ribosomal 50S subunit, which prevents translocation of
Antibiotic Summary
ANTIBACTERIALS
CELL WALL SYNTHESIS INHIBITORS
(BACTERICIDAL)
BETA-LACTAMS
Mode of Action
• beta-lactam ring competitively inhibits penicillin binding
proteins (PBPs) and prevents cross linking of
peptidoglycan strands normally needed for cell wall
integrity: osmotic lysis of the bacterium
PENICILLINS
• benzyl penicillin (narrow spectrum, not penicillinase
resistant)
 e.g. penicillin G (IV or IM), penicillin V (PO)
 effective against Streptococci, most anaerobes
(not B. fragilis), Neisseria, and T. pallidum (syphilis)
• isoxazoyl penicillin (narrow spectrum, penicillinase
resistant))
 e.g. methicillin, cloxacillin, oxacillin, nafcillin
 effective against Staphylococci and some
Streptococci; drug of choice for
penicillin-resistant S. aureus (PRSA)
• aminopenicillins (broad spectrum, penicillinase sensitive)
 e.g. ampicillin, amoxicillin
 effective against most Gram positives including
Enterococci, some Gram negatives
 amoxicillin first line therapy for acute cystitis or
asymptomatic UTI in pregnant women
 ampicillin combined with gentamicin first line
therapy for pyelonephritis
 combine with clavulanic acid (penicillinase
inhibitor) to enhance spectrum (i.e.
increase activity vs. beta-lactamase producers)
• ureidopenicillins (broad spectrum, penicillinase sensitive)
 e.g. piperacillin, carbenicillin, ticarcillin
 effective against Gram positives, Pseudomonas,
Gram negatives (e.g. Enterobacter), and anaerobes
(e.g. Bacteroides fragilis)
 combine tazobactam with piperacillin to
enhance spectrum of activity especially
against the penicillinase producing organisms
CEPHALOSPORINS
Clinical Use
• 1st generation
 e.g. cefazolin IV/IM (Ancef™); cephalexin po
(Keflex™)
 Gram positive cocci (except MRSA and
Enterococci), Gram negative bacilli
(mainly E. coli, Klebsiella, P. mirabilis)
• 2nd generation
 e.g. cefuroxime IV/IM (Kefurox™); cefuroxime
axetil po (Ceftin™), Cefotetan po (Cefotan™)
 less Gram positive activity but more Gram
negative coverage than 1st
generation (H. influenzae, E. coli, Klebsiella, Proteus)
 cefotetan has anaerobic activity and is used in
intra-abdominal and pelvic infections
• 3rd generation
 e.g. cefotaxime IV/IM, ceftriaxone IV/IM,
ceftazidime IV/IM
folic acid production and thus inhibits nucleic acid
polypeptide chain synthesis and bacterial growth
• SMX competes with paraaminobenzoic acid for
Clinical Use
dihydropteroate synthase to prevent
• Mycoplasma, Legionella, Chlamydia, Treponema,
folic acid production and thus inhibit nucleic acid
Helicobacter pylori
synthesis and bacterial growth
 broad spectrum activity against enteric Gram • Urinary Tract infections, Gram positive cocci
(streptococcal infections in patients allergic to penicillin) Clinical Use
negatives, less Gram positive
coverage than 1st generation • first line therapy for community-acquired pneumonia as • SMX alone: Nocardia
an outpatient • combination: Pneumocystis carinii, Toxoplasma, Shigella,
 crosses blood-brain barrier (unlike 1st and 2nd
generation) Salmonella, commonly used for urinary tract infections
 ceftazidime should be used if Pseudomonas LINCOSAMIDES (e.g. Clindamycin)
DNA GYRASE INHIBITORS (BACTERICIDAL)
coverage is required Mechanism of Action
• 4th generation • inhibit protein synthesis by binding to 50S ribosomal
 e.g. cefepime, cefpirome QUINOLONES
subunit, which prevents peptide bond formation
 broad spectrum activity against Gram negatives • e.g. ciprofloxacin, levofloxacin, moxifloxacin, norfloxacin,
(including P. aeruginosa) and good coverage of Clinical Use ofloxacin, gatifloxacin, nalidixic acid
Gram positive cocci (MRSA and S. pneumoniae) • Gram positives
 useful in severe hospital or community-acquired • anaerobic infections (B. fragilis, C. perfringens) Mechanism of Action
infections (pneumonia, bacteremia) • prevents supercoiling of nucleic acids by inhibiting DNA
LINEZOLID gyrase to block DNA replication
CARBAPENEMS (e.g. Imipenem, Meropenem) Mechanism of Action
• binds 23S ribosomal area of the 50S subunit, prevents
Clinical Use
Clinical Use • enteric Gram negative bacilli of urinary and GI tracts,
• broadest spectrum of activity against anaerobes, Gram funtional 70S initiation complex limited Gram positive coverage (6with levo, moxi, gati)
positives (except Enterococcus faecium and MRSA), and Clinical Use • ciprofloxacin first line therapy for uncomplicated and
Gram negatives, including P. aeruginosa • Enterococci, Staphylococci (basteriostatic): use in VRE complicated cystitis in adults
• imipenem drug of choice for drug-resistant Enterobacter • Streptococci (bactericidal)  use if Pseudomonas suspected
• always administered with cilastin (inhibitor of renal • levofloxacin, moxifloxacin, gatifloxacin useful against
dihydropeptidase I) to decrease inactivation in renal VIA 30S RIBOSOME (BACTERICIDAL) respiratory pathogens (Legionella, Chlamydia,
tubules Mycoplasma)
AMINOGLYCOSIDES  first line therapy for community acquired
GLYCOPEPTIDES (e.g. Vancomycin) (e.g. Gentamicin, Tobramycin, Amikacin, Streptomycin, pneumonia as an outpatient
Neomycin)  moxifloxacin and gatifloxacin have some
Mechanism of action
• blocks cell wall peptidoglycan polymerization (synthesis) anaerobic coverage
Mechanism of Action
resulting in loss of cell wall integrity and osmotic rupture • inhibit protein synthesis initiation by binding to the 30S
of the bacterium DNA-DEPENDENT RNA POLYMERASE INHIBITORS
ribosomal subunit, thereby causing misreading of mRNA (BACTERICIDAL)
Clinical Use Clinical Use
• only active against Gram positive organisms RIFAMPIN
• primarily Gram negative aerobes and mycobacteria
 true major penicillin allergic patients • tobramycin used for Pseudomonas aeruginosa infections
(e.g. anaphylaxis, exfoliative dermatitis, vasculitis, Mechanism of action
• requires oxygen for uptake, therefore, ineffective against • inhibits bacterial protein synthesis by inhibiting
or severe urticaria) anaerobes
DNA-dependent RNA polymerase
 MRSA infection
 coagulase-negative Staphylococcus (e.g. VIA 30S RIBOSOME (BACTERIOSTATIC) Clinical Use
S. epidermidis) in patients with prosthetic valves • Gram positive cocci, many Gram negative bacilli, most
with joint or line infections Mycobacterium species
Toronto Notes 2006 – Editors: Carolyn Shiau and Andrew Toren
TETRACYCLINES (e.g. Tetracycline, Doxycycline)
Toronto Notes 2006 – Editors: Carolyn Shiau and Andrew Toren
 oral formulation is 2nd line treatment • always used in combination to reduce resistance
for antibiotic-associated pseudomembranous Mechanism of Action • prophylaxis against meningococcus
• inhibit protein synthesis by binding to the 30S ribosomal
colitis (C. difficile)
subunit, thereby blocking amino acid linked tRNA from
binding to the A site of the ribosome DNA COMPLEX DAMAGING AGENTS
PROTEIN SYNTHESIS INHIBITORS Clinical Use (BACTERICIDAL)
• Chlamydia, Mycoplasma, Rickettsia, Borrelia burgdoferi
VIA 50S RIBOSOME (BACTERIOSTATIC) (Lyme disease) METRONIDAZOLE
• doxycycline used for malaria prophylaxis and treatment
CHLORAMPHENICOL • tetracycline used to treat acne
Mechanism of Action
• forms toxic metabolites in the bacterial cell which
Mechanism of Action damage the microbial DNA
• inhibits protein synthesis by binding to the ribosomal Side-effects
• GI upset, hepatotoxicity Clinical Use
50S subunit, which prevents the aminoacyl end of tRNA
from associating with peptidyl transferase • Fanconi’s syndrome • anaerobic bacteria (first line therapy for
• discolors teeth and inhibits bone growth in children pseudomembranous colitis)
Clinical Use (contraindicated in pregnancy, neonates, children) • several protozoan parasites (Trichomoniasis, amebiasis,
• 2nd line treatment for meningitis (H. influenzae, giardiasis)
N. meningitides, S. pneumoniae) FOLIC ACID METABOLISM INHIBITORS • used in combination with omeprazole and
(BACTERIOSTATIC) clarithromycin in patients with penicillin
MACROLIDES allergy for triple therapy against H. pylori
(e.g. Erythromycin, Clarithromycin, Azithromycin) TRIMETHOPRIM-SULFAMETHOXAZOLE (TMP-SMX) • Crohn’s disease, hepatic encephalopathy
Mechanism of Action Mechanism of Action
• inhibit protein synthesis by binding to the P site of the • TMP inhibits dihydrofolate reductase which prevents