Oxacillin Injection

Use the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not use extra medicine to make up the missed dose.

Usual Adult Dose for Bacterial Infection:

Manufacturer Recommendations:
Mild to moderate infections: 250 to 500 mg IV or IM every 4 to 6 hours
Severe infections: 1 g IV or IM every 4 to 6 hours

Duration of therapy: Therapy should continue for at least 14 days in severe staphylococcal infections. Therapy should continue for at least 48 hours after patient is afebrile, asymptomatic, and has negative cultures. Endocarditis and osteomyelitis may require a longer duration of therapy.

Approved indication: Treatment of infections caused by susceptible penicillinase-producing staphylococci

Usual Adult Dose for Endocarditis:

Manufacturer Recommendations: See Usual Adult Dose (Bacterial Infection)

American Heart Association (AHA) recommendations:
Native valve endocarditis due to staphylococci: 2 g IV every 4 hours or 3 g IV every 6 hours (total 12 g/day)

Duration of therapy:
Complicated right-sided infective endocarditis (IE), left-sided IE: 6 weeks
Uncomplicated right-sided IE: 2 weeks

Comments:
-With optional addition of gentamicin 3 mg/kg/day IV or IM in 2 or 3 equally divided doses for 3 to 5 days.
-Refer to current published guidelines for detailed recommendations.

Prosthetic valve endocarditis due to staphylococci: 2 g IV every 4 hours (total 12 g/day)
Duration of therapy: 6 weeks or longer

Comments:
-Plus rifampin 300 mg IV or orally every 8 hours for 6 weeks or longer.
-Plus gentamicin 3 mg/kg/day IV or IM in 2 or 3 equally divided doses for 2 weeks.
-Refer to current published guidelines for detailed recommendations.

Usual Adult Dose for Joint Infection:

Manufacturer Recommendations: See Usual Adult Dose (Bacterial Infection)

Some experts recommend: 2 g IV or IM every 4 to 6 hours
Duration of therapy: 3 to 4 weeks, depending on the nature and severity of the infection. Longer therapy, for 6 weeks or longer, may be required for prosthetic joint infections.
Comments: A third-generation cephalosporin, ciprofloxacin, and/or rifampin should be added, depending on the results of the Gram stain.

Usual Adult Dose for Meningitis:

Manufacturer Recommendations: See Usual Adult Dose (Bacterial Infection)

Some experts recommend: 2 g IV or IM every 4 hours
Duration of therapy: 14 days, depending on the nature and severity of the infection.

Usual Adult Dose for Osteomyelitis:

Manufacturer Recommendations: See Usual Adult Dose (Bacterial Infection)

Some experts recommend: 1.5 to 2 g IV every 4 hours
Duration of therapy: In general, treatment of acute or chronic osteomyelitis should continue for 3 to 8 weeks followed by treatment with an oral penicillinase-resistant penicillin. Parenteral penicillinase-resistant therapy for 5 to 28 days followed by oral penicillinase-resistant penicillin for 3 to 6 weeks has also been effective for acute osteomyelitis.

Usual Adult Dose for Pneumonia:

Manufacturer Recommendations: See Usual Adult Dose (Bacterial Infection)

Some experts recommend: 2 g IV or IM every 4 hours
Duration of therapy: Therapy should continue for 7 to 10 days if pneumococcus pneumonia is suspected and up to 21 days if other organisms are responsible.

Usual Adult Dose for Septicemia:

Manufacturer Recommendations: See Usual Adult Dose (Bacterial Infection)

Some experts recommend: 2 g IV or IM every 4 to 6 hours
Duration of therapy: 14 days, depending on the nature and severity of the infection.

Usual Adult Dose for Sinusitis:

Manufacturer Recommendations: See Usual Adult Dose (Bacterial Infection)

Some experts recommend: 1 to 1.5 g IV or IM every 4 to 6 hours
Duration of therapy: 10 to 14 days, depending on the nature and severity of the infection.

Usual Adult Dose for Skin or Soft Tissue Infection:

Manufacturer Recommendations: See Usual Adult Dose (Bacterial Infection)

Some experts recommend: 1 to 1.5 g IV or IM every 4 to 6 hours
Duration of therapy: 7 days, or for 3 days after acute inflammation resolves, depending on the nature and severity of the infection.

Usual Pediatric Dose for Bacterial Infection:

Manufacturer Recommendations:
Premature and neonates: 25 mg/kg/day IV or IM

Infants and children weighing less than 40 kg:
Mild to moderate infections: 12.5 mg/kg IV or IM every 6 hours
Severe infections: 100 mg/kg/day IV or IM in equally divided doses every 4 to 6 hours

Children weighing 40 kg or more:
Mild to moderate infections: 250 to 500 mg IV or IM every 4 to 6 hours
Severe infections: 1 g IV or IM every 4 to 6 hours

Duration of therapy: Therapy should continue for at least 14 days in severe staphylococcal infections. Therapy should continue for at least 48 hours after patient is afebrile, asymptomatic, and has negative cultures. Endocarditis and osteomyelitis may require a longer duration of therapy.

Approved indication: Treatment of infections caused by susceptible penicillinase-producing staphylococci

American Academy of Pediatrics Recommendations:
Less than 1 week:
Less than 1200 g: 25 mg/kg IV or IM every 12 hours
1200 to 2000 g: 25 to 50 mg/kg IV or IM every 12 hours
Greater than 2000 g: 25 to 50 mg/kg IV or IM every 8 hours

1 to 4 weeks:
Less than 1200 g: 25 mg/kg IV or IM every 12 hours
1200 to 2000 g: 25 to 50 mg/kg IV or IM every 8 hours
Greater than 2000 g: 25 to 50 mg/kg IV or IM every 6 hours

1 month or older:
Mild to moderate infections: 100 to 150 mg/kg/day IV or IM in 4 divided doses
Severe infections: 150 to 200 mg/kg/day IV or IM in 4 divided doses

Maximum dose: 12 g/day

Usual Pediatric Dose for Endocarditis:

Manufacturer Recommendations: See Usual Pediatric Dose (Bacterial Infection)

AHA recommendations:
Native valve endocarditis due to staphylococci: 200 mg/kg/day IV in 4 to 6 equally divided doses
Maximum dose: 12 g/day

Duration of therapy:
Complicated right-sided IE, left-sided IE: 6 weeks
Uncomplicated right-sided IE: 2 weeks

Comments:
-With optional addition of gentamicin 1 mg/kg IV or IM every 8 hours for 3 to 5 days.
-Refer to current published guidelines for detailed recommendations.

Prosthetic valve endocarditis due to staphylococci: 200 mg/kg/day IV in 4 to 6 equally divided doses
Maximum dose: 12 g/day
Duration of therapy: 6 weeks or longer

Comments:
-Plus rifampin 20 mg/kg/day IV or orally in 3 equally divided doses for 6 weeks or longer.
-Plus gentamicin 1 mg/kg IV or IM every 8 hours for 2 weeks.
-Refer to current published guidelines for detailed recommendations.

Intravenous administration provides peak serum levels approximately 5 minutes after the injection is completed. Slow I.V. administration of 500 mg gives a peak serum level of 43 mcg/mL after 5 minutes with a half-life of 20-30 minutes.

Oxacillin sodium, with normal doses, has insignificant concentrations in the cerebrospinal and ascitic fluids. It is found in therapeutic concentrations in the pleural, bile, and amniotic fluids.

Oxacillin sodium is rapidly excreted as unchanged drug in the urine by glomerular filtration and active tubular secretion. The elimination half-life for oxacillin is about 0.5 hours. Nonrenal elimination includes hepatic inactivation and excretion in bile.

Oxacillin sodium binds to serum protein, mainly albumin. The degree of protein binding reported varies with the method of study and the investigator, but generally has been found to be 94.2% ± 2.1%.

Probenecid blocks the renal tubular secretion of penicillins. Therefore, the concurrent administration of probenecid prolongs the elimination of oxacillin and, consequently, increases the serum concentration.

Intramuscular injections give peak serum levels 30 minutes after injection. A 250 mg dose gives a level of 5.3 mcg/mL while a 500 mg dose peaks at 10.9 mcg/mL. Intravenous injection gives a peak about 5 minutes after the injection is completed. Slow IV dosing with 500 mg gives a 5 minute peak of 43mcg/mL with a half-life of 20 to 30 minutes.

Microbiology

Mode of Action

Penicillinase-resistant penicillins exert a bactericidal action against penicillin susceptible microorganisms during the state of active multiplication. All penicillins inhibit the biosynthesis of the bacterial cell wall.

Mechanism of Resistance

Resistance to penicillins may be mediated by destruction of the beta-lactam ring by a beta-lactamase, altered affinity of penicillin for target, or decreased penetration of the antibiotic to reach the target site.

Cross-Resistance

Resistance to oxacillin (or cefoxitin) implies resistance to all other beta-lactam agents, except newer agents with activity against methicillin-resistant Staphylococcus aureus.

Susceptibility Test Methods

When available, the clinical microbiology laboratory should provide the results of in vitro susceptibility test results for antimicrobial drug products 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 antibacterial drug product for treatment.

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 method 1, 2 (broth and/or agar). The MIC values obtained should be interpreted according to the criteria in Table 1.

Diffusion Techniques

Quantitative methods that require measurement of zone diameters can also provide reproducible estimates of the susceptibility of bacteria to antimicrobial compounds. The zone size should be determined using a standardized method2, 3. It has been determined that the most accurate method to test the susceptibility of microorganisms to penicillinase resistant penicillins, including oxacillin, by disk diffusion is achieved using disks impregnated with 30 mcg cefoxitin. Interpretation involves correlation of the diameter obtained with the cefoxitin disk test with the MIC for oxacillin2. Reports from the laboratory providing results of the standard single-disk susceptibility test with a 30 microgram cefoxitin disk should be interpreted according to the following criteria in Table 1.

S=susceptible, I=intermediate, R=resistant

a  In most staphylococcal isolates, oxacillin resistance is mediated by mecA, encoding the penicillin binding protein 2a (PBP2a, also called PBP2’). Isolates that test positive for mecA or PBP2a should be reported as oxacillin resistant.”

b Cefoxitin is used as a surrogate for oxacillin; report oxacillin susceptible or resistant based on the cefoxitin result.2 

c If both cefoxitin and oxacillin are tested against S. aureus or S. lugdenensis, and either result is resistant, the organism should be reported as oxacillin resistant. 2 

d Oxacillin MIC interpretive criteria may overcall resistance for some coagulase-negative staphylococci (CoNS), because some non-S. epidermidis strains for which the oxacillin MICs are 0.5 to 2 mcg/ml lack mecA. For serious infections with CoNS other than S. epidermidis, testing for mecA or for PBP 2a or with cefoxitin disk diffusion may be appropriate for strains for which the oxaillin MICs are 0.5 to 2 mcg/ml. 2

A report of “Susceptible” indicates that the antimicrobial is likely to inhibit the growth of the pathogen if the antimicrobial compound reaches the concentrations at the infection site necessary to inhibit growth of the pathogen. A report of “Intermediate” 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. This category also provides a buffer zone that prevents small uncontrolled technical factors from causing major discrepancies in interpretation. A report of “Resistant” indicates that the antimicrobial is not likely to inhibit growth of the pathogen if the antimicrobial compound reaches the concentrations usually achievable at the infection site; other therapy should be selected.

Quality Control

Standardized susceptibility test procedures require the use of laboratory controls to monitor and ensure the accuracy and precision of supplies and reagents used in the assay, and the techniques of the individuals performing the test.1, 2, 3 Standard oxacillin powder should provide the following range of MIC values1 noted in Table 2. For the diffusion technique using the 30 mcg cefoxitin disk, the criteria provided in Table 2 should be achieved.

ATCC=American Type Culture Collection

a Despite the lack of reliable disk diffusion interpretive criteria for S. pneumoniae with certain beta-lactams, Streptococcus pneumoniae ATCC 49619 is the strain designated for QC of all disk diffusion tests with Streptococcus spp.

b Deterioration of oxacillin disk content is best assessed with QC organism S. aureus ATCC® 25923, with an acceptable zone diameter for 18-24.

A history of a hypersensitivity (anaphylactic) reaction to any penicillin is a contraindication.

Bacteriologic studies to determine the causative organisms and their susceptibility to oxacillin should always be performed. Duration of therapy varies with the type and severity of infection as well as the overall condition of the patient, therefore it should be determined by the clinical and bacteriological response of the patient. In severe staphylococcal infections, therapy with oxacillin should be continued for at least 14 days. Therapy should be continued for at least 48 hours after the patient has become afebrile, asymptomatic, and cultures are negative. The treatment of endocarditis and osteomyelitis may require a longer term of therapy.

With intravenous administration, particularly in elderly patients, care should be taken because of the possibility of thrombophlebitis.

Directions for use

For Intramuscular Use: Use Sterile Water for Injection, USP. Add 5.4 mL to the 1 gram vial, 10.6 mL to the 2 gram vial. Shake well until a clear solution is obtained. After reconstitution, vials will contain 250 mg of active drug per 1.5 mL of solution. The reconstituted solution is stable for 3 days at 70° F or for one week under refrigeration (40° F).

For Direct Intravenous Use: Use Sterile Water for Injection, USP or Sodium Chloride Injection, USP. Add 10 mL to the 1 gram vial, 20 mL to the 2 gram vial. Withdraw the entire contents and administer slowly over a period of approximately 10 minutes.

For Administration by Intravenous Drip: Reconstitute as directed above (For Direct Intravenous Use) prior to diluting with Intravenous Solution.

Stability studies on oxacillin sodium at concentrations of 0.5 mg/mL and 2 mg/mL in various intravenous solutions listed below indicate the drug will lose less than 10% activity at room temperature (70° F) during a 6-hour period.

IV Solution

5% Dextrose in Normal Saline

10% D-Fructose in Water

10% D-Fructose in Normal Saline

Lactated Potassic Saline Injection

10% Invert Sugar in Normal Saline

10% Invert Sugar Plus 0.3% Potassium Chloride in Water

Travert 10% Electrolyte #1

Travert 10% Electrolyte #2

Travert 10% Electrolyte #3

Only those solutions listed above should be used for the intravenous infusion of oxacillin sodium. The concentration of the antibiotic should fall within the range specified. The drug concentration and the rate and volume of the infusion should be adjusted so that the total dose of oxacillin is administered before the drug loses its stability in the solution in use.

If another agent is used in conjunction with oxacillin therapy, it should not be physically mixed with oxacillin but should be administered separately.

Oxacillin for Injection, USP contains oxacillin sodium equivalent to 1 gram or 2 grams oxacillin per vial.

NDC 70655-099-95 1 gram vial packaged in 10s

NDC 70655-109-95 2 grams vial packaged in 10s

Store the dry powder at 20°-25°C (68°-77°F) [See USP Controlled Room Temperature].

Pain/redness/swelling at the injection site may occur. If any of these effects last or get worse, tell your doctor or pharmacist promptly.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor right away if you have any serious side effects, including: easy bruising/bleeding, signs of a new infection (such as sore throat that doesn't go away, fever, chills), foamy/pink/bloody/dark urine, signs of kidney problems (such as a change in the amount of urine), swelling hands/ankles/feet, stomach/abdominal pain, nausea/vomiting that doesn't stop, unusual tiredness, yellowing eyes/skin, seizures, uncontrolled movements, mental/mood changes (such as confusion, hallucinations).

This medication may rarely cause a severe intestinal condition (Clostridium difficile-associated diarrhea) due to a type of resistant bacteria. This condition may occur during treatment or weeks to months after treatment has stopped. Tell your doctor right away if you develop: diarrhea that doesn't stop, abdominal or stomach pain/cramping, blood/mucus in your stool.

Do not use anti-diarrhea products or narcotic pain medications if you have any of these symptoms because these products may make them worse.

Use of this medication for prolonged or repeated periods may result in oral thrush or a new yeast infection. Contact your doctor if you notice white patches in your mouth, a change in vaginal discharge, or other new symptoms.

A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

In the US -

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch.

In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

Applies to oxacillin: injectable powder for injection, intravenous solution, oral capsule, oral powder for reconstitution

Gastrointestinal

Gastrointestinal side effects have included nausea, vomiting, diarrhea, stomatitis, black or hairy tongue, gastrointestinal irritation, and pseudomembranous colitis.[Ref]

Hematologic

Hematologic effects of oxacillin are uncommon and appear to be associated with higher doses given for prolonged periods. Oxacillin may exert a reversible toxic effect on the maturation of granulocytes. Some investigators have also suggested a possible hypersensitivity or immunologic component. Recovery generally occurs within several days to 2 weeks following discontinuation of therapy. Penicillin and some of its other semisynthetic derivatives are also associated with hematologic toxicities.[Ref]

Hematologic adverse effects have included neutropenia, leukopenia, thrombocytopenia, bone marrow depression, and agranulocytosis.[Ref]

Hepatic

Hepatic side effects have included cholestatic jaundice associated with the use of high parenteral doses. A case of severe hepatitis has also been reported. Alkaline phosphatase and GGT serum levels may take several weeks to return to normal following discontinuation of therapy.[Ref]

Serum liver enzyme levels have typically returned to normal soon after stopping therapy or changing to another antibiotic such as nafcillin, which is chemically related to oxacillin. Patients may be asymptomatic or have hepatic tenderness or enlargement and/or pronounced fever, nausea, and vomiting. Hepatotoxicity may also occur on a hypersensitivity basis and accompany some allergic manifestations such as pruritus, eosinophilia, and serum sickness.

Intravenous oxacillin has been associated with a higher incidence of hepatotoxicity than nafcillin, clindamycin, or other intravenous antimicrobials in children. The onset of hepatitis occurred after 6 to 43 days of oxacillin treatment (n=9).[Ref]

Hypersensitivity

Hypersensitivity reactions have included urticaria, pruritus, angioneurotic edema, laryngospasm, bronchospasm, hypotension, vascular collapse, anaphylaxis, death, serum sickness-like reactions, fever, and rash.[Ref]

Local

Local side effects of parenteral administration have included thrombophlebitis and tissue necrosis following extravasation.[Ref]

Renal

Renal side effects have included acute renal failure and interstitial nephritis.[Ref]

Nervous system

Nervous system side effects including seizures have occurred when large parenteral doses of oxacillin were administered to patients with renal failure.[Ref]

Metabolic

Metabolic side effects including severe hypokalemia, have been rarely associated with the use of high dose oxacillin (12 grams per day for 10 days).[Ref]

Dermatologic

Intravenous oxacillin has been associated with a higher incidence of rash than nafcillin or other intravenous antimicrobials in children. The onset of rash occurred after a mean of 19.5 days of oxacillin treatment.[Ref]

Dermatologic side effects included hypersensitivity-related urticaria, pruritus, and rash.[Ref]

Some side effects of oxacillin may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.