Ampicillin/probenecid 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 manufacturer does not recommend the use of probenecid in patients with known blood dyscrasias. Aplastic anemia, leukopenia, hemolytic anemia and other anemia have been reported infrequently during administration of probenecid. Glucose-6-phosphate dehydrogenase (G-6-PD) deficiency may increase the risk of probenecid-induced hemolytic anemia.

Probenecid may promote lithiasis by increasing uric acid concentration in the renal tubules. Adequate hydration is necessary during therapy. Patients who are dehydrated (e.g., due to severe diarrhea or vomiting) may be at increased risk for the development of uric acid kidney stones and should be encouraged to consume additional amounts of liquid or given intravenous fluid. In general, fluid intake sufficient to yield a daily urinary output of at least 2 liters is recommended. Maintenance of a slightly alkaline or neutral urine is also desirable.

The use of probenecid is not recommended in patients with a history of uric acid nephrolithiasis or a urinary urate excretion greater than 750 mg/24 hr. Probenecid may promote lithiasis by increasing uric acid concentration in the renal tubules. Adequate hydration is necessary during treatment. In general, a fluid intake sufficient to yield a daily urinary output of at least 2 liters is recommended. Maintenance of a slightly alkaline urine is also desirable.

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.

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.

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.

The manufacturer states that probenecid should be used with caution in patients with a history of peptic ulcer. Uricosuric agents can cause upper gastrointestinal irritation and aggravate or reactivate peptic ulcer. However, these effects have primarily been reported with another uricosuric agent, sulfinpyrazone. GI effects associated with probenecid are usually limited to nausea, vomiting, and anorexia.

Probenecid may not be effective in patients with chronic renal insufficiency, particularly when glomerular filtration rate is 30 mL/min or less. Probenecid has been used in patients with some renal impairment but dosage requirements may be increased.