Antibiotics/Resistance Flashcards
Aminoglycoside concerns
Ear and kidney toxicity
Aminoglycoside mechanism
Aminoglycosides bind irreversibly to bacteria 30S and 50S ribosomal subunits to prevent initiation complex formation + protein synthesis BacterioCIDAL
Aminoglycoside spectrum
Primarily effective against GRAM NEGATIVES but synergistic with beta-lactams for G+
2 drugs commonly used for anaerobes
Metranidazole or clindamycin
Nucleic acid synthesis inhibitor used for cryptococcus meningitis
5-FC
Bone marrow toxicity and resistance can develop in days so always use in combination
Antifungal with ability to form pore in cell wall
Amphotericin B
Azole mechanism
Inhibition of cytochrome P-450 to block synthesis of ergosterol
Echinocandins do not work on…
Zygomycetes
Target of echinocandins
Block B-1,3-glucan synthase inhibitors
Good drug for mycoplasma (no cell wall)
Azithromycin (Macrolide)
Classes of beta-lactams
- Penicillins 2. Cephalosporins 3. Monobactams 4. Carbapenems
Common concern for treating patients with beta-lactams
Allergies (mild to anaphylaxis)
Beta-lactam mechanism
inhibits cell wall synthesis by binding to and preventing PBP function of cross-linking NAM and NAG BacterioCIDAL
Ceftriaxone is what generation cephalosporin?
3rd
Cefezolin is what generation cephalosporin?
1st often used as surgical prophylaxis
Subclasses of cephalosporins
- Classified from 1st to 5th generation 1st narrow spectrum (G+) 5th broad spectrum and better with G-
Clindamycin limitations
Poor penetration into CSF –> don’t use for meningitis
Clindamycin mechanism
Bind 50S ribosomal subunit, prevents elongation of peptide chains—suppresses protein synthesis (same spot as macrolides) Can be bacteriostatic or bacteriocidal
Fluoroquinalone spectrum with increasing generation
Early better for G- Later better for G+
First gen fluoroquinalone
Nalidixic acid
Third gen fluoroquinalone
tosufloxacin
Second gen fluoroquinalones
Ciprofloxacin and levofloxacin
Fourth gen fluoroquinalones
Moxifloxacin and Gemifloxacin
Fluoroquinolone mechanism
Inhibit DNA gyrase +/- topoisomerase IV to inhibit chromosomal replication BacterioCIDAL
Leuconostoc has intrinsic resistance to what antibiotic
Vancomycin
Klebsiella isolate resistant to aztreonam and ceftriaxone has what resistance mechanism?
K-1 beta lactamase
Macrolide side effects
GI distress
Macrolide spectrum
Broad-spectrum: Gram positives, some Gram-negative, anaerobes, atypical mycobacteria, and “atypical” respiratory pathogens (mycoplasma, chlamydiae, Legionella) that are less susceptible to β-lactams
Macrolides mechanism
Bind reversibly to 23S of rRNA of the 50S ribosomal subunit, block translocation of tRNA from acceptor to donor side on ribosome BacterioSTATIC
A predefined stable antibiotic gradient is present on a thin carrier strip.
E-test
A paper disk with defined amount of antibiotic is used to generate a dynamically changing gradient of antibiotic concentrations in the agar in the vicinity of the disk. ZOI gives qualitative indication if whether the bug is susceptible.
Kirby-Bauer Method
the lowest concentration of an antimicrobial that will kill an organism.
MBC = Minimum Bactericidal Concentration
What density should the inoculum for Kirby-Baur tests be?
- 5 McFarland
- 5 x 108 organisms/mL
the lowest concentration of an antimicrobial that will inhibit the visible growth of a microorganism after overnight incubation.
MIC = Minimum inhibitory concentration
Metronidazole coverage
Requires reduction of nitro group under anaerobic conditions, therefore only effective against anaerobes and protozoa
Metronidazole mechanism
Causes breaks in DNA
Beta-lactam resistant to β-lactamases. Purely Gram-negative coverage, primarily active against members of the family Enterobacteriaceae
Monobactams
Polymixin concerns
Kidney and neurotoxicity
Polymixin uses
Primarily for multi-drug resistant Gram negatives (eg. Pseudomonas) Also used as a topical Ab with no toxicity concerns
Polymixins mechanism
Large polypeptides with cationic detergent effect that disrupts cell membrane
AmpC characteristics
Not inhibited by bet-lactamase inhibitors
AmpC mechanism
Cascade triggered by the sensing of damage to the cell wall. Induces AmpC expression, a beta-lactamase
Name the SPICEM organisms and what resistance patten they can carry
SPICEM organisms are members of the Enterobacteriaceae that often carry an inducible AmpC gene
- Serratia
- Providencia
- Indole-positive Proteus (vulgaris)
- Citrobacter
- Enterobacter
- Morganella
Transferrable carbapenemase
KPC
Carbapenemase detection
Hydrolysis of immipenem Modified Hodge test- test isolate produces the enzyme and allows growth of a carbapenem susceptible strain towards a carbapenem disk
Resistance to carbapenems caused by…
Efflux or carbapenemase
Erythromycin and Clindamycin resistance mechanism
Methylation of 50S ribosome
Erythromycin/Clindamycin resistance detection
D-zone test
ESBL characteristics
Sensitive to beta-lactamases
General mechanisms of antimicrobial resistance
Efflux pumps Restricted access to target Target modification Inactivating enzymes
Mechanism of MRSA
mecA gene encodes an altered penicillin-binding-protein, PBP2a, that beta-lactams cannot bind to. Often on a mobile element, SCCmec, so there are concerns for spread of resistance
What drug do we use to look for MRSA?
Cefoxitin
Historically, oxicillin has been used but cefoxitin is more stable and better able to induce the mecA gene
VISA mechanism
Cell wall thickening traps vancomycin from penetrating to deeper layers of peptidoglycan
VRE mechanism
VanA and VanB alter terminal end of D-ala so that vancomycin can no longer bind
Species of Enterococcus most likely to be VRE
E. faecium Treat with daptomycin instead
Rifampin mechanism
Inhibits bacterial DNA-dependent RNA polymerase -> inhibits transcription
Rifampin resistance mechanism
point mutations in rpoB occur quickly Always must be prescribed in combination
Sulfas/trimethoprim mechanism
inhibit folate synthesis, thereby inhibiting purine metabolism (sequential inhibition) leading to troubles in DNA synthesis.
Sulfas/trimethoprim spectrum
Broad spectrum against many G+ and G-, also some parasites (i.e. Toxo) and Pneumocystis jiroveci
Tetracyclines mechanism
Bind reversibly to 30S subunits, preventing attachment of aminoacyl-tRNA to ribosomal acceptribosomal or in RNA-ribosome complex usually bacterioSTATIC
Name two drugs where both MIC and therapeutic drug monitoring are used…
Aminoglycosides Vancomycin - pay attention to MIC because there’s a range of effective doses and the higher required doses can cause toxicity problems
Vancomycin mechanism
Vancomycin forms hydrogen bonds with D-Ala-D-Ala dipeptide, which inhibits transpeptidase and peptidoglycan crosslinks.
Vancomycin spectrum
Gram positive ONLY. Cannot diffuse across LPS outer membrane of G-
When reading a KB plate, what are conditions in which the inner “haze” is ignored and the ZOI is measured further out?
- Proteus will swarm in but it’s not actually growing
- Sulfonamides and trimethoprim disks may have an inner haze due to the organism population going through several doubling generations before inhibition.
