Meropenem/vaborbactam 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.

Carbapenems are primarily eliminated by the kidney. Patients with renal impairment may be at greater risk for adverse effects from carbapenems, including seizures and other central nervous system disturbances, due to decreased drug clearance. Dosage adjustments should be considered, with modifications based on degree of renal impairment and severity of infection in accordance with the individual product package labeling. Renal function tests should be performed periodically during therapy.

The intravenous use of carbapenems has been associated with central nervous system adverse effects such as seizures (up to 1.5%) and, less frequently, somnolence, encephalopathy, myoclonus, tremor, paresthesia, confusion, agitation, depression, and hallucinations. Therapy with carbapenems, regardless of route of administration, should be administered cautiously in patients with or predisposed to seizures or other neurologic disturbances. The normally recommended dosages should not be exceeded in such patients. In those with a known seizure disorder, anticonvulsant therapy should be continued during carbapenem therapy.

In patients undergoing hemodialysis, carbapenems are recommended only if the benefit outweighs the potential risk of seizures. Carbapenems are removed by hemodialysis and should be administered after dialysis to avoid premature removal of the drug. There is not enough information regarding the use of some carbapenems such as meropenem for injection in patients on dialysis.

Parenteral meropenem is formulated with sodium carbonate to adjust the pH of the reconstituted solution and contains 90.2 mg (3.92 mEq) of sodium per each gram of meropenem 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.

Both meropenem and vaborbactam are primarily excreted via the kidneys. The risk of adverse reactions to these drugs may be greater in patients with renal impairment. Dosage adjustment is recommended in patients with renal impairment (eGFR less than 50 mL/min/1.73m2). Care should be taken in dose selection, and it may be useful to monitor renal function. Meropenem and vaborbactam are removed by hemodialysis. It is recommended to monitor serum creatinine concentrations and eGFR at least daily and adjust the dosage accordingly in patients with changing renal function.