9/9/2020 Antibiotic Classification & Mechanism - Basic Science - Orthobullets

Overview of By Mechanism

PENICILLINS CEPHALOSPORINS FLUOROQUINOLONES AMINOGLYCOSIDES MONOBACTAMS CARBAPENEMS MACROLIDES OTHER

Natural First generation Ciprofloxacin (Cipro) Amikacin Aztreonam Ertapenem Azithromycin Vancomycin
Levofloxacin (Levaguin) Gentamicin Imienem Clarithromycin Rifampin
Moxifloxacin (Avelox) Kanamycin Meropenem Dirithromycin Doxycycline
Penicillin G Cephalothin
Norfloxacin Neomycin Erythromycin Linezolid
Penicillin-VK Cefazolin (Ancef,
Tobramycin Clindamycin Tetracycline
Kefzol)
Trimethoprim/
Cephapririn
sulfamethoxacole
Cephalexin (Keflex)
other

Penicillinase Second Generation

Resistant
Methicillin Cefacor
Nafcillin Cefotetan (Cefotan)
Oxacillin other
other
Aminopenicillins Third Generation
Ampicillin Ceftriaxone
(Rocephin)
other
Fourth Generation
Cefpirome
Cefepime

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
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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 Hypersensitivity
Aqueous penicillin G Strep. pyogenes reaction
Procaine penicillin G (Grp.A)** Hemolytic anemia
Benzathine penicillin G Step. agalactiae
Penicillin V (Grp.B)**
C. perfringens(Bacilli)**

Aminopenicillins Ampicillin Above

Amoxicillin Above +
↑ Gram-negative:
E. faecalis**
E. Coli**

Penicillinase-resistant- Methicillin Above + Above +

penicillins Nafcillin PCNase- Interstitial nephritis
Oxacillin producingStaph.
Cloxacillin aureus
Dicloxacillin
Antipseudomonal Carbenicillin Above + Above
penicillins 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 Red man syndrome
(bactericidal: disrupts MRSA** Nephrotoxicity
peptioglycan cross-linkage) PCN/Ceph allegies** Ototoxicity
S. aureus
S. epidermidis

Beta-lactamase Inhibitors Clavulanic Acid Hypersensitivity

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(bactericidal: blocking cross Sulbactam S aureus** Reaction
linking) Tazobactam S epidermis** Hemolytic anemia
E.Coli**
Klebsiella**

Carbapenems Imipenem (+ cilastatin) Broadest activity of any

Meropenem 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 Hepatotoxicity
(bacteriostatic: blocks tRNA) Doxycycline Rickettsia Tooth discoloration
Minocycline Mycoplasma Impaired growth
Demeclocycline Spirochetes (Lyme's Avoid in children <
disease) 12 years of age

Anti-50S ribosomal subunit

Macrolides Erythromycin Streptococcus
(bacteriostatic: reversibly Azithromycin H. influenzae Coumadin
binds 50S) Clarithromycin Mycoplamsa Interaction
pneumonia (cytochrome P450)

Chloramphenicol Chloramphenicol H influenzae Aplastic Anemia

(bacteriostatic) Bacterial Meningitis Gray Baby
Brain absces Syndrome
Lincosamide Clindamycin
(bacteriostatic: inhibits Bacteroides fragilis Pseudomembranous
peptidyl transferase by S aureus colitis
interfering with amino acyl- Coagulase-negative Hypersensitivity
tRNA complex) Staph & Strep Reaction
Excellent Bone
Penetration

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
Mycoplasma Phototoxicity

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Aerobic Gram + Achilles tendon
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 dysfunction
biproducts disrupt DNA) 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
(bacteriostatic: inhibition with (SMX) Proteus Thrombocytopenia
PABA) Sulfisoxazole Enterobacter Avoid in third
Sulfadiazine trimester of
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

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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

confers resistance to penicillin
e.g. E. coli, Staph epidermidis, Pseudomonas aeruginosa, Klebsiella pneumoniae
add β lactamase inhibitor e.g. clavulanic acid in amoxicillin-clavulanate (Augmentin)
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Genetic mutation of mecA

carried by Staphylococcal cassette chromosome (SCCmec) mobile genetic unit
a bacterial gene encoding a penicillin-binding protein (PBP2a).
PBP2a has reduced affinity for antibiotics
confers resistance to methicillin, oxacillin, nafcillin
e.g. MRSA
SCCmec type IV has less genetic elements and is specific to CA-MRSA,
making CA-MRSA less multi-drug resistant
Altered cell wall permeability
confers resistance to tetracyclines, quinolones, trimethoprim and β lactam antibiotics
Creation of biofilm barrier
provides an environment where offending bacteria can multiply safe from the hoste
immune system
Salmonella
Staph epidermidis
Active efflux pumps
confers resistance to erythromycin and tetracycline
e.g. msrA gene in Staph
Altered peptidoglycan subunit (altered D-alanyl-D-alanine of NAM/NAG-peptide)
confers resistance to vancomycin
e.g. vancomycin resistant enterococcus (VRE)
Ribosome alteration
erm gene confer inducible resistance to MLS (macrolide lincosamide streptogranin)
agents via methylation of 23s rRNA
demonstrate using D zone test
for inducible clindamycin resistance in Staph and beta hemolytic Strep

Penicillins

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

Cephalosporins

Overview
bactericidal
Mechanism
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.
same mechanicsm of action as beta-lactam antibiotics (such as penicillins)
Subclassification and tested examples
first generation
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cefazolin (Ancef, Kefzol)

second generation
cefaclor (Ceclor)
third generation
cefriazone (Rocephin)
fourth generation
cefepime (Maxipime)

Fluoroquinolones

Mechanism
blocks DNA replication via inhibition of DNA gyrase
Side effects
inhibit early fracture healing through toxic effects on chondrocytes
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
ciprofloxacin (Cipro)
levofloxacin (Levaquin)

Aminoglycosides

Mechanism
bactericidal
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
gentamicin (Garamycin)

Vancomycin

Coverage
gram-positive bacteria
Mechanism
bactericidal
an inhibitor of cell wall synthesis
Resistance
increasing emergence of vancomycin-resistant enterococci has resulted in the
development of guidelines for use by the (CDC)
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
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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
Pneumococcal immunization
Haemophilus influenza type B vaccine
Meningococcal group C conjugate vaccine
Influenza immunization
Lifelong prophylactic antibiotics (oral phenoxymethylpenicillin or erythromycin)

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