Antibiotics Flashcards
Mechanism of beta lactams
- Penicillins
- Cephalosporins
- penicillins bind penicillin binding proteins (PBPs)
- PBPs involved in synthesis of peptidoglycan binding –> cell wall synthesis inhibits –> lysis - inhibit cross linking of peptidoglycan chains –> weak cell wall
- facilitate damageby autolysins d/t weakened/absent cell wall - may up regulate
bacteriocidal
Penicillin coverage and toxicity
b-lactam
PCN G - IV form
PCN V - oral form
Gram + cocci: S. pneumo S. pyogenes Actinomyces Grp B strep - neonatally Spriochetes - syphilis
Gram + rods:
Clostridium
listeria
Bacillus
Gram - cocci:
Neisseris - if not penicillinase resistant
MC toxicity:
HSR
Hemolytic anemia
Thrombocytopenia
Resistance mechanisms to penicillin
Penicilinase - type b-lactamase
-produced in periplasm gram - organims
coded by plamids
alteration of b-lactam target - PBP
Penicilinase resistant penicillins
Bulky R group blocks penicillinase (b-lactamase) binding
Methicillin (lab use only)
Nafcillin
Oxacillin
Dicloxacillin
use: Staph aureus
MRSA - altered binding target site
Toxicity:
Methicillin - interstitial nephritis
Rest: HSR
Aminopenicillins
Ampicillin (IV)
Amoxicillin (PO)
Penicillinase (b-lactamase) sensitive Broader spectrum: "HEELPSS" H.flu Ecoli Enterococci Listeria Proteus mirabilis Salmonella Shigella
UTIs - kids
Neonatal infection s- ampicillin IV
Prophylaxis against Viridans strep endocarditis
SE:
HSR
Rash w/ mononucleosis caused pharyngitis
-full body rash
B-lactamase inhibitor
enhance spectrum of drug
used in combination:
Clavulanic acid + amoxicilin - resistant OM
Clavulanic acid + piperacillin
Sulbactam + ampicillin - IV, surgery
Tazobactam + piperacillin
Antipseudomonal abx
Ticarcillin
Carbenicillin
Piperacillin
Extended spectrum
Pseudomonas
gram - rods
susceptible to penicillinase
-add B-lactamase inhibitor
Cephalosporins general
B-lactam mechanism
Bactericidal
Less susceptible to penicillinases
LAME against: Listeria Atypicals - mycoplasma, chlamydia MRSA - except 5th gen Enterococci
Toxicity:
HSR - 5-10% cross reactivity to PCNs
Increased nephrotoxicity if used w/ aminoglycosides
Disulfam like rxn - rare
1st gen cephalosporins
Cefazolin
Cephalexin
Gram + cocci Gram - "PEcK" Proteus mirabilis Ecoli Klebsiella
UTIs - cephalexin for prophylaxis
URIs
Prophylaxis against viridan strep endocarditis
Cefazolin - post op surgical infection - MSSA
2nd gen cephalosporins
Cefoxitin
Cefaclor
Cefuroxime
Cefprozil
Gram + cocci w/ 1st gen Gram - "HENS PEcK" Hflu Enterobacter Neisseria sp. (not urethritis gonorrhea tx) Serratia marcescens
Proteus mirabilis
Ecoli
Klebsiella
3rd gen cephalosporins
Ceftriaxone (IV, IM)
Cefotaxime
Ceftazidine
Cefdinir
Serious Gram - infecitons, resistant to other b-lactams
“HENS PEcK” + Citrobacter
gram - meningitis
gram + S. pneumo only!
Ceftriaxone - longest t 1/2
- Neisseria gonorrhoeae - IM
- excreted in bile, good for renal failure pts
Ceftazidime - pseudomonas
Cefdinir - recurrent OM
4th gen cephalosporins
Cefepime
broad spectrum
-most gram + of 1st and 2nd gen
Gram -
Pseudomonas
5th gen cephalosporins
Ceftaroline
Broad spectrum MRSA No Pseudomonas coverage Community acq pneumonia complicated skin infections (MRSA)
Aztreonam
monocyclic B-lactam
inhibits cell wall synthesis - binds PBP3 “azTHREE-onam”
Synergicstic w/ aminoglycosides - gentamicin
no cross allergenisity w/ PCN
“Aminoglycoside pretender”
Gram - “PEcKS”
no gram + or anaerobe coverage
Can use in PCN allergy, renal insufficiency (no renal involvement)
non toxic
Carbapenems
Imipenem - cilastatin (inhibitor of renal dehydropeptidase 1 –> decreased inactivation)
Meropenem
Ertapenem
Doripenem
Broad spectrum: Gram + cocci gram - rods anaerobes Pseudomonas
B-lactamase resistant
binding PBPs
Empiric tx of life threatening infections - sick!
does NOT cover MRSA
meropenem - decrease risk of seizures, not inactivated in renal tubules
Toxicity:
GI distress
skin rash
some CNS toxicity - imipenem
Vancomycin
inhibit cell wall synthesis
inhibit cell wall mucopeptide formation by binding D-ala-D-ala moieties of cell wall precursors
inhibit cell wall glycopeptide polymerization
Bactericidal
Gram +
poor oral availability - IV for systemic
Use: MRSA Enterococci VRE C. diff - oral - stays in GI Coag - staph epidermidis endocarditis (R-side)
Toxicity: “NOT”
Nephrotoxicity
Ototoxicity
Thrombophlebitis
Vancomycin resistance mechanism
D-ala-D-ala to D-ala-D-lac
Red man syndrome
Vancomycin associated
diffuse flusing of whole body non specific mast cell degranulation avoid w/: -antihistamine pretreatment -slow down infusion -can restart
30 S and 50 S inhibitors
“buy AT 30, CCELL at 50”
30S:
Aminoglycosides
Tetracyclines
50S: Chloramphenicol Clindamycin Erythromycin (macrolides) Lincomycin Linezolid
Aminoglycosides
"GNATS" Gentamicin Neomycin Amikacin Tobramycin Streptomycin
MO: bind 30S
bactericidal
inhibits formation of initiation complex –> misreading mRNA
ineffective against anaerobes - needs O2 for uptake
“aminO2glycosides”
Use:
severe gr - rod infections
-work synergistically w/ b-lactam abx
neonatal infections: Ecoli pneumonia or sepsis
-ampicillin + gentamicin
Neomycin: bowel surgery and bowel infections
Toxicity: “NOT” (not same as Vanc)
Nephrotoxicity
Ototoxicity w/ loop diuretics
Teratogenicity
Chloramphenicol
inhibits 50s peptidyltransferase activity
bacteriostatic
harmful side effects:
anemia - dose dependent –> aplastic anemia
Gray baby sn
Uses:
meningitis - H. flu, N. meningitidis, S. pneumo
Gray baby syndrome
decreased UDPGT activity in neonates
–> build up toxic metabolites
about 9 days sx start V, ashen skin color poor muscle tone cyanosis CV collapse
Tx:
stop chloramphenicol
exchange transfusion
phenobarbital to induce UDP-GT
Linezolid
binds 23 S RNA portion of 50S
interacts w/ bacterial initiation complex
Use: MRSA, VRE
can cause serotonin syndrome w/ SSRI med use
Tetracyclines
Tetracycline
Doxycycline
Demeclocycline
Minocycline
Binds 30 S - inhibits attachment of aminoacyl t-RNA
bacteriostatic
less CNS penetration
Doxycycline fecally eliminated, good in renal failure pts
Avoid w/ milk or antacids - Iron, Ca2+, Mg2+
-divalent cations inhibit abx absorption
Toxicity: GI distress discolored teeth in kids inhibits bone growth in kids photosensitivity - bluish skin w/ minocylcine, chornic use w/ acne
Contraindication in pregnancy
Tetracycline clinical uses
“VACUUM THe BedRoom”
Vibrio cholerae Acne Chlamydia Ureaplasma Urealyticum Mycoplasma pneumoniae
Tularemia
H. pylori
Borrelia burgdorferi
Rickettsia
Macrolides
Erythromycin
Azithromycin
Clarithromycin
Inhibit protein synthesis by binding 23 S RNA of 50S –> blocking translocation
Resistance: methylation of 23S RNA binding site
Bacteriostatic
Toxicity: Prolonged QT interval GI discomfort rare acute cholestatic hepatitis (w/ erythromycin estolate) rare cause of eosinophilia
Drug interactions: increased serum concentration of theophylline; oral anticoag (e.g. warfarin)
Safe in pregnancy - erythromycin and azithromycin safest
Clinical uses of Macrolides
“PUS”
Pneumonia - atypical: mycoplasma, chlamydophila, legionella
URI - S. pneumo, H. flu
STD - Chlamydia, gonorrhea
Streptogramins
Quinupristin/Dalfopristin combo drug
synthesized by bactera Stretpomyces virginiae
binds 23 S portion of 50S ribosome
Uses:
MRSA
VRE
Staph and strep skin infections
SE: hepatotoxicity pseudomembranous colitis arthralgias myalgias
inhibits CYP450
Clindamycin
blocks peptide bond formation w/ 50S ribosomal subunit
bacteriostatic
Toxicity:
causes pseudomembranous colitis d/t C.diff overgrowth
Anaerobic infections
MRSA
protozoal infections
topically for acne
Bacterioides fragils
C. perfringens
MRSA skin abscess - oral
Sulfonamides
Sulfamethoxaole (SMX) MC
Sulfadiazine
Folic acid inhibitors - competitively inhibit dihydropteroate synthase
Gram + some
Gram - some
Nocardia
Chlamydia
UTIs
Skin infections
Resistance: alt enzyme, decrease uptake, increase PABA synthesis
Tox:
HSR - MC
hemolysis in G6PD
Nephrotoxicity - tubulointerstitial nephritis
Kernicteris in infants
Dispace other drugs from albumin - warfarin
Stevens Johnson sn
Photosensitivity (“SAT”)
Trimethoprim (TMX)
inhibits dyhydrofolate reductase
- -> megaloblastic anemia, leukopenia, granulocytopenia
- give folic acid supplement
TMP-SMX uses
UTIs Shigella Salmonella MRSA skin infections Prophyalxis for recurrent UTIs AIDS - prophylaxis against PCP (CD4 under 200)
Fluoroquinolones
Levofloxacin (3) Ciprofloxacin Norfloxacin Ofloxacin Moxifloxacin (4) Gatifloxacin
-quinolone: Nalidixic acid
Inhibits DNA gyrase (topoisomerase II)
don’t take w/ Ca2+ or Mg2+ supplements, inhibits absorption
resistance: change DNA gyrase
Use: Gram - infections Gram - rods UTIs GI infections Pseudomonas Vary gram + coverage (gen 2-4 better against S. pneumo)
Tox: GI upset Contra indicated in pregnancy Kids - damage to articular cartilage tendonitis/rupture in adults (CF pt long term tx) QT prolongation
Drugs to be avoided w/ sulfa allergy
“Sulfa Pills Frequently Cause Terrible Allergy Symptoms”
Sulfasalazine Probenecid Furosimide Celecoxib Thiazides/TMP-SMX Acetazolamide Sulfonylureas
Drugs causing Stevens Johnson Syndrome (SJS)
“Steve Jobs made APPLE PCS”
Allopurinol Phenytoin Phenobarbital Lamotrigene Ethrosuximide Penicillin Carbamazepine Sulfonamides
Nitrofurantoin
Bactericidal
reduced by bacterial proteins to reactive intermediate that inactivates bacterial ribosomes
use:
mild UTI cystitis - not pyelo- by E. coli or S. saprophyticus
(DOES NOT COVER PROTEUS)
SE:
rarely N
HA,
D
safe in pregnancy
Polymyxins B and E
Cationic detergens - attach to and disrupt bacterial cell membranes, inactivate endotoxin
IV: last resport for resistant gram - infections
Topical: used in may OTC abx ointments - OTC neosporin
Toxicity:
IV is NEUROTOXIC! and nephrotoxic (acute renal tubular necrosis)
metronidazole
forms toxic free radicals –> DNA damage
Use: “GET GAP on the Metro”
Giardia lamblia
Entamoeba histolytica
Trichomonas
Gardnerella vaginalis
Anaerobic bacteria (Clostridium spp., Bacteriodes fragilis)
Pylori
Cause disulfam like reaction - don’t drink
increased acetylaldehyde –> flushing, sweating, N, HA, hypotension
Prophylaxis coverage for meningococcal meningitis exposure
Ciprofloxacin
Rifampin
Ceftriaxone
Prophylaxis coverage for H. flu meningitis
rifampin
Prophylaxis coverage for gonorrhea - sexual assault
cetriaxone
Prophylaxis coverage for syphilis
PCN G
Prophylaxis coverage for recurrent UTIs
TMP-SMX
Nitrofurantoin
Amoxicillin
Cephaloxin
Prophylaxis coverage for Pneumocystis jirovecii CD4 under 200
1: TMP-SMX
aerosolized pentamide
Dapsone
Prophylaxis coverage for endocarditis
PCN
Amoxicillin
cephalexin
PCN allergy - Clindamycin, azythromicin
Prophylaxis coverage for Group B Strep
ampicillin intrapartum
Prophylaxis coverage for Gonorrococcal/chlamydial conjunctivitis
Erythromycin
Antimicrobials to avoid in pregnancy
Clarithromycin - embryotoxic
Sulfonamides - kernicterus close to delivery
Aminoglycosides - ototoxicity
Fluoroquinolones - cartilage damage
Metronidazole - metagenesis in 1st trimester (neural tube)
Tetracyclines - discolored teeth, inhibition of bone growth
Ribavirin - teratogenic
Griseofulvin - teratogenic
Chloramphenicol - gray baby sn
