Zosyn 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 extended-spectrum penicillin antibiotics has rarely been associated with coagulation abnormalities manifested as prolonged prothrombin and bleeding times, abnormal platelet aggregation, purpura, and clinical bleeding. These reactions have been most severe and most frequently reported in patients with renal impairment given high dosages of the drugs for prolonged periods, although they have also occurred with usual dosages in patients with normal renal function. Therapy with extended-spectrum penicillins should be administered cautiously in patients with significantly impaired renal function, severe active bleeding, or a hemorrhagic diathesis such as hemophilia, vitamin K deficiency, hypoprothrombinemia, thrombocytopenia, or thrombocytopathy. Clinical monitoring of hematopoietic and renal function is recommended during prolonged and/or high-dose therapy. Bleeding manifestations are reversible upon discontinuation of the antibiotic.

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.

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.

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.

As with other semisynthetic penicillins, piperacillin therapy has been associated with an increased incidence of fever and rash in cystic fibrosis patients.

As with other penicillins, patients may experience neuromuscular excitability or convulsions if higher than recommended doses are given intravenously (particularly in the presence of renal failure). Therapy with piperacillin should be administered cautiously in patients with preexisting neuromuscular excitability or seizure disorders.

Parenteral piperacillin sodium contains approximately 43 mg (1.85 mEq) of sodium per each gram of piperacillin activity. The combination, piperacillin-tazobactam, contains approximately 54 mg (2.35 mEq) of sodium per gram of piperacillin, or 108 mg (4.7 mEq) per 2.25 gram of total drug. 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 piperacillin and other extended-spectrum penicillin antibiotics, 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.