Colistimethate 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.

Nephrotoxicity can occur with colistimethate and is probably dose-dependent; signs/symptoms of nephrotoxicity are reversible after discontinuation of therapy. Overdosage can lead to renal dysfunction, muscle weakness, and apnea. Respiratory arrest has been reported after IM administration of colistimethate. Because renal dysfunction increases the risk of apnea and neuromuscular blockade after drug administration, it is important to follow recommended dosing guidelines.

Colistimethate is eliminated primarily by renal excretion; caution is recommended when renal function may be impaired. When renal dysfunction is confirmed, colistimethate may be used, but with particular caution and the dosage should be reduced in proportion to the extent of the impairment. Administering amounts of colistimethate that exceed renal excretory capacity will result in high serum levels and can lead to further impairment of renal function, starting a cycle which, if not recognized, can cause acute renal insufficiency, renal shutdown, and further concentration of colistimethate to toxic levels in the body; at this point, interference of nerve transmission at neuromuscular junctions may occur and lead to muscle weakness and apnea. Signs that indicate impairment of renal function is occurring include diminishing urine output, increasing BUN and serum creatinine, and decreased CrCl. Therapy should be discontinued immediately if signs of renal dysfunction develop; however, if resumption of colistimethate is necessary, dosing should be adjusted accordingly after plasma drug levels have decreased.