Merrem

Carbapenems

 
Tuberculosis patients†
Directly observed therapy (DOT) is recommended for all children as well as adolescents and adults living with HIV.[34361] [34362] [61094]

Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.

Intermittent 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.[28347]
 
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.[28347]
 
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.[62808]
 
Intermittent IV Infusion
Infuse IV over 15 to 30 minutes.
Do not use in series connections.[28347] [62808]
 
Intermittent Extended IV Infusion†
NOTE: Administration by extended infusion is not FDA-approved.[28347]
Administering as an extended infusion (3- to 4-hour infusion) may increase the likelihood of pharmacodynamic target achievement in difficult to treat infections.[35478] [35479] [35480] [35481] [35482]
 
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).[28347]
 
Intermittent IV Push
Inject doses up to 1 g (Max concentration: 50 mg/mL) IV over 3 to 5 minutes.[28347]
 
Continuous Intravenous (IV) Infusion†
NOTE: Meropenem is not FDA-approved for administration as a continuous intravenous infusion.[28347]
Powder Vials for Injection
Reconstitution
Reconstitute 1 g vials with 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.[28347]
 
Dilution
3 g/day continuous IV infusion: Further dilute in 50 mL or 250 mL of 0.9% Sodium Chloride Injection and administer over 8 hours. For continuous infusion, administer a new infusion bag every 8 hours.[35484] [35485]
4 g/day continuous IV infusion: Further dilute in 100 mL of 0.9% Sodium Chloride Injection and administer over 6 hours. For continuous infusion, administer a new infusion bag every 6 hours.[35483]
3 g/day IV continuous infusion in ambulatory infusion pump with freezer packs: Reconstitute 1 g vial according to manufacturer recommendations by adding 20 mL of 0.9% Sodium Chloride Injection to each vial. Add 3 g (60 mL) to a 100 mL medication cassette reservoir and bring the final volume to 100 mL (final concentration, 30 mg/mL). Administer over 24 hours.[35488]
 
Stability of Continuous IV Infusion Solutions
Although specific stability studies were not completed, clinical studies comparing continuous infusion to intermittent infusions of meropenem suggest similar serum concentrations between the 2 groups and possibly more therapeutic benefit.[35484] [35485]
A stability study of meropenem diluted to 1 mg/mL and 20 mg/mL with Sterile Water for Injection or 0.9% Sodium Chloride Injection found that concentrations did not decrease below the allowable concentrations (95% of initial concentration) when stored at room temperature in polyvinyl chloride bags, but did fall below 95% of initial concentrations by 8 hours. However, when these same solutions were stored at 4 to 5 degrees C, the concentration was more than 95% of initial at 24 hours. When stored at room temperature at a concentration of 2.5 mg/mL in 0.9% Sodium Chloride Injection in glass vials, more than 95% of the initial concentration was remaining at 8 hours; however, when mixed in Sterile Water for Injection or 5% Dextrose Injection in glass vials, more than 95% of the concentration was NOT remaining after 4 hours and 3 hours, respectively. When diluted in 0.9% Sodium Chloride Injection and stored in the Baxter Minibag Plus system at room temperature, more than 95% of the initial concentration remained at 4 hours. When stored at 4 to 5 degrees C, however, more than 95% of the initial concentration remained after 24 hours (20 mg/mL concentration). When diluted in 5% Dextrose Injection and stored in the Baxter Minibag Plus system at 4 to 5 degrees C, more than 95% of the initial concentration remained after 8 hours (2.5 mg/mL concentration only).[35487]
Continuous ambulatory infusion pump with freezer packs: An open-label, multidose study in 7 cystic fibrosis patients analyzed the stability of meropenem administered via a continuous ambulatory infusion pump stored between 2 freezer packs designed to maintain a refrigerated temperature of 5 degrees C or less. Current manufacturer recommendations state that meropenem is stable in 0.9% Sodium Chloride Injection at 4 degrees C for 24 hours. The mean recovery of meropenem 30 mg/mL (starting concentration) at 12 to 16 hours was 102.9% with no cassette having a concentration of less than 90% of the original concentration. At 24 to 28 hours, the mean recovery of meropenem was 103.3%, but 1 cassette had a concentration of 86.3% of the initial concentration. The temperature of meropenem was not measured.[35488]

apnea / Delayed / 1.3-1.3
GI obstruction / Delayed / 0-1.0
ileus / Delayed / 0-1.0
hepatic failure / Delayed / 0-1.0
heart failure / Delayed / 0-1.0
cardiac arrest / Early / 0-1.0
myocardial infarction / Delayed / 0-1.0
bradycardia / Rapid / 0-1.0
pulmonary edema / Early / 0-1.0
pulmonary embolism / Delayed / 0-1.0
pleural effusion / Delayed / 0-1.0
renal failure (unspecified) / Delayed / 0-1.0
seizures / Delayed / 0.7-0.7
GI bleeding / Delayed / 0.5-0.5
azotemia / Delayed / 0.2
hemolytic anemia / Delayed / Incidence not known
agranulocytosis / Delayed / Incidence not known
angioedema / Rapid / Incidence not known
acute generalized exanthematous pustulosis (AGEP) / Delayed / Incidence not known
Stevens-Johnson syndrome / Delayed / Incidence not known
Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) / Delayed / Incidence not known
erythema multiforme / Delayed / Incidence not known
anaphylactoid reactions / Rapid / Incidence not known
toxic epidermal necrolysis / Delayed / Incidence not known
C. difficile-associated diarrhea / Delayed / Incidence not known

constipation / Delayed / 1.4-7.0
anemia / Delayed / 0.1-5.5
hyperbilirubinemia / Delayed / 0-5.0
candidiasis / Delayed / 0-3.1
delirium / Early / 0-1.0
hallucinations / Early / 0-1.0
confusion / Early / 0-1.0
depression / Delayed / 0-1.0
skin ulcer / Delayed / 0-1.0
jaundice / Delayed / 0-1.0
cholestasis / Delayed / 0-1.0
chest pain (unspecified) / Early / 0-1.0
peripheral edema / Delayed / 0-1.0
hypervolemia / Delayed / 0-1.0
hypertension / Early / 0-1.0
sinus tachycardia / Rapid / 0-1.0
hypotension / Rapid / 0-1.0
dyspnea / Early / 0-1.0
dysuria / Early / 0-1.0
urinary incontinence / Early / 0-1.0
glossitis / Early / 1.0-1.0
hypokalemia / Delayed / 0-1.0
phlebitis / Rapid / 0.8-0.8
melena / Delayed / 0.3-0.3
eosinophilia / Delayed / 0.2
elevated hepatic enzymes / Delayed / 0.2
hypoglycemia / Early / 1.0
leukopenia / Delayed / Incidence not known
thrombocytopenia / Delayed / Incidence not known
thrombocytosis / Delayed / Incidence not known
neutropenia / Delayed / Incidence not known
hypoxia / Early / Incidence not known
superinfection / Delayed / Incidence not known
hyperglycemia / Delayed / Incidence not known

nausea / Early / 0.8-7.8
headache / Early / 2.3-7.8
diarrhea / Early / 3.5-7.0
rash / Early / 1.6-6.0
vomiting / Early / 0.8-3.6
injection site reaction / Rapid / 0.2-2.4
pruritus / Rapid / 1.2-1.2
anorexia / Delayed / 0-1.0
dyspepsia / Early / 0-1.0
abdominal pain / Early / 0-1.0
flatulence / Early / 0-1.0
asthenia / Delayed / 0-1.0
anxiety / Delayed / 0-1.0
agitation / Early / 0-1.0
drowsiness / Early / 0-1.0
dizziness / Early / 0-1.0
paresthesias / Delayed / 0-1.0
insomnia / Early / 0-1.0
urticaria / Rapid / 0-1.0
syncope / Early / 0-1.0
cough / Delayed / 0-1.0
fever / Early / 0-1.0
chills / Rapid / 0-1.0
pelvic pain / Delayed / 0-1.0
back pain / Delayed / 0-1.0
epistaxis / Delayed / 0.2-0.2
leukocytosis / Delayed / 0.2
infection / Delayed / 1.0
pharyngitis / Delayed / 1.0
diaper dermatitis / Delayed / Incidence not known

Merrem

Rx

IV carbapenem antibiotic
Used for complicated intraabdominal and skin and skin structure infections and bacterial meningitis
May have a lower incidence of ADRs than imipenem

500 mg to 1 g IV every 8 hours for 5 to 14 days.

10 to 20 mg/kg/dose (Max: 1 g/dose) IV every 8 hours for 5 to 14 days.

10 to 20 mg/kg/dose IV every 8 hours for 5 to 14 days.

30 mg/kg/dose IV every 8 hours for 5 to 14 days.

20 mg/kg/dose IV every 8 hours for 5 to 14 days.

20 mg/kg/dose IV every 8 hours for 5 to 14 days.

20 mg/kg/dose IV every 12 hours for 5 to 14 days.

1 g IV every 8 hours for incisional surgical site infections of the intestinal or genitourinary tract.

1 g 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.

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.

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.

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.

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.

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.

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.

500 mg to 1 g IV every 8 hours for 14 to 21 days plus vancomycin in patients with underlying conditions.

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.

10 to 20 mg/kg/dose IV every 8 hours for 14 to 21 days plus vancomycin in patients with underlying conditions.

500 mg to 1 g IV every 8 hours for 7 to 14 days for moderate or severe infections in patients with risk factors for resistant gram negative rods, ischemic limb/necrotizing/gas forming infections, or a macerated ulcer or in a warm climate. Continue treatment for up to 28 days if infection is improving but is extensive and resolving slower than expected or if patient has severe peripheral artery disease.

2 g administered over 3 hours IV every 8 hours.

1 to 2 g IV every 8 hours for 3 to 7 days. Complicated infections include peritonitis and appendicitis complicated by rupture, and intraabdominal abscess.

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.

30 mg/kg/dose IV every 8 hours for 7 to 10 days. Meropenem is an option for necrotizing enterocolitis.

20 mg/kg/dose IV every 8 hours for 7 to 10 days. Meropenem is an option for necrotizing enterocolitis.

20 mg/kg/dose IV every 8 hours for 7 to 10 days. Meropenem is an option for necrotizing enterocolitis.

20 mg/kg/dose IV every 12 hours for 7 to 10 days. Meropenem is an option for necrotizing enterocolitis.

2 g administered over 3 hours IV every 8 hours for 3 to 7 days. Complicated infections include peritonitis and appendicitis complicated by rupture, and intraabdominal abscess.

20 to 40 mg/kg/dose (Max: 2 g/dose) administered over 3 to 4 hours IV every 8 hours for 3 to 7 days. Complicated infections include peritonitis and appendicitis complicated by rupture, and intraabdominal abscess.

1 to 2 g 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.

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.

1 g IV every 8 hours for at least 5 to 7 days.

1 g intraperitoneally every 24 hours for 21 to 28 days.

2 g IV every 8 hours for 7 days.

40 mg/kg/dose (Max: 2 g/dose) IV every 8 hours for 7 days.

40 mg/kg/dose IV every 8 hours for 7 days.

40 mg/kg/dose IV every 8 hours for 7 days. [35475] [53173]

40 mg/kg/dose IV every 8 hours for 7 days. [35475] [53173]

40 mg/kg/dose IV every 12 hours for 7 days. [35475] [53173]

2 g IV every 8 hours for 10 to 14 days.

40 mg/kg/dose (Max: 2 g/dose) IV every 8 hours for 10 to 14 days.

40 mg/kg/dose IV every 8 hours for 10 to 14 days.

40 mg/kg/dose IV every 8 hours for 10 to 14 days. [35475] [53173]

40 mg/kg/dose IV every 8 hours for 10 to 14 days. [35475] [53173]

40 mg/kg/dose IV every 12 hours for 10 to 14 days. [35475] [53173]

2 g IV every 8 hours for at least 21 days.

40 mg/kg/dose (Max: 2 g/dose) IV every 8 hours for at least 21 days.

40 mg/kg/dose IV every 8 hours for at least 21 days. [35475] [53173]

40 mg/kg/dose IV every 8 hours for at least 21 days. [35475] [53173]

40 mg/kg/dose IV every 12 hours for at least 21 days. [35475] [53173]

2 g IV every 8 hours for 10 to 21 days.

40 mg/kg/dose (Max: 2 g/dose) IV every 8 hours for 10 to 21 days.

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. [35475] [53173]

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. [35475] [53173]

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. [35475] [53173]

2 g IV administered over 3 hours every 8 hours for 10 to 21 days.

40 mg/kg/dose (Max: 2 g/dose) IV administered over 3 hours every 8 hours for 10 to 21 days.

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.

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.

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.

2 g IV every 8 hours for 10 to 14 days.

40 mg/kg/dose (Max: 2 g/dose) IV every 8 hours for 10 to 14 days.

40 mg/kg/dose IV every 8 hours for 10 to 14 days. [35475] [53173]

40 mg/kg/dose IV every 8 hours for 10 to 14 days. [35475] [53173]

40 mg/kg/dose IV every 12 hours for 10 to 14 days. [35475] [53173]

1 gram IV every 8 hours has been studied for febrile neutropenia. Guidelines recommend an antipseudomonal beta-lactam, such as meropenem, as a first line therapy option with or without an aminoglycoside and/or vancomycin as a treatment option for febrile neutropenia. Alternatively, 500 mg IV every 6 hours has shown similar clinical efficacy in hospitalized patients with a variety of infections (including febrile neutropenia) and based on Monte Carlo simulations, achieves pharmacodynamic endpoints equivalent to the manufacturer's recommended dose.

20 mg/kg/dose (Max: 1 g/dose) IV every 8 hours. 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.

2 g IV administered over 3 hours every 8 hours.

1 g IV every 8 hours for 7 to 14 days.

20 to 40 mg/kg/dose (Max: 2 g/dose) IV every 8 hours.[35489]

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.[35475] [53173]

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.[35475] [53173]

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.[35475] [53173]

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.[35475] [53173]

2 g IV administered over 3 hours every 8 hours for 7 to 14 days.

40 mg/kg/dose (Max: 2 g/dose) IV administered over 3 to 4 hours every 8 hours.[53167] [53168]

2 g IV every 8 hours. Start within 1 hour for septic shock or within 3 hours for possible sepsis 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.

20 to 40 mg/kg/dose (Max: 2 g/dose) IV every 8 hours.[35489] 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.[64985]

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.[35475] [53173] 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.[64985]

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.[35475] [53173] 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.[64985]

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.[35475] [53173]

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.[35475] [53173]

2 g IV administered over 3 hours every 8 hours. Start within 1 hour for septic shock or within 3 hours for possible sepsis 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.

40 mg/kg/dose (Max: 2 g/dose) IV administered over 3 to 4 hours every 8 hours.[53167] [53168] 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.[64985]

2 g IV every 8 hours in combination with appropriate antimicrobial therapy. Meropenem, in combination with a fluoroquinolone and protein synthesis inhibitor (i.e., linezolid, clindamycin), is the preferred therapy for the treatment of systemic anthrax in which meningitis cannot be excluded. Meropenem, in combination with a protein synthesis inhibitor (i.e., clindamycin, linezolid, doxycycline), is an alternative therapy for systemic anthrax infection without CNS involvement. For systemic infection in which meningitis cannot be excluded, treatment should continue for at least 2 to 3 weeks or until clinical criteria for improvement are met. For systemic infection without CNS involvement, treatment should continue for at least 14 days or until clinical criteria for improvement are met. Prophylaxis to complete an antimicrobial course of up to 60 days will be required in both cases.

20 mg/kg/dose (Max: 2 g/dose) IV every 8 hours for systemic infection without CNS involvement and 40 mg/kg/dose (Max: 2 g/dose) IV every 8 hours for systemic infection with documented/suspected CNS involvement, in combination with appropriate antimicrobial therapy. Meropenem, in combination with a fluoroquinolone and protein synthesis inhibitor (i.e., linezolid, clindamycin), is the preferred therapy for the treatment of systemic anthrax in which meningitis cannot be excluded. Meropenem, in combination with a protein synthesis inhibitor (i.e., clindamycin, linezolid, doxycycline), is an alternative therapy for systemic anthrax infection without CNS involvement. For systemic infection in which meningitis cannot be excluded, treatment should continue for at least 2 to 3 weeks or until clinical criteria for improvement are met. For systemic infection without CNS involvement, treatment should continue for at least 14 days or until clinical criteria for improvement are met. Prophylaxis to complete an antimicrobial course of up to 60 days will be required in both cases.

20 mg/kg/dose IV every 8 hours for systemic infection without CNS involvement and 30 mg/kg/dose IV every 8 hours for systemic infection with documented/suspected CNS involvement, in combination with appropriate antimicrobial therapy. Meropenem, in combination with a fluoroquinolone and protein synthesis inhibitor (i.e., linezolid, clindamycin), is the preferred therapy for the treatment of systemic anthrax in which meningitis cannot be excluded. Meropenem, in combination with a protein synthesis inhibitor (i.e., clindamycin, linezolid), is an alternative therapy for systemic anthrax infection without CNS involvement. For systemic infection in which meningitis cannot be excluded, treatment should continue for at least 2 to 3 weeks or until clinical criteria for improvement are met. For systemic infection without CNS involvement, treatment should continue for at least 14 days or until clinical criteria for improvement are met. Prophylaxis to complete an antimicrobial course of up to 60 days will be required in both cases.

20 mg/kg/dose IV every 8 hours for systemic infection with or without CNS involvement, in combination with appropriate antimicrobial therapy. Meropenem, in combination with a fluoroquinolone and protein synthesis inhibitor (i.e., linezolid, clindamycin), is the preferred therapy for the treatment of systemic anthrax in which meningitis cannot be excluded. Meropenem, in combination with a protein synthesis inhibitor (i.e., clindamycin, linezolid), is an alternative therapy for systemic anthrax infection without CNS involvement. For systemic infection in which meningitis cannot be excluded, treatment should continue for at least 2 to 3 weeks or until clinical criteria for improvement are met. For systemic infection without CNS involvement, treatment should continue for at least 14 days or until clinical criteria for improvement are met. Prophylaxis to complete an antimicrobial course of up to 60 days will be required in both cases.

13.3 mg/kg/dose IV every 8 hours for systemic infection without CNS involvement and 20 mg/kg/dose IV every 8 hours for systemic infection with documented/suspected CNS involvement, in combination with appropriate antimicrobial therapy. Meropenem, in combination with a fluoroquinolone and protein synthesis inhibitor (i.e., linezolid, clindamycin), is the preferred therapy for the treatment of systemic anthrax in which meningitis cannot be excluded. Meropenem, in combination with a protein synthesis inhibitor (i.e., clindamycin, linezolid), is an alternative therapy for systemic anthrax infection without CNS involvement. For systemic infection in which meningitis cannot be excluded, treatment should continue for at least 2 to 3 weeks or until clinical criteria for improvement are met. For systemic infection without CNS involvement, treatment should continue for at least 14 days or until clinical criteria for improvement are met. Prophylaxis to complete an antimicrobial course of up to 60 days will be required in both cases.

2 g administered over 3 hours IV every 8 hours for at least 7 days.

40 mg/kg/dose (Max: 2 g/dose) administered over 3 to 4 hours IV every 8 hours.[53167] [53168]

1 g IV every 8 hours for at least 7 days.[34362] [64669]

20 to 40 mg/kg/dose (Max: 2 g/dose) IV every 8 hours for 5 to 7 days.[34362] [35489]

1 g IV every 8 hours for 7 days.[61215]

20 to 40 mg/kg/dose (Max: 2 g/dose) IV every 8 hours.[35489]

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.[35475] [53173]

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.[35475] [53173]

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.[35475] [53173]

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.[35475] [53173]

1 g IV every 8 hours. Use in combination with vancomycin for at least 2 weeks after drainage and defervescence.

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.

1 g IV every 8 hours.

20 to 40 mg/kg/dose (Max: 1 g/dose) IV every 8 hours.

1 g IV every 8 hours for 10 to 14 days. Consider adding azithromycin for patients who do not improve.

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.

1 g IV every 8 hours for 3 to 7 days.

2 g IV administered over 3 hours every 8 hours for 7 to 14 days.

1 g IV every 8 hours for 7 to 14 days.

1 to 2 g IV administered over 3 hours every 8 hours for 7 to 14 days.

1 g IV every 8 hours for 7 to 14 days. A single dose prior to oral therapy may be used in patients not requiring hospitalization.

1 to 2 g IV administered over 3 hours every 8 hours for 7 to 14 days. A single dose prior to oral therapy may be used in patients not requiring hospitalization.

1 to 2 g IV every 8 hours for 7 to 14 days.

1 to 2 g IV administered over 3 hours every 8 hours for 7 to 14 days.

1 g IV every 8 hours for 6 weeks as first-line therapy for infections due to P. aeruginosa. May consider addition of ciprofloxacin or aminoglycoside for P. aeruginosa infections.

1 g IV every 8 hours for 4 to 6 weeks, which may be followed by long-term suppressive therapy. May consider addition of an aminoglycoside for P. aeruginosa infections; if aminoglycoside is in spacer and organism is aminoglycoside-susceptible, then double coverage is provided with IV or oral monotherapy.

2 g administered over 3 hours IV every 8 hours.

1 g IV every 8 hours for 4 to 6 weeks.

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.

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.

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.

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.

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.

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.

1 g IV every 8 hours. Treat for 1 to 2 weeks or until clinically improved, followed by oral step-down therapy for 2 to 4 weeks.

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.

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.

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.

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.

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.

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.

1 to 2 g IV every 8 hours for 14 days with or without an aminoglycoside.

20 to 40 mg/kg/dose (Max: 2 g/dose) IV every 8 hours for 14 days with or without an aminoglycoside.

1 to 2 g 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.

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.

1 to 2 g IV every 8 hours for at least 14 days.

†Indicates off-label use

No dosage adjustment is needed.

The following is for dosage adjustment in adults with renal impairment; there is no experience with this drug in children with renal impairment.
CrCl > 50 ml/min: no dose adjustment needed.
CrCl 26—50 ml/min: give the recommended dose every 12 hours.
CrCl 10—25 ml/min: give one-half the recommended dose every 12 hours.
CrCl < 10 ml/min: give one-half the recommended dose every 24 hours.
 
Intermittent hemodialysis
Meropenem and its metabolite are readily dialyzable and effectively removed by hemodialysis. Supplemental doses should be given after hemodialysis sessions.
 
Continuous hemodialysis (CVVHD, CVVHDF)
Meropenem and its metabolite are readily dialyzable and effectively removed by hemodialysis. Effective dosing regimens for patients receiving continuous hemodialysis vary from 500 mg IV every 12 hours to 1 g IV every 8 hours. Conflicting data exist regarding the most appropriate meropenem dosing regimen for patients receiving continuous hemodialysis. Differing operational characteristics of continuous hemodialysis (e.g., dialysate flow rate, membrane or filter type) at various centers involved in the studies and whether the goal of the study was to treat infections caused by susceptible or intermediate microorganisms may explain the variable dosing recommendations for continuous hemodialysis.

Oral Contraceptives: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Probenecid: (Moderate) Concurrent administration of meropenem with probenecid is not recommended as probenecid inhibits the renal excretion of meropenem by competing for active tubular secretion. After administration of probenecid with meropenem, the mean systemic exposure of meropenem increased by 56% and the half-life increased by 38%. Meropenem is a substrate of OAT1 and OAT3 transporters in the proximal tubule of the kidney, and probenecid is an inhibitor of these drug transporters.
Probenecid; Colchicine: (Moderate) Concurrent administration of meropenem with probenecid is not recommended as probenecid inhibits the renal excretion of meropenem by competing for active tubular secretion. After administration of probenecid with meropenem, the mean systemic exposure of meropenem increased by 56% and the half-life increased by 38%. Meropenem is a substrate of OAT1 and OAT3 transporters in the proximal tubule of the kidney, and probenecid is an inhibitor of these drug transporters.
Sodium picosulfate; Magnesium oxide; Anhydrous citric acid: (Major) Prior or concomitant use of antibiotics with sodium picosulfate; magnesium oxide; anhydrous citric acid may reduce efficacy of the bowel preparation as conversion of sodium picosulfate to its active metabolite bis-(p-hydroxy-phenyl)-pyridyl-2-methane (BHPM) is mediated by colonic bacteria. If possible, avoid coadministration. Certain antibiotics (i.e., tetracyclines and quinolones) may chelate with the magnesium in sodium picosulfate; magnesium oxide; anhydrous citric acid solution. Therefore, these antibiotics should be taken at least 2 hours before and not less than 6 hours after the administration of sodium picosulfate; magnesium oxide; anhydrous citric acid solution.
Valproic Acid, Divalproex Sodium: (Major) Avoid concomitant carbapenem and valproic acid use. Consider alternative antibacterial therapies other than carbapenems to treat infections in patients whose seizures are well controlled with valproic acid or divalproex sodium. If coadministered, monitor valproic acid concentrations. Coadministration of carbapenems with valproic acid or divalproex sodium may reduce the serum concentration of valproic acid potentially increasing the risk of breakthrough seizures. Carbapenems may inhibit the hydrolysis of valproic acid's glucuronide metabolite (VPA-g) back to valproic acid, thus decreasing valproic acid serum concentrations.
Warfarin: (Moderate) The concomitant use of warfarin with many classes of antibiotics, including carbapenems, may result in an increased INR thereby potentiating the risk for bleeding. Inhibition of vitamin K synthesis due to alterations in the intestinal flora may be a mechanism; however, concurrent infection is also a potential risk factor for elevated INR. Monitor patients for signs and symptoms of bleeding. Additionally, increased monitoring of the INR, especially during initiation and upon discontinuation of the antibiotic, may be necessary.

Meropenem/Merrem Intravenous Inj Pwd F/Sol: 1g, 500mg

3 g/day IV is FDA-approved maximum; however, doses up to 6 g/day IV have been used off-label.

3 g/day IV is FDA-approved maximum; however, doses up to 6 g/day IV have been used off-label.

120 mg/kg/day (Max: 6 g/day) IV.

120 mg/kg/day (Max: 6 g/day) IV.

3 to 11 months: 120 mg/kg/day IV.
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.

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.
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 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 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.

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.[28347] 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.[28347] [35440] 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).[35441] 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.[35441] 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.[51465]
 
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.[34145] [34143] [35436] [35437] [35438] [35439] 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.[35439] 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.[35436] [35437] [35438] 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.[35441]
 
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.[28347] 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.[28347] [35440] [35441] 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.[35440] [35441]

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% excreted as the 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.

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)
Based on Monte Carlo simulations and population pharmacokinetic studies in adults, 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 greater), such as Pseudomonas. In 1 study, the 3-hour infusion achieved the pharmacodynamic target 99% of the time for bacteriostatic exposure and 93% of the time for bactericidal exposure. Additionally, this regimen had a higher probability of achieving the pharmacodynamic target than traditionally infused meropenem for intermediately resistant pathogens with an MIC of 8 mcg/mL (62% vs. less than 40%). Another study demonstrated that 2 g IV administered over 3 hours every 8 hours in combination with an aminoglycoside was able to suppress resistance and achieve the bacteriocidal pharmacodynamic parameter 79% of the time.
 
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 greater), such as Pseudomonas. In 1 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.
 
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.
 
Continuous Infusion
To maximize the likelihood of pharmacodynamic target achievement, several studies, including population pharmacokinetic studies, and Monte Carlo simulations have reviewed meropenem as a continuous intravenous infusion (CI). A retrospective cohort study of 89 patients compared intermittent meropenem dosing (1 g IV every 6 hours) to CI dosing (4 g/day IV, given as four 1 g infusions, each over 6 hours). The CI group had a greater clinical cure rate (90.47% vs. 59.7%, p less than 0.001). In a randomized study of 10 patients, CI meropenem (500 mg IV load over 3 minutes, then 3 g/day IV, given as three 1 g infusions, each over 8 hours) achieved higher median trough concentrations than intermittent dosing (1.5 g IV load, then 1 g IV every 8 hours). Another prospective crossover study of 15 patients determined CI meropenem (2 g IV load, then 3 g/day IV, given as three 1 g infusions, each over 8 hours) was equivalent to intermittent dosing (2 g IV every 8 hours), but required a smaller total daily dose.

There are insufficient data to establish whether there is a drug-associated risk of major birth defects or miscarriages with meropenem use in human pregnancy. No teratogenic effects have been demonstrated in animals given meropenem intravenously at doses up to 3.2 times the maximum recommended human dose (MRHD) based on body surface area comparison.[28347] [62808]

Meropenem is excreted in human breast milk; however, no information is available on the effects of meropenem on the breast-fed child or on milk production. Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for meropenem and any potential adverse effects on the breast-fed child from meropenem or the underlying maternal condition. In case reports in which meropenem was used during breast-feeding, no adverse events were reported in the infants.