Penicillin V indication
Less active against gram -ve than PCN G
Gram +ve (except staph b/c beta lactamase)
Most anaerobes
DOC for strep throat
Penicillin V PK/PD
Acid stable
Oral version of PCN G
Ticarcillin, Carbenicillin, Piperacillin indication
TCP-takes care of pseudomonas
DOC for P. aeruginosa infections**
Effective agianst many gram -ve bacilli (better than other PCN’s)
Combine with a beta-Lactamase inhibitor**
Ticarcillin, Carbenicillin, Piperacillin PK/PD
useful in moderate to severe infections
Penicillin G (Benzathine, procaine) indication
Gram +ve
Except staph -> beta lactamase **
Gram -ve cocci (Neisseria)
Most anaerobes
DOC for syphilis (benzathine)
Strep (preventing rheumatic fever)
Pneumococci
Penicillin G (benzathine, procaine) PK/PD
Susceptible to beta lactamases
Procaine -> IM increasing resistances so decreased use; not IV due to toxicity
Benzathine -> IM, half life 3-4 weeks; prolongs life of penicillin G
Amoxicillin, Ampicillin indication
Extended spectrum -> some gram -ve activity
Susceptible to beta lactamase -> adminitser with beta lactamase inhibitor
***URT’s (H. flu & S. pneumo); UTI’s (E. coli), P. mirabilis, Salmonella, Shigella
“HELPSS kill enterococci”
Amoxicillin -> endocarditis prophylaxis during dental or respiratory tract procedures **
Ampicillin -> used in combination with aminoglycoside to treat Listeria and enterococci
Amoxicillin, Ampicillin PK/PD
Amoxicillin -> highest oral bioavailability
**Safe for children and pregnancy**
Ampicillin rash
Nafcillin adverse
Neutropenia
Oxacillin adverse
Hepatitis
Ticarcillin adverse
inhibits platelet function therefore increased bleeding time
Methicillin, Nafcillin, Oxacillin, Dicloxacillin indication
Anti staphylococcal
Beta lactamase resistance
Methicillin never used clinically (Causes AIN)
Inactive against MRSA/ORSA
DOC for staph endocarditis without a prosthetic valve
Nafcillin PK/PD
Has erratic oral absorption and is excreted in the bile
Beta lactamase inhibitors
Clavulanic acid
Sulbactam
Tazobactam
Calvulanic acid, Sulbactam, Tazobactam description
aka: penicillinase or cephalosporinase
Contain a beta lactam ring, but do not have significant antibacterial activity
Available only in fixed combinations with specific PCN’s
Bind and inhibit most beta lactamases
Penicillin mechanism
Bactericidal -> bind to PBP’s inhibiting the last step in peptidoglycan synthesis
PCN activates autolysin - bacterial enzymes which mediates cell lysis
Autolysin + lack of cell wall synthesis= death
Oral absorption impaired by food
Distribution: do not achieve sufficient levels in prostate and eye
CSF penetration is poor except in meningitis
Nafcillin, ampicillin, and piperacillin -> high levels in bile
Penicillin excretion
Primarily excreted in kidney except for
- Nafcillin -> bile (useful when patients have renal insufficiency**)
- Oxacillin/dicloxacillin - renal and biliary excretion*
Penicillin description
Widely effective with little toxicity
Overuse -> increase levels of resistance (due to PBP mutations)
All have beta lactam ring
PCN + aminoglycoside (gram +ve and -ve)
Penicillin synergistic effect
PCN facilitates movement of AG through the cell wall
Formas an inactive complex if placed in the same IV solution
DOC for Empiric treatment of infective endocarditis … PCN G + gentamicin (nowadays a lot of MD’s use vancomycin instead of PCN)
Penicillin Hypersensitivity
Major Ag determinant -> penicilloic acid
Anything from a rash to anaphylaxis
Cross allergic reactivity between beta lactam ABx can occur (ex. cephalosporins)
Penicillin AE
Hypersensitivity
Interstitial nephritis -> esp. methicillin -> oliguria, fever, rash, + EOS in urine
GI disturbance
*Pseudomembranous colitis (esp ampicillin) or vaginal candida
Maculopapular rash when ampicillin or amoxicillin is given for a viral infection (not a hypersensitivity reaction)
Neurotoxicity in epileptics
Ticarcillin: inhibits platelet function, increase bleeding time
Nafcillin -> neutropenia
Oxacillin -> hepatitis
Penicillin mechanisms of resistance
Inactivation by betalactamase
Modified PBP’s
Impaired penetration
Increased efflux
Penicillin time dependent killing
increasing concentration only adds to risk for AE; length of time spent over MIC is the most important
Penicillin spectrum
Spectrum is based on the ability to ‘reach” the PBP’s -> based on size, charge and hydrophobicity
Gram +ve -> cell wall is easily accessed
Gram -ve -> porins permit entry
Penicillin desensitization
used in pregnant women with penicillin allergy (because nothing else can be used to treat them*
PBPs
PBPs are penicillin binding proteins (bacterial enzymes) involved in peptidoglycan synthesis
Penicillins require the microbe to be actively proliferating (cell wall synthesis must be occurring)
Beta lactam antibiotics
Penicillins
Cephalosporins
Carbapenems
Monobactams
All target PBPs
Monobactam drug
Aztreonam
Aztreonam indication
Only for aerobic gram -ve rods
Including pseudomonas, UTI’s, sepsis
Aztreonam PK/PD
IV or IM - parenteral only
Inhalation (Cystic fibrosis patients)
Penetrates CSF when inflamed
Aztreonam mechanism
Binds PBP’s -> inhibits cell wall synthesis
Eliminated in urine (monitor renal function)
Aztreonam AE
Little cross-reactivity -> can be used in patients with PCN anaphylaxis
Relatively non toxic
Rarely causes increase aminotransferase, skin rash, GI upset, vertigo, HA
Aztreonam Funcat
Resists hydrolysis by most beta lactamases
Carbapenem drugs
Imipenem
Meropenem
Carbapenem indication
Synthetic beta lactam antibiotics
DOC for Enterobacter infection and extended spectrum beta lactamase producing gram -ve’s
Carbapenem PK/PD
Very broad spectrum but not effective against MRSA
IV
Carbapenem Mechanism
Resist hydrolysis by most beta lactamases
Resistance is becoming a huge problem -> restrict use
Carbapenem AE
GI distress
Imipenem ->seizures
Partial cross reactivity with PCN
Carbapenem fun facts
Imipenem forms a nephrotoxic metabolite -> combine with Cilastatin to reduce toxicity and increase availability