Is ertapenem effective for treating diabetic foot infections?

Effectiveness of Ertapenem for Diabetic Foot Infections

Ertapenem is effective for treating moderate to severe diabetic foot infections, with clinical success rates of approximately 94% when used as parenteral therapy, though it may be slightly less effective than piperacillin-tazobactam for severe infections. 1

Efficacy Evidence

• Ertapenem has demonstrated equivalent clinical and microbiological outcomes compared to piperacillin/tazobactam in the treatment of diabetic foot infections in large randomized controlled trials 1
• In the SIDESTEP trial, ertapenem showed a 94% favorable clinical response rate versus 92% for piperacillin/tazobactam, with a between-treatment difference of 1.9% (95% CI -2.9 to 6.9) 1
• The FDA has specifically approved ertapenem for the treatment of diabetic foot infections without concomitant osteomyelitis, with clinical success rates of 75.0% for ertapenem compared to 70.8% for piperacillin/tazobactam at 10 days post-therapy 2
• However, one study found piperacillin/tazobactam to be superior to ertapenem in severe infections (clinical resolution rate: 97.2% vs 91.5%, p ≤ 0.04), while showing similar efficacy in moderate infections 3

Antimicrobial Coverage

• Ertapenem provides once-daily dosing with relatively broad-spectrum coverage that includes anaerobic organisms, making it convenient for treatment 4
• It is active against many gram-negative organisms including most Enterobacteriaceae, with >98% activity against enteric gram-negative rods and anaerobes 5
• However, ertapenem has suboptimal activity against Staphylococcus aureus and is not active against Pseudomonas aeruginosa 4
• For patients with suspected MRSA infection, ertapenem should be combined with an anti-MRSA agent such as vancomycin 2

Pharmacokinetics in Diabetic Foot Infections

• Tissue penetration studies show that ertapenem achieves higher concentrations in infected diabetic foot tissue (Cmax 4.5 ± 2.7 mg/L) compared to healthy subcutaneous tissue (2.4 ± 1.6 mg/L) 6
• For pathogens with an MIC of 1 mg/L, the free mean time above MIC in infected tissue was 38% ± 25% of the 24-hour dosing interval 6
• Bacteriostatic effects (T>MIC >20%) were achieved in 8/9 diabetic feet, while maximal bactericidal effects (T>MIC >40%) were reached in 4/9 diabetic feet 6
• Penetration of ertapenem into infected tissue was not impaired despite angiopathy in diabetic patients 6

Clinical Application

• Ertapenem (1g IV once daily) is recommended for moderate to severe diabetic foot infections, particularly when there is low suspicion of Pseudomonas aeruginosa 4
• It is particularly useful for empiric therapy of polymicrobial infections, which represent approximately 83.8% of moderate-to-severe diabetic foot infections 5
• The once-daily dosing regimen offers a practical advantage for outpatient parenteral antibiotic therapy 7
• Current guidelines suggest that ertapenem can be considered as part of group 1 carbapenems for moderate to severe diabetic foot infections, especially when there is a history of recent antibiotic exposure 4

Limitations and Considerations

• Ertapenem should not be used as monotherapy when MRSA is suspected; addition of vancomycin or another anti-MRSA agent is recommended in such cases 8, 2
• It lacks activity against Pseudomonas aeruginosa, which may be present in approximately 3.5% of diabetic foot infections 5
• Higher doses (>1g daily) might be considered to optimize bactericidal effects against moderately susceptible strains 6
• Tigecycline has been found to be significantly inferior to ertapenem in clinical outcomes and has a higher rate of adverse effects, so ertapenem is preferred between these options 4

Treatment Algorithm

1. For moderate to severe diabetic foot infections requiring parenteral therapy:

   • Use ertapenem 1g IV once daily when Pseudomonas aeruginosa is not suspected 4
   • Add vancomycin if MRSA is suspected or confirmed 8, 2

2. Duration of therapy:

   • For soft tissue infections without osteomyelitis: 10-14 days, guided by clinical response 8
   • Consider transition to oral therapy (e.g., amoxicillin/clavulanate) once clinical improvement is observed 2, 1

3. For severe infections or when Pseudomonas is suspected:

   • Consider piperacillin/tazobactam instead of ertapenem due to its superior efficacy in severe infections and coverage against Pseudomonas 3

4. Obtain proper wound cultures before initiating antibiotics to guide definitive therapy 8

5. Combine antibiotic therapy with appropriate surgical debridement and wound care for optimal outcomes 8, 7