Penicillins Flashcards
6 General Characteristics of B-lactam antibiotics
-Inhibit cell wall synthesis
-Main mechanism of resistance is due to B-lactamases
-T>MIC Time dependent
- Short elimination half life
- Most renal elimination (Except Nafcillin, Oxacillin, Cefriaxone, Cefoperazone)
- Cross allerginicity except with aztreonam
MOA
Bind to PBP and inhibit cell wall synthesis which leads to osmotic stress and decreases cell growth, bacterial lysis, and death (these are bactericidal)
3 Resistance mechanisms
- Main one if B-lactamases that open ring structure and inactivate drug (very powerful in gram - bacteria because they reside in the periplasmic space)
- Alteration in the structure of the PBPs which leads to decreased binding affinity
- Alteration of porin channels on gram negative bacteria
What are the natural penicillins and gram positive and negative coverage
Aqueous penicillin G, Benzathine penicillin G, procaine penicillin G, Penicillin VK
!DRUG OF CHOICE FOR SYPHILIS!
Gram Positive: (usually drug of choice for group and viridans)
- Group Streptococci
- Viridans Streptococci
- Enterococcus spp.
- Pen-susc S. pneumoniae
- Pen-susc S. Auereus
Gram negative Cocci:
- Neisseria spp.
-Pasteurella Multocida
Anerobes:
Above the diaphragm
Clostridium spp.
Penicillinase-Resistant Penicillins what are they and Gram positive coverage
Nafcillin, Oxacillin, Methicillin, Dicloxacillin (Diclox is oral)
developed in response to the emergence of penicilinase producing Staphy aureus (penicillinase inactivates natural product)
Gram Positive:
MSSA
Group streptococci
Viridans Streptococci
Gram Negative:
NO ACTIVITY
Aminopenicillins What are they and gram negative and positive coverage
Parental agent: ampicillin
Oral agent: amoxicillin and ampicillin
Developed due to need for agents against gram negative bacteria, have amino group added
Gram Negative: (SHEP)
- Salmonella, Shigella
- H. Influenzea (those that are B-lactamase negative)
- E. Coli (only some)
- Proteus mirabilis
Gram Positive:
-Enterococcus spp. (Drug of choice ampicillin)
- Listeria Monocytogenes (drug of choice)
- Group Streptococci
- Viridans Streptococci
- Pen-susc S. pneumoniae
- Pen-susc S. Auereus
Carboxypenicillins what are they and Gram negative Coverage
Parental: Ticarcillin
Developed in response to need for agents with enhanced activity against gram negative bacteria
Gram Negative (SHEPMEP):
- Salmonella, shigella
- H. Influenza (B-lactamases positive)
- E. coli
- Proteus mirabilis
- Psuedomonas aeruginosa*
- Enterobacter spp
Gram Positive activity is marginal due to the addition of carboxyl group
Ureidopenicillins what are they and gram negative and positive coverage
Parental agents: Piperacillin
Developed for further activity against gram negative bacteria
Gram Negatives:
-Salmonella, shigella
- H. influenza (BL+)
- E. Coli
- Proteus mirabilis
- Enterobacter spp
-Pseudomonas aeruginosa* (piperacillin is penicillin of choice for this)
- Serratia marcescens
-Klebsiella
Gram positive:
-Group strep
- Viridans strep
- some enterococcus
Anaerobes:
Fairly good activity
B-lactamase inhibitor combinations
Anaerobes coverage and gram positive coverage and gram negative
Parental agents: Unasyn (Ampicillin/Sulbactam), Zosyn(Piperacillin/Tazobactam)
Oral: Augmentin (amoxicillin/clavulanic acid)
Developed to enhance activity against B-lactamase producing bacteria
Anaerobes:
- Bacteroides spp. (target organism)
Gram negative:
- Klebsiella spp.
- E. Coli
-H. Influenza
- Proteus spp.
-Neisseria Gonorrhoeae
- Moraxella Catarrhalis
Gram Positive:
MSSA
Gram negative:
Serratia
Pseudomonas Aeruginosa
Enterobacter
Pharmacology
Bactericidal agents
time dependent (want concentration above MIC for 50% or dosing interval)
Absorption
Parental agents have better absorption than oral so oral agents should be used for mild to moderate infection and parental for moderate to severe
Distribution
Widely distributed into body tissues and fluids (NOT eye or prostate)
Adequate concentrations of penicillins in the CSF are attainable only in presence of inflamed meninges
Elimination
Mainly through kidney unchanged (10% glomerular and 90% tubular)
Probenecid can be taken in combo to block tubular secretion and extend the drugs activity
Nafacillin and oxacillin are eliminated through the liver - Dosing adjustment for renal insufficiency is not needed - EXAM Q
Half life is around 2 hours
Sodium load
MUST BE USED WITH CAUTION IN PATIENTS WITH CHF OR RENAL INSUFFICIENCY
Sodium Penicillin G - 2.0 mEq per 1 million units ( Typical dose is 24-48 mEq of sodium a day)
Nafacillin - 2.9 mEq per gram (Typical dose is 24-36 mEq per day)
Ticarcillin - 5.2 mEq per gram (typical dose is up to 90 mEq per day)
Piperacillin - 1.85 mEq per gram (typical dose is 12-32 mEq per day
Natural penicillins Clinical use
Syphilis
Potential drug of choice for penicillin-susceptible S. Pneumoniae
Penicillinase-resistant penicillins Clinical use
Infections due to MSSA
Aminopenicillins Clinical use
Enterococcal infections, Listeria monocytogenes
Carboxypenicillins and ureidopenicillins clinical use
Empiric therapy for hospital aquired infections
Infections due to pseudomonas aeruginosa (Piperacillin)
B lactamase inhibitor combinations Clinical use
Augmentin: sinusitis, otitis media, animal bite wounds
Unasyn, Zosyn:
-polymicrobial infections
- Empiric therapy for hospital accquired infections (zosyn)
Adverse reactions
- Hypersensitivity reactions
-(type I is IGE mediated and the immediate reaction that leads to itching and discomfort) (Type II is IGG or IGM mediated and is a delayed reaction that leads to rash and hives)
- Patients with penicillin allergy should not be given any other penicillin drugs and should be cautious of taking other b-lactam antibiotics - Neurologic: Direct toxic effect Happens to patients who are given large IV doses with renal insufficiency leads to confusion, jerking, seizures
- Hematologic: Neutropenia, thrombocytopenia, anemia usually seen in patients on longer durations of therapy (usually >2 weeks) - it is reversible upon discontinuation
- GI upset: Diarrhea, N/V, increased LFTs, C. Diff
- Interstitial Nephritis: Immune mediated damage to renal tubules (hapten causes this) characterized by an abrupt increase in serum creatinine
- Methicillin has many reports of this and is why it is no longer used, also seen with Nafcillin
- can lead to renal failure - Others: Phlebitis, hypokalemia, sodium overload
