You beta werk
Amino walks into a bar
Fall to the fluor-oquinline
Lincos and sulfas and glycosides oh my!
Bugs and drugs
100
What is the MOA of beta lactam antibiotics?
They binds to the penicillin binding protein (PBP), resulting in degradation of the cell wall and impaired synthesis of a new one result in permeability to the local environment and bacterial lysis
100
What is the MOA of aminoglycosides?
Aminoglycosides inhibit bacterial protein synthesis by binding to the ribosome 30S subunit. Specifically, aminoglycosides have a high affinity for the A site on the 16S ribosomal RNA and alter its conformation, allowing for tRNA to bind and cause misreading of mRNA and faulty protein synthesis
Cellular uptake:
1. The outer bacterial lipopolysaccharide membranes are negatively charged, aminoglycosides are positive. This leads to an ionic binding between the two molecules and increased wall permeability, leading to the entry of aminoglycosides into the cell.
2. Energy-dependent phase I (EPDI) - aminoglycosides in the cell creating nonspecific membrane channels and further facilitating aminoglycoside entry. This is ATP dependent
3. Energy-dependent phase II (EPDII) - Once membrane channels are inserted, aminoglycoside accumulates quickly within the cytoplasm. This leads to more inhibition and mistranslation of protein synthesis and bactericidal activity.
3.
100
What is the MOA of fluoroquinolones?
All fluoroquinolones exert antimicrobial activity via inhibition of bacterial topoisomerase IV and DNA gyrase (a member of the topoisomerase family). Inhibition of these enzymes prevents normal bacterial DNA synthesis, replication, and division, resulting in bacterial cell death. DNA gyrase catalyzes the negative supercoiling of circular bacterial DNA as well as relaxing positive supercoiling, the latter of which would otherwise interfere with DNA replication. Topoisomerase IV unlinks DNA following DNA replication, facilitating the separation of daughter cells. Inhibition of DNA gyrase is the predominant mechanism for the killing of Gram-negative bacteria, whereas inhibition of topoisomerase IV is primarily responsible for effects on Gram-positive bacteria.
100
What is the MOA of metronidazole?
Within the bacteria, it gets reduced and is incorporated within the bacterial DNA, causing a loss of helical structure, inhibition of nucleic acid synthesis, and cell death.4 The nitrous reduction of metronidazole can only be achieved in anaerobic bacteria.
100
List the anti-Pseudomonal antibiotics.
Antipseudomonal penicillins (ticarcillin and piperacillin), ceftazadime, +/- aztreonam, aminoglycosides, fluoroquinolones
200
What are the mechanism of methicillin resistance Staph and expression of this confers resistance to what antimicrobials?
Insertion of the mecA gene, which encodes a mutation in the PBP2a. Expression of this gene will make the organism resistant to the entire class of β-lactam antimicrobials except fifth-generation cephalosporins
200
What are the three mechanisms of acquired resistance in aminoglycosides and the intrinsic resistance mechanism?
Resistance to aminoglycosides involves three major mechanisms: enzymatic mutation of the aminoglycoside molecules themselves, target modification with a change in ribosomal 30S subunit structure, and an increase in aminoglycoside efflux out of the bacteria.
Intrinsic resistance: Aminoglycoside uptake requires active electron transport, which is the result of aerobic metabolism. As such, aminoglycosides are ineffective against anaerobic bacteria. Similarly, Gram-positive facultative anaerobes such as Enterococcus faecalis and Enterococcus faecium are resistant due to poor cellular uptake and the presence of AME.
200
What antibacterial spectrum do fluoroquinolones cover? 7 bacteria required for credit.
Enterobacteriaceae (Escherichia coli, Klebsiella), Pasteurella spp., Bordetella spp., Salmonella, and Campylobacter spp. Pseudomonas aeruginosa is variably susceptible to different fluoroquinolones, and resistance to fluoroquinolones can develop during the course of treatment.6 Isolates of P. aeruginosa appear to have greater susceptibility to marbofloxacin than enrofloxacin.7 Susceptible Gram-positive organisms include Staphylococcus spp. and Neisseria spp., while Streptococcus spp. are frequently resistant.Intracellular pathogens potentially susceptible to fluoroquinolones include Mycoplasma spp., Chlamydophila spp., Brucella canis, and certain mycobacteria. Of note, tick-borne rickettsial and rickettsia-like infections are variably susceptible to fluoroquinolones, and many are resistant.
200
What four antibiotics inhibit the 50 s ribosome as their mechanism of action?
Chloramphenicol, clindamycin, macrolides (erythromycin, azithromycin), linezolid
200
What are the anti-mycoplasma antibiotics?
Tetracyclines, clindamycin, chloramphenicol, aminoglycosides (?) and fluoroquinolones
300
What are the 4 mechanisms of resistance of beta lactams?
Resistance to the β-lactam class can be due to alterations in the PBPs of a bacteria, development of antimicrobial efflux pumps, changes to porins in the bacterial cell wall, or inactivation by β-lactamases.
Penicillinases, AmpC-type cephalosporinases, extended spectrum β-lactamases (ESBLs), and carbapenemases.
300
What are the PK/PD goals for maximal antibioic effects of aminoglycosides?
Maximum (peak) drug plasma concentration (CMax) over the minimum inhibitory concentration (MIC) of 8 to 10 or the area under the curve (AUC) over MIC ratio >75.16 Increasing the ratio Cmax/ MIC >10 does not significantly increase bactericidal activity
300
What are mechanisms of resistance to fluoroquinolones?
Mechanisms of bacterial resistance to fluoroquinolones include increased efflux and alterations to the antimicrobial targets: DNA gyrase and topoisomerase IV. Specifically, point mutations for the bacterial genes encoding the gyrA subunit of DNA gyrase and the parC subunit of topoisomerase are most common and result in reduced drug affinity for these complexes.17,25 Plasmid-mediated fluoroquinolone resistance has been documented, and plasmids may confer resistance to multiple classes of antimicrobials, resulting in multidrug resistant organisms
300
What is the MOA of TMS?
Sulfonamide and trimethoprim work on different steps of bacterial folic acid production. Sulfonamide is a competitive analog to P aminobenzoic acid (PABA). Trimethoprim inhibits folic acid reduction (via dihydrofolate reductase) lower down the folic acid production pathway. Each drug used individually is bacteriostatic. The combination of sulfonamide and trimethoprim results in a bactericidal and time-dependent drug.
300
What antibiotics are time dependent vs. concentration dependent? List 3 examples of each.
Time dependent:
Beta lactams, linezolid (oxazolidinones), TMS (sulfas), tetracyclines, cindamycin (lincosamides),
Concentration dependent
Daptomycin (lipopeptides), metronidazole (nitroimidazole), fluoroquinolines, aminoglycosides
400
List three beta lactamase inhibitors and their MOA.
The three β-lactamase inhibitors clavulanic acid, sulbactam, and tazobactam are weak β-lactam antimicrobials each possessing the β-lactam ring.
They irreversibly bind to β-lactamases, and when administered with a β-lactam antimicrobial (e.g., ampicillin/sulbactam, amoxicillin/clavulanate, or piperacillin/tazobactam), the β-lactam can then bind to the bacterial PBP resulting in cell death
400
What are three adverse effects of aminoglycosides?
Nephrotoxicity, ototoxicity and NMB
400
What adverse events have been reported secondary to fluoroquinolone use?
vomiting, diarrhea, nausea, and abdominal cramping; neurologic abnormalities such as seizures, tremors, and abnormal electroencephalographic findings; cartilage defects in juvenile animals, and irreversible blindness in cats.1 Fluoroquinolone-associated retinopathy in cats appears to be dose-related and has been documented with enrofloxacin doses greater than 5 mg/kg q24h
Fluoroquinolones have been shown to competitively inhibit binding of γ-aminobutyric acid, which may lower the seizure threshold in patients with idiopathic epilepsy, and thus should be avoided or used with extreme caution in patients with seizure disorders.
The injectable form of enrofloxacin has an alkaline pH (pH = 11), and subcutaneous administration has been associated with localized reactions and skin necrosis. The injectable formulation is labeled for intramuscular use, and subcutaneous use should be avoided.
Additional adverse effects have been noted in people, including peripheral neuropathy, delirium, tendinitis/acute tendon rupture, altered glucose homeostasis, QT prolongation, phototoxicity, hepatotoxicity, interstitial nephritis, hemolytic uremic syndrome, crystalluria, and Clostridioides difficile infection.
Rapid intravenous administration may result in histamine release in dogs. Higher than recommended intravenous doses of marbofloxacin (12 mg/kg) resulted in cardiovascular signs including hypotension, decreased heart rate, and prolongation of the QT interval in healthy anesthetized dogs. There is debate as to whether rapid intravenous enrofloxacin may also decrease seizure threshold in dogs, but this has not been studied or formally reported.
The use of fluoroquinolones in patients with necrotizing fasciitis is potentially detrimental. Rare reports have documented that fluoroquinolones can induce activation of a latent bacteriophage within exotoxin-producing Streptococcus spp. (i.e., S. canis) isolated from a dog with necrotizing fasciitis. Bacteriophage activation can result in rapid bacterial cell lysis, release of a bacteriophage encoded streptococcal superantigen, and the potential sequelae of toxic shock syndrome.
400
What is the MOA of vancomycin?
Vancomycin prevents the formation of peptidoglycan in Gram-positive pathogens.
400
What antibiotics are bacteriostatic?
Choramphenicol, clindamycin (vs. cidal), tetracyclines, and linezolid
500
What are the side effects of beta lactams?
Type 1 hypersensitivity reactions ranging from urticaria to acute anaphylaxis. The frequency of these is unknown in small animals; however, in people, allergic reactions occur in 0.7%–10% receiving penicillin, with acute anaphylactic reactions occurring in 0.01%–0.05%.19 Cross reaction amongst the different types of β-lactams is possible but not certain as the immunoglobulins responsible are more likely to form against the side chains than the β-lactam ring. A reported allergy to penicillins does not absolutely preclude the use of other β-lactam antimicrobials. Type 2 HS reactions: hemolytic anemia, thrombocytopenia, and neutropenia have reported. Type 3 and 4 HS reactions are also possible with unknown incidences, with the type 4 HS reactions usually manifesting as cutaneous disease. Nausea, vomiting, and diarrhea with PO administration. If they are administered in high doses, resulting seizures and other neurologic diseases are possible. These are more likely if brain disease is already present.
500
What is the antibacterial spectrum of aminoglycosides? List 7 bacteria for credit.
Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, and Proteus spp. When first discovered, aminoglycosides were extensively used to treat plague (Yersinia pestis) and tularemia (Francisella tularensis). Aminoglycosides also have good activity against Gram-positive pathogens such as Staphylococcus aureus and Staphylococcus pseudointermedius. In the past, methicillin-resistant Staphylococcus aureus and methicillin-resistant Staphylococcus pseudintermedius (MRSP) isolates retained susceptibility against aminoglycosides but more are resistant now. Pseudomonas aeruiginosa are overall susceptible to aminoglycosides and to a lesser degree Acinetobacter baumanii.
500
What is the Vd of fluoroquinolones and what tissue penetration is achieved with this class of drugs?
Fluoroquinolones have a relatively high volume of distribution (Vd) and distribute into tissues and the intracellular space soon after administration. Concentrations in kidney, lung, and prostate tissue, as well as urine, bile, macrophages and neutrophils often exceed that of serum. They are lipophilic molecules that exhibit variable protein binding within the class, ranging from low to moderate (18%–35%).
500
What are adverse effects of TMS? List 5 for credit.
Dogs have a decreased ability to acetylate sulfonamide, creating allergenic, immunogenic, and toxic metabolites. Doberman Pinschers, Samoyeds, and Miniature Schnauzers are thought to be more sensitive to TMS than other breeds. Side effects include hypersensitivity reactions such as fever, polyarthropathies, pancreatitis, hepatitis, glomerulonephritis, anemia, immune-mediated thrombocytopenia, and mucosal skin lesions, none of which are dose-dependent. Keratoconjunctivitis sicca (KCS) is the most common side effect due to the direct cytotoxic effect of sulfonamides on the lacrimal gland. Additionally, a reversible decrease in thyroid hormones has been reported in dogs.
500
What antibiotics are exhibit a post antibiotic effect (PAE)?
Aminoglycosides, fluoroquinolines, clindamycin, macrolides, glycopeptides, linezolid, carbapenams