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SOURCE

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Source: Lee GC, Burgess DS. Antimicrobial regimen selection. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM, eds. Pharmacotherapy: A Pathophysiologic Approach. 10th ed. New York, NY: McGraw-Hill; 2017. http://accesspharmacy.mhmedical.com/content.aspx?bookid=1861&sectionid=146070877. Accessed March 20, 2017.

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DEFINITIONS

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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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CONFIRMING PRESENCE OF INFECTION

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  • Determined by assessing presence of signs and symptoms, determining site of infection, and establishing microbiological diagnosis when possible.

  • Signs and symptoms.

    • Fever.

      • Body temperature above normal range of 36.7°C–37°C (98.1°F–98.6°F; measured orally)

        • Rectal temperatures are 0.6°C higher.

        • Axillary temperatures are 0.6°C lower.

      • Hallmark of infectious disease.

      • May be caused by drugs in absence of infection or other underlying condition.

        • Noninfectious etiologies of fever can be referred to as “false positives.”

    • Elevated or decreased white blood cell (WBC) count (<4000 or >10,000 cells/mm3)

      • 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.

      • Most common granulocyte defect is neutropenia, a decrease in the absolute number of circulating neutrophiles.

    • Local signs.

      • Pain and inflammation.

        • Swelling.

        • Erythema.

        • Tenderness.

        • Purulent drainage.

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IDENTIFICATION OF PATHOGEN

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  • Identification and antimicrobial susceptibility of suspected pathogen are the most important factors in determining appropriate antibiotics.

  • Collect suspected fluids or tissues; assess inflammation with deep-seated infections by examining tissues or fluids (eg, examine sputum to assess pneumonia).

    • Blood (two sets), sputum, urine, stool, wound, sinus, spinal fluid, joint fluid)

      • Assess with gram stain.

      • Perform sensitivities.

  • After positive gram stain or culture, decide if pathogen is contaminant or true pathogen.

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SELECTION OF PRESUMPTIVE THERAPY

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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.

      • 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.

      • Drug toxicity.

        • Risk–benefit analysis should be done if antimicrobial possesses high side effect profile.

    • Combination therapy should be considered to:

      • Broaden the spectrum of coverage for empiric therapy.

      • Important when multiple aerobic and anaerobic bacteria are likely ...

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