amoxicillin-potassium-clavulanate-combination and Renal-Insufficiency

Azithromycin is an antibiotic with QT-prolonging potential commonly prescribed to individuals receiving hemodialysis. Hemodialysis patients have a high prevalence of clinical conditions, such as structural heart disease, that can enhance the pro-arrhythmic effects azithromycin, but were excluded from prior investigations evaluating the cardiac safety of azithromycin. Using data from the United States Renal Data System (2007-2017), we conducted two cohort studies to examine the cardiac safety of azithromycin relative to amoxicillin-based antibiotics (amoxicillin, amoxicillin/clavulanic acid) and levofloxacin (a fluoroquinolone antibiotic known to prolong the QT-interval) in the hemodialysis population. The primary outcome was five-day sudden cardiac death. Using inverse probability of treatment weighted survival models, we estimated hazard ratios, risk differences, and 95% confidence intervals. The azithromycin vs. amoxicillin-based antibiotic cohort included 282,899 patients and 725,431 treatment episodes (381,306 azithromycin and 344,125 amoxicillin-based episodes). Azithromycin vs. amoxicillin-based antibiotic treatment was associated with higher relative and absolute risks of sudden cardiac death, weighted hazard ratio of 1.70 (95% Confidence Interval, 1.36 to 2.11) and weighted risk difference per 100,000 treatment episodes of 25.0 (15.5 to 36.5). The azithromycin vs. levofloxacin cohort included 245,143 patients and 554,557 treatment episodes (387,382 azithromycin and 167,175 levofloxacin episodes). Azithromycin vs. levofloxacin treatment was associated with lower relative and absolute risks of sudden cardiac death, weighted hazard ratio of 0.79 (0.64 to 0.96) and weighted risk difference per 100,000 treatment episodes of -18.9 (-35.5 to -3.8). Thus, when selecting among azithromycin, levofloxacin, and amoxicillin-based antibiotics, clinicians should weigh the relative antimicrobial benefits of these drugs against their potential cardiac risks.

Topics: Amoxicillin; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Azithromycin; Death, Sudden, Cardiac; Fluoroquinolones; Humans; Levofloxacin; Renal Dialysis; Renal Insufficiency; United States

To describe a patient who developed hepatic failure, Stevens-Johnson syndrome (SJS), and died after receiving amoxicillin/clavulanate therapy.. A 37-year-old white man without significant past medical history received a 10-day course of amoxicillin/clavulanate for treatment of pneumonia. Thirty-two days after starting amoxicillin/clavulanate, he developed jaundice, rash, pruritus, and increasing fatigue. On further evaluation, with the exclusion of toxicity from other drugs or diseases, the time course to development of cholestatic jaundice correlated with the use of amoxicillin/clavulanate. The patient consequently died with progressive hepatic failure, renal failure, and SJS.. Hepatic injury has been reported with amoxicillin/clavulanate. Signs and symptoms of jaundice and pruritus may appear up to to six weeks after stopping therapy. Most cases of liver injury have been benign and reversible on discontinuation of the amoxicillin/clavulanate. Reported hepatic reactions have been mainly cholestatic, with some mixed cholestatic/hepatocellular liver function test abnormalities.. Clinicians should be aware of amoxicillin/clavulanate as a drug capable of causing hepatitis with eventual systemic dysfunction. While recovery is usually complete following withdrawal of the drug, in patients with rash associated with hepatic dysfunction, renal insufficiency, or other unusual symptoms, earlier consideration of initiating systemic steroids or liver transplantation referral, in hopes of avoiding progressive systemic response, might be worthwhile.

Topics: Adult; Amoxicillin-Potassium Clavulanate Combination; Blood Chemical Analysis; Drug Therapy, Combination; Fatal Outcome; Humans; Liver Failure; Male; Pneumonia; Renal Insufficiency; Stevens-Johnson Syndrome