Unasyn 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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Patients with mononucleosis treated with an aminopenicillin antibiotic, may develop a pruritic erythematous maculopapular skin rash. The rash is usually self-limiting and resolves within days of discontinuing the offending agent. An altered drug metabolism or an immune-mediated process unrelated to drug hypersensitivity has been proposed as the underlying mechanism. Therapy with aminopenicillin antibiotics should not be administered in patients with mononucleosis.

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Parenteral ampicillin sodium contains approximately 67 to 71 mg (2.9 to 3.1 mEq) of sodium per each gram of ampicillin activity. The combination, ampicillin-sulbactam, contains approximately 115 mg (5 mEq) of sodium per 1.5 gram of total drug. The sodium content should be considered when these products are used in patients with conditions that may require sodium restriction, such as congestive heart failure, hypertension, and fluid retention.

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Beta-lactamase inhibitors are available in combination with beta-lactam antibacterial agents. Beta-lactamase inhibitors are primarily eliminated by the kidneys, with 75% to over 95% of the administered dose excreted as unchanged drug. The plasma exposures (AUC) of beta-lactamase inhibitors (and the associated beta-lactam antibacterial agents) are increased with decreasing renal function. Dosage adjustments are generally necessary for products containing beta-lactamase inhibitors, and modifications should be based on the degree of renal dysfunction in accordance with the individual manufacturer product information. Because it may change during the course of therapy, renal function should be monitored regularly and the dosage should be adjusted accordingly, as appropriate.

Beta-lactamase inhibitors and beta-lactam antibacterial agents can be removed by hemodialysis. The dose should be administered after hemodialysis on hemodialysis days.

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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.

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Penicillin antibiotics (except for agents in the penicillinase-resistant class) are removed by hemodialysis. Doses should either be scheduled for administration after dialysis or supplemental doses be given after dialysis.

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