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 (Beumier 2014; Burger 2018; Economou 2017;
Seyler 2011; Tegeder 1999; Thalhammer 1998; Ulldemolins 2015).

Continuous infusion method: 1 g loading dose (infused over 30 minutes) followed by

1 g infused over 12 hours every 12 hours (Burger 2018; Jamal 2015; Langgartner
2008).

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 (Lewis 2016) and 6 to 12 L/hour (Deshpande 2010).

IV: Traditional intermittent infusion method (over 30 minutes): 1 g every 12 hours

(Deshpande 2010; Lewis 2016). In patients with residual diuresis (urine output ≥300
mL/day ) up to 2 g every 8 hours has been recommended (Braune 2018).

Dosing: Hepatic Impairment: Adult

No dosage adjustment necessary.

Dosing: Pediatric

(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 (Bradley 2019; Red Book [AAP
2018]).
Anthrax (AAP [Bradley 2014]): 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 (Zobell 2012).

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
(Pettit 2016).

Note: Use of the continuous infusion method to optimize exposure has also been
reported in adults and a single adolescent patient with cystic fibrosis (Kuti 2004; Zobell
2014).

Febrile neutropenia, empiric treatment: Limited data available: Infants, Children, and
Adolescents: IV: 20 mg/kg/dose every 8 hours; maximum dose: 1,000 mg/dose (Bradley
2019; Lehrnbecher 2017).

Intra-abdominal infection, complicated: Note: IDSA guidelines recommend treatment

duration of 4 to 7 days (Solomkin 2010).

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 (Bradley
2019; Red Book [AAP 2018]); 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 (IDSA [Tunkel 2004]; IDSA [Tunkel 2017]).

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 (IDSA [Stevens 2014]).

Dosage adjustment for concomitant therapy: Significant drug interactions exist,

requiring dose/frequency adjustment or avoidance. Consult drug interactions database for
more information.

Dosing: Renal Impairment: Pediatric

Infants, Children, and Adolescents: There are no dosage adjustments provided in the
manufacturer's labeling. Some clinicians have used the following (Aronoff 2007): Note:
Renally adjusted dose recommendations are based on doses of 20 to 40 mg/kg/dose every
8 hours:

GFR >50 mL/minute/1.73 m2: No adjustment required.

GFR 30 to 50 mL/minute/1.73 m2: Administer 20 to 40 mg/kg/dose every 12 hours.

GFR 10 to 29 mL/minute/1.73 m2: Administer 10 to 20 mg/kg/dose every 12 hours.

GFR <10 mL/minute/1.73 m2: Administer 10 to 20 mg/kg/dose every 24 hours.

Intermittent hemodialysis (IHD): Meropenem and metabolite are readily dialyzable: 10

to 20 mg/kg/dose every 24 hours; on dialysis days give dose after hemodialysis.

Peritoneal dialysis (PD): 10 to 20 mg/kg/dose every 24 hours.

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

Dosing: Hepatic Impairment: Pediatric

No dosage adjustment necessary.

Dosing: Geriatric
Refer to adult dosing.

Dosing: Obesity: Adult

The recommendations for dosing in obese patients are based upon the best available evidence
and clinical expertise. Senior Editorial Team: Jeffrey F. Barletta, PharmD, FCCM; Manjunath P. Pai,
PharmD, FCP; Jason Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC.

Principles of body weight dosing:

Note: There are limited data on the effect of obesity on dosing requirements for
meropenem. Data are available from hospitalized patients (eg, critically ill) predominantly
at steady state. There appears to be minimal difference in trough concentrations or other
pharmacokinetic parameters (eg, clearance, Vd) between patients who are not obese and
patients with varying levels of obesity (Alobaid 2016a; Alobaid 2016b; Chung 2017). For
patients with a BMI ≥25 kg/m2, one large pharmacokinetic study evaluated meropenem
continuous infusions and recommended calculation of drug clearance using Cockcroft-
Gault estimated CrCl (CG CrCl) with adjusted body weight (AdjBW) (Pai 2015). The effect of
obesity on first-dose pharmacokinetics remains unknown.

BMI ≥ 30 kg/m2: Note: Use of traditional (intermittent) dosing in patients who are
obese is generally appropriate (Alobaid 2016a; Meng 2017; expert opinion). Renal
function should be calculated using CG CrCl with AdjBW metric (Pai 2015).

Traditional intermittent infusion method: IV: 2 g every 8 hours infused over 30

minutes (Alobaid 2016a; Meng 2017).

Extended infusion method: Note: Preferred for patients with life-threatening

infections, infections caused by resistant pathogens with MICs approaching 2
mg/mL, or CrCl >150 mL/minute to increase likelihood of achieving therapeutic
concentrations (Meng 2017; Pai 2015; expert opinion).

IV: 2 g every 8 hours infused over 3 hours (Meng 2017; Pai 2015, expert
opinion). Note: May give a loading dose of 2 g over 30 minutes when rapid
attainment of therapeutic drug concentrations is necessary (eg, sepsis)
(Crandon 2011; SCCM [Rhodes 2017]).
Dosage Forms: US
Excipient information presented when available (limited, particularly for generics); consult
specific product labeling. [DSC] = Discontinued product

Solution Reconstituted, Intravenous:

Merrem: 500 mg (1 ea [DSC]); 1 g (1 ea [DSC])

Generic: 500 mg (1 ea [DSC]); 1 g (1 ea [DSC])

Solution Reconstituted, Intravenous [preservative free]:

Merrem: 500 mg (1 ea); 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)

Generic Equivalent Available: US

Yes

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult
specific product labeling. [DSC] = Discontinued product

Solution Reconstituted, Intravenous:

Merrem: 500 mg ([DSC]); 1 g ([DSC])

Generic: 500 mg (1 ea); 1 g (1 ea)

Administration: Adult
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 (Crandon

2011; Dandekar 2003). 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 (Venugopalan 2018). Note: Must consider meropenem's
limited room temperature stability if using extended infusions.
Administration: Pediatric

Parenteral:

IV push: Infants ≥3 months, Children, and Adolescents: Administer reconstituted

solution (up to 1,000 mg) over 3 to 5 minutes; safety data is limited with 40 mg/kg
doses up to a maximum of 2,000 mg.

Intermittent IV infusion: Further dilute reconstituted solution prior to administration.

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 (Padari 2012; Shabaan 2017; van den Anker
2009).

Children and Adolescents: Administer over 3 to 4 hours (Courter 2009; Nichols

2015; Pettit 2016).

Use: Labeled Indications

Intra-abdominal infections: 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, complicated: 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.

Use: Off-Label: Adult

Anthrax; Bite wound infection, treatment, animal or human bite; 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
(including pyelonephritis)

Medication Safety Issues

Sound-alike/look-alike issues:

Meropenem may be confused with ertapenem, imipenem, metroNIDAZOLE

Adverse Reactions (Significant): Considerations

CNS effects

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 (Mohr 2008, Tunkel 2017, Zhanel 2007). Other noteworthy CNS effects
caused by meropenem include delirium, continuous epileptiform discharges, and
myoclonic jerking (Munoz-Gomez 2015, Naeije 2011, Spina Silva 2014).

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 (Miller 2011).

Risk factors:

• Preexisting neurologic conditions (eg, seizures, stroke, brain injury) (Miller 2011)

• Drug accumulation in kidney impairment

Clostridioides (formerly Clostridium) difficile infection

Clostridioides (formerly Clostridium) 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 (Hensgens 2012, IDSA [Shane 2017]).

Risk factors:

• Antibiotic exposure (highest risk factor) (CDC 2020, IDSA [Shane 2017], McDonald
2018, Vardakas 2016, Watson 2018)

• Type of antibiotic (carbapenems among highest risk) (Brown 2013, CDC 2020,
Collins 2014, Deshpande 2013, IDSA [Shane 2017], Vardakas 2016)

• Long durations in a hospital or other health care setting (recent or current) (CDC
2020, IDSA [Shane 2017], McDonald 2018, Vardakas 2016, Watson 2018)

• Older adults (CDC 2020, IDSA [Shane 2017], McDonald 2018, Vardakas 2016,
Watson 2018)

• Immunocompromised conditions (CDC 2020, IDSA [Shane 2017], McDonald 2018,

Vardakas 2016, Watson 2018)

• A serious underlying condition (CDC 2020, IDSA [Shane 2017], McDonald 2018,
Vardakas 2016, Watson 2018)

• GI surgery/manipulation (McDonald 2018, Vardakas 2016)

• Antiulcer medications (eg, proton pump inhibitors and H2 blockers) (CDC 2020,
McDonald 2018, Vardakas 2016, Watson 2018)

• Chemotherapy (CDC 2020, IDSA [Shane 2017], McDonald 2018, Vardakas 2016,
Watson 2018)

Hypersensitivity reactions (immediate and delayed)

Immediate (including anaphylaxis, angioedema, and urticaria) (Gil-Serrano 2019) 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) (Ghoshal 2015, Khalel 2010), drug
reaction with eosinophilia and systemic symptoms (Prados-Castaño 2015), Stevens-
Johnson syndrome (Sameed 2019), and toxic epidermal necrolysis (Paquet 2002).

Mechanism: Non-dose-related; immunologic. Immediate hypersensitivity reactions (eg,

anaphylaxis, angioedema, urticaria) are IgE-mediated (Brockow 2015). Delayed