Dosage guidance:
Dosing: Infusion method: Dosing is presented based on the traditional infusion method over 30 minutes, unless otherwise specified.
Clinical considerations: A prolonged infusion strategy (ie, extended or continuous infusion) has a greater likelihood of attaining pharmacokinetic/pharmacodynamic targets and may offer clinical benefit in patients with severe infections or less susceptible pathogens (Ref).
Usual dosage range:
Traditional intermittent infusion method (over 30 minutes): IV: 500 mg every 6 hours or 1 to 2 g every 8 hours; 500 mg every 6 hours achieves comparable pharmacokinetic and pharmacodynamic parameters to 1 g every 8 hours (Ref).
Extended infusion method (off-label): IV: 1 to 2 g every 8 hours over 3 hours. May give a loading dose of 1 to 2 g over 30 minutes, especially when rapid attainment of therapeutic drug concentrations is desired (eg, sepsis) (Ref). Some experts recommend 2 g every 8 hours over 3 hours for treatment of infections caused by certain resistant organisms (eg, carbapenem-resistant Acinetobacter baumannii, carbapenem-resistant Enterobacterales) (Ref).
Continuous infusion method (off-label): IV: 2 g every 8 hours over 8 hours or 3 g every 12 hours over 12 hours (Ref). May give a loading dose of 1 to 2 g over 30 minutes, especially when rapid attainment of therapeutic drug concentrations is desired (eg, sepsis) (Ref).
Anthrax (off-label use): Note: Consult public health officials for event-specific recommendations.
Systemic (meningitis excluded), treatment (alternative agent): IV: 2 g every 8 hours as part of an appropriate combination regimen for 2 weeks or until clinically stable, whichever is longer (Ref).
Meningitis, treatment: IV: 2 g every 8 hours as part of an appropriate combination regimen for 2 to 3 weeks or until clinically stable, whichever is longer (Ref).
Note: Antitoxin should also be administered. Following the course of IV combination therapy for systemic anthrax infection (including meningitis), patients exposed to aerosolized spores require oral monotherapy to complete a total antimicrobial course of 60 days (Ref).
Bloodstream infection (gram-negative bacteremia) (off-label use): For empiric therapy of known or suspected gram-negative organisms (including Pseudomonas aeruginosa) or pathogen-directed therapy for organisms resistant to other agents.
IV: 1 g every 8 hours (Ref); for empiric therapy in patients with neutropenia, severe burns, sepsis, or septic shock, give as part of an appropriate combination regimen (Ref). Note: For critical illness or infection with an organism with an elevated minimum inhibitory concentration (MIC), some experts prefer the extended or continuous infusion method and/or increasing the dose to 2 g every 8 hours (Ref).
Duration of therapy: Usual duration is 7 to 14 days depending on the source, pathogen, extent of infection, and clinical response; a 7-day duration is recommended for patients with uncomplicated Enterobacteriaceae infection who respond appropriately to antibiotic therapy (Ref). Note: If neutropenic, extend treatment until afebrile for 2 days and neutrophil recovery (ANC ≥500 cells/mm3 and increasing) (Ref). For P. aeruginosa bacteremia in neutropenic patients, some experts treat for a minimum of 14 days and until recovery of neutrophils (Ref).
Cystic fibrosis, acute pulmonary exacerbation (off-label use): For empiric or targeted therapy for P. aeruginosa or other gram-negative bacilli.
IV: 2 g every 8 hours, most often given as part of an appropriate combination regimen (Ref). Note: Some experts prefer the extended or continuous infusion method to optimize exposure (Ref).
Duration of therapy: Duration is usually 10 to 14 days depending on clinical response (Ref).
Diabetic foot infection, moderate to severe (off-label use): As a component of empiric therapy in patients at risk for P. aeruginosa (eg, significant water exposure, macerated wound) or other gram-negative bacteria resistant to other agents (Ref).
IV: 1 g every 8 hours. Duration (which may include oral step-down therapy) is usually 2 to 4 weeks in the absence of osteomyelitis (Ref).
Intra-abdominal infection, health care–associated or high-risk community-acquired infection:
Note: For community-acquired infection, reserve for patients who cannot tolerate a beta-lactam or are at risk for infection with an extended-spectrum beta-lactamase (ESBL)-producing organism (eg, known colonization or prior infection with an ESBL-producing organism) (Ref).
Cholecystitis, acute uncomplicated: IV: 1 g every 8 hours; continue for 1 day after gallbladder removal or until clinical resolution in patients managed nonoperatively (Ref).
Other intra-abdominal infection (eg, cholangitis, complicated cholecystitis, appendicitis, diverticulitis, intra-abdominal abscess): IV: 1 g every 8 hours. Total duration of therapy (which may include transition to oral antibiotics) is 4 to 5 days following adequate source control (Ref). For diverticulitis or uncomplicated appendicitis managed without intervention, duration is 10 to 14 days (Ref); for perforated appendicitis managed with laparoscopic appendectomy, 2 to 4 days may be sufficient (Ref). Note: For patients who are critically ill or at high risk for infection with drug-resistant pathogens, some experts favor the extended or continuous infusion method (Ref).
Intracranial abscess (brain abscess, intracranial epidural abscess) or spinal epidural abscess (off-label use): As a component of empiric or directed therapy in patients at risk for P. aeruginosa or other resistant gram-negative bacteria (eg, neurosurgical or immunocompromised patients).
IV: 2 g every 8 hours as part of an appropriate combination regimen; duration generally ranges from 4 to 8 weeks for brain abscess and spinal epidural abscess and 6 to 8 weeks for intracranial epidural abscess (Ref).
Melioidosis (Burkholderia pseudomallei infection ) (off-label use): Initial intensive therapy: IV: 1 g every 8 hours for 10 to 14 days; a longer duration may be necessary depending on disease severity and site of infection (Ref). Some experts recommend 2 g every 8 hours for patients with neurological involvement and adding sulfamethoxazole and trimethoprim for patients with focal disease of the CNS, prostate, bone, joint, skin, or soft tissue (Ref). Note: Following the course of parenteral therapy, eradication therapy with oral antibiotics for ≥12 weeks is recommended (Ref).
Meningitis, bacterial: As a component of empiric therapy for health care-associated infections or infections in immunocompromised patients, or as pathogen-specific therapy for gram-negative bacteria resistant to other antibiotics (eg, P. aeruginosa, Acinetobacter spp.).
IV: 2 g every 8 hours. Treatment duration is 7 to 21 days depending on causative pathogen(s) and clinical response; 10 to 14 days is the minimum duration for gram-negative bacilli, although some experts prefer ≥21 days (Ref). Note: Consider use of an extended or continuous infusion for more resistant pathogens (Ref).
Neutropenic enterocolitis (typhlitis) (alternative agent) (off-label use): Note: Reserve for patients colonized or infected with a resistant gram-negative bacillus, such as an extended-spectrum beta-lactamase (ESBL)-producing organism (Ref).
IV: 1 g every 8 hours; continue until neutropenia is resolved and clinically improved, then switch to oral antibiotics. The total duration of antibiotics is generally 14 days following recovery from neutropenia (Ref).
Neutropenic fever, high-risk cancer patients (empiric therapy) (off-label use): Note: High-risk patients are those expected to have an ANC ≤100 cells/mm3 for >7 days or an ANC ≤100 cells/mm3 for any expected duration if there are ongoing comorbidities (eg, sepsis, mucositis, significant hepatic or renal dysfunction) (Ref); some experts use an ANC cutoff of <500 cells/mm3 to define high-risk patients (Ref).
IV: 1 g every 8 hours until afebrile for ≥48 hours and resolution of neutropenia (ANC ≥500 cells/mm3 and increasing) or standard duration for the specific infection identified, if longer than the duration of neutropenia. Additional agent(s) may be needed depending on clinical status (Ref). Some experts prefer the extended or continuous infusion method, particularly in those who are critically ill (Ref).
Peritonitis, treatment (patients undergoing peritoneal dialysis) (off-label route)
Note: Reserve for resistant gram-negative infections or polymicrobial infections. Intraperitoneal administration is preferred to IV administration unless the patient has sepsis. Consider a 25% dose increase (for intermittent or continuous dosing) in patients with significant residual renal function (urine output >100 mL/day) (Ref).
Intermittent (long dwell in automated peritoneal dialysis): Intraperitoneal: 500 mg added to the dialysate solution once daily; allow to dwell ≥6 hours (Ref).
Intermittent (short dwell in continuous ambulatory peritoneal dialysis): Intraperitoneal: 1 g added to the dialysate solution once daily; allow to dwell ≥6 hours (Ref).
Continuous (with every exchange) (dose is per liter of dialysate): Intraperitoneal: 125 mg/L with each exchange of dialysate (Ref).
Duration of therapy: ≥3 weeks for patients with adequate clinical response; for patients with no improvement after 5 days, remove catheter and treat with appropriate systemic antibiotics for 14 days after catheter removal (Ref).
Pneumonia (off-label use):
Community-acquired pneumonia: For empiric therapy of inpatients at risk of infection with a multidrug-resistant, gram-negative pathogen(s), including P. aeruginosa:
IV: 1 g every 8 hours as part of an appropriate combination regimen. Total duration (which may include oral step-down therapy) is a minimum of 5 days; a longer course may be required for patients with an immunocompromising condition, severe or complicated infection, or for P. aeruginosa infection. Patients should be clinically stable with normal vital signs prior to discontinuation (Ref).
Hospital-acquired or ventilator-associated pneumonia: For empiric therapy (often as part of an appropriate combination regimen) or pathogen-specific therapy for multidrug-resistant gram-negative pathogen(s) (eg, P. aeruginosa, Acinetobacter spp.):
IV: 1 g every 8 hours. Duration of therapy varies based on disease severity and response to therapy; treatment is typically given for 7 days (Ref). Note: Some experts prefer extended or continuous infusion for critical illness or when treating a susceptible organism with an elevated minimum inhibitory concentration (Ref).
Prosthetic joint infection (pathogen-directed therapy for multidrug-resistant gram-negative bacilli, including P. aeruginosa) (off-label use): IV: 1 g every 8 hours; duration varies, but is generally 4 to 6 weeks for patients who undergo resection arthroplasty (Ref).
Sepsis and septic shock (broad-spectrum empiric therapy, including P. aeruginosa) (off-label use): IV: 1 to 2 g every 8 hours in combination with other appropriate agent(s) (Ref). Initiate therapy as soon as possible once there is recognition of sepsis or septic shock. Duration is dependent on underlying source and patient response; short courses are preferred, when appropriate. Consider discontinuation if a noninfectious etiology is identified (Ref). Note: Some experts prefer the extended or continuous infusion method (Ref).
Skin and soft tissue infection, moderate to severe:
Note: For patients with necrotizing infections, select surgical site infections (intestinal, GU tract), or patients with or at risk for pathogens resistant to other agents, including P. aeruginosa (Ref).
IV: 1 g every 8 hours; often used as part of an appropriate combination regimen. Usual duration (including oral step-down therapy) is 5 to 14 days based on severity and clinical response; for necrotizing infection, continue until further debridement is not necessary, patient has clinically improved, and patient is afebrile for ≥48 hours (Ref).
Urinary tract infection, complicated (pyelonephritis or urinary tract infection with systemic signs/symptoms) (off-label use):
Note: Reserve for critically ill patients or for patients with risk factor(s) for MDR pathogens, including ESBL-producing organisms and P. aeruginosa (Ref).
IV: 1 g every 8 hours. Switch to an appropriate oral regimen once symptoms improve, if culture and susceptibility results allow. Total duration of therapy ranges from 5 to 14 days and depends on clinical response and the antimicrobial chosen to complete the regimen (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
Altered kidney function: IV:
CrCl (mL/minute) |
If the usual recommended dose is 1 g every 8 hoursc |
If the usual recommended dose is 2 g every 8 hoursc |
---|---|---|
aChoose usual recommended dose based on indication and disease severity (see "Dosing: Adult"), then choose the adjusted dose from that column based on the patient's estimated CrCl. | ||
bExpert opinion derived from manufacturer's labeling, Burger 2018, and Golightly 2013. | ||
cDose may be administered using the traditional intermittent infusion method (over 30 minutes) or extended infusion method (over 3 hours). Extending the infusion time to 3 hours increases the likelihood of pharmacodynamic target attainment, especially in severe infections or those caused by pathogens with an elevated minimum inhibitory concentration. May give the first dose over 30 minutes when rapid achievement of pharmacodynamic targets is desired (Ahmed 2018; Yu 2018). | ||
dDialyzable (38% over a 4-hour session [Rubino 2018]). When scheduled dose falls on a dialysis day, administer after dialysis (Heintz 2009). | ||
>50 to <130 |
No dosage adjustment necessary |
No dosage adjustment necessary |
>25 to ≤50 |
1 g every 12 hours |
2 g every 12 hours |
10 to ≤25 |
500 mg every 12 hours |
1 g every 12 hours |
<10 |
500 mg every 24 hours |
1 g every 24 hours |
Hemodialysis, intermittent (thrice weekly)d |
500 mg every 24 hours |
1 g every 24 hours |
Peritoneal dialysis |
500 mg every 24 hours |
1 g every 24 hours |
Augmented renal clearance (measured urinary CrCl ≥130 mL/minute/1.73 m2): Augmented renal clearance (ARC) is a condition that occurs in certain critically-ill patients without organ dysfunction and with normal serum creatinine concentrations. Young patients (<55 years of age) admitted post trauma or major surgery are at highest risk for ARC, as well as those with sepsis, burns, or hematologic malignancies. An 8- to 24-hour measured urinary CrCl is necessary to identify these patients (Ref). Therapeutic drug monitoring is recommended when available; doses >6 g/day have been required in some cases to achieve therapeutic (pharmacodynamic) targets (Ref).
IV:
Extended infusion method: 2 g loading dose (infused over 30 minutes) followed by 2 g infused over 3 hours every 8 hours (Ref).
Continuous infusion method: 1 g loading dose (infused over 30 minutes) followed by 6 g/day infused over 24 hours (administered either as 2 g every 8 hours over 8 hours, or 3 g every 12 hours over 12 hours) (Ref).
CRRT: Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Recommendations assume high-flux dialyzers and flow rates of ~1,500 to 3,000 mL/hour, unless otherwise noted. Appropriate dosing requires consideration of adequate drug concentrations (eg, site of infection) and consideration of initial loading doses. Close monitoring of response and adverse reactions due to drug accumulation is important.
CVVH/CVVHD/CVVHDF: IV:
Traditional intermittent infusion method (over 30 minutes): 1 g loading dose followed by 500 mg to 1 g every 8 hours (Ref).
Continuous infusion method: 1 g loading dose (infused over 30 minutes) followed by 1 g infused over 12 hours every 12 hours (Ref).
PIRRT (eg, slow-low efficiency hemodiafiltration): Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Appropriate dosing requires consideration of adequate drug concentrations (eg, site of infection) and consideration of initial loading doses. Close monitoring of response and adverse reactions due to drug accumulation is important.
Note: Dosing recommendations based on 8- to 10-hour daily PIRRT sessions with effluent rates of 4 to 5 L/hour (Ref) and 6 to 12 L/hour (Ref).
IV: Traditional intermittent infusion method (over 30 minutes): 1 g every 12 hours (Ref). In patients with residual diuresis (urine output ≥300 mL/day ) up to 2 g every 8 hours has been recommended (Ref).
The hepatic dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Matt Harris, PharmD, MHS, BCPS, FAST, Jeong Park, PharmD, MS, BCPS, FCCP, FAST, Arun Jesudian, MD, Sasan Sakiani, MD.
Note: Vd is increased in the presence of ascites; use of maximum recommended indication-specific doses should be considered in patients with ascites and severe infections to ensure adequate meropenem exposure (Ref). Use of any administration method (eg, traditional intermittent, extended, or continuous) may be utilized in patients with hepatic impairment.
Hepatic impairment prior to treatment initiation (Child-Turcotte-Pugh class A to C): No dosage adjustment necessary (Ref).
Dosage adjustment in patients with chronic, worsening hepatic function during treatment (eg, progression from baseline to Child-Turcotte-Pugh class A to C): No dosage adjustment necessary (Ref).
The recommendations for dosing in patients with obesity are based upon the best available evidence and clinical expertise. Senior Editorial Team: Jeffrey F. Barletta, PharmD, FCCM; Manjunath P. Pai, PharmD, FCP; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC.
Class 1, 2, or 3 obesity (BMI ≥30 kg/m2): Note: Use of traditional (intermittent) dosing in patients with obesity is generally appropriate (Ref). Estimate renal function with Cockcroft-Gault equation using adjusted body weight metric (Ref).
Traditional intermittent infusion method: IV: 2 g every 8 hours infused over 30 minutes (Ref). For patients with less severe infections or infections caused by non-Pseudomonas pathogens with a minimum inhibitory concentration ≤1 mg/L, may consider 1 g every 8 hours over 30 minutes (Ref).
Extended infusion method: Note: Preferred for patients with life-threatening infections, infections caused by resistant pathogens with minimum inhibitory concentrations approaching 2 mg/L, or CrCl ≥130 mL/minute/1.73 m2 to increase likelihood of achieving therapeutic concentrations (Ref).
IV: 2 g every 8 hours infused over 3 hours (Ref). Note: May give a loading dose of 2 g over 30 minutes when rapid attainment of therapeutic drug concentrations is necessary (eg, sepsis) (Ref).
Rationale for recommendations: There are limited data evaluating the effect of obesity on dosing requirements for meropenem. Data are available from hospitalized patients (eg, critically ill) predominantly at steady state concentrations. There appears to be minimal difference in trough concentrations or other pharmacokinetic parameters (eg, clearance, Vd) between patients without obesity and patients with varying levels of obesity (Ref). One large pharmacokinetic study evaluated meropenem continuous infusions in patients with BMI 25 to 81.6 kg/m2 and recommended calculation of drug clearance using Cockcroft-Gault estimated CrCl with adjusted body weight since this approach displayed a high probability of maintaining concentrations above minimum inhibitory concentration for the dosing interval (Ref). The effect of obesity on first-dose pharmacokinetics remains unknown.
Refer to adult dosing.
(For additional information see "Meropenem: Pediatric drug information")
General dosing, susceptible infection (non-CNS): Infants, Children, and Adolescents: IV: 20 mg/kg/dose every 8 hours; maximum dose: 1,000 mg/dose; extended infusions may be needed for infections due to isolates with elevated MICs (Ref).
Anthrax (Ref): Infants, Children, and Adolescents: Note: Consult public health officials for event-specific recommendations; after completion of therapy, initiate antimicrobial prophylaxis to complete an antimicrobial course of 60 days from onset of illness.
Systemic, excluding meningitis: IV: 20 mg/kg/dose every 8 hours as part of an appropriate combination regimen; may switch to oral follow-up therapy when signs and symptoms of active infection are resolved; complete 14 days of therapy or until clinical improvement, whichever is longer; maximum dose: 2,000 mg/dose.
Meningitis or disseminated infection in which meningitis cannot be ruled out: IV: 40 mg/kg/dose every 8 hours as part of an appropriate combination regimen for 2 to 3 weeks or until patient is clinically stable, whichever is longer; maximum dose: 2,000 mg/dose.
Cystic fibrosis, pulmonary exacerbation: Limited data available:
Traditional intermittent infusion method: Infants, Children, and Adolescents: IV: 40 mg/kg/dose every 8 hours; maximum dose: 2,000 mg/dose (Ref).
Extended infusion method: Children ≥8 years and Adolescents: IV: 40 mg/kg/dose every 8 hours infused over 3 hours; maximum dose: 2,000 mg/dose; dosing based on a pharmacokinetic and pharmacodynamic study in pediatric patients with cystic fibrosis (n=30, 8 to 17 years of age); extended infusions were more likely to obtain targets as compared to traditional infusions for minimum inhibitory concentrations ≥1 mg/L (Ref).
Note: Use of the continuous infusion method to optimize exposure has also been reported in adults and a single adolescent patient with cystic fibrosis (Ref).
Febrile neutropenia, empiric therapy: Limited data available: Infants, Children, and Adolescents: IV: 20 mg/kg/dose every 8 hours; maximum dose: 1,000 mg/dose (Ref).
Intra-abdominal infection, complicated: Note: IDSA guidelines recommend treatment duration of 4 to 7 days (Ref).
Infants 1 to <3 months:
GA <32 weeks: IV: 20 mg/kg/dose every 8 hours.
GA ≥32 weeks: IV: 30 mg/kg/dose every 8 hours.
Infants ≥3 months, Children, and Adolescents: IV: 20 mg/kg/dose every 8 hours; maximum dose: 1,000 mg/dose.
Meningitis: Infants (limited data available in infants <3 months of age), Children, and Adolescents: IV: 40 mg/kg/dose every 8 hours; maximum dose: 2,000 mg/dose (Ref); duration should be individualized based on patient characteristics and response; treatment duration for gram-negative bacilli is a minimum of 10 to 14 days; although some experts recommend ≥21 days and at least 14 days after first negative cerebrospinal fluid culture (Ref).
Skin and skin structure infection, complicated:
Manufacturer's labeling: Infants ≥3 months, Children, and Adolescents: IV: 10 mg/kg/dose every 8 hours; maximum dose: 500 mg/dose.
Severe or necrotizing infections: Infants, Children, and Adolescents: IV: 20 mg/kg/dose every 8 hours; maximum dose: 1,000 mg/dose (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Note: Dosing is based on pharmacokinetic parameters, limited pediatric studies, adult recommendations, and expert opinion (Ref).
Altered kidney function:
Infants, Children, and Adolescents: IV:
GFR (mL/minute/1.73 m2) |
If the usual recommended dose is 20 mg/kg/dose every 8 hours |
If the usual recommended dose is 40 mg/kg/dose every 8 hours |
---|---|---|
>50 mL/minute/1.73 m2 |
No dosage adjustment necessary |
No dosage adjustment necessary |
>25 to ≤50 mL/minute/1.73 m2 |
20 mg/kg/dose every 12 hours; maximum dose: 1,000 mg/dose |
40 mg/kg/dose every 12 hours; maximum dose: 2,000 mg/dose |
10 to ≤25 mL/minute/1.73 m2 |
10 mg/kg/dose every 12 hours; maximum dose: 500 mg/dose |
20 mg/kg/dose every 12 hours; maximum dose: 1,000 mg/dose |
<10 mL/minute/1.73 m2 |
10 mg/kg/dose every 24 hours; maximum dose: 500 mg/dose |
20 mg/kg/dose every 24 hours; maximum dose: 1,000 mg/dose |
Hemodialysis, intermittent: Dialyzable; 75% to 87% cleared during 3-hour dialysis session (Ref).
Infants, Children, and Adolescents: IV:
Note: On dialysis days, administer dose after dialysis. Usual maximum dose is 2,000 mg/dose; lower maximum doses may be appropriate for some indications.
Daily dosing: IV: 25 mg/kg/dose every 24 hours.
Every-48-hour dosing: IV: 40 mg/kg/dose every 48 hours.
Peritoneal dialysis:
Infants, Children, Adolescents: IV: 10 to 20 mg/kg/dose every 24 hours; maximum dose: 1,000 mg/dose (Ref).
CRRT:
Note: Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Appropriate dosing requires consideration of adequate drug concentrations (eg, site of infection) and consideration of initial loading doses. Close monitoring of response and adverse reactions due to drug accumulation is important; consider monitoring serum concentrations if available.
CVVH/CVVHD/CVVHDF: Infants, Children, and Adolescents: IV: 20 mg/kg/dose infused over 1 to 4 hours every 8 hours; higher doses of 40 mg/kg/dose every 8 hours may be necessary in some situations (eg, when MIC is ≥4 mg/L); maximum dose: 2,000 mg/dose (Ref).
Augmented renal clearance:
Note: Augmented renal clearance is a condition that occurs in certain critically ill patients without organ dysfunction and with normal serum creatinine concentrations that results in increased drug elimination. An 8- to 24-hour measured urinary CrCl is necessary to identify these patients (Bilbao-Meseguer 2018; Udy 2010). Due to minimal data in pediatric patients with augmented renal clearance, monitor safety and efficacy closely; consider monitoring serum concentrations if available.
GFR ≥160 mL/minute/1.73 m2: Children and Adolescents (Ref). Usual maximum dose: 2,000 mg/dose.
Extended infusion method (preferred): IV: 30 to 40 mg/kg/dose infused over 4 hours every 8 hours or 30 mg/kg/dose infused over 3 hours every 6 hours.
Traditional intermittent infusion method (over 30 minutes): IV: 40 mg/kg/dose every 6 hours.
Note: Continuous infusions may be appropriate depending on clinical situation.
No dosage adjustment necessary.
Carbapenems, including meropenem, may cause CNS toxicity. Meropenem is associated with a lower seizure risk than imipenem/cilastatin and therefore may be preferred for certain indications (Ref). Other noteworthy CNS effects caused by meropenem include delirium, continuous epileptiform discharges, and myoclonic jerking (Ref).
Mechanism: Postulated to be due to the antagonism of the GABAA receptor binding site. C2 side chain basicity may affect seizure risk of individual antimicrobials. N-acetylation or N-methylation of the C2 cyclopentene ring can alter the basicity substitution of this ring; meropenem is less basic than imipenem-cilastatin (Ref).
Risk factors:
• Preexisting neurologic conditions (eg, seizures, stroke, brain injury) (Ref)
• Drug accumulation in kidney impairment
Clostridioides difficile infection, including Clostridioides difficile associated diarrhea, has been reported with meropenem.
Onset: Varied; may start on the first day of antibiotic therapy or up to 3 months postantibiotic (Ref).
Risk factors:
• Antibiotic exposure (highest risk factor) (Ref)
• Type of antibiotic (carbapenems among highest risk) (Ref)
• Long durations in a hospital or other health care setting (recent or current) (Ref)
• Older adults (Ref)
• Immunocompromised conditions (Ref)
• A serious underlying condition (Ref)
• GI surgery/manipulation (Ref)
• Antiulcer medications (eg, proton pump inhibitors and H2 blockers) (Ref)
• Chemotherapy (Ref)
Immediate (including anaphylaxis, angioedema, and urticaria) (Ref) and delayed hypersensitivity reactions have been reported. Delayed hypersensitivity reactions range from skin rash to rare severe cutaneous adverse reactions (SCARs), including acute generalized exanthematous pustulosis (AGEP) (Ref), drug reaction with eosinophilia and systemic symptoms (Ref), Stevens-Johnson syndrome (Ref), and toxic epidermal necrolysis (Ref).
Mechanism: Non-dose-related; immunologic. Immediate hypersensitivity reactions (eg, anaphylaxis, angioedema, urticaria) are IgE-mediated (Ref). Delayed hypersensitivity reactions, including maculopapular rash and SCARs, are mediated by T-cells (Ref).
Onset: Immediate hypersensitivity reactions: Rapid; IgE-mediated reactions (anaphylaxis, angioedema, urticaria) generally occur within 1 hour of administration but may occur up to 6 hours after exposure (Ref). Delayed hypersensitivity reactions: Varied; maculopapular reactions typically occur 6 to 10 days after initiation. Other delayed hypersensitivity reactions, including SCARs, generally manifest after 1 to 8 weeks after initiation (although the onset of these reactions may be delayed up to 3 months) (Ref). AGEP has been reported to occur within 24 hours after initiation of meropenem (Ref).
Risk Factors:
• Previous hypersensitivity to penicillin/cephalosporins and carbapenems: Cross-reactivity between penicillins/cephalosporins and carbapenems is considered to be 1% or less (Ref); although cross-reactivity rates of 4.6% have been reported (Ref). Despite similar core structures, cross-reactions between carbapenems have not been well described (Ref). Some patients may tolerate alternative carbapenems following a hypersensitivity reaction to meropenem (Ref).
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
1% to 10%:
Cardiovascular: Acute myocardial infarction (≤1%), bradycardia (≤1%), cardiac failure (≤1%), chest pain (≤1%), hypertension (≤1%), hypotension (≤1%), peripheral edema (≤1%), peripheral vascular disease (>1%), pulmonary embolism (≤1%), shock (1%), syncope (≤1%), tachycardia (≤1%)
Dermatologic: Dermal ulcer (≤1%), diaphoresis (≤1%), pruritus (1%), skin rash (2% to 3%, includes diaper-area moniliasis in infants), urticaria (≤1%)
Endocrine & metabolic: Hypervolemia (≤1%), hypoglycemia (>1%)
Gastrointestinal: Abdominal pain (≤1%), anorexia (≤1%), constipation (1% to 7%), diarrhea (4% to 7%), dyspepsia (≤1%), enlargement of abdomen (≤1%), flatulence (≤1%), gastrointestinal disease (>1%), glossitis (1%), intestinal obstruction (≤1%), nausea (≤8%), oral candidiasis (≤2%), vomiting (≤4%)
Genitourinary: Dysuria (≤1%), pelvic pain (≤1%), urinary incontinence (≤1%), vulvovaginal candidiasis (≤1%)
Hematologic & oncologic: Anemia (≤6%), hypochromic anemia (≤1%)
Hepatic: Cholestatic jaundice (≤1%), hepatic failure (≤1%), jaundice (≤1%)
Infection: Sepsis (2%)
Local: Inflammation at injection site (2%)
Nervous system: Agitation (≤1%), anxiety (≤1%), chills (≤1%), confusion (≤1%), delirium (≤1%), depression (≤1%), dizziness (≤1%), drowsiness (≤1%), hallucination (≤1%), headache (2% to 8%), insomnia (≤1%), nervousness (≤1%), pain (≤5%), paresthesia (≤1%), seizure (≤1%)
Neuromuscular & skeletal: Asthenia (≤1%), back pain (≤1%)
Renal: Renal failure syndrome (≤1%)
Respiratory: Apnea (1%), asthma (≤1%), cough (≤1%), dyspnea (≤1%), hypoxia (≤1%), pharyngitis (>1%), pleural effusion (≤1%), pneumonia (>1%), pulmonary edema (≤1%), respiratory system disorder (≤1%)
Miscellaneous: Accidental injury (>1%), fever (≤1%)
<1%:
Cardiovascular: Local thrombophlebitis, localized phlebitis
Endocrine & metabolic: Edema at insertion site
Gastrointestinal: Gastrointestinal hemorrhage, melena
Hematologic & oncologic: Hemoperitoneum
Local: Injection site reaction, pain at injection site
Respiratory: Epistaxis
Frequency not defined:
Endocrine & metabolic: Hypokalemia, increased lactate dehydrogenase
Genitourinary: Hematuria
Hematologic & oncologic: Decreased partial thromboplastin time, decreased prothrombin time, eosinophilia, quantitative disorders of platelets
Postmarketing:
Dermatologic: Acute generalized exanthematous pustulosis (Ghoshal 2015), erythema multiforme, Stevens-Johnson syndrome (Sameed 2019), toxic epidermal necrolysis (Paquet 2002)
Gastrointestinal: Clostridioides difficile associated diarrhea (Xie 2018)
Hematologic & oncologic: Agranulocytosis, hemolytic anemia (Oka 2015), leukopenia, neutropenia (Van Tuyl 2016), positive direct Coombs test, positive indirect Coombs test, thrombocytopenia (Huang 2017; Khan 2014)
Hypersensitivity: Anaphylaxis (Gil-Serrano 2019), angioedema
Immunologic: Drug reaction with eosinophilia and systemic symptoms (Prados-Castano 2015)
Hypersensitivity to meropenem, other drugs in the same class, or any component of the formulation; patients who have experienced anaphylactic reactions to beta-lactams
Concerns related to adverse effects:
• Superinfection: Prolonged use may result in fungal or bacterial superinfection.
Disease-related concerns:
• Renal impairment: Use with caution in patients with renal impairment; dosage adjustment required in patients with CrCl ≤50 mL/minute. Thrombocytopenia has been reported in patients with renal impairment.
Special populations:
• Older adult: Lower doses (based upon renal function) are often required in the elderly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Solution Reconstituted, Intravenous [preservative free]:
Merrem: 500 mg (1 ea [DSC]); 1 g (1 ea [DSC]) [pyrogen free]
Generic: 500 mg (1 ea); 1 g (1 ea); 1 g/50 mL in NaCl 0.9% (1 ea); 500 mg/50 mL in NaCl 0.9% (1 ea)
Yes
Solution (reconstituted) (Meropenem Intravenous)
1 g (per each): $5.70 - $36.43
500 mg (per each): $2.64 - $18.21
Solution (reconstituted) (Meropenem-Sodium Chloride Intravenous)
1 gm/50 mL (per each): $35.89
500 mg/50 mL (per each): $24.60
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Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Reconstituted, Intravenous:
Generic: 500 mg (1 ea); 1 g (1 ea)
IV: Administer IV infusion over 15 to 30 minutes; IV bolus injection (5 to 20 mL) over 3 to 5 minutes
Extended infusion administration (off-label method): Administer over 3 hours (Ref). Note: Must consider meropenem's limited room temperature stability if using extended infusions.
Continuous infusion method (off-label method): IV: Administer every 8 hours over 8 hours or every 12 hours over 12 hours (Ref). Note: Must consider meropenem's limited room temperature stability if using extended infusions.
Parenteral:
IV push: Infants ≥3 months, Children, and Adolescents: Administer reconstituted solution (up to 1,000 mg) over 3 to 5 minutes; safety data are limited with 40 mg/kg doses up to a maximum of 2,000 mg.
Intermittent IV infusion: Further dilute reconstituted solution prior to administration.
Neonates and Infants <3 months: Administer as an IV infusion over 30 minutes.
Infants ≥3 months, Children, and Adolescents: Administer IV infusion over 15 to 30 minutes.
Extended IV infusion:
Neonates: Administer over 4 hours (Ref).
Children and Adolescents: Administer over 3 to 4 hours (Ref).
Intra-abdominal infection, health care-associated or high-risk community-acquired infection: Treatment of complicated appendicitis and peritonitis in adult and pediatric patients caused by viridans group streptococci, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Bacteroides fragilis, Bacteroides thetaiotaomicron, and Peptostreptococcus species.
Meningitis, bacterial: Treatment of bacterial meningitis in pediatric patients 3 months and older caused by Haemophilus influenzae, Neisseria meningitidis, and penicillin-susceptible isolates of Streptococcus pneumoniae.
Skin and skin structure infection, moderate to severe: Treatment of complicated skin and skin structure infections in adults and pediatric patients 3 months and older caused by Staphylococcus aureus (methicillin-susceptible isolates only), Streptococcus pyogenes, Streptococcus agalactiae, viridans group streptococci, Enterococcus faecalis (vancomycin-susceptible isolates only), P. aeruginosa, E. coli, Proteus mirabilis, B. fragilis, and Peptostreptococcus species.
Anthrax; Bloodstream infection (gram-negative bacteremia); Cystic fibrosis, acute pulmonary exacerbation; Diabetic foot infection, moderate to severe; Intracranial abscess (brain abscess, intracranial epidural abscess) and spinal epidural abscess; Melioidosis (Burkholderia pseudomallei infection); Neutropenic enterocolitis (typhlitis); Neutropenic fever, high-risk cancer patients; Osteomyelitis and/or discitis; Pneumonia; Prosthetic joint infection (pathogen-directed therapy for multidrug-resistant gram-negative bacilli, including P. aeruginosa); Sepsis and septic shock (broad-spectrum empiric therapy, including P. aeruginosa); Urinary tract infection, complicated (pyelonephritis or urinary tract infection with systemic signs/symptoms)
Meropenem may be confused with ertapenem, imipenem, metroNIDAZOLE
Substrate of OAT1/3
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Bacillus clausii: Antibiotics may diminish the therapeutic effect of Bacillus clausii. Management: Bacillus clausii should be taken in between antibiotic doses during concomitant therapy. Risk D: Consider therapy modification
BCG (Intravesical): Antibiotics may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination
BCG Vaccine (Immunization): Antibiotics may diminish the therapeutic effect of BCG Vaccine (Immunization). Risk C: Monitor therapy
Cholera Vaccine: Antibiotics may diminish the therapeutic effect of Cholera Vaccine. Management: Avoid cholera vaccine in patients receiving systemic antibiotics, and within 14 days following the use of oral or parenteral antibiotics. Risk X: Avoid combination
Fecal Microbiota (Live) (Oral): May diminish the therapeutic effect of Antibiotics. Risk X: Avoid combination
Fecal Microbiota (Live) (Rectal): Antibiotics may diminish the therapeutic effect of Fecal Microbiota (Live) (Rectal). Risk X: Avoid combination
Fexinidazole: May increase the serum concentration of OAT1/3 Substrates (Clinically Relevant). Management: Avoid use of fexinidazole with OAT1/3 substrates when possible. If combined, monitor for increased OAT1/3 substrate toxicities. Risk D: Consider therapy modification
Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies): Antibiotics may diminish the therapeutic effect of Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies). Risk C: Monitor therapy
Lactobacillus and Estriol: Antibiotics may diminish the therapeutic effect of Lactobacillus and Estriol. Risk C: Monitor therapy
Leflunomide: May increase the serum concentration of OAT1/3 Substrates (Clinically Relevant). Risk C: Monitor therapy
Nitisinone: May increase the serum concentration of OAT1/3 Substrates (Clinically Relevant). Risk C: Monitor therapy
Pretomanid: May increase the serum concentration of OAT1/3 Substrates (Clinically Relevant). Risk C: Monitor therapy
Probenecid: May increase the serum concentration of Meropenem. Risk X: Avoid combination
Sodium Picosulfate: Antibiotics may diminish the therapeutic effect of Sodium Picosulfate. Management: Consider using an alternative product for bowel cleansing prior to a colonoscopy in patients who have recently used or are concurrently using an antibiotic. Risk D: Consider therapy modification
Taurursodiol: May increase the serum concentration of OAT1/3 Substrates (Clinically Relevant). Risk X: Avoid combination
Teriflunomide: May increase the serum concentration of OAT1/3 Substrates (Clinically Relevant). Risk C: Monitor therapy
Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Management: Avoid use of live attenuated typhoid vaccine (Ty21a) in patients being treated with systemic antibacterial agents. Postpone vaccination until 3 days after cessation of antibiotics and avoid starting antibiotics within 3 days of last vaccine dose. Risk D: Consider therapy modification
Vaborbactam: May increase the serum concentration of OAT1/3 Substrates (Clinically Relevant). Risk C: Monitor therapy
Valproate Products: Carbapenems may decrease the serum concentration of Valproate Products. Management: Concurrent use of carbapenem antibiotics with valproic acid is generally not recommended. Alternative antimicrobial agents should be considered, but if a concurrent carbapenem is necessary, consider additional anti-seizure medication. Risk D: Consider therapy modification
Incomplete transplacental transfer of meropenem was found using an ex vivo human perfusion model (Hnat 2005).
Information related to the use of meropenem in pregnancy is limited (Yoshida 2013).
Meropenem is present in breast milk (Sauberan 2012).
Information related to the use of meropenem in breastfeeding women is limited. Based on information from one case report, the relative infant dose (RID) of meropenem is 0.18% compared to a weight-adjusted maternal dose of 3 g/day (Sauberan 2012).
In general, breastfeeding is considered acceptable when the RID of a medication is <10% (Anderson 2016; Ito 2000).
The RID of meropenem was calculated by the authors of the case report using a milk concentration of 0.48 mcg/mL and the mothers actual weight, providing an estimated daily infant dose via breast milk of 0.097 mg/kg/day. This milk concentration was obtained following maternal administration meropenem 1 g IV every 8 hours beginning postpartum day 6. Adverse events were not observed in the breastfed infant (Sauberan 2012).
According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother. In general, antibiotics that are present in breast milk may cause nondose-related modification of bowel flora. Monitor infants for GI disturbances, such as thrush or diarrhea (WHO 2002).
Some products may contain sodium.
Perform culture and sensitivity testing prior to initiating therapy. Monitor for signs of anaphylaxis during first dose. During prolonged therapy, monitor renal function, liver function, CBC. During outpatient use, monitor for neuromotor impairment and mental alertness.
Inhibits bacterial cell wall synthesis by binding to several of the penicillin-binding proteins, which in turn inhibit the final transpeptidation step of peptidoglycan synthesis in bacterial cell walls, thus inhibiting cell wall biosynthesis; bacteria eventually lyse due to ongoing activity of cell wall autolytic enzymes (autolysins and murein hydrolases) while cell wall assembly is arrested
Distribution: Penetrates into most tissues and body fluids including urinary tract, peritoneal fluid, bone, bile, lung, bronchial mucosa, muscle tissue, heart valves (Craig 1997; Nicolau 2008), and CSF (CSF penetration: Neonates and Infants ≤3 months of age: 70%).
Vd:
Preterm and Term Neonates and Infants ≤3 months of age: Median: ~0.47 L/kg (Smith 2011).
Children: 0.3 to 0.4 L/kg (Blumer 1995).
Adults: 15 to 20 L (Craig 1997); may be increased in patients who are critically ill (~35 L) (An 2023).
Protein binding: ~2%.
Metabolism: Hepatic; hydrolysis of beta-lactam bond to open beta-lactam form (inactive) (Craig 1997).
Half-life elimination:
Preterm and Term Neonates and Infants ≤3 months of age: Median: 2.7 hours; range: 1.6 to 3.8 hours (Smith 2011).
Infants and Children 3 months to 2 years of age: 1.5 hours.
Children 2 to 12 years of age and Adults: 1 hour.
Time to peak: Tissue: ~1 hour following infusion except in bile, lung, and muscle; CSF: 2 to 3 hours with inflamed meninges.
Excretion: Urine (~70% as unchanged drug; ~28% inactive metabolite); feces (2%).
Clearance:
Preterm and Term Neonates and Infants ≤3 months of age: 0.12 L/hour/kg (Smith 2011).
Infants and Children: 0.26 to 0.37 L/hour/kg (Blumer 1995).
Adults: 14.64 ± 4.55 L/hour (Chimata 1993); Adults with critical illness: 5.28 L/hour (median CrCl: 87 mL/minute) (An 2023).
Altered kidney function: Clearance correlates with CrCl in patients with renal impairment.
Older adult: Reduction in plasma clearance correlates with age-associated reduction in CrCl (Craig 1997).
Anti-infective considerations:
Parameters associated with efficacy: Time dependent, associated with time free drug concentration (fT) > minimum inhibitory concentration (MIC).
Organism specific:
Gram-negative organisms (eg, E. coli, P. aeruginosa): Goal: ≥40% fT > MIC (bactericidal) (Drusano 2003; Mattoes 2004; Nicolau 2008; Ong 2007).
Population specific:
Critically ill patients in the ICU: Minimum goal: ≥50% fT > MIC; preferred goal: ≥100% fT > MIC (Abdul-Aziz 2020; Al-Shaer 2020; Roberts 2014); some experts favor ≥100% fT >4 times the MIC (Guilhaumou 2019).
Patients with cystic fibrosis: Goal: >65% fT > MIC (Kuti 2018).
Expected drug exposure in patients with normal renal function:
Infants and Children 2 months to 12 years of age: Cmax (peak): IV:
30-minute infusion, single-dose, hospitalized patients:
20 mg/kg (maximum dose: 1 g): 56.9 mg/L (Blumer 1995).
40 mg/kg (maximum dose: 1 g): 92.1 mg/L (Blumer 1995).
Adults: Cmax (peak): IV:
30-minute infusion, healthy volunteers:
500 mg, single dose: ~23 mg/L (range: 14 to 26 mg/L).
1 g, single dose: ~49 mg/L (range: 39 to 58 mg/L).
3-hour infusion, critically ill patients:
1 g, post first dose: 15.36 ± 1.11 mg/L (Kothekar 2020).
1 g, steady state: 14.14 ± 2.02 mg/L (Kothekar 2020).
Postantibiotic effect: Minimal postantibiotic effect; varies based on the organism:
P. aeruginosa, S. aureus, and Enterobacteriaceae: <2 hours (Bowker 1996; Nadler 1989).
Parameters associated with toxicity: In a retrospective study, trough concentrations (Cmin) of >64.2 mg/L and >44.5 mg/L were associated with neurotoxicity or nephrotoxicity, respectively (Imani 2017).
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