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
Discuss the main clinical uses of representative penicillins within each group of penicillins
Natural penicillins
IV penicillin G used for serious hospital infections, oral penicillin VK is use limited to mild/moderate infections (pharyngitis or prophylaxis)
DRUG OF CHOICE:
s. pneumonia (IV or IM)
Streptococci, including s.pyogenes, viridans streptococci pharyngitis, bacteremia, endocarditis, meningitis
Neisseria meningitdis (meningitis, meningococcemia)
Treponema pallidum - syphilis
C. perfringens or tetani
Actinomycosis
Endocarditis prophylaxis in valvular heart disease undergoing dental procedures (high risk for inducing bacteremia), prevention of rheumatic fever
Discuss the main clinical uses of representative penicillins within each group of penicillins
Penicillinase-Resitant Penicillins
Enhanced activity against s. aureus
Methicillin-susceptible staphylococcus aureus (MSSA) ie skin an dsoft tissue infections, septic arthritis, osteomyelitis, bacteremia, endocarditis. Parenteral therapy should be used for moderate/severe infections
Oral dicloxaccin for mild/moderate skin and soft tissue infections, follow-up therapy after parenteral therapy for treatment of more serious infections ie osteomyelitis or septic arthritis
Discuss the main clinical uses of representative penicillins within each group of penicillins
Aminopenicillins
Respiratory tract pathogens, oral ampicillin and amoxicillin treat mild/moderate pharyngitis, sinusitis, bronchitis, and otitis media
Uncomplicated UTI
Parenteral ampicillin for enterococcal infections and listeria monocytogenes meningitis
Endocarditis prophylaxis in patients with valvular heart disease
Treatment of salmonella and shigella
Discuss the main clinical uses of representative penicillins within each group of penicillins
Carboxypenicillins and Ureidopenicillins
Enhanced activity against gram- bacteria
Serious infections ie bacteremia, pneumonia, complicated UTI, peritonitis, intraabdominal infections, skin and soft tissue infections, bone and joint infections, meningitis caused by gram-, HOSPITAL ACQUIRED INFECTIONS
PIPERACILLIN IS MOST ACTIVE PENICILLIN FOR PSEUDOMONAS AERUGINOSA
Discuss the main clinical uses of representative penicillins within each group of penicillins
B-Lactamase Inhibitor Combination Products
Enhanced activity against B-lactamase producing bacteria
Amoxicillin-clavulanate (Augmentin PO) for otitis media, sinusitis, bronchitis, lower respiratory tract infections, human/animal bites
Expanded activity against gram+ and gram- (including anaerobes), treats polymicrobial infections ie intraabdominal infections, gynecological infections, diabetic foot infections
Ampicillin -sulbactam (Unasyn): aerobic/anaerobic infections (limited gram- coverage)
Ticarcillin-clavulanate (Timentin IV): 2nd line treatment o finfections caused by stenotrophomonas maltophilia, broad coverage to piperacillin-tazobactam (but latter is more tolerable)
Piperacillin-tazobactam (Zosyn IV): polymicrobial infections or gram- including hospital-acquired pneumonia, bacteremia, complicated UTI, complicated skin and soft tissue infections, intraabdominal infections, empiric therapy for febrile neutropenia
Clinical Uses
Natural Penicillins
Drug of choice for S.pneumoniae, infections due to other streptococci, N. meningitidis, SYPHILIS, C. perfringens or tetani, Actinomyces, B. anthracis
Endocarditis prophylaxis; prevention of rheumatic fever
Clinical Uses
Penicillinase-Resistant Penicillins
Infections due to MSSA such as skin and soft tissue infections, septic arthritis, osteomyelitis, bacteremia, endocarditis, etc
Clinical Uses
Aminopenicillins
RTI, pharyngitis, sinusitis, o. media, bronchitis, UTI ENTEROCOCCAL INFECTIONS (often treated with aminoglycoside combination) and infections dues to LISTERIA MONOCYTOGENES
Clinical Uses
Carboxypenicillins and Ureidopenicillins
Serious infections due to gram- aerobic bacteria such as pneumonia, bacteremia, complicated UTIs, skin and soft tissue infections, peritonitis
Emperic therapy for HOSPITAL ACQUIRED INFECTIONS
Infections due to PSEUDOMONAS AERUGINOSA
Clinical Uses
B-Lactamase Inhibitor Combinations
Augmentin (PO): sinusitis, o.media, upper and lower RTI, human/animal bite wounds
Unasyn, Zosyn, Timentin: used for POLYMICROBIAL INFECTIONS such as polymicrobial pneumonia (aspiration), intra-abdominal infections, gynecologic infections, diabetic foot infections
Empiric therapy for febrile neutropenia or hospital-acquired infections (Zosyn)
Adverse Effects
Hypersensitivity: antibodies produced against penicillin or its byproducts
Cross reactivity exists among ALL penicillins and even some other B-lactams
Desensitization is possible
Neurologic: direct toxic effect, high IV doses, irritability, jerking, confusion, seizures
Hematologic: leukopenia, neutropenia, thrombocytopenia (usually during prolonged therapy). Reversible upon discontinuation
GI: INcreased LFTs, nausea, vomiting, diarrhea, pseudomembranous colitis
Interstitial nephritis (immune mediated damage to renal tubules
Phlebitis, hypokalemia, Na overload
