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VANCOCIN®^ HCl Vancomycin Hydrochloride for Injection USP For Intravenous Use
To reduce the development of drug-resistant bacteria and maintain the effectiveness of Vancocin ®^ HCl (Vancomycin Hydrochloride for Injection USP) and other antibacterial drugs, Vancocin ®^ HCl (Vancomycin Hydrochloride for Injection USP) should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria.
DESCRIPTION
Vancocin ®^ HCl (Vancomycin Hydrochloride for Injection USP) is a lyophilized powder, for preparing intravenous (IV) infusions, in vials each containing the equivalent of 500 mg or 1 g vancomycin base. 500 mg of the base are equivalent to 0.34 mmol. When reconstituted with Sterile Water for Injection to a concentration of 50 mg/mL, the pH of the solution is between 2. and 4.5. This product is oxygen sensitive. Vancocin ®^ HCl (Vancomycin Hydrochloride for Injection USP) should be administered intravenously in diluted solution (see DOSAGE AND ADMINISTRATION), AFTER RECONSTITUTION FURTHER DILUTION IS REQUIRED BEFORE USE.
Vancomycin is a tricyclic glycopeptide antibiotic derived from Amycolatopasis orientalis (formerly Nocardia orientals ). The chemical name for vancomycin hydrochloride is 3S- [3 R *,6 S *( S *),7 S *,22 S *,23 R *,26 R *,36 S *,38a S *]]-3-(2-Amino-2-oxoethyl)-44-[[2-O-(3-amino- 2,3,6-trideoxy-3-C-methyl-α-L-lyxo-hexopyranosyl)-ß-D-glucopyranosyl]oxy]-10,19-dichloro- 2,3,4,5,6,7,23,24,25,26,36,37,38,38a-tetradecahydro-7,22,28,30,32-pentahydroxy-6-[[4-methyl- 2-(methylamino)-1-oxopentyl]amino]-2,5,24,38,39-pentaoxo-22 H -8,11:18,21-dietheno-23,36- (iminomethano)-13,16:31,35-dimetheno-1 H ,16 H -[1,6,9]oxadiazacyclohexadecino[4,5- m ][10,2,16]-benzoxadiazacyclotetracosine-26-carboxylic acid, monohydrochloride. The molecular formula is C 66 H 75 Cl 2 N 9 O 24 • HCl and the molecular weight is 1,485.74. Vancomycin hydrochloride has the following structural formula:
CLINICAL PHARMACOLOGY
Vancomycin is poorly absorbed after oral administration.
In subjects with normal kidney function, multiple intravenous dosing of 1 g of vancomycin ( mg/kg) infused over 60 minutes produces mean plasma concentrations of approximately 63 mcg/mL immediately after the completion of infusion, mean plasma concentrations of approximately 23 mcg/mL 2 hours after infusion, and mean plasma concentrations of approximately 8 mcg/mL 11 hours after the end of the infusion. Multiple dosing of 500 mg infused over 30 minutes produces mean plasma concentrations of about 49 mcg/mL at the completion of infusion, mean plasma concentrations of about 19 mcg/mL 2 hours after infusion, and mean plasma concentrations of about 10 mcg/mL 6 hours after infusion. The plasma concentrations during multiple dosing are similar to those after a single dose.
The mean elimination half-life of vancomycin from plasma is 4 to 6 hours in subjects with normal renal function. In the first 24 hours, about 75% of an administered dose of vancomycin is excreted in urine by glomerular filtration. Mean plasma clearance is about 0.058 L/kg/h, and mean renal clearance is about 0.048 L/kg/h. Renal dysfunction slows excretion of vancomycin. In anephric patients, the average half-life of elimination is 7.5 days. The distribution coefficient is from 0.3 to 0.43 L/kg. There is no apparent metabolism of the drug. About 60% of an intraperitoneal dose of vancomycin administered during peritoneal dialysis is absorbed systemically in 6 hours. Serum concentrations of about 10 mcg/mL are achieved by intraperitoneal injection of 30 mg/kg of vancomycin. However, the safety and efficacy of the intraperitoneal use of vancomycin has not been established in adequate and well-controlled trials (see PRECAUTIONS ).
Total systemic and renal clearance of vancomycin may be reduced in the elderly. Vancomycin is approximately 55% serum protein bound as measured by ultrafiltration at vancomycin serum concentrations of 10 to 100 mcg/mL. After IV administration of vancomycin, inhibitory concentrations are present in pleural, pericardial, ascitic, and synovial fluids; in urine; in
Listeria monocytogenes Streptococcus pyogenes Streptococcus pneumoniae (including penicillin-resistant strains) Streptococcus agalactiae
Anaerobic gram-positive microorganisms
Actinomyces species
Lactobacillus species
Susceptibility Test Methods
When available, the clinical microbiology laboratory should provide cumulative reports of in vitro susceptibility test results for antimicrobial drugs used in local hospitals and practice areas to the physician as periodic reports that describe the susceptibility profile of nosocomial and community-acquired pathogens. These reports should aid the physician in selecting the most effective antimicrobial.
Dilution Techniques
Quantitative methods are used to determine antimicrobial minimum inhibitory concentrations (MICs). These MICs provide estimates of the susceptibility of bacteria to antimicrobial compounds. The MICs should be determined using a standardized test method1,2^ (broth, agar or microdilution). The MIC values should be interpreted according to the criteria in Table 1.
Diffusion Techniques
Quantitative methods that require measurement of zone diameters also provide reproducible estimates of the susceptibility of bacteria to antimicrobial compounds. The zone size should be determined using a standardized test method 2,3^. This procedure uses paper disks impregnated with 30 mcg of vancomycin to test the susceptibility of microorganisms to vancomycin. The disk diffusion breakpoints are provided in Table 1.
Table 1. Susceptibility Test Interpretive Criteria for Vancomycin
Pathogen
Minimum Inhibitory Concentrations (mcg/mL)
Disk Diffusion Diameters (mm) Susceptible (S)
Intermediate (I)
Resistant (R)
Susceptible (S)
Intermediate (I)
Resistant (R) Enterococci ≤ 4 8 to 16a^ ≥ 32 ≥ 17 b^ 15 to 16 b^ ≤ 14 b Staphylococcus aureus c,d^ ≤ 2 4 to 8 ≥ (^16) - - -
Coagulase- negative staphylococci d,e
≤ 4 8 to 16 ≥ (^32) - - -
Streptococci spp. other than ≤ 1 f,g^ -^ -^ ≥^17
f,h (^) - -
S. pneumoniae a (^) Isolates with vancomycin MICs of 8 to 16 mcg/mL should be further screened for vancomycin resistance
using standardized procedures. 1,
b (^) Plates should be held for a full 24 hours and examined using transmitted light. Measure the diameter of
the zones of complete inhibition (as judged by the unaided eye), including the diameter of the disk. The zone margin should be considered the area showing no obvious, visible growth that can be detected with the unaided eye. Ignore faint growth of tiny colonies that can be detected only with a magnifying lens at the edge of the zone of inhibited growth. Any discernible growth within the zone of inhibition indicates vancomycin resistance. Organisms with intermediate zones should be tested by a standardized dilution method.1,
c (^) Dilution testing should be performed to determine the susceptibility of all staphylococcal isolates. Disk
diffusion testing is not reliable for testing vancomycin, as it does not differentiate vancomycin-susceptible isolates of S. aureus from vancomycin-intermediate isolates, nor does it differentiate among vancomycin- susceptible, intermediate, and resistant isolates of coagulase-negative staphylococci.^2
d (^) Any S. aureus isolate for which the vancomycin MIC is ≥ 8 mcg/mL should be sent to a reference
laboratory. 2
e (^) Any coagulase-negative Staphylcoccus isolate for which the vancomycin MIC is ≥ 32 mcg/mL should be
sent to a reference laboratory.^2
f (^) The rare occurrence of resistant isolates precludes defining any results categories other than
“Susceptible”. For isolates yielding results suggestive of a nonsusceptible category, organism identification and vancomycin susceptibility test results should be confirmed. If confirmed, isolates should be sent to a reference laboratory.^2
g (^) Interpretative criteria applicable only to tests performed by broth microdilution method using cation-
adjusted Mueller-Hinton broth with 2 to 5% lysed horse blood. 1,
h (^) Interpretative criteria applicable only to tests performed by disk diffusion method using Mueller-Hinton
agar with 5% defibrinated sheep blood and incubated in 5% CO 23.
A report of “Susceptible” (S) indicates that the antimicrobial drug is likely to inhibit growth of the pathogen if the antimicrobial drug reaches the concentrations usually achievable at the site of infection. A report of “Intermediate” (I) indicates that the result should be considered equivocal, and, if the microorganism is not fully susceptible to alternative, clinically feasible drugs, the test should be repeated. This category implies possible clinical applicability in body sites where the drug is physiologically concentrated or in situations where high dosage of drug can be used. This category also provides a buffer zone which prevents small uncontrolled technical factors from causing major discrepancies in interpretation. A report of “Resistant” (R) indicates that the antimicrobial drug is not likely to inhibit growth of the pathogen if the antimicrobial drug reaches the concentrations usually achievable at the infection site; other therapy should be selected.
Quality Control
aminoglycoside, or both in early-onset prosthetic valve endocarditis caused by S. epidermidis or diphtheroids.
Specimens for bacteriologic cultures should be obtained in order to isolate and identify causative organisms and to determine their susceptibilities to vancomycin.
To reduce the development of drug-resistant bacteria and maintain the effectiveness of Vancocin ®^ HCl (Vancomycin Hydrochloride for Injection USP) and other antibacterial drugs, Vancocin ®^ HCl (Vancomycin Hydrochloride for Injection USP) should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.
The parenteral form of vancomycin hydrochloride may be administered orally for treatment of antibiotic-associated pseudomembranous colitis produced by C. difficile and for staphylococcal enterocolitis. Parenteral administration of vancomycin hydrochloride alone is of unproven benefit for these indications. Vancomycin is not effective by the oral route for other types of infections.
CONTRAINDICATIONS
Vancomycin hydrochloride for injection is contraindicated in patients with known hypersensitivity to this antibiotic.
WARNINGS
Infusion Reactions Rapid bolus administration (e.g., over several minutes) may be associated with exaggerated hypotension, including shock and rarely cardiac arrest.
Vancomycin hydrochloride for injection should be administered in a diluted solution over a period of not less than 60 minutes to avoid rapid-infusion-related reactions. Stopping the infusion usually results in prompt cessation of these reactions.
Nephrotoxicity Systemic vancomycin exposure may result in acute kidney injury (AKI). The risk of AKI increases as systemic exposure/serum levels increase. Monitor renal function in all patients, especially patients with underlying renal impairment, patients with co-morbidities that predispose to renal impairment, and patients receiving concomitant therapy with a drug known to be nephrotoxic.
Ototoxicity
Ototoxicity has occurred in patients receiving vancomycin hydrochloride for injection. It may be transient or permanent. It has been reported mostly in patients who have been given excessive doses, who have an underlying hearing loss, or who are receiving concomitant therapy with another ototoxic agent, such as an aminoglycoside. Vancomycin should be used with caution in patients with renal insufficiency because the risk of toxicity is appreciably increased by high, prolonged blood concentrations.
Dosage of vancomycin hydrochloride for injection must be adjusted for patients with renal dysfunction (see PRECAUTIONS and DOSAGE AND ADMINISTRATION ).
Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including vancomycin hydrochloride for injection, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile.
C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibiotic use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents.
If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile , and surgical evaluation should be instituted as clinically indicated.
PRECAUTIONS
Clinically significant serum concentrations have been reported in some patients being treated for active C. difficile -induced pseudomembranous colitis after multiple oral doses of vancomycin.
Prolonged use of vancomycin hydrochloride for injection may result in the overgrowth of nonsusceptible microorganisms. Careful observation of the patient is essential. If superinfection occurs during therapy, appropriate measures should be taken. In rare instances, there have been reports of pseudomembranous colitis due to C. difficile developing in patients who received intravenous vancomycin hydrochloride for injection.
Serial tests of auditory function may be helpful in order to minimize the risk of ototoxicity.
Reversible neutropenia has been reported in patients receiving vancomycin hydrochloride for injection (see ADVERSE REACTIONS ). Patients who will undergo prolonged therapy with vancomycin hydrochloride for injection or those who are receiving concomitant drugs which may cause neutropenia should have periodic monitoring of the leukocyte count.
Animal reproduction studies have not been conducted with vancomycin. It is not known whether vancomycin can affect reproduction capacity. In a controlled clinical study, the potential ototoxic and nephrotoxic effects of vancomycin on infants were evaluated when the drug was administered to pregnant women for serious staphylococcal infections complicating intravenous drug abuse. Vancomycin was found in cord blood. No sensorineural hearing loss or nephrotoxicity attributable to vancomycin was noted. One infant whose mother received vancomycin in the third trimester experienced conductive hearing loss that was not attributed to the administration of vancomycin. Because the number of patients treated in this study was limited and vancomycin was administered only in the second and third trimesters, it is not known whether vancomycin causes fetal harm. Vancomycin should be given to a pregnant woman only if clearly needed.
Nursing Mothers
Vancomycin hydrochloride for injection is excreted in human milk. Caution should be exercised when vancomycin hydrochloride for injection is administered to a nursing woman. Because of the potential for adverse events, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
Pediatric Use
In pediatric patients, it may be appropriate to confirm desired vancomycin serum concentrations. Concomitant administration of vancomycin and anesthetic agents has been associated with erythema and histamine-like flushing in pediatric patients (see PRECAUTIONS ).
Geriatric Use
The natural decrement of glomerular filtration with increasing age may lead to elevated vancomycin serum concentrations if dosage is not adjusted. Vancomycin dosage schedules should be adjusted in elderly patients (see DOSAGE AND ADMINISTRATION ).
Information for Patients
Patients should be counseled that antibacterial drugs including vancomycin hydrochloride for injection should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When vancomycin hydrochloride for injection is prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may (1) decrease the effectiveness of the immediate treatment and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by vancomycin hydrochloride for injection or other antibacterial drugs in the future.
Diarrhea is a common problem caused by antibiotics which usually ends when the antibiotic is discontinued. Sometimes after starting treatment with antibiotics, patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as two or more
months after having taken the last dose of the antibiotic. If this occurs, patients should contact their physician as soon as possible.
ADVERSE REACTIONS
Infusion-Related Events
During or soon after rapid infusion of vancomycin hydrochloride for injection, patients may develop anaphylactoid reactions, including hypotension (see ANIMAL PHARMACOLOGY ), wheezing, dyspnea, urticaria, or pruritus. Rapid infusion may also cause flushing of the upper body (“red neck”) or pain and muscle spasm of the chest and back. These reactions usually resolve within 20 minutes but may persist for several hours. Such events are infrequent if vancomycin hydrochloride for injection is given by a slow infusion over 60 minutes. In studies of normal volunteers, infusion-related events did not occur when vancomycin hydrochloride for injection was administered at a rate of 10 mg/min or less.
Nephrotoxicity
Systemic vancomycin exposure may result in acute kidney injury (AKI). The risk of AKI increases as systemic exposure/serum levels increase. Additional risk factors for AKI in patients receiving vancomycin include receipt of concomitant drugs known to be nephrotoxic, in patients with pre-exiting renal impairment, or with co-morbidities that predispose to renal impairment. Interstitial nephritis has also been reported in patients receiving vancomycin.
Gastrointestinal
Onset of pseudomembranous colitis symptoms may occur during or after antibiotic treatment (see WARNINGS ).
Ototoxicity
A few dozen cases of hearing loss associated with vancomycin have been reported. Most of these patients had kidney dysfunction or a preexisting hearing loss or were receiving concomitant treatment with an ototoxic drug. Vertigo, dizziness, and tinnitus have been reported rarely.
Hematopoietic
Reversible neutropenia, usually starting 1 week or more after onset of therapy with vancomycin or after a total dosage of more than 25 g, has been reported for several dozen patients.
Neutropenia appears to be promptly reversible when vancomycin is discontinued. Thrombocytopenia has rarely been reported. Although a causal relationship has not been established, reversible agranulocytosis (granulocytes <500/mm 3 ) has been reported rarely.
Phlebitis
recommended in adults (see also age-specific recommendations). In selected patients in need of fluid restriction, a concentration up to 10 mg/mL may be used; use of such higher concentrations may increase the risk of infusion-related events. An infusion rate of 10 mg/min or less is associated with fewer infusion-related events (see ADVERSE REACTIONS ). Infusion-related events may occur, however, at any rate or concentration.
Patients With Normal Renal Function
Adults
The usual daily intravenous dose is 2 g divided either as 500 mg every 6 hours or 1 g every 12 hours. Each dose should be administered at no more than 10 mg/min or over a period of at least 60 minutes, whichever is longer. Other patient factors, such as age or obesity, may call for modification of the usual intravenous daily dose.
Pediatric patients
The usual intravenous dosage of vancomycin is 10 mg/kg per dose given every 6 hours. Each dose should be administered over a period of at least 60 minutes. Close monitoring of serum concentrations of vancomycin may be warranted in these patients.
Neonates
In pediatric patients up to the age of 1 month, the total daily intravenous dosage may be lower. In neonates, an initial dose of 15 mg/kg is suggested, followed by 10 mg/kg every 12 hours for neonates in the 1st week of life and every 8 hours thereafter up to the age of 1 month. Each dose should be administered over 60 minutes. In premature infants, vancomycin clearance decreases as postconceptional age decreases. Therefore, longer dosing intervals may be necessary in premature infants. Close monitoring of serum concentrations of vancomycin is recommended in these patients.
Patients With Impaired Renal Function and Elderly Patients
Dosage adjustment must be made in patients with impaired renal function. In premature infants and the elderly, greater dosage reductions than expected may be necessary because of decreased renal function. Measurement of vancomycin serum concentrations can be helpful in optimizing therapy, especially in seriously ill patients with changing renal function. Vancomycin serum concentrations can be determined by use of microbiologic assay, radioimmunoassay, fluorescence polarization immunoassay, fluorescence immunoassay, or high-pressure liquid chromatography. If creatinine clearance can be measured or estimated accurately, the dosage for most patients with renal impairment can be calculated using the following table. The dosage of vancomycin hydrochloride for injection per day in mg is about 15 times the glomerular filtration rate in mL/min (see following table).
DOSAGE TABLE FOR VANCOMYCIN
IN PATIENTS WITH IMPAIRED RENAL FUNCTION
(Adapted from Moellering et al.^4 ) Creatinine Clearance mL/min
Vancomycin Dose mg/24 h 100 1, 90 1, 80 1, 70 1, 60 925 50 770 40 620 30 465 20 310 10 155
The initial dose should be no less than 15 mg/kg, even in patients with mild to moderate renal insufficiency. The table is not valid for functionally anephric patients. For such patients, an initial dose of 15 mg/kg of body weight should be given to achieve prompt therapeutic serum concentrations. The dose required to maintain stable concentrations is 1.9 mg/kg/24 hr. In patients with marked renal impairment, it may be more convenient to give maintenance doses of 250 to 1,000 mg once every several days rather than administering the drug on a daily basis. In anuria, a dose of 1,000 mg every 7 to 10 days has been recommended. When only serum creatinine is known, the following formula (based on sex, weight and age of the patient) may be used to calculate creatinine clearance. Calculated creatinine clearances (mL/min) are only estimates. The creatinine clearance should be measured promptly.
Men: [Weight (kg) x (140 - age in years)] 72 x serum creatinine concentration (mg/dL)
Women: 0.85 x above value
The serum creatinine must represent a steady state of renal function. Otherwise, the estimated value for creatinine clearance is not valid. Such a calculated clearance is an overestimate of actual clearance in patients with conditions: (1) characterized by decreasing renal function, such as shock, severe heart failure, or oliguria; (2) in which a normal relationship between muscle mass and total body weight is not present, such as in obese patients or those with liver disease, edema, or ascites; and (3) accompanied by debilitation, malnutrition, or inactivity. The safety and efficacy of vancomycin administration by the intrathecal (intralumbar or intraventricular) routes have not been established. Intermittent infusion is the recommended method of administration.
Compatibility with Other Drugs and IV Fluids
The following diluents are physically and chemically compatible (with 4 g/L vancomycin hydrochloride):
Isolyte ®^ E Acetated Ringer’s Injection
Vancomycin solution has a low pH and may cause chemical or physical instability when it is mixed with other compounds.
Mixtures of solutions of vancomycin and beta-lactam antibiotics have been shown to be physically incompatible. The likelihood of precipitation increases with higher concentrations of vancomycin. It is recommended to adequately flush the intravenous lines between the administration of these antibiotics. It is also recommended to dilute solutions of vancomycin to 5 mg/mL or less.
Although intravitreal injection is not an approved route of administration for vancomycin, precipitation has been reported after intravitreal injection of vancomycin and ceftazidime for endophthalmitis using different syringes and needles. The precipitates dissolved gradually, with complete clearing of the vitreous cavity over two months and with improvement of visual acuity.
Parenteral drug products should be visually inspected for particulate matter and discoloration prior to administration, whenever solution and container permit.
For Oral Administration
Oral vancomycin is used in treating antibiotic-associated pseudomembranous colitis caused by C. difficile and for staphylococcal enterocolitis. Vancomycin is not effective by the oral route for other types of infections. The usual adult total daily dosage is 500 mg to 2 g given in 3 or 4 divided doses for 7 to 10 days. The total daily dose in children is 40 mg/kg of body weight in 3 or 4 divided doses for 7 to 10 days. The total daily dosage should not exceed 2 g. The appropriate dose may be diluted in 1 oz of water and given to the patients to drink. Common flavoring syrups may be added to the solution to improve the taste for oral administration. The diluted solution may be administered via a nasogastric tube.
HOW SUPPLIED/STORAGE AND HANDLING
Vancocin ®^ HCl (Vancomycin Hydrochloride for Injection USP) are available in: The 500 mg,* 10-mL vials are available as: 10-mL vials and Pack of 25 The 1 g,* 20-mL vials are available as: Pack of 25
Also available:
Vancocin ®^ HCl ADD-Vantage®†^ Vials (Vancomycin Hydrochloride for Injection USP) are available in: The 500 mg,* 15-mL vials are available as: Pack of 10 The 1 g,* 15-mL vials are available as: Pack of 10
Vancocin ®^ HCl Pharmacy Bulk Package (Vancomycin Hydrochloride for Injection USP) are available in: The 10 g,* 100-mL vials are available as: 100-mL vial
Prior to reconstitution, the vials may be stored at room temperature, 15° to 30°C (59° to 86°F).
*Equivalent to vancomycin. †ADD-Vantage ® (^) (vials and diluent containers, Abbott).
ANIMAL PHARMACOLOGY
In animal studies, hypotension and bradycardia occurred in dogs receiving an intravenous infusion of vancomycin hydrochloride 25 mg/kg, at a concentration of 25 mg/mL and an infusion rate of 13.3 mL/min.
REFERENCES
- Clinical and Laboratory Standards Institute (CLSI). Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically; Approved Standard – Tenth Edition. CLSI document M07-A10. Clinical and Laboratory Standards Institute, 950 West Valley Road, Suite 2500, Wayne, Pennsylvania 19087, USA, 2015.
- Clinical and Laboratory Standards Institute (CLSI). Performance Standards for Antimicrobial Susceptibility Testing; Twenty-fifth Informational Supplement , CLSI document M100-S25, Clinical and Laboratory Standards Institute, 950 West Valley Road, Suite 2500, Wayne, Pennsylvania 19087, USA, 2015.
- Clinical and Laboratory Standards Institute (CLSI). Performance Standards for Antimicrobial Disk Susceptibility Tests; Approved Standard – Twelfth Edition. CLSI document M02-A12. Clinical and Laboratory Standards Institute, 950 West Valley Road, Suite 2500, Wayne, Pennsylvania 19087, USA, 2015.
- Moellering RC, Krogstad DJ, Greenblatt DJ: Vancomycin therapy in patients with impaired renal function: A nomogram for dosage. Ann Inter Med 1981;94:343.
ADD-VANTAGE ®^ (vials and diluent containers) is a registered trademark of Abbott Laboratories. NORMOSOL®-M is a registered trademark of Abbott Hospital Products (Division of Abbott Laboratories). ISOLYTE®^ E is a registered trademark of McGaw, Inc.
Distributed by: ANI Pharmaceuticals, Inc. Baudette, MN 56623
