What is the recommended dose and administration of ertapenem (intramuscularly) for a patient with complicated infections, considering their medical history and potential renal impairment?

Ertapenem Intramuscular Administration

For intramuscular administration, ertapenem 1g should be reconstituted with 3.2 mL of 1% lidocaine HCl (without epinephrine), resulting in a concentration of approximately 280 mg/mL, and administered by deep IM injection into a large muscle mass within 1 hour of preparation. 1

Dosing and Administration

Standard Adult Dosing

• 1g once daily for patients 13 years and older with normal renal function 1
• IM administration may be used as an alternative to IV for up to 7 days (compared to 14 days for IV) 1
• The bioavailability of IM ertapenem is 92% compared to IV administration 2

Reconstitution Technique

• Add 3.2 mL of 1% lidocaine HCl injection (without epinephrine) to the 1g vial 1
• Shake thoroughly to form solution (final concentration ~280 mg/mL) 1
• Must use within 1 hour after preparation 1
• Inject deeply into large muscle mass such as gluteal muscles or lateral thigh 1
• The reconstituted IM solution must NOT be administered intravenously 1

Clinical Applications

Appropriate Indications

IM ertapenem is particularly valuable in specific scenarios:

• When vascular access is limited or unavailable in emergency situations 3
• Treatment of complicated intra-abdominal infections (5-14 days duration) 1
• Complicated skin and skin structure infections including diabetic foot infections (7-14 days) 1
• Community-acquired pneumonia (10-14 days) 1
• Complicated urinary tract infections including pyelonephritis (10-14 days) 1
• Acute pelvic infections (3-10 days) 1

Special Clinical Uses

• Single-dose IM ertapenem 1g has shown non-inferiority to ceftriaxone for anogenital gonorrhea 3
• For ceftriaxone-resistant gonorrhea, European guidelines recommend IM ertapenem 1g for 3 days as an alternative regimen 4
• Used as third-line therapy for hidradenitis suppurativa at 1g daily for 6 weeks 3

Renal Impairment Adjustments

Dosing Modifications

• No adjustment needed if creatinine clearance >30 mL/min/1.73 m² 1
• Reduce to 500 mg daily if creatinine clearance ≤30 mL/min/1.73 m² 1
• Reduce to 500 mg daily for end-stage renal disease (CrCl ≤10 mL/min/1.73 m²) 1

Hemodialysis Considerations

• If ertapenem is given within 6 hours prior to hemodialysis, administer a supplementary 150 mg dose after the dialysis session 1
• If given at least 6 hours before hemodialysis, no supplementary dose is needed 1
• Hemodialysis clears approximately 30% of the dose 5

Pharmacokinetic Profile

Absorption and Distribution

• Following 1g IM dose, the geometric mean AUC is 541.8 μg·hr/mL (92% of IV bioavailability) 2
• Maximum concentration is somewhat lower with IM compared to IV, but plasma profiles are comparable at later time points 2
• Volume of distribution is approximately 4.8-5.7 L in healthy subjects 6, 7
• No accumulation occurs with multiple daily 1g IM doses over 7 days 2

Elimination

• Half-life is approximately 4.5 hours in patients with normal renal function 5
• Half-life increases to 6.1 hours in moderate renal impairment, 10.6 hours in advanced renal impairment, and 14.1 hours in ESRD 5

Critical Caveats and Pitfalls

Important Limitations

• IM administration is limited to 7 days maximum (versus 14 days for IV) 1
• IM route should only be considered when timely vascular access cannot be established 3
• There are no data in pediatric patients for IM administration or in those with renal impairment 1
• No dose adjustment recommendations can be made for hepatic impairment 1

Critically Ill Patients

• In critically ill patients with severe sepsis, ertapenem shows highly variable pharmacokinetics with lower maximum concentrations and higher volume of distribution compared to healthy volunteers 8
• Unbound ertapenem levels may fail to exceed MIC of 1 mg/L for adequate duration in some critically ill patients 8
• For patients in septic shock, consider alternative carbapenems with more frequent dosing such as meropenem 1g every 6 hours or imipenem/cilastatin 500 mg every 6 hours by extended infusion 9

Drug Interactions and Compatibility

• Do NOT mix or co-infuse with other medications 1
• Do NOT use diluents containing dextrose 1
• Ertapenem is neither a substrate nor inhibitor of P-glycoprotein or cytochrome P450 enzymes, so significant drug interactions are not expected 6
• Carbapenems including ertapenem are particularly unstable after reconstitution 9

Antimicrobial Stewardship

• Always consider antimicrobial stewardship principles before using carbapenems for multidrug-resistant infections 3
• Ertapenem is specifically recommended for patients with inadequate/delayed source control or high risk of ESBL-producing Enterobacterales 9
• Limit therapy to 4-7 days unless source control is difficult to achieve 10