What is the lung penetration of Ertapenem (a carbapenem antibiotic)?

Ertapenem Lung Penetration

Ertapenem demonstrates good penetration into lung tissue with concentrations of 7.60 mg/kg tissue (range 2.5-19.4 mg/kg) at 1.5-4.5 hours after infusion, supporting its clinical efficacy in the treatment of community-acquired pneumonia (CAP). 1

Pharmacokinetic Profile in Pulmonary Compartments

Ertapenem's penetration into different pulmonary compartments has been studied in patients undergoing lung surgery, showing the following concentrations after a standard 1g intravenous dose 1:

• Lung tissue (LT): 7.60 mg/kg (range 2.5-19.4 mg/kg) at 1.5-4.5 hours post-infusion
• Epithelial lining fluid (ELF) concentrations:
  • 4.06 mg/L at 1 hour
  • 2.59 mg/L at 3 hours
  • 2.83 mg/L at 5 hours
• Plasma concentrations:
  • 63.1 mg/L at 1 hour
  • 39.7 mg/L at 3 hours
  • 27.2 mg/L at 5 hours

The ELF/plasma concentration ratio ranges from approximately 6.4-10.4%, indicating moderate penetration into the epithelial lining fluid.

Clinical Implications

The lung tissue concentrations of ertapenem exceed the MIC90 values for most common CAP pathogens, which supports its clinical efficacy in treating community-acquired pneumonia 1, 2. The Infectious Diseases Society of America (IDSA) and American Thoracic Society (ATS) guidelines recognize ertapenem as an appropriate option for:

• Hospital ward treatment of CAP in select patients 3
• Patients with risk factors for gram-negative enteric bacteria, particularly ESBL-producing strains 3

Advantages of Ertapenem for Respiratory Infections

1. Once-daily dosing: Due to its extended half-life (~4 hours) and high protein binding 4
2. Broad spectrum activity: Effective against many gram-positive and gram-negative aerobic and anaerobic bacteria commonly associated with CAP 2
3. Stability against β-lactamases: Highly resistant to nearly all beta-lactamases, including extended-spectrum beta-lactamases (ESBLs) and AmpCs 4

Limitations

1. Limited activity against non-fermenters: Unlike other carbapenems, ertapenem has limited activity against Pseudomonas aeruginosa and other non-fermentative gram-negative bacteria 4
2. Not recommended for hospital-acquired pneumonia: When Pseudomonas aeruginosa is a concern, other carbapenems (meropenem, imipenem) are preferred 3, 5
3. Alveolar cell penetration is poor: Concentrations in alveolar cells are very low (0.003-0.007 mg/L) 1

Clinical Applications

Ertapenem is particularly useful for:

• Community-acquired pneumonia requiring hospitalization (non-ICU) 3, 2
• Patients with risk factors for ESBL-producing Enterobacteriaceae 3
• Outpatient parenteral antimicrobial therapy due to once-daily dosing convenience 4

Dosing Considerations

The standard dosing of ertapenem for respiratory infections is 1g once daily intravenously or intramuscularly 2. This dosing regimen provides adequate lung tissue concentrations to treat most common CAP pathogens.

In summary, ertapenem demonstrates clinically relevant penetration into lung tissue and epithelial lining fluid, making it an appropriate choice for treating community-acquired pneumonia, particularly in patients with risk factors for resistant Enterobacteriaceae but without risk for Pseudomonas aeruginosa infection.