What is the recommended dose of vancomycin for a patient with a history of hypersensitivity reactions and impaired renal function with a suspected or confirmed Enterococcus faecium infection?

Vancomycin Dosing for Enterococcus faecium with Hypersensitivity and Renal Impairment

For a patient with hypersensitivity to beta-lactams and impaired renal function with suspected or confirmed E. faecium infection, vancomycin should be dosed at 15 mg/kg (actual body weight) with extended dosing intervals based on creatinine clearance, targeting trough concentrations of 15-20 μg/mL, combined with gentamicin for synergistic bactericidal activity. 1

Initial Dosing Strategy

Loading Dose

• Administer a loading dose of 15 mg/kg (actual body weight) regardless of renal function, as the loading dose is not affected by renal impairment 2, 3
• The loading dose should be infused over at least 60 minutes to minimize infusion-related reactions 2
• Consider antihistamine premedication given the patient's hypersensitivity history 3

Maintenance Dosing with Renal Impairment

• The maintenance dose must be adjusted by extending the dosing interval based on creatinine clearance while maintaining the weight-based dose of 15 mg/kg 2, 3
• For creatinine clearance 50-90 mL/min: dose every 24 hours 2
• For creatinine clearance 30-50 mL/min: dose every 24-48 hours 2
• For creatinine clearance 10-30 mL/min: dose every 48-72 hours 2
• For creatinine clearance <10 mL/min: dose every 7-10 days 2

Combination Therapy Requirements

Gentamicin Addition for Enterococcal Synergy

• Vancomycin alone is bacteriostatic against enterococci; bactericidal activity requires combination with gentamicin 1
• Gentamicin should be dosed at 3 mg/kg per 24 hours IV/IM in 2-3 equally divided doses for the initial 2 weeks 1
• Gentamicin must be administered in close temporal proximity to vancomycin dosing 1
• The strain must be tested for high-level gentamicin resistance; if resistant, this combination will not produce bactericidal activity 1

Duration of Therapy

• Native valve endocarditis with symptoms <3 months: 4 weeks of vancomycin-gentamicin 1
• Native valve endocarditis with symptoms ≥3 months: 6 weeks of vancomycin-gentamicin 1
• Prosthetic valve endocarditis: at least 6 weeks of therapy 1

Therapeutic Monitoring

Target Trough Concentrations

• Target vancomycin trough concentrations of 15-20 μg/mL for serious enterococcal infections 1, 3
• Obtain the first trough level before the fourth or fifth dose to ensure steady-state conditions 3, 4
• In patients with renal impairment, steady state may be delayed; consider obtaining trough before the third maintenance dose 3

Monitoring Frequency

• Recheck trough with each dose adjustment 4
• Monitor serum creatinine at least twice weekly throughout therapy 4
• More frequent monitoring is mandatory for patients with fluctuating renal function 4

Gentamicin Monitoring

• Target gentamicin 1-hour serum concentration of 3 μg/mL and trough concentration of <1 μg/mL 1
• In patients with creatinine clearance <50 mL/min, gentamicin dosing requires infectious diseases consultation 1

Critical Pitfalls to Avoid

Monotherapy Error

• Never use vancomycin alone for enterococcal endocarditis—it is bacteriostatic and will not cure the infection 1
• The combination of vancomycin with gentamicin is less active than penicillin/ampicillin with gentamicin, but is the only option with beta-lactam hypersensitivity 1

Dosing Errors in Renal Impairment

• Do not reduce the individual dose below 15 mg/kg; instead, extend the dosing interval 2, 3
• The initial dose should be no less than 15 mg/kg even in patients with mild to moderate renal insufficiency 2
• Failure to extend dosing intervals in renal impairment dramatically increases nephrotoxicity risk 3

Nephrotoxicity Risk

• The combination of vancomycin-gentamicin carries increased risk of nephrotoxicity and ototoxicity compared to penicillin-gentamicin 1
• Sustained trough concentrations >20 μg/mL significantly increase nephrotoxicity risk 3, 5
• Concomitant nephrotoxic medications (NSAIDs, contrast, piperacillin-tazobactam) substantially increase risk 3

Resistance Considerations

• Test the E. faecium isolate for vancomycin susceptibility (MIC determination) and high-level gentamicin resistance 1
• If vancomycin MIC ≥2 μg/mL, alternative agents (daptomycin or linezolid) should be considered 1, 5
• If high-level gentamicin resistance is present, the synergistic combination will fail; consider alternative aminoglycosides or non-aminoglycoside regimens with infectious diseases consultation 1

Infusion Rate Specifications

• Each vancomycin dose should be administered at no more than 10 mg/min or over at least 60 minutes, whichever is longer 2
• For doses >1 gram, infusion time should be extended proportionally (e.g., 2 hours for 2 gram doses) 2
• Infusion rates >10 mg/min or concentrations >5 mg/mL increase the risk of red man syndrome 2, 3