ANTIBIOTICS CLASSIFICATION AND MECHANISM

Antibiotic Grouping By Mechanism

Cell Wall Synthesis Penicillins
Cephalosporins
Vancomycin
Beta-lactamase Inhibitors
Carbapenems
Aztreonam
Polymycin
Bacitracin
Protein Synthesis Inhibitors Inhibit 30s Subunit
Aminoglycosides (gentamicin)
Tetracyclines
Inhibit 50s Subunit
Macrolides
Chloramphenicol
Clindamycin
Linezolid
Streptogramins
DNA Synthesis Inhibitors Fluoroquinolones
Metronidazole
RNA synthesis Inhibitors Rifampin
Mycolic Acid synthesis inhibitors Isoniazid
Folic Acid synthesis inhibitors Sulfonamides
Trimethoprim

Antibiotic Classification & Indications

 Inhibits Cell Wall Synthesis
Penicillins
(bactericidal: blocks cross linking via competitive inhibition of the transpeptidase enzyme)
Class/Mechanism Drugs Indications (**Drug of Toxicity
Choice)
Penicillin Penicillin G Strep. pyogenes Hypersensitivity
Aqueous penicillin G (Grp.A)** reaction
Procaine penicillin G Step. agalactiae Hemolytic anemia
Benzathine penicillin G (Grp.B)**
Penicillin V C.
perfringens(Bacilli)**

Aminopenicillins Ampicillin Above + Above

Amoxicillin ↑ Gram-negative:
E. faecalis**
E. Coli**
Penicillinase-resistant- Methicillin Above + Above +
penicillins Nafcillin PCNase- Interstitial nephritis
Oxacillin producingStaph.
Cloxacillin aureus
Dicloxacillin
Antipseudomonal penicillins Carbenicillin Above + Above
Ticarcillin Pseudomonas
Piperacillin aeruginosa**
Cephalosporins
(bactericidal: inhibits bacterial cell wall synthesis via competitive inhibition of the transpeptidase enzyme)
1st generation Cefazolin Staph. aureus** Allergic reaction
Cephalexin Staph. epidermidis** Coombs-positive
Some Gram-negatives: anemia (3%)
E. Coli
Klebsiella

2nd generation Cefoxitin Above + Allergic Reaction

Cefaclor ↑ Gram-negative ETOH Disulfiram
Cefuroxime reaction
3rd generation Ceftriaxone Above + Allergic Reaction
Cefotaxime ↑ Gram-negative ETOH Disulfiram
Ceftazidime Pseudomonas reaction
Cefepime (4th generation)
 Other Cell Wall Inhibitors
Vancomycin Vancomycin MRSA** Red man syndrome
(bactericidal: disrupts PCN/Ceph allegies** Nephrotoxicity
peptioglycan cross-linkage) S. aureus Ototoxicity
S. epidermidis

Beta-lactamase Clavulanic Acid S aureus** Hypersensitivity

Inhibitors Sulbactam S epidermis** Reaction
(bactericidal: blocking cross Tazobactam E.Coli** Hemolytic anemia
linking) Klebsiella**
Carbapenems Imipenem (+ cilastatin) Broadest activity of
Meropenem any antibiotic
Doripenem (except MRSA,
Ertapenem Mycoplasma)
Aztreonam Aztreonam Gram-negative rods
Aerobes
Hospital-acquired
infections
Polymyxins Polymyxin B Topical Gram-negative
Polymyxin E infections
Bacitracin Bacitracin Topical Gram-positive
infections
Protein Synthesis Inhibition
Anti-30S ribosomal subunit
Aminoglycosides Gentamicin Aerobic Gram- Nephrotoxicity
(bactericidal: irreversible Neomycin negatives Ototoxicity
binding to 30S) Amikacin Enterobacteriaceae
Tobramycin Pseudomonas
Streptomycin
Tetracyclines Tetracycline Rickettsia Hepatotoxicity
(bacteriostatic: blocks tRNA) Doxycycline Mycoplasma Tooth discoloration
Minocycline Spirochetes (Lyme's Impaired growth
Demeclocycline disease) Avoid in children <
12 years of age
Anti-50S ribosomal subunit
Macrolides Erythromycin Streptococcus Coumadin
(bacteriostatic: reversibly Azithromycin H. influenzae Interaction
binds 50S) Clarithromycin Mycoplamsa (cytochrome P450)
pneumonia
Chloramphenicol Chloramphenicol H influenzae Aplastic Anemia
(bacteriostatic) Bacterial Meningitis Gray Baby
Brain absces Syndrome
Lincosamide Clindamycin Bacteroides fragilis Pseudomembranous
(bacteriostatic: inhibits S aureus colitis
Coagulase-negative Staph &
peptidyl transferase by Strep Hypersensitivity
interfering with amino acyl- Excellent Bone Penetration Reaction
tRNA complex)
Linezolid Linezolid Resistant Gram-
(variable) positives
Streptogramins Quinupristin VRE
Dalfopristin GAS and S. aureus skin
infections
DNA Synthesis Inhibitors
Fluoroquinolones
(bactericidal: inhibit DNA gyrase enzyme, inhibiting DNA synthesis)
1st generation Nalidixic acid Steptococcus Phototoxicity
Mycoplasma Achilles tendon
Aerobic Gram + rupture
Impaired fracture
healing
2nd generation Ciprofloxacin As Above as above
Norfloxacin +Pseudomonas
Enoxacin
Ofloxacin
Levofloxacin
3rd generation Gatifloxacin As above + Gram- as above
positives
4th generation Moxifloxacin As above + Gram- as above
Gemifloxacin positives + anaerobes
Other DNA Inhibitors
Metronidazole Metronidazole (Flagyl) Anaerobics Seizures
(bacteridical: metabolic Crebelar
biproducts disrupt DNA) dysfunction
ETOH disulfram
reaction
RNA Synthesis Inhibitors
Rifampin Rifampin Staphylococcus Body fluid
(bactericidal: inhibits RNA Mycobacterium (TB) discoloration
transcription by inhibiting Hepatoxicity (with
RNA polymerase) INH)
Mycolic Acids Synthesis Inhibitors
Isoniazid Isoniazidz TB
Latent TB
Folic acid Synthesis Inhibitors
Trimethoprim/Sulfonamides Trimethoprim/Sulfamethoxazole UTI organisms Thrombocytopenia
(bacteriostatic: inhibition (SMX) Proteus Avoid in third
with PABA) Sulfisoxazole Enterobacter trimester of
Sulfadiazine pregnancy
Pyrimethamine Pyrimethamine Malaria
T. gondii
Bacteria Overview

Gram Postive Cocci

Staphylococcus Staph. aureus
MSSA
MRSA
Staph. epidermis
Staph saprophyticus
Streptococcus Strep pneumoniae
Strep pyogenes (Group A)
Strep agalacticae (Group B)
Strep viridans
Strep Bovis (Group D)
Enterococci E. faecalis (Group D strep)
Gram Positive Bacilli
Spore Forming Bacillus anthracis
Bacillus cereus
Clostridium tetani
Clostridium botulinum
Clostridium perfringens
Clostridium difficile
Non-Spore Forming Corynebacterium diphtheriae
Listeria monocytogenes
Gram Negative Cocci
Neisseria Neisseria meningitidis
Neisseria gonorrhoeae
Gram Negative Bacilli
Enterics Escherichia coli
Salmonella typhi
Salmonella enteridis
Shigella dysenteriae
Klebsiella pneumoniae
Serratia
Proteus
Campylobacter jejuni
Vibrio cholerae
Vibrio parahaemolyticus/vulnificus
Helicobacter pylori
Pseudomonas aeruginosa
Bacteroides fragilis
Respiratory bacilli Haemophilus influenzae
Haemophilius ducreyi
Bordatella pertussis
Zoonotic bacilli Yersinia enterocolitica
Yersinia pestis
Brucella
Francisella tularensis
Pasteurella multocida
 Bartonella henselae
Other Gardnerella vaginalis
Other Bacteria
Mycobacteria Mycobacterium tuberculosis
Mycobacterium leprae
MOTTS
Spirochetes Borrelia burgdorferi
Leptospira interrogans
Treponema pallidum
Chlamydiaceae Chlamydia trachomatis
Chlamydophila
Rickettsia
Ehrlichia
Mycoplasmataceae Mycoplasma pneumoniae
Ureaplasma urealyticum
Fungus-like Bacteria Actinomyces israelii
Nocardia

Antibiotic Resistance Mechanisms

 Bacteria develop ability to hydrolyze these drugs using β lactamase
o confers resistance to penicillin
o e.g. E. coli, Staph epidermidis, Pseudomonas aeruginosa, Klebsiella pneumoniae
o add β lactamase inhibitor e.g. clavulanic acid in amoxicillin-clavulanate (Augmentin)
 Genetic mutation of mecA
o a bacterial gene encoding a penicillin-binding protein. New PBP has reduced affinity
for antibiotics
o confers resistance to methicillin, oxacillin, nafcillin
o e.g. MRSA
 Altered cell wall permeability
o confers resistance to tetracyclines, quinolones, trimethoprim and β lactam
antibiotics

 Creation of biofilm barrier

o provides an environment where offending bacteria can multiply safe from the hoste
immune system
 Salmonella
 Staph epidermidis
 Active efflux pumps
o confers resistance to erythromycin and tetracycline
o e.g. msrA gene in Staph
 Altered peptidoglycan subunit (altered D-alanyl-D-alanine of NAM/NAG-peptide)
o confers resistance to vancomycin
o e.g. vancomycin resistant enterococcus (VRE)
 Ribosome alteration
o erm gene confer inducible resistance to MLS (macrolide lincosamide streptogranin)
agents via methylation of 23s rRNA
o demonstrate using D zone test
  for inducible clindamycin resistance in Staph and beta hemolytic Strep

Penicillins
 Mechanism
o interfer with bacterial cell wall synthesis
 Subclassification and tested examples
o natural
 penicillin G
o penicillinase-resistant
 methicillin (Staphcillin)
o aminopenicillins
 ampicillin (Omnipen, Polycillin)

Cephalosporins
 Overview
o bactericidal
 Mechanism
o disrupts the synthesis of the peptidoglycan layer of bacterial cell walls
 does so through competitive inhibition on PCB (penicllin binding proteins)
 peptidoglycan layer is important for cell wall structural integrity.
o same mechanicsm of action as beta-lactam antibiotics (such as penicillins)
 Subclassification and tested examples
o first generation
 cefazolin (Ancef, Kefzol)
o second generation
 cefaclor (Ceclor)
o third generation
 cefriazone (Rocephin)
o fourth generation
 cefepime (Maxipime)

Fluoroquinolones
 Mechanism
o blocks DNA replication via inhibition of DNA gyrase
 Side effects
o inhibit early fracture healing through toxic effects on chondrocytes
o increased rates of tendinitis, with special predilection for the Achilles tendon.
 tenocytes in the Achilles tendon have exhibited degenerative changes when
viewed microscopically after fluoroquinolone administration.
 recent clinical studies have shown an increased relative risk of Achilles
tendon rupture of 3.7.
 Subclassification and tested examples
o ciprofloxacin (Cipro)
o levofloxacin (Levaquin)
Aminoglycosides
 Mechanism
o bactericidal
o inhibition of bacterial protein synthesis
 work by binding to the 30s ribosome subunit, leading to the misreading of
mRNA. This misreading results in the synthesis of abnormal peptides that
accumulate intracellularly and eventually lead to cell death. These antibiotics
arebactericidal.
 Subclassification and tested examples
o gentamicin (Garamycin)

Vancomycin
 Coverage
o gram-positive bacteria
 Mechanism
o bactericidal
o an inhibitor of cell wall synthesis
 Resistance
o increasing emergence of vancomycin-resistant enterococci has resulted in the development
of guidelines for use by the (CDC)
o indications for vancomycin
 serious allergies to penicillins or beta-lactam antimicrobials
 serious infections caused by susceptible organisms resistant to penicillins (MRSA,
MRSE)
 surgical prophylaxis for major procedures involving implantation of prostheses in
institutions with a high rate of MRSA or MRSE

Rifampin
 Most effective against intracellular phagocytized Staphylococcus aureus in macrophages

Linezolid
 Linezolid binds to the 23S portion of the 50S subunit and acts by preventing the formation
of the initiation complex between the the 30S and 50S subunits of the ribosome.

Splenectomy
 Splenectomy patients or patients with functional hyposplenism require the following
vaccines and/or antibiotics
o Pneumococcal immunization
o Haemophilus influenza type B vaccine
o Meningococcal group C conjugate vaccine
o Influenza immunization
o Lifelong prophylactic antibiotics (oral phenoxymethylpenicillin or erythromycin)