General Principles of Antimicrobial Therapy: Dr. G. Tupas Flashcards
1. The following drugs inhibit the synthesis of bacterial cell wall, except: A. Penicillin B. Aminoglycoside C. Cephalosporin D. Carbapenems
B. Aminoglycoside
2. The following agents bind to the 30S ribosomal subunit and alter protein synthesis, except: A. Gentamycin B. Amikacin C. Tobramycin D. Rifampin
D. Rifampin
- Which of the following statements about antibacterial agents is true?
A. Oral administration of the drug is recommended for moderate to severe type of infection.
B. For bactericidal drugs to be effective, the immune system must be normal and active.
C. Combination drugs is recommended for the treatment of polymicrobial infections.
D. All of the above
C. Combination drugs is recommended for the treatment of polymicrobial infections.
- The presence of pus in abscesses can reduce the antimicrobial activity of an antibiotic due to the following reasons, EXCEPT:
A. Proteins contained in pus can bind to drugs decreasing their activity.
B. Pus increases the pH of infected tissues which can reduce antimicrobial activity.
C. Reduced vascular supply in abscesses impairs penetration of antimicrobial agents.
D. None of the above
B. Pus increases the pH of infected tissues which can reduce antimicrobial activity.
5. The giving of a specific antibiotic to a patient on the basis of the results of culture and sensitivity testing is an example of: A. Empiric treatment B. Definitive treatment C. Prophylactic treatment D. Combination treatment
B. Definitive treatment
6. The following bacteria can produce B-lactamase enzyme which make them resistant to penicillin and cephalosporins, EXCEPT: A. Streptococci B. Staphylococci C. Enterobacteriaceae D. Pseudomonas
A. Streptococci
- The following are mechanisms to reduce antibiotic resistance, EXCEPT:
A. Cycle antibiotic usage
B. Improve hygiene among hospital personnels
C. Discover or develop new antibiotics
D. None of the above
D. None of the above
8. One advantage of drug combination is: A. Synergism B. Indifference C. Antagonism D. Toxicity
A. Synergism
- One of the following is an example of a situation where prophylactic treatment is indicated:
A. A patient with valvular implant is undergoing a dental procedure.
B. A patient undergoing an organ transplantation
C. A patient receiving cancer chemotherapy
D. All of the above
D. All of the above
- Misuse of antibiotics is evident in the following situations, except:
A. Giving excessive or sub-therapeutic dose of the drug.
B. Giving prophylactic drug to a patient with AIDS with CD4 count below 200
C. Giving of antibiotic to a patient with mumps infection.
D. Relying on antibiotics alone in treating significant abscesses.
C. Giving of antibiotic to a patient with mumps infection.
or
B. Giving prophylactic drug to a patient with AIDS with CD4 count below 200
Antimicrobial drugs are effective in the treatment of infections
selective toxicity
Selection of Antimicrobial Agents
The organism’s identity Its susceptibility to a particular agent The site of the infection Patient factors The safety of the agent The cost of the therapy
central to selection of the proper drug.
Characterization
rapid assessment of the nature of the pathogen
Gram stain
Empiric therapy prior to identification of the organism
The acutely ill patient with infections of unknown origin
Selection of a Drug
Which arrest the growth
& replication of bacteria at serum levels
achievable in the patient.
Bacteriostatic drugs:
Which kills bacteria at serum levels achievable in patients
Bactericidal agents:
lowest concentration of antibiotics that inhibits bacterial growth
Minimum inhibitory concentration: (MIC)
To provide effective antimicrobial therapy, the clinically obtainable antibiotic concentration in body fluid should be greater than the MIC.
lowest concentration of antimicrobial agent that results in a 99.9 percent decline in colony count after overnight broth dilution incubations.
Minimum Bactericidal concentration: (MBC)
formed by the single layer of tail-like endothelial cells fused by tight junctions that impede entry from the blood to the brain of virtually all molecules, except those that are small and lipophilic.
Blood Brain Barrier
> Presence of pus – decreases the penetration of antibiotic – needs to be drained; makes the area acidic – bacteria cannot form capsules in acidic medium
> Valves – constantly moving so bacteria have difficulty attaching and colonizing – once present, also difficult to treat
> Scrotum also a protected site;
> CNS – persistent viral infections SSPE, herpes zoster
> Presence of foreign body – has to be removed
have significant penetration into the CNS.
quinolones and metronidazole
limited penetration through the intact blood brain barrier under normal circumstances.
β-lactam antibiotics, such as penicillin
ionized at physiologic PH and have low solubility in lipids
an index of renal function for adjustment of drug regimens.
serum creatinine
poorly absorbed from gastrointestinal tract that adequate serum levels can not be obtained by oral administration.
Vancomycin
Aminoglycosides
Amphotericin
used for drugs that are poorly absorbed from the gastrointestinal tract and for the treatment of patients with serious infections.
Parenteral administration
Two important pharmacodynamic properties that have a significant influence on the frequency dosing are
Concentration vs. Time dependent killing
Post-antibiotic effect
persistent suppression of microbial growth that occurs after levels of antibiotic have fallen below the MIC.
Post-antibiotic effect
significant increase in the rate of bacterial killing as the concentration of antibiotic increases from 4- to 64-fold the MIC of the drug for the infecting organism.
aminoglycosides,
fluoroquinolones,
carbapenems
The clinical efficacy of antimicrobials that have a nonsignificant, dose-dependent killing effect is best predicted by
percentage of time that blood concentrations of a drug remain above the MIC.
percentage of time that blood concentrations of a drug remain above the MIC.
concentration-independent or time-dependent killing.
ensure blood levels greater than the MIC, 60 to 70 percent of the time
penicillins and cephalosporin
T/F
some severe infections are best treated by continuous infusion of these agents rather than by intermittent dosing.
true
What antibiotics do not exhibit the time dependent killing; that is, increasing the concentration of antibiotic to higher multiples of the MIC does not significantly increase the rate of kill.
b-lactams, glycopeptides, macrolides, clindamycin, and linezolid
Agents used in bacterial infections
Penicillins Cephalosporins Tetracycline Aminoglycosides Macrolides Fluoroquinolones
What spectrum: Isoniazid is active only against mycobacteria
Narrow-Spectrum antibiotics
What spectrum: Ampicillin acts against gram positive and some gram negative bacteria
Extended-Spectrum
What spectrum: Tetracycline and chloramphenicol affect a wide variety of microbial species
Broad-Spectrum Antibiotics
When infection is of unknown origin, it shows synergism
Beta lactams and aminoglycosides
Indications for the Clinical Use of Combinations of Antimicrobial Agents
(1) for empirical therapy of an infection in which the cause is unknown
(2) for treatment of polymicrobial infections
(3) to enhance antimicrobial activity (i.e., synergism) for a specific infection
(4) to prevent emergence of resistance
Mechanism of Drug Resistance
- Reduced entry of drug into pathogens
- Absence, mutation or loss of Porin channel - Drug efflux
- P glycoprotein pump - Drug destruction or inactivation
- . B lactamase production; aminoglycoside modifying enzyme - Reduced affinity of the drug to altered
target structure - Enhanced excision of incorporated drug
- .Ribosomal modification vs macrolides
Misuse/Overuse of Antibiotics
Empiric use (no known etiologic agent)
Increased use of broad spectrum agents
Prescription not taken correctly
Antibiotics sold without medical supervision
Prophylactic use before surgery
Antibiotics for viral infections
Spread of resistant microbes in hospitals due to lack of hygiene
Patients who do not complete course (TB, AIDS)
Antibiotics in animal feeds
The Ideal Drug
Selective toxicity against target pathogen but not against host Bactericidal vs. bacteriostatic Favorable pharmacokinetics Reach target site in body with effective concentration Spectrum of activity: Broad vs. narrow Lack of “side effects” Therapeutic index Effective to toxic dose ratio Little resistance development Adverse effect profile Cost
