Cefoperazone 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.

Hypoprothrombinemia, with or without bleeding, has been reported rarely with various cephalosporins, particularly those containing an N-methylthiotetrazole (NMTT) side chain (cefamandole, cefmetazole, cefoperazone, cefotetan). The sulfhydryl group of this side chain is suspected of interfering with the hepatic synthesis of prothrombin. Risk factors include advanced age, debility, vitamin K deficiency, malnutrition, malabsorption, and severe renal or hepatobiliary impairment. Therapy with cephalosporins containing the NMTT side chain should be administered cautiously in patients with any of these risk factors and/or significant active bleeding or a hemorrhagic diathesis. Prophylactic administration of vitamin K may be indicated in some patients, especially when intestinal sterilization and surgical procedures are performed.

Cefoperazone is primarily eliminated by hepatobiliary excretion. In patients with impaired hepatic function and/or biliary obstruction, the half-life of cefoperazone is prolonged 2- to 4-fold but urinary excretion is increased. At usual dosages, adjustments are generally not necessary in either renal or hepatobiliary impairment. However, serum drug concentrations should be monitored if high dosages are used (i.e. > 4 g/day), and the dosage decreased accordingly if drug accumulation occurs. In patients with both hepatic and severe renal impairment, cefoperazone dosage should not exceed 1 to 2 grams per day without close monitoring of serum concentrations.

Parenteral cefoperazone sodium contains approximately 34 mg (1.5 mEq) of sodium per each gram of cefoperazone activity. The sodium content should be considered in patients with conditions that may require sodium restriction, such as congestive heart failure, hypertension, and fluid retention.

Most cephalosporin antibiotics are removed by hemodialysis. Doses should either be scheduled for administration after dialysis or supplemental doses be given after dialysis. Cefonicid, cefixime, and ceftriaxone are not significantly removed by hemodialysis.

Disulfiram-like reactions may occur in patients who consume alcohol within 72 hours after administration of a cephalosporin antibiotic that contains an N-methylthiotetrazole (NMTT) side chain (cefamandole, cefmetazole, cefoperazone, cefotetan). The reaction appears to result from accumulation of acetaldehyde due to inhibition of acetaldehyde dehydrogenase. Therapy with cephalosporins containing the NMTT side chain should be administered cautiously in patients with a history of alcoholism. Patients should be instructed to avoid alcohol-containing products during therapy and up to 72 hours after the last dose.

Cases of hepatitis have been reported with the use of certain cephalosporins. Transient rise in AST, ALT, and alkaline phosphatase levels have also been observed. Caution and monitoring are recommended when these agents are prescribed to patients with hepatic disorders.