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A 51-year-old alcoholic patient presents to the emergency department with fever, headache, neck stiffness, and altered mental status for 12 hours. Vital signs are blood pressure 90/55 mm Hg, pulse 120/min, respirations 30/min, temperature 40°C [104°F] rectal. The patient is minimally responsive to voice and does not follow commands. Examination is significant for a right third cranial nerve palsy and nuchal rigidity. Laboratory results show a white blood cell count of 24,000/mm3 with left shift, but other hematologic and chemistry values are within normal limits. An emergency CT scan of the head is normal. Blood cultures are obtained, and a lumbar puncture reveals the following cerebrospinal fluid (CSF) values: white blood cells 5000/mm3, red blood cells 10/mm3, protein 200 mg/dL, glucose 15 mg/dL (serum glucose 96 taken at same time). CSF Gram stain reveals gram-positive cocci in pairs. What is the most likely diagnosis in this patient? What organisms should be treated empirically? Are there other pharmacologic interventions to consider before initiating antimicrobial therapy?

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The development of antimicrobial drugs represents one of the most important advances in therapeutics, both in the control or cure of serious infections and in the prevention and treatment of infectious complications of other therapeutic modalities such as cancer chemotherapy, immunosuppression, and surgery. However, evidence is overwhelming that antimicrobial agents are vastly overprescribed in outpatient settings in the United States, and the availability of antimicrobial agents without prescription in many developing countries has—by facilitating the development of resistance—already severely limited therapeutic options in the treatment of life-threatening infections. Therefore, the clinician should first determine whether antimicrobial therapy is warranted for a given patient. The specific questions one should ask include the following:

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  1. Is an antimicrobial agent indicated on the basis of clinical findings? Or is it prudent to wait until such clinical findings become apparent?

  2. Have appropriate clinical specimens been obtained to establish a microbiologic diagnosis?

  3. What are the likely etiologic agents for the patient's illness?

  4. What measures should be taken to protect individuals exposed to the index case to prevent secondary cases, and what measures should be implemented to prevent further exposure?

  5. Is there clinical evidence (eg, from well-executed clinical trials) that antimicrobial therapy will confer clinical benefit for the patient?

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Once a specific cause is identified based on specific microbiologic tests, the following further questions should be considered:

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  1. If a specific microbial pathogen is identified, can a narrower-spectrum agent be substituted for the initial empiric drug?

  2. Is one agent or a combination of agents necessary?

  3. What are the optimal dose, route of administration, and duration of therapy?

  4. What specific tests (eg, susceptibility testing) should be undertaken to identify patients who will not respond to treatment?

  5. What adjunctive measures can be undertaken to eradicate the infection? For example, is surgery feasible for removal of devitalized tissue or foreign bodies—or drainage of an abscess—into which antimicrobial agents may be unable to penetrate? Is it possible to ...

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