Antimicrobial Agents and Resistance Practice Exam Flashcards

Comprehensive practice flashcards covering antimicrobial agent types, mechanisms of action, spectrum of activity, laboratory testing (MIC/MBC), and mechanisms of bacterial resistance based on the provided reviewer transcript.

What are the six characteristics of an ideal antimicrobial agent?

1. Kill or inhibit pathogen growth. 2. Cause little or no harm to the host (selective toxicity). 3. Cause no allergic reaction. 4. Remain stable during storage. 5. Stay in the target tissue long enough to work. 6. Eliminate pathogens before they develop resistance.

Define Bactericidal and Bacteriostatic.

Bactericidal drugs kill bacteria, whereas bacteriostatic drugs stop bacterial growth and reproduction.

What is the difference between MIC and MBC?

MIC (Minimum Inhibitory Concentration) is the lowest antibiotic concentration that prevents visible growth in broth. MBC (Minimum Bactericidal Concentration) is the lowest antibiotic concentration that kills the organism, confirmed by no growth upon subculture.

In a serial dilution where growth occurs at $0, 1, 2, \text{ and } 4 \text{ }\mu g/mL$ and the first clear tube is $8 \text{ }\mu g/mL$, what is the MIC?

$$MIC = 8 \text{ }\mu g/mL$$

What is the specific target and mechanism of Vancomycin?

Vancomycin belongs to the glycopeptides; it binds to the terminal $\text{D-Ala-D-Ala}$ of peptidoglycan precursors, preventing peptidoglycan elongation and translocation to inhibit bacterial cell-wall formation.

How does resistance to Vancomycin develop through target modification?

The $\text{D-Ala-D-Ala}$ terminal changes to $\text{D-Ala-D-Lac}$ or $\text{D-Ala-D-Ser}$, which greatly reduces vancomycin binding.

What are VISA and hVISA in the context of Staphylococcus aureus?

VISA refers to vancomycin-intermediate S. aureus, and hVISA refers to mixed susceptible and intermediate-resistant cells. Both are associated with cell-wall thickening where overproduced peptidoglycan traps vancomycin.

What is the mechanism of action and primary target of Polymyxins?

Polymyxins (e.g., Polymyxin B and Colistin) act like detergents to disrupt the bacterial cell membrane by binding to LPS and damaging the outer and inner membranes; they are more effective against Gram-negative bacteria.

Name the major adverse effects associated with Polymyxins.

Nephrotoxicity and neurotoxicity.

Which antimicrobial drugs target the 30S ribosomal subunit?

Aminoglycosides, tetracyclines, and tigecycline (glycylcyclines).

Which antimicrobial drugs target the 50S ribosomal subunit?

Chloramphenicol, macrolides, lincosamides (clindamycin), streptogramins, linezolid (oxazolidinones), and ketolides.

Describe the mechanism and spectrum of Aminoglycosides.

They bind irreversibly to the 30S ribosomal subunit, causing misreading of mRNA and production of abnormal proteins. They are bactericidal and most effective against aerobic Gram-negative bacteria because uptake requires oxygen-dependent transport.

What distinguishes Tigecycline from traditional tetracyclines?

Tigecycline is a semisynthetic glycylcycline derivative designed to resist many common tetracycline-resistance mechanisms.

What are the three serious toxicities associated with Chloramphenicol?

Bone-marrow suppression, aplastic anemia, and Gray baby syndrome.

What are the primary targets of Fluoroquinolones in Gram-negative versus Gram-positive bacteria?

In Gram-negative bacteria, the primary target is DNA gyrase. In Gram-positive bacteria, the primary target is Topoisomerase IV.

What is the mechanism of Metronidazole?

The organism's nitroreductase converts the drug into toxic free radicals that damage microbial DNA; this activation requires a low-redox, anaerobic environment.

Which enzymes in the folic-acid pathway are inhibited by Sulfonamides and Trimethoprim?

Sulfonamides inhibit dihydropteroate synthase (acting as PABA analogues). Trimethoprim inhibits dihydrofolate reductase.

What is the mechanism and primary use of Isoniazid?

Isoniazid inhibits the synthesis of mycolic acid, a component of the acid-fast cell wall. It is primarily used against Mycobacterium tuberculosis and is bactericidal against actively growing cells.

List the four major acquired resistance mechanisms (ETAE).

1. Efflux pumps. 2. Target-site modification. 3. Acquisition of new targets. 4. Enzymatic drug inactivation.

How does MRSA demonstrate resistance through the acquisition of new targets?

The $\text{mecA}$ gene produces an altered penicillin-binding protein called $\text{PBP2a}$, which has low affinity for most $\beta$-lactam antibiotics.

Identify the Ambler Classes of $\beta$-lactamases and their key features.

Class A: Serine enzymes (e.g., Penicillinases, ESBLs) often inhibited by clavulanate. Class B: Metallo-$\beta$-lactamases requiring zinc (e.g., NDM, VIM, IMP). Class C: AmpC cephalosporinases not inhibited by clavulanate. Class D: Oxacillinases (OXA enzymes).

What is the formula for the Therapeutic Index?

$$\text{Therapeutic Index} = \frac{\text{Toxic Dose}}{\text{Effective Dose}}$$

Which bacteria are the sources for Bacitracin and Polymyxin?

Bacitracin is produced by Bacillus subtilis, and Polymyxin is produced by Bacillus polymyxa.

What is the specific target of Bacitracin?

It blocks the recycling or dephosphorylation of the bactoprenol carrier, stopping the transport of $\text{NAG-NAM}$ precursors across the cell membrane.

How do $\beta$-lactam antibiotics inhibit cell-wall synthesis?

They bind to penicillin-binding proteins (PBPs), which function as transpeptidases, thereby inhibiting transpeptidation (the final cross-linking step in peptidoglycan synthesis).

What are the three horizontal gene transfer mechanisms (CTT)?

Conjugation (direct transfer via cell contact), Transformation (uptake of free DNA), and Transduction (bacteriophage-mediated transfer).

What is the clinical significance of ESBLs?

Extended-Spectrum $\beta$-lactamases hydrolyze penicillins, extended-spectrum cephalosporins, and aztreonam; they are usually inhibited by clavulanic acid, and carbapenems often remain active against them.

Which antimicrobial inhibits DNA-dependent RNA polymerase and is associated with the $\text{rpoB}$ gene mutation?

Rifampin (Rifamycin).

What is the primary use of Nitrofurantoin?

Treatment of uncomplicated lower urinary tract infections (UTI), especially acute uncomplicated cystitis.

Define Intrinsic Resistance and list its causes.

Intrinsic resistance is a natural, inherited characteristic of a species. Causes include lack of target affinity, drug inaccessibility (impermeability), chromosomally encoded efflux pumps, biofilms, and innate production of inactivating enzymes.