Drug Mechanism of Action Mechanism of Spectrum of Activity Pharmacology Indications for Use Toxicity

Resistance
Penicillin binds penicillin binding beta-lactamase bactericidal some oral use hypersensitivity
proteins (transpeptidases, cleaves beta-lactam Gram+ minor metabolism (rash; anaphylaxis)
carboxypeptidases); ring and inactivates streptococci, excreted by act as haptens to
enzymes involved in cell drug enterococci, kidneys via tubular combine with human
wall (peptidoglycan) (chromosomal or meningococci, secretion proteins
biosynthesis plasmid mediated) treponema pallidum (probenecid will major determinant=
Gram- can change (syphilis), most block) penicilloyl
porin channel anaerobes well distributed to (uticaria and late
permeability poor activity against lungs, liver, kidney, rxns)
preventing drug Gram- rods muscle, bone and minor determinant=
from reaching placenta benzylpenicilloate
receptor site high urinary and (anaphylaxis and
efflux pumps bile concentrations accelerated rxns)
alteration of PBPs
(esp. in Gram+)
Ampicillin binds pencillin binding beta-lactamase bactericidal oral and IV rash is common
(aminopenicillins) proteins cleaves beta-lactam Gram+
(transpeptidases, ring and inactivates streptococci, enterococci
carboxypeptidases); drug (unless they express
enzymes involved in cell (chromosomal or beta-lactamases)
wall biosynthesis plasmid mediated) Gram-
better penetration Gram- can change hemophilus, e.coli,
through outer mb of porin channel salmonella, shigella
permeability (but many Gram- have
Gram- than penicillin G
preventing drug plasmid mediated
and better binding to
from reaching resistance)
PBPs receptor site
efflux pumps
alteration of PBPs
(esp. in Gram+)
Semisynthetic binds penicillin binding bulk prevents them bactericidal Methicillin least serious
penicillinase- proteins (transpeptidases, from getting used primarily for protein bound of the staphylococcus
resistant penicillins carboxypeptidases); through Gram- staphylococci group aureus infections
(Nafcillin, Oxacillin, enzymes involved in cell porins Gram+ Nafcillin high (cellulites,
Methicillin) wall (peptidoglycan) pneumococci, biliary excretion endocarditis, sepsis)
biosynthesis streptococci, Isoxazolyl
bulky side chains inhibit NOT enterococci penicillins
action of staph beta- (parenteral and IV
lactamases forms)
Drug Mechanism of Action Mechanism of Spectrum of Activity Pharmacology Indications for Use Toxicity
Resistance
Beta-lactamase high affinity for
inhibitors plasmid-mediated beta-
lactamases
Sulbactam
Clavulanic acid
Tazobactam
Combination: binds PBPs; enzymes Gram- can change bactericidal ; broad
(penicillin + beta- involved in cell wall porin channel spectrum
lactamase inhibitor biosynthesis permeability Gram+
beta-lactamase preventing drug from streptococci,
Piperacilin + inhibitors reaching receptor site enterococci,
Tazobactam (tazobactam) high efflux pumps meningococci,
affinity for plasmid alteration of PBPs treponema pallidum
mediated enzymes (esp. in Gram+) (syphilis), most
anaerobes
Gram-
pseudomonas
aeruginosa,
bacteroides, proteus
Carbapenems binds PBP-2 STABLE to beta- bactericidal; HUGE allergic rxns similar to
permeability through lactamase; but alternate spectrum penicillin
Imipenem porin channels enzymes that can kills most Gram+, (?) Imipenem may
Meropenem hydrolyze Gram-, and lower seizure
alteration of porin anaerobic bacteria threshold
channels including
pseudomonas
aeruginosa;
does NOT kill:
MRSA, enterococcus,
c. difficile
Monobactams only binds Gram- STABLE to beta- bactericidal; can use in place of an
PBPs lactamase NARROW spectrum aminoglycoside
Aztreonam ONLY aerobic Gram- can use in penicillin
rods; including p. allergic pts (little cross-
aeruginosa reactivity)
Drug Mechanism of Action Mechanism of Spectrum of Activity Pharmacology Indications for Use Toxicity
Resistance
1st Generation like penicillins, inhibit permeability failure bactericidal hydrophilic molecules common infections hypersensitivity (rash,
Cephalosporins enzymatic rxns needed of cephalosporins to Gram+ cocci that achieve excellent surgical prophylaxis urticaria, eosinophilia,
for stable bacterial wall reach receptor sites s. pneumoniae, s. aureus, drug levels in lung, skin and soft tissue fever, anaphylaxis
Cefazolin, synthesis by binding to destroyed by beta- NOT enterococci kidney, muscle, bone, infections rare)
Cephalothin, PBPs lactamase Gram- rods placenta, interstitial, leukopenia and rarely
Cephalexin (oral), alteration of PBPs e. coli, klebsiella, proteus synovial, and hemolytic anemia
Cefaclor (oral) mirabilis peritoneal fluids, and in superinfection with
urine fungi or resistant
eliminated via kidney Gram- organisms
(probenecid blocks phlebitis, false+ tests
secretion of some (Coombs, glucose)
compounds)
2nd Generation like penicillins, inhibit permeability failure bactericidal parenteral drugs upper respiratory hypersensitivity (rash,
Cephalosporins enzymatic rxns needed of cephalosporins to Gram+ cocci hydrophilic molecules tract infections (h. urticaria, eosinophilia,
for stable bacterial wall reach receptor sites s. pneumoniae, less s. that achieve excellent influenzae) fever, anaphylaxis
synthesis by binding to destroyed by beta- aureus, NOT enterococci drug levels in lung, GI tract flora rare)
Cefuroxime PBPs lactamase (cefuroxime Gram- rods kidney, muscle, bone, infections leukopenia and rarely
Cefoxitin is STABLE to plasmid e. coli, klebsiella, proteus placenta, interstitial, hemolytic anemia
Cefotetan mediated penicillinases) mirabilis synovial, and superinfection with
alteration of PBPs cefuroxime covers h. peritoneal fluids, and in fungi or resistant
influenzae urine Gram- organisms
cefoxitin and cefotetan eliminated via kidney phlebitis, false+ tests
increased anaerobe coverage, (probenecid blocks (Coombs, glucose)
bacteroides secretion of some
compounds)
3rd Generation like penicillins, inhibit permeability failure bactericidal cefotaxime and cefotaxime= drug of hypersensitivity (rash,
Cephalosporins enzymatic rxns needed of cephalosporins to cefotaxime: highly ceftriaxone achieve choice for meningitis urticaria, eosinophilia,
for stable bacterial wall reach receptor sites active against s. good CSF levels; ceftriaxone= fever, anaphylaxis
synthesis by binding to STABLE to plasma pneumoniae; n. ceftazidime adequate outpatient coverage of rare)
cefotaxime PBPs mediated beta- CSF levels septic pneumococcal leukopenia and rarely
meningitides, h.
ceftriaxone lactamases ceftriaxone longer pts, n. gonorrhea, and hemolytic anemia
ceftazidime influenzae, e. coli,
alteration of PBPs half-life and more CNS lyme disease superinfection with
klebsiella, NOT p. fungi or resistant
active than
aeruginosa Gram- organisms
cefotaxime; a single
ceftriaxone: s. pneumoniae, phlebitis, false+ tests
IM does can kill for
n. gonorrhea, b. burgdorferi (Coombs, glucose)
12-24 hrs
ceftazidime: less Gram+
activity but can kill p.
aeruginosa
Drug Mechanism of Action Mechanism of Spectrum of Activity Pharmacology Indications for Use Toxicity
Resistance
Vancomycin targets d-ala-d-ala problem in bactericidal parenteral serious Gram+ low risk of
petapeptide; blocks 2 enterococcus fecium most Gram+ wide tissue infections in penicillin nephrotoxicity
steps in cell wall has plasmid-mediated, including beta- distribution and allergic pts phlebitis (frequent)
synthesis at an earlier readily transferable lactamase producers infected pleural, infections due to red man syndrome:
step than beta-lactams resistance (plasmids and methicillin pericardial, synovial, resistant s. pneumoniae when given in too rapid
have been shown resistant staph aureus; ascitic fluids and or MRstaph an infusion get
capable of replicating streptococcus, meninges generalized rash,
in s. aureus) clostridia, listeria, excreted by kidneys uticaria (due to
transposable element bacillus histamine release)
that allows organism to (?) ototoxicity
sense vancomycin and
activate transcription
leading to replacement
of d-ala-d-ala with d-
ala-d-lactate
Drug Mechanism of Action Mechanism of Spectrum of Activity Pharmacology Indications for Use Toxicity
Resistance
Chloramphenicol binds peptidyl presence of enzyme Mostly bacteriostatic higher levels with NOT drug of choice dose related bone
transferase, a chloramphenicol may be bacteriocidal ORAL vs IV for any infection; used marrow depression
component of the 50s transacetylase against pneumococcus well distributed more in developing (rare) aplastic anemia
ribosome (acetylates the drug) and neisseria throughout body; CSF world in neonates get gray
broad spectrum levels 30-50% of typhoid fever (s. baby syndrome
aerobic Gram+ serum w/o typhi) (vasomotor collapse,
most Gram- inflammation meningitis in abdominal distention,
most anaerobes metabolized to penicillin allergic pts cyanosis)
ricksettsia inactive metabolite in (pneumococcus,
liver hemophilus, neisseria)
rickettsial infections
Quinolones bind DNA-DNA mutations in bactericidal well absorbed orally empiric therapy for well-tolerated
gyrase (topoisomerase topoisomerase II or IV 1st generation andparenterally community-acquired GI symptoms
II) complex and blocks resistance is (nalidixic acid) excellent tissue pneumonia CNS symptoms
further DNA chromosomal (rather Gram- enterics distribution; bone and complicated UTI or allergic rxns (rash,
replication than plasmid) (UTIs) CSF < serum respiratory tract uticaria, drug fever)
blocks topoisomerase can emerge quickly 2nd generation high intracellular infections photosensitivity (esp.
IV inteferes with during therapy esp. (norfloxacin, concentration (PMNs) serious infections like with additional F or Cl
separation of with s. aureus, or p. ciprofloxacin) most eliminated by osteomyelitis, at position 8 of drug
interlocked replicated aeruginosa; a single better Gram- kidneys (trovofloxin pneumonia, soft tissue structure)
DNA molecules mutation leads to coverage, p. 3rd gen. eliminated by STDs: gonorrhea, liver function
other sites of action resistance aeruginosa liver) chancroid, chlamydial abnormalities rare
(?) RNA and protein active efflux system Gram+ s. aureus and decreased oral urethritis fatalities following
synthesis (?) in Gram+ and Gram- b. anthracis absorption following empiric therapy for trovafloxacin
3rd generation coadministration of travelers diarrhea joint arthralgias or
(levofloxacin) metal cations (infectious diarrhea) swelling in kids
improved Gram+ (antacids) multi-drug resistant
Gram- enteric and TB
pseudomonas
mycoplasma,
legionella, anaerobes
Drug Mechanism of Action Mechanism of Spectrum of Activity Pharmacology Indications for Use Toxicity
Resistance
Trimethoprim- sequential Sulfa Broad spectrum combo antibiotic 1:5 UTIs hypersensitivity rxns
Sulfamethoxazole interference with folic decreased bactericidal ratio of TMP:Sulfa; prostatitis (rash, fever), rare
(TMP-SMZ) acid synthesis permeability (plasmid) Gram+ serum ratio 1:20 pneumocystis carinii Stevens Johnson
Sulfa is a structural increased PABA staphylococci, oral and parenteral infection (AIDS) syndrome (mucosal
synergistic drug analog of PABA; production streptococci, listeria, well distributed; good diarrheal illness due and cutaneous illness
combo competes for enzyme TMP NOT enterococci levels in lungs, to salmonella, shigella, seen in AIDS pts)
dihydropteroate synthesis of Gram- kidneys, biliary tree, enterotoxigenic e. coli GI nausea,
synthetase dihydrofolate e. coli, klebsiella, and CNS upper and lower vomiting, diarrhea
TMP is a competitive reductase with proteus, salmonella, partially metabolized respiratory infections (rare) hepatitis,
inhibitor of decreased affinity for shigella, vibrio, in liver, excreted in infections caused by megoblastic anemia,
dihydropteroic acid TMP neisseria, h influenzae urine p. cepacia, nocardia increased serum
overproduction of misc. creatinine
dihydrofolate pneumocystis,
reductase nocardia, chlamydia