What is the recommended meropenem (Invanz) dosing regimen for an adult with moderate-to-severe cellulitis and normal renal function?

Meropenem (Invanz) 1 Gram Dosing for Cellulitis

For moderate-to-severe cellulitis in adults with normal renal function, administer meropenem 1 gram intravenously every 8 hours as a 30-minute infusion, with mandatory concurrent MRSA coverage (vancomycin or linezolid), for a total duration of 7–10 days. 1, 2

Standard Dosing Regimen

• Meropenem 1 gram IV every 8 hours is the FDA-approved dose for complicated skin and skin structure infections (cSSSI) in adults, administered as a 30-minute infusion or 3–5 minute bolus. 1
• For cellulitis with suspected Pseudomonas aeruginosa involvement, the 1 gram every 8 hours dose is specifically recommended. 1
• The standard 500 mg every 8 hours dose is insufficient for severe cellulitis and should be reserved only for mild, non-pseudomonal skin infections. 1

Mandatory Combination Therapy

• Meropenem monotherapy is inadequate for cellulitis because it lacks activity against methicillin-resistant Staphylococcus aureus (MRSA), which is a common pathogen in severe skin infections. 2
• Add vancomycin 15–20 mg/kg IV every 8–12 hours or linezolid 600 mg IV twice daily to provide MRSA coverage. 2
• This combination ensures coverage of methicillin-susceptible S. aureus, streptococci, Gram-negative organisms including Pseudomonas, and anaerobes. 1, 2

Treatment Duration

• Standard duration is 7–10 days of intravenous therapy for severe cellulitis, with reassessment at day 5 to determine if extension is needed. 2
• Extend to 10–14 days when necrotic tissue is present, source control is inadequate, systemic toxicity persists, or tissue involvement is extensive. 2
• Therapy should continue until fever resolves, white blood cell count normalizes, and wound healing progresses. 2

Administration Considerations in Critically Ill Patients

• Higher doses (2 grams every 8 hours) with extended infusion (3 hours) should be considered in ICU patients with preserved renal function due to increased drug clearance and altered pharmacokinetics. 3
• Therapeutic drug monitoring (TDM) is recommended in critically ill patients with expected pharmacokinetic variability or clinical signs of toxicity, targeting trough concentrations below 64 mg/L to avoid neurological adverse effects. 3
• Continuous infusion may be used but requires preparation of new infusion bags every 6 hours due to limited drug stability at room temperature. 3, 4

Critical Pitfalls to Avoid

• Never use meropenem alone for cellulitis—MRSA coverage is mandatory because meropenem has no activity against methicillin-resistant staphylococci. 2, 5
• Do not underdose in patients with augmented renal clearance—critically ill patients with normal or supranormal creatinine clearance (>130 mL/min) frequently achieve subtherapeutic concentrations with standard dosing. 6
• Avoid premature discontinuation—stopping antibiotics before clinical stability (afebrile >48 hours, resolving erythema, improving wound) increases relapse risk. 2
• Do not delay surgical consultation if necrotizing fasciitis is suspected—pain disproportionate to findings, skin anesthesia, rapid expansion, gas on imaging, or systemic toxicity mandate urgent surgical evaluation within 1 hour. 2

Renal Dose Adjustment

• Creatinine clearance 26–50 mL/min: Reduce to 1 gram every 12 hours. 1
• Creatinine clearance 10–25 mL/min: Reduce to 500 mg every 12 hours. 1
• Creatinine clearance <10 mL/min: Reduce to 500 mg every 24 hours. 1
• Patients on renal replacement therapy require higher doses than predicted by creatinine clearance alone due to significant drug removal; TDM is strongly recommended. 7, 3

Transition to Oral Therapy

• Criteria for oral switch: All necrotic tissue debrided, systemic toxicity resolved (afebrile >48 hours), wound showing granulation tissue, and patient tolerating oral intake. 2
• Oral step-down options:
  • Amoxicillin-clavulanate 875/125 mg twice daily for susceptible organisms. 2
  • Levofloxacin 750 mg daily plus metronidazole 500 mg three times daily for penicillin-allergic patients. 2
• Total course (IV + oral): 10–14 days. 2

Special Clinical Scenarios

• Morbidly obese patients with changing renal function may require real-time TDM to optimize meropenem exposure, as standard dosing formulas are inaccurate in this population. 8
• Patients with suspected necrotizing infection (Laboratory Risk Indicator for Necrotizing Fasciitis score ≥6) should receive high-dose daptomycin plus meropenem with urgent surgical consultation. 8
• Polymicrobial infections with anaerobes are adequately covered by meropenem's intrinsic anaerobic activity; additional metronidazole is unnecessary. 1, 5