What is the recommended adult dosing of intravenous vancomycin for serious gram‑positive infections, including loading and maintenance doses, renal dose adjustments, and oral dosing for Clostridioides difficile?

Vancomycin Adult Dosing for Serious Gram-Positive Infections

For serious gram-positive infections in adults with normal renal function, administer vancomycin at 15–20 mg/kg (actual body weight) every 8–12 hours intravenously, with a loading dose of 25–30 mg/kg for critically ill patients, targeting trough concentrations of 15–20 μg/mL. 1, 2

Intravenous Dosing for Serious Infections

Standard Maintenance Dosing

• Administer 15–20 mg/kg (actual body weight) every 8–12 hours for adults with normal renal function, not exceeding 2 g per dose 3, 1, 2
• Weight-based dosing is critical—fixed dosing of 1 g every 12 hours leads to underdosing in most patients, particularly those weighing >70 kg or with obesity 1, 2
• Each dose should be infused over at least 60 minutes at a rate not exceeding 10 mg/min 2
• For doses exceeding 1 g, extend infusion time to 1.5–2 hours to minimize infusion-related reactions 2

Loading Dose for Serious Infections

• For critically ill patients with suspected MRSA infection, sepsis, meningitis, pneumonia, endocarditis, or necrotizing fasciitis, administer a loading dose of 25–30 mg/kg (actual body weight) 1, 2
• The loading dose is NOT affected by renal function—only maintenance doses require adjustment for renal impairment 1, 2
• When administering loading doses, prolong the infusion time to 2 hours and consider premedication with an antihistamine to reduce the risk of red man syndrome 1, 2
• A standard 1-gram loading dose is inadequate and fails to achieve early therapeutic levels in most patients, particularly those weighing more than 70 kg 1

Therapeutic Monitoring

• Target trough concentrations of 15–20 μg/mL for serious infections (bacteremia, endocarditis, meningitis, pneumonia, necrotizing fasciitis) 3, 1, 2
• Obtain trough concentrations at steady state, before the fourth or fifth dose 1, 2
• The pharmacodynamic parameter that best predicts efficacy is AUC/MIC >400 1, 2
• Trough monitoring is mandatory in patients with renal dysfunction, obesity, or fluctuating volumes of distribution 1

Renal Dose Adjustments

Dosing in Renal Impairment

• Administer the full loading dose of 25–30 mg/kg based on actual body weight regardless of renal function 1, 4
• Adjust maintenance dosing by extending the dosing interval based on creatinine clearance while maintaining the weight-based dose of 15–20 mg/kg 1
• For patients on hemodialysis, obtain trough levels immediately before the next scheduled hemodialysis session 4
• Continue monitoring trough levels at least weekly throughout therapy in dialysis patients 4

Monitoring in Renal Dysfunction

• Mandatory trough monitoring before the fourth dose to guide further adjustments 1, 4
• Target trough concentrations remain 15–20 μg/mL for serious infections even in renal impairment 1, 4

Oral Dosing for Clostridioides difficile Infection

Initial Episode Dosing

• For non-severe CDI: vancomycin 125 mg orally 4 times daily for 10 days 3
• For severe CDI: vancomycin 125 mg orally 4 times daily for 10 days 3
• Severe CDI is defined as leukocytosis with WBC ≥15,000 cells/mL or serum creatinine >1.5 mg/dL 3

Fulminant CDI Dosing

• For fulminant CDI: vancomycin 500 mg orally 4 times daily 3
• If ileus is present, add vancomycin 500 mg in approximately 100 mL normal saline per rectum every 6 hours as a retention enema 3
• Intravenously administered metronidazole (500 mg every 8 hours) should be administered together with oral or rectal vancomycin, particularly if ileus is present 3
• Fulminant CDI is defined by hypotension or shock, ileus, or megacolon 3

Recurrent CDI Dosing

• For first recurrence: vancomycin 125 mg orally 4 times daily for 10 days if metronidazole was used initially 3
• Alternatively, use a prolonged tapered and pulsed vancomycin regimen (125 mg 4 times daily for 10–14 days, then 2 times daily for a week, once daily for a week, then every 2–3 days for 2–8 weeks) 3
• For second or subsequent recurrence, use vancomycin in a tapered and pulsed regimen 3

Critical Pitfalls and Caveats

Common Dosing Errors

• Never use fixed 1 g doses without considering patient weight—this results in underdosing in the majority of patients 1, 2
• Never reduce or omit the loading dose based on renal function—this is the most common error and leads to delayed achievement of therapeutic levels 1
• Do not target high trough levels (15–20 μg/mL) for non-severe infections, as this unnecessarily increases nephrotoxicity risk 1

Alternative Therapy Considerations

• If vancomycin MIC is ≥2 μg/mL, consider alternative therapies (daptomycin, linezolid, ceftaroline) as target AUC/MIC ratios may not be achievable 1, 2
• For MRSA pneumonia, consider linezolid as first-line due to superior lung penetration and documented clinical failure rates of 40% or greater with vancomycin 1

Nephrotoxicity Risk Management

• Vancomycin-associated acute kidney injury risk increases significantly when trough levels exceed 15 mg/L, especially with concurrent nephrotoxic agents 1
• Concomitant nephrotoxic medications (aminoglycosides, piperacillin-tazobactam, CT contrast, amphotericin B, NSAIDs) significantly increase the risk of nephrotoxicity 1

Intravenous Vancomycin Has No Effect on CDI

• Unlike oral vancomycin, intravenous vancomycin has no effect on CDI since the antibiotic is not excreted into the colon 3
• Vancomycin enema may be effective for patients who cannot tolerate oral preparation or patients with ileus 3