Bactocill

Generic Name: Oxacillin Sodium
Class: Penicillinase-resistant Penicillins
Chemical Name: [2S - (2α,5α,6β)] - 3,3 - Dimethyl - 6 - [[(5 - methyl - 3 - phenyl - 4 - isoxazolyl)carbonyl]amino] - 7 - oxo - 4 - thia - 1 - azabicyclo[3.2.0]heptane - 2 - carboxylic acid monosodium salt monohydrate
CAS Number: 7240-38-2

Introduction

Antibacterial; β-lactam antibiotic; isoxazolyl penicillin classified as a penicillinase-resistant penicillin.^{1 4 5 9 46 70}

Uses for Bactocill

Staphylococcal Infections

Treatment of infections caused by, or suspected of being caused by, susceptible penicillinase-producing staphylococci,^{1 6 47 66 70 71} including respiratory tract, skin and skin structure, bone and joint, and urinary tract infections and meningitis or bacteremia.^a A drug of choice for these infections.^a

Treatment of native valve or prosthetic valve endocarditis caused by susceptible staphylococci.^{50 69} A drug of choice;^{50 69} used with or without gentamicin for native valve endocarditis and used in conjunction with rifampin and gentamicin for prosthetic valve endocarditis.^{50 69}

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

Perioperative Prophylaxis

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

Bactocill Dosage and Administration

Administration

Administer by IV injection or infusion or by IM injection.¹

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.^{1 a}

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.¹

Rate of Administration

Inject appropriate dose slowly over a period of about 10 minutes.¹

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.¹ 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.¹

Alternatively, ADD-Vantage vials containing 1 or 2 g of the drug should be reconstituted according to the manufacturer’s directions.⁶³

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.² 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).²

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.⁶⁴ A precipitate may have formed in the frozen injection, but should dissolve with little or no agitation after reaching room temperature.⁶⁴ Discard thawed injection if an insoluble precipitate is present or if container seals or outlet ports are not intact.⁶⁴ Additives should not be introduced into the injection.⁶⁴ 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.⁶⁴

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.¹

IM Administration

Inject IM deeply into a large muscle (e.g., gluteus maximus) avoiding sciatic nerve injury.⁵⁸

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).¹ Shake vial well until a clear solution is obtained.¹

Dosage

Available as oxacillin sodium; dosage expressed in terms of oxacillin.¹

Duration of treatment depends on type and severity of infection and should be determined by clinical and bacteriologic response of the patient.^{1 58 64} For serious staphylococcal infections, duration usually is ≥1–2 weeks; more prolonged therapy is necessary for treatment of osteomyelitis or endocarditis.^{1 58 64 71}

Pediatric Patients

Staphylococcal Infections

General Dosage in Neonates

IV or IM

25 mg/kg daily recommended by manufacturer.¹

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.⁶⁷ The higher dosages are recommended for meningitis.⁶⁷

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.⁶⁷ The higher dosages are recommended for meningitis.⁶⁷

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.^{1 58 64}

Children weighing ≥40 kg: 250–500 mg every 4–6 hours.^{1 58 64}

Children ≥1 month of age: AAP recommends 100–150 mg/kg daily in 4 divided doses.⁶⁷

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.^{1 47 49 58 64 67 71}

Children weighing ≥40 kg: 1 g every 4–6 hours.^{1 58 64}

Children ≥1 month of age: AAP recommends 150–200 mg/kg daily in 4–6 divided doses.⁶⁷

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).⁶⁹

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.⁶⁹

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).⁶⁹

Adults

Staphylococcal Infections

Mild to Moderate Infections

IV or IM

250–500 mg every 4–6 hours.^{1 58 64}

Severe Infections

IV or IM

1 g every 4–6 hours.^{1 58 64}

Acute or Chronic Staphylococcal Osteomyelitis

IV

1.5–2 g every 4 hours.⁴⁹

When used for treatment of acute or chronic osteomyelitis caused by susceptible penicillinase-producing staphylococci, parenteral therapy generally continued for 3–8 weeks;^{48 49 52 57 71} follow-up with an oral penicillinase-resistant penicillin (e.g., dicloxacillin) generally recommended.^{49 51 71} 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.^{49 51 52 57}

Staphylococcal Native Valve Endocarditis

IV

AHA recommends 2 g every 4 hours for 4–6 weeks.⁵⁰

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.⁵⁰

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).⁵⁰ (See Staphylococci Resistant to penicillinase-resistant Penicillins under Cautions.)

Staphylococcal Infections Related to Intravascular Catheters

IV

2 g every 4 hours.⁷³

Special Populations

Renal Impairment

Modification of dosage generally is unnecessary in patients with renal impairment;^{18 53 56} 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 Cl_cr <10 mL/minute.^{22 28 54 68}

Cautions for Bactocill

Contraindications

• 
  

  Hypersensitivity to any penicillin.^{1 58 64}

  
  

Warnings/Precautions

Sensitivity Reactions

Hypersensitivity Reactions

Serious and occasionally fatal hypersensitivity reactions, including anaphylaxis, reported with penicillins.^{1 58 64} Anaphylaxis occurs most frequently with parenteral penicillins but has occurred with oral penicillins.^{1 58 64}

Prior to initiation of therapy, make careful inquiry regarding previous hypersensitivity reactions to penicillins, cephalosporins, or other drugs.^{1 58 64} Partial cross-allergenicity occurs among penicillins and other β-lactam antibiotics including cephalosporins and cephamycins.^{1 33 34 42 43}

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).^{1 58 64}

General Precautions

Superinfection/Clostridium difficile-associated Colitis

Possible emergence and overgrowth of nonsusceptible organisms.¹ Careful observation of the patient is essential.¹ Institute appropriate therapy if superinfection occurs.¹

Treatment with anti-infectives may permit overgrowth of clostridia.¹ Consider Clostridium difficile-associated diarrhea and colitis (antibiotic-associated pseudomembranous colitis) if diarrhea develops and manage accordingly.¹

Some mild cases of C. difficile-asssociated diarrhea and colitis may respond to discontinuance alone.^{1 a} 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.^{1 a}

Laboratory Monitoring

Periodically assess organ system functions, including renal, hepatic, and hematopoietic, during prolonged therapy.¹

Perform urinalysis and determine serum creatinine and BUN concentrations prior to and periodically during therapy.^{1 58 64}

To monitor for hepatotoxicity, determine AST and ALT concentrations prior to and periodically during therapy.^{1 58 64}

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.^{40 41 58 64}

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 testing¹ In the absence of such data, consider local epidemiology and susceptibility patterns when selecting anti-infectives for empiric therapy.¹

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.^a

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.¹ 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).^a

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).⁵⁰ 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.⁵⁰

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.¹

Specific Populations

Pregnancy

Category B.¹

Lactation

Distributed into milk.^{58 63} Use with caution.^{58 63}

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.^{58 63}

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.^{1 58 63}

Common Adverse Effects

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

Interactions for Bactocill

Specific Drugs

Drug	Interaction	Comments
Aminoglycosides	In vitro evidence of synergistic antibacterial effects against penicillinase-producing and nonpenicillinase-producing S. aureusa
Anticoagulants, oral (warfarin)	Possible decreased hypothrombinemic effect reported with other penicillinase-resistant penicillins (dicloxacillin, nafcillin)a	Monitor PT and adjust anticoagulant dosage if indicateda
Cyclosporine	Decreased cyclosporine concentrations reported with some other penicillinase-resistant penicillins (e.g., nafcillin)a
Probenecid	Decreased renal tubular secretion of penicillinase-resistant penicillins and increased and prolonged plasma concentrationsa
Rifampin	In vitro evidence of indifference or synergism against S. aureus with low oxacillin concentrations and antagonism with high oxacillin concentrationsa Possible delay or prevention of emergence of rifampin-resistant S. aureusa
Tetracyclines	Possible antagonisma	Concomitant use not recommendeda

Bactocill Pharmacokinetics

Absorption

Bioavailability

Rapidly absorbed from IM injection sites;^{1 14 29 30 31} peak serum concentrations generally attained within 30 minutes.^{1 14 31}

Distribution

Extent

Distributed into synovial,^{5 24} pleural,^{1 5} pericardial,¹⁰ and ascitic fluids.¹⁰ Also distributed into bone,^{10 16 17 24 55} lungs,⁶² sputum,⁵ and bile.^{1 5 31}

Only low concentrations attained in CSF.^{1 10 31}

Crosses the placenta^{5 31} and is distributed into milk.^{1 5 31}

Plasma Protein Binding

89–94% bound to serum proteins.^{4 15 19 20 70}

Elimination

Metabolism

Partially metabolized to active and inactive metabolites.^{10 23 27}

Approximately 49% of a dose is hydrolyzed to penicilloic acids which are microbiologically inactive;²³ also hydroxylated to a small extent to a microbiologically active metabolite which appears to be slightly less active than oxacillin.²⁷

Elimination Route

Oxacillin and its metabolites rapidly eliminated in urine principally by tubular secretion and glomerular filtration.^{1 5 10 27 70}

Following IM administration, 40–70% of the dose is excreted in urine as unchanged drug and active metabolites within 6 hours.³¹

Half-life

Adults with normal renal function: 0.3–0.8 hours.^{1 7 10 15 21 22 45}

Children 1 week to 2 years of age: 0.9–1.8 hours.²⁶

Neonates: 1.6 hours in those 8–15 days of age and 1.2 hours in those 20–21 days of age.⁷⁰

Special Populations

Patients with renal impairment: serum half-life slightly prolonged.^{7 15 18 28 45} Serum half-life may be 0.5–2 hours in patients with Cl_cr <10 mL/minute per 1.73 m².^{7 15 18 45}

Stability

Storage

Parenteral

Powder for Injection

15–30°C.⁶⁸

Solutions reconstituted from ADD-Vantage vials using 0.9% sodium chloride injection or 5% dextrose injection are stable at room temperature for 4 days or 6 hours, respectively.⁶³

IM solutions containing 167 mg/mL (250 mg/1.5 mL) prepared using sterile water for injection are stable for 3 days at room temperature or 7 days when refrigerated.¹

Injection (Frozen)

≤ -20° C.⁶⁴ Thawed solutions of the commercial frozen injection stable for 48 hours at room temperature (25°C) or 21 days at 5°C.^{64 65}

Do not refreeze after thawing.⁶⁴

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Solution Compatibility^HID

Compatible
Amino acids 4.25%, dextrose 25%
Dextran 70 6% in dextrose 5%
Dextran 40 10% in dextrose 5%
Dextrose 5% in Ringer’s injection, lactated
Dextrose 10% in water
Hetastarch 6% in sodium chloride 0.9%
Ringer’s injection, lactated
Variable
Dextrose 5% in sodium chloride 0.9%
Dextrose 5% in water
Sodium chloride 0.9%

Drug Compatibility

Admixture CompatibilityHID

Compatible
Chloramphenicol sodium succinate
Dopamine HCl
Potassium chloride
Incompatible
Cytarabine
Variable
Amikacin sulfate
Verapamil HCl

Y-Site CompatibilityHID

Compatible
Acyclovir sodium
Cyclophosphamide
Diltiazem HCl
Doxapram HCl
Famotidine
Fluconazole
Foscarnet sodium
Heparin sodium
Hydrocortisone sodium succinate
Hydromorphone HCl
Labetalol HCl
Levofloxacin
Magnesium sulfate
Meperidine HCl
Methotrexate sodium
Milrinone lactate
Morphine sulfate
Perphenazine
Potassium chloride
Tacrolimus
Vitamin B complex with C
Zidovudine
Incompatible
Sodium bicarbonate
Verapamil HCl

Actions and SpectrumActions

• 
  

  Based on spectrum of activity, classified as a penicillinase-resistant penicillin.^{4 5 9 10 46 58 70 64}

  
  


• 
  

  Usually bactericidal.¹

  
  


• 
  

  Like other β-lactam antibiotics, antibacterial activity results from inhibition of bacterial cell wall synthesis.¹

  
  


• 
  

  Spectrum of activity includes many gram-positive aerobic cocci, some gram-positive bacilli, and a few gram-negative aerobic cocci; generally inactive against gram-negative bacilli and anaerobic bacteria.^a Inactive against mycobacteria, Mycoplasma, Rickettsia, fungi, and viruses.^a

  
  


• 
  

  Gram-positive aerobes: active in vitro against penicillinase-producing and nonpenicillinase-producing Staphylococcus aureus and S. epidermidis, S. pyogenes (group A β-hemolytic streptococci), S. agalactiae (group B streptococci), groups C and G streptococci, S. pneumoniae, and some viridans streptococci.^a Enterococci (including E. faecalis) usually are resistant.^a

  
  


• 
  

  Like other penicillinase-resistant penicillins, oxacillin is resistant to inactivation by staphylococcal penicillinases and is active against many penicillinase-producing strains of S. aureus and S. epidermidis resistant to natural penicillins, aminopenicillins, or extended-spectrum penicillins.^{9 11 58 70}

  
  


• 
  

  Staphylococci resistant to penicillinase-resistant penicillins (referred to as oxacillin-resistant [methicillin-resistant] staphylococci) are being reported with increasing frequency.^a Complete cross-resistance occurs among the penicillinase-resistant penicillins (dicloxacillin, nafcillin, oxacillin).^a

  
  

Advice to Patients

• 
  

  Importance of discontinuing oxacillin and notifying clinician if evidence of hypersensitivity occurs.¹

  
  


• 
  

  Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.¹

  
  


• 
  

  Importance of women informing clinician if they are or plan to become pregnant or plan to breast-feed.¹

  
  


• 
  

  Importance of advising patients of other important precautionary information. (See Cautions.)

  
  

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Oxacillin Sodium

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Parenteral	For injection	1 g (of oxacillin)	Oxacillin Sodium for Injection	Sandoz
		2 g (of oxacillin)	Oxacillin Sodium for Injection	Sandoz
		10 g (of oxacillin) pharmacy bulk package	Oxacillin Sodium for Injection	Sandoz
	For injection, for IV infusion	1 g (of oxacillin)	Oxacillin Sodium ADD-Vantage	Sandoz
		2 g (of oxacillin)	Oxacillin Sodium ADD-Vantage	Sandoz

Oxacillin Sodium in Dextrose

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Parenteral	Injection (frozen), for IV infusion	20 mg (of oxacillin) per mL (1 g) in 3% Dextrose	Oxacillin Sodium in Iso-osmotic Dextrose Injection	Baxter
		40 mg (of oxacillin) per mL (2 g) in 0.6% Dextrose	Oxacillin Sodium in Iso-osmotic Dextrose Injection	Baxter

Disclaimer

This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.

The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.

AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions September 2007. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

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