Staphcillin 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.

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.

Most beta-lactam antibacterial agents are eliminated by the kidney as unchanged drug and, in some cases, also as metabolites. The serum concentrations of beta-lactam antibacterial agents and their metabolites may be increased, and the half-lives prolonged, in patients with impaired renal function. Neurotoxic reactions (e.g., encephalopathy, aphasia, asterixis, myoclonus, seizures, nonconvulsive status epilepticus, coma) have been reported in such patients treated parenterally with these agents. Dosage adjustments may be necessary, and modifications should be based on the degree of renal function as well as severity of infection in accordance with the individual manufacturer product information. Renal function tests should be performed periodically during prolonged and/or high-dose therapy since nephrotoxicity and alterations in renal function have occasionally been associated with the use of these drugs.

The penicillinase-resistant penicillins, dicloxacillin and methicillin, are both eliminated by the kidney. Renal elimination of these penicillins has been shown to increase in patients with cystic fibrosis, resulting in decreased peak serum drug concentrations and AUCs. Clinicians should be cognizant of these effects when prescribing or administering the antibiotics to patients with cystic fibrosis.

Each gram of parenteral methicillin sodium contains approximately 60 to 71 mg (2.6 to 3.1 mEq) of sodium and is buffered with 50 mg of sodium citrate. 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.