Meropenem – Uses, Dosage, Side Effects, Interactions

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

The bactericidal activity of meropenem results from the inhibition of cell wall synthesis. Meropenem readily penetrates the cell wall of most Gram-positive and Gram-negative bacteria to reach penicillin-binding-protein (PBP) targets. Its strongest affinities are toward PBPs 2, 3, and 4 of Escherichia coli and Pseudomonas aeruginosa; and PBPs 1, 2, and 4 of Staphylococcus aureus. Bactericidal concentrations (defined as a 3 log10 reduction in cell counts within 12 to 24 hours) are typically 1-2 times the bacteriostatic concentrations of meropenem, with the exception of Listeria monocytogenes, against which lethal activity is not observed.

For use as single agent therapy for the treatment of the following infections when caused by susceptible isolates of the designated microorganisms:

• complicated skin and skin structure infections due to Staphylococcus aureus (b-lactamase and non-b-lactamase producing, methicillin-susceptible isolates only), Streptococcus pyogenes, Streptococcus agalactiae, viridans group streptococci, Enterococcus faecalis (excluding vancomycin-resistant isolates), Pseudomonas aeruginosa, Escherichia coli, Proteus mirabilis, Bacteroides fragilis, and Peptostreptococcus species;
• complicated appendicitis and peritonitis caused by viridans group streptococci, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Bacteroides fragilis, B. thetaiotaomicron, and Peptostreptococcus species. Also for use in the treatment of bacterial meningitis caused by Streptococcus pneumoniae, Haemophilus influenzae (b-lactamase and non-b-lactamase-producing isolates), and Neisseria meningitidis.
• Treatment of bacterial sepsis, Treatment of bacterial meningitis
• Bacterial Infections
• Complicated Intra-Abdominal Infections
• Meningitis, Bacterial
• Complicated Bacterial Urinary Tract Infections
• Complicated skin infection bacterial
• Nosocomial Pneumonia
• Intraabdominal Infection

• Anti-Bacterial Agents
• Meropenem is used for the treatment of intra-abdominal infections, including complicated appendicitis and peritonitis, caused by susceptible bacteria. The drug may be used as monotherapy for the treatment of intra-abdominal infections caused by susceptible viridans streptococci, Escherichia coli, Klebsiella pneumonia, Pseudomonas aeruginosa, Bacteroides fragilis, B. thetaiotaomicron, or Peptostreptococcus. Because meropenem has a broad spectrum of antibacterial activity, the drug may be used empirically to treat intra-abdominal infections before identification of the causative organism.
• Meropenem is used for the treatment of bacterial meningitis caused by susceptible Streptococcus pneumoniae, Haemophilus influenzae (including beta-lactamase-producing strains), or Neisseria meningitidis in children 3 months of age and older.
• The drug also is used in the treatment of meningitis in adults.
• Meropenem is considered a drug of choice for empiric treatment of nosocomial pneumonia.
• Meropenem is used in the treatment of respiratory tract infections, including community-acquired pneumonia (CAP) and nosocomial pneumonia, caused by susceptible bacteria.
• Meropenem is used for the treatment of complicated skin and skin structure infections caused by susceptible Staphylococcus aureus (including beta-lactamase-producing strains, but not oxacillin-resistant [methicillin-resistant] strains), S. pyogenes (group A beta-hemolytic streptococci), S. agalactiae (group B streptococci), viridans streptococci, Enterococcus faecalis (except vancomycin-resistant strains), Ps. aeruginosa, E. coli, Proteus mirabilis, B. fragilis, or Peptostreptococcus.
• Meropenem has been used for the treatment of septicemia caused by susceptible bacteria.
• Although safety and efficacy have not been established, meropenem has been used for the treatment of complicated urinary tract infections caused by susceptible bacteria.
• Meropenem is used as an alternative to imipenem or ceftazidime for the treatment of melioidosis caused by Burkholderia pseudomallei.
• Meropenem is used for the treatment of infections caused by Bacillus cereus. Although vancomycin is considered the drug of choice, carbapenems (imipenem or meropenem) or clindamycin are alternatives.
• Although data are not available regarding in vivo activity of meropenem against Bacillus anthracis, the drug has in vitro activity against the organism and it has been suggested that meropenem is one of several anti-infectives that can be included in multiple-drug regimens used for the treatment of anthrax, including inhalational anthrax and anthrax meningitis.
• Meropenem is used alone or in conjunction with other anti-infectives for empiric anti-infective therapy of presumed bacterial infections in febrile neutropenic patients.
• Meropenem in conjunction with vancomycin is recommended for the treatment of infections caused by Rhodococcus equi.
• Meropenem is used for the treatment of infections caused by Nocardia.
• Meropenem is recommended by some clinicians as an alternative to penicillin G for the treatment of infections caused by Clostridium perfringens in individuals with penicillin hypersensitivity or for polymicrobial infections.
• Meropenem has been recommended for the treatment of infections caused by Capnocytophaga canimorsus.
• Meropenem is used for the treatment of systemic infections caused by Campylobacter fetus. Some clinicians suggest that the drug of choice for these infections is a third-generation cephalosporin or gentamicin, and alternatives are ampicillin, imipenem, or meropenem.
• Meropenem has been recommended for the treatment of glanders caused by Burkholderia mallei.
• Meropenem used alone or in conjunction with an aminoglycoside (amikacin, gentamicin, tobramycin) is a drug of choice for the treatment of infections caused by Acinetobacter.

Contraindications of Meropenem

Hypersensitivity to meropenem, other drugs in the same class, or any component of the formulation; patients who have experienced anaphylactic reactions to beta-lactams

• diarrhea from infection with Clostridium difficile bacteria
• decreased blood platelets
• lesion of the brain
• seizures
• chronic kidney disease stage 4 (severe)
• chronic kidney disease stage 5 (failure)
• kidney disease with likely reduction in kidney function

Allergies:

• Beta lactams
• Carbapenems

Dosage of Meropenem

Strengths: 500 mg; 1000 mg; 1000 mg/ 50 mL-NaCl 0.9%

• Note: Infusion method: Dosing is presented based on the traditional infusion method over 30 minutes unless otherwise specified.

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 (Kuti 2003; Lodise 2006).

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) (Crandon 2011; SCCM [Rhodes 2017]).

Continuous infusion method (off-label)

• IV: 2 g every 8 hours over 8 hours or 3 g every 12 hours over 12 hours (Venugopalan 2018). 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) (SCCM [Rhodes 2017]).

Indication-specific dosing

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 (CDC [Hendricks 2014]).
• 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 (CDC [Hendricks 2014]).

Bite wound infection, treatment, animal or human bite (alternative agent) (off-label use)

• IV: 1 g every 8 hours; duration of treatment for established infection (which may include oral step-down therapy) is typically 5 to 14 days (Baddour 2019a; Baddour 2019b; IDSA [Stevens 2014]).

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 (IDSA [Mermel 2009]); for empiric therapy in patients with neutropenia, severe burns, sepsis, or septic shock, give as part of an appropriate combination regimen (Kanj 2019a; Moehring 2019a; SCCM [Rhodes 2017]).

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 (Del Bono 2017; Moehring 2019a; SCCM [Rhodes 2017]).

• Duration of therapy: Usual duration is 7 to 14 days depending on the source, pathogen, extent of the infection, and clinical response; a 7-day duration is recommended for patients with uncomplicated Enterobacteriaceae infection who respond appropriately to antibiotic therapy (Moehring 2019a; Yahav 2018).

Note: If neutropenic, extend treatment until afebrile for 2 days and neutrophil recovery (ANC ≥500 cells/mm³ and increasing) (IDSA [Freifeld 2011]). For P. aeruginosa bacteremia in neutropenic patients, some experts treat for a minimum of 14 days and until recovery of neutrophils (Kanj 2019b).

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 (Chmiel 2014; Flume 2009).
• Duration of therapy: Duration is usually 10 days to 3 weeks or longer based on clinical response (Flume 2009; Simon 2019).
• Note: Some experts prefer the extended or continuous infusion method to optimize exposure (Delfino 2018; Kuti 2004; Simon 2019).

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 resistant gram-negative bacteria.

• 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 (IDSA [Lipsky 2012]; Weintrob 2019).

Intra-abdominal infection, healthcare-associated or high-risk community-acquired infection 

• Cholecystitis, acute: IV: 1 g every 8 hours; continue for 1 day after gallbladder removal or until clinical resolution in patients managed nonoperatively (Gomi 2018; SIS [Mazuski 2017]; SIS/IDSA [Solomkin 2010]; Vollmer 2019).
• Other intra-abdominal infection (eg, cholangitis, perforated appendix, diverticulitis, intra-abdominal abscess): IV: 1 g every 8 hours. Total duration of therapy (which may include oral step-down therapy) is 4 to 7 days following adequate source control (Gomi 2018; SIS [Mazuski 2017]; SIS/IDSA [Solomkin 2010]); for infections managed without surgical or percutaneous intervention, a longer duration may be necessary (Barshak 2020; Pemberton 2019).

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 (Barshak 2020; WSES [Sartelli 2017]).

Note: For community-acquired infection, reserve for severe infection or patients at high risk of adverse outcome and/or resistance (Barshak 2020; IDSA [Solomkin 2010]). As a component of empiric therapy in patients at risk for P. aeruginosa or other resistant gram-negative bacteria.

Intracranial abscess (brain abscess, intracranial epidural abscess) and 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 (Bodilsen 2018; Sexton 2019a; Sexton 2019b; Southwick 2019).

Melioidosis (Burkholderia pseudomallei infection) (off-label use)

• Initial intensive therapy: IV: 1 g every 8 hours for 10 to 14 days; longer duration may be necessary depending on disease severity and site of infection (Cheng 2004; Inglis 2006; Lipsitz 2012). 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 (Currie 2019).
• Note: Following the course of parenteral therapy, eradication therapy with oral antibiotics for ≥12 weeks is recommended (Lipsitz 2012).

Meningitis, bacterial

• As a component of empiric therapy for healthcare-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 the causative pathogen(s) and clinical response; 10 to 14 days is the minimum duration for gram-negative bacilli, although some experts prefer ≥21 days (Hasbun 2019; IDSA [Tunkel 2004]; IDSA [Tunkel 2017]).

Neutropenic enterocolitis (typhlitis) (alternative agent) (off-label use): 

• 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 (IDSA [Freifeld 2011]; Wong Kee Song 2019).
• Note: Reserve for patients colonized or infected with a resistant gram-negative bacillus, such as an extended-spectrum beta-lactamase (ESBL)-producing organism (Wong Kee Song 2019).

Neutropenic fever, high-risk cancer patients (empiric therapy) (off-label use)

• 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 (IDSA [Freifeld 2011]; Ohata 2011; Wingard 2019). Some experts prefer the extended or continuous infusion method, particularly in those who are critically ill (Fehér 2014; Moehring 2019b; SCCM [Rhodes 2017]; Wingard 2019).
• 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) (IDSA [Freifeld 2011]); some experts use an ANC cutoff of <500 cells/mm³ to define high-risk patients (Wingard 2019).

Osteomyelitis and/or discitis (off-label use)

• IV: 1 g every 8 hours for ≥6 weeks (IDSA [Berbari 2015]; Osmon 2019). For empiric therapy, use in combination with other appropriate agents (IDSA [Berbari 2015]).

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 P. aeruginosa infection. Patients should be clinically stable with normal vital signs prior to discontinuation (ATS/IDSA [Metlay 2019]).
• Hospital-acquired or ventilator-associated pneumonia: For empiric therapy or pathogen-specific therapy for multidrug-resistant gram-negative pathogen(s) (eg, P. aeruginosa, Acinetobacter spp.):
• IV: 1 g every 8 hours, as part of an appropriate combination regimen. Duration of therapy varies based on disease severity and response to therapy; treatment is typically given for 7 days (IDSA/ATS [Kalil 2016]), but a longer course may be required for severe or complicated infection or for P. aeruginosa infection (Kanj 2019c).
• Note: Some experts reserve meropenem for patients at risk of infection with a multidrug-resistant (MDR) gram-negative pathogen(s), including P. aeruginosa (Klompas 2020). Some experts prefer the extended or continuous infusion method, particularly in those who are critically ill (Klompas 2020; Moehring 2019b; SCCM [Rhodes 2017]).

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 (IDSA [Osmon 2013]).

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 another appropriate agent (s) (Jaruratanasirikul 2015; Moehring 2019a; Schmidt 2019; Sjövall 2018). Initiate therapy as soon as possible once there is recognition of sepsis or septic shock. The usual duration of treatment is dependent on the underlying source but is typically 7 to 10 days or longer depending upon clinical response. Consider discontinuation if a noninfectious etiology is identified (SCCM [Rhodes 2017]; Schmidt 2019).
• Note: Some experts prefer the extended or continuous infusion method (Moehring 2019b; SCCM [Rhodes 2017]; Sjövall 2018).

Skin and soft tissue infection (moderate to severe infection, necrotizing infection, select surgical site infections [intestinal, GU tract]), broad-spectrum empiric coverage, including P. aeruginosa 

• IV: 1 g every 8 hours as part of an appropriate combination regimen. The usual duration is 10 to 14 days based on clinical response; for necrotizing infection, continue until further debridement is not necessary, the patient has clinically improved, and the patient is afebrile for ≥48 hours (Fish 2006; IDSA [Stevens 2014]; Kanj 2019d).

Urinary tract infection, complicated (including pyelonephritis) (off-label use)

•  IV: 1 g every 8 hours; when used for empiric therapy, use alone or in combination with other appropriate agents. Switch to an appropriate oral regimen once the patient has improvement in symptoms if culture and susceptibility results allow.
• The duration of therapy depends on the antimicrobial chosen to complete the regimen and ranges from 5 to 14 days. Note: Reserve for critically ill patients or for patients with risk factor(s) for MDR pathogens, including ESBL-producing organisms and P. aeruginosa (Hooton 2019).

Dosage adjustment for concomitant therapy

• Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Usual Pediatric Dose

Skin and Structure Infection

• 3 months or older: 10 mg/kg IV every 8 hours
  Maximum dose: 500 mg/dose
• Complicated infections due to P aeruginosa: 20 mg/kg IV every 8 hours
  Maximum dose: 1 g/dose
• Uses: As a single-agent therapy for the treatment of complicated skin and skin structure infections due to S aureus (methicillin-susceptible isolates only), S pyogenes, S agalactiae, viridian group streptococci, E faecalis (vancomycin-susceptible isolates only), P aeruginosa, E coli, P mirabilis, B fragilis, Peptostreptococcus species

Intraabdominal Infection

Less than 3 months

• Infants less than 32 weeks gestational age (GA) and postnatal age (PNA) less than 2 weeks: 20 mg/kg IV every 12 hours
• Infants less than 32 weeks GA and PNA 2 weeks or older: 20 mg/kg IV every 8 hours
• Infants 32 weeks or older GA and PNA less than 2 weeks: 20 mg/kg IV every 8 hours
• Infants 32 weeks or older GA and PNA 2 weeks or older: 30 mg/kg IV every 8 hours
• 3 months or older: 20 mg/kg IV every 8 hours
  Maximum dose: 1 g/dose

• 3 months or older: 40 mg/kg IV every 8 hours
• Maximum dose: 2 g/dose

IDSA recommendations:

• Infants and children: 40 mg/kg IV every 8 hours
• Maximum dose: 2 g/dose

Side Effects of Meropenem

The Most common

• headache
• diarrhea
• constipation
• nausea
• vomiting
• pain
• redness, pain, or swelling at the injection site
• tingling or pricking sensation
• difficulty falling asleep or staying asleep
• sores in the mouth or throat

Common

• seizures
• severe diarrhea (watery or bloody stools) that may occur with or without fever and stomach cramps (may occur up to 2 months or more after your treatment)
• hives
• itching
• rash
• flushing
• swelling of the face, throat, tongue, lips, and eyes
• difficulty swallowing or breathing
• unusual tiredness or weakness
• pale skin
• fast or irregular heartbeat
• shortness of breath
• a return of fever or other signs of infection

Rare

• Agitation
• black, bloody, or tarry stools
• black, bloody vomit
• bloating or swelling of the face, arms, hands, lower legs, or feet
• blurred vision
• burning sensation while urinating
• burning, crawling, itching, numbness, prickling, “pins and needles”, or tingling feelings
• cough
• dark urine
• decreased awareness or responsiveness
• decreased urine output
• depression
• diarrhea (watery and severe), which may also be bloody
• difficult or painful urination
• difficulty with breathing
• dilated neck veins
• extreme tiredness or weakness
• fever with or without chills
• headache
• hives or welts
• hostility
• irregular breathing
• irritability
• light-colored stools
• loss of consciousness

Meropenem injection may cause other side effects. Call your doctor if you have any unusual problems while using this medication.

Drug Interaction of Meropenem

View interaction reports for meropenem and the medicines listed below.

• Acetylsalicylic Acid (aspirin)
• Adrenalin (epinephrine)
• Augmentin (amoxicillin / clavulanate)
• Bactrim (sulfamethoxazole / trimethoprim)
• Cipro (ciprofloxacin)
• Clexane (enoxaparin)
• Combivent (albuterol / ipratropium)
• Dextrose (glucose)
• Heparin Sodium (heparin)
• Lasix (furosemide)
• Metoprolol Tartrate (metoprolol)
• Paracetamol (acetaminophen)
• Valproate Sodium (valproic acid)
• Vancocin (vancomycin)
• Vitamin B12 (cyanocobalamin)
• Vitamin C (ascorbic acid)
• Vitamin D3 (cholecalciferol)
• Vitamin K (phytonadione)
• metrizamide
• mycophenolate mofetil
• mycophenolic acid
• nitisinone
• pemetrexed
• polyethylene glycol 3350 with electrolytes
• pretomanid
• probenecid
• teriflunomide
• tramadol
• typhoid vaccine, live
• valproic acid
• Zofran (ondansetron)
• Zyvox (linezolid)