General dosing, susceptible infection (nonmeningitis) (Bradley 2018; Red Book [AAP 2015]): IM, IV:
|
Body Weight |
Postnatal Age |
Dose |
|---|---|---|
|
<1 kg |
≤14 days |
25 mg/kg/dose every 12 hours |
|
15 to 28 days |
25 mg/kg/dose every 8 hours | |
|
29 to 60 days |
37.5 mg/kg/dose every 6 hours | |
|
1 to 2 kg |
≤7 days |
25 mg/kg/dose every 12 hours |
|
8 to 28 days |
25 mg/kg/dose every 8 hours | |
|
29 to 60 days |
37.5 mg/kg/dose every 6 hours | |
|
>2 kg |
≤7 days |
25 mg/kg/dose every 8 hours |
|
8 to 28 days |
25 mg/kg/dose every 6 hours | |
|
29 to 60 days |
37.5 mg/kg/dose every 6 hours |
Meningitis (Bradley 2018): IV:
|
Body Weight |
Postnatal Age |
Dose |
|---|---|---|
|
<1 kg |
≤14 days |
50 mg/kg/dose every 12 hours |
|
15 to 28 days |
50 mg/kg/dose every 8 hours | |
|
1 to 2 kg |
≤7 days |
50 mg/kg/dose every 12 hours |
|
8 to 28 days |
50 mg/kg/dose every 8 hours | |
|
>2 kg |
≤7 days |
50 mg/kg/dose every 8 hours |
|
8 to 28 days |
50 mg/kg/dose every 6 hours |
General dosing, susceptible infection (Red Book [AAP 2015]):
Mild to moderate infections: Infants, Children, and Adolescents: IM, IV: 100 to 150 mg/kg/day in divided doses every 6 hours; maximum daily dose: 4,000 mg/day
Severe infections: Infants, Children, and Adolescents: IM, IV: 150 to 200 mg/kg/day in divided doses every 4 to 6 hours; maximum daily dose: 12 g/day
Endocarditis, treatment: Children and Adolescents: IV: 200 mg/kg/day in divided doses every 4 to 6 hours; maximum daily dose: 12 g/day; treat for at least 4 weeks; longer durations may be necessary; may use in combination with gentamicin for some resistant organisms (AHA [Baltimore 2015])
Meningitis/Ventriculitis: Infants, Children, and Adolescents: IV: 200 mg/kg/day in divided doses every 6 hours; maximum daily dose: 12 g/day (IDSA [Tunkel 2004]; IDSA [Tunkel 2017])
Pneumonia, community-acquired (CAP) moderate to severe infection, S. aureus (methicillin-susceptible): Infants >3 months, Children, and Adolescents: IV: 150 to 200 mg/kg/day divided every 6 to 8 hours (IDSA/PIDS [Bradley 2011])
Skin and soft tissue infections (IDSA [Stevens 2014]): Infants, Children, and Adolescents:
Methicillin-susceptible Staphylococcus aureus (MSSA): IV: 100 to 150 mg/kg/day in divided doses every 6 hours; maximum daily dose: 12 g/day
Necrotizing infection due to MSSA: IV: 200 mg/kg/day in divided doses every 6 hours; maximum daily dose: 12 g/day; continue until further debridement is not necessary, patient has clinically improved, and patient is afebrile for 48 to 72 hours
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Not dialyzable (0% to 5%). There are no dosage adjustments provided in the manufacturer's labeling; however, manufacturer suggests considering a reduction in total dosage if renal impairment is known or suspected.
There are no dosage adjustments provided in the manufacturer's labeling.
(For additional information see "Oxacillin: Drug information")
Note: May contain a significant amount of sodium; consult product specific labeling for amount.
Catheter-related bloodstream infections (off-label use): IV: 2 g every 4 hours (Mermel 2009).
Endocarditis, treatment: Methicillin-susceptible Staphylococcus aureus (MSSA) (off-label dose): IV:
Native valve: 12 g/day in 4 or 6 divided doses (ie, 2 g every 4 hours or 3 g every 6 hours) for 6 weeks. Note: Dosing intended for complicated right-sided infective endocarditis (IE) or left-sided IE. For uncomplicated right-sided IE, 2 weeks of therapy may be adequate (AHA [Baddour 2015]).
Prosthetic valve: 12 g/day in 6 divided doses (ie, 2 g every 4 hours) for at least 6 weeks (use with rifampin for entire course and gentamicin for first 2 weeks) (AHA [Baddour 2015]).
Meningitis, bacterial: Methicillin-susceptible S. aureus: (off-label dose): IV: 2 g every 4 hours; consider addition of rifampin if organism is susceptible and prosthetic material is present (IDSA [Tunkel 2004]; IDSA [Tunkel 2017]).
Osteomyelitis, native vertebral (off-label dose): Staphylococcus (oxacillin-susceptible): IV: 1.5 to 2 g every 4 to 6 hours or via continuous infusion for 6 weeks (IDSA [Berbari 2015]).
Pneumonia: Pathogen-directed therapy for methicillin-susceptible S. aureus: IV: 2 g every 4 hours (Klompas 2022). Minimum duration is generally 5 days for community-acquired pneumonia and 7 days for hospital-acquired or ventilator-associated pneumonia; patients should be clinically stable with normal vital signs before therapy is discontinued (IDSA/ATS [Kalil 2016]; IDSA/ATS [Metlay 2019]).
Prosthetic joint infection: IV: 2 g every 4 hours with rifampin.
Staphylococcus aureus, methicillin-susceptible infections, including brain abscess, bursitis, erysipelas, mastitis, mastoiditis, osteomyelitis, perinephric abscess, pneumonia, pyomyositis, scalded skin syndrome, toxic shock syndrome: IV: 2 g every 4 hours.
Skin and soft tissue infection:
Cellulitis (nonpurulent) in patients without risk for methicillin-resistant S. aureus: IV: 1 to 2 g every 4 hours. Total duration of therapy is ≥5 days (including oral step-down therapy); may extend up to 14 days depending on severity and clinical response (IDSA [Stevens 2014]; Spelman 2021).
Necrotizing infection due to methicillin-susceptible S. aureus (MSSA) (off-label use): IV: 1 to 2 g every 4 hours; continue until further debridement is not necessary, patient has clinically improved, and patient is afebrile for 48 to 72 hours (IDSA [Stevens 2014]).
Surgical site infections (trunk or extremity [away from axilla or perineum]) (off-label use): IV: 2 g every 6 hours (IDSA [Stevens 2014]).
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.
Altered kidney function:
CrCl ≥10 mL/minute: No dosage adjustment necessary (Golightly 2013; expert opinion).
CrCl <10 mL/minute: No specific dosage adjustment recommended; however, monitor closely as high oxacillin concentrations and neurotoxicity have been reported in this population (Neuville 2017). When treating less severe infections, a maximum daily dose of 8 g/day may be considered (expert opinion).
Intermittent hemodialysis (thrice weekly): Not significantly dialyzed (Bulger 1964): No specific dosage adjustment recommended; however, monitor closely as high oxacillin concentrations and neurotoxicity have been reported in this population (Neuville 2017). When treating less severe infections, a maximum daily dose of 8 g/day may be considered (expert opinion).
Peritoneal dialysis: Minimally dialyzed (5%) (Ruedy 1966): No specific dosage adjustment recommended; however, monitor closely as high oxacillin concentrations and neurotoxicity have been reported in this population (Neuville 2017). When treating less severe infections, a maximum daily dose of 8 g/day may be considered (expert opinion).
CRRT: No dosage adjustment necessary (Golightly 2013; expert opinion).
PIRRT (eg, sustained, low-efficiency diafiltration): No dosage adjustment necessary (expert opinion).
There are no dosage adjustments provided in the manufacturer’s labeling.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous:
Generic: 1 g/50 mL (50 mL); 2 g/50 mL (50 mL)
Solution Reconstituted, Injection:
Generic: 1 g (1 ea); 2 g (1 ea)
Solution Reconstituted, Injection [preservative free]:
Generic: 1 g (1 ea); 2 g (1 ea)
Solution Reconstituted, Intravenous:
Generic: 10 g (1 ea)
Solution Reconstituted, Intravenous [preservative free]:
Generic: 10 g (1 ea)
Yes
Parenteral:
IM: Administer by deep IM injection into a large muscle mass (eg, gluteus maximus); avoid sciatic nerve injury
IV:
Direct IV injection: Administer over 10 minutes at a concentration of 100 mg/mL
Intermittent IV infusion: Administer over 15 to 30 minutes (Klaus 1989); extending the infusion over 60 minutes has been used for peripheral administration by some ambulatory centers to decrease the risk of phlebitis in homecare patients (Dahlgren 1997)
IV: Administer IVP over 10 minutes or IVPB over 30 minutes.
Premixed infusions: Store in a freezer at -20°C (-4°F). Thaw at room temperature or under refrigeration only. Thawed bags are stable for 21 days under refrigeration or 48 hours at room temperature. Do not refreeze.
Vials: Store intact vials at 20°C to 25°C (68°F to 77°F); refer to manufacturer’s labeling for specific storage instructions after dilution (varies by concentration and diluent).
Treatment of bacterial infections, such as osteomyelitis, septicemia, endocarditis, and CNS infections, due to susceptible penicillinase-producing strains of Staphylococcus (FDA approved in all ages)
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
Frequency not defined:
Gastrointestinal: Clostridioides difficile associated diarrhea, clostridioides difficile colitis
Hepatic: Hepatotoxicity, increased serum aspartate aminotransferase
Renal: Acute interstitial nephritis, acute renal tubular disease
<1%, postmarketing, and/or case reports: Drug reaction with eosinophilia and systemic symptoms (Sharpe 2019)
Hypersensitivity (eg, anaphylaxis) to oxacillin, any penicillin, or any component of the formulation.
Concerns related to adverse effects:
• Anaphylactic/hypersensitivity reactions: Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported in patients on penicillin therapy, especially with a history of beta-lactam hypersensitivity, history of sensitivity to multiple allergens, or previous IgE-mediated reactions (eg, anaphylaxis, angioedema, urticaria). Use with caution in patients with histories of significant allergies and/or asthma; discontinue treatment and institute appropriate therapy if an allergic reaction occurs
• Hepatitis: Acute hepatitis and reversible elevations of serum transaminases have been reported sometimes accompanied by rash and leukopenia; onset after 2 to 3 weeks of therapy; monitor periodically throughout therapy (Dahlgren 1997; Faden 2009; Maraqa 2002).
• Superinfection: Prolonged use may result in fungal or bacterial superinfection, including C. difficile-associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been observed >2 months postantibiotic treatment.
Disease-related concerns:
• Renal impairment: Use with caution in severe impairment.
Special populations:
• Elderly: May contain a significant amount of sodium; consult product specific labeling for amount. The elderly population may respond with a blunted natriuresis to salt loading. This may be clinically important in diseases such as congestive heart failure.
• Neonates: Use with caution in neonates; elimination of drug is decreased; dosage adjustment is needed.
In neonates, elimination rate is decreased due to immature renal function; dosage adjustment is needed; hematuria and azotemia have occurred in neonates and infants receiving high-dose oxacillin. In a study of pediatric patients (5 to 19 years) receiving outpatient oxacillin, significantly less rash was reported in the nafcillin group (10.3%) compared to the oxacillin group (31.7%) (Maraqa 2002).
None known.
Acemetacin: May increase the serum concentration of Penicillins. Risk C: Monitor therapy
Aminoglycosides: Penicillins may decrease the serum concentration of Aminoglycosides. Primarily associated with extended spectrum penicillins, and patients with renal dysfunction. Risk C: Monitor therapy
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
Dichlorphenamide: Penicillins may enhance the hypokalemic effect of Dichlorphenamide. Risk C: Monitor therapy
Immune Checkpoint Inhibitors: Antibiotics may diminish the therapeutic effect of Immune Checkpoint Inhibitors. Risk C: Monitor therapy
Lactobacillus and Estriol: Antibiotics may diminish the therapeutic effect of Lactobacillus and Estriol. Risk C: Monitor therapy
Methotrexate: Penicillins may increase the serum concentration of Methotrexate. Risk C: Monitor therapy
Mycophenolate: Penicillins may decrease serum concentrations of the active metabolite(s) of Mycophenolate. This effect appears to be the result of impaired enterohepatic recirculation. Risk C: Monitor therapy
Probenecid: May increase the serum concentration of Penicillins. 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
Tetracyclines: May diminish the therapeutic effect of Penicillins. 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
Vitamin K Antagonists (eg, warfarin): Penicillins may enhance the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy
Some products may contain sodium.
Oxacillin crosses the placenta.
Although it is highly protein bound, therapeutic concentrations can be found in the amniotic fluid following IV administration (Nau 1987).
As a class, penicillin antibiotics are widely used in pregnant women. Based on available data, penicillin antibiotics are generally considered compatible for use during pregnancy (Ailes 2016; Bookstaver 2015; Crider 2009; Czeizel 1999; Damkier 2019; Lamont 2014; Muanda 2017a; Muanda 2017b).
Periodic CBC with differential, urinalysis, BUN, serum creatinine, AST and ALT; number and type of stools/day for diarrhea; observe IV site for extravasation
Inhibits bacterial cell wall synthesis by binding to one or more of the penicillin-binding proteins (PBPs); which in turn inhibits the final transpeptidation step of peptidoglycan synthesis in bacterial cell walls, thus inhibiting cell wall biosynthesis. Bacteria eventually lyse due to ongoing activity of cell wall autolytic enzymes (autolysins and murein hydrolases) while cell wall assembly is arrested.
Distribution: Into bile, pleural fluids; insignificant concentrations in CSF and aqueous humor
Protein binding: ~94% (mainly albumin)
Metabolism: Hepatic
Half-life elimination:
Neonates (PNA: 8 to 15 days): 1.6 hours
Infants and Children ≤2 years: 0.9 to 1.8 hours
Adults: 20 to 30 minutes; prolonged with renal impairment
Time to peak, serum: IM: 30 minutes; IV: 5 minutes
Excretion: Urine and bile (unchanged drug)
Anti-infective considerations:
Parameters associated with efficacy: Time dependent, associated with time free drug concentration (fT) > minimum inhibitory concentration (MIC); goal: ≥50% fT > MIC (bactericidal) (Drusano 2003; Turnidge 1998).
Critically ill patients in the ICU: Minimum goal: ≥50% fT > MIC; preferred goal: ≥100% fT > MIC (Abdul-Aziz 2020; Al-Shaer 2020; Roberts 2014); some experts favor ≥100% fT > 4 times the MIC (Guilhaumou 2019).
Expected drug exposure:
Cmax (peak): Single dose: IV: Adults: 500 mg: 43 mg/L.
Postantibiotic effect: Minimal bacterial killing continues after concentration of penicillins fall below the MIC of targeted pathogen and varies based on the organism:
Gram-positive cocci: 1.5 to 3.5 hours (Craig 1991).
Gram-negative bacilli: 0 to 1.5 hours (Craig 1991).
May contain a significant amount of sodium; consult product specific labeling for amount.
Solution (Oxacillin Sodium in Dextrose Intravenous)
1 gm/50 mL (per mL): $0.41
2 gm/50 mL (per mL): $0.59
Solution (reconstituted) (Oxacillin Sodium Injection)
1 g (per each): $13.50 - $14.50
2 g (per each): $12.38 - $29.00
Solution (reconstituted) (Oxacillin Sodium Intravenous)
10 g (per each): $66.30 - $145.00
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