Antibiotics Flashcards
Define MIC
the lowest concentration of an antimicrobial (like an antifungal, antibiotic or bacteriostatic) drug that will inhibit the visible growth of a microorganism after overnight incubation
Define MBC
is the lowest concentration of an antibacterial agent required to kill a particular bacterium as the lowest concentration of antimicrobial that will prevent the growth of an organism after subculture on to antibiotic-free media
What determines if an antimicrobial drug is classified as bactericidal or bacteriostatic (there is a specific definition relating to the MIC)?
Bactericidal antibiotics kill bacteria; bacteriostatic antibiotics inhibit their growth or reproduction- which means that the host’s immune system does the killing. Cidial- MBC 4 times or less the MIC of that drugStatic if the MBC is more than 4 times MIC of that drugSpecific to the bacteria and the drug
Discuss the concepts of synergistic antimicrobial combinations, antagonistic antimicrobial combinations, indifferent antimicrobial combinations
Additive: the combined effect is equal to the sum of the independent effectsSynergistic: the combined effect is greater than the sum of the independent effects; example beta lacatam/aminoglycoside; amoxi/clav; tms;Indifferent if the combined effect is similar to the greatest effect produced by either drug alone
Describe how to interpret and use susceptibility testing
Susceptibiltiy testing: in general, the peak serum concentration of a drug should be 4-10 times greater than the MIC in order for a pathogen to be susceptible to a drug. Pathogens with intermediate sensitivity may respond to treatment with maximal doses of an abx
Cell Wall Inhibitiors
Penicillins, cephalosporins, vancomycin, bactiracin, carbapenem, imipenem
DNA Gyrase inhibitors
quinolones, fluoroquinolones
Folate synthesis inhibitors
sulfonamides, trimethoprim
RNA polymerase inhibitor
rifampin
Cell Membrane inhibitors
amophotericin, polymixin
Protein Synthesis
aminoglycosides, chloramphenociol, clindamycin, macrolides, mupirocin, tetracyclines, stretogramins
What is a CLSI breakpoint
Clinical and laboratory standards institute specific for each of the following: animal species, target tissue, target organism, antibmicrobal drug, route administration
Broth dilution test
Tubes that contain a nutrient broth are inoculated with equal numbers of bacteria and serially diluted concentrations of an antibiotic. After incubation the MIC is identified as the lowest antibiotic concentration that prevents visible growth of bacteria
Disk diffusion- Kirby Bauer
each disk used is impregnated with a different antibiotic. The discs are palced on augar plates seeded with the test organism. During the incubation period the antibiotic diffuses from the disk and inhibits bacterial growth. The zone inhibitied by each antibiotic is measured. The zone diameter for each is comparted with standard values for that antibiotic
E-Test Strip
uses a diffusion method to determine the MIC. The device is a plastic strip that is impregnated with a gradient of antibiotic concentrations. After the strip is placed on an agar culutre of the organism the culture is incubated. A tear shaped zone of inhibition is formed. The scale displaced on the strip is the MIC- able to get MBC/MIC
Episolon test
Card with wells, color change of the wells- MBC/MIC
Natural resistance to enterococcus
Cephalsporins
Promote resistance by pressure to express Mech A for Staph
Cephalsporins and fluoroquinolones
Beta Lacatams
Bind to a group of bacterial enxymes BPBs which are anchored on the cytoplasmic membrane and extend into the periplasmic space. They form a covalent bond with PBPs and thereby inhibit the catalytic activity of these enzymes. All are bacterialcidial
Penicillin ADME
Acid stable- PO; Acid liable IV; Widely distributed exceot to CNS; readily penitrates CSF when meninges are inflammed. Active renal tubular secretion; Ampicillin is primarly excreted in bile
Penicillin Antibacterial Activity
Grame +, anaerobic
Cephalosporins ADME
Oral or parental (cefuroxime is both); mostly renal tubular excretion; ceftriaxone is bile- longer half life
Cephalosporins Antibacterial Activity
1st: Gram + Cocci (limited G- baccili;) 2:G+ better G- bacilli; 3rd: better G- bacilli, anaerobes and psuedomonas
Beta lactase inhibitors ADME
Binds to active site of pencillinase rendering the enzyme inactive; Time dependent; side effect hemolytic anemia
Carbapenams ADME
Admin- IV, Eliminated via Renal tubular secretion
Carbamenams Antibacterial Activity
G+, G-, anaerobic and aerobic
Monobactams ADME
Administered IV, Extensively metabolized, renal excretion
Monobactams Antibacterial Activity
Aerobic G- Bacilli
Monobactams advantages
Can be used with B-lactam allergies; used with MDR; can cause thrombophelbitis in people
Polymyxins MOA
Cationic detergents that interact and interfere with phospholipid of the bacterial cell membrane resulting in increase permeability: Bacterialcidial
Polymyxins ADME
Weak bases and are not orally bioavailable. Renal elimination primary site (toxicity as well); Used primarily topically
Polymyxins Antibacterial Activity
Most G- exceptions include proteus and serratia
Polymyxins Complications
Glomerular and tubular epithealial damage, respiratory paralysis (not reported in cats). CNS dysfunction, fever and anorexia
Glycopeptides/Vancomycin MOA
Cell wall inhibitor. Used to targe MRSA, Enterococcus (designed for)
Glycopeptides/Vancomycin ADME
Only IV; Not absorbed from the gut- therefore used orally for C-diff
Glycopeptides/Vancomycin Antibacterial Activity: Cidal/static; Time vs Conc?
Gram +; Bactericidal; Time dependent
Glycopeptides/Vancomycin advantages
Can be used with allergies to beta lactam
Glycopeptides/Vancomycin complications
Bad pheblitis and horrible sloughing of the SQ
Bacitracin MOA
Inhibits cell wall peptidoglycan synthesis by blocking the regeneration of bactopernol lipid carrier molecule
Bacitracin Antibacterial Activity
Gram + Cocci
Bacitracin Contraindications
Nephrotoxic so don’t use systemically
Fosamycin MOA
Cell wall inhibitor
Fosamycin ADME
Phosphoric acid; Low pH useful for bacteria express MDR
Fosamycin Antibacterial Activity: Cidal/static; Time vs concentration?
E-Coli and Gram +/-; Bacterialcidal; Concentration dependent
Clindamycin/Lincosamides MOA
50s Subunit at a site distinct from macrolides and chloramphenicol; peptidyl transferase is inhibitied
Clindamycin/Lincosamides ADME
Highly protein bound, Food impairs absorption; good for skin and bones; eliminated primarily for biliary excretion; Crosses BBB
Clindamycin/Lincosamides Antibacterial Activity
G+, aerobic cocci, anaerobic and cell wall deficient organismis; mycoplasma; Static; Time dependent
Clindamycin additional notes
Accumulates in white blood cells up to forty fold or more- increases the probability of reaching bactericidal concentrations at some sites of infection. Penetrates pus in pyothorax; In people may lead to C-Diff
Pleuromutilins MOA
50s Subunit- Static; Occasionall used in SA
Macrolides/ Azythromycin MOA
50s subunit and impair the translocation step of protein synthesis
Macrolides/ Azythromycin ADME
Lipid soluble and accumulates in phagocytic WBCs; Urine secretion is not significant and conentration is often less than in plasma. Pentrates the lung very well
Macrolides/ Azythromycin Antibacterial Activity
G+/-; bordetella; Static in vitro- scidial against susceptible organisms; time and concentration dependent- exhibits post antibiotic effect
Macrolides/ Azythromycin complications
GI side effects
Streptogramins/ quinupristin MOA
50s subunit
Streptogramins/ quinupristin Antibiotic Activity
Vancomycin resitant enterococcus; Static
Ketolides
Are semisynthetic modificaions of erythromycin designed to minimize barriers to pentration in gram negative organisms
Aminoglycosides/Amikacin/Gentomycin MOA
30s ribosome; enters through porins; efficacy is dependent on active transprt- which is reduced to absent in anaerobic environments
Aminoglycosides/Amikacin/Gentomycin ADME
Synovia, pleural and peritonel fluid better in bronchial secretions; Actively accumulated in renal tubular cells; Reduce efficacy in acidic environments. Eliminated through glomerular filtration; Not absorbed through the gut- good for shunt dogs
Aminoglycosides/Amikacin/Gentomycin Antibacterial activity
Aerobic G-; Static; concentration
Aminoglycosides/Amikacin/Gentomycin side effects
Dose reduce for obesity; Nephrotoxicity- tubular and glomerular- which is reversible
Tetracyclines MOA
Bind to the 16s portion of the 30s ribosomal subunit preventing access to the amino-acryl tRNA to the acceptor site on the mRNA ribosome complex. Enters through porins or active transport pumps
Tetracyclines ADME
Doxy- 100% bioavailable, lipid soluble; decreased with divalent and trivalent cations such as milk or antacids; widely absorbed through body tissues. Biliary and renal excretion
Tetracyclines Antibacterial Activity
Gram +/-; anaerobic, rickettsial, and cell wall deficient; Static
Tetracyclines Adverse effects
Caution in immunocompromised patients; GI upset; rarely hepatotoxicity; Rapid IV infusion results in collapse/shock; tooth discoloration esophageal stricture in cats
Chloramphenicol MOA
50s subunit with inhibition of peptidyl transferase
Chloramphenicol ADME
Liquid is not well absorbed; excellent tissue distribution and relatively long half life
Chloramphenicol Antibacterial activity
G+/- anaerobic; static
Chloramphenicol Use (what not to do)
Don’t use with macrolides as compete with for same binding site
Chloramphenicol Adverse effects
People: bone marrow suppression- aplasial of all lines- both dose dependent and independent; Dogs and cats may get dose dependent suppression; Decreased rate of digoxin elimination
Sulfonamides MOA
Folate acid inhibitors; Structurally similar to PABA and act as competitive substrates (antimetabolites) for the synthetase enxyme. Potintiated acts at two steps which make it cidal
Sulfonamides ADME
Good oral absorption; enterohepatic circulation and eliminated in urine; 70% metabolized by colonic bacteria. Some will have hepatic metabolisim. Good for prostate/CNS
Sulfonamides Antibacterial Activity
G+/-; anaerobic; Static but if potinetiated cidal; Time dependent
Sulfonamides Adverse effects
Immunological disease of the skin, kidney, liver and eye which are not dose dependeint. Incidence of 0.25%; thyroid suppression. Monitor STT and CBCs throughout treatment; Black/Tan delayed type 2 hypersensitivity
Fluoroquinolones MOA
Disrupts DNA gyrase and DNA Topoisomerase activity
Fluoroquinolones ADME
Renal elimination primarly with some fecal and hepatic; Not good CSF; Good tissue penetration because is lipid soluble and accumulates in phagocytic WBC; Oral bioavability is drug dependent.
Fluoroquinolones Antibacterial Activity
G- and some G+; Cidial, Concentration dependent
Fluoroquinolones Adverse effects
GI, cartilage deformities and ligament and tedon repair; Seizures and other CNS; dose dependent retinal degeneration. Induction of bacteriophage supergenes
Ionophores (monincyn, improlium) MOA
Allow ions to cross cell membranes tag along through the channels
Ionophores (monincyn, improlium) ADME
Feed additive for chicken and beef
Ionophores (monincyn, improlium) activity
G+; Used to treat coccidia
Nitrofurans MOA
Mechanism is unclear- may damage DNA
Nitrofurans ADME
Reduced in liver, excreted by kidney, Reduced dose if renal compromised; Is not systemically distributed
Nitrofurans what are they used for
Urinary pathogens; But not pseudomonas, klebsiella, proteus, serratia, acinetobactor
Nitrofurans adervese effect
Neurological
Nitroimidazoles Metronidazole MOA
Impairs microbal RNA and DNA synthesis but must first undergo nitrous reduction in the organism
Nitroimidazoles Metronidazole ADME
Pirmarly liver elimination; distributes well to all tissues
Nitroimidazoles Metronidazole Antibacterial activity
Anaerobic; Can be both time and concentration dependent
Nitroimidazoles Metronidazole Adverse effects
Discolored urine (red-brown); GI upset; CNS adverse effects including seizures (not normal BBB more likely at small doses)
Rifamycins MOA
Inihibits the B subunit of DNA-dependent RNA polymerase; suppressing RNA Synthesis
Rifamycins ADME
Absorption may be higher in dogs with p-glycoprotein deficiency; Lipid soluble; excreted in bile
Rifamycins Antibacterial Activity
G+, mycobacterium, neisseria, chlamydia, clostridium and bacteroides; static/cidial depending on tissue; concentration
Rifamycins Adverse effects
Rapid resistance limits use to combination therapy; Red to orange colored excretions; Alk phos increase; MDR-1 dogs increased risk of adverse reactions
Nitroimidazoles Metronidazole Reistance
Bacteria that lack necessary electron transport systems necessary to geneerate single electrons
How do you treat metronidazole neurological sidefects
Give diazepam will help to recover faster
Oral dose as well
Chloramphenicol benefits
Shown to inhibit production of beta-lactamases; potent inhibitor of drug metabolizing enzymes
Macrolides GI motility
Improves for 2-3 doses then resitance to it in the gut; motilin mimitic