empyema*:
Intravenous dosage:
Infants, Children, and Adolescents: 20 to 40 mg/kg/dose (Max: 2 g/dose) IV every 8 hours. Use in combination with vancomycin for at least 2 weeks after drainage and defervescence.
-for the treatment of pneumonia, including infections due to resistant gram-negative organisms, using extended-infusion dosing*:
Intravenous dosage:
Infants, Children, and Adolescents: 40 mg/kg/dose (Max: 2 g/dose) administered over 3 to 4 hours IV every 8 hours.

For the treatment of drug-resistant tuberculosis infection* paired with clavulanic acid as part of combination therapy:
Intravenous dosage:
Infants, Children, and Adolescents: 20 to 40 mg/kg/dose (Max: 2 g/dose) IV every 8 hours.

For the treatment of severe or complicated extensively drug-resistant typhoid fever*:
Intravenous dosage:
Infants, Children, and Adolescents: 20 mg/kg/dose (Max: 1 g/dose) IV every 8 hours for 10 to 14 days. Consider adding azithromycin for patients who do not improve.

For the treatment of bone and joint infections*, including osteomyelitis* and infectious arthritis*:
-for the treatment of osteomyelitis*:
Intravenous dosage:
Neonates younger than 32 weeks gestation and 0 to 13 days: 20 mg/kg/dose IV every 12 hours. Consider 40 mg/kg/dose IV every 12 hours for severe infections due to Pseudomonas sp. or other more resistant organisms; pharmacokinetic data in neonates (including premature neonates) have suggested the need for the higher dose to achieve optimal pharmacodynamic targets for these infections. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections.
Neonates younger than 32 weeks gestation and 14 days and older: 20 mg/kg/dose IV every 8 hours. Consider 40 mg/kg/dose IV every 8 hours for severe infections due to Pseudomonas sp. or other more resistant organisms; pharmacokinetic data in neonates (including premature neonates) have suggested the need for the higher dose to achieve optimal pharmacodynamic targets for these infections. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections.
Neonates 32 weeks gestation and older and 0 to 13 days: 20 mg/kg/dose IV every 8 hours. Consider 40 mg/kg/dose IV every 8 hours for severe infections due to Pseudomonas sp. or other more resistant organisms; pharmacokinetic data in neonates (including premature neonates) have suggested the need for the higher dose to achieve optimal pharmacodynamic targets for these infections. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections.
Neonates 32 weeks gestation and older and 14 days and older: 30 mg/kg/dose IV every 8 hours. Consider 40 mg/kg/dose IV every 8 hours for severe infections due to Pseudomonas sp. or other more resistant organisms; pharmacokinetic data in neonates (including premature neonates) have suggested the need for the higher dose to achieve optimal pharmacodynamic targets for these infections. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections.
Infants 1 to 2 months: 20 to 40 mg/kg/dose IV every 8 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections.
Infants, Children, and Adolescents 3 months to 17 years: 20 to 40 mg/kg/dose (Max: 2 g/dose) IV every 8 hours. Treat for 2 to 4 days or until clinically improved, followed by oral step-down therapy for a total duration of 3 to 4 weeks for uncomplicated cases. A longer course (i.e., 4 to 6 weeks or longer) may be needed for severe or complicated infections.
-for the treatment of infectious arthritis*:
Intravenous dosage:
Neonates younger than 32 weeks gestation and 0 to 13 days: 20 mg/kg/dose IV every 12 hours. Consider 40 mg/kg/dose IV every 12 hours for severe infections due to Pseudomonas sp. or other more resistant organisms; pharmacokinetic data in neonates (including premature neonates) have suggested the need for the higher dose to achieve optimal pharmacodynamic targets for these infections. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections.
Neonates younger than 32 weeks gestation and 14 days and older: 20 mg/kg/dose IV every 8 hours. Consider 40 mg/kg/dose IV every 8 hours for severe infections due to Pseudomonas sp. or other more resistant organisms; pharmacokinetic data in neonates (including premature neonates) have suggested the need for the higher dose to achieve optimal pharmacodynamic targets for these infections. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections.
Neonates 32 weeks gestation and older and 0 to 13 days: 20 mg/kg/dose IV every 8 hours. Consider 40 mg/kg/dose IV every 8 hours for severe infections due to Pseudomonas sp. or other more resistant organisms; pharmacokinetic data in neonates (including premature neonates) have suggested the need for the higher dose to achieve optimal pharmacodynamic targets for these infections. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections.
Neonates 32 weeks gestation and older and 14 days and older: 30 mg/kg/dose IV every 8 hours. Consider 40 mg/kg/dose IV every 8 hours for severe infections due to Pseudomonas sp. or other more resistant organisms; pharmacokinetic data in neonates (including premature neonates) have suggested the need for the higher dose to achieve optimal pharmacodynamic targets for these infections. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections.
Infants 1 to 2 months: 20 to 40 mg/kg/dose IV every 8 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections.
Infants, Children, and Adolescents 3 months to 17 years: 20 to 40 mg/kg/dose (Max: 2 g/dose) IV every 8 hours. Treat for 2 to 4 days or until clinically improved, followed by oral step-down therapy for a total duration of 2 to 3 weeks for uncomplicated cases. A longer course (i.e., 4 to 6 weeks or longer) may be needed for septic hip arthritis or severe or complicated infections.

For the treatment of bronchiectasis*:
-for the treatment of acute exacerbations of bronchiectasis*:
Intravenous dosage:
Infants, Children, and Adolescents: 20 to 40 mg/kg/dose (Max: 2 g/dose) IV every 8 hours for 14 days with or without an aminoglycoside.
-for the eradication of first or new isolates of Pseudomonas aeruginosa in patients with bronchiectasis*:
Intravenous dosage:
Infants, Children, and Adolescents: 20 to 40 mg/kg/dose (Max: 2 g/dose) IV every 8 hours for 14 days with or without a systemic aminoglycoside or inhaled antibiotics, followed by inhaled antibiotics for 4 to 12 weeks.

Maximum Dosage Limits:
-Neonates
Neonates younger than 32 weeks gestation and 0 to 13 days: 40 mg/kg/day IV is FDA-approved maximum; however, doses up to 80 mg/kg/day IV have been used off-label.
Neonates younger than 32 weeks gestation and 14 days and older: 60 mg/kg/day IV is FDA-approved maximum; however, doses up to 120 mg/kg/day IV have been used off-label.
Neonates 32 weeks gestation and older and 0 to 13 days: 60 mg/kg/day IV is FDA-approved maximum; however, doses up to 120 mg/kg/day IV have been used off-label.
Neonates 32 weeks gestation and older and 14 days and older: 90 mg/kg/day IV is FDA-approved maximum; however, doses up to 120 mg/kg/day IV have been used off-label.
-Infants
1 to 2 months: 90 mg/kg/day IV is FDA-approved maximum; however, doses up to 120 mg/kg/day IV have been used off-label.
3 to 11 months: 120 mg/kg/day IV.
-Children
120 mg/kg/day (Max: 6 g/day) IV.
-Adolescents
120 mg/kg/day (Max: 6 g/day) IV.

Patients with Hepatic Impairment Dosing
No dosage adjustment is needed.

Patients with Renal Impairment Dosing
The following dose adjustments are based on a usual recommended dose in children of 20-40 mg/kg/dose IV every 8 hours. These dose adjustments are consistent with the manufacturer's recommendations for adults with renal impairment.
CrCl > 50 ml/min/1.73 m2: No dose adjustment needed.
CrCl 30-50 ml/min/1.73 m2: 20-40 mg/kg/dose IV every 12 hours.
CrCl 10-29 ml/min/1.73 m2: 10-20 mg/kg/dose IV every 12 hours.
CrCl < 10 ml/min/1.73 m2: 10-20 mg/kg/dose IV every 24 hours.

Intermittent hemodialysis
10-20 mg/kg/dose IV every 24 hours after hemodialysis.

Peritoneal hemodialysis
10-20 mg/kg/dose IV every 24 hours.

Continuous renal replacement therapy (CRRT)
20-40 mg/kg/dose IV every 12 hours.

*non-FDA-approved indication

Monograph content under development

Mechanism of Action: Meropenem, a carbapenem beta-lactam antibiotic, is mainly bactericidal. It inhibits the third and final stage of bacterial cell wall synthesis by preferentially binding to specific penicillin-binding proteins (PBPs) that are located inside the bacterial cell wall. PBPs are responsible for several steps in the synthesis of the cell wall and are found in quantities of several hundred to several thousand molecules per bacterial cell. PBPs vary among different bacterial species. Meropenem readily penetrates the outer membrane of bacteria cells. After penetrating the bacterial cell wall, it binds to several PBPs. Meropenem has a high affinity for PBP-2, PBP-3, and PBP-4 of E. coli and P. aeruginosa and PBP-1, PBP-2, and PBP-4 of S. aureus. The rapid bactericidal activity of the carbapenems against gram-negative bacteria is associated with their great affinity for PBP-1a, PBP-1b, and PBP-2, rather than PBP-3 (the primary target for other beta-lactams). There are differences in preferential binding sites between the carbapenems. Imipenem preferentially binds to PBP-2, then PBP-1a and PBP-1b, with a weak affinity for PBP-3. Meropenem and ertapenem preferentially bind to PBP-2, then PBP-3, but also have a strong affinity for PBP-1a and PBP-1b. Doripenem has a strong affinity for PBP-3 in P. aeruginosa, PBP-1, PBP-2, and PBP-4 in S. aureus, and PBP-2 in E. coli. Cell lysis is mediated by bacterial cell wall autolytic enzymes (i.e., autolysins). The relationship between PBPs and autolysins is unclear, but it is possible that the beta-lactam antibiotic interferes with an autolysin inhibitor. Prevention of the autolysin response to beta-lactam antibiotic exposure through loss of autolytic activity (mutation) or inactivation of autolysin (low-medium pH) by the microorganism can lead to tolerance to the beta-lactam antibiotic resulting in bacteriostatic activity.

Beta-lactams, including meropenem, exhibit concentration-independent or time-dependent killing. In vitro and in vivo animal studies have demonstrated that the major pharmacodynamic parameter that determines efficacy for beta-lactams is the amount of time free (non-protein bound) drug concentrations exceed the minimum inhibitory concentration (MIC) of the organism. This microbiological killing pattern is due to the mechanism of action, which is acylation of PBPs. There is a maximum proportion of PBPs that can be acylated; therefore, once maximum acylation has occurred, killing rates cannot increase. Free beta-lactam concentrations do not have to remain above the MIC for the entire dosing interval. The percentage of time required for both bacteriostatic and maximal bactericidal activity is different for the various classes of beta-lactams. Carbapenems require free drug concentrations to exceed the MIC for 20% of the dosing interval for bacteriostatic activity and 40% of the dosing interval for maximal bactericidal activity. Carbapenems also are reported to have a post-antibiotic effect (PAE). PAE is defined as the suppression of bacterial growth that continues after the antibiotic concentration falls below the bacterial MIC. PAE has been reported to be 1.3 to 4 hours with imipenem, 4 to 5 hours with meropenem, and 1.5 hours with ertapenem.

The susceptibility interpretive criteria for meropenem are delineated by pathogen. Breakpoints for Enterobacterales, P. aeruginosa, Aeromonas sp., and Vibrio sp. are based on a dosage regimen of 1 g IV every 8 hours while breakpoints for Acinetobacter sp. are based on a dosage regimen of 1 g IV every 8 hours or 500 mg IV every 6 hours. The MICs are defined for Enterobacterales, Lactobacillus sp., Aeromonas sp., and Vibrio sp. as susceptible at 1 mcg/mL or less, intermediate at 2 mcg/mL, and resistant at 4 mcg/mL or more. The MICs are defined for Acinetobacter sp. and P. aeruginosa as susceptible at 2 mcg/mL or less, intermediate at 4 mcg/mL, and resistant at 8 mcg/mL or more. The MICs are defined for B. cepacia complex, other non-Enterobacterales, anaerobes, Aggregatibacter sp., and Bacillus sp. (excluding B. anthracis) and related genera as susceptible at 4 mcg/mL or less, intermediate at 8 mcg/mL, and resistant at 16 mcg/mL or more. The MICs are defined for H. influenzae, H. parainfluenzae, beta-hemolytic streptococci, S. viridans group, Aerococcus sp., and as E. rhusiopathiae susceptible at 0.5 mcg/mL or less. The MICs are defined for S. pneumoniae, Corynebacterium sp., and Lactococcus sp. as susceptible at 0.25 mcg/mL or less, intermediate at 0.5 mcg/mL, and resistant at 1 mcg/mL or more. The MICs are defined for N. meningitidis and L. monocytogenes as susceptible at 0.25 mcg/mL or less. The MICs are defined for Cardiobacterium sp., E. corrodens, Kingella sp., Gemella sp., Abiotrophia sp. and Granulicatella sp. as susceptible at 0.5 mcg/mL or less, intermediate at 1 mcg/mL, and resistant at 2 mcg/mL or more. Considering site of infection and appropriate meropenem dosing, oxacillin-susceptible staphylococci may be considered susceptible to meropenem.

There are 4 general mechanisms of carbapenem resistance including decreased permeability of the outer membrane of gram-negative organisms due to decreased porin channel production, decreased affinity for the target PBPs, over-expression of efflux pumps, and enzymatic degradation. Generally, carbapenems show stability to the majority of beta-lactamases, including AmpC beta-lactamases and extended-spectrum beta-lactamases (ESBLs). However, specific intrinsic or acquired beta-lactamases, generally called carbapenemases, can hydrolyze the carbapenems. These include some class A enzymes, several class D (OXA) enzymes, and the class B metallo-beta-lactamases. A deficiency in the outer membrane porin protein (Opr) D2 is associated with decreased carbapenem susceptibility in gram-negative bacteria. However, it is theorized that a combination of resistance mechanisms is required for significant carbapenem resistance. Decreased porin OprD in combination with activity of a chromosomal AmpC beta-lactamase is associated with imipenem, doripenem, and to a lesser extent meropenem resistance. Doripenem and meropenem may also require over-expression of efflux pumps for resistance to emerge; imipenem is not subject to efflux. Theoretically, efflux activity plus loss of membrane permeability is less likely to happen in vivo than AmpC beta-lactamase expression and loss of membrane permeability.

Pharmacokinetics: Meropenem is administered intravenously. Plasma protein binding is approximately 2%. After administration, it is distributed into most body fluids and tissues including cerebrospinal fluid (CSF). Higher CSF concentrations have been noted with increasing CSF white blood cells suggesting better penetration in the presence of meningeal inflammation. Meropenem is minimally metabolized to 1 microbiologically inactive metabolite. Approximately 70% (50% to 75%) of the dose is excreted unchanged in the urine over 12 hours and 28% is excreted as the microbiologically inactive metabolite; fecal elimination is minimal (2%). Urinary concentrations more than 10 mcg/mL are maintained for up to 5 hours in adults after a 500 mg dose. In adult patients with normal renal function, the elimination half-life is approximately 1 hour.

Affected cytochrome P450 isoenzymes and/or drug transporters: OAT1, OAT3
Meropenem is a substrate of OAT1 and OAT3 transporters in the proximal tubule of the kidney. Carbapenems have not shown the potential for CYP450 inhibition or induction.


-Route-Specific Pharmacokinetics
Intravenous Route
IV Push (over 5 minutes)
In healthy adults, the mean peak plasma concentration after a 500 mg dose is 45 mcg/mL (range, 18 to 65 mcg/mL) and after a 1 g dose is 112 mcg/mL (range, 83 to 140 mcg/mL).

Short Infusion (over 30 minutes)
In healthy adults, the mean peak plasma concentration after a 500 mg dose is 23 mcg/mL (range, 14 to 26 mcg/mL) and after a 1 g dose is 49 mcg/mL (range, 39 to 58 mcg/mL). Peak CSF concentrations in adult patients with uninflamed meninges have been reported to be 0.2 mcg/mL (range, 0.1 to 0.3 mcg/mL) 2 hours after a 1 g dose (data based on 4 samples). In pediatric patients (1 month to 15 years of age) with inflamed meninges who received meropenem 40 mg/kg IV, the mean peak CSF concentration was 3.3 mcg/mL (range, 0.9 to 6.5 mcg/mL) 3 hours after the dose.

Extended Infusion (over 3 to 4 hours)
Peak concentrations are achieved at the end of infusion for extended infusion administration. In a pharmacokinetic trial in neonates, a lower Cmax and longer time to Cmax were observed with extended infusions compared to shorter infusions; all other pharmacokinetic parameters were similar between the 2 infusion methods. Unlike in older populations studied, meropenem infusions over 30 minutes are optimal for achieving a 40% T more than the MIC in the majority of very low birth weight neonates.

Based on Monte Carlo simulations and population pharmacokinetic studies in children, an extended infusion (3 to 4 hours) may increase the likelihood of pharmacodynamic target achievement (amount of time free drug concentrations exceed the minimum inhibitory concentration (MIC) of the organism [%T more than the MIC]), particularly for bacteria with higher MICs (2 mcg/mL or more), such as Pseudomonas. In one study using population pharmacokinetic modeling based on data from 50 children, the probability of target attainment (PTA; 50% T more than the MIC) against Pseudomonas was increased from 60.7% with a 30-minute infusion to 89.9% with a 4-hour infusion (40 mg/kg/dose every 8 hours). In another study using a Monte Carlo simulation, a 3-hour meropenem infusion was necessary to obtain bactericidal PTAs for organisms at the susceptibility breakpoint. PTA (40% T more than the MIC) for Pseudomonas aeruginosa isolates at the susceptibility breakpoint increased from 33% with a 30-minute infusion to 97% with a 3-hour infusion.


-Special Populations
Pediatrics
Neonates and Infants younger than 3 months
Neonates have a larger volume of distribution and slower clearance of meropenem compared to adults. The clearance of meropenem is lowest in premature neonates and increases with postmenstrual age (PMA) and postnatal age (PNA). The elimination half-life in premature and term infants is approximately 3 to 4 hours and 2 hours, respectively. Due to slower meropenem clearance, the extended infusion method of administration (over 3 to 4 hours) does not appear to have the same benefit in very low birth weight (VLBW) neonates as is seen in older age groups; infusions over 30 minutes are optimal for achieving a 40% T more than the MIC in the majority of VLBW neonates.

The following pharmacokinetic parameters were derived from a population pharmacokinetic analysis of neonates and infants younger than 3 months:
Gestational Age younger than 32 weeks
Postnatal Age younger than 2 weeks (20 mg/kg every 12 hours)
Vd (L/kg) = 0.489
AUC (mcg x hour/mL) = 448
t 1/2 (hours) = 3.82
Postnatal Age 2 weeks and older (20 mg/kg every 8 hours)
Vd (L/kg) = 0.467
AUC (mcg x hour/mL) = 491
t 1/2 (hours) = 2.68

Gestational Age 32 weeks and older
Postnatal Age younger than 2 weeks (20 mg/kg every 8 hours)
Vd (L/kg) = 0.463
AUC (mcg x hour/mL) = 445
t 1/2 (hours) = 2.33
Postnatal Age 2 weeks and older (30 mg/kg every 8 hours)
Vd (L/kg) = 0.451
AUC (mcg x hour/mL) = 444
t 1/2 (hours) = 1.58

Infants 3 months and older and Children
As with many other drugs that are primarily renally eliminated, the clearance of meropenem is slightly lower in infants compared to older children and adults and increases with age. An elimination half-life of approximately 1.5 hours has been reported in children 3 months to younger than 2 years, decreasing to approximately 1 hour in children 2 to 5 years and 0.8 hours in children 6 to 12 years. A volume of distribution of approximately 0.4 L/kg has been reported in infants and young children (i.e., 3 months to 5 years) and 0.3 L/kg in older children (6 to 12 years).

Renal Impairment
The clearance of meropenem is significantly lower in patients with renal impairment; plasma clearance of meropenem correlates with creatinine clearance. In a pharmacokinetic study of 7 pediatric patients (1.4 to 17 years) with end-stage renal disease, the elimination half-life of meropenem off dialysis was approximately 7.3 hours (range, 4.9 to 11.7 hours). The elimination half-life on dialysis was approximately 1.3 hours (range, 1.1 to 1.7 hours). In adult patients with renal failure, the elimination half-life of meropenem is prolonged to approximately 10 to 14 hours.

Hemodialysis
Adult data have shown that approximately 50% of meropenem is removed by hemodialysis. In a pharmacokinetic study of 7 pediatric patients with end-stage renal disease, meropenem clearance was increased from 22.4 mL/minute/1.73 m2 to 90.7 mL/minute/1.73 m2 with hemodialysis. The elimination half-life on dialysis was approximately 1.3 hours (range, 1.1 to 1.7 hours).

Continuous renal replacement therapy (CRRT)
Data are unavailable in pediatric patients receiving meropenem and CRRT. In adult patients, the removal of meropenem has been shown to be approximately 13% to 53% by CVVHDF and 25% to 50% by CVVHF.