Penicillins Flashcards
Natural Penicillins
Gram+: excellent activity against non-B lactamase bacteria. Strep (ABCFG, viridans), some enterococcus, some streptococcus pneumoniae, bacillus, cornynebacterium spp. Very little activity against staphylococcus spp due to penicillinase production
Gram-: Only against some, n. meningitidis, n. gonorrhoeae
Anaerobes: good activity, mouth anaerobes above the diaphragm, below the diaphragm, clostridium, not c.diff
Aqueous penicillin G, Benzathine penicillin, procraine penicillin G, penicillin VK
Penicillin G is DRUG OF CHOICE for syphilis, n.meningitidis, corynebacterium diptheriae, anthrax, C. perfringens and tetani, viridans and group streptococci
Penicillinase-Resistant Penicillins
Sterically inhibits penicillanse Gram+: ***Methicillin Susceptible Staphylococcus auerus MSSA*** (not MRSA), viridans and group streptococci, no enterococcus or S.pneumoniae Gram-: no activity Anaerobes: limited Nafcillin, Oxacillin, Dicloxacillin
Aminopenicillins
Extended activity against gram- aerobes
Gram+: similar to natural penicillins, also ineffective against staph. aureus, better for enterococcus, excellent against listeria monocytogenes
Gram-: better activity than natural penicillins, H.influenzae, e. coli, proteus mirabilis, salmonella spp., shigella spp.
Anaerobes: similar to Pen G
Ampicillin, Amoxicillin
DRUG OF CHOICE for infections due to listeria monocytogenes, enterococcus
Carboxypenicillins
Developed for more resistant gram- bacteria and pseudomonas aeruginosa
Gram+: generally weak, less active against strep spp. not against against enterococcus or staphyloccus spp.
Gram-: enhanced activity, same gram- as aminopenicillins (including proteus mirabilis), enterobacter, providencia, morganella, PSEUDOMONAS AERUGINOSA
Not active against klebsiella, serratia, or actinobacter
Ticarcillin
Ureidopenicillins
Further activity against gram-, greater cell wall penetration and increased PBP affinity
Gram+: good against viridans and group strep, some against enterococcus, no against staphylococcus
Gram-: activity against most enterobacteriaceae
Active against Klebsiella and serratia marcescens PSEUDOMONAS AERUGINOSA (piperacillin is the most active penicillin)
Anaerobes: similar to Pen G against clostridium and peptostreptococcus
Piperacillin
B-Lactamase Inhibitor Combinations
Combination product containing penicillin and B-lactamase inhibitor, inhibitor irreversibly binds to catalytic site of enzyme. These combinations retain same activity of parent penicillin for non B-lactamase organisms and have ENHANCED activity against B-lactamase producing bacteria
Gram+: Provide activity against B-lacta producing strains of STAPHYLOCCUS AUREUS** (and MSSA)
Gram-: enhanced against E.coli, proteus, klebsiella, H.influenze, M.catarrhalis, N.gonorrhoeae
Not very activite against Serratia marcescens, P. aeruginosa, indole=positive proteus, citrobacter, and enterobacter (SPICE bacteria) TICARCILLIN/CLAVULANATE IS ACTIVE AGAINST STENOTROPHOMONAS MALTOPHILI
Anaerobes: ENAHNCED ACTIVITY AGAINST B. FRAGILIS AND B.FRAGILIS GROUP (DOT) ORGANISMS
Ampicillin-Sulbactam (Unasyn), Amxocicillin-Clavulanic Acid (Augment), Ticarcillin-clavulanic acid (Timentin), Piperacillin-Tazobactam (Zosyn)
B-LACTAMS
Penicillins, Cephalosporins, Carbapenems, Monobactams
Describe the differences in the spectrum of activity between the natural penicillins, penicillinase-resistant penicillins, the aminopenicillins, the carboxypenicillins, the ureidopenicillins, and the B-lactamase inhibition combinations with special emphasis on the specific penicillin agents that have activity against staphylococcus aureus, pseudomonas aeruginosa, and bacteroides fragilis. List examples of commonly used agents within each of the penicillin classes
Staphylococcus aureus: Penicillinase- resistant penicillins (nafcillin, methicillin, oxacillin, dicloxacillin)
Pseudomonas aeruginosa: carboypenicillins (Ticarcillin), ureidopenicillins (Piperacillin, most active)
Bacteroides fragilis: B-lactamase inhibitior combinations
Describe the distribution characteristics of the penicillins into the cerebrospinal fluid, urinary tract, lungs, skin/soft tissue, and bone.
Widely distributed into body tissues and fluids including pleural, synovial, bone, bile, placenta, and pericardial
DO NOT penetrate eye or prostate
Adequate concentrations of penicillins in CSF are attained only in presence of INFLAMED MENIGES WHEN HIGH DOSES OF PARENTERAL PENICILLINS ARE USED
Describe the major adverse effects associated with the penicillin antibiotics
Hypersensitivity: more frequent in IV, anaphylaxis is rare, mediated by antibodies produced against penicillin degradation products, desensitization is possible in some patients. CROSS-ALLERGENICITY IN OBSERVED AMONG NATURAL AND SEMISYNTHETIC PENICILLINS DUE TO COMMON NUCLEUS, PTS ALLERGIC TO ONE SHOULD BE CONSIDERED ALLERGIC TO ALL (caution should be used with some other B-lactams)
Neurologic: Direct toxic effect in large IV or pts with renal dysfunction, irritability, jerking, confusion, generalized SEIZURES
Hematologic: Cytotoxic IgG or IgM develop that bind to WBC or platelets, cause cell lysis when penicillin is encountered via complement. Leukopenia, neutropenia, thrombocytopenia (especially in long-term therapy)
GI: transient increases in liver enzymes, nausea and vomiting, diarrhea, pseudomembranous colitis
Interstitial nephritis: immune mediated damage to renal tubules b/c penicillin binds to tubule cells METHICILLIN, NAFCILLIN, cause fever, eosinophilia, pyuria, EOSINOPHILURIA, INCREASE IN SERUM CREATININE
PHLEBITIS (nafcillin), pain, HYPOKALEMIA (ticarcillin), SODIUM OVERLOAD and FLUID RETENTION (ticarcillin, piperacillin)
General characteristics of B-Lactam antibiotics
Same mechanism of action - inhibit cell wall synthesis (bind to and inhibit enzymes responsible for working with peptidoglycan)
Same mechanism of resistance- destruction of B-lactamase enzymes, alteration in penicillin binding proteins, decreased permeability of outer cell membrane in gram- bacteria
Pharmacodynamic properties- time-dependent bactericidal activity (except against enterococcus)
Short elimination half life-
Enterococcus spp
Penicillins are bactericidal except against this bacteria, where they cause bacteriostatic activity
Bactericidal activity (synergy) can be achieved against Enterococcus by adding an aminoglycoside (gentamicin or streptomycin)
B-lactamase enzyme
Produced by bacteria, hydrolyzes cyclic amide of B-lactam ring in the antibiotic
Produced by many gram- bacteria, some gram+ and some anaerobic
Pharmacokinetics
Time dependent bactericidial activity (time above MIC)
PAE from gram+, no significant PAE for gram-
List the penicillins that are not primarily eliminated by the kidneys. List the penicillins that require dosage adjustment in renal insufficiency, and those that are removed by hemodialysis
Most penicillins are eliminated via kidney and require dosage adjustment in the presence of renal insufficiency
Not eliminated by kidneys: Nafcillin and oxacillin (liver), piperacillin (dual elimination)
Most penicillins are removed during hemodialysis or peritoneal dialysis (requiring supplemental dosing after hemodialysis procedure) EXCEPT NAFCILLIN AND OXACILLIN
