meropenem

Binds to bacterial cell wall, resulting in cell death.
Meropenem resists the actions of many enzymes that degrade most other penicillins and penicillin-like anti-infectives.

Therapeutic effects:

Bactericidal action against susceptible bacteria.

Spectrum:

Active against the following gram-positive organisms:
- Staphylococcus aureus,
- Streptococcus agalactiae,
- Streptococcus pneumoniae,
- Streptococcus pyogenes,
- viridans group streptococci,
- Enterococcus faecalis.
Also active against the following gram-negative pathogens:
- Escherichia coli,
- Haemophilus influenzae,
- Klebsiella pneumoniae,
- Neisseria meningitidis,
- Proteus mirabilis,
- Pseudomonas aeruginosa.
Active against the following anaerobes:
- Bacteroides fragilis,
- Bacteroides thetaiotaomicron,
- Peptostreptococcus spp.

Pharmacokinetics ⬆ ⬇

Absorption: IV administration results in complete bioavailability.

Distribution: Widely distributed to tissues; enters CSF when meninges are inflamed.

Metabolism/Excretion: Primarily metabolized by the liver; 50–75% excreted unchanged by the kidneys.

Half-Life: Premature neonates: 3 hr; Term neonates: 2 hr; Infants (3 mo–2 yr) 1.4 hr; Children >2 yr and Adults: 1 hr (↑ in renal impairment).

Time/Action Profile ⬆ ⬇

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
IV	rapid	end of infusion	8 hr

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity to meropenem or imipenem;
Serious hypersensitivity to other beta-lactams (penicillins or cephalosporins; cross-sensitivity may occur).

Use Cautiously in:

Renal impairment (↑ risk of thrombocytopenia and seizures; dose ↓ recommended if CCr <50 mL/min);
History of seizures, brain lesions, or meningitis;
OB: Safety not established in pregnancy;
Lactation: Use during breastfeeding only if potential maternal benefit outweighs potential risk to infant;
Pedi: Children 3 mo (safety and effectiveness not established for complicated skin/skin structure infections and meningitis).

Adv. Reactions/Side Effects ⬆ ⬇

Derm: acute generalized exanthematous pustulosis, DRUG REACTION WITH EOSINOPHILIA AND SYSTEMIC SYMPTOMS (DRESS), ERYTHEMA MULTIFORME, moniliasis (children only), pruritus, rash, STEVENS-JOHNSON SYNDROME (SJS), TOXIC EPIDERMAL NECROLYSIS (TEN)

GI: diarrhea, nausea, vomiting, CLOSTRIDIOIDES DIFFICILE-ASSOCIATED DIARRHEA (CDAD), constipation, glossitis (↑ in children), thrush (↑ in children)

Hemat: thrombocytopenia (↑ in renal impairment)

Local: inflammation at injection site, phlebitis

Neuro: dizziness, headache, paresthesias, SEIZURES

Resp: APNEA

Misc: HYPERSENSITIVITY REACTIONS (INCLUDING ANAPHYLAXIS)

Interactions ⬆ ⬇

Drug-drug:

Probenecid↓ renal excretion and ↑ levels; concurrent use not recommended.
May ↓ serum valproate levels and ↑ the risk of seizures.

Route/Dosage ⬆ ⬇

Complicated Skin/Skin Structure Infections

IV (Adults ): 500 mg every 8 hr or 1 g every 8 hr (if caused by
Pseudomonas aeruginosa
).
IV (Children ≥3 mo–12 yr): 10 mg/kg (max dose = 500 mg) every 8 hr or 20 mg/kg (max dose = 1 g) every 8 hr (if caused by
Pseudomonas aeruginosa
).

Renal Impairment

IV (Adults ): CCr 26–50 mL/min: 500 mg every 12 hr; CCr 10–25 mL/min: 250 mg every 12 hr; CCr <10 mL/min: 250 mg every 24 hr.

Intra-abdominal Infections

IV (Adults ): 1 g every 8 hr.
IV (Children ≥3 mo–12 yr): 20 mg/kg (max dose = 1 g) every 8 hr.
IV (Children <3 mo): <32 wk gestational age (GA) and postnatal age (PNA) <2 wk: 20 mg/kg every 12 hr; <32 wk GA and PNA ≥2 wk: 20 mg/kg every 8 hr; ≥32 wk GA and PNA <2 wk: 20 mg/kg every 8 hr; ≥32 wk GA and PNA ≥2 wk: 30 mg/kg every 8 hr.

Renal Impairment

IV (Adults ): CCr 26–50 mL/min: 1 g every 12 hr; CCr 10–25 mL/min: 500 mg every 12 hr; CCr <10 mL/min: 500 mg every 24 hr.

Bacterial Meningitis

IV (Children ≥3 mo): 40 mg/kg (max dose = 2 g) every 8 hr.

Availability ⬆ ⬇

(Generic available)

Powder for injection (requires reconstitution): 500 mg/vial; 1 g/vial; 2 g/vial
Premixed infusion: 500 mg/50 mL 0.9% NaCl; 1 g/50 mL 0.9% NaCl

Assessment ⬆ ⬇

Assess for infection (vital signs; appearance of wound, sputum, urine, and stool; WBC) at beginning of and throughout therapy.
Obtain a history before initiating therapy to determine previous use of and reactions to penicillins. Persons with a negative history of penicillin sensitivity may still have an allergic response.
Obtain specimens for culture and sensitivity prior to initiating therapy. First dose may be given before receiving results.
Monitor bowel function. Diarrhea, abdominal cramping, fever, and bloody stools should be reported to health care professional promptly as a sign of CDAD. May begin up to several wk following cessation of therapy.
Observe for signs and symptoms of anaphylaxis (rash, pruritus, laryngeal edema, wheezing). Discontinue the drug and notify health care professional immediately if these symptoms occur. Have epinephrine, an antihistamine, and resuscitative equipment close by in the event of an anaphylactic reaction.
Assess injection site for phlebitis, pain, and swelling periodically during administration.
Monitor for signs and symptoms of DRESS (fever, rash, lymphadenopathy, and/or facial swelling, associated with involvement of other organ systems (hepatitis, nephritis, hematologic abnormalities, myocarditis, myositis) during therapy. May resemble an acute viral infection. Eosinophilia is often present. Discontinue therapy if signs occur.
Assess patient for skin rash frequently during therapy. Discontinue meropenem at first sign of rash; may be life-threatening. SJS or TEN may develop. Treat symptomatically; may recur once treatment is stopped.

Lab Test Considerations:

Monitor hematologic, hepatic, and renal functions periodically during therapy.
- BUN, AST, ALT, LDH, serum alkaline phosphatase, bilirubin, and creatinine may be transiently ↑.
- Hemoglobin and hematocrit concentrations may be ↓.
- May cause positive direct or indirect Coombs’ test.

Implementation ⬆ ⬇

IV Administration:

Reconstitution: Reconstitute 500-mg and 1-g vials with 10 mL and 20 mL, respectively, of sterile water for injection.Concentration: 50 mg/mL.
Rate: Administer over 3–5 min.
Intermittent Infusion: Reconstitution: Reconstitute 500-mg and 1-g vials with 10 mL and 20 mL, respectively, of sterile water for injection, 0.9% NaCl, or D5W. Vials reconstituted with sterile water for injection are stable for 3 hr at room temperature and 13 hr if refrigerated; if reconstituted with 0.9% NaCl, stable for 1 hr at room temperature and 15 hr if refrigerated; if reconstituted with D5W, should be used immediately.Diluent: Further dilute in 0.9% NaCl or D5W to achieve concentration below. Infusions further diluted in 0.9% NaCl are stable for 4 hr at room temperature and 24 hr if refrigerated. Infusions further diluted in D5W are stable for 1 hr at room temperature and 4 hr if refrigerated.Concentration: 1–20 mg/mL.
Rate: Infuse over 15–30 min.

Patient/Family Teaching ⬆ ⬇

Explain purpose of meropenem to patient.
Advise patient to report the signs of superinfection (black, furry overgrowth on the tongue; vaginal itching or discharge; loose or foul-smelling stools) and allergy.
May cause dizziness. Caution patient to avoid driving or other activities requiring alertness until response to drug is known.
Caution patient to notify health care professional if rash or fever and diarrhea occur, especially if stool contains blood, pus, or mucus. Advise patient not to treat diarrhea without consulting health care professional. May occur up to several wk after discontinuation of medication.
Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications.
Rep: Advise female patient to notify health care professional if pregnancy is planned or suspected, or if breastfeeding. Monitor breastfed infants for disturbances (thrush, diarrhea).

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇