Antimicrobial Regimen Selection

SOURCE

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.

DEFINITIONS

• “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.

CONFIRMING PRESENCE OF INFECTION

• 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.

IDENTIFICATION OF PATHOGEN

• 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.

SELECTION OF PRESUMPTIVE THERAPY

• 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 ...