1 Antibiotic Introduction Handout

Southwest College of Naturopathic Medicine 1
Introduction to antibiotics
Debra Wollner, PhD
Southwest College of
Naturopathic Medicine
Tempe, AZ
Antibiotics
Classifications and mechanisms
A little microbiology
Clinical applications
Respiratory infections
Urinary tract infections
GI infections
Viral infections
STDs
Fungal infections
Parasites
Vaccinations
Medications affecting the immune system

Course objectives
At the conclusion of this course students will be able to
Correctly identify the mechanisms of action of a variety of
medications used to treat microbial diseases.
Correctly identify, using current treatment guidelines, when the
use of anti-microbial medications is NOT indicated.
Correctly prescribe the proper medications to treat conditions
presented by theoretical patients.
Recognize contraindications of given medications and apply
them to theoretical patients.
Recognize known and suspected interactions of given
medications and apply them to theoretical patients.
Recognize likely adverse effects of given medications and apply
them to analysis of theoretical patient case studies.

Lecture objectives
Identify by classification antimicrobial medications
based upon the mechanism of action.
Explain the mechanisms of action of commonly used
antibiotics.
Recall basic microbiology as it relates specifically to
the use of antibiotics.
Identify and use basic terminology, including
antibiotic, selective toxicity, bacteriostatic and
bacteriocidal.
Define bacterial resistance and apply to the use of
antibiotics.
Interactions in general
Gut microbes are critical to many body processes
Gut microbes are important for the uptake and
efficacy of several medications
Bacteria make and secrete much of our vitamin K
Bacteria metabolize medications prior to absorption
This may increase or reduce drug uptake
Numerous interactions are expected when using
antibiotics in addition to other medications
ANTIBIOTIC
CLASSIFICATION
Mechanisms of action
Spectrum of activity (not very reliable)
Choice of antibiotic
Classifications
Based on mechanisms
Cell wall synthesis inhibitors
Penicillins, cephalosporins, imidazole antifungal
Cell membrane disruptors
Detergents and polyene antifungals
Protein synthesis inhibitors
Tetracyclines, aminoglycosides
DNA synthesis inhibitors
Rifamycins, TMP, acyclovir
How Resistance develops
Drug fails to reach target
Drug is inactivated
Target is changed

Mutation, transformation, conjugation
Antibiotics exert selective pressure
Selecting for the resistant strains
More than 50% of persons carry multiply resistant
coliform bacilli, also found in sewage
New antibiotics
Uncontrolled use (abuse) has led to the
development of multiple resistances
Requires the constant influx of new drugs
Increases costs dramatically

Drug resistant epidemics
MRSA, MDRTB, XDRTB
Require more responsible use of antibiotics
May see a return to the pre-antibiotic era (60 years ago)
Limit resistance
Usually, no antibiotic is necessary
Follow specific published guidelines for
recognizing when an antibiotic is needed
Dont prescribe antibiotics when not needed
When clearly indicted
Do not select the most broad spectrum medication
Choose antibiotic most likely to be effective given
the specific infection
Be aware of the spread of resistant strains
Dont use the newest antibiotics unless clearly
necessary

Selection of appropriate antibiotic
If an antibiotic is required
Empirical
Determine most likely infectious agent
May try to identify organism
Definitive - tailored to the organism
Institute as soon as the infectious agent is
identified
Use narrow spectrum, low toxicity to complete
therapy

-cidal vs -static
Bactericidal kills microbes
Bacteriostatic prevents microbial growth
Does not kill the existing microbes
Must use -cidal for
Immune suppressed
Endocarditis
Meningitis
Pseudomonas in CF
Watch for toxin producers
May release more toxin when using cidal drugs
May add corticosteroids to reduce inflammation
http://www.bmb.leeds.ac.uk/mbiology/ug/ugteach/icu8/images/antibiotics/cidal.jpg
Sensitivity testing
Disk diffusion and agar or broth dilution
Clear zone show sensitivity to a given drug
Minimal inhibitory concentration (MIC)
Lowest concentration that prevents growth
Minimal bactericidal concentration
(MBC)
Lowest dose that kills 99.9% of the
infectious organisms

http://www.phototakeusa.com/Pix/0513/06U/051306U000052-01_T.JPG
Other considerations
Access of antibiotic to site of infections
Transport across membranes
Transport out of fluids
Decrease in integrity of membranes during
inflammation
Plasma binding of drug and other kinetic
considerations
Dosing schedules
Pulse-intermittent or continuous
Patient status
Renal functions
Use nomograms to change dosage
Liver functions
Age of patient, genetics, allergy, seizures
Route of administration
Host defense mechanisms
Location of infection-abscess, prosthetic
device
Combination therapy
Consider interactions
May potentiate activity, toxicity
Different mechanisms
Additive or synergistic effects
Necessary for mixed infections
Unknown organism
Prevention of resistance
Always in H.pylori, HIV, TB
Prophylaxis
30-50% of antibiotics
Sometimes may be effective
STDs, UTIs, endocarditis, surgery
Destroys some normal defenses of host
Increases risk of fungal infections

Superinfections
New infections appearing during treatment
Due to death of normal protective flora
Competition for nutrients
Broader spectrum more likely to produce

Resistant bacteria
Fungal infections
Major problems of usage
Untreatable infections
Viruses, measles, mumps
Fever of undetermined origin
Short or long term
Cause may not be bacterial
Improper dosage
May need adjunctive therapy
Abscess drainage
Herb-drug interactions
Typically, ginseng potentiates antibiotic
effects
CI pregnancy
Aminoglycosides
Tetracyclines
Chloramphenicol
Quinolones
Caution sulfamethoxazole (cleft palate in rats)
Caution trimethoprim (folate antagonist)
Caution clarithromycin- animal studies show
harm yet category C
MECHANISMS OF
ACTION
ANTI-BACTERIALS
Anti-metabolites
DNA inhibitors
Membrane disrupters
Others
Penicillins
Cephalosporins
Bacitracin
Vancomycin
Examples
Amoxicillin
Amoxicillin/clavulin (clavamox)
Cephalexin

History
Fleming
Penicillin has been available since the
40s
Beta lactam ring
Penicillin
International Units
Activity in 0.6 mg of Na-penicillin G
1 mg pen G-Na = 1667 units
1 mg pen G-K = 1595 units
Mechanism: b lactam
antibiotics
Penicillin binding protein (PBP) is the
target
PBP is a transpeptidase
Links a dipeptide (d-Ala-d-Ala) into
peptidoglycan chain
Forms the cell wall
Inhibited by the b lactam antibiotics
These are generally bactericidal
Mechanisms of resistance
Bacteria develop b lactamases
or
Develop a different dipeptide
Make new transpeptidase
Alter porins, prevent access to PBP
Penicillins works best in log phase
Penicillins wont kill invasive organisms in
host cells
Ineffective with invasive infections

Serious side effects
Usually cross sensitization among b
lactams
Rash is common
Anaphylaxis possible and most
serious
Dysbiosis common
Including pseudo membranous colitis
Classification by spectrum
Penicllin G and V
Useful against sensitive gram positive microbes
G is more active against some anaerobes
Methicillin (iv), nafcillin, oxacillin, cloxacillin, dicloxacillin
Penicillinase resistant antibiotics
Ampicillin, amoxicillin
Gram positive and negative
Others available
Excretion
Mostly through kidney
Rapid

Probenecid impairs tubular secretion
Penicillinase resistant
antibiotics
Oxacillin, cloxacillin, dicloxacillin
Oral
Nafcillin
Not as active as Pen G
Usually injected
Binds plasma proteins
May be used in CSF for meningitis
Ampicillin, amoxicillin
Broader spectrum
Lactamase sensitive
Not useful for most staphyloccal infections
b-lactamase inhibitors
Clavulanic acid
Streptomyces clavuligerus
Suicide inhibitor of b-lactamase
Found in Augmentin (oral) and Timentin
(inj)
CEPHALOSPORINS
Cephalosporins
Fungal culture
b lactam
Classified by generations
Generations
First generation
cephalexin (keflex), cefadroxil (Duricef)
Gram positive, some negative, some anaerobes
Second generation
cefaclor (Ceclor), cefuroxime (Ceftin), cefprozil
(Cefzil)
More active against gram negative, less than 3rd
Third generation
cefpodoxime (Vantin), cefixime (Suprax)
Less active than first against gram positive
More active against entrobacteriaceae and pseudomonas
Fourth generation
cefepime
Increased activity, stability

Ceftriaxone
When administered with calcium to
neonates
May precipitate in kidney
May cause a lethal interaction
CARBAPENEMS
Carbapenems
b lactam antibiotic
Aztreonam (Azactam)
Monobactam
Given iv, limited cross sensitivity
Imipenem
Broader spectrum
Administered with cilastatin
Inhibits dipeptidase in renal tubule
Carbapenem
Meropenem (iv)/ Merrem
Used for multi-drug resistant infections
Including staphs and streps
Interaction with valproic acid
IV only
Pregnancy B
Carbapenem
Doripenem /Doribax iv
complicated intra-abdominal infections
caused by E.coli, Klebsiella,
Pseudomonas, Bacteroides, Strep,
peptostreptococcus
Complicated pyelonephritis
Decreases serum concentration of
valproic acid
May precipitate seizures

Ertapenem/Invanz
Injectable
Effective against complicated
Intra-abdominal
Skin (NOT MRSA)
CAP
UTI
Acute pelvic infections
Side effects include seizures and
anaphylactic reactions
VANCOMYCIN
Vancomycin
Effective against many Gram positive
Inhibitor of cell wall synthesis
Bactericidal
Resistance
Changes transpeptidase

Vancomycin
Usually given iv
Oral for GI infections
C. dificile
S. aureus
Vancomycin side effects
Major
Ototoxicity
Anaphylaxis
red man syndrome
Phlebitis at site of injection
TELAVANCIN/VIBATIV
Televancin/Vibativ
Developed for complicated skin
infections
MRSA, Strep pyogenes, Strep agalactiae,
Strep anginosus, Enterococcus faecalis
IV only
Nephrotoxic, c.dif, may prolong QT
interval
Black box warning pregnancy
Aminoglycoside
Tetracycline
Chloramphenical
Erythromycin
Clindamycin
Ketolides
Examples
Azithromycin
Erythromycin
Tetracycline
Doxycycline
Tobramycin
Mupirocin

Resistance
Mutations in bacterial ribosomes
Metabolizing enzymes
Impaired transport of drug into bacteria
AMINOGLYCOSIDES
Streptomycin
Neomycin
Kanamycin
Gentamicin
Aminoglycosides
Streptomycin
aerobic gram positive and negative
Neomycin
Not used orally, severe renal toxicity
Kanamycin (rarely used)
Gentamicin (broader spectrum)

Aminoglycosides

Useful in aerobic gram negative
TB, particularly multi-drug resistant
Relatively toxic
Binds 30S ribosomal subunit

Aminoglycosides
Pharmacokinetics
Polar, not widely distributed
Little plasma binding
High concentrations in renal tubule and
endo-and perilymph of the ear
Relatively high renal and ototoxicity

CHLORAMPHENICOL
Chloramphenicol
Protein synthesis inhibitor, binds 50S
Inhibits mitochondria
Causes many side effects
Wide spectrum
Resistance
Acetyltransferase inactivates drug
Some decreased permeability to drug

Chloramphenicol kinetics
Oral or parenteral
Well distributed
Found in CSF, milk, bile, placenta
Excreted by kidney

Chloramphenicol Toxicity
(severe)
Mitochondrial
Hypersensitivity
Bone marrow effects
Potentially fatal aplastic anemia
More likely with genetic predisposition
Nausea, dysgeusia, vomiting
Fatal toxicity in neonates, gray baby syndrome (due
to liver problem)

Chloramphenicol
Drug interactions
Irreversibly inhibits cP450
Enzyme inducers shorten t1/2
Rifampin, phenobarbital
Prolong t 1/2 of
Dicoumeral, phenytoin

MACROLIDES
Erythromycin
Azithromycin
Clarithromycin
Macrolides
Erythromycin
Clarithromycin
Azithromycin


Macrolides
Bacteriostatic
Often used in pen allergic patients
Aerobic gram positive
Resistance is developing
Lack of uptake
Decreased affinity of ribosome
Enzymatic degradation

Macrolide Drug interactions
Erythromycin
Potentiates the effects of
Carbamazepine, corticosteroids,
cyclosporine, digoxin, ergots, theophylline,
valproate, warfarin
Inhibits cP450 metabolism

Macrolide Toxicities
Allergy
Hepatitis and jaundice
GI distress
Ototoxicity
Cardiac arrythmias- erythromycin
prolong QT interval

CLINDAMYCIN
Clindamycin
A protein synthesis inhibitor
Broad spectrum, aerobes and
anaerobes
Oral, topical

Clindamycin Toxicity
Diarrhea
Black box warning
Pseudomembranous colitis
May give with vancomycin
Skin rashes

TETRACYCLINES
Tetracycline
Doxycycline
Minocycline
Tigecycline
Tetracyclines
Aerobic and anaerobic gram positive
and negative
Bacteriostatic

Tetracyclines Mechanisms
Inhibit protein synthesis
Bind 30 S ribosomal subunit
Also effect eukaryotic cells at high
concentration

Tetracyclines Resistance
Decreased uptake, increased efflux
Development of ribosomal protection
proteins
Enzymatic cleavage of tetracyclines
Tetracyclines
Pharmacokinetics
Orally available
Widely distributed
Found in most secretions
Milk, tears, saliva
Excreted through kidneys
Some hepatobiliary recycling

Tetracyclines Toxicity
GI irritation
Do not take with dairy products
Photosensitivity
Liver toxic
Renal toxic
Pregancy category D
Not for use in children
Tooth discoloration in children
Some bone problems

Novel use for minocycline
Anti-apoptotic and anti-inflammatory
effects in vitro
Has been used in ALS
Gorden et al. suggests not effective
412 patients, those on minocycline 9 mos.
declined more rapidly than placebo
Lancet Neurol. 2007 Dec;6(12):1045-53.
Is still used to treat stroke and multiple
sclerosis
Tigecycline/Tygacil
Used IV for MRSA and other multi-drug
resistant microbial infections
Not for pregnant women
Discolors teeth, not for children unless
necessary
Associated with pseudomembranous
colitis
KETOLIDES
Telithromycin
Ketolides
Telithromycin/Ketek
Binds the 50S ribosomal subunit
Indicated for URI, chronic bronchitis, acute
bacterial sinusitis, community acquired
pneumonia
Effective against multidrug resistant
Streptococcus pneumoniae
Do not use in myasthenia gravis
Has caused acute liver failure

MUPIROCIN
Mupirocin
Topical, intra-nasal
Produced by Pseudomonas fluorescens
Used in impetigo
Effective against
Staphylococcus aureus
Including MRSA and b lactamase producers
Staphylococcus epidermidis
Staphylococcus saprophyticus
Streptococcus pyogenes
Caution when using over large parts of skin in
patients with kidney damage
Due to absorption of polyethylene glycol base
Antimetabolites
Folate antagonists
sulfonamides
trimethoprim
Examples
Sulfamethoxazole
Trimethoprim

Sulfonamides, trimethoprim +
sulfamethoxazole(TMP-SMX)
UTIs, otitis, bronchitis, sinusitis,
pneumonia
Broad spectrum
Gram negative bacilli and cocci,
staphylococci
Orally available
Sulfonamides
Bacteriostatic
Gram positive and negative
Often used in combination therapy
Mechanisms
PABA analogs
Folic acid inhibitors
Inhibit dihydropteroate synthase
Trimethoprim is considered synergistic with
suflonamides (Bactrim, Septra)
Inhibits dihydrofoalte reductase
Anti-metabolite Resistance
Change in dihydropteroate synthase
Inactivation of drug
Alternative pathway for the production
of folic acid
Production of excess PABA
Anti-metabolite Toxicity
Crystallization in the urine
Hydration therapy
Acute hemolytic anemia
Hypersensitivity
Drug interactions
Oral anticoagulants
Sulfonylurea hypoglycemics
Hydantoin anticonvulsants
Are potentiated by sulfa drugs

Anti-metabolite Use in
newborns
Depends on status
Must be conjugated in liver
In immature liver, conjugation reaction
is compromised
This may cause increased sensitivity in the
newborn to the sulfonamides antibiotic
Nucleic acid synthesis
inhibitors
Quinolones
Rifampin
Quinolones
DNA gyrase inhibitors
Ciprofloxacin (Cipro), ofloxacin (Floxin),
levofloxacin (Levaquin)
Norfloxacin, moxifloxacin, gemifloxacin,
ofloxacin
Nalidixic acid
Broad spectrum, oral, some resistance
developing
Bactericidal

Quinolones Mechanisms
Inhibitor of DNA gyrase
Superwinds the DNA, causing breaks
Resistance from mutation in gyrase
Can crossreact with eukaryotic
topoisomerase, but only at high
concentration
Examples
Levofloxacin
Quinolones Toxicity
Nausea
Hallucinations and seizures
Rashes and photosensitivity
Arthropathy in young animals
Tendonitis
Not recommended for pregnant women
and prepubertal children
CI with NSAIDs
RIFAMPIN
RNA Polymerase inhibitor
Membrane disruptors
Polymixins
Cyclic lipoproteins
Polymixin B
Used topically, otc
Gram negative
Amphipathic
Detergent action
Cell wall and membrane disruption

Cyclic lipoproteins
Daptomycin/Cubicin
Inserts into bacterial membrane, allowing K efflux and
cell death but not cell lysis
Active against aerobic gram positive
Useful in vancomycin resistant MRSA
Depolarizes bacterial membrane-bactericidal
Associated with pseudomembranous colitis
Associated with myopathy, caution with statins
Quinpristin/dalfopristin (Synercid)
Approved for life threatening infections associated with
vancomycin-resistant Enterococcus faecium (VREF)
Accelerated approval regulations that allow marketing of
products for use in life-threatening conditions when other
therapies are not available.
Approval of drugs for marketing under these regulations is
based upon a demonstrated effect on a surrogate endpoint that
is likely to predict clinical benefit.
Enterococcus faecium (Vancomycin-resistant and multi-drug
resistant strains only)
Staphylococcus aureus (methicillin-susceptible strains only)
Streptococcus pyogenes
NOT enterococcus faecalis

Lantibiotic
Nisin
Made in lactococcus lactus
Effective against many gram positive microbes
Inclu. Food borne pathogens
bactieriCidal
Disrupts cell wall biosyntheses
Binds lipid II
Essential intermediate in peptidoglycan biogenesis
Forms pores in the cell membrane
GRAS
Food additive
Not currently listed as drug
Urinary antiseptic
Methenamine and nitrofurantoin
Urinary antiseptics
Inhibit many species of bacteria growth
High concentration in renal tubules
Not useful systemically

Methenamine
Decomposes to formaldehyde at pH 5-6
Enteric coating
Nearly all bacteria are sensitive
No resistance
Side effects
GI distress, painful micturition
May be okay in renal insufficiency
CI with sulfamethizole (antagonistic)
Nitrofurantoin (Furadantin)
Damage DNA when reduced
Reduced well by bacteria
Some resistance
Nausea and vomiting, chills, fever, liver
toxic
Blackbox warning
Lung toxicity
Phenazopyridine (Pyridium)
Not an antiseptic
Analgesic
Alleviates symptoms of UTI
Azo dye, can cause GI upset
Azo Gantrisin is phenazopyridine plus
sulfisoxazole

On the blueprints
Lecture recap
Introduction to antibiotics and their
mechanisms of action
Basic information regarding side effects
and contraindications
Next, basic microbiology recall
BRIEF OVERVIEW OF
MICROBIOLOGY
Choice of antibiotic depends on most likely cause of infection
Infections
URI, LRI
ABECB
CAP
UTI
STD
Acute diarrhea and ulcer
Skin
Microbial classifications
Gram
Cocci v bacilli
Aerobic v anaerobic
Common infectious aerobes
GPC (gram positive cocci)
Streptococci
S. pneumoniae (pneumococcus, diplococcus)
S. pyogenes (Group A)
S. agalactiae [B]
Viridans Strep
Staphylococci
S. aureus (MSSA, MRSA)
Enterococcus sp.
GNC
Neisseria
N. gonorrhea, N. meningitidis
Moraxella catarrhalis
Common pathogenic aerobes
GPB (gram positive bacilli)
Bacillus anthracis
Few other human pathogens
GNB
Enterobacteriaceae
E.coli, Proteus mirabilis, Klebsiella pneumonia, Prov
stuartii, M. morganii, Citrobacter sp., Salmonella sp.,
Shigella sp.
Non-enterobacteriaceae
Hemophilus influenzae, Helicobacter pylori,
Pseudomonas aeruginosa, Acinetobacter sp., others.
Common pathogenic - anaerobes
GPC
Peptostreptococcus sp., Peptococcus sp.
GNC
Few human pathogens
GPB
Clostridia sp.
Gas gangrene
Botulinum
Dificile
Resident of the gut
Grows in intrabdominal stabbings and ileal infections
GNB
Bacteroides sp., Fusobacterium sp.
Culturing
Shows many microbes
Not all are causes of infection
Dont need to treat all organisms

Can guess which organism is mostly
likely to be responsible, treat that
organism
ORGANISMS BY INFECTIONS
Strep infections- GPC
Pneumonia
Pyrogenes (A)
Agalactial (B)
Viridans
Otitis
Sinusitis
Pneumonia
Strep throat
Cellulitis
Neonatal sepsis
Chronic adult skin
Diabetic foot
UTI
Staph-GPC
Aureus
MSSA, MRSA
Meth sensitive
Meth resistant

Skin
Boils
Abcesses
Impetigo
Cellulitis

Enterococcus-GNB
Fecalis
Faecium
Nosocomial
Chronic adult UTI
Skin
Diabetic foot
Neisseria- GNC
Gonorrhea-

Meningitiditis-

Moraxella -
STD

Meningitis

RTI
Otitis
Sinusitis
Pneumonia
Bronchitis
Bacillus-GPB
Anthracis Anthrax
Inhalational
Skin
Enterobacteriaceae-GNB;
coliforms
E.Coli
Most common UTI
Proteus mirabilis-
Express urease, alkaline urine
2
nd
most common UTI
Klebsiella pneumonia
3
rd
most common UTI
Prov stuartii and M. morganii
UTI in nursing homes
Relatively uncommon
Citrobacter sp.
Found in normal stool
Non-enterobacteriaceae-GNB
Hemophilus influenzae
2
nd
most common RTI
Helicobacter pylori
Ulcer
Psuedomonas aeruginsa
Pulmonary, usually found only in chronic illness
Actinetobacter sp.
Some pneumonia
Others less common
These are not usually found in the gut

Pathogens in stool
Salmonella sp.
Shigella sp.
Diarrhea
Most common causes of
common infections
RTI
UTI
Skin
other
Respiratory Tract Infections
Strep pneumonia
Neissaria moracella
Hemophilus
influenza
Otitis
Simusitis
Bronchitis
Pneumonia
UTI
E.Coli
Proteus mirabilis
Klebsiella pneumonia
Skin infections
Staph
Some others (MRSA, MSA)
Other organisms
Bacteria
Fungi/yeast
Virus
Protozoa
Worms
Lice and scabies
Other important Bacteria
Legionella (pneumonia)
Chlamydia pneumoniae (atypical pneumonia)
Chlamydia trachomatis (STP, urethritis)
Mycoplasma sp. (pneumonia)
M.hominis (genital urethritis)
M.genitalium (genital urethritis)
Ureaplasma urealyticum (urethritis)
Mycobacterium tuberculosis
MAC (avium complex, seen in HIV)
Treponema pallidum (syphillis spirochete)
Lecture recap
Overview of anti-bacterial antibiotics
Overview of basic microbiology
Now put them together

1 Antibiotic Introduction Handout

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Southwest College of Naturopathic Medicine 1

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