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Source: Burgess DS. Antimicrobial Regimen Selection. In: DiPiro, JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM. Pharmacotherapy: A Pathophysiologic Approach. 8 ed. http://accesspharmacy.com/content.aspx?aid=8001114. Accessed June 23, 2012.

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  • “Empiric” regimen: initiated before offending organism is identified and sometimes prior to documentation of presence of infection.
  • “Definitive” regimen: instituted when causative organism is known.

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  • Obtain careful history and physical.
  • Signs and Symptoms
    • Fever
      • Body temperature above normal range of 36.7–37°C (98.1–98.6°F; measured orally)
      • Hallmark of infectious disease
      • May be caused by drugs in absence of infection or other underlying condition.
    • Elevated white blood cell (WBC) count
      • Granulocytes and/or lymphocytes are mobilized to destroy invading microbes.
      • Bacterial infections associated with
        • Elevated granulocyte counts (neutrophils and basophils)
        • Increased band neutrophils in peripheral smear (left-shift)
        • Low neutrophil counts (neutropenia), indicating abnormal response; associated with poor prognosis
      • Tuberculosis, viral, or fungal infections associated with relative lymphocytosis even with normal or slightly elevated total WBC count
    • Local signs
      • Pain and inflammation
        • Swelling
        • Erythema
        • Tenderness
        • Purulent drainage

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  • Collect infected body material.
    • Assess with Gram stain.
    • Perform blood cultures and sensitivities.
    • Perform serologic tests for presence of antibodies.
  • Collect suspected fluids or tissues (e.g., spinal fluid in meningitis).
  • Assess inflammation with deep-seated infections by examining tissues or fluids (e.g., examine sputum to assess pneumonia).

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  • Factors to consider
    • Severity and acuity of disease
    • Local susceptibility data rather than national compilations
    • Host factors
      • Allergy or history of adverse drug reactions
      • Age of patient
      • Pregnancy
      • Metabolic abnormalities
      • Renal and hepatic function: Adjust dosage with diminished renal and/or hepatic function to avoid drug accumulation.
      • Concomitant drug therapy: Potential for drug interactions (Table 1)
      • Concomitant disease states
    • Drug factors
      • Use generally accepted drugs based on pathogen (Table 2)
      • Consider pharmacokinetic and pharmacodynamic properties of agent
        • Bactericidal effects may be concentration-dependent (aminoglycosides and fluoroquinolones) or time-dependent (β-lactams).
        • Treatment outcome can be predicted by area under concentration-time curve (AUC) and maximal plasma concentration.
        • Duration that drug concentration exceeds minimal inhibitory concentration (MIC) is most important pharmacodynamic relationship for antimicrobials that display time-dependent bactericidal effects.
      • Antibiotic tissue penetration varies with site of infection.
        • Clinically relevant drug concentrations found in blood, urine, synovial fluid, and peritoneal fluid.
    • Combination therapy should be considered to:
      • Broaden the spectrum of coverage for empiric therapy
        • Important when multiple aerobic and anaerobic bacteria are likely to be present (e.g., in intraabdominal and female pelvic infections)
      • Achieve synergistic activity against infecting organism
        • Advantageous for infections caused by gram-negative bacilli in immunosuppressed patients.
        • May produce better results in infections caused by Pseudomonas aeruginosa and certain infections caused by Enterococcus spp.
      • Prevent the emergence of resistance

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Table Graphic Jump Location
Table 1. Major Drug Interactions with Antimicrobials

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