Rational Antimicrobial Therapy: Culture and Susceptibility testing

A set of Q&A flashcards covering interpretive criteria for susceptibility testing, breakpoints, organism- and drug-related factors, pitfalls of testing, and principles of bactericidal vs. bacteriostatic therapy, as well as the rationale and risks of combination antibacterial therapy.

What do the designation codes S, I, and R stand for in culture and susceptibility testing?

S = sensitive (high likelihood of success at label dose)

I = intermediate (buffer zone to prevent errors)

R = resistant (poor likelihood of success at label dose).

What is the purpose of break-point MICs in susceptibility testing?

They provide cut-off values to assign S, I, or R codes based on MICs/zones and are influenced by historic patterns, PK, and clinical responses.

How are clinical break-point values defined?

Approximate blood levels of a drug safely achieved at label doses that can result in a clinical cure against the organism.

Which factors influence clinical break-point values?

Historic susceptibility patterns; pharmacokinetics (Cmax) of the drug; clinical responses at label doses.

Name two common pitfalls related to MICs and infection site drug levels.

MICs may not reflect drug levels at the infection site; host factors or local factors (penetration) can affect drug levels achieved.

What assumption does culture & susceptibility testing rely on that can limit accuracy?

That the causative bug is isolated and being tested.

List some sample-related pitfalls in C/S testing.

Sample error; normal flora versus infecting flora; testing limited to non-fastidious bugs.

Why might in vitro findings not predict in vivo outcomes?

Host target site may be hostile and local immunity factors may be absent in vitro.

On what basis may interpretive criteria be developed?

Based on human pathogens and total plasma drug levels rather than tissue levels.

What are the two broad categories of antimicrobial action discussed?

Bactericidal and bacteriostatic.

What does the MBC/MIC ratio indicate?

Whether an agent is bactericidal (low ratio, typically 1–2 tubes) or bacteriostatic (high ratio).

How is a bactericidal agent defined?

Kills susceptible organisms; does not rely on host defenses; MBC/MIC ratio is low and MBC is usually safely attainable in the host.

How is a bacteriostatic agent defined?

Inhibits growth and relies on host defenses; MBC/MIC ratio is large; MBC often not safely attainable.

Name a chronic infection where bactericidal agents are preferred.

Endocarditis or urinary tract infections (UTIs).

Name a patient population where bactericidal therapy is particularly important.

Immunocompromised or neutropenic patients.

List life-threatening or serious infections where bactericidal drugs are recommended.

Osteomyelitis, bacterial meningitis, septicemia, peritonitis (and cases with compromised blood supply).

What is the rationale for initial therapy in life-threatening conditions?

To extend the antibacterial spectrum when the pathogen is unknown or susceptibility is unpredictable, and the infection site is uncertain.

Provide one parenteral example from the four-quadrant approach to combination therapy.

Aminoglycoside + penicillin (parenteral).

Provide one oral example from the four-quadrant approach to combination therapy.

Fluoroquinolone + potentiated-penicillin (oral).

Name a parenteral antibiotic used in the four-quadrant approach other than the aminoglycoside/penicillin combo.

Imipenem-cilastin (used in severe and resistant infections, need permission with reason to use)

Give an example of a known favorable drug interaction (synergism).

Amoxicillin + clavulanic acid; aminoglycoside + beta-lactam; trimethoprim + sulfonamide.

These combinations enhance efficacy against bacteria.

Why are certain drug combinations used to prevent resistance?

To reduce resistance development;

• erythromycin + rifampin

• aminopenicillins + clavulanic acid

• trimethoprim + sulfonamide.

What are common risks associated with combination antibacterial therapy?

Superinfection; increased toxicity; antagonistic combinations; cost; inconvenience.

What is antagonism in drug combinations?

Chemical antagonism (don’t mix in the same syringe) or pharmacodynamic antagonism (cidal + static) that can reduce efficacy.