Oxacillin

Brand names: Bactocill
Drug class: Antineoplastic Agents

Usage of Oxacillin

Staphylococcal Infections

Treatment of infections caused by, or suspected of being caused by, susceptible penicillinase-producing staphylococci, including respiratory tract, skin and skin structure, bone and joint, and urinary tract infections and meningitis or bacteremia. A drug of choice for these infections.

Treatment of native valve or prosthetic valve endocarditis caused by susceptible staphylococci. A drug of choice; used with or without gentamicin for native valve endocarditis and used in conjunction with rifampin and gentamicin for prosthetic valve endocarditis.

If used empirically, consider whether staphylococci resistant to penicillinase-resistant penicillins (oxacillin-resistant [methicillin-resistant] staphylococci) are prevalent in the hospital or community. (See Staphylococci Resistant to Penicillinase-resistant Penicillins under Cautions.)

Perioperative Prophylaxis

Has been used for perioperative prophylaxis† [off-label] in patients undergoing neurosurgery or cardiovascular or orthopedic surgery associated with high risk of staphylococcal infections. Not considered a drug of choice.

Relate drugs

How to use Oxacillin

Administration

Administer by IV injection or infusion or by IM injection.

To reduce risk of thrombophlebitis and other adverse local reactions associated with IV administration (particularly in geriatric patients), administer slowly and take care to avoid extravasation.

IV Injection

Reconstitution

Reconstitute vials containing 1 or 2 g of oxacillin by adding 10 or 20 mL, respectively, of sterile water for injection or 0.45 or 0.9% sodium chloride injection to provide solutions containing approximately 100 mg/mL.

Rate of Administration

Inject appropriate dose slowly over a period of about 10 minutes.

IV Infusion

Reconstitution and Dilution

Reconstitute vials containing 1 or 2 g of oxacillin by adding 10 or 20 mL, respectively, of sterile water for injection or 0.45 or 0.9% sodium chloride injection to provide a solution containing approximately 100 mg/mL. Reconstituted solution should then be further diluted with a compatible IV solution (see Solution Compatibility under Stability) to a concentration of 0.5–40 mg/mL.

Alternatively, ADD-Vantage vials containing 1 or 2 g of the drug should be reconstituted according to the manufacturer’s directions.

Reconstitute 10-g pharmacy bulk package with 93 mL of sterile water for injection or 0.9% sodium chloride injection to provide a solution containing 100 mg/mL. Pharmacy bulk packages of the drug are not intended for direct IV infusion; prior to administration, doses of the drug from the reconstituted pharmacy bulk package must be further diluted in a compatible IV infusion solution (see Solution Compatibility under Stability).

Thaw the commercially available injection (frozen) at room temperature or in a refrigerator; do not force thaw by immersion in a water bath or by exposure to microwave radiation. A precipitate may have formed in the frozen injection, but should dissolve with little or no agitation after reaching room temperature. Discard thawed injection if an insoluble precipitate is present or if container seals or outlet ports are not intact. Additives should not be introduced into the injection. The injections should not be used in series connections with other plastic containers, since such use could result in air embolism from residual air being drawn from the primary container before administration of fluid from the secondary container is complete.

Rate of Administration

The rate of IV infusion should be adjusted so that the total dose is administered before the drug is inactivated in the IV solution.

IM Administration

Inject IM deeply into a large muscle (e.g., gluteus maximus) avoiding sciatic nerve injury.

Reconstitution

For IM injection, reconstitute vial containing 1 or 2 g of oxacillin by adding 5.7 or 11.4 mL, respectively, of sterile water for injection to provide solutions containing 167 mg/mL (250 mg/1.5 mL). Shake vial well until a clear solution is obtained.

Dosage

Available as oxacillin sodium; dosage expressed in terms of oxacillin.

Duration of treatment depends on type and severity of infection and should be determined by clinical and bacteriologic response of the patient. For serious staphylococcal infections, duration usually is ≥1–2 weeks; more prolonged therapy is necessary for treatment of osteomyelitis or endocarditis.

Pediatric Patients

Staphylococcal Infections General Dosage in Neonates IV or IM

25 mg/kg daily recommended by manufacturer.

Neonates <1 week of age: AAP recommends 25 mg/kg every 12 hours for those weighing <1.2 kg; 25–50 mg/kg every 12 hours for those weighing 1.2 to 2 kg; and 25–50 mg/kg every 8 hours for those weighing >2 kg. The higher dosages are recommended for meningitis.

Neonates 1–4 weeks of age: AAP recommends 25 mg/kg every 12 hours for those weighing <1.2 kg; 25–50 mg/kg every 8 hours for those weighing 1.2 to 2 kg; and 25–50 mg/kg every 6 hours for those weighing >2 kg. The higher dosages are recommended for meningitis.

Mild to Moderate Infections in Infants and Children IV or IM

Children weighing <40 kg: 50 mg/kg daily given in equally divided doses every 6 hours.

Children weighing ≥40 kg: 250–500 mg every 4–6 hours.

Children ≥1 month of age: AAP recommends 100–150 mg/kg daily in 4 divided doses.

Severe Infections in Infants and Children IV or IM

Children weighing <40 kg: 100–200 mg/kg daily given in equally divided doses every 4–6 hours.

Children weighing ≥40 kg: 1 g every 4–6 hours.

Children ≥1 month of age: AAP recommends 150–200 mg/kg daily in 4–6 divided doses.

Staphylococcal Native Valve Endocarditis IV

AHA recommends 200 mg/kg daily given in divided doses every 4–6 hours for 6 weeks (maximum 12 g daily).

In addition, during the first 3–5 days of oxacillin therapy, IM or IV gentamicin (3 mg/kg daily given in divided doses every 8 hours; dosage adjusted to achieve peak serum gentamicin concentrations approximately 3 mcg/mL and trough concentrations <1 mcg/mL) may be given concomitantly if the causative organism is susceptible to the drug.

Staphylococcal Prosthetic Valve Endocarditis IV

AHA recommends 200 mg/kg daily given in divided doses every 4–6 hours for 6 weeks or longer (maximum 12 g daily).

Used in conjunction with oral rifampin (20 mg/kg daily given in divided doses every 8 hours for 6 weeks or longer) and IM or IV gentamicin (3 mg/kg daily given in divided doses every 8 hours during the first 2 weeks of oxacillin therapy; dosage adjusted to achieve peak serum gentamicin concentrations approximately 3 mcg/mL and trough concentrations <1 mcg/mL).

Adults

Staphylococcal Infections Mild to Moderate Infections IV or IM

250–500 mg every 4–6 hours.

Severe Infections IV or IM

1 g every 4–6 hours.

Acute or Chronic Staphylococcal Osteomyelitis IV

1.5–2 g every 4 hours.

When used for treatment of acute or chronic osteomyelitis caused by susceptible penicillinase-producing staphylococci, parenteral therapy generally continued for 3–8 weeks; follow-up with an oral penicillinase-resistant penicillin (e.g., dicloxacillin) generally recommended. In treatment of acute osteomyelitis, a shorter course of parenteral penicillinase-resistant therapy (5–28 days) followed by 3–6 weeks of oral penicillinase-resistant penicillin therapy also has been effective.

Staphylococcal Native Valve Endocarditis IV

AHA recommends 2 g every 4 hours for 4–6 weeks.

Although benefits of concomitant aminoglycosides have not been clearly established, AHA states that IM or IV gentamicin (1 mg/kg every 8 hours) may be given concomitantly during the first 3–5 days of oxacillin therapy.

Staphylococcal Prosthetic Valve Endocarditis IV

AHA recommends 2 g every 4 hours for ≥6 weeks in conjunction with oral rifampin (300 mg every 8 hours for 6 weeks or longer) and IM or IV gentamicin (1 mg/kg every 8 hours during the first 2 weeks of oxacillin therapy). (See Staphylococci Resistant to penicillinase-resistant Penicillins under Cautions.)

Staphylococcal Infections Related to Intravascular Catheters IV

2 g every 4 hours.

Special Populations

Renal Impairment

Modification of dosage generally is unnecessary in patients with renal impairment; some clinicians suggest that the lower range of the usual dosage (1 g IM or IV every 4–6 hours) be used in adults with Clcr <10 mL/minute.

Warnings

Contraindications

Hypersensitivity to any penicillin.

Warnings/Precautions

Sensitivity Reactions

Hypersensitivity Reactions

Serious and occasionally fatal hypersensitivity reactions, including anaphylaxis, reported with penicillins. Anaphylaxis occurs most frequently with parenteral penicillins but has occurred with oral penicillins.

Prior to initiation of therapy, make careful inquiry regarding previous hypersensitivity reactions to penicillins, cephalosporins, or other drugs. Partial cross-allergenicity occurs among penicillins and other β-lactam antibiotics including cephalosporins and cephamycins.

If a severe hypersensitivity reaction occurs, discontinue immediately and institute appropriate therapy as indicated (e.g., epinephrine, corticosteroids, maintenance of an adequate airway and oxygen).

General Precautions

Superinfection/Clostridium difficile-associated Colitis

Possible emergence and overgrowth of nonsusceptible organisms. Careful observation of the patient is essential. Institute appropriate therapy if superinfection occurs.

Treatment with anti-infectives may permit overgrowth of clostridia. Consider Clostridium difficile-associated diarrhea and colitis (antibiotic-associated pseudomembranous colitis) if diarrhea develops and manage accordingly.

Some mild cases of C. difficile-asssociated diarrhea and colitis may respond to discontinuance alone. Manage moderate to severe cases with fluid, electrolyte, and protein supplementation; appropriate anti-infective therapy (e.g., oral metronidazole or vancomycin) recommended if colitis is severe.

Laboratory Monitoring

Periodically assess organ system functions, including renal, hepatic, and hematopoietic, during prolonged therapy.

Perform urinalysis and determine serum creatinine and BUN concentrations prior to and periodically during therapy.

To monitor for hepatotoxicity, determine AST and ALT concentrations prior to and periodically during therapy.

Because adverse hematologic effects have occurred with penicillinase-resistant penicillins, total and differential WBC counts should be performed prior to and 1–3 times weekly during therapy.

Selection and Use of Anti-infectives

To reduce development of drug-resistant bacteria and maintain effectiveness of oxacillin and other antibacterials, use only for treatment or prevention of infections proven or strongly suspected to be caused by susceptible bacteria.

When selecting or modifying anti-infective therapy, use results of culture and in vitro susceptibility testing In the absence of such data, consider local epidemiology and susceptibility patterns when selecting anti-infectives for empiric therapy.

Staphylococci Resistant to Penicillinase-resistant Penicillins

Consider that staphylococci resistant to penicillinase-resistant penicillins (referred to as oxacillin-resistant [methicillin-resistant] staphylococci) are being reported with increasing frequency.

If oxacillin used empirically for treatment of any infection suspected of being caused by susceptible staphylococci, the drug should be discontinued and appropriate anti-infective therapy substituted if the infection is found to be caused by any organism other than penicillinase-producing staphylococci susceptible to penicillinase-resistant penicillins. If staphylococci resistant to penicillinase-resistant penicillins (oxacillin-resistant [methicillin-resistant] staphylococci) are prevalent in the hospital or community, empiric therapy of suspected staphylococcal infections should include another appropriate anti-infective (e.g., vancomycin).

In treatment of endocarditis, consider that coagulase-negative staphylococci causing prosthetic valve endocarditis usually are resistant to penicillinase-resistant penicillins (especially when endocarditis develops within 1 year after surgery). Therefore, coagulase-negative staphylococci involved in prosthetic valve endocarditis should be assumed to be resistant to penicillinase-resistant penicillins unless results of in vitro testing indicate that the isolates are susceptible to the drugs.

Sodium Content

Each 1 g of oxacillin sodium powder for injection contains approximately 2.5 mEq of sodium and is buffered with 20 mg of dibasic sodium phosphate.

Specific Populations

Pregnancy

Category B.

Lactation

Distributed into milk. Use with caution.

Pediatric Use

Elimination of penicillins is delayed in neonates because of immature mechanisms for renal excretion; abnormally high serum concentrations may occur in this age group.

If used in neonates, monitor closely for clinical and laboratory evidence of toxic or adverse effects, determine serum oxacillin concentrations frequently, and make appropriate reductions in dosage and frequency of administration when indicated.

Common Adverse Effects

Hypersensitivity reactions; local reactions (phlebitis, thrombophlebitis); renal, hepatic, or nervous system effects with high dosage.

What other drugs will affect Oxacillin

Specific Drugs

Drug

Interaction

Comments

Aminoglycosides

In vitro evidence of synergistic antibacterial effects against penicillinase-producing and nonpenicillinase-producing S. aureus

Anticoagulants, oral (warfarin)

Possible decreased hypothrombinemic effect reported with other penicillinase-resistant penicillins (dicloxacillin, nafcillin)

Monitor PT and adjust anticoagulant dosage if indicated

Cyclosporine

Decreased cyclosporine concentrations reported with some other penicillinase-resistant penicillins (e.g., nafcillin)

Probenecid

Decreased renal tubular secretion of penicillinase-resistant penicillins and increased and prolonged plasma concentrations

Rifampin

In vitro evidence of indifference or synergism against S. aureus with low oxacillin concentrations and antagonism with high oxacillin concentrations

Possible delay or prevention of emergence of rifampin-resistant S. aureus

Tetracyclines

Possible antagonism

Concomitant use not recommended

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