Severe Confusion Possibly Caused by levofloxacin 5-311 Teodora C. Stefan, PharmD Candidate1, Kimberly A. Couch, PharmD, MA, FIDSA, FASHP1,2 1University of Maryland Eastern Shore School of Pharmacy and Health Professions 2CompleteRx Abstract Discussion Results Levofloxacin is a third generation fluoroquinolone antibiotic which is generally well • The major reported adverse effects of fluoroquinolones are tolerated, and has a very low rate of clinically relevant neurological adverse events (0.2- • 91 yo male with CAP gastrointestinal (3-17%) and CNS (0.9-11%) disturbances4. 1.1%)1. The more common central nervous system(CNS) adverse effects are • PMH: HTN, dyslipidemia, hypothyroidism, BPH • Predisposing factors for CNS related adverse events include5 headache, dizziness, restlessness, tremor, insomnia, anxiety and depression. Delirium • CrCl = 28 mL/min • elderly age and hallucinations have been reported with fluoroquinolones as well as seizures. This • male gender case report describes changes in mental status experienced by an elderly patient who was receiving levofloxacin for presumed pneumonia. This 91 year old male was HD#1 HD#2 HD#3 HD#4 HD#5 HD#6 • diabetes mellitus admitted to the hospital with fever, cough, and rigors and started empirically on • Hypoxemia • any neurological illness levofloxacin for community acquired bacterial pneumonia. The patient became severely confused, agitated and combative approximately 12 hours after the first dose of • severe atherosclerosis levofloxacin. The patient’s oxygen saturations were within normal limits, electrolytes within normal limits, and no other cause for his change in mental status was apparent. Conclusions The patient received 2 doses of levofloxacin 750 mg administered 48 hours apart which was appropriate for his renal function. The patient received 2 doses of alprazolam and 2 Levofloxacin 750 mg IV Q48 Levofloxacin 750 mg IV Q48 Ceftriaxone 1 g IV Q24 • Fluoroquinolones are an under-recognized cause of changes in doses of haloperidol because of his agitation and combative behavior. Levofloxacin was AAO x3 AAO to self only Azithromycin 500 mg IV Q24 mental status. discontinued after the second dose on recommendation of the pharmacist and within 24 Lung sounds diminished Lung sounds diminished at bases AAOx3 • Elderly patients should be monitored carefully for the CNS Tmax = 102.9F (rectal) Tmax = 99.3F (oral) Lung sounds diminished at bases hours of discontinuation, the patient was alert and oriented to person, time, and place. + cough + cough Tmax = 98.6F (oral) symptoms. The patient’s pneumonia improved on alternate antibiotics and the patient was able to +confusion, restlessness, agitation Pt more cooperative, pleasant be discharged on hospital day 4 with no sequelae. This case illustrates that, while very Haloperidol 0.5 mg IV x1 for agitation Ambulating with walker in hallway with PT • Many signs of possible adverse reactions, such as confusion, useful, fluoroquinolones should be used with caution in elderly patients who may be at Family stayed with patient day/night Family able to visit/leave weakness, loss of appetite, tremor or depression, are often risk for changes in mental status. mistakenly attributed to old age and may remain unreported. AAO to self only • Thus, before initiating a fluoroquinolone it is important to account for Lung sounds diminished at bases Levofloxacin D/C Pt discharged to home with family Ceftriaxone 1 g IV Q24 Cefdinir 600 mg PO daily the risk of neurotoxicity especially in the elderly and with patients Tmax = 98.4F (oral) Background Azithromycin 500 mg IV Q24 AAOx3 + cough with a past neurological history. +confusion, agitation, threatening staff AAOx3 Cough less frequent Lung sounds diminished at bases T =98.4F Haloperidol 0.5 mg IV x1 for agitation max • Most common CNS disturbances reported with levofloxacin include Family stayed overnight with patient Tmax = 99.6F (oral) Pt cooperative, pleasant + cough References headache, dizziness and drowsiness, usually occur on Day 1 and Pt more cooperative, pleasant resolve after discontinuation. Pt worked with PT in afternoon Lipsky B, Baker C. Fluoroquinolones toxicity profiles: a review focusing on newer agents. • Less commonly reported CNS events include increased intracranial Family able to leave Clin Infec Dis. 1999; 28:352-64. pressure and CNS stimulation which may lead to tremors, Segev S, Rehavi M, Rubinstein E. Quinolones, theophylline and diclofenac interactions with the gamma-aminobutyric acid receptor. Antimicrob Agents Chemother. restlessness, anxiety, lightheadedness, confusion, hallucinations, 1988;32:1624–6. paranoia, depression, nightmares, insomnia, and suicidal Lipsky BA, Baker CA. Fluoroquinolone toxicity profiles: a review focusing on newer thoughts/acts. • Naranjo Score = 6 agents. Clin Infect Dis1999;28(2):352-64. • Mechanism for levofloxacin-induced change in mental status involves Levaquin [package insert]. Raritan, NJ: Ortho-McNeil-Janssen Pharmaceuticals Inc; August 2011. inhibition of the binding of γ-aminobutyric acid (GABA) at its N-methyl- • Possible ADR Ball P, Mandell L, Niki Y, Tillotson G. Comparative tolerability of newer fluoroquinolone D-aspartate (NMDA) receptor site as well as activation of excitatory antibacterials. Drug Saf. 1999;21:407–21. NMDA receptors leading to CNS excitation2. • Case reports of fluoroquinolone-induced altered mental status Disclosures involving levofloxacin have been previously published. Authors of this presentation have the following to disclose concerning possible financial or • The reported overall trend in incidence of drug-related CNS adverse personal relationships with commercial entities that may have a direct or indirect interest in events is as follows norfloxacin > ciprofloxacin > ofloxacin > the subject matter of this presentation: levofloxacin3. Teodora C. Stefan: nothing to disclose Kimberly A. Couch, PharmD: nothing to disclose .