Ceftobiprole medocaril 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 effect of hepatic dysfunction on ceftobiprole pharmacokinetics is unknown.

The ceftobiprole dosage is reduced in adult patients with renal dysfunction (CrCl less than 50 mL/min, including CrCl less than 15 mL/min with or without hemodialysis); the dosage is also reduced in pediatric patients (aged 2 to less than 18 years) with renal dysfunction (estimated GFR 15 to less than 50 mL/min/1.73 m2). Renal dysfunction increases the AUC of ceftobiprole in adult patients (and is predicted to increase ceftobiprole AUC in pediatric patients), which may increase the risk of drug-related adverse reactions. The effect of any degree of renal dysfunction in pediatric patients younger than 2 years or in those aged 2 to less than 18 years with an estimated GFR less than 15 mL/min/1.73 m2 (receiving or not receiving hemodialysis) on ceftobiprole pharmacokinetics is unknown.

Use of cephalosporins may result in a false-positive reaction for glucose in urine with certain methods (e.g., Clinitest tablets). Glucose tests based on enzymatic glucose oxidase reactions are recommended for patients receiving cephalosporins.

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.

Cephalosporins have been implicated in triggering seizures. Nonconvulsive status epilepticus, encephalopathy, coma, asterixis, neuromuscular excitability, and myoclonia have been reported with cephalosporins, particularly in patients with a history of epilepsy and/or when recommended dosages of cephalosporins were exceeded due to renal dysfunction. Dosage should be adjusted based on the degree of renal function. Anticonvulsant therapy should be continued in patients with known seizure disorders. If CNS adverse reactions including seizures occur, patients should undergo a neurological evaluation to determine whether treatment should be discontinued.