Nafcillin Disease Interactions

Clostridioides difficile-associated diarrhea (CDAD), formerly pseudomembranous colitis, has been reported with almost all antibacterial drugs and may range from mild diarrhea to fatal colitis. The most common culprits include clindamycin and lincomycin. Antibacterial therapy alters the normal flora of the colon, leading to overgrowth of C difficile, whose toxins A and B contribute to CDAD development. Morbidity and mortality are increased with hypertoxin-producing strains of C difficile; these infections can be resistant to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea after antibacterial use. Since CDAD has been reported to occur more than 2 months after antibacterial use, careful medical history is necessary. Therapy with broad-spectrum antibacterials and other agents with significant antibacterial activity should be administered cautiously in patients with history of gastrointestinal disease, particularly colitis; pseudomembranous colitis (generally characterized by severe, persistent diarrhea and severe abdominal cramps, and sometimes associated with the passage of blood and mucus), if it occurs, may be more severe in these patients and may be associated with flares in underlying disease activity. Antibacterial drugs not directed against C difficile may need to be stopped if CDAD is suspected or confirmed. Appropriate fluid and electrolyte management, protein supplementation, antibacterial treatment of C difficile, and surgical evaluation should be started as clinically indicated.

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The use of penicillinase-resistant penicillins has been associated with adverse hematologic effects, including neutropenia, leukopenia, granulocytopenia and thrombocytopenia, particularly when given in high parenteral dosages. Agranulocytosis and prolonged bleeding time have been reported rarely. Therapy with penicillinase-resistant penicillins should be administered cautiously in patients with preexisting blood dyscrasias or bone marrow depression, and hematopoietic function should be monitored. Blood counts with differential should be performed prior to initiation of therapy and 1 to 3 times weekly during therapy. Hematologic abnormalities are generally reversible and resolve within several days to two weeks following discontinuation of therapy.

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Nafcillin is primarily metabolized by the liver but also partially excreted unchanged by the kidney. The serum concentration of nafcillin may be increased and the half-life prolonged in patients with significantly impaired renal and/or hepatic function. In general, dosage adjustments are not necessary in either renal or hepatic impairment alone, but may be appropriate in patients with both renal and hepatic failure. Renal and liver function tests should be performed periodically during prolonged therapy.

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Each gram of parenteral nafcillin sodium contains approximately 67 mg (2.9 mEq) of sodium and is buffered with 40 mg of sodium citrate. Each 250 mg capsule of nafcillin sodium contains approximately 17 mg (0.7 mEq) of sodium buffered with calcium carbonate. The sodium content should be considered in patients with conditions that may require sodium restriction, such as congestive heart failure, hypertension, and fluid retention. In addition, hypokalemia has been reported rarely during therapy with the penicillinase-resistant penicillins, which may be particularly important to bear in mind when treating patients with low potassium reserves or fluid and electrolyte imbalance. Clinical monitoring of electrolytes is recommended if these agents are used for prolonged periods.

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