Antibiotics Flashcards
Penicillin G,V
Mechanism?
D-Ala-D-Ala structural analog. Bind penicillin-binding proteins (transpeptidases).
Block transpeptidase cross-linking of peptidoglycan in cell wall.
Activate autolytic enzymes.
Penicillin G,V
Clinical Use?
Mostly used for gram ⊕ organisms (S pneumoniae, S pyogenes, Actinomyces). Also used for gram ⊝
cocci (mainly N meningitidis) and spirochetes (mainly T pallidum). Bactericidal for gram ⊕ cocci,
gram ⊕ rods, gram ⊝ cocci, and spirochetes. β-lactamase sensitive.
Penicillin G,V
Adverse Effects
Hypersensitivity reactions, direct Coombs ⊕ hemolytic anemia, drug-induced interstitial nephritis.
Penicillin G,V
Resistance
β-lactamase cleaves the β-lactam ring. Mutations in PBPs.
Penicillinase-sensitive
penicillins
Examples?
Amoxicillin, ampicillin; aminopenicillins
Penicillinase-sensitive
penicillins
Mechanisms?
Same as penicillin. Wider spectrum;
penicillinase sensitive. Also combine with
clavulanic acid to protect against destruction
by β-lactamase.
AMinoPenicillins are AMPed-up penicillin.
AmOxicillin has greater Oral bioavailability
than ampicillin.
Penicillinase-sensitive
penicillins
Clinical Use?
Extended-spectrum penicillin—H influenzae,
H pylori, E coli, Listeria monocytogenes,
Proteus mirabilis, Salmonella, Shigella,
enterococci.
Coverage: ampicillin/amoxicillin HHELPSS
kill enterococci.
Penicillinase-sensitive
penicillins
Adverse Effects?
Hypersensitivity reactions, rash,
pseudomembranous colitis.
Penicillinase-sensitive
penicillins
Resistance?
Penicillinase (a type of β-lactamase) cleaves
β-lactam ring
Penicillinase-resistant
penicillins
Examples
Dicloxacillin, nafcillin, oxacillin.
Penicillinase-resistant
penicillins
Mechanisms
Same as penicillin. Narrow spectrum;
penicillinase resistant because bulky R group
blocks access of β-lactamase to β-lactam ring.
Penicillinase-resistant
penicillins
Clinical Use
S aureus (except MRSA).
“Use naf (nafcillin) for staph.”
Penicillinase-resistant
penicillins
Adverse Effects
Hypersensitivity reactions, interstitial nephritis
Penicillinase-resistant
penicillins
Resistance
MRSA has altered penicillin-binding protein
target site.
Antipseudomonal
penicillins
Examples?
Piperacillin, ticarcillin.
Antipseudomonal
penicillins
Mechanism?
Same as penicillin. Extended spectrum. Penicillinase sensitive; use with β-lactamase inhibitors.
Antipseudomonal
penicillins
Clinical Use?
Pseudomonas spp. and gram ⊝ rods.
Antipseudomonal
penicillins
Adverse Effects
Hypersensitivity reactions.
Cephalosporins
Mechanism
β-lactam drugs that inhibit cell wall synthesis
but are less susceptible to penicillinases.
Bactericidal
Cephalosporins
What organisms are not covered by 1st-4th generation cephalosporins?
Listeria, Atypicals (Chlamydia, Mycoplasma),
MRSA, and Enterococci
Clinical Use and examples
1st generation Cephalosporins
1st generation (cefazolin, cephalexin)—gram ⊕
cocci, Proteus mirabilis, E coli, Klebsiella
pneumoniae. Cefazolin used prior to surgery to
prevent S aureus wound infections.
1st generation—⊕ PEcK
Clinical Use and examples
2nd generation Cephalosporins
2nd generation (cefaclor, cefoxitin, cefuroxime,
cefotetan)—gram ⊕ cocci, H influenzae,
Enterobacter aerogenes, Neisseria spp., Serratia
marcescens, Proteus mirabilis, E coli, Klebsiella
pneumoniae.
2nd graders wear fake fox fur to tea parties.
2nd generation—⊕ HENS PEcK
Clinical Use and examples
3rd generation Cephalosporins
3rd generation (ceftriaxone, cefotaxime, cefpodoxime, ceftazidime)—serious gram ⊝ infections resistant to other β-lactams.
Can cross blood-brain barrier.
Ceftriaxone—meningitis, gonorrhea,
disseminated Lyme disease.
Ceftazidime—Pseudomonas.
Clinical Use and examples
4th generation Cephalosporins
4th generation (cefepime)—gram ⊝ organisms, with increased activity against Pseudomonas and gram ⊕ organisms.
Clinical Use and examples
5th generation Cephalosporins
5th generation (ceftaroline)—broad gram ⊕ and
gram ⊝ organism coverage; unlike 1st–4th
generation cephalosporins, ceftaroline covers
MRSA, and Enterococcus faecalis—does not
cover Pseudomonas.
Cephalosporins
Adverse effects
Hypersensitivity reactions, autoimmune
hemolytic anemia, disulfiram-like reaction,
vitamin K deficiency. Low rate of crossreactivity even in penicillin-allergic patients.
increase nephrotoxicity of aminoglycosides.
Cephalosporins
Resistance mechanism?
Inactivated by cephalosporinases (a type of
β-lactamase). Structural change in penicillinbinding proteins (transpeptidases).
β-lactamase inhibitors
Examples
Include Clavulanic acid, Avibactam,
Sulbactam, Tazobactam. Often added to
penicillin antibiotics to protect the antibiotic
from destruction by β-lactamase.
CAST (eg, amoxicillin-clavulanate,
ceftazidime-avibactam, ampicillin-sulbactam,
piperacillin-tazobactam).
Carbapenems
Examples
Doripenem, Imipenem, Meropenem, Ertapenem (DIME antibiotics are given when there is a
10/10 [life-threatening] infection).
Carbapenems
Mechanism
What is Imipenem commonly prescribed along with?
Imipenem is a broad-spectrum, β-lactamase–
resistant carbapenem. Always administered
with cilastatin (inhibitor of renal
dehydropeptidase I) to decrease inactivation of drug
in renal tubules.
With imipenem, “the kill is lastin’ with
cilastatin.”
Newer carbapenems include ertapenem (limited
Pseudomonas coverage) and doripenem
Carbapenems
Clinical Use
Gram ⊕ cocci, gram ⊝ rods, and anaerobes.
Wide spectrum and significant side effects
limit use to life-threatening infections or
after other drugs have failed. Meropenem
has a decrease risk of seizures and is stable to
dehydropeptidase I
Carbapenems
Adverse effects
GI distress, rash, and CNS toxicity (seizures) at
high plasma levels.
Carbapenems
Mechanism of resistance
Inactivated by carbapenemases produced by,
eg, K pneumoniae, E coli, E aerogenes
Monobactams
Example
Aztreonam
Monobactams
Mechanism
Less susceptible to β-lactamases. Prevents peptidoglycan cross-linking by binding to penicillinbinding protein 3. Synergistic with aminoglycosides. No cross-allergenicit
Monobactams
Clinical Use
Gram ⊝ rods only—no activity against gram ⊕ rods or anaerobes. For penicillin-allergic patients
and those with renal insufficiency who cannot tolerate aminoglycosides
Monobactams
Adverse effects
Usually nontoxic; occasional GI upset
Vancomycin
Mechanism
Inhibits cell wall peptidoglycan formation by binding D-Ala-D-Ala portion of cell wall precursors.
Bactericidal against most bacteria (bacteriostatic against C difficile). Not susceptible to
β-lactamases.
Vancomycin
Adverse Effect
Well tolerated in general but NOT trouble Free.
Nephrotoxicity, Ototoxicity, Thrombophlebitis, diffuse Flushing (red man syndrome A idiopathic
reaction largely preventable by pretreatment with antihistamines), DRESS syndrome
Vancomycin
Clinincal Use
Gram ⊕ bugs only—for serious, multidrug-resistant organisms, including MRSA, S epidermidis,
sensitive Enterococcus species, and Clostridium difficile (oral dose for pseudomembranous colitis
Vancomycin
Resistance mechanism
Occurs in bacteria (eg, Enterococcus) via amino acid modification of D-Ala-D-Ala to D-Ala-D-Lac.
“If you Lack a D-Ala (dollar), you can’t ride the van (vancomycin).”
Name Protein synthesis inhibitor antibiotics?
Which are bacteriostatic and which are bactericidal?
30S inhibitors Aminoglycosides Tetracyclines 50S inhibitors Chloramphenicol, Clindamycin Erythromycin (macrolides) Linezolid “Buy AT 30, CCEL (sell) at 50.
All are bacteriostatic, except aminoglycosides
(bactericidal) and linezolid (variable)
Aminoglycosides
Mechanism
Bactericidal; irreversible inhibition of initiation
complex through binding of the 30S subunit.
Can cause misreading of mRNA. Also block
translocation. Require O2 for uptake; therefore
ineffective against anaerobes
Aminoglycosides
Clinical Use
Severe gram ⊝ rod infections. Synergistic with
β-lactam antibiotics.
Neomycin for bowel surgery.
Aminoglycosides
Adverse Effects
Nephrotoxicity, Neuromuscular blockade
(absolute contraindication with myasthenia
gravis), Ototoxicity (especially with loop
diuretics), Teratogenicity.
Aminoglycosides
Mechanism of Resistance
Bacterial transferase enzymes inactivate the
drug by acetylation, phosphorylation, or
adenylation.
Aminoglycosides
Examples
Gentamicin, Neomycin, Amikacin,
Tobramycin, Streptomycin.
“Mean” (aminoglycoside) GNATS caNNOT
kill anaerobes
Nephrotoxicity, Neuromuscular blockade
(absolute contraindication with myasthenia
gravis), Ototoxicity (especially with loop
diuretics), Teratogenicity
Tetracycline
Mechanism
Bacteriostatic; bind to 30S and prevent attachment of aminoacyl-tRNA. Limited CNS penetration.
Doxycycline is fecally eliminated and can be used in patients with renal failure. Do not take
tetracyclines with milk (Ca2+), antacids (eg, Ca2+ or Mg2+), or iron-containing preparations
because divalent cations inhibit drugs’ absorption in the gut.
Tetracycline
Clinical Use
Borrelia burgdorferi, M pneumoniae. Drugs’ ability to accumulate intracellularly makes them very
effective against Rickettsia and Chlamydia. Also used to treat acne. Doxycycline effective against
community-acquired MRSA
Tetracycline
Adverse effects
GI distress, discoloration of teeth and inhibition of bone growth in children, photosensitivity.
Contraindicated in pregnancy
Tetracycline
Mechanism of Resistance
decrease uptake or increase efflux out of bacterial cells by plasmid-encoded transport pumps.
Tigecycline
Mechanism
Tetracycline derivative. Binds to 30S, inhibiting protein synthesis. Generally bacteriostatic.
Tigecycline
Clinical Use
Broad-spectrum anaerobic, gram ⊝, and gram ⊕ coverage. Multidrug-resistant organisms (MRSA,
VRE) or infections requiring deep tissue penetration
Tigecycline
Adverse Effects
GI symptoms: nausea, vomiting
Chloramphenicol
Mechanism
Blocks peptidyltransferase at 50S ribosomal subunit. Bacteriostatic.
Chloramphenicol
Clinical Use
Meningitis (Haemophilus influenzae, Neisseria meningitidis, Streptococcus pneumoniae) and
rickettsial diseases (eg, Rocky Mountain spotted fever [Rickettsia rickettsii]).
Limited use due to toxicity but often still used in developing countries because of low cost.
Chloramphenicol
Adverse effects
Anemia (dose dependent), aplastic anemia (dose independent), gray baby syndrome (in premature
infants because they lack liver UDP-glucuronosyltransferase)
Chloramphenicol
MECHANISM OF RESISTANCE
Plasmid-encoded acetyltransferase inactivates the drug
Clindamycin
Mechanism
Blocks peptide transfer (translocation) at 50S
ribosomal subunit. Bacteriostatic.
Clindamycin
Clinical Use
Anaerobic infections (eg, Bacteroides spp.,
Clostridium perfringens) in aspiration
pneumonia, lung abscesses, and oral
infections. Also effective against invasive
group A streptococcal infection.
Treats anaerobic infections above the diaphragm
vs metronidazole (anaerobic infections below
diaphragm)
Clindamycin
Adverse Effects
Pseudomembranous colitis (C difficile overgrowth), fever, diarrhea.
Linezolid
Mechanism
Inhibits protein synthesis by binding to 50S subunit and preventing formation of the initiation
complex
Linezolid
Clinical Use
Gram ⊕ species including MRSA and VRE.
Linezolid
Adverse Effects
Bone marrow suppression (especially thrombocytopenia), peripheral neuropathy, serotonin
syndrome (due to partial MAO inhibition)
Linezolid
Mechanism of Resistance
Point mutation of ribosomal RNA
Macrolides
Examples
Azithromycin, clarithromycin, erythromycin
Macrolides
Mechanism
Inhibit protein synthesis by blocking translocation (“macroslides”); bind to the 23S rRNA of the
50S ribosomal subunit. Bacteriostatic
Macrolides
Clinical Use
Atypical pneumonias (Mycoplasma, Chlamydia, Legionella), STIs (Chlamydia), gram ⊕ cocci (streptococcal infections in patients allergic to penicillin), and B pertussis.
Macrolides
Adverse Effects
MACRO: Gastrointestinal Motility issues, Arrhythmia caused by prolonged QT interval, acute
Cholestatic hepatitis, Rash, eOsinophilia. Increases serum concentration of theophylline, oral
anticoagulants. Clarithromycin and erythromycin inhibit cytochrome P-450
Macrolides
Mechanism of Resistance
Methylation of 23S rRNA-binding site prevents binding of drug
Polymyxins
EXAMPLE
Colistin (polymyxin E), polymyxin B
Polymyxins
Mechanism
Cation polypeptides that bind to phospholipids on cell membrane of gram ⊝ bacteria. Disrupt cell
membrane integrity leakage of cellular components cell death
Polymyxins
Clinical Use
Salvage therapy for multidrug-resistant gram ⊝ bacteria (eg, P aeruginosa, E coli, K pneumoniae).
Polymyxin B is a component of a triple antibiotic ointment used for superficial skin infections.
Polymyxins
Adverse Effects
Nephrotoxicity, neurotoxicity (eg, slurred speech, weakness, paresthesias), respiratory failure.
Sulfonamide
Mechanism
Inhibit dihydropteroate synthase, thus inhibiting
folate synthesis. Bacteriostatic (bactericidal
when combined with trimethoprim).
Sulfonamide
Clinical Use
Gram ⊕, gram ⊝, Nocardia. TMP-SMX for
simple UTI
Sulfonamide
Adverse Effects
Hypersensitivity reactions, hemolysis if G6PD
deficient, nephrotoxicity (tubulointerstitial
nephritis), photosensitivity, Stevens-Johnson
syndrome, kernicterus in infants, displace
other drugs from albumin (eg, warfarin)
Sulfonamide
Mechanism of Resistance
Altered enzyme (bacterial dihydropteroate synthase), uptake, or PABA synthesis.
Sulfonamide
Examples
Sulfamethoxazole (SMX), sulfisoxazole,
sulfadiazine
Trimethoprim
Mechanism
Inhibits bacterial dihydrofolate reductase.
Bacteriostatic
Trimethoprim
Clinical Use
Used in combination with sulfonamides
(trimethoprim-sulfamethoxazole [TMPSMX]), causing sequential block of folate
synthesis. Combination used for UTIs,
Shigella, Salmonella, Pneumocystis jirovecii
pneumonia treatment and prophylaxis,
toxoplasmosis prophylaxis.
Trimethoprim
Adverse Effects
Hyperkalemia (high doses), megaloblastic
anemia, leukopenia, granulocytopenia, which
may be avoided with coadministration of
leucovorin (folinic acid).
TMP Treats Bone Marrow
Poorly.
Fluroquinolones
Examples
Ciprofloxacin, enoxacin, norfloxacin, ofloxacin; respiratory fluoroquinolones—gemifloxacin,
levofloxacin, moxifloxacin.
Fluroquinolones
Mechanism
Inhibit prokaryotic enzymes topoisomerase
II (DNA gyrase) and topoisomerase IV.
Bactericidal. Must not be taken with antacids
Fluroquinolones
Clinical Use
Gram ⊝ rods of urinary and GI tracts (including
Pseudomonas), some gram ⊕ organisms, otitis
externa.
Fluroquinolones
Adverse Effects
GI upset, superinfections, skin rashes,
headache, dizziness. Less commonly, can
cause leg cramps and myalgias.
Contraindicated in pregnant women, nursing
mothers, and children < 18 years old due
to possible damage to cartilage. Some may
prolong QT interval.
May cause tendonitis or tendon rupture in
people > 60 years old and in patients taking
prednisone. Ciprofloxacin inhibits cytochrome
P-450.
Fluoroquinolones hurt attachments to your
bones
Fluroquinolones
Mechanism of Resistance
Chromosome-encoded mutation in DNA
gyrase, plasmid-mediated resistance, efflux
pumps
Daptomycin
Mechanism
Lipopeptide that disrupts cell membranes of
gram ⊕ cocci by creating transmembrane
channels.
Daptomycin
Clinical Use
S aureus skin infections (especially MRSA),
bacteremia, endocarditis, VRE.
Not used for pneumonia (avidly binds to and is
inactivated by surfactant). “Daptomyskin” is
used for skin infections
Daptomycin
Adverse effects
Myopathy, rhabdomyolysis.
Metronidazole
Mechanism
Forms toxic free radical metabolites in the
bacterial cell that damage DNA. Bactericidal,
antiprotozoal.
Metronidazole
Clinical Use
Treats Giardia, Entamoeba, Trichomonas,
Gardnerella vaginalis, Anaerobes (Bacteroides,
C difficile). Can be used in place of amoxicillin
in H pylori “triple therapy” in case of penicillin
allergy.
GET GAP on the Metro with metronidazole!
Treats anaerobic infection below the diaphragm
vs clindamycin (anaerobic infections above
diaphragm)
Metronidazole
Adverse Effects
Disulfiram-like reaction (severe flushing,
tachycardia, hypotension) with alcohol;
headache, metallic taste.
