Antibiotics Flashcards
What organisms can you treat with aminopenicillins (amoxicillin, ampicillin)
HEELPS
gram positives Also, gram negative rods including HEELPSS h. influenzae h. pylori e. coli listeria monocytogenes proteus mirabilis salmonella shigella enterococci
Antipseudomonal penicillins
ticarcillin
carbenicillin
piperacillin
bacterial resistance against penicillin agents
production of beta- lactamase (hydrolyzes the beta- lactam ring)
alteration of beta lactamase targets
beta- lactamase inhibitors
sulbactam
clavulanic acid
tazobactam
clinical use of dicloxacillin, nafcillin, oxacillin
these are penicillinase- resistant penicillins. THey have a bulky R group that blocks access of beta- lactamase to beta- lactam rings.
Used for s. aureus (but only methicillin sensitive strains)
side effects of penicillin
hypersensitivity reactions, hemolytic anemia, thrombocytopenia
side effects of amoxicillin and ampicilin
hypersensitivity, rash, pseudomembranous colitis
ampicillin and amoxicillin- what are they?
extended- spectrum penicillins. Combine with clavulanic acid to protect against destruction by beta lactamase.
Amoxicillin is PO and has greater oral bioavailability than ampicillin, which is given by IV.
cephalosporins
like penicillins in that they inhibit cell wall synthesis and are therefore bactericidal
but they are less susceptible to penicillinases and have more gram + and gram - coverage.
organisms not covered by cephalosporins are LAME
listeria
atypicals (chlamydia, mycoplasma)
MRSA
Enterococci
Exception: ceftaroline covers MRSA
1st generation cephalosporins
cefazolin, cephalexin PEcK proteus mirabilis E. coli Klebsiella pneumoniae
cefazolin (ancef) used prior to surgery to prevent s. aureus wound infections
cephalexin commonly used for UTI
Can be used against URIs
Prophylaxis against viridans endocarditis
2nd generation cephalosporins
cefoxitin, cefaclor, cefuroxime, cefprozil
HENS PEcK
Haemophilis influenzae
Enterobacter aerogenes
Neisseria spp (gonorrhea resistance is growing so we generally don’t use cephalosporins to treat gonorrhea)
Serratia marcescens
Proteus mirabilis
E. coli
Klebsiella pneumoniae
3rd generation cephalosporins
ceftriazone, cefotaxime, ceftazidime, cedinir
coverate of serious gram neg infections that would be resistant to other beta lactams
E. coli Proteus mirabilis Klebsiella Enterobacter Serratia Citrobacter Neisseria Haemophilus influenzae
Strep pneumoniae!! still!
choice for gram negative meningitis
Ceftriaxone IV
3rd generation cephalosporin,
choice for neisseria gonorrhea, meningitis, disseminated Lyme
safety increased because it is excreted in the bile
3rd generation cephalosporin with pseudomonas coverage
Ceftazidime
3rd generation PO cephalosporin used for resistant otitis media
Cefdinir
Big gun 4th gen cephalosporin
Cefepime- 4th generation, gram negative organisms with increased activity against Pseudomonas and gram- positive organisms
5th generation cephalosporin that covers MRSA
ceftaroline
Broad gram positive and gram negative organism coverage including MRSA.
Does not cover Pseudomonas
Cephalosporins are LAME against
Listeria
Atypicals (mycoplasma, chlamydia)
MRSA (except ceftaroline)
Enteroccoci
for PNA (CAP), azythromycin can be added on for atypicals. Ceftriaxone and azythromycin are a common combination
Caphalosporin hypersensitivity reaction
5-10% cross- reactivity with PCNs
nephrotoxicity risk if used with aminoglycosides
example- gentamycin
disulfiram- like reaction seen with alcohol when combined with some cephalosporins
broad spectrum coverage for appendicitis
imipenem/cilastatin or meropenem
cell wall inhibitors effective against pseudomonas
cefepime
axtreonam
carbapenems
carboxypenicillins (eg ticarcillin)
resistance to vancomycin
D-ala D-ala is converted to
D-ala D-lac
Aztreonam
monocyclic beta lactam resistant to penicillinases, inhibits cell wall synthesis, binds to penicillin binding protein 3.
gram negative rods ONLY
for PCN- allergic patients and those with renal insufficiency
"aminoglycoside pretender" covers gram negative E. Coli Klebsiella Pseudomonas Serratia
Usually nontoxic (few side effects), no cross- sensitivity to PCNs
Vancomycin
inhibits cell wall formation by binding D-ala D-ala cell wall precursor.
Not susceptible to beta- lactamases
use for gram positive bugs, including MRSA
S. epidermidis, enterococcus, clostridium difficile (PO for pseudomembranous colitis, but use metronodozile instead possible)
Side effects: Nephtoxocity, Ototoxicity, Thrombophlebitis
Red man is diffuse flushing. When this happens, treat with antihistamines and a slower infusion rate
Reisistance via D-ala D-lac
Carbapenems
imipenem (broad spectrum, must be used with cilastin)
meropenem
ertapenem
doripenem
Gram positive cocci, gram negative rods, wide spectrum but significant side effects limit use to life- threatening infections (empiric threatment)
Won’t cover MRSA.
Meropenem has decreased risk of seizures
Toxicity- GI distress, skin rash, CNS toxicity (seizures) at high plasma levels
Imipenem is more neurotoxic than meropenem which has a decreased risk of seizures,
won’t be inactivated in the renal tubules
but AT 30, CCEL at 50
protein synthesis inhibitors
30S inhibitors
Aminoglycosides (bactericidal)
Tetracyclines (bacteriostatic)
50S inhibitors
Chloramphenical, Clindamycin (bacteriostatic)
Erythromycin (macrolides, bacteriostatic)
Linezolid (variable)
Tetracyclines- how do they work and what do they cover?
- tetracycline
- doxycycline
- minocycline
Bacteriostatic, binds 30S and prevents tRNA interaction. limited CNS penetration.
Fecally eliminated, which makes amenable to patients who have renal failure. Divalent cations block absorption ion the gut; not to be combined with milk or iron.
Side effects: GI distress (don’t use antacids- then the antibiotic won’t be absorbed at all!), discolored teeth, inhibited bone growth in children, photosensitivity, contraindicated in pregnancy
Minocycline can give blue discoloration after prolonged use
VACCUUM THe BedRoom Vibrio cholerae Acne Chlamydia Ureaplasma urealyticum Mycoplasma pneumoniae Tularemia Helicobacter pylori Borrelia burgdorferi Rickettsia
resistance via decreased uptake or increased efflux out of bacterial cells by plasmid- encoded transport pumps
Oxazoladinone- Linezolid
binds 23S RNA component of 50S large ribosomal subunit, interacts with and inhibits formation of bacterial initiation complex
used against MRSA, VRE, and is used orally against MRSA! Outpatient MRSA therapy is possible with linezolid if well controlled
Toxicity- bone marrow suppression, thrombocytopenia, peripheral neuropathy, serotonin syndrome for pts who are on SSRIs
resistance via point mutation on RNA
AminO2glycosides
- gentamycin
- neomycin
- amikacin
- tobramycin
- streptomycin
binds 30S ribosome
bactericidal
IRREVERSIBLY inhibits formation of initiation complex, causes mRNA misreading, ineffective against anaerobes (requires oxygen)
These are for severe gram neg rod infections, and work synergistically with beta lactam antibiotics (eg am+gent)
neomycin for bowel surger
Toxicity: NNOT
nephrotoxicity (especially when used with cephalosporins)
neuromuscular blockade
ototoxicity (especially if combined with loop diuretics)
Teratogen
resistance comes with bacterial transferase enzymes capable of acetylating, phosphorylating, or adenylating the aminoglycoside
Macrolides. macroslides
- erythromycin
- azithromycin
- clarithromycin
inhibit protein synthesis by blocking translocation (macroslides) at the 23rRNA of the large 50S ribosomal subunit.
Bacteriostatic
used for PUS
PNA (atypical especially- mycoplasma, chlamydophila, legionella) b. pertussis
URI (strep pneumoniae, strep pyogenes)
STD (chlamydia, gonorrhea)
Toxicity:
MACRO: GI motility issues, Arrythmia due to prolonged QT, acute Cholestatic hepatitis (with erythromycin estolate), Rash, rare cases of eOsinophilia
increases serum concentration of theophyllines and oral anticoagulants (warfarin)
mostly safe in pregnancy
-azythromycin
Resistance via methylation of 23S rRNA binding site (prevents drug from binding)
chloramphenicol
inhibits 50S subunit of ribosomal RNA, thereby inhibiting peptidyltransferase activity. Bacteriostatic
treats
meningitis:
haemophilus influenzae
neisseria meningitidis, streptococcus pneumoniae
RMSF
unpopular due to toxicity:
dose- dependent anemia
grey baby syndrome (babies need UDPGT to metabolize chloramphenicol, and they experience a buildup of toxic metabolites)
symptoms include vomiting, ashen gray skin tone, poor muscle tone, cyanosis, CV collapse
stop the chloramphenicol and do an exchange transfusion to treat this
try phenobarbitol to induce UDPGT
resistance: plasmid- encoded acetyltransferase can inactivate the drug
Clindamycin
Clindamycin blocks peptide bond formation with the 50S ribosomal subunit. It is bacteriostatic.
Use: ANAEROBES (bacteriodes, clostridium perfringens) in aspiration PNA, lung abscesses, oral infections, invasive GAS
- above the diaphragm (versus metronidazole which is used below the diaphragm)
Can also be used against MRSA skin abscesses (oral clindamycin is a nice outpatient option), protozoal infections
topical use for acne treatment
Toxicity:pseudomembranous colitis (C. Diff), fever, diarrhea
Streptogramins
-Quinupristin/Dalfopristin (Synercid)
mechanism: binds to the 23S portion of the 50S ribosome
(synthesized by the bacteria streptomyces virginiae)
Use: MRSA, VRE,
Staphylococcus and streptococcus skin infections that are very serious- this drug has a lot of side effects
Side effects: hepatotoxicity
pseudomembranous colitis, arthralgia, myalgia
inhibits CYP450
Sulfonamides
- sulfamethoxazole (SMX)
- sulfdiazone
bacteria need to absorb folic acid- they can’t make their own
Sulfonamides inhibit folate synthesis
Para-aminobenzoic acid (PABA) antimetabolites inhibit dihydropteroate synthase
Bacteriostatic (bactericidal when combined with trimethoprim)= TMP SMX
Dapsone, used to treat lepromatous leprosy is a closely related drug that also inhibits folate synthesis
Covers gram positives AND negatives
Nocardia
Chlamydia
UTIs like E Coli
Skin infections
Toxicity-
hypersensitivity reactions
hemolysis if G6PD deficient
nephrotoxicity (tubulointerstial nephritis)
photosensitivity
kernicterus in infants- do not give to pregnant females who are about to deliver
SJS
displace other drugs from albumin (warfarin)
Resistance to the drug
altered bacterial dihydropteroate synthesis
decreased uptake
increased PABA synthesis (if this were the case you could give a bigger dose?)
Sulfa Pills Frequently Cause Terrible Acute Symptoms
drugs that cause sulfa allergy
Sulfa Pills Frequently Cause Terrible Acute Symptoms
Sulfasalazine Probenecid Furosemide Celecoxib Thiazides/TMP-SMX Acetazolamide Sulfonylureas
Drugs that cause SJS
Penicillin drugs Sulfa drugs Seizure drugs -ethosuximide -lamotrigine -carbamazepine -phenobarbital -phenytoin Allopurinol
Trimethoprim
Dihydrofolate reductase inhibitor
bacteriostatic
combine with sulfonamaides to cause sequential block of folate synthesis. TMP-SMX can be used for UTIs shigella salmonella pneumocystis jirovecii pneumonia treatment and ppx when CD4
Drugs that inhibit dihydrofolate reductase
methotrexate
trimpethoprim
pyrimethamine
nitrofurantoin
bacteriocidal
reduced by bacterial proteins to a reactive intermediate that inactivates bacterial ribosomes
It has be reduced in the presence of bacteria to be effective- only effective in the URINE
useful only for mild UTI (so, not pyelonephritis)
-e.coli
staphylococcus
side effects: rarely nausea, HA, diarrhea
safe in pregnancy
Fluoroquinolones
- levofloxacin
- ciproflozacin
- norfloxacin
- levofloxacin
- ofloxacin
- moxifloxacin
- gemifloxacin
- enoxacin
- gatifloxacin
- nalidixic acid
inhibits DNA gyrase (aka topoisomerase I)
absorption inhibited if taken with antacids
used for gram negative infections, UTIs, GI tract
infections, pseudomonas
varying amounts of gram + coverage
ok for CF children if they are getting a lot of lung infections
toxicity: GI upset cartilage damage in children tendinitis and tendon rupture QT interval prolongation
Resistance: chromosome-encoded DNA gyrase mutation
Metronidazole
absorbed by micro-organisms, forms toxic ROS that damage DNA
use for GET GAP on the Metro Giardia lamblia Entamoeba histolytica Trichomonas Gardnerella vaginalis Anaerobic bacteria (c. diff, perfringens, tetani, bacteriodes species) Pylori (helicobacter pylori)
Can cause a disulfiram-like reaction with alcohol (sweating, nausea, hypotension)
Polymyxins
Polymyxin E, polymyxin B
Cationic detergents that attack and disrupt cell membranes and also inactivate endotoxin
Use for last resort therapy against gram- negative infections (give by IV)
toxicity: neurotoxicity, nephrotoxicity (ATN)
almost always used topically
ppx meningococcal meningitis
ciprofloxacin, rifampin, ceftriaxone
ppx h. influenzae meningitis
rifampin
Gonorrea
ceftriaxone, especially after sexual assault
syphilis
benzathine penicillin G
recurrent UTI
TMP-SMX, nitrofurantoin, amoxicillin, cephalexin
prevent pneumocystis jirovecii
TMP-SMX, when CD4
endocarditis from dental procedure
penicillin, amoxicillin, cephalexin, azythromycin
Target= viridans strep
GBS
ampicilin during labor
gonocccal/ chlamydial conjunctivitis
erythromycin ointment
SAFe Children Take Really Good Care
Sulfonamides-kernicterus Aminoglycosides-ototoxicity Fluoroquinolones- cartilage damage Clarythromycin- embryotoxic Tetracyclines- discolored teeth, inhibition of bone growth Ribavirin (antiviral)- teratogenic Griseofulvan (antifungal)- teratogenic Chloramphenicol- gray baby syndrome
