Mechanism of beta lactams - Penicillins - Cephalosporins

1. penicillins bind penicillin binding proteins (PBPs) - PBPs involved in synthesis of peptidoglycan binding --> cell wall synthesis inhibits --> lysis 2. inhibit cross linking of peptidoglycan chains --> weak cell wall 3. facilitate damageby autolysins d/t weakened/absent cell wall - may up regulate bacteriocidal

Antibiotics Flashcards by Daniel Coquyt

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

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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

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Resistance mechanisms to penicillin

Penicilinase - type b-lactamase
-produced in periplasm gram - organims
coded by plamids

alteration of b-lactam target - PBP

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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

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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

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B-lactamase inhibitor

enhance spectrum of drug
used in combination:

Clavulanic acid + amoxicilin - resistant OM
Clavulanic acid + piperacillin
Sulbactam + ampicillin - IV, surgery
Tazobactam + piperacillin

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Antipseudomonal abx

Ticarcillin
Carbenicillin
Piperacillin

Extended spectrum
Pseudomonas
gram - rods

susceptible to penicillinase
-add B-lactamase inhibitor

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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

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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

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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

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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

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4th gen cephalosporins

Cefepime

broad spectrum
-most gram + of 1st and 2nd gen
Gram -

Pseudomonas

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5th gen cephalosporins

Ceftaroline

Broad spectrum
MRSA
No Pseudomonas coverage
Community acq pneumonia
complicated skin infections (MRSA)

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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

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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

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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

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Vancomycin resistance mechanism

D-ala-D-ala to D-ala-D-lac

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Red man syndrome

Vancomycin associated

diffuse flusing of whole body
non specific mast cell degranulation
avoid w/:
-antihistamine pretreatment
-slow down infusion
-can restart

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30 S and 50 S inhibitors

“buy AT 30, CCELL at 50”

30S:
Aminoglycosides
Tetracyclines

50S:
Chloramphenicol
Clindamycin
Erythromycin (macrolides)
Lincomycin
Linezolid

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Aminoglycosides

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"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

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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

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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

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binds 23 S RNA portion of 50S
interacts w/ bacterial initiation complex

Use: MRSA, VRE

can cause serotonin syndrome w/ SSRI med use

Tetracyclines

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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

Antibiotics Flashcards

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