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Case Study Choosing an Antibiotic Therapy

A 65-year-old man came to the emergency department via ambulance after a generalized seizure. Relatives accompanied the patient and described a 1-day history of fever and intermittent confusion. The patient had a 10-year history of chronic lymphocytic leukemia; 2 months ago, he had a trial of oral chlorambucil because of progressive fatigue, anemia, thrombocytopenia, and splenomegaly. Then, 3 weeks ago, the patient attended a family reunion at a cousin's dairy farm. He enjoyed eating homemade soft cheese, sausage, and fresh vegetables from the garden. Several family members who attended the reunion reported transient febrile gastroenteritis. The patient's physical examination in the emergency department revealed a stuporous man with temperature 103.3°F (39.6°C), blood pressure 122/68 mm Hg, pulse 112 beats per minute, and respirations 26 per minute. He had nuchal rigidity, diffuse adenopathy, and hepatosplenomegaly. Passive flexion of the neck caused flexion at hips and knees (Brudzinski's sign). The patient resisted passive extension of the flexed knee and hip (Kernig's sign). Papilledema was absent. There were no focal neurological deficits. Skin examination revealed no eruption. Peripheral blood tests showed 36,000 leukocytes (66% lymphocytes), hemoglobin 9.0 g/dL, platelet count 99,000. A lumbar puncture was performed. The opening pressure of cerebrospinal fluid was 220 mm of water. Cerebrospinal fluid tests revealed no organisms on Gram stain, glucose 60 mg/dL, protein 200 mg/dL, lactate 50 mg/dL, leukocytes 2000 per mm3 (10% neutrophils, 60% lymphocytes, 30% monocytes). Bacterial antigen tests on cerebrospinal fluid were negative for H. influenzae type B, S. pneumoniae, Neisseria meningitidis, E. coli K1, and group B streptococci. What is the best empirical antibiotic therapy for this patient?

Answer: The emergency department physician suspected acute bacterial meningitis in a patient with impaired immunity secondary to hematologic malignancy. The physician also noted the exposure to a food-borne pathogen associated with dairy products. The epidemiological risk assessment suggested the need for empirical antibiotic therapy to cover potential gram-negative enteric pathogens and L. monocytogenes. Immediately after obtaining blood and spinal fluid specimens, the emergency department personnel initiated therapy with ampicillin 2 g intravenously every 4 hours and ceftazidime 2 g intravenously every 8 hours. On the next day, the clinical microbiology laboratory reported diphtheroids growing in the patient's blood culture bottles. On the second hospital day, the laboratory identified L. monocytogenes growing in blood and spinal fluid specimens. Ceftazidime was discontinued. The patient completed a 21-day course of ampicillin and gentamicin 1.7 mg/kg intravenously every 8 hours.

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Aminoglycoside Antibiotics

Steven M. Belknap

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