Principles of Antimicrobial Therapy Flashcards
What is the simplest and most common way to identify a pathogen?
gram stain
Why does bacteria stain differently? Gram positive will stain what color? Gram negative will stain what color?
structural components of the cell wall
+ : purple
- : pink/red
Describe acid-fast staining.
mycobacterium class, presumptive results, requires confirmation with cultures
stains every cell, non-acid fast bacteria become de-stained, counter stain applied (non-acid fast become blue, acid-fast become pink/red)
Describe India ink staining.
KOH, identifies fungi, cannot identify organism involved (need body fluids)
Describe ELISA.
used to identify antigens + antibodies and proteins + glycoproteins
Describe latex agglutination.
identification of antibodies of blood groups, can be used to respond to patient’s refractory to treatment
Name some drug factors that narrow antimicrobial agent choice.
availability, dosage form, cost
Name some host factors that narrow antimicrobial agent choice.
allergies, organ function, infection site, concomitant disease/therapies
What type of information on susceptibility is gathered using Kirby-Bauer disk diffusion?
qualitative
diameter of disk determines if bacteria is susceptible to resistant to antibiotic
Describe the E-test (MIC).
helps determine concentration of drug needed, minimal concentration of antibiotic needed to inhibit growth
Describe serial dilution of antimicrobial drugs.
multiple test tubes each containing a higher concentration of antibiotic, determines minimal bactericidal concentration or minimal inhibitory concentration
Describe drug resistance.
adaptive response in which microbes begin to tolerate an amount of drug that would ordinarily by inhibitory or harmful, due to genetic versatility, more virulent, can be intrinsic or acquired
Define intrinsic drug resistance.
bacteria must be resistant to any antibiotic that they produce
Define acquired drug resistance.
The adaptive response by a microbe that was previously sensitive to a drug
List some mechanisms of bacterial resistance.
enzymes that degrade antibiotics, alteration of bacterial cell walls/membranes
How is antimicrobial therapy achieved without harming the host cell?
disrupting the cellular processes or structures of bacteria, fungi, protozoa or to inhibit the virus multiplication cycle
List some characteristics of the ideal drug.
maintain potency, compliments host defences, does not negatively affect the host’s health, reasonably priced/readily available, can be quickly delivered to site of infection, remains active in tissue and body fluids, and does not contribute to microbial resistance
Define antimicrobials.
all-inclusive term for any antimicrobial drug, regardless of its origin
Define prophylaxis.
use of a drug to prevent the potential for infection of a person at risk
Define chemotherapeutic drug.
any chemical used in the treatment, relief, or prophylaxis of a disease
Define antimicrobial chemotherapy.
use of chemotherapeutic drugs to control infection (will have effect on actual organism)
Define synergism.
coordinated/correlated action by 2 microbes that results in a heightened response or greater activity
Define microbial antagonism.
microbes compete for survival in a common environment by taking actions that inhibit or destroy another organism
Antimicrobials can be divided into 3 different groups, what are they?
natural antibiotics, synthetic drugs, and semi-synthetic drugs
Describe broad-spectrum range of activity.
greatest range of activity, exert effects on cellular components which are found in most pathogens
Describe medium-spectrum range of activity.
effective on a wider range of cell types
Describe narrow-spectrum range of activity.
effective on a small range of cell types, goal of antibiotic stewardship is to prescribe this type (lower antibiotic resistance)
List the 5 mechanisms of drug action.
inhibition of cell wall synthesis, breakdown of the cell membrane structure/function, inhibition of DNA and RNA structure/function, inhibition of protein synthesis, blocking key metabolic pathways
How do drugs affect cell wall synthesis?
interfere with enzymes (peptidases) that aid in the production of PG, makes the cell osmotically fragile and more susceptible to outside water/pressure
*cells unable to produce PG will not be affected
B lactams led to the development of what class of antibiotics?
broad
Chemical alterations of B-lactam ring led to development of new antibiotics, name them. (4)``
penicillins, cephalosporins, carbapenems, monobactams
Describe the B lactase and B lactase inhibitor combination. What type of infection is this useful for?
B lactase producing bacteria inhibit the activity of penicillins
B lactase inhibitors overcome this resistance
useful for polymicrobial infections
Natural penicillin is effective against what?
gram + bacteria and anaerobes
List some adverse effects of penicillin.
hypersensitivity, thrombocytopenia, GI disturbances, interstitial nephritis, CNS toxicities
List some adverse reactions so cephalosporins.
hypersensitivity, minor GI complaints. hypoprothrominemia flushing (nausea, thirst, palpitations, chest pain, vertigo, death)
List some clinical uses of carbapenems.
broad spec: gram - bacilli, most anaerobes, gram +, MSSA, strep
List clinical uses and adverse reaction for Monobactams (Aztreonam).
uses - gram - aerobic bacilli
rxn - rare rash, anaphylaxis
Describe the action of Vancomycin.
prevents formation of rigid cell wall by inhibiting PG
bactericidal against gram +, bacteriostatic against enterococci
List the clinical uses and adverse reactions of vancomycin.
uses - MRSA, C. diff, when treatment with other antibiotics has failed
rxn - red man syndrome, ototoxicity, nephrotoxicity
How do drugs effect cell membrane function?
damage membrane which disrupts metabolic functions or cell lysis, membrane loses selective permeability and death occurs by osmosis
What type of specificity do drugs that affect cell membrane function exhibit?
particular microbial groups based on differences in membrane composition
Do drugs that affect cell membrane function inhibit PG synthesis?
no, may affect human cell membranes
List the clinical uses and adverse reactions of Colistin (Colistmethate).
uses - systemic infections by gram - bacteria, nebulizer against multi drug-resistance P. aeruginosa and acinetobacter
rxn - reversible nephrotoxicity, dose-dependent neuromuscular blockade
surface active agent that causes disruptions in cell membranes
How do drugs affect nucleic acid synthesis?
block synthesis of structural nucleotides, 3 different stages: inhibition of replication, inhibition of helicases, or stopping transcription, can cause damage to host cell
Describe the clinical uses and adverse reactions of Quinolones (Fluoroquinolones).
uses - upper/lower respiratory infections, GI infections, skin infections
rxn - nausea, vomiting, diarrhea, prolonged Q-T interval
How do Quinolones act?
block nucleic acid synthesis by inhibiting an enzyme that bacteria use to coil DNA into a double helix for translation/replication, stops bacterial growth
Rifampin and Rifabutin are active against what type of microorganisms? How do these drugs act?
mycobacteria
inhibits RNA polymerase
List some adverse reactions of Rifampin and Rifabutin.
hepatotoxicity, fever, chills, nausea, vomiting, orange bodily fluids
Drugs that block protein synthesis DO or DO NOT have selective action against bacteria?
do
*can cause damage to eukaryotic mitochondria
How do drugs that block protein synthesis act?
blocks formation of bacterial ribosomes to block synthesis of bacterial proteins (critical enzymes involved in translation/multiplication)
Describe the mechanism of action of aminoglycosides.
bind irreversibly to bacterial ribosomes, inhibit RNA translation into proteins (production of non-functional proteins), destabilize cell wall, cell lysis
List some clinical uses and adverse reactions of aminoglycosides.
uses - nosocomial gram -
rxn - nephrotoxicity, ototoxicity, NM blockade (with rapid high dose, rare)
List the mechanism of action and the adverse reactions of Streptomycin Antimycobacterial.
MOA - block protein synthesis
rxn - nephro/ototoxicity
Describe the mechanism of action and adverse reactions of Isoniazid.
*used against TB
MOA - inhibits cell wall synthesis by blocking protein synthesis, bactericidal
rxn - hepato/neurotoxicity
List the clinical uses and mechanism of action of tetracyclines. (7)
gram + and gram -, Rickettsiae, Chlamydiae, Mycoplasmas, Spirochetes, Protozoa, Mycobacteria
MOA - prevents formation of polypeptide chain of the protein being synthesized, no function for cell
List some adverse reactions of tetracyclines.
nausea, vomiting, diarrhea, inhibit bone growth/Ca/Mg/Al/Fe absorption
List the clinical uses and adverse reactions of Tigecycline.
uses - complicated skin and intraabdominal infections
rxn - nausea, vomiting, diarrhea, abdominal pain
*mostly bacteriostatic, can be bactericidal
List the clinical uses and adverse reactions of chloramphenicol.
uses - gastroenteritis/sepsis, salmonella, rickettsial diseases
rxn - bone marrow suppression, optic neuritis
Describe the MOA of chloramphenicol.
Prevents binding of new AA to polypeptide chain that results from transcription/translation phase
List the clinical uses and adverse reactions/precautions of macrolides.
uses - atypical/community-acquired pneumonia
rxn - GI complaints, can increase concentration of other drugs (theophylline, warfarin, triazolam)
*bacteriostatic
Describe the competitive inhibition that occurs with drugs that affect metabolic pathways.
act like false substrates to disrupt the central pathways in susceptible microbes, increased concentrations of the drug ensure that the enzyme needed in a metabolic pathway is constantly occupied by the metabolic analog rather than the true substrate, cellular metabolism is slowed/stopped
Describe the mechanism of action and clinical use of TMP-SMX.
MOA - blocks enzymes needed for bacteria to produce folic acid
uses - PCP prophylaxis, acute bronchitis, otitis media, shigellosis, good activity against MRSA
List some adverse reactions of TMP-SMX.
nausea, vomiting, diarrhea, hypersensitivity, neutropenia, thrombocytopenia, hemolytic anemia, jaundice, hepatic necrosis, drug-induced lupus (autoimmune)
Oseltamivir and Zanamavir fall under what category?
neuraminidase inhibitors
List the clinical uses and adverse reactions/precautions of Oseltamivir and Zanamavir.
uses - influenza A/B
rxn - nausea and vomiting for first 2 days
Ribavirin: AKA? variable results in treatment of what? how to deliver aerosolized dosage? side effects?
virazole, severe RSV, SPAG, teratogenic effect
Why are antifungals a difficult therapy?
may harm human cells, airborne/GI/skin entry
Describe the clinical uses and adverse reactions of Polyenes (amphotericin B and nystatin)
uses - aspergillosis, blastomycosis, histoplasmosis, coccidioidomycosis, and cryptococcosis
rxn - flushing, fever, chills, renal impairment