Antibiotics Flashcards
Mechanism of Action
Penicillins
beta-lactam antibiotic
binds to penicillin binding proteins:
- Inhibit transpeptidase cell wall cross link
- Activation autolysin
weakens the cell wall
results in bacterial cell lysis
SE of Penicillins
- CNS toxicity (hallucinations, delusions, seizures)
Renal dose adjustment required - Anaphylaxis 7/100 people
- GI upset
- Blood dyscaria
- phlebitis if IV
Penicillins and pregnancy
safest antibiotic
PBPs only exist in bacteria
Safe in pregnancy, infancy, childhood, old age
Amoxicillin safe in breast feeding
First line treatment for pregnancy UTIs
Penicillin G and V Coverage
Gram positive bacteria
Anaerobic Spirochettes (Treponem pallidum - syphillus)
Penicillin is used to treat…
Meningitis - streptococcus pneumoniae
Group A strep infections (GAS)
Syphillus
MOA and SE of Cephalosporins
MOA:
beta-lactam antibiotic
weaken cell wall
bind PBP
*same as penicillins
- CNS toxicity (renal dose adjustment required)
- Disulfram reaction (acetaldehyde build up if you drink)
- C. diff infections (during and post)
- Bleeding (inhibits Vitamin K coagulation factor synthesis)
Which Cephalosporins cross the BBB
Third generation
- Cefixime, Cefotaxime, Ceftazidime, Ceftriaxone
Fourth Generation
- Cefepime
Fifth Generation (USA only)
- Ceftaroline
Which Cephalosporins cover pseudomonas infections?
Third generation (ceftazidime)
Fourth generation
(cefepime)
Which cephalosporins cover MRSA infections
Fifth generation
Ceftaroline
First generation Cephalosporins
Cephalexin
Cefazolin
Cefadroxil
*cross reactivity with penicillin 1%
contraindicated with penicillin anaphylaxis
Second generation cephalosporins
Cefaclor
cefuroxime
cefoxitin
cefprozil
cefotetan
Third generation cephalosporins
Cefotaxime
Ceftriaxone
ceftazidime
Cefixime
Fourth and fifth generation cephalosporins
Cefepime
ceftaroline
Penicillins
Penicillin G
Penicillin V
Cloxicillin
Amoxicillin/Clavulanate
Ampicillin/Sulbactam
Pipperacillin/tazobactam
Carbapenems MOA and route
beta-lactam antibiotic
bind to PBPs 1. transpeptidase inhibitor 2. autolysin disinhibitor
Imipenem
Meropenem
Ertapenem
*IV Only
Prescribing considerations and contraindications of carbapenems
IV only
gram positive, negative, pseudomonas infections - broad spectrum, empric
Do not give alone to treat pseudomonas to avoid resistance (prescribe with pipperacillin/tazobactam and/or aminoglycosides)
Contraindicated with VPA (seizures)
Renal dose adjustment
1% cross reactivity with penicillins
Super infections
Carbapenem SE
N/V/D
superinfections
hypersensitivity
cross reactivity with penicillins 1%
seizures with VPA
Mechanism of action carbapenems
- inhibition transpeptidase
- activation autolysin
Disrupt cell wall synthesis resulting in bacterial lysis
Only active against actively growing and dividing bacteria
Resistant against beta-lactamases - do not need to prescribe sulbactam, clavulanate, or tazobactam
Mechanism of action cephalosporins
- Inhibition transpeptidase
- Activation autolysin
Disrupt cell wall synthesis resulting in lysis of bacteria
*beta-lactam antibiotic
same as penicillins and carbapenems
3rd and 4th resistant against beta lactamases, BBB penetration, and pseudomonas coverage
5th generation MRSA coverage
Cephalosporins SE, and pregnancy
SE:
N/V/D, c.diff
disulfram reaction
neuerotoxicity
cross reaction with penicillins 1% first generaitons
bleeding risk
safe in pregnancy
safe in breastfeeding
3rd generations used to treat infants
dose reduction in kidney disease
Vancomycin
Mechanism of Action
Disrupts cell wall synthesis by binding to cell wall precursors - peptidoglycans
Results in cell lysis
Not absorbed systemically through PO administration - too big
Vancomycin
SE
Ototoxic - high pitch, low pitch, blance
Nephrotoxic - casts, proteinuria
Blood trough level (low trough)
TDM required
Monitor BUN, creatinine clearance
Pathophysiology of
C. Difficile
Antibiotics kill microbiome
Overgrowth of bad bacteria such as C. Diff
Toxin A and B produced and damage colon
Inflammation, pus, watery diarrhea
Gram positive, spore forming bacteria
First line treatment: Metronidazole IV and Vancomycin PO
Vancomycin and Pregnancy
PO vancomycin does not get absorbed systemically (too big, hydrophilic), safe in pregnancy and breast feeding
Vancomycin Coverage
Gram positive bacteria and MRSA
MRSA (gram positive cocci in clusters) - methicillin resistance, PBP different shape
C. difficile (gram positive bacilli)
Fosfomycin Coverage
Gram positive,
Gram negative,
Pseudomonas
*Cannot be used to treat pyelonephritis/renal infections (systemic) - too big to be absorbed
Fosfomycin mechanism of action
Prevents production of the building blocks of the cell wall peptidoglycan layer
Disrupts cell wall synthesis
Penicillin and Cephalosporin Drug interactions
Oral contraceptives
Probenicid (increases level)
Synergistic with aminoglycosides
Antibiotics that inhibit 50S Ribosome Subunit
Macrolides (Azithromycin, Erythromycin, Clarithromycin)
Licosamides (Clindamycin, linomycin)
Linezolid
Macrolide SE
- Prolonged QT interval
- Ototoxic
- Diarrhea (Motilin receptors) and metallic taste in mouth
- Elevated LFTs (biliary clearance)
- Renal dose adjustment needed
Macrolide Drug interactions
Inhibition CYP450
Synergistic with beta-lactam antibiotics
Macrolide coverage
Atypical infections (GERD, CAP, STIs)
Gram positive, gram negative (no pseudomonas coverage)
Erythromycin Drug Interactions
CYP3A4 metabolism
Cardiac death increases 6x when prescribed with CYP3A4 inhibitors
- CCB
- Azoles
- HIV protease inhibitors
- Anti-depressants
Inhibits CYP450 Enzyme, increasing level of
- warfarin
- theophylline
- carbamazepine
Macrolide mechanism of action
Inhibition 50S subunit on the ribosome
Bacteriostatic and bacteriocidal at higher concentrations
Licosamide antibiotics and mechanism of action
Clindamycin
Linomycin
Bacteriostatic and bacteriocidal
Inhibit 50S ribosomal subunit
Macrolides and Pregnancy
Safe in pregnancy however crosses the placenta
> 1 month of age
Do not breast feed
Clindamycin SE
- QT Interval prolonged
- LFT elevation
- renal dose adjustment
(similar to macrolide) - C. diff infection (4 -6 weeks post, fatal)
- Rash/hypersensitivity/SJS*
Clindamycin Coverage
MRSA
Gram positive
Anaerobes
Examples:
Gardenella Vaginalis
Clostridium
MRSA
Acne
Intra-abdominal infections and ulcers
Gangrene
Clindamycin and Pregnancy
Safe in pregnancy
Avoid breast feeding - secreted in breast milk
Drugs that CANNOT cross the BBB
- 1st and 2nd generation cephalosporins
- Clindamycin
- Macrolides
- Fluroquinolones
Mechanism of Action Linezolid
Binds to the 23S portion of the 50S ribosomal subunit and stop s protein synthesis
bacteriostatic
SE of linezolid
Myelosupression (monitor CBC weekly)
demyelination CNS
Hypertensive crisis
Serotonin Syndrome
Linezolid coverage
gram positive organisms
MRSA
V
Linezolid drug interactions
Do not prescribe with
- MAOI
- SSRI
- Sympatheticomimetics (methylphenidate, etc.)
Aminoglycosides
Gentamycin
Tobramycin
Streptomycin
Neomycin
Amikacin
*end in mycin
Aminoglycoside mechanism of action
bind to the 30S ribosomal subunit and
- prevent activation
- early termination of protein synthesis
- mis-reading of proteins, mutation
Bacteriostatic
Bacteriocidal - mutated proteins inserted into membrane and lysis results
Aminioglycoside SE and contraindications
Neurotoxic
Nephrotoxic
Ototoxic (hearing, and balance)
Teratogenic (do not use if pregnant)
Do not breast feed *lacking data
Aminoglycoside coverage
Pseudomonas
Gram negative bacteria
*no coverage for gram positive
*no coverage for anaerobes
* does not cross the BBB or GI (too positively charged)
IV form or IM form only
Aminoglycoside drug interactions
Caution with
- Nephrotoxic drugs
- ototoxic drugs
- perforated ear drum D/C
Synergistic with
- beta-lactam antibiotics or vancomycin
- do not mix in the same IV bag *precipitates out
Aminoglycoside monitoring
Peak and trough levels
*high trough is associated with high SE, want it as close to zero as possible
Tetracyclines
Tetracycline
doxycycline
minocycline
Tetracycline mechanism of action
Inhibits 30S ribosomal subunit
prevents synthesis of the protein / misread / early termination
Tetracycline contraindications
Children < 8 years
Pregnancy
Post-Partum women
Breastfeeding
Tetracycline SE
Deposition in bones (growth suppression)
Deposition in enamel (yellow/grey teeth) and hypoenamel
Hepatotoxic / Renal toxicity (higher in pregnant and post partum women)
GI upset
sunburn / photosensitivity
C. difficile infections
Tetracycline drug interactions
Increase levels of digoxin and warfarin
Cations decrease absorption, do not take with food (1 hour before, 2 hours after)
Tetracycline coverage
MRSA, Gram positive, some gram negative
*Used to treat peridontal, acne, and atypical infections (spotted fever, lyme disease, anthrax etc.)
Nitrofurantoin drugs
Nitrofurantoin
Macrobid
Nitrofurantoin Mechanism of Action
Binds to 30S ribosomal subunit and inhibits protein synthesis
Prodrug is activated by bacterial enzyme
Nitrofurantoin Coverage
Gram positive, gram negative
*Pseudomonas is resistant
Nitrofurantoin SE
Lungs
- inflammation lungs (dyspnea, infiltration) D/C
- Chronic lung fibrosis
Blood
- Agranulocytosis, thrombocytopenia, hemolytic anemia (newborn, G6PD deficiency)
NEUROTOXICITY
- demyelination of sensory and motor neurons
- chronic use
Heptatotoxicity
Birth defects
- Do not give in 38th week of pregnancy
- Do not breast feed
Nitrofurantoin contraindications
Pregnancy 38 weeks
Breastfeeding
Children < 1 month
G6PD Deficiency
*hemolytic anemia
Nitrofurantoin monitoring
CrCl > 50mL/min in order to reach the bladder
If < 50mL/min do not prescribe, it will not reach effective concentration
CBC
G6PD status
Lung function
Fosfomycin dosing
Concentration dependent killing
one dosage, high concentration, with lots of water
Fosfomycin monitoring
Requires CrCl > 50mL/min
*similar to Nitrofurantoin
Fluroquinolone antibiotics
Ciprofloxacin
Moxifloxacin
Levofloxacin
Fluroquinolone
Mechanism of Action
Inhibits DNA replication and cell division through 2 actions:
DNA topoisomerase inhibitor
- Cannot separate daughter strands during cell division
DNA gyrase inhibitor
- Supercoils DNA for replication (condenses DNA)
Fluroquinolone SE and Contraindications
Contraindications
- Pregnancy
- Infants/children
- Myasthenia gravis
- Caution - greater than 60 years, glucocorticoid use, transplants, renal disease (increased risk of tendon rupture)
SE
- Prolonged QT interval
- Tendon rupture
- Sunburn / phototoxicity
- CNS toxicity - seizures
- C. Diff infections
Fluroquinolone Coverage
Gram positive
Gram negative
Pseudomonas
*Neisseria gonorrhea is resistant
Fluroquinolone drug interactions
Cations decrease absorption
increase warfarin, theophylline and carbamazepine (CYP450 inhibitor)
Fluroquinolone monitoring
CrCl
high risk for CNS toxicity and tendon rupture if renal disease
Metronidazole mechanism of action
Prodrug activated by bacterial enzyme
Generates ROS which damage DNA
Concentration dependent killing
Metronidazole coverage
Anaerobes, protozoa
fusobacterium, gardenella vaginalis, trichomatis, C. difficile, etc.
Metronidazole SE and education
VRE
Carcinogenic in mice
GI upset
hepatotoxic (metabolism)
Disulfram reaction (do not drink)
Metronidazole contraindications
- alcohol
- caution in liver disease
Metronidazole in pregnancy and breast feeding
Can take while pregnant
Will result in bitter tasting breast milk
Sulfonamide SE
Rash
Phototoxicity
Hemolytic anemia (< 2 months, G6PD deficiency)
agranulocytosis, thrombocytopenia
kernicterus (displaces from bilirubin)
Renal toxicity - crystalizes
Sulfonamide Education
- do not breast feed (kernicterus, hemolytic anemia)
- drink 8-10 glasses of water a day
Sulfonamide drug interactions
Increases dose of
- hypoglycemics
- warfarin
- AEDs (phenytoin)
Sulfonamide Contraindications
- Sulfa allergy
- Pregnancy first / third trimester
- breast feedin
- infants < 2 months old
- G6PD deficiency
- Caution in elderly - more likely to have TEN, SJS, and neutropenia
Trimethoprim mechanism of action
inhibition of folate synthesis
unable to replicate DNA/RNA
SE of Trimethoprim
Megaloblastic anemia (more common pregnant, alcoholics)
hyperkalemia (worsened by ACE inhibitors, ARBs, potassium sparing diuretics)
Do not give in first and third trimester (Neural tube risk)
Trimethoprim contraindications
- folate deficiency
- pregnancy (first trimester - NTD)
- lactation
TMP/SMX monitoring
- CBC and WBC differential
- CrCl (reduce dose by 50% if CrCl < 30)
- Potassium
- Pregnancy stage
TMP/SMX ratio
1:5
