Unit-II/Lecture-IV

Antibiotics

By: Muhammad Aurangzeb

BSN, MSPH, MSN
Lecturer-INS/KMU
 Objectives

At the completion of this unit the students will be able to;

• Define the most commonly used categories of antibiotics that is
used to prevent and treat infections.
• Briefly discuss action and effects of selected drug category

• List some of the most commonly used drugs for each drug
category
• Discuss the nursing measures/patient education which can be
taken if patient is using to treat and prevent infections.
 Antimicrobial therapy

• An antimicrobial therapy kills or inhibits the growth of

microorganisms such as bacteria, fungi, or protozoans.
• Therapies that kill microorganisms are called microbiocidal
therapies
• and therapies that only inhibit the growth of microorganisms
are called microbiostatic therapies.
 Antimicrobial therapy
• Empiric
– Infecting organism(s) not yet identified
– More “broad spectrum”
• Definitive
– Organism(s) identified and specific therapy chosen
– More “narrow” spectrum
• Prophylactic or preventive
– Prevent an initial infection or its recurrence after infection
 Antibiotics
• “ANTIBIOTIC” is derived from antibiosis which means “
against life”
• Antibiotics are agents made from living micro-organisms, or
synthetic that are used to inhibit specific bacteria.
• Bacteria that can produce them:
– Streptomyces, bacillus
• Molds
– Penicillum notatum, cephalosporium
 Bacteria and Antibiotics:

• Bacteria are microorganisms that invade the human body

through many routes like respiratory, GI, and skin.
• Human immune response is activated. As the body tries to rid
itself of bacteria, classic signs of inflammation (e.g. swelling,
heat, redness, and pain), fever begin to show up.
• The goal of antibiotic therapy is to decrease the population of
invading bacteria to a point at which the human immune
system can effectively deal with the invader.
 Gram Positive vs. Gram Negative Bacteria

• Most bacteria can be broadly classified as Gram +ve or Gram -ve.

• Gram +ve bacteria have cell walls composed of thick layers of
peptidoglycan.
• Gram +ve cells stain purple when subjected to a Gram stain
procedure.
• Gram -ve bacteria have cell walls with a thin layer of
peptidoglycan. The cell wall also includes an outer membrane
with lipopolysaccharide (LPS) molecules attached.
• Gram -ve bacteria stain pink when subjected to a Gram stain
procedure.
• While both Gram +ve and Gram -ve bacteria produce exotoxins,
only Gram -ve bacteria produce endotoxins.
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 Definitions
• Chemotherapy: It means using chemical agents that are
selectively toxic to the causative agent of the disease, such
as a microorganisms or malignant cells.
• Chemotherapy means the use of drugs to eradicate micro-
organisms and parasitic worms or malignant cells in the
body is called chemotherapy
• Antimicrobial drugs: Drugs that are used to treat infections
with micro-organisms are known as antimicrobial drugs.
• Antibiotics: Antibiotics are chemical substances produced
from various microorganisms (bacteria and fungi) that kill or
inhibit the growth of other microorganisms.
• Antibiotic resistance: Antibiotic resistance is the ability of
bacteria/fungi to resist the effects of an antibiotic. 9
 Cont….
• Infection: the invasion and multiplication of pathogenic
microorganisms in body tissues, causing disease in the host.
• Sepsis: The presence of bacteria (bacteremia), other
infectious organisms, or toxins created by infectious
organisms in the bloodstream with spread throughout the
body.  It is a potentially life-threatening complication of an
infection. Sepsis occurs when chemicals released into the
bloodstream to fight the infection trigger inflammatory
responses throughout the body damage multiple organ
systems.
• Super infection: a new infection occurring in a patient having
a preexisting infection; for example, bacterial infection may
occur in patients with viral respiratory disease. 10
 Principles of Antimicrobial Therapy

• Antimicrobial therapy takes advantage of the biochemical

differences that exist between microorganisms and human
beings.
• Antimicrobial drugs are effective in the treatment of
infections because of their selective toxicity;
• that is, they have the ability to injure or kill an invading
microorganism without harming the cells of the host.
 Selection of Antimicrobial Agents
• Selection of the most appropriate antimicrobial agent
requires knowing
A) the organism’s identity,
B) the organism’s susceptibility to a particular agent,
C) the site of the infection,
D) patient factors,
E) the safety of the agent, and
F) the cost of therapy.
• However, some patients require empiric therapy (immediate
administration of drug(s) prior to bacterial identification and
susceptibility testing).
 A) Identification of the infecting organism

• Characterization of the organism is central to selection of the

proper drug.
• It is generally necessary to do culture & sensitivity test to
arrive at a conclusive diagnosis and determine the
susceptibility to antimicrobial agents.
• Thus, it is essential to obtain a sample culture of the organism
prior to initiating treatment.
 A) Empiric Therapy Prior to Identification of
the Organism

• Ideally, the antimicrobial agent used to treat an infection is

selected after the organism has been identified and its drug
susceptibility established.
• However, in the critically ill patient, such a delay could be
fatal, and immediate empiric therapy is indicated.
 B. Determining antimicrobial susceptibility of
infective organisms

After a pathogen is cultured, its susceptibility to specific

antibiotics serves as a guide in choosing antimicrobial therapy
1. Bacteriostatic versus bactericidal drugs: Bacteriostatic
drugs: Which arrest the growth & replication of bacteria.
Bactericidal agents: Which kills bacteria. For example,
linezolid is bacteriostatic against Staphylococcus aurous and
enterococci but is bactericidal against most strains of S.
pneumoniae.
 Cont…
• Minimum inhibitory concentration: Minimum Inhibitory
Concentration (MIC) is the lowest concentration of antibiotics
that inhibits bacterial growth. To provide effective
antimicrobial therapy, the clinically obtainable antibiotic
concentration in body fluid should be greater then the MIC.
• Minimum Bactericidal concentration: Minimum bactericidal
concentration (MBC) is the lowest concentration of
antimicrobial agent that results in a 99.9 percent decline in
colony count after overnight broth dilution incubations.
 C. Effect of the site of injection on therapy

• The blood Brain Barrier: this barrier is formed by the single

layer of tail-like endothelial cells fused by tight junctions that
impede entry from the blood to the brain of virtually all
molecules, except those that are small and lipophilic.
• The penetration and concentration of an antibacterial agent
in the CSF is particularly influenced by the following factors:
 Cont….

1. Lipid soluble drug, such as quinolones and metronidazole,

have significant penetration into the CNS. In contrast, β-
lactum antibiotics, such as penicillin, are ionized at
physiologic PH and have low solubility in lipids. They
therefore have limited penetration through the intact blood
brain barrier under normal circumstances.

2. Molecular Weight of the drug

3. Protein binding of the drug
 E. Patient factors

1. Immune System
2. Renal Dysfunction: serum creatinine levels are frequently
used as an index of renal function for adjustment of drug
regimens.
3. Hepatic dysfunction
4. Poor perfusion
5. Age
6. Pregnancy
7. Lactation
F. Safety of the agent
G. Cost of the therapy
 Presence
of bacterial infection?

yes no

Determine probable
site of infection Observe closely
Obtain cultures

Obtain cultures
including blood Patients worsens

Begin empiric
therapy

At day 3 Streamline antibiotic:

Chek culture and - narrowest spectrum
Gram stains - fewest drug possible

Negative, or
Colonisation
 Spectrum of Antibiotics

• Narrow-Spectrum antibiotics: Isoniazid is active only against

mycobacteria
• Extended-Spectrum: Ampicillin acts against gram positive and
some gram negative bacteria
• Broad-Spectrum Antibiotics: Tetracycline and
chloramphenicol affect a wide variety of microbial species
Chlamydia trachomatis.

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 What is antimicrobial resistance?

• Antimicrobial resistance is the ability of microbes to resist the

effects of drugs in same dosage. When the drug loose the
ability to either kill or inhibit the growth of microbes and the
microbes gain the ability to survive in the presence of drug to
which they were previously susceptible this is called
resistance.

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 Intrinsic resistance
• Intrinsic resistance is the innate ability of a bacterial species
to resist activity of a particular antimicrobial drug. This can
also be called “insensitivity” since it occurs in organisms that
have never been susceptible to that particular drug.
• Lack of affinity of the drug for the bacterial target
for example penicillin's are not effective against
mycobacterium tuberculosis, as the later does not contain
peptidoglycan in cell wall.
• Inaccessibility of the drug into the bacterial cell
For example: Gram –ve bacteria are naturally resistant to
vancomycin and penicillin G/V.  Because of inability to
penetrate outer membrane.
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 Acquired resistance
• Acquired resistance means when the microbes gains the
ability to grow in the presence of a drug. Acquired resistance
develops when micro-organisms no longer respond to a drug
to which they were previously susceptible.
• β-Lactamase activity: This family of enzymes hydrolyzes the
cyclic amide bond of the β-lactam ring, which results in loss of
bactericidal activity
• Altered PBPs: Modified PBPs have a lower affinity for β-lactam
antibiotics

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26
 Antimicrobial drugs

Common microbes causing diseases

• Bacteria......anti bacterial
• Viruses……anti viral
• Fungi………anti fungal

• Protozoa ……antiprotozoal

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 History of antibiotics
• Before penicillin introduction there was no effective treatment
for treating infections.
• In 1928 penicillin, the first true antibiotic, was discovered by
Alexander Fleming, Professor of Bacteriology at St. Mary's
Hospital in London.
• Alexander Fleming was a bit disorderly in his work. He left his
petridishes uncovered. Upon returning from holidays he noticed
that a fungus, Penicillium notatum, had contaminated a culture
plate of Staphylococcus bacteria. The fungus had created
bacteria-free zones wherever it grew on the plate.

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 Cont…

• Fleming isolated and grew the mould in pure culture. He

found that P. notatum proved extremely effective even at very
low concentrations, preventing Staphylococcus growth even
when diluted 800 times.
• Fleming published his findings in the British Journal of
Experimental Pathology in June 1929.
 Classification of Antimicrobials
•• Alter nucleic acid metabolism
Inhibit cell wall synthesis
–
– Quinolones
Penicillins
– Cephalosporins
• Inhibit folate metabolism
– Carbapenems
– Trimethoprim
Monobactams (Aztreonam)
– Glycopeptide
Sulfamethoxazole(Vancomycin)
• Inhibit protein synthesis
– Chloramphenicol
– Tetracycline
– Macrolides
– Oxazolidinones (linezolid)
– Aminoglycosides
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 Cell wall synthesis inhibitors
• Penicillins are antibiotics derived from several strains of
common moulds.
• All penicillin's and cephalosporin's have beta lactam ring,
therefore they are called beta lactam antibiotics.

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33
 Penicillins

1. Natural penicilins (penicillin G and V)

2. Aminopenicilins (Amoxycillin, Ampicillin)
3. Anti-staphylococcal (Penicillinaze-resistent pencillins) e.g.
Cloxacillin and Dicloxacillin
4. Anti-pseudomonal (Carboxypencillins and ureidopencillins)
e.g. Tikarcilin-clavulanate, Piperacilin-tazobactam
 Mechanism of Action Penicillin's & Cephalosporin

• The synthesis of cell wall of bacteria depends upon an enzyme

named as transpeptidase (Penicillin binding proteins (PBPs)).
This enzyme cross-links peptidoglycan chains to form rigid cell
walls.
• Penicillins & cephalosporin's inhibits transpeptidase and
block the peptidoglycan of bacteria cell wall
 Important to know
• They are inactive against organisms lacking of cell wall
(peptidoglycan), such as mycobacteria, protozoa, fungi, and
viruses.
• Production of autolysins: Many bacteria, particularly the gram-
positive cocci, produce degradative enzymes (autolysins)
• Thus, the antibacterial effect of a penicillin is the result of both
inhibition of cell wall synthesis and destruction of the existing
cell wall by autolysins.
• In general, gram-positive microorganisms have cell walls that
are easily reached by penicillin, and, therefore they are easily
targeted.
• Gram-negative bacteria have water-filled channels (called
porins) to drug entry.
 Penicillin's Resistance
• Penicillins are inactivated by β-lactamases (penicillinases) that
are produced by the resistant bacteria
• Antistaphylococcal Penicillins: Methicillin, nafcillin, oxacillin,
and dicloxacillin are β-lactamase (penicillinase)-resistant
Penicillins. Their use is restricted to the treatment of
infections caused by penicillinase-producing staphylococci
• Clavulanic acid, sulbactam , and tazobactam are β-lactamase
inhibitors
• Antipseudomonal Penicillins: Piperacillin and ticarcillin are
called antipseudomonal penicillin because of their activity
against Pseudomonas aeruginosa
 Therapeutic uses

• Bacterial infections (only Peptidoglycan cell walled bacteria)

• Streptococcal infections: pharyngitis, sinusitis, otitis media
and cellulitis etc.
• Syphilis
• Diphtheria

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 Adverse reactions

• Skin rashes, urticaria

• Hypersensitivity: Approximately 5% percent of patients have
some kind of reaction, ranging from rashes to angioedema
(marked swelling of the lips, tongue) and anaphylaxis. Cross-
allergic reactions occur among the β-lactam antibiotics.
• Diarrhea: Diarrhea is a common problem that is caused by a
disruption of the normal balance of intestinal microorganisms.

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 Cephalosporin

• Cephalosporin drugs are beta lactam antibiotics that inhibit

the cell wall of bacteria. Cephalosporin was first isolated from
a fungus named as Cephalosporium acremonium by Dr.
Abraham in 1948. These are bactericidal antibiotics as they kill
the micro-organisms when used at therapeutic dose.
• Mode of Action: As penicillin

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 First Generation

• First Generation: The optimum activity of all first generation

cephalosporin drugs is against Gram-positive bacteria such as
staphylococci and streptococci.
Drugs:
 Cefazolin
 Cefadroxil

 Cephradine
 Cephalexin
 Second Generation
• The second generation drugs have more activity against
Gram-negative bacteria (Haemophilus
influenzae, Enterobacter aerogenes) in comparison to the first
generation. Their Gram positive spectrum is less than the first
generation.
• Drugs:
 Cefamandole
 Cefoxitin
 Cefaclor
 Cefpodoxime

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 Third Generation

Third generation cephalosporin drugs are broad spectrum and

the effective against both Gram positive and gram negative
bacteria.
Drugs:
 Cefotaxime
 Ceftriaxone
 Ceftazidime
 Cefixime
 Fourth Generation

• Fourth Generation:
• These are extended spectrum antibiotics. They are resistant to
beta lactamases.
Drugs:
 Cefipime
 Fifth Generation

• Ceftaroline, and Ceftobiprole are broad-spectrum, advanced-

generation cephalosporins that is administered IV. They are
the only commercially available β-lactam in the United States
with activity against MRSA and is indicated for the treatment
of complicated skin and skin structure infections and
community-acquired pneumonia. The unique structure allows
ceftaroline to bind to PBP2a found with MRSA and PBP2x
found with Streptococcus pneumoniae.

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 Important about cephalosporins
• The cephalosporins are β-lactam antibiotics that are closely
related both structurally and functionally to the penicillins
• The first-generation cephalosporins are effective against
staphylococcal infections
• The third-generation cephalosporins have enhanced activity
against gram-negative bacilli
• Cefepime is classified as a fourth-generation cephalosporin
and must be administered parenterally.
• Ceftaroline is a fifth generation, and is effective against MRSA

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 Adverse effects

• Hypersensitivity (rarely anaphylaxis)

• The patient may be informed that diarrhea is a common
problem caused by antibiotics which usually ends when the
antibiotic is discontinued.
• Cross allergy with cephalosporins should be considered.
• Nephrotoxicity may occur rarely

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 Carbapenems
• Carbapenems are a class of highly effective antibiotic agents
commonly used for the treatment of severe or high-risk
bacterial infections. This class of antibiotics is usually reserved
for known or suspected multidrug-resistant (MDR) bacterial
infections.
• Mechanism of Action: as cephalosporin's
• However, these agents individually exhibit a broader
spectrum of activity compared to most cephalosporins and
penicillins. Furthermore, Carbapenems are typically
unaffected by emerging antibiotic resistance, even to other
beta-lactams.
 Uses of Carbapenems
• Intra-abdominal infections
• Complicated urinary tract infections
• Pneumonia
• Bloodstream Infections

Side effects: Nausea, vomiting and rashes are common side

effects and rarely, seizures have also been reported
 Monobactams 
• Monobactams are monocyclic and bacterially-produced β-
lactam antibiotics. The β-lactam ring is not fused to another
ring, in contrast to most other β-lactams. 
• Monobactams are effective only against aerobic Gram-
negative bacteria (e.g., Neisseria, Pseudomonas).
• Aztreonam is a commercially available monobactam
antibiotic. 
• Used for bone infections, endometritis, intra abdominal
infections, pneumonia, urinary tract infections, and sepsis.
• Adverse effects to monobactams can include skin rash and
occasional abnormal liver functions.
 Glycopeptide antibiotics (Vancomycin)
• Vancomycin is in a class of medications called glycopeptide
antibiotics.
• Mechanism of Action: Inhibits cell wall synthesis in Gram-
positive bacteria by binding to the D-Ala-D-Ala terminal of the
growing peptide chain during cell wall synthesis, resulting in
inhibition of the transpeptidase, which prevents further
elongation and cross-linking of the peptidoglycan
• It is recommended intravenously as a treatment for
complicated skin infections, bloodstream infections,
endocarditis, bone and joint infections, and meningitis caused
by methicillin-resistant Staphylococcus aureus
 Side effects

• Common side effects include pain in the area of injection

and allergic reactions.
• Occasionally, hearing loss, low blood pressure, or bone
marrow suppression occur.
• Ototoxicity
• Nephrotoxicity

• Red man syndrome

 Fosfomycin
• It is a novel class of antibacterial drugs with a chemical
structure unrelated to other known antibiotics. It disrupts cell
wall synthesis by inhibiting phosphoenolpyruvate synthetase
and thus interferes with the production of peptidoglycan.
• It is bactericidal against a range of gram positive and gram
negative bacteria including staph.aureus
• Is demonstrates synergistic effects when combined with
penicillin, cephalosporin, aminoglycosides or fluroquinolones
• UTI- single 3g dose
• P/K-orally and parenterally
• Excreted unchanged in urine-90-95%
• ADR-GIT distress, visual disturbances, asthma
Proteins synthesis inhibitors

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 Aminoglycosides

• Mechanism of action: aminoglycosides irreversibly bind to the

30S ribosomal subunit of bacteria. This binding inhibit protein
synthesis.
• Aminoglycosides are mostly used against Gram-negative
enteric bacteria (gram-negative rods that inhabits the
gastrointestinal tract. V. cholera, Escherichia coli  )
• They can be used in combination with a β-lactam antibiotic to
extend coverage (synergism)
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 Spectrum of activity

• Broad spectrum as it effective against Aerobic Gram-negative

& Gram-positive bacteria
• But NOT effective against anaerobic bacteria because of it
Oxygen dependent active transport (this required step makes
aminoglycosides ineffective against anaerobic bacteria).

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 Clinical Uses
• Mycobacterial Infections
• Brucellosis: Brucellosis is a zoonotic infection caused by the
bacterial genus Brucella. The bacteria are transmitted from
animals to humans by ingestion through infected food
products, direct contact with an infected animal.
• Plague: it is a disease that affects humans and other
mammals. It is caused by the bacterium, Yersinia pestis.
• Tularemia: it  is a serious infectious disease caused by the
intracellular bacterium Francisella tularensis

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Important to remember about aminoglycosides

• Aminoglycosides are poorly absorbed from the gastro

intestinal tract and have to be given parenterally as
aminoglycosides are strongly polar molecules.
• They are eliminated by the kidneys, therefore, in kidney
patients dose needs to be adjusted
• Aminoglycosides are bactericidal. Aminoglycosides do not
cross the blood brain barrier, but can cross placental barrier
• nephrotoxic
• Check renal function: BUN and creatinine

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 Macrolides
• Macrolides are protein synthesis inhibitors.
• Mechanism of action: Macrolide antibiotics do so by binding
reversibly to the P site on the 50S subunit of the bacterial
ribosome.
• This action is considered to be bacteriostatic.
• Macrolides are actively concentrated within leukocytes, and
thus are transported into the site of infection.
• Common drugs: erythromycin, clarithromycin, azithromycin

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 Antibacterial spectrum
• Erythromycin: This drug is effective against many of the same
organisms as penicillin G. Therefore, it may be used in patients
with penicillin allergy.
• Clarithromycin: Clarithromycin has activity similar to
erythromycin, but it is also effective against Haemophilus
influenzae. Its activity against intracellular pathogens, such as
Chlamydia, Helicobacter pylori, is higher
than that of erythromycin.
• Azithromycin: more active against respiratory infections due
to H. influenzae and Moraxella catarrhalis.
 Adverse effects

• Gastric distress and motility

• Ototoxicity
• Cholestatic jaundice
 Tetracyclines

Mechanism of action: They are protein synthesis inhibitors

 Tetracyclines bind reversibly to 30S subunit and block the

binding of the amino acid containing tRNA on the mRNA-

ribosome complex.

 Tetracyclines prevent binding of tRNA.

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 Anti bacterial spectrum

• Tetracyclines are active against many Gram-positive and Gram

negative bacteria, including certain anaerobes, rickettsiae,

chlamydiae, and mycoplasmas.

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 Important to learn
• Tetracyclines bind to calcium in newly formed teeth in young children.
This can result in a brown to yellow discoloration.
• Tetracyclines can bind to calcium in growing bone, resulting in deformity.
• Tetracycline & doxycycline can cause phototoxic skin reactions due to their
ability to absorb UV radiation present in sunlight.
• They are bacteriostatic.
• Calcium in the milk binds the Tetracyclines and prevents gut absorption.
Other metal which affect the absorption of tetracycline are aluminum, ,
magnesium, iron)
• Tetracyclines cross the placenta, enter fetal circulation, accumulate in fetal
bones, and, if used during the 2nd or 3rd trimester, may cause permanent
discoloration of the fetus's teeth.
Mechanism of action

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 Chloramphenicol

• The use of chloramphenicol, a broad-spectrum antibiotic which

is obtained from Streptomyces Venezuela, is restricted to life-
threatening infections for which no alternatives exist.

• Mechanism of action: Chloramphenicol binds reversibly to the

bacterial 50S ribosomal subunit and inhibits protein synthesis at
the peptidyl transferase reaction
Antimicrobial Spectrum

Broad spectrum antibiotic

Active against both aerobic
and anaerobic Gram +ve &
gram –ve bacteria, Rickettsiae,
Mycoplasma

Primarily Bacteriostatic
High concentrations
bactericidal effect on some
bacteria i.e.
H. Infleunza, N.
meningitidis,
Bacteriodes
 Adverse effects

•Bone marrow suppression:

• Aplastic anemia
• Thrombocytopenia
•Irritating effects:
• Nausea, vomiting, diarrhea
•Gray baby syndrome:
• cyanosis, vomiting, green stools and
vasomotor collapse
•Hypersensitivity Reactions:
• Rashes, fever, angioedema
 Oxazolidinones (Linezolid)
• Linezolid is a synthetic Oxazolidinones developed to combat
resistant gram-positive organisms, such as methicillin-resistant
Staphylococcus aureus, and penicillin-resistant streptococci.
• Antibacterial spectrum
The antibacterial action of linezolid is directed primarily
against gram positive organisms, such as staphylococci,
streptococci, and enterococci.
• Like other agents that interfere with bacterial protein
synthesis, linezolid is bacteriostatic. However, it is bactericidal
against streptococci.
 Oxazolidinones (Linezolid)

• Mechanism of Action-it inhibits bacterial protein synthesis by

binding to 50S ribosomal subunit near the interface with 30S.
Thus the formation of initiation complex is prevented
• Adverse effects- Myelosuppression, including anemia,
leukopenia, pancytopenia, and reversible thrombocytopenia,
reversible neutropenia, reversible optic neuropathy
 DNA synthesis inhibitors
(Fluroquinolones)
General properties:
• Synthetic antimicrobials
• Bactericidal
• Broad spectrum
• Quinolones can enter cells easily and, therefore, are often
used to treat intracellular pathogens such as Legionella
pneumophila and Mycoplasma pneumoniae.

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 Common Quinolones

• Ciprofloxacin (Cipro)
• Gemifloxacin (Factive)
• Levofloxacin (Levaquin)
• Moxifloxacin (Avelox)

• Norfloxacin (Noroxin)
• Ofloxacin (Floxin)
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75
 Mechanism of action

• Fluroquinolones block bacterial DNA synthesis by inhibiting

bacterial topoisomerase II (DNA gyrase) and topoisomerase IV.
• Inhibition of DNA gyrase prevents the relaxation of positively
supercoiled DNA that is required for normal transcription and
replication. Inhibition of topoisomerase IV interferes with
separation of replicated chromosomal DNA into the respective
daughter cells during cell division.

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 Clinical uses
• Urinary tract infections
• Upper and lower respiratory tract infections
• Bacterial diarrhea
• Tuberculosis
• Soft tissues, bones, and joints and in intra-abdominal and
respiratory tract infections, including those caused by
multidrug-resistant organisms such as Pseudomonas(diabetic
foot).
• Ciprofloxacin is a drug of choice for prophylaxis and treatment
of anthrax
• Gonorrhoea (norfloxacin, ofloxacin).
• Bacterial prostatitis
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 Adverse effects

The most frequent side-effects are:

• Gastrointestinal reactions (nausea, dyspepsia, vomiting)

• CNS reactions such as dizziness, insomnia and headache.

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 Folate antagonists
(Cotrimoxazole (trimethoprim + sulfamethoxazole)

• These drugs stop bacterial cells from using folic acid to make

DNA

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 Sulfamethoxazole
• Dihydrofolic acid: Dihydrofolic acid is a folic acid derivative
which is converted to tetrahydrofolic acid. Tetrahydrofolate is
needed to make both purines and pyrimidines, which are
building blocks of DNA and RNA
• Dihydrofolate synthase: it is the enzyme which convert the
Dihydrofolic acid to tetrahydrofolate
• In many microorganisms, dihydrofolic acid is synthesized from
p-aminobenzoic acid (PABA),
• Sulfonamides are a synthetic analogs of PABA, the
sulfonamides compete with PABA for the bacterial enzyme,
dihydropteroate synthetase.

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 Trimethoprim

• Trimethoprim prevent the conversion of Dihydrofolate to

tetrahydrofolate
• The enzymatic reaction is inhibited by trimethoprim,
• Ultimately, there is decreased availability of the
tetrahydrofolate cofactors required for purine, pyrimidine,
and amino acid synthesis

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Pyrimethamine

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 Adverse effects

• They are eliminated via kidney, require dose adjustments for

renal dysfunction
• Crystalluria is a major side effect of sulfonamides. Avoid Vitamin
C use. It acidifies urine
• Megaloblastic anemia, leukopenia, and thrombocytopenia may
occur with use of Cotrimoxazole
• Due to the danger of kernicterus, sulfa drugs should be avoided
in newborns and infants less than 2 months of age,
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 References
• Lippincott Illustrated Reviews: Pharmacology
Sixth Edition