An 80-year-old man is brought to the emergency department due to 2 days of fever, productive cough, and shortness of breath. The patient has a history of hypertension, coronary artery disease, and ascending aortic aneurysm with moderate aortic insufficiency. He has not been hospitalized or used antibiotics recently. The patient is an ex-smoker with a 30-pack-year history and has no drug allergies. Temperature is 38.4 C (101.1 F), blood pressure is 110/68 mm Hg, pulse is 102/min, and respirations are 20/min. Physical examination reveals right-sided lung crackles and a soft, early diastolic murmur. Leukocytes are 14,000/mm³, and a chest x-ray shows infiltrates in the right upper lobe of the lung. Which of the following antibiotics should be avoided in this patient to prevent complications associated with his comorbid conditions?

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This patient with fever, cough, and a pulmonary infiltrate on chest x-ray most likely has community-acquired pneumonia (CAP). All of the antibiotics listed can play a part in the management of CAP. However, given this patient's aortic aneurysm, the use of fluoroquinolones (eg, levofloxacin, moxifloxacin, ciprofloxacin) is relatively contraindicated. Fluoroquinolones upregulate cell matrix metalloproteases, leading to increased collagen degradation; this mechanism is likely responsible for several associated adverse effects, including Achilles tendon rupture, retinal detachment, and aortic aneurysm rupture. The increased risk of aortic aneurysm rupture with fluoroquinolones is small overall, but it warrants serious consideration due to the high morbidity and mortality of rupture. Hence, when possible, these drugs should be avoided in patients with known aortic aneurysm or substantial risk factors for aortic aneurysm (eg, Marfan syndrome, Ehlers-Danlos syndrome, advanced atherosclerotic disease, uncontrolled hypertension). Other adverse effects of fluoroquinolones that are likely unrelated to collagen degradation include encephalopathy, peripheral neuropathy, and QT-interval prolongation. (Choice A) Amoxicillin is sometimes used for outpatient treatment of CAP. Adverse effects include hypersensitivity reactions (eg, urticaria, acute interstitial nephritis) and nonallergic skin rash (eg, erythema multiforme). (Choice B) Macrolides (eg, azithromycin, clarithromycin) are sometimes used as monotherapy for outpatient treatment of CAP when rates of resistance in Streptococcus pneumoniae are low in the community; they can also be combined with a beta-lactam antibiotic for inpatient treatment. Adverse effects include gastrointestinal disturbance (eg, nausea) and QT-interval prolongation. (Choice C) Ceftriaxone is usually the beta-lactam of choice for inpatient treatment of CAP. Like most beta-lactams, ceftriaxone is associated with hypersensitivity reactions. It is also associated with cholestasis in some patients. (Choice D) Doxycycline monotherapy is appropriate for outpatient treatment of CAP, and the drug is sometimes combined with a beta-lactam for inpatient treatment. Adverse effects include skin photosensitivity and medication-induced esophagitis. Educational objective: Fluoroquinolones (eg, levofloxacin) increase collagen degradation and are associated with adverse effects, including Achilles tendon rupture, retinal detachment, and aortic aneurysm rupture. When possible, fluoroquinolone use should be avoided in patients with a known aortic aneurysm or substantial risk factors for aortic aneurysm. References: Aortic dissection and aortic aneurysms associated with fluoroquinolones: a systematic review and meta-analysis. (http://www.ncbi.nlm.nih.gov/pubmed/28739200) Fluoroquinolones and collagen associated severe adverse events: a longitudinal cohort study. (http://www.ncbi.nlm.nih.gov/pubmed/26582407)

An 80-Year-Old Man Is Brought to the Emergency Department Due