MFM II - Antimicrobial Chemotherapy

what are the essential properties of antibacterials?

• selective toxicity to bacteria (interferes with essential structures or properties common in the prokaryotic cells)

• antimicrobial action (bacteriostatic vs bactericidal)

• spectrum of activity (broad-spectrum vs narrow-spectrum)

• effects of combinations

what synthesis processes do antibacterial agents usually target?

• cell wall synthesis

• folate synthesis

• nucleic acid synthesis

• protein synthesis

what describes bacteriostatic?

inhibit or slow down the growth and reproduction of bacteria without necessarily killing them

• they work by interfering with vital bacterial processes, such as protein synthesis, DNA replication, or cell wall synthesis

what describes bacteriocidal?

are capable of killing bacteria by causing irreversible damage to their structure or essential cellular processes leading to their death

• disrupt bacterial cell walls, membranes, or metabolic pathways critical for bacterial survival

what describes synergistic?

additive effect is greater than either drug alone

what describes antagonistic?

one agent blocks the action of another

what describes resistant?

microorganisms are not inhibited by clinically achievable concentrations

what describes sensitive?

microorganisms are inhibited by clinically achievable concentrations

what are factors that dictate antibiotic efficacy?

• location of infection

• pharmacokinetics and pharmacodynamics

• host physiology

• antibiotic effectiveness

what are factors associated to location of infection?

• blood

• deep tissue

• intracellular pathogen (requires drugs with higher lipid solubility)

• prosthetic devices (biofilms are difficult to penetrate)

what are host physiology factors?

• liver and kidney function (drug interactions)

• weight

• critical illness

• pregnancy (all antimicrobials cross the placenta in varying degrees)

what are some circumstances that limit the effectiveness (MIC) of any antimicrobial agent?

• abscess formation

• immunosuppression

• superinfections

• drug antagonism

• foreign bodies/biofilms

what describes chemoprophylaxis?

drug given to patient currently not infected but may be at risk of acquiring an infection

chemoprophylaxis may add to what challenge?

resistance selection

what are some factors that should be considered before a patient receives a drug for chemoprophylaxis?

• characteristics of the patient

• risk vs. benefit

• short vs long term therapy

what are examples of justified chemoprophylaxis?

• treatment of neonates with erythromycin

• prophylaxis against malaria and other endemic pathogens

• animal or human bites

• surgeries that cross a mucosal barrier

what are examples of unjustified chemoprophylaxis?

• patient demands antibiotic treatment

• clean surgeries (does not cross a mucosal barrier)

what is a big challenge in many hospitals around the globe?

multidrug resistance

antimicrobial susceptibility testing (AST) can help determine what?

• MIC (minimal inhibitory concentration)

• MBC (minimal bactericidal concentration)

• MSC (antimicrobial serumcidal concentration)

what are two methods of antimicrobial susceptibility testing (AST)?

• Kirby-Bauer (disk diffusion, qualitative)

• Epsilometer/E-Test (quantitative)

what describes MIC (minimal inhibitory concentration)?

• lowest concentration prevents growth in vitro

• qualitative measurement

what describes MBC (minimal bactericidal concentration)?

• lowest concentration that kills 99.9%

• quantitative measurement

what describes MSC (antimicrobial serumcidal concentration)?

minimum concentration required to kill a patient’s bacterial isolate in the presence of the patient’s own serum

the Kirby-Bauer test is a qualitative assay that can lead to what three classifcations?

• sensitive

• intermediate

• resistant

what describes E-test?

• uses a strip of plastic marked with a gradient unique to each antibiotic

• read zone of occlusion

• produces a ug/ml value (quantitiative assay)

what are inhibitors of cell wall synthesis?

• Beta-lactam drugs

• vancomycin

• bacitracin

what describes the mechanism of action for Cell Wall Synthesis Inhibition?

• blocks peptidoglycan formation

• weakens cell wall → osmotic lysis (cell bursts)

Cell Wall Synthesis Inhibitiors are most effective on what kind of bacteria?

actively dividing bacteria

how to beta lactam drugs work?

competitively inhibit enzymes that catalyze the formation of peptide bridges

• binds to the transpeptidase enzymes called penicillin-binding proteins

what describes the mechanism of action for Protein Synthesis Inhibition?

targets 30S and 50S (70S) ribosomes

protein synthesis inhibitors block what process?

blocks translation → no protein production

clindamycin presents a risk of developing what?

clostridium difficile infections due to altering gastrointestinal normal flora

what describes the mechanism of action of Metabolic Pathway (Folate) Inhibition?

blocks folic acid synthesis (bacteria must make their own) → prevents DNA and RNA synthesis

what describes the mechanism of action for DNA Replication Inhibition?

• inhibits enzymes involved in DNA replication (ex: DNA gyrase)

• prevents bacterial cell division (DNA damage → fragmentation)

• leads to cell death

what describes the mechanism of action for RNA Synthesis Inhibition?

• blocks RNA polymerase

• prevents transcription → no protein production

what are important in vivo requirements for antimicrobials?

• favorable pharmacokinetics

• minimal adverse effects (including minimal suppression of normal microbiota)

• overcome resistance