Polymyxin b 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.

Albuminuria, cellular casts/cylindruria, and azotemia are generally seen in patients with nephrotoxicity due to polymyxin B sulfate; nephrotoxic reactions have also included rising blood levels without any increase in dosage. Renal function should be carefully determined, and the dosage should be reduced in patients with renal damage and nitrogen retention. Polymyxin B sulfate should be discontinued if urine output decreases and BUN increases.

Neurotoxic reactions with polymyxin B sulfate may be shown by drowsiness, irritability, weakness, perioral paresthesia, numbness of the extremities, ataxia, and blurring of vision; such reactions are generally associated with high serum levels found in patients with impaired renal function and/or nephrotoxicity. The neurotoxicity of polymyxin B sulfate can lead to respiratory paralysis from neuromuscular blockade, particularly when administered soon after anesthesia and/or muscle relaxants. If signs of respiratory paralysis develop, respiration should be assisted as required and polymyxin B sulfate should be discontinued.

Baseline renal function should be determined before therapy, and renal function and blood polymyxin B sulfate levels should be monitored frequently during parenteral therapy. Coadministration with or sequential use of other neurotoxic and/or nephrotoxic agents should be avoided.