Lecture 1 - Clinically relevant organisms & Penicillins Flashcards
For antibiotic to work….
- Enter bacterial cell
- reach its site of action
- bind to target that is involved in essential bacteria function
- significantly impair that function
Gram + Peptidoglycan layer is….
thick
Gram - Peptidoglycan layer is….
thin
have some other layers too on outer & inner sides
Enzymes vital for cell wall synthesis, cell shape, and structural integrity are…
Penicillin binding proteins
Gram - structure
Outer membrane (contains LPS, porins)
Periplasmic space = between inner/outer membrane (location of beta-lactamases)
Gram + color
purple
Gram - color
pink
Gram +, Aerobic, Cocci, Clusters, Coagulase +
Staphylococcus aureus
Gram +, Aerobic, Cocci, Clusters, Coagulase -
Other Staphylococcus species
- epidermis
- hominis
- haemolyticus
- capitus
- saprophyticus
Gram +, Aerobic, Pairs & Chains
Streptococcus spp.
Enterococcus spp.
Gram +, Aerobic, Rods
Listeria
Nocardia
Gram +, Anaerobic, Cocci
Peptostreptococcus
Gram +, Anaerobic, Rods
Clostridium spp. (spore-forming)
Propionibacterium
Actinomyces
Gram -, Aerobic, Rods, Lactose-fermenting
Enterobacteriaceae family (gut bacteria)
- Escherichia coli
- Klebsiella pneumoniae
- Enterobacter spp.
- Proteus mirabillis
- Salmonella spp.
Gram -, Aerobic, Cocci
Neisseria meningitidis
Neisseria gonorrhoeae
Moraxella catarrhalis
Gram -, Aerobic, Rods, Non-lactose fermenting
Non-enterobacteriaceae (usually nosocomial pathogens)
- Pseudomonas aeruginosa
- Acinetobacter baumannii
- Stenotrophomonas maltophilia
Gram -, Anaerobic, Rods (Bacilli)
Bacteroides spp.
Prevotella
Fusbacterium
Clinically important Atypical Organisms
Chlyamydia spp.
Mycoplasma spp.
Legionella spp.
Chlyamydia spp.
C. pneumonia
C. trachomatis
Mycoplasma spp.
M. pneumonia
M. genitalium
Legionella spp.
L. pneumophilia
4 Classes of Beta-Lactams
Penicllins
Cephalosporins
Carbapenems
Monobactam
Natural Penicillins
Penicillin G = IV
Benzathine Penicillin = IM
Penicillin V Potassium = PO
Natural Penicillins MOA
- Bind to penicillin binding proteins
2. Inhibit cross-linking of peptidoglycan in cell wall
Natural Penicillins MOR
- Beta-lactamase enzymes destroy abx (Gram -)
- Failure to penetrate outer membrane n reach site ( Gram - )
- Pumped out of cell via pump ( Gram - )
- Alteration of binding site ( Gram + )
Natural Penicillins Spectrum of Activity (Gram +)
Pen G = good v E. faecalis
Pen VK = not good v E. Faecalis
Limited/no activity vs S. aureus
** Treatment of choice for susceptible Strep spp.**
Natural Penicillins Spectrum of Activity (Gram - )
Minimal activity
some activity against susceptible Neisseria meningitidis
No activity for Atypical
Natural Penicillins Spectrum of Activity (Anaerobes)
Good against Gram + anaerobes (oral flora)
- Actinomyces spp.
- Peptostreptococci
- Propionibacterium acnes
** Txm of choice against Clostridium perfringens **
Limited activity Gram - anaerobes due to resistance
Natural Penicillins Spectrum of Activity (other)
** Txm of choice for Syphillis **
Spirochete, Treponema pallidum
If severe drug allergy, can use alternative agent for non-CNS disease
If neuropathy/ocular-syphilis, will desensitize to Penicillin and give
Natural Penicillins M & E
- substrates of OTA 1/3
- Poor pen across BBB
- 1/2 life in normal renal function = 30-60min, q4h or continuous IV
Excreted in urine, mostly unchanged…req renal adjustment
Natural Penicillins ADE
CNS, seizures at high doses
Hematologic = neutropenia
Hypersensitivity
Renal - AIN, Renal tubular disease
Natural Penicillins Drug Interactions
Drugs that interact w/ OTA 1/3 (Pretomanid, Teriflunomide, Fexinidazole)
Probenecid, inc plasma lvls and used to extend 1/2 life
Penicillinase-resistant Penicillins
Nafcillin (IV)
Oxacillin (IV)
Dicloxacillin (PO)
Penicillinase-resistant Penicillins MOA
Bind to PBPs
Inhibit cross-linking of peptidoglycan in cell wall
- Developed in response to penicillinase-producing S. aureus*
Acyl side chain prevented disruption of the B-lactam ring
Penicillinase-resistant Penicillins Spectrum of Activity Gram +
** Txm of choice MSSA **
no activity against E. faecalis, MRSA
GOOD activity against penicillin-susceptible Strep. spp.
Penicillinase-resistant Penicillins Spectrum of Activity (Gram -, Anaerobes, Atypical)
** No activity **
Penicillinase-resistant Penicillins M & E ( Nafcillin/Oxacillin)
Naficillin = moderat CYP3A4 inhib
Good for CNS infections, high CSF pen
90-95% protein bound
Short 1/2life, dose Q4h
No dose adjustment, N excreted through poop, O = urine/bile
Penicillinase-resistant Penicillins M & E (Dicloxacillin)
Rapid/ incomplete absorption affected by food
95-99% protein bound
Low CSF pen
45min 1/2 life = q6h
Excreted in poop/urine = no renal dose adjustment
Penicillinase-resistant Penicillins ADE
GI (dicloxacillin) Hepatic (N + O) Hematologic (N + O) Renal (N + O) Local (N + O) inj site
Penicillinase-resistant Penicillins DI
Cyp3A4 substates will be effected by Nafcillin
- Antifungl azaleas, anti-epileptics, statins, transplant meds
Dicloxacilin
- Transplant meds… Sirolimus, tacrolimus, mycophenolate (CYP3A4)
- Carbamazepine = CYP3A4
- Fosphenytoin/ Phenytoin CYP2C19
- Omeprazole = CYP2C19
Decreases lvls of these meds
Aminopenicillins
Ampicillin (IV)
Amoxicillin (PO)
Aminopenicillins MOA
- Bind to PBS
2. Inhibit cross-linking peptidoglycan in cell wall
Aminopenicillins Spectrum of activity Gram +
** Txm of choice for E. Faecalis **
Limited/no activity against Staph aureus.
Same as penicillin against Strep spp., but broader
** Txm of choice for Listeria monocytogenes) **
Aminopenicillins Spectrum of activity Gram -
Limited activity overall
E.coli + P.mirabilis can be susceptible, especially in younger patients w/o prior exposure
H.influenzae covered if B-lactamase negative
Atypical = no activity
Aminopenicillins Spectrum of activity Anaerobes
Good against Gram + anaerobes (oral flora)
- Actinomyces spp
- Peptostreptococci
- Propionibacterium acnes
Limited agents Gram - due to resistance
Aminopenicillins M & E (Ampicillin)
Distributes well into bile, pens CSF w/ inflamed meninges
10-18% Protein bound
1/2 life 1-2hrs, extended up to 20hrs
excreted in urine unchanged ~90%, renal adjustment req
Aminopenicillins M & E ( Amoxicillin)
widely distributed
20% protein bound
1/2 life = 2hrs
excreted in urine unchanged, ~60%, renal adjustment req
Aminopenicillins ADE
GI = Amoxicillin
Dermatologic = Ampicillin
Hematologic = Ampicillin
Renal (AIN) = Ampicillin
Aminopenicillins DI
no significant DI
Penicillin + Beta-lactamase inhibitors
Ampicillin/ subactam (IV)
Amoxicillin/clavulanate (PO)
Piperacillin/ tazobactam (IV)
Penicillin + Beta-lactamase inhibitors MOA
- Bind to PBPs
- Inhibit Cross-lining of peptidoglycan in cell wall
B-lactamase inhibitors have specific spectrums of activity and affinities for certain enzymes
Penicillin + Beta-lactamase inhibitors Spectrum of Activity Gram +
no activity against MRSA
Added activity against MSSA
Activity against Strep spp.
Amox / Clav & Amp/sulb are active against….
** Txm of choice for ***
H.influenza & M. catarrhalis (community acquired pneumonia)
P. multocida & Capnocytophaga species (animal bites)
susceptive E.coli, Klebsiella pneumoniae, P. mirabilis
Drug preferred in Acinetobacter baumannii is….
ampicillin/sulbactam due to sulbactam
Piperacillin/Tazobactam has more activity against…
all Gram -, including more resistant E.coli, Klebsiella, and Proteus spp.
active agents Pseudomonas aeruginosa**
Penicillin + Beta-lactamase inhibitors Spectrum of activity Anaerobes
Txm of choice against Gram + anaerobes causing oropharyngeal infections
- Actinomyces spp.
- Peptostreptococci
- P. acnes
Txm of choice agents Gram - anaerobes
Penicillin + Beta-lactamase inhibitors have Atypical coverage?
nah
Sulbactam M & E
Widely distributed
Protein bound 38%
1/2 life 1-1.3hrs
Excretion urine w/in 8hrs, dose adjusted renal
Clavulanic acid M & E
Protein bound
1/2 life 1hr
Urine excretion, dose adjusted renal
Piperacillin/tazobactam M & E
widely distributed
excreted in urine, dose adjusted renal
Penicillin + Beta-lactamase inhibitors ADE
GI (amoxicillin/Clav) Dermatologic Hematologic Hepatic Renal
Penicillin + Beta-lactamase inhibitors DI
Piperacillin/tazobactam + Vanco = increase risk of nephrotoxicity
If want to cover Strep & E. coli then give….
Piperacillin & Tazobactam
