Antibiotics Flashcards
natural penicillins
penicillin G
penicillin V
anti-staph penicillins
oxacillin
dicloxacillin
nafcilin
aminopenicillins
ampicillin
amoxicillin
anti-pseudomonal penicillins
tricarcillin
piperacillin
1st gen cephalosporins
cefazolin
cephalexin
2nd gen cephalosporins
cefoxitin
cefuroximne
3rd gen cephalosporins
ceftriaxone
ceftazimine
4th gen cephalosporin
cefepime
carbapenems
imipenem/cilastatin
meropenem
ertapenem
b-lactamase inhibitors
ampicillin-subactam
amoxicillin-clavulanic acid
piperacillin-taxobactam
glycopeptides
vancomycin
fluroquinolones
ciprofloaxin
levofloxacin
moxifloxacin
aminoglycosides
amikacin
tobramycin
gentamicin
tetracyclines and glyclcyclines
minocycline
doxycycline
tigecycline
macrolides and ketolides
clarithomycin
axithromycin
telithromycin
lincosamides
clindamycin
streptogramins
quinipristin/dalfopristin
oxazolidinoes
linezolid
polymyxins
colistin
polymyxin B
lipopeptides
daptomycin
sulfonamides and trimethoprim
sulfamethozazole/trimiethoprim
urinary tract antiseptics
methenamine
nitrofurantoin
MIC
minimum inhibitory concentration
lowest concentration of drug required to inhibit growth
determined by CLSI
tests to determine MIC
dilution
disk diffusion
optical diffusion
bacteriostatic
arrests growth and replication of bacteria
bactericidal
kills bacterial
targets of antimicrobials
cell wall synthesis cell membrane synthesis synthesis of 30S and 50S ribosome subunits nucleic acid metabolism fnx of topoisomerases folate synthesis
resistance mechansims
- reduced entry of antibiotic into pathogen
- enhanced export of antibiotic by efflux pumps
- release of microbial enzymes which destroy antibiotic
- alteration of microbial proteins that transform pro-drugs to effective drugs
- alteration of target proteins
- development of alternative pathways to those inhibited by antibiotics
classification based on
class and spectrum of microorganism it kills biochemical pathway it interferes with chemical structure
inhibitors of cell wall synthesis
penicillins cephalosporins carbapenems monobactams glycopeptides
B-lactams MOA
structural analogs of D-Ala-D-Ala
covalently bind penicillin-binding proteins inhibitin the last transpeptidation step in cell wall synthesis
B-lactam resistance
structural differences in PBPs
decreased PBP affinity for B-lactams
inability for drug to reach site of action
active efflux pumps
drug destruction and inactivation by B-lactamases
Natural penicillins spectrum
highly effective against gram + cocci, but easily hydrolyzed by penicillinase
natural penicillins therapeutic use
narrow spectrum
strep pneumoniae pneumonia and menigitis
penicillin V uses
strep pyogens, strep viridans (endocarditis), syphilis
anti-staphylococcal penicillins spectrum
penicllinase resistant thus agents of choice for staph aureus and staph epidermis that are not methicillin resistant
anti-staphylococcal penicillins uses
restricted to infections w/known staph sensitivity
aminopenicillins spectrum
extended-spectrum
frequently administered w/b-lactamase inhibitor
gram + and -
aminopenicillin uses
URI (S. pyogenes, S. pneumonia, H. influenza)
sinusitis
otitis media
enterococcal infections
anti-pseudomonal penicillins spectrum
extends sepctrum to pseudomonas aeruginosa
enterobacter
proteus
anti-pseudomonal penicillins uses
serious gram - infections hospital acquired pneumonia immunocompromised bacteremia burn infections UTIs
penicillin adverse effects
allergic rxns anaphylaxis interstitial nephritis (rare) nausea, vomiting, mild-severe diarrhea pseusomembranous colitis
first generation cephalosproins spectrum
good gram + coverage
modest gram - (moraxella, E. coli, klebsiella pneumoniae, P. mirabilis)
first generation cephalosporins uses
skin and soft tissue infections
surgical prophylaxis
second generation cephalosporins spectrum
somewhat increased activity against gram -, but less active then 3rd generation
subset active against bacteroides fragilis
second generation cephalosporins uses
gram neg mixed anaerobic
intra-abdominal infections
PID
diabetic foot infections
third generation cephalosporins
less active against gram +
more against enterobacteriaceae
resistance increasing
third generation uses
DOC for serious gram - infections (klebsiella, enterobacter, proteus, providencia, serratia, Haemophilus)
DOC for gonorrhea and sever Lyme, meningits
fourth generation cephalosporin spectrum
extends beyond 3rd gen psuedomnas
fourth generation uses
empirical Tx of nosocomial infections
cephlosporins adverse effects
1% cross-reactivity to penicllins
diarrhea
intolerance to alcohol
carbapenems sepctrum
aerobic and anaerobic gram + enterobacteriaceae pesugomonas acinetobacter
resistant to carbapenems
stenotrophomonas maltophilia
carbapenem uses
UTI LRTIs intra-abdominal gynocological SSTI bone joint
carbapenem adverse effects
nausea/vomiting
seizures
hypersensativity
monobactam spectrum
gram - enterobacteria pseudomonas H. influenza gonococci not against gram + or anaerobes
monobactam uses
allergic to B-lactams
B-lactamases class A
entended spectrum
most worrisome KPC carbapenemase rapidly emerging in enterobacteriaceae
B-lactamases class B
Zn dependent enzymess destroys all B-lactams except aztreonam
B-lactamases class C
active against cephalosporins
B-lactamases calss D
cloxacillin degrading enzymes
B-lactamase inhibitors MOA
prevent destruction of B-lactam antibiotics, most active against plasmid encoded bB-lacamases, but inactive against chromosmal B-lactamase induced gram-
glycopeptides MOA
inhibits cell wall synthesis binding w/high affinity to D-ala-D-ala target to D-alaynl-D-lactate or D-ananyl-D-serine which binds glycopeptides poorly
glycopeptides spectrum
broad gram +
S. aureus, S. epidermidis, strep, bacillus, corynebacterium, actinomuces, clostrdium
glycopeptides resistance
gram -
mycobacterium
glycopeptides uses
osteomyelitis endocardits MRSA strep enterococci CNS infections bacteremia orally for clostridium difficle
glycopeptides adverse effects
macular skin rash, chills, fever, rash red-man syndrome (histamine release) extreme flushing tachycardia hypotension ototoxicity neprhotoxicity
fluroquinolones MOA
concentration dependent
targets bacterial DNA gyrase, topoisomerase IV
prevents relaxation of supercoils
fluroquinolones resistance
mutation in genes encoding DNA gyrase or topisomerase IV
active transport out of cell
fluroquinolones spectrum
E. coli salmonella shigella enterobacter campylobacter neisseria pseudomonas S. aureus limited coverage of strep
fluroquinolones uses
UTI prostatitis STI travelers diarrhea shigelllosis bone and joint infections diabetic foot infection
fluroquinolones adverse effects
GI CNS rash, photosensitive, Achilles tendon rupture CI in kids
30s inhibitors
aminoglycosides
tetracyclines
50s inhibitors
macrolides
chloramphenicol
clindamycin
aminoglycosides MOA
concentration dependent
binds 30S
disrupts protein synthesis
exhibit post antibiotic effect
aminoglycoside resistance
AG metabolizing enzymes
impaired transport of drug into cell
altered ribosome
aminoglycosides spectrum
aerobic gram - bacteria
limited against gram + synergistic bactericidal effects in gram + w/cell wall active agent
Aminoglycoside uses
UTI (not uncomplicated) used if resistant to other agents seriously ill pneumonia (Strep and anaerobes) HAP peritonitis synergy in bacterial endocarditis tobramycin inhalation in CF
aminoglycosides adverse effects
ototoxicity
nephrotoxicity
neuromuscular block and apnea
tetracyclines/glycylcyclines MOA
bacteriostatic
inhibits bacterial protein synthesis by binding 30s
prevents access of aminoacyl tRNA to acceptor site on mRNA
tetracyclines/glyclycyclines resistance
decreased influx acquisition of energy dependent efflux ribosomal protection proteins enzymatic inactivation all stains of pseudomonas
tetracyclin/glycylcyclines spectrum
wide range of aerobic and anerobic gram + and gram - rickettsia coxiella burnetii mycoplasma pneumoniae chlamydia legionella atypical mycobacterium plasmodium borrelia burgdorferi treponema pallidum
tigecycline
no proteus and providencia
tetracyclin/glycylcyclines uses
CAP atypical CAP community acquired MRSA ance rickettsial infections Q fever anthrax
tetracyclin/glycylcyclines adverse effects
GI superinfections of C. difficile photosensitivity teeth discoloration thrombophlebits
macrolides/ketolides MOA
bacteriostatic
binds reversibly to 50s
inhibits translocation
macrolides/ketolides resistance
drug efflux
ribosomal protection proteins
hydrolysis
ribosomal mutations
macrolides/ketolides uses
respiratory infections alternative of otitis media sinusitis bronchitis SSTIs pertussis gastroentertis H. pylori mycobacterium
macrolides/ketolides drug interactions
CYP3A4 inhibition
prolongs effects of digoxin, warfarin
lincosamides MOA
binds 50s
lincosamides resistance
ribosomal methylation
all aerobic gram - bacillli
lincosamides spectrum
penumococci S. pyogens, viridans Streptococci MSSA anerobes (B. fragilis)
lincosamides uses
SSTIs necrotizing SSTIs lung abscesses anaerobic lung and pleural space infections topically for acne vulgaris
lincosamides adverse effects
diarrhea pseudomembranous colitis skin rashes reversible increase in aminotransferase activity potentiate neuromuscular blockade
Streptogramins MOA
bactericidal, protein synthesis inhibitors, bind 50s
streptogramins resistance
ribosomal methylase, acetyltransferase inactivation of dalfopristin
streptogramins spectrum
gram + cocci s. peumoniae beta and alpha hemolytic strep E. faecium coagulase + and - staph atypical organisms (m. pneumoniae, legionella c. pneumoniae)
streptogramins uses
vancomycin resistant E. faecium
complicated SSTI by MSSA or S. pyogenes
streptogramins adverse effects
infusion related pain and phelbitis
arthralgia and myalgia
streptogramins drug interactions
CYP3A4 inhibition anticovulsants macrolides some FQs antidepressents
oxazolidinones MOA
inhibits protein synthesis
50s
oxazolidinones resistance
ribosomal mutation
oxazolidinones spectrum
gram + staph, strep, enterococci, anaerobic, gram + rods
oxazolidinones uses
VRE faecium
nosocomial penumonia due to MSSA and MRSA
CAP
complicated and uncomplicated SSTI
oxazolidinones adverse effects
myelosupression
headache
rash
oxazolidinones drug interactions
weak nonspecific inhibitor of monoamine oxidase
inhibitors of cell membrane fnx
polymyxins
lipopeptides
polymyxins MOA
interacts w/phospholipids
disrupts structure of cell membranes
changes permeability
polymyxins spectrum
restricted to gram -
enterobacter, E. coli, klebsiella, salmonella, pasteurella, bordetella, shigella, P. aeruginosa, acinetobacter
polymyxin resistance
proteus
serratia
polymyxin uses
topical, skin, mucous membranes, eye, ear, urinary bladder irrigation, ihalation
polymyxin adverse effects
nephrotoxicity
mm weakness and apnea
lipopeptides MOA
binds bacterial membranes -> depolarization, loss of membrane potential -> cell death
lipopeptides resistance
may be due to changes in cell membrane charge
lipopeptides spectrum
bacteriacideal
concentration dependent
active against aerobic faculagie and anaerobic gram +
lipopeptides uses
complicated SSTIs
complicated bacteremia
right sided endocarditis
lipopeptides adverse effects
msk damage
elevations in creatine kinase
rare rhabdomyolysis
metronidazole MOA
prodrug, requires reductive activation of nitro grps by susceptible organisms
highly reactive nitro radical anions kill organsims by targeting DNA
metronidazole resistance
decreased formation of nitro radicals
metronidazole spectrum
anaerobic cocci anaerobic gram - bacilli anaerobic spore forming gram + bacilli trichomoniasis amebiasis giardiasis helicobacter campylobacter
metronidazole uses
bacterial vaginosis amebic liver abscess anaerobic bacterial infections bones, joints, CNS C. difficile Chron's disease
metronidazone adverse effects
HA, dry mouth, metallic taste
vomiting, diarrhea, abdominal distress
disulfiram effect
metronidazone drug interactions
induced meta of phenobarbital, prednisone, rifampin, warfarin
sulfonamides MOA
bacteriostatic, competitive inhibitors of dihyropteroate synthase
prevents bacterial use of PABA for synthesis of folic acid
trimethoprim MOA
inhibition of microbial dihydrofolate reductase
sulfonamide and trimethoprim resistance
lower enzyme affinity
decrease permeability or active efflux
alternative pathway or increased production of folic acid
sulfonamide and trimethoprim uses
UTI bacterial prostatitis bronchitis shigellosis travelers diarrhea salmonella pneumocystis jiroveci nocardia stenotrphomonas maltophilia DO NOT use in strep pharyngitis
sulfonamide and trimethoprim adverse effects
allergic skin rashes nausea, vomiting CNS (HA and depression) photosensitivity renal dysfnx stevens-johnson syndrome
sulfonamide and trimethoprim drug interaactions
potentiated effects of warfarin
methenamine MOA
decomposes in water to formaldehyde
methenamine resistance
nome
methenamine spectrum
all bacterial
methenamine uses
not primary drug for actue UTI
methenamine adverse effects
GI
painful and frequent micturition
albuminuria, hematuria
rashes, low systemic toxicity at usual doses
nitrofurantoin MOA
highly reactive intermediates damage DNA
bacteria reduce drug more rapidly than mammalian cells
nitrofuantoin uses
UTI
not recommended for pyleonephritis or prostatitis
nitrofuantoin adverse effects
nausea, vomiting, diarrhea
course of therapy should not exceed 14 days
nitrofuantoin contraindications
pregnant women
impaired renal fnx
< 1month
