Antibacterial Agents/Antimicrobial resistance/Stewardship

• What is an antibiotic?

  A chemical substance produced by various species of microorganisms that is capable in small concentrations of inhibiting the growth of other microorganisms
• What are semi-synthetic antibiotics?

  Synthetic derivatives of naturally occurring antibiotics
• What are chemotherapeutic agents?

  Chemical antimicrobial compounds
• What are the mechanisms of action for antibacterial agents?

  Interference with cell wall synthesis.

  Disruption of cell membrane.

  Inhibition of protein synthesis.

  Interference with nucleic acid synthesis.
• How do sulphonamides affect bacteria and which mechanism of action do they use?

  They affect folic acid metabolism

  They interfere with nucleic acid synthesis.
• What are sulphonamides analogues of?

  PABA
• Name three sulphonamides

  Sulfamethoxazole

  Sulfadoxine

  Sulfadiazine
• What do diaminopyrimidines prevent?

  Reduction of DHF to THF
• Name three diaminopyrimidines

  Trimethoprim

  Pyrimethamine

  Cycloguanil
• Which groups of antibacterial drugs interfere with nucleic acid synthesis?

  Sulphonamides

  Diaminopyrimidines

  Quinolones

  Nitroimidazoles

  Nitrofurans

  Novobiocin

  Rifamycins
• What are quinolones classified as?

  Synthetic chemotherapeutic agents
• What is the primary target of quinolones in gram-negative bacteria?

  DNA gyrase-A subunit
• What is the primary target of quinolones in gram-positive bacteria?

  Topoisomerase type IV
• What is nalidixic acid active against?

  Gram-negative bacteria
• Name two fluoroquinolones

  Ciprofloxacin

  Ofloxacin
• What are nitroimidazoles active against?

  Anaerobic and certain microaerophilic bacteria
• Name four nitroimidazoles

  Metronidazole

  Tinidazole

  Ornidazole

  Nimorazole
• What is the only nitrofuran mentioned?

  Nitrofurantoin
• What does novobiocin act on?

  β subunit of DNA gyrase
• What do rifamycins inhibit?

  RNA transcription
• Name 2 rifamycins

  Rifampicin - antituberculus drug

  Rifabutin - M.avium complex
• What is synergism in antimicrobial combinations?

  Effect greater than the sum of components
• What is antagonism in antimicrobial combinations?

  Activity of one interferes with the other

  E.g a bacteriostatic antibiotic like tetracycline combined with a beta lactam antibiotic like penicillin which acts on dividing cells
• What is inherent resistance?

  Natural resistance to antimicrobial agents
• What are the mechanisms of natural drug resistance?

  Lack of a transport system

  Lack of the target of the antimicrobial molecule.

  Outer membrane that establishes a permeability barrier against the agent - in gram-negative bacteria
• What is chromosomal-mediated resistance?

  Resistance due to mutation
• What is plasmid-mediated resistance?

  Resistance through gene exchange
• What is drug inactivation or modification?

  Usually plasmid-mediated resistance mechanism
• What is an example of drug inactivation?

  Production of β-lactamases that hydrolyze the beta-lactam ring

  Eg penicillins and cephalosporins
• What do β-lactamases hydrolyze?

  β-lactam ring
• What do aminoglycosides undergo in drug inactivation resistance?

  Enzymatic phosphorylation or adenylation
• What does chloramphenicol undergo in drug inactivation resistance?

  Acetylation
• What is alteration of target site?

  Changes in binding targets of antibiotics
• What is an example of alteration of target site?

  Alteration of PBP - the binding site of penicillins in MRSA and other penicillin-resistant bacteria.
• What is another example of alteration of target site?

  Mutational changes in 30S ribosomal binding site e.g resistance of Enterococci to Streptomycin
• What do aminoglycosides undergo in resistant bacteria?

  Altered protein in 30S ribosome
• What do macrolides undergo in resistant bacteria?

  Methylation of 23S ribosomal RNA blockig erythromycin binding (plasmid-mediated)
• What is alteration of metabolic pathway?

  Changes in how bacteria utilize nutrients
• Give an example of alteration of metabolic pathway.

  Some sulphonamide-resistant bacteria do not require PABA,

  Instead, like mammalian cells, they turn to utilizing preformed folic acid
• What is reduced drug accumulation?

  Decreased drug permeability or increased efflux