antibacterials

• Bacteriostatic- stop growth, need good immune sys to clear the bugs. DO NOT use in immunocompromised pts, meningitis, endocarditis!
• - Erythromycin, Clindamyclin, Sulfamethoxazole, Trimethoprim, Tetracyclines, Chloramphenicol.

• Bacteriocidal- kill!
• -Peniciliin, Vancomycin, Fluoroquinolone, Aminoglycoside, Cephalosporins, Metronidazole

NEVER mix Bactericidal + Bacteriostatic!

Penicillin + Aminoglycoside= synergy!

Penicillin + Tetracycline= antagonism!

bacteriocidals! (lactams!)

• Penicillin
• cephalosporins
• imipenem/ meropenem
• aztreonam
• vancomycin (not lactam)

bacteriostatic!

• Aminoglycoside (bacteriocidal)
• Chloramphenicol
• macrolide
• tetracycline
• streptogramins
• linezolid

bacteriocidal!

• Fluoroquinolones
• Rifampin

• Sulfonamide
• Trimethoprim
• Pyrimethamine

• bacteriocidals with beta-lactam ring structure : D-ala-D-ala analog
• -bind Penicillin-binding proteins (PBP)
• -inhibit transpeptidation (block crosslinking PG-final step in cell wall syn)

• Penicillins (b-lactam+5C ring)
• Cephalosporins (+6C ring)
• Imipenem,Meropenem (carapenems)
• Aztreonam (monobactams)

• beta-lactamases ex. Staph
• change transpeptidase structure ex.MRSA
• change porins (gram- so drug can't enter) ex. Pseudomonas

All Mycoplasma are resistant to all beta-lactams! b/c no cell wall!

• 1st gen penicillin
• narrow spectrum b-lactam
• short half life
• beta-lactamase sensitive

• USE- Syphillis!
• some gram+ streps, meningococci
• SE- hypersensitivity (+coombs- hapten), Hemolytic anemia
• Jarisch-Herxheimer reaction (from syphillis rx)

• Benzathine Penicillin G-repository form for syphilis (2week half life!)

• 2nd gen penicillin
• very narrow spectrum
• beta-lactamase resistant (bulky R)

• USE- Staph! except MRSA
• (use Vancomycin for MRSA)

• SE- Methicillin- interstitial nephritis
• Nafcillin, oxacillin- hepatotoxic (b/c eliminate by bile)

• 3rd gen penicillin
• broader spectrum!
• beta-lactamase sensitive
• Amoxicillin better oral-bioavailability

• USE-Gram+: Streps,Enterococci listeria !
• Gram-: E.coli, H. influenzae, Proteus
• H.pylori (Amoxicillin)
• Borrelia (Amoxicillin)

• SE-Hypercensitivity (ampicillin rash!)
• Pseudomembranous colitits (Rx- metronidazole)

• 4th gen Penicillin
• antipsuedomonals!!
• extended spectrum
• beta-lactamase sensitive

• USE- Pseudomonas!
• more Gram- rods (enterobacteracea)

SE-Hypersensitivity

• suicide inhibitors of beta-lactamases
• add to penicillins (except Nafcillin, Methicillin)

-enhance activity with clavulanic acid, sulbactam..

• -synergy with aminoglycosides
• (amoxicillin+ aminoglycoside-->Enterococci)
• (Ticarcillin + aminoglcoside-->pseudomonas)

- all eliminated by kidney except Nafcillin, Oxacillin (bile)!- so adjust dose for bad kidneys!

-Cross-allergenicity betwm penicilins!

Type1: IgE- rapid onset, anaphylaxis, andioedma, laryngospasm

Type2: IgM, IgG- fixed to cells--> vasculitis, neutropenia, +Coombs

Type3: Immune-complex-->vasculitis, serum sickenss, glomerulo/interstitial nephritis

Type4: Tcell med--> urticarial maculopapular rashes, Stevens-Johnson syndrome

• beta-lactams w/ 6c ring
• -less susceptable to penicillinases
• -bacteriocidal!

• 1st gen: Cefazolin, Cephalexin
• 2ng gen: Cefotetan, Cefaclor, Cefuroxime
• 3rd gen: Ceftriaxone, Cefotaxime, Cefdinir, Cefixime, Cefoperazone
• 4th gen: Cefepime

• 1st gen cephalosporin
• same mech as penicillin
• long half life

• USE- gram+ cocci
• gram- : Proteus, E.coli, Klebsiella
• (PEcK), dur Surgery!

• SE- hypersensitivity, Vit-K deficiency
• ,increase nephrotoxicity with Aminoglycosides!

• 2nd gen cephalosporin
• same mech as penicillin
• -does NOT cross BBB!
• -Cefuroxime does!

• USE-gram + cocci
• more gram- coverage (HEN PEcK)- H. influenzxa, Enterobacter, Neisseria, Proteus, E.coli, Klbesiella

SE-Disulfram-like effect w/Cefotetan! Hypersensitivity, Nephrotoxicity with aminoglycosides

• 3rd gen cephalosporins (the work horse!)
• -Cross BBB!! except Cefoperazone
• -broad spectrum!
• -Ceftriaxone, Cefoperazone eliminated by bile, NOT kidney.
• -Cefoperazone is too lipid soluble to be free to cross BBB.

• USE- Meningitis, Sepsis!
• -many gram+, gram-
• -Ceftriaxone- Meningitis,Gonorrhea
• -Ceftazidime - pseudomonas!

• SE- Disulfram-like effects w/ Cefperazone, Hypersensitivity,
• Hepatotoxicity w/ Ceftriaxone, Cefoperazone (bile)

• 4th gen cephalosorin
• very broad spectrum
• resistant to penicillinase
• cross BBB, IV only

USE- Pseudomonas, more gram +s

SE- Hypersensitivity, nephrotoxicity w/ Aminoglycosides

LAME

• -Listeria (use amoxicillin/ampicillin)
• -Atypicals (mycoplasma, Chlamydia) (use, macrolides)
• -MRSA (use vancomycin)
• -Enterococci (use amoxicillin/ampicillin)

• -Cross allergenicity with Penicillins!
• -just use Macrolides (gram+), Aztreonam (gram- rods)

-Disulfram-like effects w/ Cefoperazone, Cefotetan

• -Renal clearance similar to Penicillins (active tubular secr. blocked by Probenecid)
• -Ceftriaxone, Cefoperazone eliminated by bile, not kidney.

• Carbapenem
• broad spectrum beta-lactam!
• -same mech as penicilin
• -resistant to penicillinase
• -must use w/ Cisplatin (dehydropeptidase inhibitor) to block inactivation in kidney.

• USE- almost anything! (not MRSA)
• -gram+ cocci, gram- rods, anaerobes
• -used in hospital for severe-life-threatening infections!!
• SE- Seizure! GI distress, hypersensitivity, dose adjust for kidney

• Carbapenem
• broad spectrum beta-lactam!
• -same mech as penicilin
• -resistant to penicillinase

• USE- almost anything! (NOT MRSA)
• -gram+ cocci, gram- rods, anaerobes
• -used in hospital for severe-life-threatening infections!

SE-GI distress, hypersensitivity, dose adjust for kidney, NO seizures

• Monobactam (beta lactam)
• -same mech as penicillin
• -resistant to penicillinase
• -NO cross allergenicity w/ Penicilliins, cephalosporins!!
• -synergistic w/ aminoglycosides
• -does NOT cross BBB!

• USE- only gram - rods!!
• -good for penicilin-allergic pt
• -good for kidney failure pt who can't tolerate aminoglycoside
• -NOT for gram+, or anaerobes

SE-GI distress but not much..

• NOT beta lactam
• -inhibit PG elongation (transglycosylation) by binding at D-ala-D-ala muramyl pentapeptide
• -bacteriocidal
• -IV, oral (not absorbed, stay in gut)
• -goes everywhere except BBB
• -kidney eliminated

USE- gram + only! -MRSA, Enterococci, C.Difficile (PO, backup. Metronidazole better)

SE-red man syndrome (typeI-histamine), ototoxicity, nephrotoxicity, thrombophlebitis

• Resistance-VRSA, VRE emerging! VRE change target as D-ala-D-lactate!
• -use Linezolid, Streptogramins for these nasty ones!

all bacteriostatic except aminoglycosides

• 1.Block initiation complex formation
• Aminoglycosides (30S),
• Linezolid (50S)-VRSA, VRE
• -block mRNA assoc w/ 50S ribosome (static)- cause misreading of mRNA (cidal-aminoglycoside)

• 2.block AA incorporation to A site-
• Tetracycline (30S), Dalfopristin/Quinupristin(50S)

• 3.Block peptide bond formation-peptidyltransferase
• -Chlormaphenicol (50S)

• 4.Block translocation-
• Macrolides, Clindamycine (50S)

• Aminoglycosides
• -bacteriocidal
• -block initiation complex form, cause misread (frameshift)in mRNA
• -require O2 for uptake! go thru ETC
• -CANNOT kill anaerobes, streps!
• -synergy w/ Beta lactams
• -polar, not good orally, poor distribute (stay in ECF)
• -low TI (once/day dose good)

• USE-gram - rods!
• -synergy w/ampicllin-->enterococci
• -synergy w/4th gen penicillin-->pseudomonas

• SE-nephrotoxicity (esp w/cephalosporins), ototoxicity, esp w/ loos), NMJ blockade (block Ach release like botox!) contact dermatitis w/ Neomycin

bugs make conjugation enzyme that inactivate aminoglycoside!

aminoglycoside


USE- TB, choice for Bubonic Plague, Tularemia

NOT nephrotoxic!

topical aminoglycoside

SE-contact dermatitis!

• Antibacterial effects depend mainly on peak drug levels (rather than time) and continue w/ blood levels less than MIC
• = Post-antibiotic effect!

Toxicity depends on both blood level and time that levels are greater than threshold (ex. total dose)

• Tetracycline
• -bacteriostatic
• -inhibit A site on 30S (block attachment of AA-tRNA)
• -broad spectrum! actively taken up by bug-->accum in cell
• -chelate cations, so do NOT take w/food (esp. antiacids, milk, Ca, decr absoption)
• -antagonistic w/ penicillins!!

• USE-good for intracellular, atypicals
• -Chlamydia, Rickettsia, Borrelia, Vibrio, Treponema (backup)

• SE-chelate Ca, Mg, Fe..
• - decr bone! brown teeth, inhibit bond growth in kids!, phototoxicity
• -vestibular disfunction (minocycline)
• -kidney dose adjust except Doxycycline
• do NOT use in pregnancy and kids!!

transport PUMPS pump drug out of the cell

• tetracycline
• -bacteriostatic
• -block A site on 30s
• -NO nephrotoxicity b/c eliminated by liver!
• -more lipid soluble

• USE- Borrelia burgdorferi (Lyme disease!)
• -good for prostatitis (chlamydia, gonnorrea)

• SE-inhibit bone, phototoxicity
• do NOT use in pregnancy, kids!

• Tetracycline
• -bacteriostatic
• block A site on 30S
• -too water soluble

• USE- dental issues, gingivitis
• get in high conc in saliva, tears

• SE- bone inhibit, vestibular dysfunctinon, kidney
• do NOT use in pregnancy, kids!

• Tetracycline
• -bacteriostatic
• -block A site on 30s
• -inhibit ADH receptor in collecting duct!!
• --> cause nephrogenic diabetes insipidus!!

USE- SIADH (paraneoplastic in renal cell carcinoma, bronchogenic squaous cell carcinoma)

• bacteriostatic
• -inhibit 50S peptidytransferase (peptide bond formation)
• -very wide spectrum
• -lipid soluble, cross BBB
• -glucuronidated by liver
• -cross placenta!

• USE- meningitis! (H.influenza, N.meningitis, S.pneumonia)
• -backup for Samonella typhi, B.fragilis, Rickettsia

• SE-does dependent marrow suppression (like anticancer),
• gray baby syndrome! (baby's liver can't handle, can't eliminate-->kernicterus), hemolysis in G6PD
• ,inhibit Cyps!!
• do NOT use in pregnancy!

Resistance- inactivating acetyltransferases

• Macrolide
• -bacteriostatic
• -block translocation by binding to 23S rRNA on 50S
• -wide-spectrum
• -inhibit CYPS!
• -can use Azithromycin in pregnancy b/c more water soluble.

• USE- atypical pneumonia (mycoplasma, chalmydia, legionella!)
• -URIs, STDs (Neisseria), MAC
• -gram + cocci (not MRSA)esp. penicillin-allergic pts
• -GI motility disorders (activate motilin receptors)

• SE- Prolong QT (esp. Erythromycin), GI distress (motilin), reversible deafness, acute cholestatic hepatitis, eosinophilia, increase conc. of theophyllines, oral anticoagulants
• -inhibit CYPS!

methylation of 23S rRNA so Macrolide cannot recognize it!

Telithromycin - ketolide

• bacteriostatic
• -block traslocation at 50s
• -narrow spectrum
• -accum high conc in bone!
• (anaerobes above diaphram)

• USE- gram+ anaerobic infections! (B. fragilis, Clostridium perfringens)
• -aspiration pneumonia
• -osteomyelitis (S. aureus)
• NOT gram- osteomyelitis ex. Sickle cell osteomyelitis (salmonella), Diabetic osteomyelitis (pseudomonas)

SE-pseudomembramous colitis (Rx w/ Metronidazole or Vancomycin (backup)

• bacteriostatic
• -block formation of initiation complex (same as aminoglycosides but at 50s)
• -very toxic!

• USE- VRSA, VRE, drug-resistant pneumococci
• -both E. faecalis and E. faecium!

SE-bone marrow suppression! (esp. thrombocytopenia)

• Streptogramins
• -bacteriostatic
• -block A site (like tretracycline) from 50S
• block release of peptide from ribosome.

• USE-VRSA, VRE (alternative to Vancomycin resistance-D-ala-D-lactate)
• -E. faecium, but NOT E. faecalis

• Aminoglycosides
• Fluoroquinolones
• Sulfonamides
• Tetracyclines

• inhibitor of bacterial folic acid synthesis
• -bacteria make their folate from PABA + Pteridine w/ Dihydropteroate synthetase
• -inhibit dihydropteroate synthetase
• -bacteriostatic
• -acetylated by liver-->less soluble metabolite!!-->renal excreted

• USE- see w/ Trimethoprim
• -synergy w/ dihydrofolate reductase inhibitors
• -sulfonamides alone useless b/c multiple drug resistance!!

• SE- hypersensitivity (rash, steven-johnson syndrome)
• Hemolysis in G6PD deficiency, crystalluria in kidney!, phototoxic
• high protein binding-->kernicterus in neonates! (displace bilirubin from albumin)

• inhibitor of bacterial folic acid synthesis
• -bock dihydrofolate reductase (in humans too)
• -bacteriostatic

USE- combo w/ sulfonamides

• SE-anticancer like effects!
• -Megaloblastic anemia, leukopenia, granuloytopenia (give leucovorin!)

inhibit Dihydropteroate synthetase + dihydrofolate reductase (synergy)

• USE-Nocardia! Listeria (backup to amoxicillin) UTIs!
• -gram- (E.coli, samonella, shigella, H.influenza)
• -gram+ (staph, MRSA)
• -Pneumocystis jiroveci !! CD4<200

USE- Toxoplasma gondii (CD4 <100)

• Sulfa-allergic pts:
• do NOT give

• -sulfa drugs- sulfasalazine, sulfonylureas
• -thiazides
• -acetazolamide
• -furosemide
• -celecoxib
• -probenecid

• Fluororquinolones
• -direct DNA synthesis inhibitor
• -bacteriocidal
• -block DNA gyrase (topoiosomerase II)-neg supercolis
• -block topoisomerase IV- separate replicated DNA
• -Fe,Ca limit absopriton (like tetracyclines)-don't eat w/ food
• -renal excretion (inhibited by probenecid)

• USE-UTIs, STDs, PID (Chlamydia, gonorrhea)
• - gram- skin, soft tissue, bone infections (salmonella, pseudomonas)
• -Diarrhea by Shigella, Salmonella, E.coli, Campylobacter
• -drug resistant pneumococci (levofloxacin)
• -Anthax!

• SE-Phototoxcity, rash, insomnia/headache, Tendonitis, tendon rupture, QT prolong!
• do NOT use in pregnancy and Kids!

• bacteriocidal
• -form free radicals--> damage bacterial DNA
• -anaerobes below diaphram

• USE- 1st choice for Giardia,Entamoeba,Trichomonas
• -most anaerobes: Bacteroides, Clostridium (not Actinomyces)
• -1st choice for C.diff Pseudomembranous colitis!
• -triple therapy for H. Pylori (Bismuth +tetracycline/amoxicillin)

SE- metallic taste, Disulfram-like effect, peripheral neuropathy

• 1. BMT regimen:
• Bismuth, Metronidazole, Tetracycline

2. Clarithromycin, amoxicillin, omeptrazole

-decrease peptic ulcer, decrease risk of adenocarcinoma, MALT lymphoma

• Isoniazid
• Rifampin
• Ethambutol
• Pyrazinamide
• Streptomycin

• backups:
• Aminoglycosides (Streptomycin, amikacin, kanamycin)
• Fluoroquinolones
• Capreomycin (hearing loss)
• Cycloserine (neurotoxic)

• anti-TB drug
• -inhibit mycolic acid synthesis
• -must be activated by bacterial catalase (KatG-gene)
• -HIGH resistance (mutate KatG gene)

• USE- only one for solo prophylaxis for TB
• -combo therapy for TB
• - give with vit B6!

SE- hepatotoxic! Pyridoxine deficiency!! (use up all B6--> neurotoxicity from sideroblastic anemia (high Ferritin, %sat, low TIBC) (give Pyridoxine B6), SLE-like in slow acetylators

• anti-TB drug
• -block bacterial transcription of DNA
• (RNA polymerase inhibitor)

• USE- combo therapy for TB
• -meningococcal prophylaxis
• -prophylaxis of H. influenza
• -Leprosy

• SE- hepatotoxic, induce CYPs!
• -Red oragne body fluids!!

• anti-TB drug
• -inhibit cell wall carbohydrate polymerization by blocking arabinosyltransferase

USE- combo therapy for TB

SE- optic neuritis! can't tell red vs green!!

• anti-TB drug
• -prodrug
• -effective in acidic pH of phagolysosomes of Macs where TB lives

USE- combo therapy for TB

SE- hepatotoxic, Hyperuricemia (compete w/ uric acid for excretion)

aminoglycoside

USE- IV for TB

SE- ototoxicity, nephrotoxicity, NMJ blockade

Prophylaxis- Isoniazid

Rx- Isoniazid, Rifampin, Pyraxinamide, Ethambutol

Prophylaxis- Azihromycin or Clarithromycin

Rx-Rifampin, Azithromycin, Ethambutol, Streptomycin

Prophylaxis- none

Rx- Dapsone, Rifampin, Clofazimine

• Rifampin
• Minocycline (backup)

Ceftiaxone (cephalosporin)

Benzathine Penicillin G

TMP-SMX

TMP-SMX

Pentamidine (backup)

Penicillin

Azithromycin