Penicillins Flashcards
Beta Lactam similarities
Hypersensitivity reactions Mild rash Drug fever Acute interstitial nephritis (AIN) Anaphylaxis Similarities between side chains may be responsible for cross-sensitivity
Cause seizures at high doses
Other neurologic effects
Accumulation to toxic levels in renal insufficiency: need to adjust dose for renal function
MOA: inhibit transpeptidases (penicillin binding proteins) in bacterial cell wall
Inhibit cross linking of peptidoglycan in the cell wall, leading to autolysis and cell death
Lack activity against atypical organisms
Mycoplasma pneumoniae
Chlamydophila pneumoniae
Lack MRSA activity (except ceftaroline)
Penicillins similarities
Very short half lives
< 2 hours
Half life prolonged in renal dysfunction
If IgE mediated hypersensitivity reaction, avoid other penicillins
If not severe, may use cephalosporins or carbapenems
Relatively poorly absorbed
Can lead to diarrhea in oral therapy
In IV to PO switch, likely will be substantial decrease in amount of active drug in body
Natural Penicillins
Penicillin G
Penicillin V
Discovered by Sir Alexander Fleming in 1929
Staphylococci almost universally resistant due to production of penicillinases
Natural Penicillins Spectrum
Good
Treponema pallidum
Most streptococci, including Streptococcus pneumoniae
Moderate
Enterococci
Poor
Almost everything else
Natural Penicillins Important Facts
Very short half life
Dose frequency or given by continuous infusion
IM long acting depot formulations available (procaine, benzathine); giving them IV can be fatal
V is oral form
G is IV
G remains drug of choice for syphilis
Poor empiric choice for most infections due to resistance
IV penicillin breakpoint for S pneumoniae was lowered for the percent of isolates considered resistant
Only applies to IV penicillin
Does not apply to CNS infections; old breakpoint remain in effect
Natural Penicillins What They’re Good For
Syphilis, especially neurosyphilis
Pharyngitis or Endocarditis in susceptible streptococcal infection
Antistaphylococcal Penicillins
Nafcillin
Oxacillin
Dicloxacillin
Methacillin
Cloxacillin
Did not add to poor Gram- activity of natural penicillins
Possibly higher incidence of AIN
Antistaphylococcal Penicillins Spectrum
Good
MSSA
Streptococci
Poor GNRs Enterococci Anaerobes MRSA
Antistaphylococcal Penicillins Important Facts
Short half life; must be dosed frequently
Cause phlebitis; use 1G cephalosporin if phlebitis; easier to administer and better tolerated
Eliminated in large part by liver
Do not need dose adjustment in renal dysfunction
Standard resistance tests usually done with oxacillin or cefoxitin
Beta Lactams kill staph more quickly than vancomycin
In serious MSSA infections without serious beta lactam allergy, use antistaphylococcal penicillins or 1G over vancomycin
Good for infections caused by MSSA
Endocarditis
Skin and soft tissue infections
Aminopenicillins
Amoxicillin
Ampicillin
More water soluble
Pass through porin channels in the cell wall of some Gram- organisms
Susceptible to betalactamases
Rarely effective agains staph
Not useful against pseudomonas
High incidence of diarrhea when given orally
Aminopenicillins Spectrum
Good
Streptococci
Enterococci
Moderate
Enteric GNR
Haemophilus
Poor
Staph
Anaerobes
Pseudomonas
Aminopenicillins Important Facts
Amoxicillin is more bioavailable, better tolerated, and administered less frequently than oral ampicillin
Use Ampicillin for IV
Ampicillin is drug of choice for susceptible enterococci
Faecalis is almost always susceptible
Faecium is often resistant
Alternative regimen for UTIs in pregnant women
Pregnancy category B
Eliminated renally
Resistance in E. coli is very high
Perform susceptibility testing and follow up cultures in pregnant women with UTIs because even asymptomatic bacteruria is dangerous
Good for infections caused by susceptible GNRs, enterococci, and streptococci
Resistance among GNRs is prevalent, so used infrequently in complicated nosocomial infections
Amoxicillin frequently prescribed for infections of upper respiratory tract including Streptococcal pharyngitis (strep throat) Otitis media (ear infection)
Ampicillin (or other beta lactam) must be combined with an aminoglycoside to achieve bactericidal activity against enterococci
Do this in serious infections like endocarditis
Antipseudomonal Penicillins
Piperacillin
Ticarcillin
Active against P. aeruginosa and other more drug resistant GNRs
Not active against staph due to betalactamases; some GNRs also produce them
Rarely used by themselves
Antipseudomonal Penicillins Spectrum
Good
P. aeruginosa
Streptococci
Enterococci
Moderate
enteric GNRs
Haemophilus
Poor
Staphylococci
Anaerobes
Antipseudomonal Penicillins Important Facts
Retain Gram+ activity of penicillin
Nowadays used with betalactamase inhibitor
Penicillin / Betalactamase Inhibitor Combinations
Ampicillin / sulbactam
Amoxicillin / Clavulanate
Piperacillin / Tazobactam
Inhibitors mimic the structure of beta Lactams but have little antimicrobial activity; bind to betalactamases irreversibly
Inhibitors restore activity to the beta lactam, not add to it
Penicillin / Betalactamase Inhibitor Combinations Spectrum
Good MSSA Streptococci Enterococci Many anaerobes Enteric GNRs P. aeruginosa (only P/T)
Moderate
GNRs with advanced betalactamases
Poor
MRSA
Extended spectrum betalactamase producing (ESBL) GNRs
Penicillin / Betalactamase Inhibitor Combinations Important Facts
Amox/Clav available orally
Higher doses associated with more diarrhea
Clavulanate is 125mg in all forms
Inhibitors not active against all betalactamases
New ases are being discovered and becoming more prevalent
Inhibitors are not available on their own
Sulbactam has useful activity against Acinetobacter baumannii (highly drug resistant GNR that causes nosocomial infections)
Can use high doses of Amp/Sul
Clav more potent than Sul
Need to give higher doses of Sul to account for this
Both drugs have nearly identical spectra
Low concentration of Sul may cause differences in susceptibility testing
Penicillin / Betalactamase Inhibitor Combinations good for
Empiric therapy of nosocomial infections
Nosocomial pneumonia (not aminopenicillin combinations)
Mixed infections (intraabdominal, diabetic ulcers, aspiration pneumonia
Amox/Clav for upper and lower respiratory infections with betalactamase producing organism
Useful for UTI if other drugs resistant (do not give for short 3 day course like FQ or Bactrim)
Good choice for empiric therapy but narrow coverage once organism identified
