Azithromycin/trovafloxacin 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.

Azithromycin is contraindicated in patients with a history of cholestatic jaundice/hepatic dysfunction associated with prior use of azithromycin. Azithromycin is primarily eliminated by biliary excretion; however, the pharmacokinetics of azithromycin have not been established in patients with liver dysfunction. Therapy with azithromycin should be administered cautiously in patients with liver and/or biliary disease. Abnormal liver function, hepatitis, cholestatic jaundice, hepatic necrosis, and hepatic failure have been reported, with some fatal cases. Treatment should be discontinued immediately if signs/symptoms of hepatitis occur.

Quinolones may cause CNS stimulation manifested as tremors, agitation, restlessness, anxiety, confusion, hallucinations, paranoia, insomnia, toxic psychosis, and/or seizures. Benign intracranial hypertension has also been reported. Therapy with quinolones should be administered cautiously in patients with or predisposed to seizures or other CNS abnormalities. In addition, these patients should be advised to avoid the consumption of caffeine-containing products during therapy with some quinolones, most notably ciprofloxacin, enoxacin, and cinoxacin, since these agents can substantially reduce the clearance of caffeine and other methylxanthines, potentially resulting in severe CNS reactions.

Fluoroquinolones have neuromuscular blocking activity and may exacerbate muscle weakness in persons with myasthenia gravis. Postmarketing serious adverse events, including deaths and requirement for ventilatory support, have been associated with fluoroquinolones use in persons with myasthenia gravis. Fluoroquinolones should be avoided in patients with history of myasthenia gravis.

The use of quinolones has been associated with an increased risk of peripheral neuropathy. Monitor closely and discontinue their use in patients experiencing symptoms of peripheral neuropathy. It is recommended to avoid these agents in patients who have previously experienced peripheral neuropathy.

Tendonitis and ruptures of the shoulder, hand, and Achilles tendons have been reported in patients receiving quinolones, both during and after treatment. Avoid the use of these agents in patients who have a history of tendon disorders or have experienced tendinitis or tendon rupture. Therapy with quinolones should be administered cautiously in patients with patients with kidney, heart, and lung transplant, since it may delay the recognition or confound the diagnosis of a quinolone-induced musculoskeletal effect. Factors that may independently increase the risk of tendon rupture include strenuous physical activity, renal failure, and previous tendon disorders such as rheumatoid arthritis. It is recommended to discontinue these agents if, at any time during therapy, pain, inflammation or rupture of a tendon develops and institute appropriate treatment.

Trovafloxacin undergoes metabolism by the liver as well as excretion by the hepatobiliary system. Patients with hepatic impairment or biliary obstruction may be at greater risk for adverse effects from trovafloxacin due to decreased drug clearance. Therapy with trovafloxacin should be administered cautiously in these patients. The manufacturer recommends a dosage reduction in mild to moderate cirrhosis. Periodic assessment of hepatic function is advised, especially during prolonged therapy (>= 21 days), since trovafloxacin can also cause elevations of liver enzymes.

Prolonged cardiac repolarization and QT interval have been reported in patients receiving treatment with azithromycin. Providers should consider the risk of QT prolongation, which can be fatal, when weighing the risks and benefits of azithromycin for at-risk patients including: patients with known prolongation of the QT interval, history of torsades de pointes, congenital long QT syndrome, bradyarrhythmias, or uncompensated heart failure; patients with ongoing proarrhythmic conditions such as uncorrected hypokalemia or hypomagnesemia, clinically significant bradycardia, or receiving other drugs that prolong the QT interval.

The use of macrolide antibiotics has been reported to exacerbate symptoms of myasthenia gravis and trigger new onset of symptoms of myasthenic syndrome. Therapy with these agents should be administered cautiously in patients with a history of myasthenia gravis.