Susceptibility Testing, Aerobic and Facultatively Anaerobic Organisms

Susceptible: This category implies that an infection due to the strain may be appropriately treated with the dosage of antimicrobial agent recommended for that type of infection and infecting species, unless otherwise contraindicated.

Intermediate: This category provides a “buffer zone,” which should prevent small, uncontrolled, technical factors from causing major discrepancies in interpretations (eg, species that should have few or no endpoints in this range, or drugs with in vitro results affected by media variation or drugs with narrow pharmacotoxicity margins).

Resistant: Strains falling in this category are not inhibited by the usually achievable systemic concentrations of the agent with normal dosage schedules and/or fall in the range where specific microbial resistance mechanisms are likely (eg, β-lactamases), and clinical efficacy has not been reliable in treatment studies.

Major Mechanisms of Bacterial Antimicrobial Resistance

Enzymatic inactivation or modification of drug:

• β-lactamase hydrolysis of β-lactam ring with subsequent inactivation of β-lactam antibiotics

• Modification of aminoglycosides by acetylating, adenylating, or phosphorylating enzymes

• Modification of chloramphenicol by chloramphenicol acetyltransferase

Decreased drug uptake or accumulation

• Intrinsic or acquired lack of outer membrane permeability

• Faulty or lacking antibiotic uptake and transport system

• Antibiotic efflux system (eg, tetracycline resistance)

Altered or lacking antimicrobial target

• Altered penicillin-binding proteins (β-lactam resistance)

• Altered ribosomal target (eg, aminoglycoside, macrolide, and lincomycin resistance)

• Altered enzymatic target (eg, sulfonamide, trimethoprim, rifampin, and quinolone resistance)

Circumvention of drug action consequences

• Hyperproduction of drug targets or competitive substrates (eg, sulfonamide and trimethoprim resistance)

Uncoupling of antibiotic attack and cell death

• Bacterial tolerance and survival in the presence of usually bactericidal drugs (eg, β-lactams and vancomycin)