Antibiotics Flashcards
what is an infection
invasion of the body by various microorganisms: bacteria, fungus, protozoans, viruses, and worms- and the associated reaction of the body to them
how are bacterial infections treated
with antibiotics after appropriate diagnosis
pathogen identification requires
culturing and other laboratory work…time and money
what is empiric therapy
practical and necessary with life threatening cases but also has significant potential problems
drug resistance due to
USE and exacerbated by misuse of antibiotics
clinical diagnosis include
- symptoms of infection
- physical exam
- patient history
clinical lab test include
microbiological diagnosis
- gram stain analysis
- identify the unique peptidoglycan cell wall of bacteria
- differentiates bacteria as: gram +, gram -(+) or gram -, gram-(-)
- antibody screening, others: x-ray
what type of wall does gram-(+) bacteria have
- many layers peptidoglycan (90% of wall)
- a polymer composed of polymerized sugar (polysaccharide) and peptide chains connected by amino acid bridges
what type of wall does gram-(-) bacteria have
- much thinner peptidoglycan layer (only 20% of the wall); associated with an OM periplasmic space, and lipopolysaccharide layer
- cell wall is not regulatory structure like cell membrane; it is not selectively permeable
what are bactericidal antibiotics
destructive to bacteria, concentration-dependent killing or time-dependent killing
what are bacteriostatic antibiotics
inhibit the growth or multiplication of bacteria, let the immune system eradicate them
what is pharmacokinetics
absorption, distribution, and drug elimination
when selecting antibiotics what should you consider
- adverse effects
- drug interaction
- resistance
- post antibiotic effects
- contraindications: not given during pregnancy, to children, elders, or others (liver, kidney, allergy)
- multiple antibiotic therapy:polymicrobial infections, etc
- cost of therapy
what bacteria pathogens are susceptible
gram-(+) and gram -(-); cocci, bacilli, clostridium, mycobacterium, bacteroides
what Chlamydia pathogens are susceptible
gram-(-), spherical microorganisms
what Spirochete pathogens are susceptible
gram-(-), flexible, sprial-shaped
what mycoplasma pathogens are susceptible
smallest free-living microorganisms
how do bacteria become resistant to antibiotics
- antibiotic fails to reach its target
- antibiotic is inactivated
- target is altered
how do antibiotics fails to reach its target
some bacteria have impermeable membrane for the drug (lack of transport system or reduced porins)
how are antibiotic is inactive
bacteria produce enzyme destruction (eg. B-lactamases destroy the B-lactam ring of penicillins), or metabolism of the drug
how is the target altered
due to down-reguation of porin, and drug mutation of transpeptidase, reduced drug access elimination by energy-depdendent efflux, etc
efflux pumping causes
- resistance to antibiotics by mutation may be transmitted via plasmids or chromosomal DNA
- alternative pathways…other mechanisms
what are the die hard bacteria
Methicillin-resistant staphylococcus aureus Pseudomonas Aeruginosa Vancomycin-resistant enterococci Clostridium Enterobacteriacea
Methicillin-resistant staphylococcus aureus (MRSA) “golden staph” is the major cause of
nosocomial infection
-cause illnesses from minor skin infections to life-threatening pneumonia, meningitis, endocarditis, and septicaemia
what type of bacteria is Pseudomonas aeruginosa
gram-(-), aerobic
pseudomonas aerguinosa is a major cause of
hospital infections
-prevalent among patients with burn wounds, acute leukemia, IV drug additions
what type of bacteria is Vancomycin-Resistant Enterococci
gram-(-) anaerobic
what type of bacteria is Clostridium
gram- (+), anaerobic, produces destructive exotoxins
what type of baxter is enterobacteriaceae
gram-(-), anaerobic, can cause fatal abscesses and bacteremias
what are the bacteria cell wall synthesis inhibitors
- penicillins “-cillin”
- cephalosporins “cef~1-4th gen”
- carbapenems and monobactam
- others: vancomycin, bacitracin, fosfomycin & cycloserine
mechanism of bacteria cell wall synthesis inhibitors
mechanism of protein synthesis in micoorganisms are not identical to those of mammalian cells
- bacteria have 70s ribosomes, whereas mammalian cells have 80s ribosomes
- differences exist in ribosome subunits and in the chemical composition and functional specificities of component nucleic acids and proteins
- such difference form the basis for the selective toxicity of these drugs against microorganisms
what are the B-lactam antibiotics
penicillins:
- penicillin G
- penicillin V
- Oxacillin
- Dicloxacillin
- Ampicillin
- Amoxicillin
- Ticarcillin
- Mezlocillin
what is the structure of penicillin
- penicillins contain a thiazolidine ring (a) and a B-lactam ring (b)
- A side-chain of penicillin (R) can be added to 6-aminopenicillanic acid with action of amidase to form a different penicillin
what is penicillin G
- the only natural penicillin
- used in the form of benzathine, procaine, potassium & sodium salts
what is penicillin V
semi-synthetic
what are the narrow spectrum penicillins
- oxacillin
- dicloxacillin
what are the broad-spectum pencillins
- ampicillin (amino pencillins)
- amoxicillin (amino penicillin)
- ticarcillin (carboxy penicillins)
- mezlocillin (acylureido penicillins)
define bactericidial
kill bacteria
define bacteriostatic
inhibit microbial growth
define beta-lactam antibiotics
drugs with structures containing a beta-lactam ring
what is MIC
lowest concentration of antimicrobial drug capable of inhibiting growth of an organism
what is penicillin-binding proteins (PBPS)
bacterial cytoplasmatic membrane proteins that act as the initial receptors for penicillins and other beta-lactam antibiotics
what is peptidoglycan
chains of polysaccharides and peptides polypeptides that are cross-linked to form the bacteria cell wall
what is selective toxicity
more toxicity to the invader than to the host
what is transpeptidases
bacterial enzymes involved in the cross-linking of linear peptidoglycan chains, the final step in cell wall synthesis
penicillins and cephalosporins are the major antibiotics that inhibit
- bacterial cell wall synthesis
- inhibit the synthesis of peptidoglycan (PG) by inhibiting transpeptidase (transpeptidation)
what are the antimicrobials are narrow spectrum
-natural penicillin (G)
-semisynthetic penicillin V
-anti-staphylococcal pencillins:
Isoazolyl penicillins:
Oxacillin
Dicloxacillin
what are the antimicrobials that are broad spectrum
amino penicillins (ampicillin, amoxicillin) Carboxy penicillins (ticarcillin) Acyleureido penicillins (mezlocillin)
- bactericidal (if bacteria are growing and dividing)
- effective for gram-(+), some gram-(-) and anaerobes
what are the clinical uses of antimicrobials
- septicicemia
- meningitis
- hospital-acquired (bacterial) penumonia
- cellulitis
- bone and joint infections
- acute/chronic urinary tract infections
how does resistance to antimicrobials occur
- inactivation by bacterial B-lactamases
- mutant transpeptidases
- down-regulation of porins
- efflux pump
inactivation by bacterial B-lactmase is most common in what bacteria
Staphylococcus aureus
Pseudomonas aeruginosa
E.coli
enterobacters
what is mutant transpeptidases
alterations in the drug targeted Penicillin binding proteins, reduce the affinity for drug binding in staphylococci, pneumococci and enterococci
effects of down-regulation of porins
impairs drug penetration via porins in gram-(-) bacteria
pharmacokinetics of antimicrobials
poor oral absorption, except:
Penicillin V - Isoxazolyl penicillins (oxacillin, dicloxacilllin), Amino penicillins (ampicillin, amoxicillin)
-variable distribution throughout the body, do not enter the CNS unless there is inflammation
-not metabolized and generally excreted by the kidney
what are the adverse rxns of antimicrobials
- hypersensitivity/allergic rxns (1-5%) may cause anaphylactic shock
- GI distress: nausea, vomiting with oral high doses (not to be mistaken as allergic run)
- Seizures (with high doses)
- Hypokalemia (with high doses)
- superinfections: chronic use may lead to a new/secondary infection, occuring in a patient having a pre-exisitng infection
what are the drug interactions with penicillin
-very few; in vitro mixing with aminoglycosides reduces the activity of both
what is probenecid
an uricosuric agent which increases excretion of uric acid in hyperuricemia, decreases excretion of penicillins
describe the structure of B-lactamase inhibitors
- they have a B-lactam ring (like penicillins & cephalosporins) but lack antimicrobial activity
- bind irreversible to and inhibit bacterial B-lactmases
- neither bactericidal nor bacteriostatic (not antibiotics)
see slide 31
see slide 31
what is septicemia
commubity and hospital-acquired pneumonia, cellulitis, sinusitis, bone and joint infection
how is clavulanate absorbed
after oral administration
how is sulbactum & tazobactum administered
IV due to poor oral administration
piperacillin increases the half life of
tazobactum
describe the structure of cephalosporins
- have a B-lactam ring
- different structures (extra carbon) makes them more resistant to B-lactamases than penicillins
- group R1 and R2 can be substituted to produce a variety of cephalosporins
see slide 34: generations of cephalosporins
see slide 34: generations of cephalosporins
MAO of cephalosporins
-inhibit cell wall synthesis by inhibiting transpeptidase, this blocking cross-link of peptidoglycan
see charts
see charts
