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AGENTS THAT INTERFERE

WITH MICROBIAL GROWTH


(ANTI-INFECTIVES)
Isaac Amankwaa

Introduction
Antiinfective

agents are used to


treat infections resulting from
pathogens.
Examples of anti-infective agents are:
Antibiotics
Antivirals
Antifungals
Antiprotozoal
Anthelminthic

TERMINOLOGIES
CHEMOTHERAPY

Use of chemicals to eradicate parasites,


bacteria, viruses or cancer cells from the
body
ANTIBIOTICS

A chemical produced by microorganism


and has the ability to harm other
microbes

Terminologies
ANTIMICROBIAL

Any agent, natural or synthetic, that


has the ability to kill or suppress
microorganisms
In current practice, the terms
antibiotics and antimicrobials are
used interchangeably

Terminologies
Bacteriostatics

These are antibiotics that


prevent the growth of
bacteria
Bactericidal

These are antibiotics that


directly kill bacteria

Terminologies
Broad

spectrum
antibiotics
These are antibiotics that
interfere with a biochemical
reaction common to many
organisms.

The principle of selective


toxicity
It

is the ability of a drug to


injure a target cell or target
organism without injuring
other cells or organisms that
are in intimate contact with
the target

Principle of selective
toxicity
Toxicity

to the parasite or the


unwanted cell but non-toxic to the
host (leaves the host or environment
relatively unharmed.

How is selective toxicity


feasible?
Exploitation

of biochemical differences
between the parasite and the host cell.
The more closely the unwanted cell or
parasite resembles the host the more
difficult it is to achieve selective toxicity

Mechanism of action of
antimicrobials
Inhibition
Alteration

of cell wall synthesis


in membrane permeability

Inhibition

of protein synthesis

Inhibition

of synthesis of essential

metabolites

CLASSIFICATION OF
ANTIBACTERIAL DRUGS
A.

Classification by susceptible
organism
Narrow-spectrum antibiotics
Broad spectrum antibiotics

B.

Classification by mechanism of
action

Sulfonamides
Sulfonamides

are structural analogs


of para-aminobenzoic acid (PABA)
Examples
Sulfadiazine
Sulfasalazine
Sulfisoxazole
cotrimoxazole
sulphamethoxazole

Mechanism of action
All

cells require folic acid for the


biosynthesis of DNA, RNA, and
proteins
Bacteria are not able to take folic
acid from their environment, but
mammalian cells simply take up folic
acid obtained from diet
Bacteria must synthesize folate from PABA

Mechanism of action
Because

of their structural similarities to

PABA, sulfonamides compete with PABA


for enzyme dihydropteroate synthetase.
The

effect of sulphonamides can be

overcome by adding excess PABA

Mechanism of action
Sulphonamides

are bacteriostatic, hence host

defences are essential for complete


elimination of infection
It

also means that successful treatment

require adequate concentration long enough


to allow cellular defence mechanisms

Clinical uses
Simple

UTI
Ophthalmic preps for
bacterial conjunctivitis
Chronic inflammatory bowel
disease (IBD)

Contraindications
Newborns

and Infants < 2 months


Also pregnant women, possible
terratogenic effects

Adverse reaction
Nausea

and vomiting.
hypersensitivity reactions e.g. rashes,
fever, crystalluria (nephrotoxicity)
haemolytic anaemia in G-6PD
patients.
Kernicterus in newborns,

Nursing implications
Check

culture and sensitivity


reports.
Monitor renal function test
Ensure patient receives the
full course of sulphonamides

Nursing intervention
Administer

the oral drug on


empty stomach 1 hour before or
two hours after meals with a full
glass of water
Discontinue the drug
immediately if hypersensitivity
occurs

Trimethoprim
In

structure, trimethoprim
resembles folate
It antagonizes the enzyme
dihydrofolate reductase.
It is active against most common
bacterial pathogens, and it is
bacteriostatic.

Trimethoprim
It

is given in combination with a


sulphonamide, sulphamethoxazole.
This is called cotrimoxazole
since sulphonamides affect an earlier
stage in the same metabolic pathway
in bacteria, they strongly potentiate
the action of trimethoprim

Inhibition of bacterial cell


wall
Bacterial

encased in rigid cell wall


Osmotic pressure high in bacterium
protoplasm
The cell wall prevents it from
absorbing water and swelling -burst
Drugs act to weaken the cell wall
and thereby promote bacterial lysis

www.uccs.edu/

DRUGS INHIBITING CELL WALL


SYNTHESIS

Penicillins

Cephalosporins

Vancomycin

Fosfomycin

-lactams

Beta-lactam antibiotics

It consist of all antibiotic agents that contain


a-lactam ringin their molecular
structures. Includes:
Penicillin derivatives(penams),
cephalosporins(cephems),
monobactams,
carbapenems.

Beta-lactam antibiotics

Beta-lactam
characteristics
Same Mechanism of Action : Inhibit cell
wall synthesis
Bactericidal (except against Enterococcus
sp.); time-dependent killers
Short elimination half-life
Primarily renally eliminated
Cross-allergenicity - except aztreonam

Mechanism of action

Interfere with cell wall synthesis by binding to


penicillin-binding proteins (PBPs) which are
located in bacterial cell walls

Inhibition of PBPs leads to inhibition of


peptidoglycan synthesis Cell death

Mechanism of Resistance
1.

Production of -lactamase enzymes

2.

Trapping mechanism

3.

Modification of target penicillin binding


proteins (PBPs)

4.

Impaired penetration of drug to target PBPs

5.

The shortage of autolytic enzyme.

6.

The presence of an efflux pump.

Mechanisms of Resistance
Production of -lactamase enzymes

1.

most important and most common

hydrolyzes beta-lactam ring causing inactivation

Trapping mechanism.

2.

Some b -lactams tightly bind with b - lactamase


and stay outside the bacterial cell.

Thus, these beta-lactams cant enter the


bacterial cell wall to combine with the PBPs

Mechanisms of Resistance
Modification of target PBPs

3.

Responsible for methicillin resistance in


staphylococci and penicillin resistance in
pneumococci.

4.

Impaired penetration of drug to target PBPs.


which occurs only in gram negative (G-) species, is
due to impermeability of the outer membrane that
is present in G- but not in G (+) bacteria.

Mechanism of Resistance
The shortage of autolytic enzyme.

5.

Under this circumstance, the beta-lactams have


normal inhibiting action, but their kill effects are
very poor.

The presence of an efflux pump.

6.

Some organisms also may transport beta-lactam


antibiotics from the periplasm back across the
cell wall via an efflux pump

PENICILLINS

Introduction
Alexander Fleming
discovered penicillin in
1928
Penicillin is a antibiotic
used in the treatment
of bacterial infections
caused by susceptible.

Introduction
The structure of the
penicillins consists of a
thiazolidine ring connected
to a beta-lactam ring, which
is attached to a side chain.
The various penicillins differ
in their side chain structure

Mechanism of action
Penicillin belongs to the beta-lactam
family of antibiotics (the members of
which use a similar mechanism of action)
Bacteria cells are surrounded by cell wall.
One of the primary components of the
bacterial cell wall is peptidoglycan (a
net-like composition that provides rigidity
and support)

Mechanism of action

The cell wall (peptidoglycan crosslinks) is


continuously remodeled in order to
accommodate for repeated cycles of cell
growth and replication
Penicillins and other antibiotics in the betalactam family contain a characteristic fourmembered beta-lactam ring.
Penicillin kills bacteria through binding of the
beta-lactam ring to penicillin binding proteins
(PBPs), inhibiting its cross-linking activity and
preventing new cell wall formation.

Classification of penicillin

Spectrum of activity
Both bacteriostatic and bactericidal
agents.

Types of penicillin
natural and semisynthetic penicillin.

Types of penicillin: natural


Natural penicillin
extracted from the cultural solution of

penicillia.
1. Penicillin G (benzyl penicillin)

prototype
2. Penicillin V. (phenoxymethylpenicillin)
. Derived from the mold penicillium

Examples of natural
penicillins
Penicillin G benzathine:

1.2-2.4 million units IM

Penicillin G potassium : 1-20 million U/d IM or IV


Penicillin G procaine: 600,000 to 1.2 million U IM
Penicillin V:

250-500mg 6 hourly (oral)

Penicillin G (Benzyl
Penicillin)

Penicillin G (Benzyl
Penicillin)
This was the first penicillin to be used
clinically
Characteristics
Acid labile
Inactivated rapidly in the GIT
Absorbed erratically if taken orally
Hence given by parenteral route

Penicillin V
Acid stable (suitable for oral use)
Less potent than penicillin G
Other penicillins are either wholly or

partially synthetic which makes them


either broad spectrum, penicillinase
resistant and prolonging their action

Penicillinase-resistant penicillins
Exs. are Cloxacillin, methicillin &
flucloxacillin
chemical modifications of the prototype;
provide protection against penicillinase
Hence, Flucloxacillin is not inactivated by
penicillinase and therefore used in the
treatment of Staph infections.

Staph areus strains


resistant to methicillin have
emerged
Referred to as:
Methicilin-resistant staph areus
MRSA

Extended Spectrum
penicillins
e.g. amoxicillin and ampicillins
Effective against numerous species of
gram-negative bacteria
They are inactivated by penicilinase
Amoxicillin is a derivative of ampicillin;
amox is better absorbed by mouth

Examples of extended
spectrum penicillin
Ampicillin
hourly,

250mg-500mg IM or IV 6
500mg PO 6 hourly

when oral use is feasible.


Amoxicillin:

250-500mg PO 8 hourly

Others: carbenicillin and piperacillin

Adjuncts for greater protection against Betalactamase (beta-lactamase inhibitors)


E.g. clavulanic acid
Inactivate bacterial beta-lactamases and are used
to enhance the antibacterial actions of betalactam antibiotics.
Only have weak antibacterial action
Clavulanic acid is an inhibitor of beta-lactamases
This extend spectrum of activity of penicillin to
strains of staph areaus, eg. Co-amoksiclav


Pharmacokinetics
Rapidly absorbed from the GIT
Should be taken on an empty stomach to
ensure adequate absorption.

Uses or indication
Streptococcal pharyngitis,
Pneumococcal pneumonia,
Endocarditis,
Meningitis,
Otitis media

Adverse Reactions

1. Hypersensitivity reactions
2. Superinfections: E.g. candidiasis
3. GI tract: nausea, vomiting & diarrhea,.
4. Blood disorders: anemia &
thrombocytopenia,

Precautions
Contraindicated in clients:
With a history of previous
hypersensitivity to penicillins.
Clients with severe renal insufficiency.

Nursing interventions
1. Question the client concerning history of drug allergies.
2. Observation: signs of hypersensitivity, respiratory
distress, N & V.
3. Management of allergic reactions
Mild:
diphenhydramine (phenergan)
Severe: (respiratory ):
epinephrine

4. Oral penicillin
Give on an empty stomach, one hour before or 1 to 2 hours
after meals,
Amoxicillin give with food.
Take with full glass of water, never with acidic fluids like
orange juice.

5. IM injections
deep into a large muscle mass.

Client Education
1. Take the medication around the clock
2. Finish taking the drugs as ordered, even if condition
improves.
3. Never share this medication because other individuals
4. Report white patches on oral mucosa, vaginal discharge
5. Ingest yoghurt if diarrhea develops to help replace
intestinal flora
6. Notify health professional if symptoms do not improve.

CEPHALOSPORINS

Introduction
The cephalosporins are closely related in
structure to penicillin.
They have a beta-lactam ring.
They are relatively stable in dilute acid
and are highly resistant to penicillinase.
Bactericidal
Broad spectrum
Resistant to beta-lactamases

Mechanism of action
Cephalosporins

inhibit the
peptidoglycan synthesis of bacterial
cell wall in a manner similar to that
of penicillin and are considered
bactericidal.

Spectrum of Activity and Clinical


uses of Cephalosporins
Divided into 4 major groups called
Generations
Are divided into Generations based on

parallel their chronological development


their antimicrobial spectrum

classification
1st

generation:

Cephalexin, cephadroxil (oral),


cephradine (parenteral)
2nd

generation

cefuroxime (oral), cefamandole


(parenteral)
3rd

generation

cefixime (oral), cefotaxime (parenteral)


4th

generation-eg cefditoren

First Generation
cephalosporins

They have a stronger antimicrobial action


on G+ bacteria than that of the other
generations, but their action on G- bacteria
is relatively poor.

These cephalosporins have nephrotoxicity


to a certain degree.

They are NOT effective against


pseudomonas.

Second Generation
Cephalosporins
Examples cefamandole, cefoxitin, cefaclor,
cefonicid, cefuroxime, cefotetan, cefprozil.
Action of this generation on G+ bacteria is
the same or a little bit less than that of the
first generation.
Their antimicrobial action on G- bacteria is
obviously increased
Some of them are effective against
anaerobes such as B.fragilis.

Second Generation
Cephalosporins

Cefuroxime is the only second-generation


drug that crosses the blood-brain barrier
well enough to be used for the treatment of
meningitis, especially H.influenzae
meningitis, and sepsis

Third Generation
Cephalosporins

Examples cefotaxime, ceftizoxime,


ceftriaxone, cefoperazone, ceftazidime,
cefixime, cefpodoxime

The broadest spectrums of all


cephalosporins
The highest activities against G- bacteria.
The lowest activities against G+ bacteria.
The highest resistance to -lactamase

Third Generation
Cephalosporins

The best penetration into the CSF;

almost no nephrotoxicity.

They are chiefly used in the infections of the


urethral or biliary tract with the drugresistant strains and Pseudomonas.

They are also used in some serious


pneumonia, sepsis and meningitis

Third Generation
Cephalosporins

There are also some unique properties of


individual 3rd generation.
Ceftriaxone has the longest half-life(8h) of any
cephalosporin.
Cefixime is an oral preparation.
Ceftazidime is the best anti-pseudomonal
cephalosporin.
Cefoperazone is eliminated(70%) in the bile, and is
thus very useful in patients with renal failure

Adverse reactions
Relatively few and low
The most common ones are Allergy
-hypersensitivity reactions (5%-10%)

anaphylaxis, fever, skin rashes, nephritis,


granulocytopenia, and hemolytic anemia.

During treatment with third-generation


drugs, these resistant bacteria, as well as
fungi, often proliferate and may induce
superinfection

Adverse reactions

Nephrotoxicity
The first-generation cephalosporins have
certain nephrotoxicity. (Renal damage, including
interstitial nephritis and even tubular necrosis )
The second-generation have slight
nephrotoxicity.
The third-generation have almost no
nephrotoxicity

Contraindication

Patients with known allergy to


cephalosporins and penicillin

Nursing implications
Check

culture and sensitivity report to


ensure that this is the drug of choice
Ensure that patient complete full course
Advise the patient to take oral
cephalosporins with food if gastric upset
occurs
Instruct the patient to refrigerate oral
suspension

Nursing intervention
Make

IM injections deep into


a large muscle. These
injections are usually painful,
forewarn the patient.
Instruct the patient to report
any signs of allergy eg skin
rash, itching.

Nursing intervention
Observe

patient for signs of


bleeding; if bleeding develops,
discontinue drug use.
Monitor patient for any sign of
super infection
The patient should be encouraged
to drink a lot of fluids and to
maintain nutrition

Drugs that inhibits


protein synthesis

Aminoglycosides
Potent
used

& bactericidal

to treat only serious or life-

threatening infections.
Have

high incidence of toxic effects

on several body systems.


Use with extreme caution

Aminoglycosides
Examples

include:

Amikacin

Gentamicin
Kanamycin
Neomycin
Streptomycin

Aminoglycosides
Indication

Reserved for gram-negative


bacteria causing bone infections,
septicemia, skin etc

Aminoglycosides
Mechanism

of action

inhibit bacteria protein synthesis.


inhibiting the translation of mRNA
to protein.
Leads to loss of functional integrity
of the bacterial cell membrane,
causing cell death.

Aminoglycosides
Contraindication/

caution

Known allergy to any aminoglycoside


Renal and hepatic disease
Preexisting hearing loss
Active infection with herpes or
mycobacterial infection
Myasthenia gravis or Parkinson
Lactation women.

Aminoglycosides
Adverse

effects

Ototoxicity.
Confusion, depression,
disorientation
Nephrotoxicity
GI effect, nausea, vomiting
Cardiac effect: palpitations,
Hypersensitivity reaction.

Aminoglycosides
Adverse

effects

Ototoxicity.
Confusion, depression,
disorientation
Nephrotoxicity
GI effect, nausea, vomiting
Cardiac effect: palpitations,
Hypersensitivity reaction.

Aminoglycosides
Nursing

Implication

Check culture and sensitivity report to


ensure that this is the drug choice for the
patient.
Ensure that the patient receives the full
course of the aminoglycosides as
prescribed.
Monitor the site of infection and
presenting signs and symptoms
throughout the course of treatment.

Aminoglycosides
Nursing

Implication

Monitor the patient regularly for


signs of adverse effects such as
nephrotoxicity
Provide safety measures to protect
patient if CNS effects, such as
confusion occur.

Aminoglycosides
Nursing

Implication

Ensure adequate hydration minimize


renal toxicity.
Provide small, frequent meals as
tolerated to maintain nutrition,
Ensure that the patient is instructed
about the appropriate dosage
regimen and possible adverse
effects.

Tetracyclines
Overview

Broadspectrum, bacteriostatic antibiotics


whose value has decreased owing to
increasing bacterial resistance.
They remain however, treatment of choice
for infections caused by Chlamydia &
rickettsia.
Examples

include:

Tetracycline
Doxycycline

Tetracyclines
Mechanism

of action

Inhibits protein synthesis after uptake


into susceptible organisms by active
transport.
It binds reversibly to the bacterial
ribosome and interferes with attachment
of tRNA to mRNA ribosome complex.
Tetracyclines have toxic effect on human
in high concentration because the
affected protein is similar to the protein
of the human cells.