Antimicrobial Susceptibility Testing Flashcards
Antibiotic
a substance produced by a microorganism that kills or inhibits other microorganisms
Antimicrobial agent
a substance that kills or inhibits a microorganism (can be natural like an antibiotic or synthetic)
Antibacterial agent
an antimicrobial that affects bacteria
Bactericidal
agents that kill bacteria
Bacteriostatic
agents that inhibit bacteria
Spectrum of activity
the range of organisms that are adversely affected by an antimicrobial agent
Plasmid
extrachromosomal DNA that can replicate and may carry resistance genes that can be transferred among organisms
Additive drug interaction
the antimicrobial agent effect is the sum of the activity of the individual antimicrobial agents (drugs work together but the effect is not amplified)
Synergy drug interaction
the effect of the antimicrobial agents is greater than the sum (amplified)
Antagonism drug interaction
one antimicrobial agent interferes with the activity of another (two drugs are less effective than one)
Indifferent drug interaction
the antimicrobial agents are independent of one another
Intrinsic resistance
inherent/it is a characteristic of a species, genus, or group
Ex: GNRs being resistant to vancomycin because it cannot cross the outer membrane
Acquire resistance
a change in a bacterial strain’s susceptibility from gene mutation and transfer of resistance genes
Enzyme inactivation resistance mechanism
produce enzymes that inactivate antimicrobial agents
Ex: penicillinase
Permeability barriers
unable to reach their intended target sites
Drug efflux
use an energy-dependent system to pump an antimicrobial agent out of the bacterial cell
Low-affinity target sites
the drug binds poorly or not at all to its target site
Bypass mechanisms
able to circumvent the metabolic block caused by an antimicrobial agent
Constitutive resistance expression
the microorganism is constantly expressing the resistance mechanism
Inducible resistance expression
the microorganism expresses the resistance mechanism only when exposed to the appropriate antimicrobial agent
Constitutive-inducible resistance expression
constantly expresses resistance at a low level and a high level when the antimicrobial agent is present
B-lactam agents
inhibit cell wall synthesis by binding to enzymes involved in peptidoglycan production (penicillin-binding proteins); bactericidal
Penicillin-binding proteins (PBPs)
enzymes involved in the formation of peptidoglycan cross-links
Acyl-D-alanyl-D-alanine
the normal substrate required for synthesis of the linear glycopeptide in the bacterial cell wall; the ring for beta-lactams are similar to this ring
B-lactamases
enzymes that inactivate B-lactam agents by cleaving the B-lactam ring
Includes: penicillinases and cephalosporinases
Which antimicrobial agents are B-lactams?
Penicillins, cephems, carbapenems, and monobactams
Which staphylococci are resistant to B-lactams
Methicillin-resistant staphylococci are resistant to all B-lactam agents
What are the key steps for antimicrobial action?
- The agent must be in an active form
- It must be able to achieve sufficient levels at the site of infection
- It must be able to inhibit growth or kill the bacteria
Which antibacterial agents inhibit cell wall synthesis?
Beta-lactams, fosfomycin tromethamine, glycopeptides, and lipoglycopeptides
Fosfomycin tromethamine
inhibits cell wall formation by inactivating enzymes involved in the first step of peptidoglycan synthesis; generally used for uncomplicated UTIs caused by Enterococcus faecalis and E. coli
Glycopeptides
inhibit bacterial cell wall synthesis by binding to the end of peptidoglycan interfering with transpeptidation (cross-linking); Ex: vancomycin
Effect for GP organisms, but too big for GN ones
Lipoglycopeptides
structurally similar to vancomycin but they have hydrophobic chemical groups to increase cell permeability and causes depolarization of the cell membrane potential
Which agents inhibit cell membrane function?
Lipopeptides: daptomycin and polymyxins
Lipopeptides bind to and disrupt the cell membrane
Daptomycin
binds to the cytoplasmic membrane and inserts its hydrophobic tail into the membrane, increasing its permeability
For GP bacteria but should not be used for lung infections because it can cause eosinophilic allergic pneumonia
Polymyxins
cyclic lipopeptide agents that act as detergents, interacting with phospholipids in the cell membrane to increase permeability; most effect on GN bacteria, but it can be a neutrotoxin and nephrotoxin so it is a last resort for MDRO
Which agents inhibit protein synthesis/ disrupt cellular metabolism?
Aminoglycosides, Macrolide-Lincosamide-Streptogramin group, ketolides, oxazolidinones, chloramphenicol, tetracyclines, and glycylglycines
Aminoglycosides
inhibit bacterial protein synthesis by irreversibly binding to protein receptors on the organism’s 30S ribosomal subunit; this interrupts formation of the protein synthesis complex, reading of mRNA, and formation of the ribosomal-mRNA complex
What drugs are aminoglycosides and which bacteria do they work on?
Gentamicin, amikacin, streptomycin, and tobramycin; used in combination with cell-wall antibiotics like beta-lactams or vancomycin; cannot be used on anaerobic bacteria; can be a nephrotoxin and auditory or vestibular toxin
Macrolides
the most common MLS; inhibits protein synthesis by binding to the 23S rRNA on the bacterial 50S ribosomal subunit, disrupting the growing peptide chain by blocking translocation
What drugs are macrolides and which bacteria do they work on?
Erythromycin, azithromycin, and clarithromycin; effective against GP, mycoplasmas, treponemes, and rickettsiae
Lincosamides
bind to the 50S ribosomal subunit and prevent elongation by interfering with peptidyl transfer during protein synthesis
What drugs are lincosamides and which bacteria do they work on?
Clindamycin and lincomycin; Clindamycin works on anaerobic GP and some anaerobic GN while lincosamides work on GPC; increase the risk of C. diff. associated disease after use
Streptogramins
enter bacterial cells by passive diffusion and bind irreversibly to the 50S subunit, induing a conformation change that interferes with peptide bond formation; effective against GP and some GN
Ketolides
same mechanism as macrolides, but maintains activity against most macrolide-resistant GP organisms; particularly effective against Mycoplasma, Mycobacteria, Chlamydia, Rickettsia, and Francisella tularensis; includes telithromycin
Oxazolidinones
interact with the 23S rRNA in the 50S ribosomal subunit, inhibiting 70S initiation complex formation and blocking translation of any mRNA; effect against most GP and mycobacteria; includes linezolid and tedizolid
Chloramphenicol
inhibits the addition of amino acids to the growing peptide chain by reversibly binding to the 50S ribosomal subunit, inhibiting transpeptidation; has bone marrow toxicity, which can lead to aplastic anemia
Tetracyclines
inhibit protein synthesis by binding reversibly to the 30S ribosomal subunit, interfering with the binding of the tRNA-amino acid complexes to the ribosome; can treat GP and GN, some intracellular pathogens, some protozoa, N. gonorrhoeae, mycoplasma, and spirochetes; effects upper GI and has cutaneous phototoxicity
Glycylglycines
tetracyline derivatives that work against the most common tetracycline-resistant bacteria; includes tigecycline
Which agents inhibit DNA and RNA synthesis?
Fluoroquinolones, Metraonidazole, and Rifamycin
Fluoroquinolones
bind to and interfere with DNA gyrase enzymes involved in the regulation of DNA supercoiling; some also inhibit topoisomerase
What drugs are fluoroquinolones?
Ciprofloxacin, levofloxacin, ofloxacin, and moxifloxacin; can lead to tendinitis and rupture of the Achilles tendon
Metronidazole
contains a nitro group that is reduced by nitroreductase in the bacterial cytoplasm, generating cytotoxic compounds and free radicals; most potent against GN anerobes and microaerophilic bacteria and protozoans
Rifamycin
bind to the enzyme DNA-dependent RNA polymerase and inhibit synthesis of RNA; includes rifampin and is frequently used with other agents
Which agents inhibit other metabolic processes
Sulfonamides, Trimethoprim, and nitrofuratoin
Sulfonamides
bind to dihydropteroate synthase, disrupting the folic acid pathway, which produces precursors required for DNA synthesis; active against GP and GN but not P. aeruginosa; can be antagonistic for other medications
Trimethoprim
targets the folic acid pathway by inhibiting dihydrofolate reductase; combined with sulfamethoxazole
Nitrofuratoin
converted by bacterial nitroreductases to reactive intermediates that bind ribosomal proteins and rRNA, disrupting synthesis of RNA, DNA, and proteins; used to treat uncomplicated UTIs; can lead to chronic pulmonary conditions like irreversible pulmonary fibrosis
What are the three resistance pathways for beta-lactams?
- Enzymatic disruption: beta-lactamase enzymes that destroy the beta-lactam ring; Ex: penicillin resistance
- Altered target: mutational changes to PBPs or PBPs that do not bind to beta-lactams; Ex: MRSA
- Decreased uptake: porin channels change in # or character so beta-lactams cannot cross the outer membrane; Ex: imp. resistance
What are the two resistance pathways for glycopeptides?
- Altered target: alteration in the molecule structure of cell wall precursor components, decreasing vanc. binding
- Target overproduction: excess peptidoglycan
What are the three resistance pathways for aminoglycosides?
- Enzymatic modification: enzymes modify sites on the aminoglycoside molecule
- Decreased uptake: porin channels change in # or character so uptake is diminished; Ex: GN resistance
- Altered Target: mutational changes in ribosomal binding sites; Ex: enterococci resistance to streptomycin
What are the two resistance pathways for quinolones?
- Decreased uptake: alteration in outer membrane diminish uptake of drug and/or activation of an efflux pump that removes drugs before sufficient intracellular concentration; Ex: GNR and Staph resistance
- Altered target: changes in DNA gyrase subunits decreases ability of drugs to bind to the enzyme
What are the two resistance pathways for macrolides?
- Efflux: pumps drug out of cell before target binding; Ex: some staph and strep
- Altered target: enzymatic alteration of ribosomal target reduces drug binding; Ex: some staph and strep
Anaerobic bacteria resistant to aminoglycosides
lack of oxidative metabolism to drive uptake of aminoglycosides = resistance
Gram positive bacteria resistant to aztreonam
lack of PBP targets that bind this antibiotic = resistance
Gram negative bacteria resistant to vancomycin
Lack of uptake resulting from inability of vancomycin to penetrate outer membrane
P. aeruginosa resistant to sulfonamides, trimethoprim, tetracycline, or chloramphenicol
lack of uptake resulting in ineffective intracellular concentrations = resistance
Klebsiella spp. resistant to ampicillin
production of beta-lactamases destroy ampicillin before it reaches its PBP target = resistance
Enterococci resistant to aminoglycosides
lack of sufficient oxidative metabolism to drive uptake of aminoglycosides
Enterococci resistant to all cephalosporins
lack PBPs that effectively bind
STENMA resistant to imipenem
production of enzymes that destroy imipenem before it reaches PBP targets
