Download Penicillins

Antibiotics: Part I
1. Penicillins
2. Macrolides
3. Tetracylines
4. Glycyclines
5. Carbapenems
Antimicrobial Objectives Part I and Part II
1. Discuss the general principles of antibiotic therapy.
2. Explain how antibiotics work to rid the body of infection.
3. Discuss the pros and cons of antibiotic usage.
4. Describe the signs and symptoms, diagnostic criteria, and common treatment of the
superinfections: candidiasis and clostrium difficile colitis.
5. Discuss the MOA, indications, cautions, common and serious adverse reactions associated
with selected antibiotic groups:
Antibiotics Part I:
•Penicillins
•Macrolides
•Tetracyclines/Glycyclines
•Carbapenems
Antibiotics Part II:
•Cephalosporins
•Sulfonamides
•Aminioglycosides
•Fluroquinolones
•Oxazolidinones
•Lincosamides
Introduction to Antibiotics:
Penicillins, Macrolides,
Tetracyclines & Carbapenems
Match the Drug to the Bug!!
Penicillins
(some are SENSITIVE to
penicillinase producing
bacteria and some are
RESISTANT)
Macrolides
Tetracyclines
NARROW
SPECTRUM
Gram (+) only
BROAD SPECTRUM, but many
bacteria now resistant
erythromycin
*penicillin V (PenVeeK) (po)
azithromycin
(Zithromax)
(po/IV)
(EES) (po)
*amoxicillin (Amoxil) (po)
doxycycline (Vibramycin)
(po)
minocycline (Minocin) (po)
tigecycline (Tygacil)
A derivative of minocycline
= Glycycline
+amoxicillin + clavulanic acid
(Augmentin) (po)
+dicloxacillin (Dynapen) (po)
+piperacillin + tazobactam
(Zosyn) (IV)
carbenicillin
(Geopen) anti-pseudomonas
(IV)
“INEFFECTIVE” by bacteria that
secrete penicillinase
Glycyclines – newer
and less resistant
*procaine penicillin
(IM/IV)
***penicillinase sensitive
abx – Abx is rendered
Carbapenems
+ penicillinase
resistant abx – Abx
is “EFFECTIVE”
against bacteria that
secrete pencillinase
meropenem (Merrem)
PENICILLINS
Natural and synthetic
Penicillins are the most widely effective and extensively
used antibiotics
Structural component is a BETA-LACTAM RING
The job of penicillin is to
DESTROY the bacterial cell
wall
It does this by attacking
the cell wall with its beta lactam
ring….. Aka the penicillin missile
contains
a beta- lactam ring
Penicillin “missile” is its beta-lactam ring
Bacteria after penicillin “attack”
What are penicillinase/betalactamase
enzymes?
Some bacteria ‘got smart’ and developed a defense

an ENZYME that DESTROYS the penicillin beta lactam ring
This “ANTI-MISSILE” aka the “ENZYME”– renders these bacteria
RESISTANT to the penicillin
Betalactamase enzymes that act directly on penicillin are known as
“PENICILLINASES”
Betalactamase enzymes that act on other antibiotic classes (cephalosporins) are known
as “BETALACTAMASES”
The “anti-missile” of resistant bacteria:
penicillinase for penicillin
betalactamase for cephalosporins
Bacteria resisting an antibiotic
Superbugs in acute care
1. VRE (enterococci)
2. MRSA (staph aureus)
3. Acinentobacter
Penicillins: Side Effects All Classes
Allergic reactions including: urticaria, pruritus, and
angioedema

Most are mild, but about 10% of allergic reactions are lifel-threatening
Treatment of acute allergic reaction includes: epinephrine,
steroids, and antihistamines

Some cross-sensitivity between cephalosporins and penicillins exist - so
may see allergy to both
Generally well tolerated with *GI effects (N-V-D) most common
problem
Nursing alert: always check allergy before administering
penicillin. When giving IM, observe patient closely for at least 30
minutes

Foods may decrease absorption
angioedema
Urticaric Rash
Typical urticaric rash from penicillin allergy
Erythematous, maculopapular rash
What is the MOA of Natural Penicillins?
MOA:

Inhibits cell wall synthesis (bacteriocidal) by interrupting the enzyme
needed for bacterial cell division

Narrow spectrum


However, bacteria that can produce PENICILLINASE render the
natural penicillins INEFFECTIVE 


Natural penicillins are effective against mild to moderate infections (strep & staph)
These bacteria are known as “penicillin resistant
bacteria”
Natural penicillin was originally used to treat STAPH INFECTIONS

but by 1953, 80% of all hospital strains of staph aureus were
penicillin-resistant = (MRSA)

Bacteria produce penicillinase making them resistant to natural
penicillins
Natural Penicillins
NARROW spectrum agents
penicillinase SENSITIVE penicillins
the
PENICILLIN
the
is destroyed by
BACTERIA
bacteria that produce penicillinase
OR
are penicillin resistant
Natural Penicillins

*aqueous penicillin


G (Bicillin) (P)
Destroyed by gastric acid so cannot be given po
short duration of action and very painful

procaine penicillin

Milky color and less painful

*penicillin V (PenVeeK) (PO)

Penicillin Pearls:





(P) longer duration
Effective against mostly Gram (+) bacteria, some gram(-)
Derived from a mold or fungus
Look for “cillin” suffix
Injectable form given deep IM
Prescribed in “units”
AMINOPENICILLINS
BROADER spectrum action
but NOT penicillinase resistant
Have an amino group attached
to their penicillin nucleus that
makes them more effective
against gram (-) bacteria
Also still effective against some
gram (+) bacteria
Sensitive to penicillinase
producing bacteria, so…. NOT
effective against staph aureus
(MRSA) which DO produce
Common
drugs:
 amoxicillin
(Amoxil) (po)most commonly Rx
penicilinase
Therapeutic uses: treatment
of sinusitis, otitis media, and
bacterial endocarditis
prophylaxis
Otitis media =
Ear infection
Frontal sinusitis
PENICILLINASE RESISTANT PENICILLINS
Betalactam ABX that CAN destroy betalactamase
sooo… EFFECTIVE against pencillinase/betalactamase
producing bacteria
Commonly rx drugs
*dicloxacillin
(Dynapen) (PO)
These agents ARE
effective against gram +
betalactamase/penicillinase
producing bacteria
 1/3 of all otitis media bacteria
now produce penicillinase
Therapeutic Uses: to
treat serious infections:
bone and joint, CNS,
endocarditis, septicemia
Anti-staphlococcal
penicillin= EFFECTIVE
against infections caused
by staph..MRSA
Staph Aureus Infections
Staph r/t illnessess



Mild to severe skin
infections
Toxic shock syndrome
Food poisoning
Methicillin resistant
staph aureus (MRSA)


Bacteria that can cause
SERIOUS infections.
These bacteria are
RESISTANT to
methicillin/penicillins


Rendering the penicillins
ineffective
Causes wound
infections, urinary tract
infections, pneumonia,
sepsis
MRSA Skin Infections
Penicillinase /betalactamase
INHIBITORS
Combination of a broad
spectrum penicillin
(amoxicillin) WITH a betalactamase inhibitor
(clavulanic acid)
Three
betalactamase
inhibitors
1.
Broader spectrum
2.
3.
Effective against gm (+), gm
(-), anaerobes, AND
betalactamase producing
bacteria
Clavulanic acid
Sulbactam
Tazobactam
Extended Spectrum Penicillins
Beta-Lactamase Inhibitors
Oral: amoxicillin + clavulanic acid =
Augumentin
Parenteral:
1.
ampicillin + sulbactam = Unasyn
2.
piperacillin + tazobactam =
3.
ticarcillin + clavulanic acid = Timentin
Zosyn
** Most beta-lactam abx are excreted via the
kidneys. Important to assess renal function.
Penicillins: Newest Extended
Spectrum Penicillin
Common drug;

*carbenicillin
(Geopen) (IV, IM,
po)
Are important in treating
SERIOUS GRAM (–)
infections d/t Pseudomonas
However, NO coverage
against bacteria that produce
betalactamase

So not a good choice for staph
MRSA infections
Often used in combination
with aminoglycosides
Made by making a few
changes in basic penicillin
structure
Penicllins: Summary Slide
1. NARROW spectrum
(gram +) penicillinase
SENSITIVE


Procaine Penicillin
PenVeeK
2. NARROW spectrum
(gram +) penicillinase
RESISTANT  anti-staph
penicillins
 dicloxacillin (Dynapen)
3. BROAD spectrum
(gram + and gram –) penicillinase
sensitive aminopenicillins
 amoxicillin (Amoxil)
4. EXTENDED spectrum
gram (+) and gram (-) AND
penicillinase resistant
• amoxicillin + clauvalnic
(Augmentin)
•
pipercillin + tazobactam (Zosyn)
•
5.Newest Extended
Spectrum Antibiotic
•
anti-pseudomonas penicillin
•
Pseudomonas serious Gm (-)
•
carbenicillin (Geopen)
What is Pseudomonas?

Pseudomonas is a gram (-) bacterium

Newest extended spectrum: effective against gram (-); but NOT
resistant to penicillinase producing bacteria

Causes serious infections in hospitalized patients:



Skin/surgical site
Blood
Pneumonia
Macrolides
MOA: inhibit bacterial protein synthesis

Bacteriostatic at low concentrations
Bactriocidal at high concentrations

PO or IV use only. Too painful to give IM!

1st Macrolide was erythromycin, which is
known for its bad taste and GI upset

Macrolides (cont)
Therapeutic uses:

Narrow spectrum

Mostly active against gram (+) organisms

Suitable replacement for penicillin in hypersensitive
pts

* Used for “atypical” infections (chlamydia,
mycoplasma, bacteria that commonly cause STDs
and pneumonia

Used to treat H pylori , bacteria that causes peptic
ulcers
Macrolides
Adverse Effects

*GI distress the
most common complaint.
GI motility

Superinfections

Hepatotoxicity

 effect of theophyllin,
coumadin, and
carbamazepine
(anticonvulsant)
Oral agents have a
bad taste and many
trade names have
been developed
trying to make more
acceptable
Macrolides
Drug interactions:

E-mycin can INHIBIT the
metabolism of many
other drugs. (theophyllin,
warfarin, seizure drugs)
Common drugs

*erythromycin
(many trade names

E-mycin, eryped,
EES)

Newer macrolide

azithromycin
(Zithromax)

Erythromycin is MR YUK!
Tastes bad and causes diarrhea
Zithromax has 
duration, can be given
QD
Tetracyclines
protein synthesis –
bacteriostatic
True “broad spectrum”
antibiotics, however
many bacteria have
developed
RESISTANCE
Distributed well in body
– crosses the BBB so
WILL reach CSF
Effective against
MOA: inhibit bacterial






Some Gram (+)
Some Gram (-)
Rickettsia
Mycoplasma
Chlamydia
H. pylori (stomach
bacteria that causes
peptic ulcer
No milk with tetracyclines
TETRACYCLINES
Chemically related group of 5 antibiotics
Bind (chelate) to Calcium and Magnesium
and metallic ions to form insoluble
complexes

So co-administration with milk, antacids, or iron
salts causes  absorption of antibiotic
Not usually given to children younger than
8 years of age d/t adverse effects!
Tetracyclines
Do not give to children under 8 years
Many Adverse Effects!








GI irritation
Photosensitivity
Superinfections
Hepatoxicity
Renal toxicity
In children –
discoloration of teeth,
depression of bone
growth
Known teratogenic
drug
Blood dyscrasias
Therapeutic uses:

Drug of choice for
chlamydia, rickettsia
infections, Lyme
disease, Rocky
Mountain spotted
fever

Often used to treat acne
and serious skin
infections
Tetracyclines
Look for “cycline”
suffix
Common drugs:

doxycycline –
(Vibramycin)
(P), (PO)

minocycline
(Minocin) (PO)
Interactions:

absorption when
given with milk,
antacids, iron, or
calcium
New Class: Glycylcline
(2006)
MOA

a broad spectrum abx similar in structure
to tetracycline

Is a derivative of minocycline

Blocks protein synthesis in bacterial cells
 bacteriostatic
Glycycline
tigecycline/Tygacil
ADVANTAGE: does not have resistant seen
in older tetracyclines
BROAD SPECTRUM
IV use only for complicated skin and intra-abdominal
infections
SE: similar to tetracyclines: photosensivity, GI upset,
discoloration of teeth
Tygacil:
for complicated skin and
intra-abdominal infections
IV only!
Infected deep leg ulcer
Staph cellulitis
Carbapenem
meropenem (Merrem)
ULTRA broad spectrum
IV route only (phlebitis common)
Used to treat serious mixed infections
Carbapenems
Have a beta lactam structure

Must be given IV
Broadest spectrum of all


Used for complicated abdominal infections,
meningitis
Well tolerated; with few adverse reactions
Can be used to treat “MIXED INFECTIONS”



Staph
Gm (-)
Gm (+)
That’s all Folks!!