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139 Cards in this Set
- Front
- Back
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all penicillins are derivatives of
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6-aminopenicillanic acid
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what is essential for penicillin's antibacterial activity
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beta lactam ring
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PCNs vary in oral bioavailability because
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vary in their resistance to gastric acid
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parenteral forms of PCN include
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ampicillin, piperacillin, ticarcillin
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metabolism of PCN causes their excretion via
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glom filtration and tubular secretion unchanged
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elimination half lives of many beta lactams are prolonged by
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probenecid
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which PCN is excreted mainly in the bile
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nafcillin
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which PCN undergoes enterohepatic cycling
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ampicillin
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plasma half lives of most PCNs
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30min to 1 hr
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forms of PCN G given IM and have long half lives
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procaine and benzathine
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do PCNs cross BBB
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only when meninges are inflamed
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beta lactams = cidal or static?
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cidal
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steps that beta lactams inhibit cell wall synth
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1. bind PBPs in bacterial cytoplasmic membrane
2. inhibit transpep rxn 3. activate autolytic enzymes that cause lesions in bacterial cell wall |
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major mechanism of bacterial resistance
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formation of beta lactamases by staph and gram - organisms
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what inhibitors are used in combo w PCNs to prevent their inactivation by beta lactamases
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clavulanic acid, sulbactam, tazobactam
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mechanism responsible for MRSA and PCN G resistance in pneumococci and enterococci
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structural change in target PBPs
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which organisms change porin structures in their outer cell wall memb to cause PCN resistance by impeding access to PBPs
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gram - rods (pseudomonas)
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prototype of subclass of PCNs that have limited spectrum and susceptible to beta lactamases
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PCN G
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PCN G clinical uses include therapy of infections caused by common
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strep, meningococci, gram + bacilli and spirochetes
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most strains of s. aureus and many neisseria are PCN resistant due to
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prod of beta lactamases
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drug choice for trxt of syphilis
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PCN G
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PCN G + aminoglycoside provides enhanced activity against
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enterococci
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oral drug used mainly in oropharyngeal infections
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PCN V
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prototype of very narrow spectrum penicillinase-resistant drugs
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methicillin
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why is methicillin rarely used
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nephrotoxic potential
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nafcillin and oxacillin are characterized as
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very narrow spec penicillinase-resistant drugs
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primary use of nafcillin, oxacillin and methicillin are for
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known or suspected staph infections
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MRSA and MRSE are resistant to
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all PCNs
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ampicillin and amoxicillin belong to which group
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wider spec penicillinase-susceptible drugs
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clinical uses of ampicillin and amoxicillin are
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similar to PCN G as well as enterococci, listeria, e coli, proteus, h. influ and moraxella catarrhalis
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antibacterial activity of ampicillin and amoxicillin is enhanced when they are combined with
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inhibitors of penicillinases (clavulanic acid)
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ampicillin is synergistic with aminoglycosides in which infections
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enterococci and listerial
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these drugs have activity against several gram - rods, incl pseudomonas, enterobacter and some klebsiella species
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piperacillin and ticarcillin
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piperacillin and ticarcillin have synergistic actions when used with
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aminoglycosides
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piperacillin and ticarcillin are often used in combo with what to enhance their activity
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penicillinase inhibitors (tazobactam and clavulanic acid)
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allergic rxns to PCNs include
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uritcaria, pruritis, fever, jt swelling, hemolytic anemia, nephritis, anaphylaxis
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methicillin causes
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interstitial nephritis
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nafcillin is assoc w what side effect
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neutropenia
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antigenic determinant include
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degradation pdts of PCNs such as penicilloic acid
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ampicillin often causes what that doesn't appear to be an allergic rxn
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maculopapular skin rash
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what GI effects occur w oral PCNs esp ampicillin
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nausea and diarrhea
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GI upset by PCNs is caused by
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direct irritation or by overgrowth of gram + organisms or yeasts
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what has been implicated in pseumembranous colitis
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ampicillin
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derivatives of 7-aminocephalosporanic acid and contain beta lactam ring
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cephalosporins
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most cephalosporins are administered via
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parenterally
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which cephalosporins may indergo hepatic metab
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those with side chains
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major elim mech for cephalosporins is
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renal excretion via active tubular secretion
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cefoperazone and cetriaxone are excreted mainly via
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bile
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do 1st and 2nd gen cephalosporins enter CSF when meninges are inflamed?
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no
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MOA of cephalosporins
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bind to PBPs on bacterial cell membranes to inhibit cell wall synth
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cephalosporins = cidal or static?
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cidal
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cephalosporins less susceptible to penicillinases prod by staph due to
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structural differences
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resistance to cephalosporins can result from
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decreases in memb permeability and changes in PBPs
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MRSA = resistant or sensitive to cephalosporins?
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resistant
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cefazolin and cephalexin = what gen cephalosporin and admin route
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1st; lexin=oral, zolin=parenteral
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1st gen cephalosporins are active against
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gram + cocci, e coli and k.pneumoniae
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1st gen cephalosporins have minimal activity against
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gram - cocci, enterococci, MRSA, most gram - rods
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2nd gen cephalosporins have less activity against ___ but extended coverage for ___
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gram +, gram -
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cefotetan, cefoxitin, cefamandole, cefuroxime, cefaclor are what generation cephalosporins?
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2nd
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cefotetan and cefoxitin used clinically for
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infectios by bacteroides
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cefamandole, cefuroxime and cefaclor used clinically for
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sinus, ear, resp inf from h.influenza or m.catarrhalis
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which 3rd gen cephalosporins do NOT cross BBB
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cefoperazone and cefixime
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ceftazidime, cefoperazone, cefotaxime are what gen cephalosporins?
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3rd
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characteristic features of 3rd gen cephalosporins are
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incr activity against gram - organisms resistant to other beta lactams and ability to penetrate BBB (ceftazidime only)
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most active cephalosporins against PRSP strains
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ceftriaxone and cefotaxime
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activity against B fragilis
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ceftizoxime
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which gen cephalosporins are active against providencia, serratia marcescens, beta lactamase prod h.influenza and neisseria
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3rd
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admin route for ceftriaxone and cefixime
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parenteral, oral
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drugs of choice in gonorrhea
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ceftriaxone, cefixime
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in acute otitis media a single injection of what is usually as effective as a 10d course of amoxicillin
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ceftriaxone
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4th gen cephalosporin
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cefepime
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4th gen cephalosporins are more resistant to
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beta lactamase prod by gram -
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4th gen cephalosporins combine activity of
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gram + activity of 1st gen with wider gram - spec of 3rd gen
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cross hypersensitivity between all PCNs?
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yes
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cross hypersensitivity between all cephalosporins?
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yes
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range of allergic rxns by cephalosporins
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skin rash to anaphylaxis
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cross reactivity b/t PCNs and cephalosporins?
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incomplete (5-10%)
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what pts should NOT be treated with cephalosporins
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those w a hx of anaphylaxis to PCN
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pain at IM injection site and after IV admin are side effects of
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cephalosporins
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cephalosporins may increase the nephrotoxicity of ___ when administered together
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aminoglycosides
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drugs containing a methylthiotetrazole group may cause ____ with ethanol
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hypoprothrombinemia and disulfiram-like rxns
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monobactam that is resistant to beta lactamases prod by gram - rods
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aztreonam
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aztreonam has no activity against
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gram + or anaerobes
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aztreonam is synergistic with
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aminoglycosides
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aztreonam inhibits cell wall synth by preferentially binding
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PBP3
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admin and elim of aztreonam?
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IV, renal tubular secretion
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what drugs half life is prolonged in renal failure
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aztreonam
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aztreonam cross allerginicity w PCNs?
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no
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adverse effects of aztreonam
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GI upset w possible superinfection, vertigo, h/a, rarely hepatotoxicity, skin rash
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imipenem, meropenem, ertapenem are
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cabapenems
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carbapenems have low or high susceptibility to beta lactamases
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low
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carbapenems have wide activity against
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gram + cocci (incl PRSP), gram - rods and anaerobes
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carbapenems + aminoglycosides used for which infections
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pseudomonal
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admin of carbapenems
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parenterally
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MRSA resistant or sensitive to carbapenems?
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resistant
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co-drugs of choice for infections caused by enterobacter, citrobacter, serratia?
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carbapenems
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imipenem is rapidly inactivated by ____and is admin in fixed combo w ___, an inhibitor of this enzyme
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renal dehydropeptidase I; cilastatin
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what increases the plasma half life of imipenem and inhibits the formation of a potentially nephrotoxic metabolite
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cilastatin
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adverse effects of imipenem-cilastatin include
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GI distress, skin rash and CNS toxicity at very high levels
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carbapenems cross allergenicity w PCNs?
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partial
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meropenem is similar to imipenem except
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not metabolized by renal dehydropeptidases and less likely to cause seizures
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ertapenem half life? what is it less active against and what does iM injection cause?
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longer, enterococci and pseudomonas, pain and irritation
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used in fixed combos w certain hydrolyzable PCNs
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beta lactamase inhibitors (clavulanic acid, sulbactam, tazobactam)
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beta lactamase inhibitors are most active against
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plasmid encoded beta lactamases such as those encoded by gonococci, strep, e coli and h.influenza
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clavulanic acid, sulbactam, tazobactam are not good inhibitors of
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inducible chromosomal beta lactamases formed by enterobacter, pseudomonas and serratia
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what can limit the oral absorption of PCNs
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lability in gastric acid
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final step in cell wall synthesis
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transpeptidation
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polysacc and polypeps that are cross linked =
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peptidoglycan
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act as initial receptors for PCNs and other beta lactams
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PBPs
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MIC =
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lowest conc of antimicrobial drug capable of inhibiting growth
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cidal glycoprotein that binds to D-ala terminal of nascent peptidoglycan pentapeptide side chain and inhibits transglycosylation
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vancomycin
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vancomycin action prevents
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elongation of polypep chain and interferes w cross-linking
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resistance to vancomycin involves
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D-ala replaced by D-lactate
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spectrum of activity of vancomycin=
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narrow
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drug of choice for MRSA
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vancomycin
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vancomycin + 3rd gen cephalosporin used for trxt of
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PRSP
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vancomycin is backup drug for trxt of
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c.difficile
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another gylcopeptide that has similar characteristics to vancomycin
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teicoplanin
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vancomycin may be given orally for
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bacterial entercolitis
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what admin allows vancomycin to penetrate most tissues and be elim unchanged in the urine
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parenterally
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absorption of vancomycin in GI?
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no
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dosage modification of vancomycin is mandatory in pts w
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renal impairment
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toxic effects of vancomycin include
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chills, fever, phlebitis, ototoxicity, nephrotoxicity
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rapid IV infusion of vancomycin may cause
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diffuse flushing from histamine release
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antimetabolite inhibitor of cytosolic enolpyruvate transferase
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fosfomycin
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fosfomycin action prevents
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formation of NAM acid, precursor for peptidoglycan chain formation
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resistance of fosfomycin occurs via
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decr intracell accum of the drug
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excretion of fosfomycin via
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kidney
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single dose of fosfomycin is less effective than
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7d trxt w fluoroquinolones
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multiple dosing of fosfomycin causes
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resistance and diarrhea
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fosfomycin may be synergistic w
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beta lactam and quinolones
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peptide antibiotic that interferes w a late stage wall synth in gram +
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bacitracin
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why is bacitracin limited to topical use
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marked nephrotoxicity
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antimetabolite that blocks incorp of D-ala into pentapeptide side chain of peptidoglycan
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cycloserine
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cycloserine is only used to treat TB resistant to first line anti-TB drugs because
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potential nephrotoxicity (tremors, seizures, psychosis)
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novel cyclic lipopeptide w spectrum similar to vancomycin
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daptomycin
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activity against VRSE and VRS
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daptomycin
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daptomycin elim via
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kidney
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what should be monitored w daptomycin admin
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CPK due to myopathy
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