Drug Interactions: Synergism and Antagonism: Videos & Practice Problems

Which pair of definitions correctly describes synergism and antagonism in the context of antibiotic combinations?

A patient receives Drug X and Drug Y. In vitro testing shows the combination kills 10-fold more bacteria than predicted from independent effects of each drug. Which term best describes this interaction and why?

Which list best matches the three primary mechanisms by which antibiotic synergism commonly occurs?

Trimethoprim and sulfamethoxazole inhibit sequential steps in folate synthesis. Which mechanism of synergism best explains their combined effect and what is the practical pharmacological consequence?

A new beta-lactam antibiotic increases the intracellular concentration of Drug Z (an antibiotic that targets an intracellular enzyme). Which experimental observation would best support the hypothesis that the beta-lactam enhances uptake to produce synergy?

You are given MICs for two antibiotics: Drug A inhibits step 1 of a biosynthetic pathway (MIC = 8 µg/mL alone) and Drug B inhibits step 2 (MIC = 4 µg/mL alone). In combination, inhibitory concentrations are 2 µg/mL for A and 1 µg/mL for B. Calculate the fractional inhibitory concentration (FIC) index and interpret whether the interaction is synergistic, additive/indifferent, or antagonistic.

Which explanation best describes why inhibiting two sequential enzymatic steps in a metabolic pathway often requires lower concentrations of each inhibitor to shut down the pathway?

Which statement accurately differentiates bacteriostatic and bactericidal antibiotics and explains a common mechanism for antagonism between them?

A culture in exponential growth is treated with penicillin (bactericidal, cell wall active) and chloramphenicol (bacteriostatic, inhibits translation). Which outcome is most likely and why?

Which experimental observation would best demonstrate antagonism between a bacteriostatic and a bactericidal agent in time-kill assays?

Gentamicin (aminoglycoside requiring energy-dependent uptake into cells) is often combined with a beta-lactam. Which outcome is most likely and what is the mechanistic explanation?

Which antibiotic pair is most likely to show antagonism in vitro when used together against actively dividing bacteria?

A patient with a severe bacteremia due to an aminoglycoside-susceptible Gram-negative pathogen is critically ill. Which of the following combination rationales best balances potential benefits of synergy with safety concerns?

Which clinical advantage is directly attributable to antibiotic synergism?

Why is understanding Gram-negative outer membrane structure important when predicting synergism between an outer-membrane–disrupting agent and an intracellular-acting antibiotic?

During which bacterial growth phase are bactericidal antibiotics that target cell wall synthesis generally most effective, and why is this relevant to drug interactions?

You observe in vitro that adding Drug Q to Drug R reduces the MIC of Drug R 8-fold. To determine if the synergy is due to increased uptake of R caused by Q disrupting the membrane, which experimental follow-up would best test this hypothesis?

A clinical isolate of Pseudomonas shows bacteriostatic response to doxycycline but is killed when doxycycline is combined with a novel peptide that permeabilizes membranes. Propose an experimental plan (two key experiments) to confirm the mechanism of synergy and support clinical use.

A synergistic combination reduces the necessary dose of Drug A by 4-fold while maintaining clinical efficacy. Which clinical consideration should most strongly influence whether to adopt this combination as standard therapy?

Which pair below is most likely to be synergistic in treating a severe Gram-negative infection and why?

Design a short clinical decision rule for when to use a synergistic combination empirically in severe infections (three key criteria). Which rule is most defensible?

You perform a checkerboard assay and obtain the following FIC indices: Drug X + Drug Y = 0.40, Drug X + Drug Z = 1.20, Drug Y + Drug Z = 0.60. Which pairing shows the strongest synergy, which is indifferent, and what is the best interpretation regarding which mechanism to investigate first?

Which clinical example best illustrates the mechanism 'one drug inhibits an inhibitor of another'?

In an in vivo mouse infection model, combining Drug M (bactericidal) with Drug N (bacteriostatic) yields worse survival than Drug M alone. What are the most plausible explanations to test experimentally and which initial experiment would best distinguish between them?

A chronic wound infection contains biofilm-associated bacteria in slow-growth states. Propose a multi-component therapeutic strategy that addresses both metabolic inactivity of the bacteria and poor antibiotic penetration, giving two specific interventions and their rationale.

A published study reports synergy based only on improved survival in a mouse infection model without reporting in vitro MICs, pharmacokinetics, or mechanism. As a reviewer, which critiques and requests for follow-up are most appropriate to validate the claim?

Match the example to the mechanism: Which mechanism explains why clavulanic acid restores amoxicillin activity against beta-lactamase–producing bacteria?

Laboratory data show that combining drug A (membrane disruptor) with drug B (intracellular enzyme inhibitor) lowers bacterial CFU faster than either alone. However, the intracellular concentration of B does not increase in the presence of A. Which alternate mechanism best explains synergy and what experiment would confirm it?

Given a nephrotoxic antibiotic that is essential for treating a pathogen but causes kidney injury at high doses, synthesize a therapeutic plan using synergy principles to preserve efficacy while minimizing toxicity. Provide two concrete pharmacologic strategies.

A hospital study reports that empiric use of a bacteriostatic plus bactericidal antibiotic combination led to higher treatment failure rates. What are the strongest evidence-based policy changes the antimicrobial stewardship team should consider?