ANTI-INFECTIVE

AGENTS
 ANTI-INFECTIVES AGENTS

►Drugs that are designed to

act selectively on foreign
organisms that have invaded
and infected the body of a
human host
Anti-infective Therapy Includes:
►Antibiotics
►Antivirals
►Antifungals
►Antiprotozoans
►Antihelmintics
►Antineoplastics
 Mechanism of Action (MOA)

►Act on the cells of the invading

organism in different ways
►The goal is interference with the
normal function of the invading
organism to prevent it from
reproducing and to cause cell death
without affecting host cells
 Anti-infective Activity

Narrow-spectrum of Activity
► Effective
against only a few
microorganisms with a very specific
metabolic pathway
Broad-spectrum of Activity
► Interferes with the biochemical reactions
in many different kind of microorganisms
and useful in the treatment of a wide
variety of infections
Microorganisms Develop Resistance By:

► Producing an enzyme that deactivates

the antimicrobial drugs
Example:
► Some strains of bacteria that were
once controlled by penicillin now
produce an enzyme called penicillinase
which deactivates penicillin before it
can affect the bacteria
►Changing cellular permiability to prevent
the drug from entering the cell or altering
transport systems to exclude the drug from
active transport into the cell
►Altering binding sites on the membranes
or ribosomes, which then no longer accept
the drug
►Producing a chemical that acts as an
antagonist to the drug
 Preventing Resistance:

Drug Dosage
►doses should be high enough and
the duration of drug therapy should
be long enough to eradicate even
slightly resistant microorganisms
►Cautious about the indiscriminate use of
anti-infectives
⮚ the drug is prescribed for treating the
particular and current infection of the
patient
⮚ do not use this drug to treat other types of
infections
 Treatment of Systemic Infections

Identification of the Pathogen

►Identification of the infecting
pathogen is done by culture of a
tissue from the infected areas
Sensitivity of the
Pathogen
►Sensitivity
testing which
drugs are
capable of
controlling the
particular
microorganism
Combination Therapy
►Combination of two or more types of drugs
effectively treats the infection
Reason:
►Allow the health care provider to use
smaller dosage of each drug, leading to
fewer adverse effects but still have a
therapeutic impact on the pathogens
►Some drug are synergistic (powerful when
given in combination)
►Many bacterial infection are caused by
more than one organism and each
pathogen react to a different anti-infective
►Combine effects of the different drugs
delay the emergence of resistant strains
 Adverse Reactions to Anti-infective
Therapy
Kidney Damage
►Occurs most frequently with drugs
that are metabolized by the kidneys
and then eliminated in the urine
►To prevent accumulation of the drug
in the kidney, patients should be
well-hydrated throughout the course
of the drug
Gastrointestinal Toxicity
►Very common
►Direct toxic effects on the cells lining the
GIT causing nausea, vomiting, stomach
upset, or diarrhea
Neurotoxicity
►Affects the 8th cranial nerve and can cause
dizziness, vertigo, and loss of hearing
Hypersensitivity Reactions
►These agents are protein bound for
transfer through the cardiovascular system
are able to induce antibody formation in
susceptible people
Superinfections
►Broad-spectrum anti-infective destroys the
normal flora and the opportunistic
pathogens that were kept in check by the
normal bacteria have the opportunity to
invade tissues and cause infection
Example:
►Vaginal or GI yeast infection
 Prophylaxis

►Travelling to an area where malaria

is endemic
►Undergoing GI or GU surgery which
might introduce bacteria from those
areas into the system
►Known cardiac valve disease, valve
replacements and other conditions prone
to the development of subacute bacterial
endocarditis because of the vulnerability of
their heart valves
 Antibiotics/Antibacterial

►Are chemicals or substances that

inhibit the growth or kill bacteria
and other microorganisms
Bacteriostatic drugs:
⮚ inhibit the growth of bacteria
Bactericidal drugs:
⮚ kill bacteria
Goal of Antibiotic Therapy:
►Decrease the population of the invading
bacteria to a point at which the human
immune system can effectively deal with
the invader
Gram-positive Bacteria
► Those whose cell
wall retains Gram's
stain or resist
decolorization with
alcohol during
culture and
sensitivity testing
► Commonly associated
with infections of the
respiratory tract and
soft tissues
Gram-negative
Bacteria
► Those whose cell
walls lose a stain
or are decolorized
by alcohol
► Associated with
infections of the
genitourinary
tract or
gastrointestinal
tract
 Aminoglycosides

►A group of powerful
antibiotics used to treat
serious infections caused by
gram-negative aerobic bacilli
Therapeutic Actions

►Bactericidal
►Inhibit protein
synthesis in usceptible
strains of gram-
negative bacteria,
which in turn leads to
loss of functional
integrity of the
bacterial cell
membrane, causing
cell death
Indications:
► Used to treat serious infetions caused by susceptible strains of gram-
negative bacteria:
⮚ P. aeruginosa
⮚ E. coli
⮚ Proteus species
⮚ Klebsiella-Enterobacter-Serratia group
⮚ Citrobacter sp.
⮚ Staphylococcus sp.
► Indicated to treat serious infections that are susceptible to penicillin
when penicillin is C/I
Amikacin
►available for short-term IM or IV use for
serious gram-negative infections
Gentamicin
►It covers a wide variety of infections
including pseudomonal diseases and once-
rare infections seen in patients with AIDS
Kanamycin
►Used to treat hepatic coma when
ammonia-producing bacteria in the GIT
cause serious illness
►Also used as an adjunctive therapy to
decrease GI bacterial flora
►Should not be used for longer than 7 to 10
days because of its potential toxic effects
Neomycin
►A slightly milder aminoglycosides that is
used to suppress GI bacteria
preoperatively and to treat hepatic coma
►Topical neomycin, is used to treat skin
wounds and infections
Streptomycin
►Very toxic to CN VIII and kidney
►Used as 4th drug in combination therapy
for tuberculosis
Tobramycin
►Also available in opthalmic
form for the treatment of
ocular infection caused by
susceptible bacteria
 Cephalosporins
► Similar to penicillins in structure
and in activity
Therapeutic Actions
► Bactericidal and bacteriostatic
► Basically interfere with the cell
wall-building ability of bacteria
when they divide
⮚ bacteria with weakened cell
walls swells and burst as a result
of the osmotic pressure within
the cell
First-generations
►Effective against same gram-negative
bacteria that are affected by penicillin G as
well as gram-negative bacteria Proteus
mirabilis, E.coli, and Kebsiella pneumoniae
(PEcK)
⮚ Cefadroxil
⮚ Cefazolin
⮚ Cefalexine
⮚ Cefadrine
Second-generations
►Effective against those strains as well as
✔Haemophilus influenzae
✔Enterobacter aerogenes
✔Neisseria sp.
HENPeCK
►Less effective against gram-positive
bactria
⮚cefaclor
⮚cefmetazole
⮚cefprozil
⮚cefuroxime
⮚loracarbef
Third-generations
► Relatively weak against gram-positive bacteria but are more potent
against gram-negative bacilli as well as Serratia marcescens
(HENPeCKS)
⮚ cefdinir
⮚ cefoperazone
⮚ cefotaxime
⮚ cefpodoxime
⮚ ceftazidime
⮚ ceftibuten
⮚ ceftizoxime
⮚ ceftriaxone
Fourth-generations
►Active against gram-negative and gram-
positive organisms, including
cephalosporin-resistant sataphyloccoci and
P. aeruginosa
⮚ cefditoren
⮚ cefepime
►When a patient consumes alcohol
while receiving cephalosporins or
up to 72 hours after
discontinuation of the drug, in
many cases a disulferam-like
reaction occurs
 Fluorquinolones

►Relatively new class of

antibiotics with a broad
spectrum of activity and
are associated with
relatively mild adverse
reactions
Therapeutic Actions:
►Enter the bacterial cell by
passive diffusion through
channel in the cell
membrane
🡻
interfere with the action of
DNA enzymes necessary for
the growth and
reproduction of the
bacteria
Indication:
► Use to treat infections caused by:
⮚ E. coli
⮚ P. mirabilis
⮚ P. vulgaris
⮚ K. pneumoniae
⮚ E. cloacae
⮚ P. rettgeri
⮚ Morganella morganii
⮚ Moraxella catarrhalis
⮚ H. influenzae
⮚ H. parainfluenzae
⮚ P. aureginosa
⮚ Citrobacter freundii
⮚ S. aureus
⮚ Staphylococcus epidermidis
⮚ N. gonorrheae
⮚ Gruop D streptococci
►These infections frequently include urinary tract,
respiratory tract, and skin infections
Ciprofloxacin
►The most widely used fluorquinolone
►Effective against a wide spectrum f gram-
negative
►Approved for prevention of anthrax infection
(2001)
►Also effective against typhoid fever
Gemifloxacin
►Oral agent used to treat acute exacerbation of
chronic bronchitis and for treating CAP
Levofloxacin
► Used to treat respiratory, urinary tract, skin and sinus
infections caused by susceptible gram-negative bacteria
► Preferred for severe infection or for use wen the patient
cannot take oral drugs
Lomefloxacin
► Oral drug that can be used to treat lower respiratory tract
infections, as well as many urinary tract infections
► Drug of choice for preoperative and postoperative
prophylaxis to prevent UTI after transurethral procedures
or transrectal prostate biopsies
Moxifloxacin
►An oral agent used to treat sinusitis, bonchitis,
and pneumonia in adults
Norfloxacin
►Recommended only for treatment of various UTI
caused by susceptible gram-negative bacteria
Ofloxacin
►Used to treat skin, respiratory, and UTI, as well
as pelvic inflammatory disease (PID)
Sparfloxacin
►Oral agent used to treat CAP and acute bronchitis
 Macrolides
Therapeutic Actions:
►Exert their effect by
binding to the bacterial
cell membrane and
changing protein function
which may prevent the
cell from dividing
(bacteriostatic) or cause
cell death (bactericidal)
Indications:
►For acute infections caused by:
⮚ S. pneumoniae
⮚ Mycoplasma pneumoniae
⮚ Listeria monocytogenes
⮚ Legionella pneumophila
⮚ Group A beta-hemolytic
⮚ PID caused by N. gonorrheae
⮚ URTI caused by H. influenzae
⮚C. diphtheriae
⮚Corynebacterium minutissimum
⮚Intestinal amebiasis
⮚Chlamydia trachomatis
Erythromycin
► First macrolide to be developed
► Good alternative for patient who were allergic to
penicillin
► Drug of choice to treat:
⮚ Legionnaire's disease
⮚ Infections caused by C. diphtheriae
⮚ Ureaplasma
⮚ Syphilis
⮚ Mycoplasmal pneumonias
⮚ Chlamydial infections
Azithromycin
►Used to treat:
⮚ Mild to moderate respiratory infections and
urethritis in adults
⮚ Effective in treating otitis media, pharyngitis, and
tonsilitis in children
►Half-life is 68 hours
useful for patients who have trouble remembering
to take pills since it can be given once a day
Clarithromycin
►An expensive oral agent that is
effective in treating several
respiratory, skin, sinus, and
maxillary infections
►Effective against mycobacteria
Dirithromycin
►Effective in treating upper and
lower respiratory tract
infections, skin infections,
pharyngitis, and tonsilitis
 Lincosamides

Clindamycin
► Reserved for severe infections caused by the
same sns of bacteria that are susceptible to
macrolides
Lincomycin
► Indicated to treat severe infections when
penicillin cannot be given and other less
effective antibiotics
 Monobactam Antibiotics

Therapeutic Actions:
► Disrupt cell wall synthesis, which promotes
leakage of cellular contents and cell death
Indications:
► Used to treat UTI, skin, intra-abdominal, and
gynecological infections
► Infections caused by:
⮚ E.coli
⮚ Enterobacter
⮚ Serratia
⮚ Proteus
⮚ Salmonella
⮚ Providencia
⮚ Pseudomonias
⮚ Citrobacter
⮚ Haemophilus
⮚ Nesisseria
⮚ Klebsiella
Aztreonam
►The only monobactam
antibiotic available
Penicillins and Penicillinase- Resistance
Antibiotics
► The first antibiotic introduced for clinical use
► Sir Alexander Flemming used Penicillum molds
to produce the original penicillin in the 1920's
Therapeutic Actions:
► Produced bactericidal effects by interfering with
the ability of susceptible bacteria to build their
cell walls when they are dividing
Indications:
► Used to treat:
⮚ Streptococcal infections (tonsilitis, scarlet fever,
pharyngitis, endocarditis)
⮚ Pneumococcal infections
⮚ Staphyloccal infections
⮚ Fusospirochetal infections
⮚ Ratbite fever
⮚ Diphtheria
⮚ Anthrax
⮚ Syphilis
⮚ Uncomplicated gonococcal infections
 Sulfonamides
Therapeutic Actions:
►Competitively block
para-aminobenzoic
acid (PABA) to
prevent the
synthesis of folic
acid for the
production of or
RNA and DNA
Indications:
►Used to treat against:
⮚ C. trachomatis
⮚ Nacordia
⮚ H. influenzae
⮚ E. coli
⮚ P. mirabilis
⮚ Used also to treat UTI and STI
Sulfadiazine
► An oral agent with broad use in infections caused by
susceptible bacteria
► Sulfisoxasole
► Recommended by the Centers for Disease Control and
Prevention (CDC) for the treatment of STIs and as
prophylaxis for recurrent otitis media
Sulfasalazine
► A sulfapyridine that is carried by aminosalicylic acid
(aspirin) that release the aminosalicylic acid in the colon
► Used to treat ulcerative colitis and Crohn's disease
because of the direct anti-inflammatory effect of the
aspirin
Cotrimoxazole
►A combination drug that contains
sulfamethoxazole and trimethropin
►Proven to be very effective in the
treatment:
⮚ Otitis media
⮚ Bronchitis
⮚ UTI
⮚ Pneumonitis caused by Pneumocystis
carinii
 Tetracyclines

► Developed as semisynthetic antibiotics based on the

structure of a common soil mold
► They are composed of four rings, which is how they got
their name
Therapeutic Actions:
► Inhibits protein synthesis in susceptible bacteria, leading
to the inability of the bacteria to multiply
► The affected protein is similar to a protein found in human
cells, these drugs can be toxic to humans at high
concentration
Indications:
► Effective against infections caused by:
⮚ rickettsiae
⮚ M. pneumoniae
⮚ Borrelia recurrentis
⮚ H. influenzae
⮚ H. ducreyi
⮚ Pasteurella pestis
⮚ P. tularensis
⮚ Bortonella bacilliformis
⮚ Bacteroides sp.
⮚ Vibrio comma
⮚ Vibrio fetus
⮚ Brucella sp.
⮚ E. coli
⮚ E. aerogenes
⮚ Shigella sp.
⮚ Acinetobacter calcoaceticus
⮚ Klebsiella sp.
⮚ Diplococcus pneumoniae
⮚ S. aureus
►Used also for treatment of acne and
uncomplicated GU infections caused C.
trachomatis
Tetracycline
►Used for treatment of wide variety of infections,
including acne vulgaris and minor skin infections
►Used when penicillin is C/I
►Available in opthalmic agent to treat superficial
ocular lesions and as a prophylaxis agent for
opthalmia neonatorum caused by N. gonorrheae
and C. trachomatis
Demeclocycline
►Available in oral form
Doxycycline
►Recommended to treat traveler's diarrhea,
peridontal disease, acne, and some STIs
Minocycline
►Used to treat severe infections caused by
susceptible bacteria
►Drug of choice in treating meningococcocal carriers
and uncomplicated GU and gynecological infections
Oxytetracycline
►Used as an adjunctive therapy in the treatment of
acute intestinal amebiasis
►Tetracycline should be given on an empty
stomach 1 hour before or 2-3 hours after
any meal or other medications
►Tetracycline should be used with caution in
children younger than 8 years of age, and
during pregnancy and lactation
⮚ because they can potentially damage the
bones and teeth
 Antituberculosis

►Because M. tuberculosis is
slow growing, the treatment
must be continued for 6
months to 2 years
1st-line Drugs
1. Isoniazid (INH)
► affects the mycolic acid coating of the bacterium
2. Rifampin
► alters the DNA and RNA activity of the bacterium
3. Ethionamide
► prevents cell division
4. Rifapentine
► alters DNA and RNA activity, causing cell death
► These drugs are used in combination of two or more agents until
bacterial conversion occurs or maximum improvement is seen
2nd-line Drugs
1. Ethambutol
►inhibits cellular metabolism
2. Pyrazinamide
►both bactericidal and bacteriostatic
►These drugs are used in combination with at
least one other antituberculosis drug
3rd-line Combination
1. Capreomycin
►MOA is not known
2. Cycloserine
►inhibits cell wall synthesis and leads cell death

►Using the drugs in combination helps to decrease

the emergence of resistant strains and to affect
the bacteria at various phases during their long
and slow life cycle
Major Side Effects:
Rifampicin 🡺red-orange secretions or urine
Isoniazid 🡺peripheral neuritis
Pyrazinamide 🡺 increased uric acid
Ethambutol 🡺visual problems
Streptomycin 🡺ototoxicity
 Leprostatic Drugs

Dapsone
►Has been the mainstay of leprosy
treatment for many years, although
resistant strains are emerging