Version May 2024
A formulation of vancomycin injection contains the excipients polyethylene glycol (PEG 400) and N-acetyl D-alanine (NADA), which resulted in fetal malformations in animal reproduction studies at dose exposures approximately 8 and 32 times, respectively, higher than the exposures at the human equivalent dose. If use of vancomycin is needed during the first or second trimester of pregnancy, use other available formulations of vancomycin.
Dosage guidance:
Dosing: Dosing presented in mg/kg/dose and mg/kg/day; routes of administration may vary (IV, oral, intrathecal); use caution.
General dosing:
Note: Determination of dosing interval requires consideration of multiple factors including concomitant medications (eg, ibuprofen, indomethacin), history of birth depression, birth hypoxia/asphyxia, and presence of cyanotic congenital heart disease. Dosage should be individualized based upon serum concentration monitoring. Utilize local antibiogram and protocols for further guidance. Optimal dose and frequency not established in extracorporeal membrane oxygenation (ECMO) patients; available data are limited (Ref). Patient-specific considerations (eg, reason for ECMO) and variability with ECMO circuitry/filters as well as potential use of renal replacement therapies make extrapolation of pharmacokinetic data and dosing to all patients receiving ECMO difficult; closely monitor serum concentrations.
Initial dosage recommendations: Note: Use of a model-based approach for individualizing empiric dosing regimens may result in higher likelihood of target attainment (Ref).
Postmenstrual age-directed dosing: Various dosing regimens have been studied; optimal dose not established. Consider risks and benefits of different regimens, infectious indication, and clinical status of patient; monitor closely.
Preterm and term neonates (Ref): Note: Dosing based on a pharmacokinetic model and randomized trial comparing a "standard" vancomycin regimen for 10 days and an "optimized" regimen for 5 days in a total of 242 patients with mostly culture-negative or coagulase-negative staphylococcus sepsis; patients with Staphylococcus aureus bacteremia were excluded from the randomized outcomes trial.
"Standard regimen": Note: Standard regimen was associated with similar or better efficacy and less ototoxicity compared to the optimized regimen; however, a pharmacokinetic model showed this standard regimen was less likely than the optimized regimen to achieve the pharmacodynamic target (AUC24 ≥400 mg•hour/L) desired for treatment of S. aureus infections (Ref).
IV:
|
Postmenstrual Age |
Dose |
|---|---|
|
<29 weeks |
15 mg/kg/dose every 24 hours |
|
29 to 35 weeks |
15 mg/kg/dose every 12 hours |
|
>35 weeks |
15 mg/kg/dose every 8 hours |
"Optimized regimen": Note: Optimized regimen was associated with more ototoxicity and similar or worse efficacy; however, a pharmacokinetic model showed the optimized regimen is more likely than the standard regimen to achieve the pharmacodynamic target (AUC24 ≥400 mg•hour/L) desired for treatment of S. aureus infections (Ref).
IV:
|
Postmenstrual Age |
Loading Dose |
Dose |
|---|---|---|
|
<29 weeks |
25 mg/kg |
15 mg/kg/dose every 12 hours |
|
29 to 35 weeks |
25 mg/kg |
15 mg/kg/dose every 12 hours |
|
>35 weeks |
25 mg/kg |
15 mg/kg/dose every 8 hours |
Kidney function-based dosing (Ref): Note: Serum creatinine fluctuates and may be influenced by maternal concentrations during the first week of life; use caution and frequently reassess renal function in neonates ≤7 days old receiving vancomycin (Ref). Dosing regimen was designed for a target trough concentration of 5 to 10 mg/L, though this may not be the optimal target based on newer data (Ref):
Preterm and term neonates:
Loading dose: All patients: IV: 20 mg/kg once, followed by maintenance dose.
Maintenance dose: IV:
|
Gestational Age |
Serum Creatinine |
Dose |
|---|---|---|
|
≤28 weeks |
<0.5 mg/dL |
15 mg/kg/dose every 12 hours |
|
0.5 to 0.7 mg/dL |
20 mg/kg/dose every 24 hours | |
|
0.8 to 1 mg/dL |
15 mg/kg/dose every 24 hours | |
|
1.1 to 1.4 mg/dL |
10 mg/kg/dose every 24 hours | |
|
>1.4 mg/dL |
15 mg/kg/dose every 48 hours | |
|
>28 weeks |
<0.7 mg/dL |
15 mg/kg/dose every 12 hours |
|
0.7 to 0.9 mg/dL |
20 mg/kg/dose every 24 hours | |
|
1 to 1.2 mg/dL |
15 mg/kg/dose every 24 hours | |
|
1.3 to 1.6 mg/dL |
10 mg/kg/dose every 24 hours | |
|
>1.6 mg/dL |
15 mg/kg/dose every 48 hours |
Meningitis; treatment: Note: For neonates <2 kg, consider use of smaller doses and longer intervals (Ref):
PNA ≤7 days and ≥2 kg: IV: Initial: 20 to 30 mg/kg/day divided every 8 to 12 hours (Ref).
PNA >7 days and ≥2 kg: IV: Initial: 30 to 45 mg/kg/day divided every 6 to 8 hours (Ref).
Ventriculitis (including health care-associated ventriculitis and cerebrospinal fluid [CSF] shunt infections): Limited data available: Intraventricular or intrathecal: Use a preservative-free preparation: 3 to 20 mg/day (Ref); a dose of 5 mg is likely sufficient in neonates based on a study of 13 neonates which compared CSF vancomycin concentrations in patients receiving 5, 10, and 20 mg doses (Ref).
Dosing: Altered Kidney Function: Neonatal: IV: Consider single-dose administration with serum concentration monitoring rather than scheduled dosing in patients with urine output <1 mL/kg/hour or if serum creatinine significantly increases from baseline.
Dosage guidance:
Dosing: For IV dosing, initial dosage recommendations for patients with normal kidney function presented; doses should be adjusted based on serum concentration monitoring; doses require adjustment in renal impairment. Consider single-dose administration with serum concentration monitoring rather than scheduled dosing in patients with urine output <1 mL/kg/hour or if serum creatinine significantly increases from baseline. Dosing presented in mg/kg/dose and mg/kg/day; routes of administration may vary (eg, IV, oral, intrathecal, intracatheter, intraperitoneal, rectal); use caution.
Clinical considerations: Optimal dose and frequency not established in patients receiving extracorporeal membrane oxygenation (ECMO); available data are limited (Ref). Patient-specific considerations (eg, reason for ECMO) and variability with ECMO procedure itself make extrapolation of pharmacokinetic data and dosing to all patients receiving ECMO difficult; closely monitor serum concentrations and determine individual dosing needs in these patients.
General dosing, susceptible infection: Infants, Children, and Adolescents: IV: Initial: 45 to 60 mg/kg/day divided every 6 to 8 hours; dose and frequency should be individualized based on serum concentrations (Ref). Note: Based on adult data, an AUC24 target of 400 mg•hour/L is recommended in patients with serious methicillin-resistant S. aureus (MRSA) infections; specific dosing recommendations may be higher when targeting this range (Ref). See "MRSA infection, serious; treatment".
In general, monitoring of serum concentrations and assurance of adequate hydration status is recommended; utilize local antibiogram and protocols for further guidance.
Antibiotic lock therapy; catheter salvage: Limited data available: Optimal dose not established:
Note: For infections caused by susceptible organisms when the vascular catheter cannot be removed; use in addition to systemic antibiotics. Catheter salvage not effective in all cases; removal of catheter is recommended for infections with S. aureus (Ref). Dosing regimens variable; consider age and size of patient and catheter size (including number of lumens) when determining dose due to potential for lock to be delivered intravenously.
Infants, Children, and Adolescents: Intracatheter: Usual concentrations of lock solution: 2 to 5 mg/mL of vancomycin with or without heparin additive; most common concentrations reported: vancomycin 2 mg/mL, 2.5 mg/mL, or 5 mg/mL; refer to institutional protocol if available (Ref). Concentrations described in literature range from 0.025 to 10 mg/mL with or without heparin or citrate (Ref); a vancomycin concentration of 5 mg/mL has been shown to be more efficacious than 1 mg/mL when biofilm present (Ref). Instill into each lumen of the catheter access port using a volume sufficient to fill the catheter, with a dwell time of ideally ≥8 to 12 hours and up to 72 hours, depending on frequency of catheter use. Withdraw lock solution prior to catheter use; replace with fresh vancomycin lock solution after catheter use. Antibiotic lock therapy is given for the same duration as systemic antibiotics (Ref). Note: If heparin is utilized in the lock solution, the dose used should not approach therapeutic unit/kg dose.
C. difficile infection; treatment:
Manufacturer's labeling: Infants, Children, and Adolescents: Oral: 40 mg/kg/day divided every 6 to 8 hours for 7 to 10 days; maximum daily dose: 2,000 mg/day.
Guideline recommendations:
Non-severe infection, initial or first recurrence: Children and Adolescents: Oral: 10 mg/kg/dose 4 times daily for 10 days; maximum dose: 125 mg/dose (Ref).
Severe/fulminant infection, initial: Children and Adolescents:
Oral: 10 mg/kg/dose 4 times daily for 10 days; maximum dose: 500 mg/dose; may consider adding IV metronidazole in critically ill patients (Ref). If patient is unable to tolerate oral therapy, may use nasogastric administration (Ref).
Rectal: Note: Consider use when ileus is present. Limited data available: Rectal enema: 500 mg in 100 mL NS; dose volume is determined by age (Ref); the optimal doses have not been established in pediatric patients; suggested volumes for children: 1 to 3 years: 50 mL; 4 to 9 years: 75 mL; >10 years: 100 mL (Ref); administer 4 times daily with or without IV metronidazole (Ref).
Second or subsequent recurrence: Children and Adolescents: Pulsed-tapered regimen: Oral: 10 mg/kg/dose 4 times daily for 10 to 14 days; then 10 mg/kg/dose twice daily for 7 days, then 10 mg/kg/dose once daily for 7 days, then 10 mg/kg/dose every 2 or 3 days for 2 to 8 weeks; maximum dose: 125 mg/dose (Ref).
Endocarditis, treatment: Note: Dosage adjustment to target trough serum concentrations of 10 to 15 mg/L is recommended in pediatric endocarditis by the AHA (Ref). Dosage adjustment to target AUC24 of 400 mg•hour/L has been recommended in the treatment of proven or suspected MRSA infections based on adult data (Ref).
Empiric therapy/culture negative: Children and Adolescents: IV: Initial: 60 mg/kg/day divided every 6 hours; initial maximum daily dose: 2,000 mg/day; use in combination with other antibiotics for at least 4 to 6 weeks; longer duration may be required if prosthetic material is present or in cases of recurrent endocarditis (Ref).
Streptococcus (including enterococcus): Children and Adolescents: IV: Initial: 40 mg/kg/day divided every 8 to 12 hours; initial maximum daily dose: 2,000 mg/day; treat for at least 4 to 6 weeks; a longer duration and additional antibiotics may be required depending on organism and presence of prosthetic material (Ref).
S. aureus:
Non-methicillin resistant: Children and Adolescents: IV: Initial: 40 mg/kg/day divided every 8 to 12 hours; initial maximum daily dose: 2,000 mg/day; treat for at least 4 to 6 weeks; a longer duration and additional antibiotics may be required depending on organism and presence of prosthetic material (Ref).
Methicillin-resistant: Children and Adolescents: IV: Initial: 40 mg/kg/day divided every 8 to 12 hours for at least 6 weeks; usual initial maximum daily dose: 2,000 mg/day (Ref); however, higher initial doses have been recommended for patients with serious MRSA infection with normal renal function, though dosing based on studies and models that were not specific to endocarditis (Ref). See "MRSA infection, serious; treatment".
Enterocolitis (S. aureus): Infants, Children, and Adolescents: Oral: 40 mg/kg/day divided every 6 to 8 hours for 7 to 10 days; maximum daily dose: 2,000 mg/day.
Meningitis, including health care-associated meningitis: Infants, Children, and Adolescents: IV: Initial: 15 mg/kg/dose every 6 hours (Ref). Higher initial doses have been recommended for patients with serious MRSA infection with normal renal function, though dosing based on studies and models that were not specific to meningitis (Ref). See "MRSA infection, serious; treatment".
MRSA infection, serious; treatment:
Note: Doses should be adjusted based on patient-specific serum concentrations to a target AUC24 of 400 mg•hour/L, but potentially up to 600 mg•hour/L, based on adult data. In pediatric patients, an AUC24 of ≥400 mg•hour/L has been associated with trough concentrations of 7 to 10 mg/L, though trough concentrations do not clearly predict AUC on an individual level and trough-only monitoring is not recommended (Ref). Some studies have indicated that doses on the lower end of the range (ie, 60 mg/kg/day divided every 6 hours) will achieve target AUC24 in most children (Ref). To minimize risk of acute kidney injury, maintain AUC24 <800 mg•hour/L and trough <15 mg/L. For obese patients, start with a one-time loading dose of 20 mg/kg (based on total body weight), then start maintenance dosing (Ref).
Infants ≥3 months and Children <12 years: IV: Initial: 60 to 80 mg/kg/day in divided doses every 6 hours; initial maximum daily dose: 3,600 mg/day.
Children ≥12 years and Adolescents: IV: Initial: 60 to 70 mg/kg/day in divided doses every 6 to 8 hours; initial maximum daily dose: 3,600 mg/day.
Peritonitis (peritoneal dialysis) (Ref): Limited data available:
Prophylaxis: Infants, Children, and Adolescents:
Touch contamination of PD line (if known MRSA colonization): Intraperitoneal: 25 mg per liter.
High-risk gastrointestinal procedures: Note: Use should be reserved for patients at high risk for MRSA: IV: 10 mg/kg administered 60 to 90 minutes before procedure; maximum dose: 1,000 mg.
Treatment: Infants, Children, and Adolescents:
Intermittent: Intraperitoneal: Initial dose: 30 mg/kg in the long dwell; subsequent doses: 15 mg/kg/dose every 3 to 5 days during the long dwell; Note: Increased clearance may occur in patients with residual renal function; subsequent doses should be based on serum concentration obtained 2 to 4 days after the previous dose; redosing should occur when serum concentration <15 mcg/mL.
Continuous: Intraperitoneal: Loading dose: 1,000 mg per liter of dialysate; maintenance dose: 25 mg per liter.
Pneumonia, community-acquired: Infants >3 months, Children, and Adolescents: IV: Initial: 40 to 60 mg/kg/day in divided doses every 6 to 8 hours; (Ref). Note: Higher doses may be necessary when treating MRSA infections; doses should be adjusted based on patient-specific serum concentrations to a target AUC24 of 400 mg•hour/L (Ref). See "MRSA infection, serious; treatment".
Skin and skin structure infection, complicated: Note: Duration of treatment should be individualized and is dependent on severity of infection, adequacy of source control, and clinical improvement. For necrotizing fasciitis, continue treatment until further debridement is not necessary, patient has clinically improved, and patient is afebrile for 48 to 72 hours.
Necrotizing infections, mixed (non-MRSA): Infants, Children, and Adolescents: IV: Initial: 10 to 13 mg/kg/dose every 8 hours (Ref).
Serious MRSA infection, including necrotizing infection and pyomyositis: Note: Dosage adjustment to target AUC24 of 400 mg•hour/L recommended for serious MRSA infections based on adult data. A loading dose of 20 mg/kg (based on total body weight) is recommended in obese patients (Ref).
Infants ≥3 months and Children <12 years: IV: Initial: 60 mg/kg/day in divided doses every 6 hours; maximum daily dose: 3,600 mg/day (Ref). Based on pharmacokinetic modeling studies, doses up to 80 mg/kg/day may be necessary to achieve target AUC24 (Ref).
Children ≥12 years and Adolescents: IV: Initial: 60 mg/kg/day in divided doses every 6 to 8 hours; maximum daily dose: 3,600 mg/day (Ref). Based on pharmacokinetic modeling studies, doses up to 70 mg/kg/day may be necessary to achieve target AUC24 (Ref).
Surgical (perioperative) prophylaxis: Infants, Children, and Adolescents: IV: 15 mg/kg/dose within 120 minutes prior to surgical incision. May be administered in combination with other antibiotics depending upon the surgical procedure (Ref).
Ventriculitis (including health care-associated ventriculitis and cerebrospinal fluid [CSF] shunt infections):
Infants, Children, and Adolescents: Limited data available: Intraventricular or intrathecal: Use a preservative-free preparation: 5 to 20 mg/day; usual dose: 10 or 20 mg/day (Ref); due to the smaller CSF volume in infants, some guidelines recommend decreasing the infant dose; adult dosage recommendations are based on ventricle size (Ref).
Continuous infusion dosing: Limited data available; optimal dosing unknown:
Infants, Children, and Adolescents: IV: Loading dose: 10 to 15 mg/kg/dose administered over 1 to 2 hours, followed by maintenance infusion of 40 to 60 mg/kg/day; adjust dose to achieve target serum concentration (Ref). Note: Required dose to achieve target concentration varies significantly between patients and depending on age, renal function, and target concentration; total daily doses of 30 to 110 mg/kg/day have been reported (Ref). Pediatric patients with cancer or who are critically ill may require higher doses to achieve target concentrations (Ref). Note: When transitioning from intermittent to continuous infusion, an initial loading dose may not be required; the total daily dose will likely need reduced depending on patient-specific factors, concentrations achieved during intermittent dosing, and clinical considerations (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Oral: There are no dosage adjustments provided in manufacturer's labeling; however, dosage adjustment unlikely due to low systemic absorption.
IV: Note: Vancomycin levels should be monitored in patients with any renal impairment:
Infants, Children, and Adolescents: The following adjustments have been recommended (Ref): Note: Renally-adjusted dose recommendations are based on intravenous doses of 10 mg/kg/dose every 6 hours or 15 mg/kg/dose every 8 hours.
GFR 30 to 50 mL/minute/1.73 m2: 10 mg/kg/dose every 12 hours.
GFR 10 to 29 mL/minute/1.73 m2: 10 mg/kg/dose every 18 to 24 hours.
GFR <10 mL/minute/1.73 m2: 10 mg/kg/dose; redose based on serum concentrations.
Intermittent hemodialysis: 10 mg/kg/dose; redose based on serum concentrations.
Peritoneal dialysis (PD): 10 mg/kg/dose; redose based on serum concentrations.
Continuous renal replacement therapy (CRRT): 10 mg/kg/dose every 12 to 24 hours; monitor serum concentrations.
Oral: There are no dosage adjustments provided in the manufacturer's labeling; however, dosage adjustment unlikely needed due to low systemic absorption.
IV: There are no dosage adjustments provided in the manufacturer's labeling; however, degrees of hepatic dysfunction do not affect the pharmacokinetics of vancomycin (Ref).
(For additional information see "Vancomycin: Drug information")
Dosage guidance:
Safety: Risk of toxicity (eg, acute kidney injury) increases as a function of trough concentration, especially when trough is maintained above 15 to 20 mg/L; recent data suggest risk increases along the vancomycin AUC continuum, especially when daily AUC exceeds 650 to 1,300 mg•h/L (Ref).
Dosing: Initial IV dosing in patients without obesity should be based on actual body weight; subsequent dosing should generally be adjusted based on therapeutic monitoring.
Clinical considerations: The oral route is ineffective for treating systemic infections; the IV route is ineffective for treating C. difficile infection. Trough monitoring has traditionally been used for therapeutic monitoring; however, for serious methicillin-resistant S. aureus (MRSA) infections (eg, bacteremia, infective endocarditis, meningitis, osteomyelitis, pneumonia, sepsis), AUC monitoring is preferred (Ref). For patients with uncomplicated skin and soft tissue infections who are not obese and have normal renal function, therapeutic monitoring is generally not needed (Ref).
Usual dosage range:
Oral: 125 to 500 mg 4 times daily.
IV:
Intermittent infusion: 15 to 20 mg/kg/dose (rounded to the nearest 250 mg) every 8 to 12 hours initially; for serious MRSA infections (eg, bacteremia, infective endocarditis, meningitis, osteomyelitis, pneumonia, sepsis), adjust based on therapeutic monitoring to achieve a target AUC/minimum inhibitory concentration (MIC) determined by broth microdilution (MICBMD) ratio of 400 to 600 (assuming a vancomycin MICBMD of 1 mg/L). Trough-only monitoring (target trough: 15 to 20 mg/L) is no longer recommended in patients with serious MRSA infections (Ref), but may be needed in nonserious MRSA or non-MRSA infections. Early and frequent monitoring for dosage adjustments is recommended, especially when empiric doses exceed 4 g/day (Ref).
Loading dose: Seriously ill patients with documented/suspected MRSA infection: A loading dose of 20 to 35 mg/kg (based on actual body weight; maximum: 3 g/dose) may be considered to rapidly achieve target concentrations. After administration of the loading dose, the initiation of the maintenance dose should occur at the next dosing interval (eg, for a prescribed interval of every 8 hours, initiate the maintenance dose 8 hours after the start of the loading dose) (Ref).
Continuous infusion: Note: May be considered for critically ill patients who are unable to achieve AUC target with intermittent infusion dosing. Loading dose: 15 to 20 mg/kg, followed by a maintenance continuous infusion dose of 30 to 40 mg/kg/day (up to 60 mg/kg/day) to achieve a target steady state concentration of 20 to 25 mg/L (Ref).
Bloodstream infection:
Empiric therapy or pathogen-specific therapy for methicillin-resistant S. aureus: IV: 15 to 20 mg/kg/dose every 8 to 12 hours initially; adjust based on therapeutic monitoring (Ref). A loading dose may be considered in seriously ill patients (Ref). Treat uncomplicated S. aureus infection for ≥14 days from first negative blood culture, with longer courses warranted for endocarditis or metastatic sites of infection (Ref).
Empiric therapy or pathogen-specific therapy for methicillin-resistant coagulase-negative staphylococci: IV: 15 to 20 mg/kg/dose every 8 to 12 hours initially; adjust based on therapeutic monitoring. Treat uncomplicated bacteremia for 5 to 7 days from day of first negative blood culture, with longer courses warranted for endocarditis or metastatic sites of infection (Ref). For catheter-related bloodstream infections, consider antibiotic lock therapy for catheter salvage, in addition to systemic therapy (Ref).
Antibiotic lock technique (catheter-salvage strategy) (off-label use): Note: For infections caused by susceptible organisms when the catheter cannot be removed; use in addition to systemic antibiotics. Catheter salvage is not recommended for S. aureus (Ref).
Intracatheter: Prepare lock solution to final concentration of vancomycin 2.5 to 5 mg/mL; may be combined with heparin. Instill into each lumen of the catheter access port using a volume sufficient to fill the catheter (2 to 5 mL) with a dwell time of up to 72 hours, depending on frequency of catheter use. Withdraw lock solution prior to catheter use; replace with fresh vancomycin lock solution after catheter use. Antibiotic lock therapy is given for the same duration as systemic antibiotics (Ref).
Cerebrospinal fluid shunt infection (off-label use): As a component of empiric therapy or pathogen-specific therapy (eg, methicillin-resistant S. aureus or coagulase-negative staphylococci ):
IV: 15 to 20 mg/kg/dose every 8 to 12 hours initially; adjust based on therapeutic monitoring (Ref). A loading dose may be considered in seriously ill patients (Ref).
Intraventricular (adjunct to systemic therapy; use a preservative-free preparation): 5 to 20 mg/day; some experts recommend adjusting dosage and administration interval based on cerebrospinal fluid (CSF) vancomycin concentrations (goal: 10 to 20 times MIC of causative organism), ventricular size, and daily output from ventricular drain (Ref); data for monitoring are limited (Ref). When intraventricular vancomycin is administered via a ventricular drain, clamp drain for 15 to 60 minutes after administration (allows solution to equilibrate in CSF) (Ref). Note: Intraventricular administration is generally reserved for use in patients who fail parenteral therapy despite removal of CSF shunt or when CSF shunt cannot be removed (Ref).
Clostridioides difficile infection, prophylaxis (off-label use):
Note: For patients with a recent history of C. difficile infection (CDI) who subsequently require systemic antibiotics. Some experts reserve for patients who are older (≥65 years of age) or are significantly immunocompromised who have been hospitalized with severe CDI in the past 3 months (Ref); other experts consider use for any patients with CDI in the prior 12 months (Ref).
Oral: 125 mg once daily; continue for 5 to 7 days after completion of systemic antibiotics (Ref).
Clostridioides difficile infection, treatment:
Note: Criteria for disease severity is based on expert opinion and should not replace clinical judgment. There is no role for vancomycin doses other than 125 mg and 500 mg (Ref).
Initial, nonfulminant infection (alternative agent): Oral: 125 mg 4 times daily (Ref). Usual duration is 10 days; if delayed response to treatment, a longer duration (eg, up to 14 days) may be considered (Ref). If antibiotic(s) for a primary infection are essential, some experts extend CDI treatment one week beyond other antibiotic(s) (Ref).
Recurrent, nonfulminant infection (alternative agent): Note: Regimen selection depends on prior treatment (Ref).
Oral: 125 mg 4 times daily (Ref). Some experts reserve for patients who did not receive vancomycin for the initial episode (Ref). Usual duration is 10 days; if delayed response to treatment, a longer duration (eg, up to 14 days) may be considered (Ref). If antibiotic(s) for a primary infection are essential, some experts extend CDI treatment one week beyond other antibiotic(s) (Ref).
Pulsed-tapered regimen: Oral: 125 mg 4 times daily for 10 to 14 days, then 125 mg twice daily for 7 days, then 125 mg once daily for 7 days, then 125 mg every 2 or 3 days for 2 to 8 weeks (Ref).
Combination regimen with rifaximin: Note: Rifaximin resistance may be a concern; some experts avoid in patients who have previously received rifamycins, and others do not routinely recommend this regimen (Ref).
Oral: 125 mg 4 times daily for 10 days followed by rifaximin (Ref).
Fulminant infection (ie, ileus, megacolon, and/or hypotension/shock): Oral or via nasogastric tube: 500 mg 4 times daily with IV metronidazole; if ileus is present, may consider vancomycin retention enema (Ref). Usual duration is 10 days; if delayed response to treatment, a longer duration (eg, up to 14 days) may be considered (Ref). If antibiotic(s) for a primary infection are essential, some experts extend CDI treatment one week beyond other antibiotic(s) (Ref).
Fulminant infection with ileus: Rectal retention enema (off-label route): 500 mg in 100 mL NS; retained for as long as possible and replaced every 6 hours. Use in combination with oral vancomycin (if the ileus is partial) or in place of oral vancomycin (if the ileus is complete) plus IV metronidazole (Ref). Note: Optimal regimen not established. Use of rectal vancomycin should be reserved for patients who have not responded to standard therapy and performed by individuals with expertise in administration, as there is risk of colonic perforation. Usual duration is 10 days; if delayed response to treatment, a longer duration (eg, up to 14 days) may be considered. If antibiotic(s) for a primary infection are essential, some experts extend CDI treatment one week beyond other antibiotic(s) (Ref).
Cystic fibrosis, acute pulmonary exacerbation, moderate to severe (off-label use): Empiric or pathogen-directed therapy for methicillin-resistant S. aureus: IV: 15 to 20 mg/kg/dose every 8 hours initially; adjust based on therapeutic monitoring (Ref). Duration is usually 10 to 14 days depending on clinical response (Ref).
Diabetic foot infection, moderate to severe (off-label use): Empiric or pathogen-directed therapy for methicillin-resistant S. aureus: IV: 15 to 20 mg/kg/dose every 8 to 12 hours initially; adjust based on therapeutic monitoring (Ref). Duration (which may include appropriate oral step-down therapy) is usually 2 to 4 weeks in the absence of osteomyelitis (Ref).
Endocarditis, treatment:
Enterococcus (native or prosthetic valve) (penicillin-resistant strains or patients unable to tolerate beta-lactams): IV: 15 mg/kg/dose every 12 hours initially; adjust to obtain a trough concentration of 10 to 20 mg/L (Ref); some experts favor a trough of 15 to 20 mg/L (Ref). Administer in combination with gentamicin for 6 weeks (Ref).
S. aureus, methicillin-resistant or methicillin-susceptible (severe-beta lactam hypersensitivity) (alternative agent): IV:
Native valve: 15 to 20 mg/kg/dose every 8 to 12 hours initially; adjust based on therapeutic monitoring (Ref). A loading dose may be considered in seriously ill patients (Ref). Duration of therapy is 6 weeks (Ref).
Prosthetic valve: 15 to 20 mg/kg/dose every 8 to 12 hours initially; adjust based on therapeutic monitoring (Ref). A loading dose may be considered in seriously ill patients (Ref). Duration of therapy is at least 6 weeks (combine with rifampin for the entire duration of therapy and gentamicin for the first 2 weeks) (Ref).
Viridans group streptococci and S. bovis (native or prosthetic valve) (penicillin or ceftriaxone intolerance): IV: 15 mg/kg/dose every 12 hours initially; adjust based on therapeutic monitoring. Duration of therapy is 4 weeks (native valve) or 6 weeks (prosthetic valve) (Ref).
Endophthalmitis, treatment (off-label use): Intravitreal: Usual dose: 1 mg per 0.1 mL NS or sterile water injected into vitreum, usually in combination with ceftazidime (Ref). A repeat dose(s) may be considered at 24 to 48 hours based on culture result, severity of the infection, and response to treatment (Ref).
Intra-abdominal infection, health care–associated (off-label use): Empiric or pathogen-directed therapy for Enterococcus spp. in high-risk patients (eg, postoperative infection or health care–associated infection in patients with prior use of antibiotics that select for Enterococcus, immunocompromising condition, valvular heart disease, or prosthetic intravascular material): IV: 15 to 20 mg/kg/dose every 8 to 12 hours initially; adjust based on therapeutic monitoring (Ref). Use as part of an appropriate combination regimen (Ref). Total duration of therapy (which may include transition to oral antibiotics) is 4 to 5 days following adequate source control (Ref).
Intracranial abscess (brain abscess, intracranial epidural abscess) or spinal epidural abscess (off-label use): As a component of empiric therapy or pathogen-specific therapy for methicillin-resistant S. aureus : IV: 15 to 20 mg/kg/dose every 8 to 12 hours initially; adjust based on therapeutic monitoring. A loading dose may be considered in seriously ill patients (Ref). Duration generally ranges from 4 to 8 weeks for brain abscess and spinal epidural abscess and 6 to 8 weeks for intracranial epidural abscess (Ref).
Meningitis, bacterial (off-label use): As a component of empiric therapy or pathogen-specific therapy (eg, methicillin-resistant S. aureus or penicillin- and cephalosporin-resistant S. pneumoniae): IV: 15 to 20 mg/kg/dose every 8 to 12 hours initially; adjust based on therapeutic monitoring (Ref). A loading dose may be considered in seriously ill patients (Ref).
Osteomyelitis : As a component of empiric therapy or pathogen-specific therapy (eg, methicillin-resistant S. aureus): IV: 15 to 20 mg/kg/dose every 8 to 12 hours initially (Ref); adjust based on therapeutic monitoring. A loading dose may be considered in seriously ill patients (Ref). Duration is generally ≥6 weeks; shorter courses are appropriate if the affected bone is completely resected (Ref).
Peritonitis, treatment (peritoneal dialysis patients) (off-label use): Note: Intraperitoneal administration is preferred to IV administration. Adjust to obtain a trough concentration between 15 and 20 mg/L (Ref). Consider a 25% dose increase in patients with significant residual renal function (urine output >100 mL/day) (Ref).
Intermittent (preferred): Intraperitoneal: 15 to 30 mg/kg added to one exchange of dialysate every 5 to 7 days (allow to dwell for ≥6 hours); supplemental doses and more frequent monitoring of serum levels may be needed for patients receiving automated peritoneal dialysis (Ref).
Continuous (with every exchange): Intraperitoneal: Loading dose: 30 mg/kg added to first exchange of dialysate; maintenance dose: 1.5 mg/kg/bag for each subsequent exchange of dialysate (Ref).
Pneumonia, as a component of empiric therapy or pathogen-specific therapy for methicillin-resistant S. aureus: IV: 15 to 20 mg/kg/dose every 8 to 12 hours initially; adjust based on therapeutic monitoring (Ref). A loading dose may be considered in seriously ill patients (Ref). Note: Duration of therapy varies based on disease severity and response to therapy; treatment is typically given for 7 days. When used for empiric therapy, give as part of an appropriate combination regimen (Ref).
Prosthetic joint infection (off-label use): IV:
Pathogen-specific therapy for methicillin-resistant or susceptible S. aureus (alternative agent in beta-lactam intolerance): 15 to 20 mg/kg/dose every 8 to 12 hours initially (Ref); adjust based on therapeutic monitoring. A loading dose may be considered in seriously ill patients (Ref). Duration ranges from 2 to 6 weeks depending on prosthesis management, use of rifampin, and other patient-specific factors (Ref).
Pathogen-specific therapy for Enterococcus spp (penicillin susceptible [alternative agent] or penicillin resistant): 15 mg/kg/dose every 12 hours initially; adjust based on therapeutic monitoring. Duration: 4 to 6 weeks (Ref).
Note: In select cases (eg, debridement and retention of prosthesis or one-stage arthroplasty), give oral suppressive antibiotic therapy with an appropriate regimen following completion of initial treatment (Ref).
Sepsis/septic shock: As a component of empiric therapy or pathogen-specific therapy for methicillin-resistant S. aureus : IV: 15 to 20 mg/kg/dose every 8 to 12 hours; adjust based on therapeutic monitoring (Ref). A loading dose is recommended; administer within 1 hour of suspected or confirmed sepsis (Ref). Duration is dependent on underlying source and patient response; short courses are preferred, when appropriate (Ref).
Septic arthritis, without prosthetic material: As a component of empiric therapy or pathogen-specific therapy for methicillin-resistant S. aureus or coagulase-negative staphylococci: IV: 15 to 20 mg/kg/dose every 8 to 12 hours initially; adjust dose on therapeutic monitoring. A loading dose may be considered in seriously ill patients (Ref). Total treatment duration is 3 to 4 weeks (in the absence of osteomyelitis), including appropriate oral step-down therapy (Ref); some experts recommend 4 weeks of parenteral therapy for patients with concomitant bacteremia (Ref).
Skin and soft tissue infection (hospitalized patient): As a component of empiric therapy or pathogen-specific therapy for methicillin-resistant S. aureus : IV: 15 mg/kg/dose every 12 hours initially (Ref). For patients with uncomplicated skin and soft tissue infections who are not obese and have normal renal function, therapeutic monitoring is generally not needed; for complicated or severe infections, adjust based on therapeutic monitoring (Ref). Note: For empiric therapy of necrotizing infection, must be used in combination with other agents (Ref).
Streptococcus (group B), maternal prophylaxis for prevention of neonatal disease (alternative agent) (off-label use):
IV: 20 mg/kg at the onset of labor or prelabor rupture of membranes, then every 8 hours until delivery; maximum single dose: 2 g (Ref). Some experts prefer vancomycin 2 g initially and then 1 g every 12 hours thereafter until delivery (Ref). Note: Vancomycin is reserved for patients with penicillin allergy at high risk for anaphylaxis that have documented clindamycin-resistant group B Streptococcus or no available susceptibility data (Ref).
Surgical prophylaxis (in combination with other appropriate agents when coverage for methicillin-resistant S. aureus is indicated or for gram-positive coverage in patients unable to tolerate beta-lactams) (off-label use): IV: 15 mg/kg (usual maximum: 2 g/dose initially (Ref)) started within 60 to 120 minutes prior to initial surgical incision. Vancomycin doses may be repeated intraoperatively in 2 half-lives (approximately 8 to 12 hours in patients with normal renal function) if procedure is lengthy or if there is excessive blood loss (Ref). In cases where an extension of prophylaxis is warranted postoperatively, total duration should be ≤24 hours (Ref). Postoperative prophylaxis is not recommended in clean and clean-contaminated surgeries (Ref).
Surgical site infection: As a component of empiric therapy or pathogen-specific therapy for methicillin-resistant S. aureus : IV: 15 mg/kg/dose every 12 hours initially; adjust based on therapeutic monitoring (Ref).
Toxic shock syndrome, staphylococcal: As a component of empiric therapy or pathogen-specific therapy for methicillin-resistant S. aureus : IV: 15 to 20 mg/kg/dose every 8 to 12 hours initially; adjust based on therapeutic monitoring (Ref). A loading dose may be considered in seriously ill patients (Ref). Duration varies based on underlying etiology; 10 to 14 days of treatment is recommended in the absence of bacteremia or other distinct focus of infection (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
Oral: There are no dosage adjustments provided in the manufacturer's labeling. However, dosage adjustment unlikely due to low systemic absorption.
IV:
Note: Initial IV dosing in nonobese patients should be based on actual body weight; subsequent dosing should generally be adjusted based on therapeutic monitoring. Trough monitoring has traditionally been used for therapeutic monitoring; however, for serious methicillin-resistant S. aureus (MRSA) infections (eg, bacteremia, infective endocarditis, meningitis, osteomyelitis, pneumonia, sepsis), AUC monitoring is preferred (Ref). A ratio of AUC over 24 hours to minimum inhibitory concentration (AUC/MIC) of ≥400 is the primary pharmacokinetic/pharmacodynamic predictor of vancomycin efficacy in serious MRSA infections (Ref). Serum concentration monitoring should be conducted within the first 48 hours of therapy for patients with suspected or documented serious infections due to MRSA, with subsequent dosing adjusted to maintain AUC/MIC between 400 to 600 in order to maximize efficacy and minimize risk of vancomycin nephrotoxicity (Ref).
Altered kidney function:
Intermittent infusion: Note: The following table provides general recommendations (expert opinion derived from ASHP/IDSA/PIDS/SIDP [Rybak 2020]; Golightly 2013). Refer to institution-specific policies and procedures for more detailed guidance.
|
CrCl (mL/minute) |
Suggested loading dose (when applicable)a |
Suggested initial maintenance dose |
Suggested dosing interval |
|---|---|---|---|
|
aLoading doses recommended in critically ill patients with suspected/documented serious MRSA infections. A loading dose of up to 35 mg/kg may be considered in critically ill patients with sepsis. Obese patients usually require 20 to 25 mg/kg loading doses. Maximum recommended loading dose is 3 g (ASHP/IDSA/PIDS/SIDP [Rybak 2020]). bMonitor vancomycin serum concentrations more frequently, especially early on in therapy, to achieve target concentrations as these patients may have unstable or less predictable drug clearance. Care should be taken not to administer maintenance doses when serum concentrations remain >20 mg/L (Golightly 2013; expert opinion). | |||
|
>90 to <130 |
25 to 30 mg/kg |
15 to 20 mg/kg |
8 to 12 hours |
|
50 to 90 |
20 to 25 mg/kg |
15 to 20 mg/kg |
12 hours |
|
15 to <50 |
20 to 25 mg/kg |
10 to 15 mg/kg |
24 hours |
|
<15b |
20 to 25 mg/kg |
10 to 15 mg/kg |
48 to 72 hours |
Continuous infusion:
Loading dose: Administer an appropriate loading dose (eg, 15 to 20 mg/kg) (Ref); higher loading doses may be considered in critically ill patients with sepsis (Ref); also refer to institution-specific policies and procedures.
Maintenance dose: Various protocols have been developed (Ref); recommendations may vary based on the population studied. The following is an example protocol (Ref), and doses should be adjusted to achieve a target steady state concentration of 20 to 25 mg/L (Ref); also refer to institution-specific policies and procedures.
CrCl >80 to 119 mL/minute: 30 mg/kg administered over 24 hours.
CrCl >50 to 80 mL/minute: 25 mg/kg administered over 24 hours.
CrCl 25 to 50 mL/minute:14 mg/kg administered over 24 hours.
CrCl <25 mL/minute: 7 mg/kg administered over 24 hours.
Augmented renal clearance (measured urinary CrCl ≥130 mL/minute/1.73 m2): Augmented renal clearance (ARC) is a condition that occurs in certain critically ill patients without organ dysfunction and with normal serum creatinine concentrations. Young patients (<55 years of age) admitted post-trauma or major surgery are at highest risk for ARC, as well as those with sepsis, burns, or hematologic malignancies. An 8- to 24-hour measured urinary CrCl is necessary to identify these patients (Ref).
Intermittent infusion: Loading dose (when applicable): 25 to 35 mg/kg (Ref) followed by 15 to 20 mg/kg every 8 hours depending on degree of augmented kidney function; some patients may require more frequent dosing (eg, 15 mg/kg every 6 hours) to attain target concentrations (Ref); utilize frequent serum concentration monitoring.
Continuous infusion:
Loading dose: Administer an appropriate loading dose (eg, 15 to 20 mg/kg) (Ref); higher loading doses (eg, 25 mg/kg) have been used in some protocols and may vary based on population studied (Ref); also refer to institution-specific policies and procedures.
Maintenance dose: 40 to 60 mg/kg/day depending on degree of augmented kidney function with frequent serum concentration monitoring; adjust to achieve a target steady state concentration of 20 to 25 mg/L (Ref).
Hemodialysis, intermittent (thrice weekly): Dialyzable (25% to 40% depending on dialyzer permeability) (Ref).
|
Dose timing and dialyzer permeability |
Vancomycin doseb |
|---|---|
|
aASHP/IDSA/PIDS/SIDP [Rybak 2020] bInitial recommended loading/maintenance doses. The optimal pharmacokinetic/pharmacodynamic target in this population is unknown, but targeting predialysis concentrations of 15 to 20 mg/L are likely to achieve AUCs of 400 to 600 mg•hour/L (ASHP/IDSA/PIDS/SIDP [Rybak 2020]; Crew 2015). Predialysis serum concentrations should be obtained no less than weekly and should determine subsequent dosing (ASHP/IDSA/PIDS/SIDP [Rybak 2020]). cThrice-weekly dose administration. Typically, patients may require ~25% larger doses for the 3-day interdialytic period (eg, Friday to Monday) to maintain sufficient vancomycin exposure on the third day. | |
|
Dose given after dialysis ends | |
|
Low permeability (low flux) |
Loading dose: 25 mg/kg Maintenance dose: 7.5 mg/kgc |
|
High permeability (high flux) |
Loading dose: 25 mg/kg Maintenance dose: 10 mg/kgc |
|
Dose given during last hours of dialysis (intradialytic) | |
|
Low permeability (low flux) |
Loading dose: 30 mg/kg Maintenance dose: 7.5 to 10 mg/kgc |
|
High permeability (high flux) |
Loading dose: 35 mg/kg Maintenance dose: 10 to 15 mg/kgc |
Peritoneal dialysis:
Loading dose: 20 to 25 mg/kg (Ref). A vancomycin serum concentration should be obtained ~48 to 72 hours after the loading dose, and subsequent doses (usually 10 to 15 mg/kg) should be administered based on attainment of goal serum concentrations (Ref). Doses may vary based on infection site and severity, as well as the presence or absence of residual renal function. Some experts use maintenance doses of up to 20 mg/kg/dose (Ref).
CRRT: Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Recommendations are based on high-flux dialyzers and effluent flow rates of 20 to 25 mL/kg/hour (or ~1,500 to 3,000 mL/hour) unless otherwise noted. Close monitoring of response and adverse reactions due to drug accumulation is important.
Loading dose: 20 to 25 mg/kg followed by 7.5 to 10 mg/kg every 12 hours with more frequent serum concentration monitoring (Ref). In patients with suspected or confirmed serious MRSA infections, dose adjustments should be made based on AUC monitoring occurring in the first 24 to 48 hours of therapy (Ref).
PIRRT (eg, sustained, low-efficiency diafiltration): Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Close monitoring of response and adverse reactions due to drug accumulation is important.
Loading dose (administer even if PIRRT is occurring): 20 to 25 mg/kg, followed by 15 mg/kg after each PIRRT session ends (or during the final 60 to 90 minutes of the session) with more frequent serum concentration monitoring (Ref). In patients with suspected or confirmed serious MRSA infections, dose adjustments should be made based on AUC monitoring occurring in the first 24 to 48 hours of therapy (Ref).
Oral: There are no dosage adjustments provided in the manufacturer’s labeling. However, dosage adjustment unlikely due to low systemic absorption.
IV: There are no dosage adjustments provided in the manufacturer’s labeling. However, degrees of hepatic dysfunction do not affect the pharmacokinetics of vancomycin (Ref).
Vancomycin may rarely cause life-threatening immune-mediated anaphylaxis, which may present as generalized and extensive pruritus and/or erythema of skin, respiratory distress, bronchospasm, hypoxia, and hypotension. Clinical presentation is similar to vancomycin infusion reaction (a nonimmune-mediated anaphylactoid infusion-related reaction; formerly called “red man syndrome”), making it difficult for clinicians to distinguish between the 2 reactions (Ref).
Mechanism: Non-dose-related; immunologic; IgE-mediated with specific antibodies formed against a drug allergen following initial exposure (immunologically mediated) or result in direct mast cell stimulation (Ref). IgE binding and cross-linking of the high affinity IgE receptor (FcεRI) on the surface of mast cells causes release of histamine and other mediators that can result in urticaria, flushing, airway obstruction, hypotension, and tachycardia (Ref).
Onset: Rapid; IgE-mediated reactions generally occur within 1 hour of administration but may occur up to 6 hours after exposure (Ref). In a systematic review analyzing 7 case reports of vancomycin-induced anaphylaxis, the median time to onset of signs/symptoms was 2 minutes (range: 1 to 35 minutes) (Ref).
Risk factors:
• Previous exposure to vancomycin (necessary for IgE-mediated anaphylaxis) (Ref)
Although oral vancomycin is used for the treatment of Clostridioides difficile infection (CDI), Clostridioides difficile-associated diarrhea and Clostridioides difficile colitis have been reported with intravenous vancomycin (Ref). Clinical symptoms range from mild diarrhea to life-threatening colitis, toxic megacolon, and sepsis. In patients with severe CDI, frequent symptoms include watery diarrhea, abdominal pain, fever, nausea, anorexia, and malaise (Ref).
Mechanism: Non-dose-related; antibiotics disrupt the indigenous gut microbiota which promotes C. difficile spore germination, growth, and toxin production, leading to epithelial damage and colitis (Ref).
Onset: Varied; may start on the first day of antibiotic therapy or up to 3 months postantibiotic (Ref).
Risk factors:
• Antibiotic exposure (highest risk factor); antibiotics most frequently associated with C. difficile include clindamycin, fluoroquinolones, and third-/fourth-generation cephalosporins (Ref)
• Long durations in a hospital or other health care setting (recent or current) (Ref)
• Advanced age (Ref)
• Immunocompromised conditions or a serious underlying condition (Ref)
• GI surgery/manipulation (Ref)
• Antiulcer medications, such as proton pump inhibitors and H2 blockers (suggested risk factors) (Ref)
• Chemotherapy (suggested risk factor) (Ref)
Drug-induced immune thrombocytopenia (DITP) has been associated with use. Vancomycin-induced ITP has been associated with severe bleeding characterized by petechial hemorrhages, ecchymoses, and oozing from the buccal mucosa. Rarely, acutely-ill patients have experienced gross hematuria, lower GI hemorrhage, intrapulmonary hemorrhage, and excessive bleeding from venipuncture sites (Ref).
Mechanism: Non-dose-related; immunologic; platelet-reactive antibodies of the IgG class, the IgM class, or both, have been detected in patients with thrombocytopenia while receiving vancomycin. These antibodies reacted with platelets only in the presence of vancomycin, suggesting that the mechanism is similar to quinine-induced thrombocytopenia rather than a hapten-specific antibody (Ref).
Onset: Varied; DITP; typically occurs within 1 to 2 weeks after initiating therapy or longer in patients with intermittent exposure (Ref). In case reports, the mean time to platelet nadir count was ~8 days following first exposure. However, there are rare case reports describing a rapid onset (within 24 hours) of acute severe thrombocytopenia, primarily in settings of reexposure to vancomycin (Ref).
Maculopapular rash and severe cutaneous adverse reactions (SCARs), including drug rash with eosinophilia and systemic symptoms (DRESS), toxic epidermal necrosis (TEN), Stevens-Johnson syndrome (SJS), and acute generalized exanthematous pustulosis (AGEP), have occurred rarely with use and may be life-threatening (Ref). In addition, vancomycin-induced dermatologic disorder (linear IgA bullous dermatosis [LABD]) has been reported rarely and clinical presentation may mimic TEN, making it difficult to distinguish (Ref). Other reactions include erythema multiforme, exfoliative dermatitis, and hypersensitivity angiitis (Ref).
Mechanism: Non-dose-related; immunologic. Delayed hypersensitivity reactions are mediated by T-cells or antibodies other than IgE (eg, IgG-mediated, such as some cytopenias) (Ref). SCARs are delayed type IV hypersensitivity reactions involving a T-cell mediated drug-specific immune response (Ref). The mechanism behind vancomycin-induced LABD is unknown; LABD is a rare immune-mediated blistering disorder resulting in linear deposition of IgA at the basement membrane zone (Ref).
Onset: Delayed; type IV reactions are delayed hypersensitivity reactions that typically occur days to weeks after drug exposure but may occur more rapidly (usually within 1 to 4 days) upon reexposure (Ref). DRESS usually does not develop until after 2 weeks of administration (Ref). In a systematic case review, a median onset of 9 days and 21 days was observed for SJS/TEN and DRESS, respectively (Ref). In vancomycin-induced LABD, lesions typically appear 1 to 15 days after the first vancomycin dose (Ref); a median latency of 7 days was observed in a systematic review (Ref).
Risk factors:
• Patients with end-stage renal disease (suggested risk factor) (Ref)
• In DRESS, a strong association was observed for patients with the HLA-A*32:01 allele in a study involving predominantly European ancestry (Ref)
• Cross-reactivity with teicoplanin (Ref)
Systemic exposure is associated with nephrotoxicity (usually reversible), which may result in acute kidney injury (or acute renal failure), predominantly occurring in patients with multiple risk factors (Ref). Cases of systemic absorption and nephrotoxicity with oral vancomycin have been reported (Ref).
Mechanism: Non-dose-related; most commonly attributed to acute tubular necrosis (or renal tubular necrosis), resulting from direct oxidative stress on proximal tubule cells or obstructive tubular cast formation. In addition, acute interstitial nephritis has also been described, characterized by tubular and interstitial inflammation, resulting from an immunologically mediated (non-IgE) process (Ref).
Onset: Intermediate; usually occurs 5 to 7 days and up to 14 days following monotherapy (Ref). Acute interstitial nephritis was observed at a median onset of 26 days in a systematic case review (Ref).
Risk factors:
• Vancomycin exposure (trough levels ≥15 mg/L, larger AUC [>650 to 1,300 mg-h/L], high daily doses [>4 g/day]) (Ref)
• Duration of therapy >7 days (Ref)
• Obesity (Ref)
• Preexisting kidney dysfunction (Ref)
• Critical illness (Ref)
• Concurrent nephrotoxin therapy or concurrent prolonged use of piperacillin/tazobactam (Ref)
• Older adults >65 years:
• Parenteral: Less commonly associated risk factor (Ref)
• Oral: Increases the risk of systemic absorption from oral vancomycin
Neutropenia (severe) and agranulocytosis have been observed in numerous case reports and case series; in some cases, drug fever also accompanied the neutropenia (Ref). Reversible pancytopenia has also been reported in case reports (Ref).
Mechanism: Non-dose-related; available data suggest a peripheral mechanism mediated by antibodies and direct toxicity to the bone marrow (Ref).
Onset: Varied; usually occurs after 7 to 12 days of treatment, with most cases occurring after 20 days (Ref). However, 1 case report described an onset of 8 weeks following discontinuation of a 3-week course, and then upon rechallenge, neutropenia recurred 3 days following reinitiation (Ref).
Risk factors:
• Prolonged exposure (ie, >7 days) (Ref)
• Teicoplanin: In patients experiencing neutropenia who were switched to teicoplanin (another glycopeptide), 50% of these patients also developed teicoplanin-induced neutropenia (Ref)
Vancomycin is infrequently associated with ototoxicity, manifested as tinnitus, sensorineural hearing loss, dizziness, or vertigo; some cases have reported irreversible hearing loss (Ref). Of note, vancomycin has not been found to be ototoxic in animal models (Ref).
Mechanism: Non-dose-related; proposed to be via direct damage to the auditory branch of the eighth cranial nerve, although data are conflicting and unclear if ototoxicity is directly attributable to vancomycin or to other confounding factors (Ref).
Risk factors:
• Older adults (Ref)
• Coadministration with ototoxic agents (eg, aminoglycosides) (Ref)
• Kidney dysfunction (potential risk factor) (Ref)
Vancomycin infusion reaction, a non-IgE-mediated drug reaction most often characterized by an erythematous rash, generalized flushing, and pruritus, may occur. Severe reactions, which are uncommon, may also include hypotension, chest pain, and dyspnea. Rarely, vancomycin infusion reaction may be life-threatening and cause severe hypotension and cardiac arrest or cardiovascular collapse. Clinical presentation can be similar to IgE-mediated anaphylaxis making it difficult for clinicians to distinguish between the 2 reactions (Ref). Reactions usually cease promptly after infusion is stopped.
Mechanism: Non-IgE-mediated drug reaction caused by histamine release from mast cells and basophils found in the skin, lung, GI tract, myocardium, and vascular system (Ref). The mast cell receptor MRGPRX2 has also been identified as a cause of non-IgE-mediated drug reactions (Ref).
Onset: Rapid; usually occurs 4 to 10 minutes after the start of the infusion with the first dose but may also occur at any time (Ref).
Risk factors:
• Typically caused by rapid IV infusion (<1 hour) of large doses (Ref)
• Concomitant medications that also induce histamine release including ciprofloxacin; barbiturates; opioids (except fentanyl which rarely induces histamine); certain neuromuscular antagonists (atracurium, cisatracurium, doxacurium, mivacurium, succinylcholine, tubocurarine); propofol; plasma expanders (dextran, polygeline); and radiocontrast agents (Ref).
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
IV:
Frequency not defined:
Cardiovascular: Chest pain, flushing, hypotension, shock, vasculitis
Dermatologic: Bullous dermatitis, erythema of skin, exfoliative dermatitis (Forrence 1990), pruritus, Stevens-Johnson syndrome (Lin 2014)
Hematologic & oncologic: Agranulocytosis (di Fonzo 2018), eosinophilia, leukopenia, thrombocytopenia
Hypersensitivity: Hypersensitivity reaction (Kupstaite 2010)
Local: Injection site phlebitis, irritation at injection site, pain at injection site
Nervous system: Chills, dizziness, malaise, vertigo
Neuromuscular & skeletal: Myalgia
Otic: Hearing loss (Klibanov 2003), ototoxicity (Forouzesh 2009), tinnitus (Traber 1981)
Renal: Increased blood urea nitrogen (Bergman 1988), increased serum creatinine, interstitial nephritis (Bergman 1988), renal tubular necrosis (Shah-Khan 2011)
Respiratory: Dyspnea, wheezing
Miscellaneous: Fever (Smith 1999)
Postmarketing:
Cardiovascular: Hypersensitivity angiitis (Pingili 2017)
Dermatologic: Acute generalized exanthematous pustulosis (Mawri 2015), dermatologic disorder (linear IgA bullous dermatosis) (Tashima 2014), erythema multiforme (Khicher 2019), maculopapular rash (Marik 1997), toxic epidermal necrolysis (Changela 2013)
Gastrointestinal: Clostridioides difficile associated diarrhea (Hecht 1989), Clostridioides difficile colitis (Hecht 1989), peritonitis (following intraperitoneal administration during CAPD) (Freiman 1992)
Hematologic & oncologic: Henoch-Schonlein purpura (Min 2017), immune thrombocytopenia (Al Jafar 2015; Mohammadi 2017), neutropenia (reversible) (literature suggests an incidence ranging from 2% to 12%) (Black 2011; di Fonzo 2018), pancytopenia (Carmichael 1986)
Hypersensitivity: Anaphylaxis (Anne 1994), fixed drug eruption (Gilmore 2004), vancomycin infusion reaction (literature suggests an incidence ranging from 4% to as high as 47%) (Alvarez-Arango 2021; Austin 2020; Symons 1985; Wazny 2001)
Immunologic: Drug reaction with eosinophilia and systemic symptoms (Cacoub 2011)
Renal: Acute kidney injury (Sawada 2018), nephrotoxicity (Lodise 2009)
Oral:
>10%:
Endocrine & metabolic: Hypokalemia (13%)
Gastrointestinal: Abdominal pain (15%), nausea (17%)
1% to 10%:
Cardiovascular: Peripheral edema (6%)
Gastrointestinal: Diarrhea (9%), flatulence (8%), vomiting (9%)
Genitourinary: Urinary tract infection (8%)
Nervous system: Fatigue (5%), headache (7%)
Neuromuscular & skeletal: Back pain (6%)
Renal: Nephrotoxicity (5%)
Miscellaneous: Fever (9%)
Frequency not defined:
Cardiovascular: Hypotension
Gastrointestinal: Constipation
Hematologic & oncologic: Anemia
Nervous system: Depression, insomnia
Renal: Increased serum creatinine, renal failure syndrome, renal insufficiency
Postmarketing:
Cardiovascular: Vasculitis
Dermatologic: Acute generalized exanthematous pustulosis, dermatologic disorder (linear IgA bullous dermatosis) (Tashima 2014), exfoliative dermatitis (Forrence 1990), pruritus, skin rash, Stevens-Johnson syndrome (An 2011), toxic epidermal necrolysis (An 2011), urticaria
Hematologic & oncologic: Eosinophilia, thrombocytopenia
Hypersensitivity: Anaphylaxis, flushing (Arroyo-Mercado 2019), nonimmune anaphylaxis
Immunologic: Drug reaction with eosinophilia and systemic symptoms (Cacoub 2011)
Nervous system: Chills, dizziness, drug fever, pain, vertigo
Neuromuscular & skeletal: Muscle spasm (chest and back)
Otic: Tinnitus
Respiratory: Dyspnea, wheezing
Hypersensitivity to vancomycin or any component of the formulation
Concerns related to adverse effects:
• Extravasation and thrombophlebitis: IV vancomycin is an irritant; ensure proper needle or catheter placement prior to and during infusion; avoid extravasation. Pain, tenderness, and necrosis may occur with extravasation. If thrombophlebitis occurs, slow infusion rates, dilute solution (eg, 2.5 to 5 g/L) and rotate infusion sites.
• Superinfection: Prolonged use may result in fungal or bacterial superinfection.
Disease-related concerns:
• Inflammatory bowel disease: Clinically significant serum concentrations have been reported in patients with inflammatory disorders of the intestinal mucosa who have taken oral vancomycin (multiple doses) for the treatment of C. difficile-associated diarrhea. Although use may be warranted, the risk for adverse reactions may be higher in this situation; consider monitoring serum trough concentrations in patients with renal insufficiency, severe colitis, and a prolonged course (IDSA/SHEA [McDonald 2018]; Pettit 2015).
• Renal impairment: Use with caution in patients with renal impairment or those receiving other nephrotoxic drugs; dosage modification required and close monitoring is recommended in patients with preexisting renal impairment and those at high risk for renal impairment. Accumulation may occur after multiple oral doses of vancomycin in patients with renal impairment; consider monitoring serum concentrations in this circumstance.
Other warnings/precautions:
• Appropriate use: Oral vancomycin is only indicated for the treatment of CDI or enterocolitis due to S. aureus and is not effective for systemic infections; parenteral vancomycin is not effective for the treatment of enterocolitis.
• Intraocular administration (off-label route): Hemorrhagic occlusive retinal vasculitis (HORV), including permanent visual loss, has been reported in patients receiving intracameral or intravitreal administration of vancomycin during or after cataract surgery.
• Intraperitoneal administration (off-label route): Use caution when administering intraperitoneally (IP); in some continuous ambulatory peritoneal dialysis (CAPD) patients, chemical peritonitis (cloudy dialysate, fever, severe abdominal pain) has occurred. Symptoms are self-limited and usually clear after vancomycin discontinuation.
First-Vancomycin oral solution is a compounding kit. Refer to manufacturer’s labeling for compounding instructions.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Capsule, Oral, as hydrochloride:
Vancocin: 125 mg, 250 mg [contains fd&c blue #2 (indigotine,indigo carmine)]
Generic: 125 mg, 250 mg
Solution, Intravenous, as hydrochloride:
Generic: 750 mg/150 mL (150 mL); 1000 mg/200 mL (200 mL); 1250 mg/250 mL (250 mL); 1500 mg/300 mL (300 mL); 1750 mg/350 mL (350 mL)
Solution, Intravenous, as hydrochloride [preservative free]:
Generic: 500 mg/100 mL (100 mL); 2000 mg/400 mL (400 mL); 1 g/200 mL in Dextrose 5% (200 mL); 1 g/200 mL in NaCl 0.9% (200 mL); 500 mg/100 mL in Dextrose 5% (100 mL); 750 mg/150 mL in Dextrose 5% (150 mL)
Solution Reconstituted, Intravenous [preservative free]:
Generic: 1.25 g (1 ea)
Solution Reconstituted, Intravenous, as hydrochloride:
Generic: 500 mg (1 ea); 1 g (1 ea); 1.5 g (1 ea); 10 g (1 ea)
Solution Reconstituted, Intravenous, as hydrochloride [preservative free]:
Generic: 250 mg (1 ea [DSC]); 500 mg (1 ea); 750 mg (1 ea); 1 g (1 ea); 1.5 g (1 ea); 5 g (1 ea); 10 g (1 ea); 100 g (1 ea)
Solution Reconstituted, Oral, as hydrochloride:
Firvanq: 25 mg/mL (150 mL, 300 mL); 50 mg/mL (150 mL, 300 mL) [contains fd&c red #40 (allura red ac dye), quinoline yellow (d&c yellow #10), sodium benzoate; grape flavor]
Firvanq: 50 mg/mL (150 mL [DSC], 300 mL [DSC]) [contains fd&c red #40 (allura red ac dye), quinoline yellow (d&c yellow #10), sodium benzoate; white grape flavor]
Generic: 25 mg/mL (150 mL, 300 mL); 50 mg/mL (150 mL, 300 mL); 250 mg/5 mL (80 mL, 150 mL, 300 mL)
Yes
Capsules (Vancocin Oral)
125 mg (per each): $103.35
250 mg (per each): $190.55
Capsules (Vancomycin HCl Oral)
125 mg (per each): $31.31
250 mg (per each): $57.72
Solution (Vancomycin HCl in Dextrose Intravenous)
1GM/200ML 5% (per mL): $0.16
500 mg/100 mL 5% (per mL): $0.09
750MG/150ML 5% (per mL): $0.10
Solution (Vancomycin HCl in NaCl Intravenous)
1GM/200ML 0.9% (per mL): $0.14
500 mg/100 mL 0.9% (per mL): $0.09
750MG/150ML 0.9% (per mL): $0.10
Solution (Vancomycin HCl Intravenous)
500 mg/100 mL (per mL): $0.11
750 mg/150 mL (per mL): $0.10
1000 mg/200 mL (per mL): $0.10
1250 mg/250 mL (per mL): $0.09
1500MG/300ML (per mL): $0.09
1750MG/350ML (per mL): $0.09
2000MG/400ML (per mL): $0.08
Solution (reconstituted) (Firvanq Oral)
25 mg/mL (per mL): $0.99
50 mg/mL (per mL): $1.31
Solution (reconstituted) (Vancomycin HCl Intravenous)
1 g (per each): $4.14 - $19.54
1.25 g (per each): $24.12
1.5 g (per each): $28.94 - $29.22
5 g (per each): $19.72 - $108.31
10 g (per each): $39.18 - $260.68
100 g (per each): $600.00
500 mg (per each): $2.96 - $9.79
750 mg (per each): $8.02 - $11.81
Solution (reconstituted) (Vancomycin HCl Oral)
25 mg/mL (per mL): $0.83 - $0.90
50 mg/mL (per mL): $1.09 - $1.19
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Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, Oral, as hydrochloride:
Vancocin: 125 mg, 250 mg [contains fd&c blue #2 (indigotine,indigo carmine)]
Generic: 125 mg, 250 mg
Solution, Intravenous, as hydrochloride:
Generic: 1 g/200 mL in NaCl 0.9% (200 mL)
Solution Reconstituted, Intravenous, as hydrochloride:
Generic: 500 mg (1 ea, 10 mL); 1000 mg (1 ea); 1 g (1 ea, 20 mL, 30 mL); 5 g (1 ea); 10 g (1 ea)
Note: A vancomycin oral solution (25 mg/mL or 50 mg/mL) is commercially available (Firvanq).
Oral Solution
Using a vial of vancomycin powder for injection (reconstituted to 50 mg/mL), add the appropriate volume for the dose to 30 mL of water and administer orally or via NG tube. For oral administration, common flavoring syrups may be added to improve taste.
25 mg/mL Oral Solution
A vancomycin 25 mg/mL solution in Ora-Sweet and water (1:1) may be prepared by reconstituting vancomycin for injection with sterile water, then dilute with a 1:1 mixture of Ora-Sweet and distilled water to a final concentration of 25 mg/mL; transfer to amber prescription bottle. Stable for 75 days refrigerated or for 26 days at room temperature.
Oral:
Oral solution (Firvanq): Shake reconstituted oral solution well before each use.
Powder for injection: Reconstituted powder for injection (not premixed solution) may be diluted and used for oral administration; common flavoring syrups may be added to improve taste. The unflavored, diluted solution may also be administered via nasogastric tube.
Parenteral:
IV:
Intermittent: Administer intermittent IV infusion over 60 minutes. Vancomycin infusion reaction (formerly "red man syndrome") may occur if the infusion is too rapid. It is not an allergic reaction, but may be characterized by hypotension and/or a maculopapular rash appearing on the face, neck, trunk, and/or upper extremities; if this should occur, slow the infusion rate to administer dose over 90 to 120 minutes (Ref) and increase the dilution volume; the reaction usually dissipates in 30 to 60 minutes; administration of antihistamines just before the infusion may also prevent or minimize this reaction.
Continuous: After loading dose, administer over 24 hours (Ref).
Irritant; ensure proper needle or catheter placement prior to and during infusion. Avoid extravasation. If extravasation occurs, stop infusion immediately and disconnect (leave cannula/needle in place); gently aspirate extravasated solution (do NOT flush the line); remove needle/cannula; elevate extremity. Information varies regarding the use of dry cold or dry warm compresses (Ref); however, dry warm compresses may be of benefit in increasing local blood flow to enhance drug removal from the extravasation site. Intradermal hyaluronidase may be considered for refractory cases (Ref).
Intrathecal/Intraventricular: Use preservative-free preparations only. Administer as diluted solution (1 to 10 mg/mL) over 1 to 2 minutes (Ref). When administered through a ventricular drain, clamp drain for 15 to 60 minutes to allow vancomycin solution to equilibrate in the cerebrospinal fluid (CSF) (Ref).
Intracatheter (vascular); antibiotic lock technique: Instill prepared vancomycin lock solution into each lumen of the catheter access port using a volume sufficient to fill the catheter with a dwell time of ≥8 to 12 hours and up to 72 hours (dependent on frequency of catheter use). Withdraw lock solution prior to catheter use; replace with fresh vancomycin lock solution after catheter use (Ref).
Rectal: Instill vancomycin enema solution via rectal foley; retain for 1 hour. In pediatric patients the optimal doses have not been established; suggested volumes for pediatric patients: 1 to 3 years of age: 50 mL; 4 to 9 years of age: 75 mL; >10 years of age: 100 mL (Ref).
Intravenous: Administer vancomycin with a final concentration not to exceed 5 mg/mL by IV intermittent infusion over at least 60 minutes (recommended infusion period of ≥30 minutes for every 500 mg administered (Ref)); in adult patients in need of fluid restriction, a concentration up to 10 mg/mL may be used, but risk of infusion-related reactions is increased. Not for IM administration.
If a maculopapular rash appears on the face, neck, trunk, and/or upper extremities (vancomycin infusion reaction [formerly “red man syndrome”]), slow the infusion rate to over 11/2 to 2 hours and increase the dilution volume (Ref). Hypotension, shock, and cardiac arrest (rare) have also been reported with too rapid of infusion. Administration of antihistamines prior to infusion may prevent or minimize this reaction (Ref).
Irritant; ensure proper needle or catheter placement prior to and during infusion. Avoid extravasation.
Extravasation management: If extravasation occurs, stop infusion immediately; leave cannula/needle in place temporarily but do NOT flush the line; gently aspirate extravasated solution, then remove needle/cannula; elevate extremity. Information conflicts regarding the use of dry cold or dry warm compresses (Ref); however, dry warm compresses may be of benefit in increasing local blood flow to enhance drug removal from the extravasation site. Hyaluronidase may be considered for refractory cases (Ref).
Hyaluronidase: Intradermal or SUBQ: Inject a total of 1 mL (15 units/mL) as 5 separate 0.2 mL injections (using a tuberculin syringe) around the site of extravasation; if IV catheter remains in place, administer IV through the infiltrated catheter; may repeat in 30 to 60 minutes if no resolution (Ref).
Antibiotic lock technique (off-label use): Instill prepared vancomycin lock solution into each lumen of the catheter access port using a volume sufficient to fill the catheter (2 to 5 mL) with a dwell time of 48 to 72 hours (dependent on frequency of catheter use). Withdraw lock solution prior to catheter use; replace with fresh vancomycin lock solution after catheter use (Ref).
Intraventricular (off-label route): Use preservative-free preparations only. May be administered intraventricularly with a final concentration of 2.5 to 10 mg/mL for the treatment of CSF shunt infections. When administered through a ventricular drain, clamp drain for 15 to 60 minutes before opening the drain to allow vancomycin solution to equilibrate in the CSF (Ref).
Intravitreal (off-label route): May administer vancomycin intravitreally with a final concentration of 1 mg/0.1 mL NS or sterile water (Ref).
Oral:
Solution (Firvanq): Shake reconstituted oral solution well before each use.
Injection: Reconstituted powder for injection (not premixed solution) may be diluted and used for oral administration; common flavoring syrups may be added to improve taste. The unflavored, diluted solution may also be administered via nasogastric tube.
Rectal (off-label route): May be administered as a retention enema per rectum (Ref); 500 mg in 100 to 500 mL of NS, volume may depend on length of segment being treated. If sodium chloride causes hyperchloremia could use solution with lower chloride concentration (eg, LR) (Ref).
Capsules: Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F).
Flexible bags: Store below 25°C (77°F) in the original package. Use within 28 days of removal from aluminum overpouch. Stable at room temperature for 28 days.
Galaxy containers: Store Galaxy containers at or below -20°C (-4°F). Handle frozen product containers with care; may be fragile in the frozen state. Thaw frozen containers at 25°C (77°F) or 5°C (41°F). Do not immerse in water bath or microwave. Thawed solution in remains chemically stable for 72 hours at 25°C (77°F) or for 30 days when stored at 5°C (41°F). Do not refreeze thawed antibiotics.
Oral solution (Firvanq): Store at 2°C to 8°C (36°F to 46°F) prior to and following reconstitution; discard reconstituted solution after 14 days or if appears hazy or contains particulates. Protect from light.
Vials: Store intact vials at 20°C to 25°C (68°F to 77°F). Reconstitute vial using an appropriate diluent; recommendations may vary by product; refer to manufacturer's labeling for choice of diluent and for appropriate storage conditions and timeframes. Prior to administration, further dilution in a compatible solution is required; recommendations may vary by product; refer to manufacturer's labeling for list of compatible solutions and appropriate storage conditions and timeframes.
Pharmacy bulk packages: Store at 20°C to 25°C (68°F to 77°F). Discard pharmacy bulk packages no later than 4 hours after initial closure puncture.
Parenteral: Treatment of patients with the following infections or conditions: Infections due to documented or suspected methicillin-resistant Staphylococcus aureus or beta-lactam resistant coagulase negative Staphylococcus; serious or life-threatening infections (eg, endocarditis, meningitis, osteomyelitis) due to documented or suspected staphylococcal or streptococcal infections in patients who are allergic to penicillins and/or cephalosporins; empiric therapy of infections associated with central lines, VP shunts, hemodialysis shunts, vascular grafts, prosthetic heart valves (FDA approved in all ages). Has also been used for prophylaxis of peritonitis in patients with peritoneal dialysis (PD) catheters undergoing invasive gastrointestinal procedure, touch contamination prophylaxis of PD catheter, and for the treatment of peritonitis in patients with peritoneal catheters.
Oral: Treatment of Clostridioides difficile infection and treatment of enterocolitis caused by S. aureus (including methicillin-resistant strains) (All indications: FDA approved in pediatric patients [age not specified] and adults).
IV vancomycin may be confused with INVanz
Vancomycin may be confused with clindamycin, gentamicin, tobramycin, valACYclovir, vecuronium, Vibramycin
The Institute for Safe Medication Practices (ISMP) includes this medication (intrathecal administration) among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Aminoglycosides: Vancomycin may enhance the nephrotoxic effect of Aminoglycosides. Vancomycin may enhance the neurotoxic effect of Aminoglycosides. Management: Consider avoiding coadministration of aminoglycosides and vancomycin unless clinically indicated. If coadministered, monitor closely for signs of nephrotoxicity and neurotoxicity. Risk D: Consider therapy modification
Amphotericin B: Vancomycin may enhance the nephrotoxic effect of Amphotericin B. Risk C: Monitor therapy
Bacillus clausii: Antibiotics may diminish the therapeutic effect of Bacillus clausii. Management: Bacillus clausii should be taken in between antibiotic doses during concomitant therapy. Risk D: Consider therapy modification
BCG (Intravesical): Antibiotics may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination
BCG Vaccine (Immunization): Antibiotics may diminish the therapeutic effect of BCG Vaccine (Immunization). Risk C: Monitor therapy
Cholera Vaccine: Antibiotics may diminish the therapeutic effect of Cholera Vaccine. Management: Avoid cholera vaccine in patients receiving systemic antibiotics, and within 14 days following the use of oral or parenteral antibiotics. Risk X: Avoid combination
Cloxacillin: May enhance the nephrotoxic effect of Vancomycin. Risk C: Monitor therapy
Colistimethate: Vancomycin may enhance the nephrotoxic effect of Colistimethate. Management: Avoid coadministration of colistimethate and vancomycin whenever possible due to the potential for additive or synergistic nephrotoxicity. If coadministration cannot be avoided, closely monitor renal function. Risk D: Consider therapy modification
Fecal Microbiota (Live) (Oral): May diminish the therapeutic effect of Antibiotics. Risk X: Avoid combination
Fecal Microbiota (Live) (Rectal): Antibiotics may diminish the therapeutic effect of Fecal Microbiota (Live) (Rectal). Risk X: Avoid combination
Flucloxacillin: May enhance the nephrotoxic effect of Vancomycin. Risk C: Monitor therapy
Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies): Antibiotics may diminish the therapeutic effect of Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies). Risk C: Monitor therapy
Lactobacillus and Estriol: Antibiotics may diminish the therapeutic effect of Lactobacillus and Estriol. Risk C: Monitor therapy
Loop Diuretics: May enhance the nephrotoxic effect of Vancomycin. Risk C: Monitor therapy
Neuromuscular-Blocking Agents: Vancomycin may enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Risk C: Monitor therapy
Nonsteroidal Anti-Inflammatory Agents: May increase the serum concentration of Vancomycin. Risk C: Monitor therapy
Piperacillin: May enhance the nephrotoxic effect of Vancomycin. Risk C: Monitor therapy
Sodium Picosulfate: Antibiotics may diminish the therapeutic effect of Sodium Picosulfate. Management: Consider using an alternative product for bowel cleansing prior to a colonoscopy in patients who have recently used or are concurrently using an antibiotic. Risk D: Consider therapy modification
Taurolidine: Vancomycin may diminish the therapeutic effect of Taurolidine. Risk C: Monitor therapy
Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Management: Avoid use of live attenuated typhoid vaccine (Ty21a) in patients being treated with systemic antibacterial agents. Postpone vaccination until 3 days after cessation of antibiotics and avoid starting antibiotics within 3 days of last vaccine dose. Risk D: Consider therapy modification
May be taken with food.
Pregnancy status should be evaluated in patients who may become pregnant prior to using the IV formulation containing the excipients polyethylene glycol (PEG 400) and N-acetyl D-alanine (NADA).
Vancomycin crosses the placenta and can be detected in fetal serum, amniotic fluid, and cord blood (Bourget 1991; Reyes 1989). Adverse fetal effects, including sensorineural hearing loss or nephrotoxicity, have not been reported following maternal use during the second or third trimesters of pregnancy.
The pharmacokinetics of vancomycin may be altered during pregnancy and pregnant patients may need a higher dose of vancomycin. Maternal half-life is unchanged, but the volume of distribution and the total plasma clearance may be increased (Bourget 1991). Individualization of therapy through serum concentration monitoring may be warranted.
Vancomycin is recommended for the treatment of mild, moderate, or severe Clostridioides difficile infections in pregnant patients. Standard doses should be used (ACG [Surawicz 2013]).
Vancomycin is recommended as an alternative option to prevent the transmission of group B streptococcal (GBS) disease from mothers to newborns. Untreated asymptomatic GBS disease can result in maternal urinary tract infection, intraamniotic infection, endometritis, preterm labor, and/or stillbirth. Vertical transmission from the mother can cause sepsis, pneumonia, or meningitis in the newborn. Vancomycin IV is recommended for use in women who are at high risk for anaphylaxis to penicillin (or whose risk is unknown), and the GBS isolate is resistant to clindamycin. Dose and rate of infusion should be based on maternal weight and renal function, similar to nonpregnant patients (ACOG 2020).
In patients known to be colonized with methicillin-resistant S. aureus (MRSA), a single dose of vancomycin is recommended as part of the antibiotic regimen for prophylactic use prior to cesarean delivery. Monotherapy with vancomycin does not provide sufficient coverage for cesarean delivery surgical prophylaxis (ACOG 2018).
Based on limited data, vancomycin is considered likely compatible with pregnancy when used for the treatment of airway diseases, such as cystic fibrosis (ERS/TSANZ [Middleton 2020]).
The formulation of vancomycin injection containing the excipients polyethylene glycol (PEG 400) and N-acetyl D-alanine (NADA) has caused fetal malformations in animal reproduction studies. If use of vancomycin is needed during the first or second trimesters of pregnancy, use other available formulations of vancomycin.
Renal function tests (eg, BUN, SCr, urine output), serum vancomycin concentrations (See "Reference Range"), WBC; hearing test (especially in patients receiving concurrent ototoxic agents); fluid status. Monitor for vancomycin infusion reaction during administration.
Parenteral therapy:
AUC-based monitoring (ASHP/IDSA/PIDS/SIDP [Rybak 2020]): Note: Evaluate vancomycin exposure using area under the curve over 24 hours (AUC24). AUC can be determined in neonatal and pediatric patients using either a neonatal- or pediatric-specific Bayesian software program with 1 or 2 concentrations (ie, trough only or peak and random or trough) or standard first-order pharmacokinetic equations using 2 vancomycin concentrations. AUC24 should be ≤800 mg•hour/L to minimize risk of nephrotoxicity.
Staphylococcus aureus target: AUC24:MIC: 400; potentially up to 600.
Note: Target for S. aureus is based on an MIC determined by broth microdilution (BMD); it is recommended to assume a minimum inhibitory concentration (MIC) of 1 mg/L, unless MIC is demonstrated to be >1 mg/L by BMD. Decreasing the dose when MIC <1 mg/L by BMD is not recommended. AUC24 should be ≤800 mg•hour/L and trough concentration ≤15 mg/L to minimize risk of nephrotoxicity.
Coagulase-negative staphylococci target: Neonates and infants ≤3 months of age (targets associated with bacteremia bacteriological cure): AUC24 ≥300 mg•hour/L in first 24 hours of therapy or AUC24 ≥424 mg•hour/L in the second 24 hours of therapy (Gwee 2022).
Trough-based monitoring: Note: Trough concentrations ≥15 mg/L have been associated with increased risk for acute kidney injury, likely due to association with elevated AUCs (ASHP/IDSA/PIDS/SIDP [Rybak 2020]).
Coagulase-negative staphylococci: Neonates: Trough concentrations 5 to 15 mg/L have been suggested based on limited data for AUC targets (Frymoyer 2019); however, AUC monitoring may be preferred (Gwee 2022).
Endocarditis: 10 to 15 mg/L; may target higher trough of 15 to 20 mg/L in patients with methicillin-resistant S. aureus (MRSA) with MIC >1 mg/L or who are not responding to appropriate therapy (AHA [Baltimore 2015]).
Meningitis, including health care-associated ventriculitis/meningitis: 15 to 20 mg/L (IDSA [Tunkel 2004]; IDSA [Tunkel 2017]).
MRSA infections: Though trough-only monitoring is not recommended for serious infections, trough serum concentration might be used as a surrogate marker for AUC when AUC monitoring is not available or for less serious infections; trough concentrations may not accurately predict AUC on an individual level (ASHP/IDSA/PIDS/SIDP [Rybak 2020]; Frymoyer 2014; Stockmann 2015).
Neonates: Trough concentrations of 8 to 15 mg/L have been associated with AUCs of ≥400 mg•hour/L (ASHP/IDSA/PIDS/SIDP [Rybak 2020]; Frymoyer 2014; Gwee 2019; Gwee 2022; Mulubwa 2020; Stockmann 2015; Tseng 2018).
Infants, Children, and Adolescents: Trough concentrations of 7 to 10 mg/L have been associated with AUCs >400 mg•hour/L; significant variability observed; lower trough concentrations (ie, 6 mg/L) may be associated with AUC >400 mg•hour/L when dose is divided every 8 hours (Frymoyer 2013; Le 2013).
Continuous infusion dosing:
Target steady-state concentration: Optimal target unknown.
General reported range: 15 to 30 mg/L; a variety of target concentrations have been reported in pediatric patients (Cies 2016; Genuini 2018; Guilhaumou 2016; Hurst 2019; McKamy 2012).
Note: Treatment of MRSA: 20 to 25 mg/L is recommended in adults. AUC24 can be estimated by multiplying the steady-state concentration by 24; a target steady-state concentration of 20 to 25 mg/L equates to an AUC24 of 480 to 600 mg•hour/L (ie, a steady-state concentration of ≥16.7 mg/L would equate to an AUC24 of ≥400 mg•hour/L) (ASHP/IDSA/PIDS/SIDP [Rybak 2020]).
Timing of serum sampling:
AUC: Monitoring may begin within 24 to 48 hours of drug initiation; Bayesian-derived AUC calculation programs do not require steady-state serum concentrations. First-order pharmacokinetic analytic equations to estimate AUC require collection of 2 serum concentrations; postdistributional peak concentration (Cmax) drawn 1 to 2 hours after infusion and trough concentration (Cmin) drawn at the end of the dosing interval. It is preferable that a near steady-state postdistributional peak and trough concentration within the same dosing interval (if possible) are used with the equation-based method. For Bayesian monitoring, 1 (ie, trough only) or 2 concentrations may be used. (ASHP/IDSA/PIDS/SIDP [Rybak 2020]).
Trough monitoring: Draw trough concentration just before the administration of a dose, at the end of the dosing interval, at steady-state conditions. Steady-state conditions generally occur approximately after the third dose; therefore, may begin monitoring vancomycin trough concentrations before the fourth dose (usually within 1 hour of administration). (ASHP/IDSA/SIDP [Rybak 2009]).
Continuous infusion monitoring: Obtain after steady-state has been reached, ≥24 hours after initiation of infusion; may obtain sooner if Bayesian-derived program is utilized (Berthaud 2019; Hurst 2019; McKamy 2012). Ensure that sample is obtained from a separate line or site than that through which vancomycin is infused; obtaining from the same line, even a separate lumen, or stopping the infusion is not recommended (Hurst 2019).
Frequency of serum sampling: Should be based on clinical judgment; close monitoring (more frequent or daily) recommended for hemodynamically unstable patients, patients with renal dysfunction, and patients with potential augmented renal clearance; hemodynamically stable patients may be monitored less frequently (once weekly) (ASHP/IDSA/PIDS/SIDP [Rybak 2020]).
Oral/rectal therapy: Serum sample monitoring is not typically required; systemic absorption of enteral vancomycin may occur in patients with mucosal disruption due to colitis, especially in patients with renal failure. Monitoring serum vancomycin levels may be considered for patients with renal failure who have severe colitis and require a prolonged course of enteral vancomycin (IDSA/SHEA [McDonald 2018]; Pettit 2015).
Inhibits bacterial cell wall synthesis by blocking glycopeptide polymerization through binding tightly to D-alanyl-D-alanine portion of cell wall precursor
Absorption: Oral: Poor; Rectal: significant absorption through inflamed colonic mucosa may occur; Intraperitoneal (IP): 60% of an IP dose absorbed in 6 hours.
Distribution: Distributes widely in body tissue and fluids, except for cerebrospinal fluid (CSF).
Vd:
Neonates, term: 0.57 to 0.69 L/kg (de Hoog 2004).
Infants: 0.56 L/kg (Rainkie 2015).
Children ≤6 years of age: 0.61 L/kg (Rainkie 2015).
Children >6 years of age: 0.47 L/kg (Rainkie 2015).
Adolescents: 0.49 L/kg (Rainkie 2015).
Adults: 0.4 to 1 L/kg (ASHP/IDSA/SIDP [Rybak 2009]); 0.3 to 0.5 L/kg in patients who are morbidly obese (Adane 2015; Bauer 1998; Hong 2015).
Relative diffusion from blood into CSF: Good only with inflammation (exceeds usual MICs).
Children:
CSF concentrations: 0.2 to 17.3 mg/L (de Hoog 2004).
CSF:blood level ratio: Normal meninges: Nil; Inflamed meninges: 7.1% to 68% (de Hoog 2004).
Adults:
Uninflamed meninges: 0 to 4 mg/L; serum concentration dependent (ASHP/IDSA/SIDP [Rybak 2009]).
Inflamed meninges: 6 to 11 mg/L; serum concentration dependent (ASHP/IDSA/SIDP [Rybak 2009]).
CSF:serum level ratio: Normal meninges: Nil; Inflamed meninges: ~80% (Shokouhi 2014).
Protein binding: ~55%.
Metabolism: No apparent metabolism.
Half-life elimination: Biphasic: Terminal:
Preterm neonates (GA: 32 to 34 weeks); PNA ~3 to 5 days: 5.9 to 9.8 hours (Schaad 1980).
Term neonates; PNA ~2 to 3 days: 6.7 hours (Schaad 1980).
Infants: 2.8 hours (Rainkie 2015).
Children <6 years of age: 2.4 hours (Rainkie 2015).
Children ≥6 years of age: 2.9 hours (Rainkie 2015).
Adolescents: 3.2 hours (Rainkie 2015).
Adults: 4 to 6 hours; significantly prolonged with renal impairment.
End-stage renal disease: 7.5 days.
Time to peak, serum: IV: Immediately after completion of infusion.
Excretion: Primarily via glomerular filtration; IV: Urine (75% as unchanged drug in the first 24 hours); Oral: Primarily feces.
Clearance: presence of malignancy in children is associated with an increase in vancomycin clearance.
Neonates: 0.63 to 1.5 mL/minute/kg; dependent on GA and/or PMA (de Hoog 2004).
Pediatric patients: Median: 1.1 mL/minute/kg (range: 0.33 to 1.87 mL/minute/kg) (Marsot 2012).
Adults: 1.6 to 6.2 L/hour (Matzke 1984); patients who are obese: ~6 L/hour (rarely exceeds 9 L/hour) (ASHP/IDSA/PIDS/SIDP [Rybak 2020]).
Pediatric: Extracorporeal membrane oxygenation (ECMO): Reported pharmacokinetic parameters in pediatric patients receiving ECMO vary widely based on ECMO circuitry/filters, age, weight, kidney function, and underlying diseases. In general, volume of distribution may be increased and clearance may be increased or decreased; reported parameters vary significantly; elimination half-life appears to be dependent upon renal function (Amaker 1996; Buck 1998; Cies 2017; Moffett 2018; Mulla 2005; Zylbersztajn 2018).
Older adult: Total systemic and renal clearance may be reduced.
Anti-infective considerations:
Parameters associated with efficacy: Note: Ratios, including the minimum inhibitory concentration (MIC), depend upon the methodology used; MIC determined by E-test is typically 1.5 to 2 times MIC determined by broth microdilution (ASHP/IDSA/PIDS/SIDP [Rybak 2020]).
Staphylococcus aureus: AUC/MICBMD ≥400 mg•hour/L (ASHP/IDSA/PIDS/SIDP [Rybak 2020]; Kullar 2011; Lodise 2014; Moise-Broder 2004); specific cutoff for efficacy has varied slightly between studies.
Enterococcus spp.: AUC/MICEtest ≥389 (Jumah 2018).
Coagulase-negative staphylococci (neonates): AUC24 ≥300 mg•hour/L in first 24 hours of therapy or AUC24 ≥424 mg•hour/L in the second 24 hours of therapy (Gwee 2022).
Parameters associated with toxicity: Nephrotoxicity: AUC ≥600 to 650 mg•hour/L (adults); ≥800 mg•hour/L (pediatrics); risk continues to increase along AUC continuum (Aljefri 2019; ASHP/IDSA/PIDS/SIDP [Rybak 2020]; Fiorito 2018; Le 2015; Lodise 2020); Cmin ≥15 mg/L (ASHP/IDSA/PIDS/SIDP [Rybak 2020]; van Hal 2013).
Postantibiotic effect: A short postantibiotic effect has been observed in E. faecalis (0.5 to 1 hour) and S. aureus (0.6 to 2 hours); slightly longer in S. epidermidis (4.3 to 6.5 hours) (Hanberger 1991; Löwdin 1998).
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