Ther. Class.

Pharm. Class.
penicillinase resistant penicillins


Treatment of the following infections due to penicillinase-producing staphylococci:

  • Respiratory tract infections,
  • Sinusitis,
  • Osteomyelitis,
  • Skin and skin structure infections.


Bind to bacterial cell wall, leading to cell death. Not inactivated by penicillinase enzymes.

Therapeutic Effect(s):

Bactericidal action.

  • Active against most gram-positive aerobic cocci.
  • Spectrum is notable for activity against:

    • Penicillinase-producing strains of Staphylococcus aureus,
    • Staphylococcus epidermidis.
  • Not active against methicillin-resistant bacteria.


Absorption: Rapidly but incompletely (35–76%) absorbed from the GI tract.

Distribution: Widely distributed; penetration into CSF is minimal but sufficient in the presence of inflamed meninges; cross the placenta and enter breast milk.

Protein Binding: 96–98%.

Metabolism and Excretion: Some metabolism by the liver (6–10%) and some renal excretion of unchanged drug (60%); small amounts eliminated in the feces via the bile.

Half-life: 0.5–1 hr (↑ in severe hepatic and renal dysfunction).


Dicloxacillin PO30 min30–120 min6 hr


Contraindicated in:

  • Previous hypersensitivity to penicillins (cross-sensitivity exists with cephalosporins and other beta-lactam antibiotics).

Use Cautiously in:

Severe renal or hepatic impairment.

Adverse Reactions/Side Effects


GI: CLOSTRIDIUM DIFFICILE-ASSOCIATED DIARRHEA (CDAD), diarrhea, epigastric distress, nausea, vomiting, ↑ liver enzymes

GU: interstitial nephritis

Derm: rash, urticaria

Hemat: eosinophilia, leukopenia


* CAPITALS indicate life-threatening.
Underline indicate most frequent.



  • May ↓ effectiveness of oral contraceptive agents.
  •  Probenecid  ↓ renal excretion and ↑ blood levels (therapy may be combined for this purpose).
  •  Neomycin  may ↓ absorption.
  • Concurrent use with  methotrexate  ↓ methotrexate elimination and ↑ risk of serious toxicity.


PO (Adults and Children  ≥40 kg): 125–250 mg q 6 hr (up to 2 g/day).

PO (Children  <40 kg): 25–50 mg/kg/day divided q 6 hr; (up to 50–100 mg/kg/day divided q 6 hr has been used for osteomyelitis), maximum: 2 g/day.

Availability (generic available)

Capsules: 250 mg, 500 mg


  • Assess for infection (vital signs; appearance of wound, sputum, urine, and stool; WBC) at beginning of and throughout therapy.
  • Obtain a history before initiating therapy to determine previous use of and reactions to cephalosporins or other beta-lactam antibiotics. Persons with a negative history of penicillin sensitivity may still have an allergic response.
  • Obtain specimens for culture and sensitivity prior to initiating therapy. First dose may be given before receiving results.
  • Observe for signs and symptoms of anaphylaxis (rash, pruritus, laryngeal edema, wheezing, abdominal pain). Discontinue the drug and notify health care professional immediately if these occur. Keep epinephrine, an antihistamine, and resuscitation equipment close by in the event of an anaphylactic reaction.
  • Monitor bowel function. Diarrhea, abdominal cramping, fever, and bloody stools should be reported to health care professional promptly as a sign of Clostridium difficile-associated diarrhea (CDAD). May begin up to several wk following cessation of therapy.

Lab Test Considerations:

May cause leukopenia and neutropenia, especially with prolonged therapy or hepatic impairment.

  • May cause positive direct Coombs' test result.
  • May cause ↑ in AST, ALT, LDH, and serum alkaline phosphatase concentrations.

Potential Diagnoses


  • PO Administer around the clock on an empty stomach at least 1 hr before or 2 hr after meals. Take with a full glass of water; acidic juices may decrease absorption of penicillins.

Patient/Family Teaching

  • Instruct patient to take medication around the clock and to finish the drug completely as directed, even if feeling better. Missed doses should be taken as soon as remembered. Advise patient that sharing of this medication may be dangerous.
  • Advise patient to report signs of superinfection (black, furry overgrowth on the tongue; vaginal itching or discharge; loose or foul-smelling stools) and allergy.
  • Instruct patient to notify health care professional if fever and diarrhea develop, especially if stool contains blood, pus, or mucus. Advise patient not to treat diarrhea without consulting health care professional.
  • Instruct patient to notify health care professional if symptoms do not improve.

Evaluation/Desired Outcomes

Resolution of the signs and symptoms of infection. Length of time for complete resolution depends on the organism and site of infection.

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