Can an elderly patient with impaired renal function (creatinine level of 4.5) and a severe Klebsiella infection, who is moderately sensitive to Meropenem (Meropenem), Imipenem (Imipenem), and Piperacillin-Tazobactam (Piperacillin-Tazobactam), use Ertapenem (Ertapenem) for once-daily dosing?

Ertapenem is NOT Recommended for This Patient

Do not use ertapenem in this elderly patient with severe renal impairment (creatinine 4.5) and Klebsiella bacteremia that shows only moderate sensitivity to carbapenems. The patient requires dose-adjusted aminoglycoside therapy or alternative carbapenem-based regimens with appropriate renal dosing adjustments.

Critical Problems with Ertapenem in This Clinical Scenario

Severe Renal Impairment Mandates Dose Reduction

• Ertapenem requires a 50% dose reduction (500 mg every 24 hours instead of 1 g) when creatinine clearance is ≤30 mL/min/1.73 m², which this patient almost certainly has given a creatinine of 4.5 1
• The unbound AUC of ertapenem increases 4.4-fold in advanced renal impairment (CrCl 5-30 mL/min) and 7.6-fold in end-stage renal disease compared to healthy subjects 1
• Approximately 30% of an ertapenem dose is removed during a 4-hour hemodialysis session, requiring supplemental dosing if the patient progresses to dialysis 1

Moderate Carbapenem Sensitivity Negates the "Once-Daily Advantage"

• The organism shows only moderate sensitivity to meropenem and imipenem, which strongly suggests reduced carbapenem susceptibility, likely from KPC or other carbapenemase production 2
• Ertapenem is the weakest carbapenem against KPC-producing Klebsiella and should never be used as monotherapy when other carbapenems show only moderate sensitivity 2
• The "once-daily dosing advantage" becomes meaningless when you must use a suboptimal antibiotic at a reduced dose (500 mg instead of 1 g) against a moderately resistant organism 1

Elderly Patients with Renal Impairment Face Compounded Risks

• Elderly patients (this patient qualifies) with renal impairment have substantially increased risk of drug accumulation and toxicity with renally cleared medications 3, 4
• 99% of patients aged 85+ have renal impairment necessitating dosing adjustment for drugs eliminated through renal excretion 4
• The combination of advanced age and severe renal dysfunction (creatinine 4.5) creates a high-risk scenario for adverse drug events 5, 6

The Correct Treatment Approach

First-Line: Aminoglycoside Therapy with Renal Dosing

Use amikacin, gentamicin, or tobramycin (to which the organism is fully sensitive) with extended-interval dosing adjusted for renal function:

• Aminoglycosides show concentration-dependent killing and can be given once daily even in renal impairment, though the dosing interval must be extended 3
• For severe renal impairment (CrCl <30 mL/min), administer aminoglycosides at 12-15 mg/kg per dose two or three times per week (not daily) 3
• This provides the full therapeutic dose needed for concentration-dependent killing while avoiding accumulation 3
• Monitor serum drug concentrations closely to ensure adequate absorption without excessive accumulation and to avoid nephrotoxicity and ototoxicity 3

Alternative: Meropenem or Imipenem with Appropriate Dosing

If aminoglycosides are contraindicated or not tolerated:

• Meropenem 1 g every 12-24 hours (depending on calculated creatinine clearance) provides better activity than ertapenem against moderately resistant Klebsiella 3
• Imipenem/cilastatin 500 mg every 12 hours (adjusted for renal function) is another option 3
• Consider combination therapy: piperacillin/tazobactam with meropenem showed synergy against 70.8% of KPC-producing Klebsiella isolates in vitro, with greater bactericidal activity than ertapenem combinations 2

Why Not Ertapenem Specifically

• Ertapenem combined with meropenem showed synergy in only 58.3% of KPC-producing Klebsiella isolates, less than piperacillin/tazobactam combinations 2
• The reduced dose required for renal impairment (500 mg vs 1 g) further compromises efficacy against moderately resistant organisms 1
• Ertapenem is specifically recommended for community-acquired infections in non-critically ill patients at risk for ESBL producers, not for healthcare-associated infections with carbapenem-resistant organisms 3

Critical Monitoring Requirements

Renal Function and Drug Levels

• Calculate actual creatinine clearance using the Cockcroft-Gault equation rather than relying on serum creatinine alone, which significantly underestimates renal impairment in elderly patients with reduced muscle mass 7, 6
• Monitor aminoglycoside levels (peak and trough) to optimize dosing and minimize nephrotoxicity 3
• Check renal function every 2-3 days during aminoglycoside therapy 3

Clinical Response

• Monitor for clinical improvement (defervescence, hemodynamic stability, resolution of bacteremia) within 48-72 hours 3
• Repeat blood cultures after 48-72 hours to document clearance of bacteremia 3

Common Pitfalls to Avoid

• Never assume normal renal function based on serum creatinine alone in elderly patients—a creatinine of 1.0-1.5 mg/dL may represent severe renal impairment in a frail elderly patient with low muscle mass 5, 6, 4
• Do not use ertapenem for serious infections when other carbapenems show only moderate sensitivity—this indicates carbapenemase production requiring more potent therapy 2
• Avoid the temptation to choose "convenient" once-daily dosing when it compromises efficacy—the patient's life-threatening bacteremia demands optimal antimicrobial therapy, not convenient dosing 3
• Do not forget to adjust aminoglycoside dosing intervals (not just doses) in renal impairment—once-daily dosing becomes two or three times weekly 3