ANTIBIOTICS

Antibiotics work in 4 different ways:

1. Inhibition of cell wall synthesis
a. Bind to cytoplasmic-protein binding protein (PBPs) Inhibit transpeptidation Inhibit cross-linking of bacterial wall
2. Inhibition of protein synthesis
a. Interfere w/ formation of initiation complex
b. Interfere w/ incorporation of next amino acid
c. Interfere w/ formation of peptide bond
d. Interfere w/ translocation
3. Inhibition of folic acid synthesis
4. Inhibition of nucleic acid synthesis
Bactericidal vs. Bacteriostatic
Bactericidal- kills bacteria
Bacteriostatic- does NOT kill the bacteria
Type
1. Cell Wall
Synthesis (-)

Drug
Penicillins*
Cephalosporins*
Impenem*
Meropenem*
Aztreonam*
(Monobactam)
Vancomycin*

2. Protein
Synthesis (-)
Interfere w/
formation of
initiation complex

Indication

Antibiotic Drugs
MOA
Inhibit
transpeptidation
Inhibit cross-linking of
bacterial wall

MOA of Resistance

Additional Info

-lactamase cleavage
of drugs w/ -lactam
ring (transpeptidation

IV against gram
bacteria
MRSA

Aminoglycoside
(30s)*
Linezolid (50s)*

Drug of Choice (DOC)

for MRSA/VRSA

Spectinomycin

DOC for Gonorrhea

Inhibits peptidoglycan
synthasebinds to DAlanine*
Doesnt cause
misreading of genetic
code
Bactericidal-misread
genetic code carried by
mRNA incorporation
of wrong AA
(-) Protein synthesis
binds to 30s Doesnt
caused misreading of

Production of
conjugating enzymes
that drug clearance

NOT an
aminoglycoside

genetic code
2. Protein
Synthesis (-)
Interfere w/
incorporation of
next AA

Tetracyclines
(30s)*
Tetracycline
Doxycycline
Minocycline
Demeclocycline

2. Protein
Synthesis (-)
Interfere w/
formation of
peptide bond

Dalfopristin (50s)*
Quinupristin
(50s)*
Chloramphenicol
(50s)*

Chlamydia
Rickettsia
Mycoplasma
Brucella
Yersinia
Vibrio Cholera
Prostatitis
(Doxycyclinepenetrated prostate)
Gonorrhea
(Doxycycline)
SIADH
(Demeclocycline)

Bacteriostatic-inhibits
insertion of
aminoacyl t-RNA into
A-site
Demeclocycline (-)
ADH

Production of
active transport
systems that push
drugs out of the cell
1. Contraindicated in
Children < 8yrs
permanent
discoloration of teeth
2. Use sunscreen +
protective clothing
outdoors
phototoxicity
3. Outdated
tetracyclines
Fanconi-like
syndrome
4. Hepatotoxicity (in
pregnant woment)
5. Nephrogenic
Diabetes Insipidus
(Demeclocycline)
6. Vestibular
Ototoxicity
(Minocycline)
ALL tetracyclines
required dose
adjustment (except
doxycycline)
renal impairment

DOC for MRSA

Bacteriostatic-inhibition
of peptidyltransferase

Formation of
acetylating enzymes
that inactivate drugs

Used in patients
allergic to penicillin
Dairy products
should be avoided
w/ tetracyclines
due to
absorption
(chelators-except
doxycycline +
minocycline)

2. Protein
Synthesis (-)
Interfere w/
translocation

Macrolide (50s)*
Clindamycin
(50s)*

Bacteriostatic- inhibit
translocation of peptidyltRNA from acceptor
donor site

Methylation of base in
RNA that alter drugs
binding

3. Folic Acid
Synthesis (-)

Sulfonamide*

(-) Dihydropteroate
synthetase (from
beginning)

Formation of PABA
resistance to
inhibition of
dihydropteroate
synthetase

Trimethoprim*
Pyrimethamine*

4. Nucleic Acid
Synthesis (-)

Fluroquinolones
(Ciprofloxacin)*
Rifampin

(-) Dihydropteroate
reductase (more from
the end)
(-) DNA gyrase
(topoisomerase II)
(-) DNA-dependent RNA
polymerase

Transport systems
to push drugs out
Resistance to
inhibition of
topoisomerase II

Antibiotic Resistance:
R-factor plasmid-mediated transmission* (plasmids are outside of chromosome + can carry DNA producing mutation)
Selection of resistant cells*
o Antibiotics target certain cells w/ bacteria once bacteria have simple mutation reproduction in large #s produce resistance to
that antibiotic
o During antibiotic presence, cell mutates and becomes resistant
Antibiotic Combination:
Additive Effect: 1+1= 2
o The antibiotics added together take the effects of BOTH drugs and add them together
Synergistic Effective: 1+1= 3
o Ex. Penicillins + Aminoglycosides
o Adding antibiotics together makes a greater and better effect
o Potentiation- like synergism but 1 drug has ZERO effect when given alone, while the other has an effect
Antagonistic Effect: 1+1=0
o Ex. Penicillins + Tetracylines (in pneumococcal meningitis)
CLINICALLY
o Bateriostatic- active host defense dependent (inhibits growth)

Bacteriocidal- usually given to immunocompromised

BACTERIA CLASSIFICATION
Gram + (Purple)
Gram - (Red)
*Staphylococcus*
E. Coli
Streptococcus
Neisseria
Clodtridium
H. Influenza
Pseudomonas*
Bacteroids
Klebsiella
Legionella
Staphyloccocus Aureus (Gram +) 4 Types
1. Non-Penicillinase /Non--Lactamase Producing
2. Penicillinase Producing/ -Lactamase Producing
3. Methicillin Resistant Staph Aureus (MRSA)
4. Vancomycin Resistant Staph Aureus (VRSA)
ANTIOBIOTIC CHRONOLOGY
1st- Penicilliins
Penicillin is very effective against Staphyloccocus Aureus until about age 50
Good against gram + (Streptococcus + Staphyloccocus), rheumatic fever, sore throat, glomerularnephritis
DOC for syphilis, trepenema pallidum
Penicillian VK (Oral)*
Penicillian G (IV-IM)*
nd
2 - Penicillinase Resistant Penicillins
Developed when some penicillanase producing staphylococcus aureus appeared
o Oxacilin (IV), Cloxacillin (PO), Dicloxacillin (PO), Nafcillin (IV), Methicillin (only used in lab get interstitial nephritis)
o Good against staphylococcus aureus
Developed when strains of MRSA appeared
o VANCOMYCIN*
Rx of MRSA
NOT a penicillin
3rd-Broad Spectrum Antibiotics (Aminopenicillins)
Amoxacillin, Ampicillin*
Good against Streptococcus & Gram - bacteria
o But NOT Staphylococcus Aureus
4th- Extended Spectrum Penicillins (Antipseudomonads)

 Pipercillin, Ticarcillin, Carbenicillin

o Good against Streptococcus & Gram - bacteria (including pseudomonas)
But NOT Staphylococcus Aureus
th
5 -B-Lactamase Inhibitors
Clavulanate, Sulbuctam*
Combined it w/ Broad Spectrum + Extended Spectrum to cover EVERYTHING, including Staphylococcus Aureus
o Amoxacillin + Clavulanate
o Ampicilln + Sulbactam
o Pipercillin + Tazobactum
o Ticarcillin + Caluvulunate
o Good against gram + & gram -, but NOT MRSA
CAUTIONS WITH ANTIBIOTICS
1. ALWAYS, assess for ALLERGIES
2. If allergic to penicillin also allergic to cephalosporins
3. If normal flora is disturbed during antibiotic therapy SUPERINFECTION*
a. Signs: black + furry overgrowth on tongue, loose or foul smelling stools, vaginal itching or discharge (women)
b. Caused by microorganisms resistant to given antibiotics
4. Avoid taking oral penicillin with acidic juices or soda due to drug absorption
5. ALWAYS teach patient about completing full therapeutic course, even if feeling better due to risk of resistant organism forming
a. *Bacterial Resistance* occurs when:
i. Patient stops taking antibiotics prematurely
ii. Environmental dispersion of liquid antibiotics
iii. Antibiotics are prescribed to Rx Viral Infection

CEPHALOSPORINS
4 Generations of Cephalosporins
o Later generations are better for gram
o CNS entry occurs in the later generations
o achieved through inhibition of the bacterial cell wall synthesis.

Generation
First

Drug
Cefazolin
Cephalothin

Second
Cefotetan

Indication
Gram + Bacteria
Surgical prophylaxis

MOA

Side Effects

Additional Info
NO CNS entry
Renal Tubular Necrosis

Gram Bacteria
Bacterioid Fragilis

Disulfiram like

NO CNS entry, except

Cefuroxime

Cefaclor
Third
Ceftriaxone (IV)

action
Pseudomembranous colitis
Biliary sludge w/ cholecytitis like
illness Ceftriaxone* &
Cefoperazone*

Gram Bacteria &

Pseduomonas
Single dose for
gonorrhea

Cefixime (PO)
Fourth

Cefepime (IV)

Some serum sickness

Same as 3rd Gen &

Gram + Bacteria

Enters CNS except

Cefoperazone

Enters CNS

Dose adjustment in renal impairment*

o EXCEPT: Ceftriaxone & Cefoperazone
IF patient allergic to penicillins DONT PRESCRIBE CEPHALOSPORINS*
o If Gram + Macrolides (Erythromycin)
o If Gram - Aztreonam
Cephalosporins NOT affective against:
o Chlamydia
o MRSA
o Mycoplasma
o Enteroccoci
o Listeria
NEW -Lactams
Drug

Indication

MOA

Monobactams
(Aztreonam*)

IV against Gram -

Binds to PBPs 1a & 3 (-)

transpeptidation

Adverse Effects

Additional Info

Carbepenems
Imipenem*
Cilastatin*

IV against Gram +,Gram -,

and anaerobes
Imipenem + Cilastatin
always given together

Imipenem is rapidly
metabolized by renal
dipeptidase
Ciliastatin is a specific (-) of
dipeptidase duration of

Imipenem-Seizure
w/ renal dysfunction

NO cross-sensitivity to
penicillins
Resistant to -lactamase
Synergistic to
aminoglycosides
Carbapenem resistant to
-lactamase

Meropenem

Serious infections

action of Imipenem

VANCOMYCIN

NOT a penicillin or cephalosporin

Indication:
o Gram + bacteria ONLY
o IV effective against MRSA*
o Oral effective against clostridium difficile* (pseudomembranous colitis)
MOA: (-) bacterial cell wall + (-) elongation of peptidoglycan chains Bacterialcidal
*Adverse Effects*:
1. Red Man Syndrome
a. Chills, fever, rash, red face+ neck (due to histamine release)
2. Ototoxicity
3. Hypersensitivity
4. Nephrotoxicity
Resistance: VRSA + VRE
NOT effective against Gram (ex. E.Coli)

MACROLIDES
DOC for Community Acquired Pneumonia + Mycoplasma Pneumoniae
NOT effective against MRSA
MOA: Binds to motilin receptors Diarrhea
Adverse Effects: Reversible ototoxicity
Inhibits: Cytochrome P450
Drug

Indication

Adverse Effects

Erythromycin*

Good against
staphyloccocs,
streptococcous,
mycoplasma, legionella

Azithromycin*

Erythromycin + Chlamydial
urethritis

Erythromycin estolate
cholestatic jaundice
GI problems (diarrhea
+vomiting)
High dose prolonged
QT interval
Less side effects than
erythromycin

Clarithromycin*

Erythromycin + H.
influenza + H. pylori
*Good against MAC
(mycobacterium
avium complex)* in
AIDS patients

KETOLIDES
New class related to macrolides Same MOA as macrolides
Telithromycin*
o Similar to azithromycin
Adverse Effects:
o Prolonged QT interval
o Inhibits cytochrome P450
o Produces exacerbation of Myasthenia Gravis

ANAEROBIC INFECTIONS
For Bacteroids:
Clindamycin
o Oral Infections (above diaphragm)
o Risk for Antibiotic-Associated PseudoMembranous Colitis (AAPMC)*
Metronidazole
o Intraabdominal (below diaphragm)
o Rx of AAPMC*
o DOC for:
Protozoa Giardia Lamblia, Trichomonas Vaginalis, Entamoeba Histolytica*
Bacterial AAPMC, Bacteroids Fragilis, G. Vaginalis*
o MOA: Bactericidal (MOA unknown)
o Adverse Effects:
Furry tongue
Glossitis
Peripheral Neuropathy
Disulfiram-like action*
Other Disulfiram-like action drugs:
o Metronidazole, Cefamandole, Cefoperazone, Cefotetan, Griseofulvin (anti-fungal)
1st give Metronidazole 2nd choice is Vancomycin

FLUOROQUINOLONES
Ciprofloxacin, Norfloxacin, Ofloxacin, Enoxacin, Sparfloxacin, Trovafloxacin
Analogues of Nalidixic Acid*
DOC for anthrax (ciprofloxacin) 2nd choice= penicillins or tetracyclines
Indication:
o Gram Sepsis (PO)
o Ciprofloxacin/ Ofloxacin single dose for gonorrhea
o Sparfloxacin Resistant Pneumococcus
o Ofloxacin Chlamydia
Contraindication*: Pregnancy; careful <18 yr old (-) chondrocytes

AMINOGLYCOSIDES
Gentamycin, Tobramycin, Paromomycin, Amikacin, Neomycin, Kanamycin, Streptomycin
Indication: Gram Infections
MOA: Targets active transport by O2 dependent systems (for aerobic bacteria)
Used in Combination:
o Endometritis: Triple Antibiotics Gentamycin + Ampicillin + Metronidazole
o Enterococcus Infection: Synergistic w/ Ampicillin
o Pseudomonal Infection: Synergistic w/ Extended Spectrum Penicillin (Piperacillin, Ticarcillin, Carbenicillin)
Adverse Effects:
o Ototoxicity (2%)
Auditory-irreversible (cochlear), high pitch 1st
Vestibular- reversible
o Nephrotoxicity (7%)
Proteinuria, hypokalemia, acute tubular necrosis
o Neuromuscular Blockade- prejunctional release of Ach
o ALL aminoglycosides require dose adjustment renal impairment
Drug Interactions:
o Enhanced ototoxicity Fuerosemide, ethacrynic acid
o Enhanced nephrotoxicity Amphotericin B, Vancomycin, Cisplatin, Cyclosporin

Drug
Sulfisoxazole*

Indication
UTI*
Nocardial Infection* (lung
abscess)

SULFONAMIDES
Adverse Effects
1. Hypersensitivity: Rash to Steven Johnson
Syndrome
2. Hemolysis in G6PD deficiency

Additional Info
Drug Interactions:
warfarin activity

Sulfasalazine*
Sulfacetamide*
Silver Sulfadizine*
Sulfadiazine
Pyrimethamine
Trimethoprin/
Sulfamethoxazole
(TMZ-SMX; CoTrimoxazole)*

Ulcerative Colitis*
Trachoma (Topical)*
Burns (Topical)*
Toxoplasmosis*

3. Photosensitivity
phenytoin activity
4. Crystalluria (Rx w/ fluids/IV)
its an
Contraindication: 3rd trimester of pregnancy
antiepileptic
(cross BBB Kernicterus (jaundice of
sclera) bile in basal ganglia seizure)
drug. Seizures
DOC for Prophylaxis & Rx of
TMZ-SMX Only:
Pneumocystis Carinii
Thrombocytopenia
Pneumonia (PCP)*
Leukopenia
2nd choice: Salmonella,
GI distress (AIDS patients)
Chancroid, MRSA
Hemolysis
** Prophylaxis (Greek: to guard or prevent beforehand) is any medical or public health procedure whose purpose is to prevent, rather
than treat or cure a disease.
Urinary Tract Antiseptics
o Methenamine Mandelate
o Nitofurantoin
Urinary Tract Anelgesics
o Phenazopyridine
Produces orangered urine* that may stain clothing
Broad Spectrum Antibacterial
o Chloramphenicol
Adverse Effect: Aplastic Anemia*, Gray Baby Syndrome is a condition where bone marrow does not produce sufficient new
cells to replenish blood cells
Not used in US anymore
MRSA (Methecillin-Resistant Staph Aureus)
o *Vancomycin*
VRE (Vancomycin Resistant Enterococcus) & VRSA (Vancomycin Resistant Staph Aureus)
o *Linezolid*
o Quinupristin/Dalfopristin
50S stop incorporation of next AA