Antimicrobial Therapy Principles Flashcards

A patient with infective endocarditis caused by Enterococcus faecalis is treated with a combination of ampicillin and gentamicin. What is the primary rationale for using this specific combination?

Answer: To achieve a synergistic bactericidal effect.

This is a classic example of antimicrobial synergy. Ampicillin, a beta-lactam, inhibits cell wall synthesis, which increases the permeability of the bacterial cell to the aminoglycoside, gentamicin. This enhanced uptake allows gentamicin to more effectively reach its intracellular target (the 30S ribosome), resulting in a bactericidal effect that is greater than the individual agents alone.

A bacterial strain isolated from a wound culture is found to be resistant to ampicillin but susceptible to amoxicillin-clavulanate. What is the most likely mechanism of resistance to ampicillin in this strain?

Answer: Production of a beta-lactamase enzyme.

The addition of clavulanate, a beta-lactamase inhibitor, restores the activity of the beta-lactam antibiotic (amoxicillin). This indicates that the bacterium's resistance mechanism is the production of a beta-lactamase enzyme, which inactivates the antibiotic by hydrolyzing the beta-lactam ring.

Which of the following best describes the primary pharmacodynamic property of beta-lactam antibiotics, such as piperacillin, which dictates their dosing strategy?

Answer: Their efficacy is best correlated with the duration that the drug concentration remains above the minimum inhibitory concentration (T > MIC).

Beta-lactam antibiotics demonstrate time-dependent killing. Their effectiveness is maximized by keeping the drug concentration above the minimum inhibitory concentration (MIC) for as long as possible during the dosing interval (fT > MIC). This principle supports the use of frequent intermittent dosing or continuous infusions to optimize therapeutic outcomes.

Sulfonamide antibiotics, such as sulfamethoxazole, exhibit selective toxicity against bacteria. Why are human cells typically unaffected by this mechanism?

Answer: Human cells utilize pre-formed folic acid from dietary sources.

Sulfonamides competitively inhibit dihydropteroate synthase, an enzyme essential for the de novo synthesis of folic acid in bacteria. Human cells lack this pathway and instead acquire folic acid from the diet, making them insusceptible to the action of sulfonamides.

A physician notes that an aminoglycoside has a significant post-antibiotic effect (PAE). Which of the following statements best describes the clinical implication of the PAE?

Answer: Bacterial growth suppression continues for a period after the plasma concentration has fallen below the MIC.

The post-antibiotic effect (PAE) is the phenomenon of persistent suppression of bacterial growth even after the antibiotic concentration has fallen below the minimum inhibitory concentration (MIC). This property, characteristic of drugs like aminoglycosides, allows for less frequent, high-dose administration schedules (once-daily dosing), which can maximize efficacy and minimize certain toxicities.

A 68-year-old patient with a complicated urinary tract infection is being treated with ciprofloxacin, a fluoroquinolone. This class of antibiotics achieves its bactericidal effect by targeting which of the following?

Answer: DNA gyrase and topoisomerase IV.

Fluoroquinolones exert their bactericidal effect by inhibiting two key bacterial enzymes: DNA gyrase (topoisomerase II) and topoisomerase IV. Inhibition of these enzymes prevents the relaxation of supercoiled DNA and separation of daughter DNA strands, which are essential for DNA replication and cell division.