Antibiotics/Antifungal/Antiviral Flashcards
Metronidazole Benzoate
- Antibacterial (anaerobic), Antiparasitic (protozoal)
- Second generation nitroimidazole. Generation of free nitrordicals via metabolism within organism. Disrupts DNA via reaction with intracellular metabolite. May have some immune-modulating activity in instetines of animals being treated for IBD
- Tx: diarrhea + GI protozoa + anareoic infections
- SE: toxicity to CNS (often high doses, >60 mg/kg/day)- ataxia, tremors seizures- due to inhibition of action of GABA. GI upset.
Papich
Define MIC vs MBC?
The MIC (Minimum Inhibitory Concentration) is defined as the lowest concentration of an antibiotic which will inhibit the in vitro growth of an infectious organism.
The MBC (Minimum Bactericidal Concentration) is defined as the lowest concentration of an antimicrobial agent needed to kill 99.9% of the initial organism inoculum. (So- a higher concentration).
internet
What determines if AB is bactericidal or bacteriostatic?
Minimum inhibitory concentration (MIC) is the minimum bacteriostatic drugs concentration required to prevent growth of bacteria, while minimum bactericidal concentration (MBC) is the minimum bactericidal concentration required to kill bacteria
Internets
Cidal if the MCB is 4 x or less the MIC, if more then 4 x MIC then it is a static drug. - pigott/small animal antimicrobial therapy in veterinary medicine
Static vs cidal, as explained by cockroaches!
An example of this is the effect of bug spray on a cockroach. A light spray will only slow the cockroach down (a cockroach-static level). By tomorrow, the cockroach will recover. However, if one drowns the cockroach in bug spray (a cockroach-cidal level), the cockroach will perish.
:)
Discuss syngergistic AB combinations
Synergy between antimicrobial agents means that, when studied in vitro, the combined effect of the agents is greater than the sum of their independent activities when measured separately
ex) treatment of endocarditis caused by Enterococcus species with a combination of penicillin and gentamicin. In this setting, the addition of gentamicin to penicillin has been shown to be bactericidal, whereas penicillin alone is only bacteriostatic and gentamicin alone has no significant activity.
Mayo Clin Proc. 2011 Feb; 86(2): 156–167.
Discuss antagonistic AB combinations
Antagonism, when a drug hinders the effect of another drug.
ex) In a (human) study of patients with pneumococcal meningitis, 30% of those treated with penicillin alone failed treatment and died, while 79% of comparable patients who were treated with the same dosage of penicillin plus chlortetracycline, an antibiotic that antagonizes penicillin, died.
Antimicrob. Agents Chemother. August 2014 vol. 58 no. 8 4573-4582
Cidal and static drugs together or ones that use the same binding sites- pigott
Discuss indifferent AB combinations
Additive (indifferent) effect: the activity of two drugs in combination is equal to the sum (or a partial sum) of their independent activity when studied separately
Internet
Define Synergistic, Antagonistic, Indifferent AB combiations.
•Additive (indifferent) effect: the activity of two drugs in combination is equal to the sum (or a partial sum) of their independent activity when studied separately
•Synergistic effect: the activity of two drugs in combination is greater to the sum of their independent activity when studied separately
•Antagonistic effect: the activity of two drugs in combination is less to the sum (or a partial sum) of their independent activity when studied separately
Internet PPT by Mazen Kherallah, MD,
What does CLSI stand for?
Only two international standard-setting groups, the Clinical and Laboratory Standards Institute (CLSI; formerly known as the NCCLS) and the European Union Committee on Antimicrobial Susceptibility Testing (EUCAST), have published guidelines on which data are required for, and how these data are applied to, breakpoint setting
CLINICAL MICROBIOLOGY REVIEWS, July 2007, p. 391–408
Discuss CLSI Breakpoints
In general, all susceptibility testing methods require breakpoints, also known as interpretive criteria, so that the results of the tests can be interpreted as susceptible, intermediate, or resistant and reported as such to a broad range of clinicians.
a) Wild-type (or microbiological) breakpoint- on bacteria without any aquired resistance
b) Clinical breakpoints- based on MIC of individual strains
c) Pharmacokinetic (PK/PD) breakpoints- based on experimental animal models and extrapolated to human medicine
Clin. Microbiol. Rev. July 2007 vol. 20 no. 3 391-408 1 July 2007
Breakpoints are specific for organism, patient species, target tissue , route, and drug- pigott
**Brakpoints are in vitro data! - Pigott
Susceptability testing methods- listed
1) Disk Diffusion
2) gradient strips
3) Broth based dilutions
4) Agar based dilutions
AP
Describe disk diffusion susceptibility testing
Because of convenience, efficiency and cost, the disk diffusion method is probably the most widely used method for determining antimicrobial resistance in private veterinary clinics.
A growth medium, usually Mueller-Hinton agar, is first evenly seeded throughout the plate with the isolate of interest that has been diluted at a standard concentration (approximately 1 to 2 x 108 colony forming units per ml). Commercially prepared disks, each of which are pre-impregnated with a standard concentration of a particular antibiotic, are then evenly dispensed and lightly pressed onto the agar surface. The test antibiotic immediately begins to diffuse outward from the disks, creating a gradient of antibiotic concentration in the agar such that the highest concentration is found close to the disk with decreasing concentrations further away from the disk. After an overnight incubation, the bacterial growth around each disc is observed. If the test isolate is susceptible to a particular antibiotic, a clear area of “no growth” will be observed around that particular disk.
The zone around an antibiotic disk that has no growth is referred to as the zone of inhibition since this approximates the minimum antibiotic concentration sufficient to prevent growth of the test isolate. This zone is then measured in mm and compared to a standard interpretation chart used to categorize the isolate as susceptible, intermediately susceptible or resistant. MIC measurement cannot be determined from this qualitative test, which simply classifies the isolate as susceptible, intermediate or resistant.
Microbiology
Describe broth (and agar) dilution methods of susceptability testing
The Broth dilution method involves subjecting the isolate to a series of concentrations of antimicrobial agents in a broth environment. Microdilution testing uses about 0.05 to 0.1 ml total broth volume and can be conveniently performed in a microtiter format. Macrodilution testing uses broth volumes at about 1.0 ml in standard test tubes. For both of these broth dilution methods, the lowest concentration at which the isolate is completely inhibited (as evidenced by the absence of visible bacterial growth) is recorded as the minimal inhibitory concentration or MIC. The MIC is thus the minumum concentration of the antibiotic that will inhibit this particular isolate. The test is only valid if the positive control shows growth and the negative control shows no growth.
A procedure similar to broth dilution is agar dilution. Agar dilution method follows the principle of establishing the lowest concentration of the serially diluted antibiotic concentration at which bacterial growth is still inhibited.
Microbiology
Discribe the gradient strip (or E-test) susceptability testing method
E-test (AB Biodisk, Solna, Sweden) is a commercially available test that utilizes a plastic test strip impregnated with a gradually decreasing concentration of a particular antibiotic. The strip also displays a numerical scale that corresponds to the antibiotic concentration contained therein. This method provides for a convenient quantitative test of antibiotic resistance of a clinical isolate. However, a separate strip is needed for each antibiotic, and therefore the cost of this method can be high
Microbiology
Other susceptability testing mechanisms….
1) AUTOMATED ANTIMICROBIAL SUSCEPTIBILITY TESTING SYSTEMS- provide automated inoculation, reading and interpretation.
2) MECHANISM-SPECIFIC TESTS- Resistance may also be established through tests that directly detect the presence of a particular resistance mechanism. For example, beta lactamase detection can be accomplished using an assay such as the chromogenic cephalosporinase test
3) GENOTYPIC METHOD- Since resistance traits are genetically encoded, we can sometimes test for the specific genes that confer antibiotic resistance. However, although nucleic acid-based detections systems are generally rapid and sensitive, it is important to remember that the presence of a resistance gene does not necessarily equate to treatment failure, because resistance is also dependent on the mode and level of expression of these genes.
Microbiology
