Meropenem (Intravenous): Comprehensive Clinical Guide

Indications and Clinical Use

Meropenem is a broad-spectrum carbapenem antibiotic indicated for complicated skin and skin structure infections, complicated intra-abdominal infections, and bacterial meningitis, with particular utility in severe infections requiring coverage of multidrug-resistant gram-negative organisms. 1

Primary Indications

Complicated intra-abdominal infections: Recommended as effective monotherapy by surgical infection guidelines 2
Necrotizing skin, fascia, and muscle infections: Used as part of combination therapy at 1 gram IV every 8 hours 2
Bacterial meningitis: Approved for pediatric patients 3 months and older 1
Carbapenem-resistant Enterobacteriaceae (CRE) infections: Used in combination therapy with extended infusion 2
Multidrug-resistant gram-negative infections: Including carbapenem-susceptible strains with elevated MICs 2

Spectrum of Activity

Effective against: Gram-negative organisms (including Pseudomonas aeruginosa), gram-positive organisms (methicillin-susceptible Staphylococcus aureus), anaerobes, and beta-lactamase producers 2, 3
NOT effective against: MRSA (methicillin-resistant S. aureus) and VRE (vancomycin-resistant enterococci) 2

Dosing Regimens

Standard Adult Dosing (Normal Renal Function)

For most severe infections, meropenem 1 gram IV every 8 hours is the standard regimen, with escalation to 2 grams IV every 8 hours for pneumonia, meningitis, or infections with elevated MIC values. 2

Infection-Specific Dosing

Community-acquired intra-abdominal infections (non-critically ill): 1 gram IV every 8 hours 2
Healthcare-associated intra-abdominal infections (critically ill): 1 gram IV every 8 hours with extended infusion 2
Hospital-acquired/ventilator-associated pneumonia: 1 gram IV every 8 hours (low MDR risk) or as part of combination therapy (high MDR risk) 2
Meningitis (Enterobacteriaceae or ESBL organisms): 2 grams IV every 8 hours 2
Necrotizing infections: 1 gram IV every 8 hours as part of combination therapy 2
CRE infections: 1 gram IV every 8 hours by extended infusion (3 hours) in combination therapy 2
High MIC KPC-producing K. pneumoniae (MIC ≥16 mg/L): 2 grams IV every 8 hours with 3-hour extended infusion 2

Loading Dose Considerations

Meropenem does NOT require a loading dose for standard administration in patients with normal renal function. 2 This contrasts with colistin (requires 5 mg CBA/kg IV loading dose), tigecycline (requires 100 mg IV loading dose), and vancomycin (benefits from 35 mg/kg loading dose) 2

Extended Infusion Strategy

Extended infusion over 3 hours is strongly recommended for carbapenem-resistant Enterobacteriaceae infections or when treating organisms with MIC ≥8 mg/L to optimize pharmacodynamic targets. 2

Rationale for Extended Infusion

Meropenem exhibits time-dependent bactericidal activity, requiring plasma concentrations above the MIC for approximately 40% of the dosing interval (40% T>MIC) for optimal efficacy 3
For critically ill patients, higher targets (Cmin/MIC >4-6) increase success rates 2
Extended infusion maximizes time above MIC, particularly crucial for organisms with elevated MICs 2, 4

When to Use Extended Infusion

Mandatory: CRE infections, MIC ≥8 mg/L, critically ill patients with healthcare-associated infections 2
Preferred: Severe pneumonia, deep infection foci, major pharmacokinetic changes 2

Important Caveat

Meropenem is unstable during continuous infusion; stability issues may occur, making extended infusion (3 hours) preferable to continuous infusion. 2 This differs from imipenem, which cannot use extended infusion due to drug instability 5

Dosing in Renal Impairment

Meropenem undergoes primarily renal elimination and requires dosage adjustment in patients with renal impairment, but always administer the full loading dose regardless of renal function. 1, 3, 6

Pharmacokinetic Changes in Renal Impairment

Normal renal function (CLCR >80 mL/min): Half-life approximately 1 hour 6, 7
Moderate impairment (CLCR 30-80 mL/min): Predicted clearance 59% lower than normal 4
Severe impairment (CLCR 5-29 mL/min): Nonrenal clearance accounts for ~50% of elimination 7
End-stage renal disease: Half-life prolonged up to 13.7 hours 6

Dose Adjustments by Creatinine Clearance

CLCR 20-50 mL/min: Reduce to 1 gram every 12 hours 8
CLCR <20 mL/min: Reduce to 500 mg every 12-24 hours 8
CLCR <60 mL/min: Recommended regimens appropriately cover MIC90 with standard dosing 4

Critical Pitfall: Augmented Renal Clearance

Patients with CLCR ≥90 mL/min are at high risk for subtherapeutic meropenem concentrations with standard dosing. 4 For CLCR 60-90 mL/min, 6 grams/day is needed for appropriate MIC90 coverage 4. For CLCR ≥90 mL/min, achieve appropriate exposure through increased dose, frequency, extended infusion duration, or continuous infusion 4

Dosing During Renal Replacement Therapy

Meropenem is readily dialyzable, with approximately 50% eliminated by intermittent hemodialysis and 25-50% by continuous venovenous hemofiltration. 6

Intermittent Hemodialysis (IHD)

Dialysis clearance: 79 mL/min/1.73 m² 7
Approximately 50% of drug removed during dialysis 6
Dosing strategy: Administer dose after dialysis session 6

Continuous Renal Replacement Therapy (CRRT)

CVVHF: 25-50% elimination 6
CVVHDF: 13-53% elimination 6
Peak concentrations during CRRT: 18-45 mg/L after 1 gram dose 6
Critical consideration: Treatment modality significantly influences drug elimination; physicians risk underdosing due to variable recommendations 6

Treatment Duration

Treatment duration for most infections is 5-7 days, individualized based on infection site, source control adequacy, and clinical response. 2

Duration by Infection Type

Standard Durations

Meningococcal sepsis: 5 days in recovered patients 2
Complicated intra-abdominal infections: 5-7 days; discontinue within 24 hours if no infection beyond gallbladder wall for cholecystitis with cholecystectomy 2
Complicated urinary tract infections: 5-7 days 2
Bloodstream infections/sepsis: 7-14 days depending on source control and clinical response 2
Pneumonia: Minimum 7 days 2
Pneumococcal meningitis: 10 days if stable, up to 14 days if slower response 2
Haemophilus influenzae meningitis: 10 days 2

Extended Durations

Enterobacteriaceae meningitis: 21 days 2
Listeria monocytogenes meningitis: 21 days 2
Burkholderia pseudomallei (melioidosis): 14 days intensive phase, followed by 4-8 weeks or longer eradication phase with oral antibiotics 2
Complicated skin/soft tissue infections: Minimum 4 months 8
Bone infections: 6 months 8
Prosthetic joint infections: 6 months total antimicrobial therapy following two-stage revision 8

Indications for Extended Therapy

Extend treatment beyond standard duration when: 2

Patient not responding within standard timeframe
Deep-seated infections or organ abscesses present
Inadequate source control achieved
Critically ill patients with extensive disease
Central nervous system involvement
Osteomyelitis or septic arthritis present

Adverse Effects and Monitoring

Common Adverse Effects

Gastrointestinal disturbances: Diarrhea, nausea, vomiting, abdominal pain 1
Injection site reactions: Pain, inflammation 1
Headache 1

Serious Adverse Effects Requiring Medical Attention

Hypersensitivity Reactions

Anaphylaxis and severe cutaneous adverse reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis) reported 1
Cross-reactivity possible in patients with penicillin allergy 1

Seizure Risk

High doses of meropenem (particularly 2 grams every 8 hours) are associated with increased seizure risk, especially in patients with CNS disorders or renal impairment. 5, 1

Drug Interaction: Valproic Acid

Meropenem significantly reduces valproic acid serum concentrations, potentially leading to breakthrough seizures; avoid concomitant use or consider alternative antibacterial or anticonvulsant therapy. 1

Hematologic Toxicity

Thrombocytopenia: Monitor platelet counts during therapy 1
Neutropenia: Rare but reported 1

Clostridioides difficile Infection

C. difficile-associated diarrhea reported with meropenem use 1
Consider diagnosis in patients developing diarrhea during or after therapy 1

Renal Toxicity

Monitor renal function, particularly in patients with pre-existing impairment 1
Adjust doses based on creatinine clearance 1

Monitoring Requirements

Daily renal function assessment is recommended in patients with shock or hemodynamic instability. 9 Monitor for:

Creatinine clearance (for dose adjustments) 9, 4
Platelet counts (thrombocytopenia risk) 1
Neurological status (seizure risk, especially with high doses) 1
Clinical response and infection markers 2

Special Clinical Scenarios

Combination Therapy Considerations

For carbapenem-resistant Acinetobacter baumannii (CRAB) infections, meropenem 2 grams IV every 8 hours in combination with colistin is recommended. 2 Combination therapy may be beneficial in severely ill patients with carbapenem-resistant infections 2

Carbapenem-Sparing Principles

Reserve meropenem for documented resistance to first-line agents or critically ill patients, following carbapenem-sparing principles to preserve this critical antibiotic class. 8

Source Control Requirements

Surgical debridement, drainage, or removal of infected foreign material is essential for treatment success in invasive infections; medical therapy alone has high failure rates. 8 Never delay surgical source control 8

Catheter-Related Bloodstream Infections

Remove the catheter when Morganella morganii or other resistant organisms are isolated from catheter-related bloodstream infections. 8

De-escalation and Step-Down Therapy

Clinical Stability Criteria for De-escalation

Consider step-down therapy after 48 hours of clinical stability, defined as: 2

Temperature ≤37.8°C
Heart rate ≤100 beats/min
Respiratory rate ≤24 breaths/min
Systolic blood pressure ≥90 mmHg
Oxygen saturation ≥90%
Ability to maintain oral intake
Normal mental status

Pathogen-Specific Step-Down Options

Enterobacteriaceae (Susceptible Strains)

Oral fluoroquinolones: Ciprofloxacin 500-750 mg twice daily or levofloxacin 750 mg daily for susceptible organisms 2
Ertapenem: 1 gram IV daily as intermediate step for complicated infections requiring continued parenteral therapy 2

Pseudomonas aeruginosa

De-escalate from combination to monotherapy once susceptibility confirmed 2
Continue antipseudomonal agent (oral ciprofloxacin 750 mg twice daily if susceptible) 2

Mixed Intra-Abdominal Infections

Oral amoxicillin-clavulanate: For susceptible organisms once clinical stability achieved 2
Oral fluoroquinolones plus metronidazole: For gram-negative coverage with anaerobic activity 2

Critical Pitfall: Melioidosis Exception

For Burkholderia pseudomallei (melioidosis), a mandatory two-phase approach is required: 2

Intensive phase: Meropenem, ceftazidime, or imipenem for minimum 14 days
Eradication phase: Trimethoprim-sulfamethoxazole for 3-6 months to prevent relapse

Never attempt step-down before completing the intensive phase, as this risks treatment failure and relapse. 2

Scenarios Requiring Continued Therapy

Do not attempt step-down in: 2

Persistent clinical instability (fever, hemodynamic instability, worsening organ dysfunction)
Critically ill patients with extensive disease
Deep-seated infections or undrained abscesses
CNS infections before completing recommended duration

Preparation and Administration

Reconstitution and Infusion

Standard infusion: Administer over 30 minutes 1
Extended infusion: Administer over 3 hours for resistant organisms or elevated MICs 2
Maximum infusion rate: Follow manufacturer guidelines 1

Drug Interactions

Probenecid: Inhibits renal excretion of meropenem, prolonging half-life; avoid concomitant use 1
Valproic acid: Meropenem reduces valproic acid levels; avoid combination or use alternative agents 1

Storage and Stability

Follow manufacturer guidelines for reconstituted solutions 1
Important: Meropenem is unstable during prolonged storage; use extended infusion rather than continuous infusion 2

Pediatric Considerations

Meropenem is approved for pediatric patients 3 months of age and older for complicated skin and skin structure infections and bacterial meningitis. 1 Dosing in pediatric patients requires weight-based calculations and adjustment for renal function 1

Key Clinical Pearls

Always administer full loading dose regardless of renal function; adjust only maintenance doses 9
Augmented renal clearance (CLCR ≥90 mL/min) is a major risk factor for treatment failure due to subtherapeutic concentrations 4
Extended infusion (3 hours) is mandatory for CRE infections and MIC ≥8 mg/L 2
Meropenem does not cover MRSA or VRE; add vancomycin or linezolid if these pathogens suspected 2, 9
Large inter- and intra-patient variability in meropenem concentrations occurs in critically ill patients 10, 4
Avoid concomitant use with valproic acid due to risk of breakthrough seizures 1
Source control is essential; medical therapy alone has high failure rates 8
Reserve meropenem for documented resistance or critically ill patients to preserve this critical antibiotic 8

What is the use, dosage, and potential side effects of Intravenous (IV) Meropenem (generic name) in patients with severe infections, including those with impaired renal function?

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