Antibiotics 1 Flashcards
Describe gram positive bacterial structure
Cytoplasmic membrane –> Thick peptidoglycan layer - has penicillin binding proteins (PBPs)
Describe gram negative bacterial structure
Cytoplasmic membrane –> thin peptidoglycan layer - has PBPs –> periplasmic space - location of beta lactamases (only in gram -ve) –> outer membrane - has porins and LPS
Clinically important gram positive aerobic organisms - coccus and occuring in clusters
Coagulase positive - Staphylococcus aureus
Coagulase negative - Staphylococcus spp. –> epidermidis, hominis, haemolyticus capitus, saprophyticus
Clinically important gram positive aerobic organisms - coccus and occuring in pairs/chains
Streptococcus spp. and enterococcus spp.
Clinically important gram positive aerobic organisms - Rods
Listeria and Nocardia
Clinically important gram positive anaerobic organisms - coccus
Peptostreptococcus
Clinically important gram positive anaerobic organisms - Rods
Clostridium spp.
Propionibacterium
Actinomyces
Clinically important gram negative aerobic organisms - rods and Lactose fermenting
Enterobacteriaceae family
E.coli, Klebsiella pneumoniae, enterobacter spp., proteus mirabilis, salmonella spp.
Clinically important gram negative aerobic organisms - Rods and non - Lactose fermenting
Non-enterobacteriaceae - usually nasocomial pathogens
Pseudomonas aeruginosa, Actinobacter baumannii, Stenotrophomonas maltophilia
Clinically important gram negative aerobic organisms - coccus
Neisseria meningitidis, Neisseria gonorrhea, Moraxella catarrhalis
Clinically important gram negative anaerobic organisms - rods
Bacteroides, Prevotella, Fusobacterium
Clinically important Atypical organisms
Chlamydia spp. – C. pneumoniae, C. trachomatis
Mycoplasma spp. – M. pneumoniae, M. genitalium
Legionella spp. - L. pneumophilia
Name 3 drugs that are natural penicillins
Pen VK (PO) Penicillin G (IV) Benzathine Penicillin (IM)
Natural penicillin MOA
Binds to PBPs
Inhibits cross-linking of peptidoglycan layer in the cell wall which causes autolysis and cell death
Natural penicillin mechanism or resistance - gram negative
- efflux pump
- beta lactamase enzyme –> destruction of antibiotic
- failure to penetrate outer membrane of bacteria (porins) and reach binding site
Natural penicillin mechanism or resistance - gram positive
Alteration of binding site
Natural penicillin spectrum of activity in gram positive bacteria
Good activity against enterococcus faecalis
Limited to no activity against S. aureus
Natural penicillin is a tx of choice in?
Gram positive bacteria
Streptococcus spp.
Group A - S. pyogenes –> skin flora - cellulitis
Group B - S. agalactiae –> skin and vaginal flora
Group C,F,G - Streptococcus –> skin flora - cellulitis
S. pneumoniae –> respiratory flora - pneumonia
Viridans streptococcus –> oral flora - dental infxn, endocarditis
Natural penicillin has activity against which gram negative bacteria?
Neisseria meningitidis
Natural penicillin: spectrum of activity in gram positive anaerobes
Good activity against gram positive anaerobes in oral flora
- Actinomyces spp.
- Peptostreptococci
- Propionibacterium
Natural penicillin
Tx of choice against which anaerobic bacteria?
Clostridium perfringens - anaerobe that causes gas gangrene necrotizing fascitis and clostridial toxic shock
Does natural penicillin have activity against gram negative anaerobes?
Limited activity due to resistance
- Bacteroides considered resistant
- Prevotella and fusobacterium have high likelihood of producing beta-lactamases and being resistant
Natural penicillin - activity against other organisms
Spirochete - treponema pallidum - causes STI –> syphilis
Natural penicillin - metabolism and elimination (humans)
Substrate of organic anion transporter (OAT) 1/3
- drugs that effect OAT 1/3 transporters effect concentrations
Poor penetration against BBB but with inflamed meningitis, does exceed MIC of susceptible organisms with new breakpoints (streptococcus)
T 1/2: 30-60 mins –> needs frequent dosing
- dose: 2 - 3 million units every 4 hrs –> max dose = 24mill U/day divided in q4 dosing
- continuous infusion to optimize Pk-Pd parameters given its short T1/2
Excreted in urine, mostly unchanged –> requires dose adjustment in renal dysfunction
Natural penicillins adverse effects
CNS - seizures at high doses (40-100 million u/day)
Hematologic - neutropenia
Hypersensitivity - ranges from rash/hives to anaphylaxis, serum sickness can occur but is uncommon
Renal - AIN, renal tubular disease
Natural penicillins drug interactions
Drugs that interact with OAT 1/3 - pretomanid, teriflunomide, fexinidazole
Probenecid - increase plasma levels of penicillin by competitively inhibiting renal tubular secretion
- used as alternative dosing strategy to extend T1/2 and increase drug concentrations
Name penicillinase resistant penicillins (PRP)
Nafcillin (IV)
Oxacillin (IV)
Dicloxacillin (PO)
PRP MOA
- bind to PBPs
- inhibit cross-linking of peptidoglycan in the cell wall –> autolysis –> cell death
PRP has no activity against which gram positive organism?
Enterococcus faecalis
PRP is a tx of choice for?
Staph. aureus (MSSA)
- Skin and soft tissue infxn due to MSSA (abscess or cellulitis)
- Osteomyelitis, septic arthritis, or prosthetic joint infxn
- Bacteremia or infective endocarditis
NO activity against MRSA
Good activity against penicillin susceptible streptococcus spp.
PRP activity in other organisms
Gram negative, anaerobes, atypical –> no activity
PRP - Metabolism and elimination
Nafcillin/Oxacillin (IV)
- moderate CYP3A4 inducer
- widely distributed with increased CSF penetration with meningeal information
- 90-95% protein bound
- T1/2 - 20 to 60 mins –> dosed q4h
- excreted in feces (nafcillin) and bile/urine (oxacillin) –> no renal dose adj needed
Dicloxacillin
- moderate CYP2C19, weak CYP2C9 and weak CYP3A4 inducer
- rapid and incomplete absorption that is affected by food
- low CSF-penetration
- 95-99% protein bound
- 45 min half life –> dosed q6h
- excreted in feces and urine as unchanged drug –> no renal dose adj needed.
PRP adverse effects
GI (dicloxacillin) - abdominal pain, diarrhea, nausea
Hepatic (nafcillin/oxacillin) - increased serum transaminases, hepatotoxicity
Hematologic (n/o) - neutropenia
Renal (n/o) - AIN, renal tubular disease
local (n/o) - injection site rxn, phlebitis
PRP drug interactions
CYP3A4 substrates will be affacted by Nafcillin and should be monitored
- antifungal azoles, anti-epileptics, statins, transplant meds etc.
Dicloxacillin:
- transplant meds (sirolimus, tacrolimus, mycophenolate) CYP3A4
- carbamazepine 3A4
- Fosphenytoin/phenytoin CYP2C19
- Omeprazole CYP2C19
Aminopenicillins
Ampicillin (IV)
Amoxicillin (PO)
Aminopenicillins - MOA
Bind to PBPs
Inhibit cross linking of peptidoglycan in the cell wall –> autolysis –> cell death
Aminopenicillins - spectrum of activity
Gram positive: tx of choice for enterococcus faecalis
- Intra abdominal infxn
- Polymicrobial diabetic foot infections
- Bacteremia and infective endocarditis (ampicillin + gentamicin)
Does Aminopenicillin work against S. aureus?
No
Aminopenicillin is a tx of choice for?
Listeria monocytogenes
- neonatal sepsis
- Bacteremia and meningitis (ampicillin + gentamicin)
Ampicillin activity in gram negatives
- limited activity overall –> expanded activity compared to natural penicillins
- E.coli and P. mirabilis can be susceptible, especially in younger patients w/o prior abx exposure
- H. influenzae is covered if beta-lactamases negative (otitis media or sinusitis)
Atypical - no activity
Aminopenicillin activity in gram + anaerobes
- good activity in gram positive anaerobes - oral flora –> actinomyces spp., peptostreptococci, propionibacterium acnes (Cutibacterium acnes)
Aminopenicllin act in gram negative anaerobes
- limited activity against gram negative anaerobes due to resistance
- Bacteroides fragilis is considered resistant
- Prevotella spp. and Fusobacterium necrophorum have high likelihood of producing beta-lactamases and being resistant
