Antibiotics Flashcards
antibiotics
molecules produced by microorganisms that kill other microorganisms or inhibit their growth; streptomyces, bacillus, penicillium, cephalosporium
selective toxicity
central concept of antimicrobial action; the growth of the infecting organism is selectively inhibited or the organism is killed without damage to the cells of the host
ideal agent
- low in toxicity to host’s cells
- should not induce hypersensitivity
- low dose
- host should not destroy or excrete the drug until it has functioned
- no resistance
penicillin
streptococcal pharyngitis, pneumococcal pneumonia, meningitis, endocarditis
bactericidal
kills, important for serious infection or when natural ability is impaired
bacteriostatic
inhibits bacterial growth, allowing host defenses to catch up
examples of bactericidals
beta-lactams, vancomycin, aminoglycosides, quinolones, anti-TB, anti-folates
examples of bacteriostatics
tetracyclines, macrolides, anti-folates, clindamycin, chloramphenicol
inhibition of cell wall synthesis
vancomycin, bacitracin, penicillins, cephalosporins, monobactams, carbapenems
inhibition of folic acid metabolism
trimethoprim, sulfonamides, dapsone
action on cell membrane
polymyxins, platensimycin
50S inhibitors (protein synthesis)
macrolides, chloramphenicol, clindamycin, oxazolidinones
30S inhibitors (protein synthesis)
tetracycline, spectinomycin, aminoglycosides
inhibition of DNA directed RNA polymerase
rifampin, fidaxomicin
inhibition of DNA synthesis
metronidazole
inhibition of gyrase/topoisomerase
quinolones
penicillin G and penicillin V
limited spectrum; beta-lactamase sensitive
ampicillin and amoxicillin
broad spectrum
methicillin
beta-lactamase resistant; acid labile; for gram pos
oxacillin
beta-lactamase resistant; acid stable; for gram pos
carbenicillin
extended spectrum; pseudomonas
When does penicillin inhibit peptidoglycan synthesis?
at transpeptidase step
are penicillins bactericidal or bacteriostatic?
cidal, require active growth
penicillin mechanism of resistance
beta lactamases or penicillin binding protein mutations
penicillin side effects
allergy (use macrolides instead), stevens johnson syndrome, diarrhea, colitis
cephalosporins
broader spectrum, more resistant to beta-lactamase, low cross reaction with penicillins
disadvantages of cephalosporins
less potent but more expensive; still around 40% of antibiotics prescribed
cefamycins
subset of second generation of cephalosporins and are more stable to beta-lactamases
beta-lactamase
enzyme in bacteria that can break structure of some beta-lactam antibiotics
cephalosporin mechanism of action
inhibits peptidoglycan biosynthesis at transpeptidation step
are cephalosporins cidal or static?
cidal, require active growth
cephalosporins not used for _
listeria, atypical/anaerobes (except cefoxitin), MRSA (except ceftaroline), or enterococci (LAME)
cephalosporin mechanism of resistance
PBP mutations
cephalosporin toxicity
OK for penicillin allergy; colitis
carbapenems/monobactam MofA
inhibit peptidoglycan biosynthesis at transpeptidation biosynthesis
Are carbapenems/monobactams cidal/static?
cidal, require active growth
carbapenems/monobactems spectrum
not usually first resort; pseudomonas
carbapenems/monobactems mechanism of resistance
beta-lactamase
carbapenems/monobactems side effects
allergy, colitis
bacitracin MofA
inhibits dephosphorylation of lipid intermediate in cell wall
vancomycin MofA
prevents precursor from being added to growing chain in cell wall
is vancomycin cidal/static?
cidal, requires active growth
vancomycin spectrum
gram(+) cocci including MRSA and enterococci; not gram (-)
vancomycin mechanism of resistance
change of D-ala-D-ala to D-ala-D-lactate or D-ala-D-ser
vancomycin side effects
GI, diarrhea, nausea, nephrotoxicity
polymyxins
target lipid A biosynthesis & phosphatidylethanolamine; cidal
polymyxin spectrum
gram(-) only; colistin, topical (neosporin)
polymyxins side effects
nephrotoxicity and neurotoxicity
polymyxins mechanism of resistance
mutations in lipid A biosynthesis
rifampin inhibits _
DNA to mRNA
quinolones/metronidazole inhibit _
DNA replication
bactericidal protein synthesis inhibitors are _
irreversible; aminoglycosides
aminoglycosides MofA
inhibit protein synthesis at 30S ribosomal subunit
aminoglycosides are static/cidal?
cidal
aminoglycosides spectrum
gram negative (pseudomonas) and some gram(+) in synergy with pen; anaerobes
aminoglycosides mechanism of resistance
acetylation, adenylation, phosphorylation
AG toxicity
ototoxicity, nephrotoxicity, not for pregnant women
chloramphenicol toxicity
limits clinical use by causing aplastic anemia (bone marrow suppression) or gray baby syndrome
chloramphenicol MofA
reversibly binds to 50S to inhibit protein synthesis by preventing peptide bond formation
chloramphenicol static/cidal?
static, broad spectrum
chloramphenicol primary uses
salvage therapy for meningitis, enterococcus, atypicals, conjunctivitis
tetracyclines MofA
inhibit protein synthesis at 30S
tetracyclines static/cidal?
static
tetracyclines spectrum
+/-, atypicals, excellent for intracellulars, anti-protozoal
penicillin DOC
syphilis, GASM GAB, Lyme disease, MSSAca
carbapenems DOC
febrile neutropenia
AG DOC
plague, tularemia
tetracycline DOC
chlamydia, rickettsia, lyme, brucella, Q fever, anthrax, malaria
tetracycline mechanism of resistance
efflux pump
tetracycline side effects
CI in pregnant women and <12; bones/teeth, hepatoxicity, phototoxicity
lincomycin MofA
interference with peptide bond formation at 50S; static
lincomycin is effective against _
anaerobes; bacteriodes fragilis, malaria
problems with lincomycin
may induce overgrowth of C. difficile and macrolide-clindamycin resistance
lincosamides (clindamycin) spectrum
gram(+) cocci; anaerobes, good tissue penetration for soft tissue infections; not for enterococci or aerobic gram (-)
lincosamides mechanism of resistance
methylation of 23S rRNA; usually confers cross-resistance to macrolides
macrolides MofA
inhibit protein synthesis at 50S at 23S rRNA
macrolides static/cidal?
static
macrolides spectrum
gram(+), alternative for pen allergy, atypicals
macrolides mechanism of resistance
23S methylation or subunit mutations
macrolides toxicity
GI issues, macrolide-induced clindamycin resistance
oxazolidinones
new class of agents synthesized from scratch
oxazolidinones MofA
inhibit protein synthesis at 50S (23S specifically)
oxazolidinones static/cidal?
static
oxazolidinones spectrum
gram(+) cocci including MRSA; not for gram negative due to efflux pumps
oxazolidinones mechanism of resistance
chromosomal mutation of 23S or L3/L4, 23S methylation, efflux pumps
oxazolidinones side effects
headache, insomnia, GI, yeast infections
rifamycins should not be used as _
monotherapy due to emergence of spontaneous resistance
rifamycins MofA
inhibit bacterial transcription at RNA polymerase step
rifamycins static/cidal?
cidal
rifamycins spectrum
used in conjunction with other drugs for TB and leprosy, prophylaxis for meningitis (NOT ACTIVE MENINGITIS)
rifamycin mechanism of resistance
chromosomal RNA polymerase beta subunit mutations
rifamycin side effects
GI, hepatotoxicity, decrease BC effectiveness
ciprofloxacin (fluoroquinolones)
mostly gram(-); pseudomonas and MSSA
levofloxacin (fluoroquinolone)
mostly gram(+); pneumococcus and pseudomonas
moxifloxacin (fluoroquinolones)
atypicals, anaerobes
quinolones static/cidal?
cidal
quinolones MofA
gyrase/topoisomerase inhibitor
quinolones spectrum
mostly gram(-) and some gram(+) [strep, steph], atypicals
quinolones mechanism of resistance
DNA gyrase chromosomal mutations or efflux pump
quinolones side effects
GI, dizziness, headache, CI in pregnancy, nerve damage, colitis
metronidazole MofA
inhibits DNA replication but requires activation by a nitroreductase in microaerophiles, anaerobes, protozoa (prodrug)
metronidazole static/cidal?
cidal
metronidazole spectrum
atypicals, microaerophiles, anaerobes, protozoa, C. diff
metronidazole DOC
many GI and diarrheal diseases - vaginosas, trich, amoeba, giardia (NOT for yeast infections)
metronidazole side effects
GI, dizziness, dry mouth and metallic taste; CI with alcohol
anti-folate examples
sulfonamides (no PABA –> DHA) and trimethoprim (no DHA –> THA)
anti-folates static/cidal?
static (1drug), cidal (2 drugs)
anti-folates spectrum
gram(+/-)
anti-folates mechanism of resistance
duplicate enzyme production that is resistant to drug
anti-folate side effects
allergies, stephens johnson syndrome