ANTIBACTERIAL AND

ANTIINFECTIVE AGENTS
BY: ABDUL HAFIZ M. PITAMANAN, RN
OBJECTIVES:
PATHOPHYSIOLOGY
BACTERIA
• Known as prokaryotes
• Are single-celled organisms lacking a true nucleus
and nuclear membrane.
• Most have a rigid cell wall, and the structure of the
cell wall determines its shape.
• Reproduce by cell division about every 20minutes
• Produce toxins that cause cell lysis (cell death).
• Produce the enzyme beta-lactamase , which destroy
beta-lactam antibiotics such as penicillins and
cephalophorins.
 HOW TO CLASSIFY

1. MICROSCOPIC USE
 Identifies appearance or shape

Eg:
bacillus= rod shaped
cocci= spherical
staphylococci= cocci arranged in clusters
stretococci= cocci arranged in chains

*Bacteria reproduce by cell division about every

20minutes
 HOW TO CLASSIFY

2. GRAM STAINING METHOD

Devised in 1882 by Hans Christian Gram, a
Danish Bacteriologist
Determined by the ability of the bacterial cell
wall to retain in purple stain by a basic dye
(crystal violet or substituted by methylene blue).
• Gram-positive microorganisms- if bacteria
retain a purple stain
• Gram-negative microorganisms- if not stained
 EXAMPLE

GRAM-POSITIVE GRAM-NEGATIVE
• Staphylococcus aureus • Neisseria meningitides
• Streptococcus • E. Coli
pneumoniae • Haemophilus
• Group B. streptococcus Influenzae
• Clostridium perfringens
 ANTIBACTERIAL
DRUGS/ANTIBIOTICS
• Are substances that inhibit bacterial growth
(bacteriostatic action) or kill bacteria and
other microorganisms (bactericidal action)
• Technically refers to the chemicals
produced by one kind of microorganisms
that inhibits the growth of or kills another.
• Do not act alone in destroying bacteria. (natural
body defenses or surgical procedures of infected wound and dressing)
 ANTIBACTERIAL
DRUGS/ANTIBIOTICS
• Are obtained from natural sources or
manufactured.
Example: moldy bread on wounds to fight
infection
1928, a British bacteriologist named
Alexander Fleming discovered penicillin
when he noticed that mold contaminating
his bacterial cultures and inhibiting bacterial
growth.
That mold was called Penicillium notatum.
 MECHANISMS OF ANTIBACTERIAL
ACTION

1. Inhibition of bacterial cell-wall synthesis

2. Alteration of membrane permeability
3. Inhibition of protein synthesis
4. Inhibition of the synthesis of bacterial RNA
and DNA
5. Interference with metabolism within the
cell
BODY DEFENSES

Defense mechanism (body defenses) +

antibacterial drug to stop the infectious process

FACTORS: that influence the body’s ability to fight infectious process

• Age
• Nutrition
• Immunoglobulins (Ig)
• White blood cells (WBC)
• Organ function
• Circulation
RESISTANCE TO ANTIBACTERIALS

SENSITIVE BACTERIA RESISTANT BACTERIA

• Pathogen is • Pathogen continues
destroyed or to grow, despite of
inhibited administration the
antibacterial drug
RESISTANCE TO ANTIBACTERIALS
INHERENT RESISTANCE ACQUIRED
(NATURAL) RESISTANCE
• Resistance occurs • Is caused by prior
without previous exposure to the
exposure to antibacteria.
antibacterial drug • Occurs due to repeated
exposure to antibiotics.
Eg: Pseudomonas  evolvement resistant
aeruginosa (gram-  S. Aureus x Pen. G
negative/non-gram-  Penicilinase= an enzyme
produced by the
staining) is inherently microorganism
resistant to penicillin G. metabolizes Pen. G drug
becomes ineffective
resistance
METHICILLIN (STAPHCILLIN)

• Was the first penicillinase-resistant penicillin

developed in 1959 in response to a
resistance of S. Aureus.
• In 1968, S. Aureus x Methicillin
 METHICILLIN-RESISTANT
STAPHYLOCOCCUS AUREUS (MRSA)
• Highly resistant bacteria
• Resistant to all penicillins, methicillin, cephalosphorins

• TREATMENT OF CHOICE:
 Vancomycin (Cancocin)

VANCOMYCIN-RESISTANT S.AUREUS (VRSA)

Other tx:
 Linezolid (Zyvox)
 Daptomycin (Cubicin)
 Trimethoprim/sulfamethoxazole (Bactrim)
 Doxycycline (Vibramycin)
 Clindamycin (cleocin)
 Telavancin (Vibativ)
 VANCOMYCIN-RESISTANT
ENTEROCOCCUS FAECIUM (VREF)
• Another big resistance problem
• Resistant to penicillin, ampicillin gentamycin,
streptomycin, and vancomycin.
• Caused deaths in many persons with weakened immune
system

• Linezolid= effective against MRSA, VREF, and penicillin-

resistant Streptococci.
• Quinupristin/dalfopristin (Synercid)= consists of
streptogramin antibacterials, is marketed in a
combination of 30:70n for IV use against life-threatening
infection caused by VREF and for treatment of
bacteremia, S. aureus, and Streptococcus pyogenes.
WAYS TO ATTACK ANTIMICROBIAL
RESISTANCE
1. Antibiotic – • 2. Bacterial Vaccine
Reistance disabler • Against pneumococcus--- lessen
pneumonia cases and meningitis among
• People would take the disabler with the age groups
available antibiotic, making the drug
effective again
 REASONS OF DEVELOPING
RESISTANCE TO ANTIBACTERIALS
• Antibiotic misuse • NURSING
Antibiotics are taken RESPONSIBILITY
unncessarily (viral Consumer education
infections or no Health teachings
infection is present) about proper use of
Antibiotics are taken antibiotics
incorrectly (skipping
doses, not taking the
full antibiotic
regimen)
CROSS RESISTANCE

• Can also occur between antibacterial drugs

that have similar actions, such as penicillin
and cephalosphorins.
CULTURE AND SENSITIVITY (C&S)

• Antibiotic susceptibility
• Performed to ascertain the effect of antibacterial drugs
have or specific organism.
• Detects the infective microorganisms present in a
sample (blood, sputum, swab) and what drug can kill
it.

Culture= determines the organis causing th infection.

Sensitivity=determines the antibiotics that organism is
sensitive to.

Multiantibiotic therapy
• daily use of several antibiotic
• Delays the development of microorganisms resistance.
GENERAL ADVERSE REACTIONS TO
ANTIBIOTICS

1. ALLERGIC (HYPERSENSITIVITY) REACTIONS

2. SUPERINFECTIONS
3. ORGAN TOXICITY
 SPECTRUM ANTIBIOTICS

NARROW-SPECTRUM BROAD SPECTRUM

• Are primarily effective • Effective against both
against one type of gram-positive and
organism
• Eg.: penicillin and
negative organisms
erythromycin= effective • Eg.: tetracycline and
against gram positive cephalosphorins
bacteria
• Frequently used when
• Selective more active
against those single the offending
organisms than the microorganism has not
broad-spectrum been identified by C&S.
antibiotics
PENICILLINS AND
CEPHALOSPORINS
 PENICILLIN
• A natural antibacterial agent obtained from the
mold genus Penicillium.
• “miracle drug” in 1945
• Introduced to the military during World War II
• Bacteriostatic and bactericidal, depending on the
drug and dosage.
• It’s beta lactam structure (beta-lactam ring)
interferes with bacterial cell-wall synthesis by
inhibiting the bacterial enzyme that is necessary for
cell-division and cellular synthesis cell-lysis (cell
breakdown) bacteria die Beta-lactam antibiotics
PENICILLIN G
• Is primarily bactericidal.
• The first penicillin administered orally and by
injection.
• More effective when given by injection (IM
and IV) to achieve a therapeutic serum
penicillin level.
• Poor absorption when given orally. Only one third of
the dose is absorbed.
 PENICILLIN G
AQUEOUS PROCAINE
• Short-time duration of • Milky color
action • Longer-acting form
• IM injection= very • Procaine= decreases
painful (aqueous pain.
solution)
PENICILLIN V
• The next type of penicillin that was produced
• Less potent antibacterial drug than pen. G.
• Two thirds of the dose is absorbed by the GI
tract.
• Effective against mild to moderate infections,
including anthrax (biologic weapon of
bioterrorisim).
• Should be taken after meals. Eg: Amoxicillins
• Its absorption is not significantly altered by food.
 BROAD-SPECTRUM PENICILLINS
(AMINOPENICILLINS)
• Are used to treat both gram-positive and gram-negative
bacteria
• Costly
• Not as “broadly” effective against all microorganisms as
they were before.
• Ineffective against some gram-negative organisms: E.
coli, H. Influenzae, Shigella dysenteriae, Proteus mirabilis,
and Salmonella.
• Not penicillinase resistant
• Readily inactivated by beta-lactamases ineffective
against S. aureus.
• eg. Ampicillin (Omnipen), and amoxicillin (Amoxil) which
is the most prescribed derivative for adults and children.
 PENICILLINASE-RESISTANT
PENICILLINS (ANTISTAPHYLOCOCCAL
PENICILLINS)
• Are used to treat penicillinase-producing S.
aureus
• Is not effective against gram-negative
organisms
• Less effective than pen. G against gram
positive organisms.

Eg.
Dicloxacillin= oral antibiotic
Nafcillin and oxacillin= IM and IV preparations
EXTENDED –SPECTRUM PENICILLINS
(ANTIPSEUDOMONAL PENICILLINS)

• Broad-spectrum penicillins
• Effective against Pseudomonas aeruginosa,
a gram-negative bacillus that is difficult to
eradicate.
• Useful against many gram-negative
organisms such as Proteus spp., Serratia spp.,
Klebsiela pneumoniae, enterobacter spp.,
and Acinetobacter spp.
• Not penicillinase-resistant
• Similar pharmacologic action with
aminoglucosides but less toxic.
 BETA-LACTAMASE INHIBITORS

• Effective and its antimicrobial effect is extended

when combined with broad-spectrum antibiotics as
it inhibits beta lactamases.

3 Beta-lactamase inhibitors
1. Clavulanic acid (oral use)
2. Sulbactam (parenteral )
3. Tazobactam (parenteral)

• Mostly excreted via the kidneys

 BETA-LACTAMASE INHIBITORS

SIDE EFFECTS ADVERSE REACTIONS

• GI DISTURBANCES • HYPERSENSITIVITY
• Nausea • Mild to moderate
• rashes
• Vomiting
• Severe
• diarrhea • Laryngeal edema
• Severe bronchoconstriction
with stridor
• Hypotension

• SUPERINFECTION
• occurrence of a
secondary infection when
the flora of the is disturbed.
 BETA-LACTAMASE INHIBITORS;
PHARMACOKINETICS
• Amoxicillin
• well absorbed from the GI tract
• 20% protein bound
• 60% is excreted in the urine
• Dicloxacillin
• partially absorbed
• Highly protein-bound (95%)
• Excreted in the bile and urine
• If added with other highly protein-bound drugs, drug toxicity
may occur.
• Both have short half-lives.
 BETA-LACTAMASE INHIBITORS;
PHARMACODYNAMICS
• Bactericidal
• Interferes bacterial cell-wall synthesis---cell lysis.
• Amoxicillin or dicloxacillin + probenecid (uricosuric drug- treat
gout) = increased antibacterial serum levels

• Amoxicillin + erythromycin + tetracylcline =

decreased amoxicillin effect
 BETA-LACTAMASE INHIBITORS;
NURSING MANAGEMENT

MANAGEMENT
• Monitor renal funcion
of older adults.
• BUN, crea= if with
decreased renal function,
dose should be
decreased.
• Monitor closely during
the first dose and
subsequent doses of
penicillin.
RATIONALE
• Mostly excreted via the
kidneys
• Allergic reaction occurs
in 5% to 10% op people
receiving penicillin
compounds.
 BETA-LACTAMASE INHIBITORS;
DRUG INTERACTIONS

• Broad-spectrum penicillins-amoxicillin
and ampicillin--- may decreace the
effectiveness of oral contraceptives
• Potassium supplements + potassium
pen. G and V = increasing potassium
serum levels
• Penicillin + aminoglycosides in IV
solution= both drugs are inactivated
 CEPHALOSPORINS
• CEPHALOSPORIM ACREMONIUM
• Discovered in seawater at a sewer outlet off the coast of
Sardinia in 1948
• Active against gram-positive and gram-negative bacteria
and resistant to beta lactamase.

• Were used with clinical effectiveness in 1960

• Molecules were chemically altered, and
semisynthetic were produced for it to be effective
against numerous organisms.
• Have a beta-lactam structure like penicillin and act
by inhibiting the bacterial enzyme necessary for cell
wall synthesis lysis bactericidal.
 CEPHALOSPORINS;
GROUPS

• First Generation- destroyed by beta

lactamases
• Second Generation- some are
affected by beta lactamases
• Third Generation- resistant to beta-
lactamses
• Fourth Generation
 CEPHALOSPORINS

SIDE EFFECTS ADVERSE REACTION/S

• GI DISTURBANCES • NEPHROTOXICITY in
• Nausea individuals with a
• Vomiting preexisting renal
• Diarrhea disorder
• Increased bleeding-
alteration in blood
clotting time with
administration of large
doses
 CEPHALOSPORINS;
DRUG INTERACTIONS

• Alcohol consumption may cause flushing,

dizzines, headache, nausea, vomiting, and
muscular cramps while taking cefamandole,
or cefoperazone.
• With uricosuric drugs, decrease the
excretion of cephalosporins---- greatly
increasing serum levels.
 MACROLIDES, TETRACYCLINES,
AMINOGLYCOSIDES, AND
FLUOROQUINOLONES
SIMILAR TO PENICILLIN, DIFFERENT IN STRUCTURE
PENICILLIN SUBSTITUTES (ERYTHROMYCIN)-PEOPLE ALLERGIC TO PENICILLIN
 MACROLIDES
• Broad-spectrum antibiotics (azithromycin, clarithromycin,
erythromycin)
• Bind to the 50S ribosomal subunits and inhibit protein
synthesis.
• Bacteriostatic at low to moderate dosage
• Bactericidal at high drug doses
• Given orally or IV slowly to prevent phlebitis
• Never give via IM painful
• Active against most gram-positive bacteria and
moderately active against some gram-negative
bacteria.
• Used to treat mild to moderate infection of the
respiratory tract, sinuses, GI tract, skin, and soft tissue,
and diphtheria, impetigo contagiosa, and STI.
 MACROLIDES

• ERYTHROMYCIN
• The first macrolide
• Derived from the funguslike bacteria Streptomyces erytheus
• First introduced in the early 1950s.
• Acid-resistant salts are added to decrease the dissolution in
the stomach because the drug is destroyed by gastric acid
in the stomach------this allows the drug to be absorbed in
the intestines.
• Drug of choice for the treatment of mycoplasmal
pneumonia and Legionnaire’s disease (atypical neumonia)
• Should not be taken with clindamycin or incomycin
because they compete for receptor sites.
• Increase eryhtromycin blood concentration and risk of
sudden cardiac death when given with verapamil (Calan),
diltiazem (Cardizem), clarithromycin (Biaxin), fluconazole
(Diflucan), ketoconazole (Nizoral), itraconazole (Sporanox).
 MACROLIDES

SIDE EFFECTS ADVERSE REACTIONS

• GI DISTURBANCES • HEPATOXICITY
• Nausea • Usually reversible if
• Vomiting discontinues
• Diarrhea • High dose + other
• Abdominal cramping hepatotoxic drugs in high
dose (acetaminophen,
• CONJUNCTIVITIS phenothiazines,
• Avoid wearing contact sulfonamides)
lenses if occurs
 MACROLIDES;
DRUG INTERACTIONS

• Increase serum level of theophylline

(bronchodilator), carbamazepine
(anticonvulsant), and warfarin
(anticoagulant).monitor drug serum levels
• Never take erythromycin with other
macrolides. To avoid severe toxic effects
• Antacids may reduce zithromycin peak
levels when taken at the same time.
 EXTENDED MACROLIDE GROUP
ELIMINATION OF THESE DRUGS IS VIA BILE AND FECES

AZITHROMYCIN
CLARITHROMYCIN (BIAXIN) (ZITHROMAX)
• Side effects • Long half-life of up to
• Nausea 40-68hours----only
• Diarrhea prescribed once a day
• Abdominal discomfort for 5days.
• Frequently prescribed
for URTI and LRTI, STI’s,
and uncomplicated
skin infection.
 LINCOSAMIDES

• Inhibit bacterial protein synthesis and have both

bacteriostatic and bactericidal action, depending
on drug dosage.
examples:
CLINDAMYCIN (CLEOCIN)
• More widely prescribed than lincomycin because it is active
against most gram-positive organisms including S. aureus
and anaerobic microorganism.
• Not effective against gram-negative bacteria (E. coli,
proteus, pseudomonas)
• Absorbed bette than lincomycin and has fewer toxic
effects.
 LINCOSAMIDES

SIDE EFFECTS ADVERSE REACTIONS

• GI IRRITATION • COLITIS
• Nausea • ANAPHYLACTIC
• Vomiting SHOOCK
• Stomatitis
 LINCOSAMIDES;
DRUG INTERACTIONS

• Incompatible with aminophylline, phenytoin

(Dilantin), barbiturates, ampicillin.
 GLYCOPEPTIDES

• VANCOMYCIN (VANCOCIN)
• Bactericidal
• Widely used in the 1950s to treat staphylococcus
infections
• Is used against drug-resistant S. aures and in
cardiac surgical prophylaxis for individuals with
penicillin allergies
• Has become ineffective for treating enterococci--
-resistance (VREF)---can cause staphylococcal
endocarditis and life threatening----treatment:
Quinupristin/dalfopristin
 GLYCOPEPTIDES

• TELEVANCIN (VIBATIV)
• Treats selected gram-positive bacteria and skin infections.
• Semisynthetic derivative of vancomycin, with bactericidal
action against MRSA.
• Has an advantage of once-daily dosing.
 GLYCOPEPTIDES;
PHARMACOKINETICS
• VANCOMYCIN
• Given orally for S. enterocolitis and antibioti-associated
pseudomembranous colitis due to Clostridium difficile.
• Not absorbed systematically when given orally and is
excreted in the feces.
• Given IV for severe infections due to MRSA; septicemia; and
bone, skin, LRT infections that do not respond or are resistant
to anibiotics.
• Intermittent vancomycin doses should be diluted in 100ml
for 500mg and 200ml for 1g of D5W, NS, or LR at a rate of
10mg/min or a min. of 60 mins.
• Excreted in the urine when given IV.
• 30% protein-bound
• Half-life is 6hours.
 GLYCOPEPTIDES;
PHARMACODYNAMICS
• VANCOMYCIN
• Inhibits bacterial cell wall synthesis and is active
against several gram-positive microorganism.
• Peak action- 30mins after the end of the infusion.
 GLYCOPEPTIDES
ADVERSE EFFECTS
SIDE EFFECTS • NEPHROTOXICITY
• Chills • OTOTOXICITY
• Auditory damage- permanent
• Dizziness hearing loss
• Vestibular branch damage
• Fever (cranial nerve VIII)- temporary
or permanent loss of balance
• Rashes • “red man” syndrome or red
• Nausea neck syndrome- red blotching
of the face, neck, and chest---
• Vomiting toxic effect due to rapid IV
injection
• Thrombophlebitis at the • Eosinophilia, neutropenia, and
injection site Stevens-Johns syndrome,
severe hypotension,
tachycardia, generalized
tingling, and rarely cardiac
arrest
 GLYCOPEPTIDES;
DRUG INTERACTIONS
• Vancomycin + dimenhydrinate (Dramamine)=
masking of ototoxicity
• Vancomycin + furosemide, aminoglycosides,
amphotericin B, colistin, cisplatin, and cyclosporine=
Potentiated nephrotoxicity and ototoxicity
• Vancomycin + methotrexate ---inhibits
methotrexate excretion---methotrexate toxicity
• Oral vancomycin + cholestyramine colestipol---
decreased absorption of vancomycin
 KETOLIDES

• Structurally related to macrolides

Telithromycin (Ketek)
• Is used for adults 18years of age and older to treat mild to
moderate community-acquired pneumonia that are usually
caused by Streptococcus pneumoniae and Haemophilus
influenza.
 KETOLIDES
• PHARMACOKINETICS
• Telithromycin is given PO
and is well absorbed by
the GI tract and not
affected by food intake
• Excreted in the feces and
urine
• 60%-70% protein bound
• Half-life: 10hours
• PHARMACODYNAMICS
• Inhibits protein synthesis in
microorganisms by
binding to the bacterial
ribosomal RNA site of the
50S subunit---bacterial
cell death.
• Peak action is 1hour
 KETOLIDES;
DRUG INTERACTIONS
• Telithromycin + antilipidemics (simvastatin, lovastatin, and
atorvastatin), itraconazole, ketoconazole, benzodiazipines=
increase trlithromycin levels
• + Class 1A or class III antidysrhythmics= may lead to life
threatening dysrhythmias
• Telithromycin + rifampin, phenytoin, carbamazepine, or
phenobarbital= subtherapeutic effect; decreased
telithromycin blood levels
• Telithromycin x cisapride and pimozide= toxicity of the two
drugs
• Telithromycin + digoxin, metoprolol, midazolam, ritonavir
sirolimus, and tacrolimus= increase levels of the 5 drugs
• Telithromycin + ergot alkaloid derivatives antimigraine = ergot
toxicity (severe peripheral vasospasm and impaired
sensation).