This document discusses antimicrobial drugs and infections. It defines different types of infections like acute, chronic, and opportunistic infections. It also describes different causative agents of infections like bacteria, viruses, fungi and protozoa. The document then discusses the classification of antimicrobial drugs based on their chemical structure, mechanism of action, spectrum of activity and more. It provides examples for each category. The principles of antimicrobial therapy and factors considered in selecting antimicrobial agents are also summarized.

1. Antimicrobial Drugs
The presence and growth of a microorganism that
produce tissue damage is known as infection.
Infection may also be defined as the lodgment and
multiplication of an infecting organism in or on the tissue
of a host cell.
The extent of infection depends on the number and
virulence of the microorganism and the ability of the
body to contain or destroy them.
The infective organism known as pathogens is usually
considered as microorganism including bacteria, virus,
parasites, fungi, protozoa etc.
They may interfere the normal functioning of the host
cell and can lead to inflammation, chronic wounds,
gangrene or even cell death.

2. Types of Infection
Acute Infection: An infection that appears suddenly and
may be of brief or prolonged duration.
Sub-acute infection: An infection intermediate between
acute and chronic infection.
Chronic Infection: An infection having a protracted coarse
or prolonged duration.
Primary Infection: An initial infection is known as primary
infection.
Secondary Infection: An infection made possible by a
primary infection that lowers the host's resistance ( for
example, bacterial pneumonia following influenza).
Concurrent or Super Infection: The existence of two or
more infections at the same time.
Cross Infection: The transfer of an infectious organism or
disease from one patient to another.

3. Cryptogenic Infection: The invasion of bacteria without
outward evidence of entry into the body.
Contagious Infection: It is usually refers to those that are
easily transmitted and commonly seen. Such as influenza or
chicken pox.
Droplet Infection: An infection acquired by the inhalation
of a microorganism in the air, especially, one added to the
air by someone's breath or cough.
Local Infection: An infection that has not spread but
remains contained near the entry side.
Nosocomial Infection: An infection that is acquired during
hospitalization.
Apical Infection: An infection located at the tip of root of a
tooth.
Blood- borne infection: An infection transmitted through
contact with the blood of an individual. For example,
Hepatitis, AIDS etc.

4.  Air- borne Infection: An infection caused by inhalation of
pathogenic organism in the air.
 Opportunistic Infection: Any infection that results from a defective
immune system that cannot defends against pathogens normally
found in the environment.
 Sub Clinical Infection: An infection that is immunologically
conformed but does not show clinical symptoms in the individuals.
 Systemic Infection: An infection in which the infecting agents are
throughout the body rather than restricted to a local area.
 Exogenous Infection: Infection caused by Infective organism from
outside.
 Endogenous Infection: Infection caused by body organism.
 Bacterial Infection: An infection caused by Bacteria
 Viral Infection: An infection caused by virus
 Fungal Infection: An infection caused by fungus.
 Protozoal Infection: An infection caused by protozoa
 Pyogenic Infection: An infection resulting from pus-forming
organism.

5. Clinical Effects of Infection on the body
There are different effects shown in the body when an
individual is infected, such are:
Acute Effects: Normally is a short infection or initial
infection including pain, inflammation, tissue damage
or fever.
Chronic Effects: It is a long term infection including
diarrhea, bronchial pneumonia, Tuberculosis, Hepatitis
B etc.
Allergic Effects: It includes rashes (Urticaria with
helminthes, Arthritis with rheumatic fever)
Toxic Effects: It includes toxic diarrhea (caused by
staphylococcal enterotoxin).
Organ Disturbance: It includes Diphtheria.

6. Causative Agents
Various pathogens may cause different diseases.
Some of the diseases commonly caused by the
following organisms:
Bacteria: Typhoid (salmonella typhi), Bacillary
Dysentery (bacillus of shigella group), Amoebic
Dysentery ( Entamobea histolytica) , Tuberculosis
(Mycobacterium tuberculosis) etc.
Virus: AIDS (HIV or Retro Virus), Hepatitis B
(Hepadna virus), Hepatitis C (RNA Virus) etc.
Fungi: Ringworm, Oral candidiasis (Candida
albicans, Candida tropicalis, Candida glabrata) etc.
Protozoa: Amoebic dysentery, Visceral
leishmaniasis or Kala-a-zar (Leishmania donovani)
etc.

7. • Antibiotics are the substances produced by
microorganisms which selectively suppress the
growth or kill other microorganisms at very low
concentrations.
• Sources of antibiotics:
Fungi
• Penicillin, Cephalosporin
Bacteria
• Bacitracin, Polymixin B
Actinomycetes
• Aminoglycosides, Chloramphenicol, Tetracyclines

9. CLASSIFICATION
According to Chemical Structure
1. Sulfonamides and related drugs, e.g., Sulphadiazine,
sulphomethoxazole, Sulfunes (Dapsones) etc.
2. Diaminopyrimidines, e.g., Trimethoprim
3. Quinolones, e.g. Norfloxacine, Ciprofloxacine,
Levofloxacine, Ofloxacine etc.
4. ß-Lactam Antibiotics, e.g., Penicillin, Cephalosporin etc.
5. Tetracyclines, e.g. Tetracycline, oxytetracycline,
Doxycycline etc.
6. Nitrobenzene derivatives. e.g., Cholramphenicol etc.
7. Aminoglycosides, e.g., Streptomycin, Gentamycin,
Kanamycin, Amikacin etc.
8. Macrolides, e.g., Erythromycin, Clarithromycin,
Roxithromycin, Azithromycin etc.

10. 9. Lincosamide Antibiotics, e.g., Lincomycin, Clindamycin
etc.
10. Glycopeptide antibiotics, e.g., Vincomycin etc,
11. Oxazolidinones, e.g., Linezolid etc.
12. Polypeptide Antibiotics, e.g., Polymycin-B, Bacitracin
etc.
13. Nitrofuran Derivatives, e.g., Nitrofurantoin etc.
14. Nitro-Imidazoles, e.g., Metronidazole, Tinidazole etc.
15. Nicotinic Acid Derivatives, e.g., Isoniazid, Pyrazinamide
etc.
16. Polyene Antibiotics, e.g., Nystatin, Amphotericin B etc.
17. Azole Derivative, e.g., Fluconazole, Clotrimazole etc.
18. Others including, Rifampin, Ethambutol, Griseofluvin
etc.

11. According to Mechanism of Action
1. Interfere with cell wall synthesis: Penicillin, Cephalosporins,
Bacitracin, Vancomycin and Cyclosporine.
2. Damage to the cytoplasmic membrane: Polymyxins,
Colistin, Polyene antibiotics and Detergents.
3. Inhibition of Protein Synthesis and impairment of function
of the ribosomes: Aminoglycosides, Tetracyclines,
Chloramphenicol, Macrolides and Lincomycin.
4. Interfere with transcription/Translation of genetic
information: Quinolones, Metronidazole and rifampicin.
5. Inhibit DNA Gyrase: Fluoroquinolones
6. Interfere with DNA function: Rifampin, Metronidazole
7. Antimetabolic action: Sulfonamide, Sulfones, Para amino
salicylate (PAS) and Trimethoprim.
8. Binding to viral enzymes essential for DNA synthesis:
Protease inhibitors and Acyclovir.

12. According to Spectrum of Activity
1. Narrow Spectrum: Chemotherapeutic agents acting
only on a single or a limited group of microorganisms
are said to have a narrow spectrum. For example,
isoniazid is active only against mycobacteria.
2. Extended-spectrum antibiotics: Extended spectrum is
the term applied to antibiotics that are effective
against gram-positive organisms and also against a
significant number of gram-negative bacteria. For
example, ampicillin is considered to have an extended
spectrum, because it acts against gram-positive and
some gram-negative bacteria
3. Broad Spectrum: Drugs such as tetracycline and
chloramphenicol affect a wide variety of microbial
species and are referred to as broad-spectrum
antibiotics.

13. According to Types of Action (or Mode of Action)
1. Bacteriosatic: The antimicrobials that stop the
growth of microorganism. For example,
Sulphonamides, Tetracyclines, Erythromycin,
Chloramphenicol etc.
2. Bactericidal: The antimicrobials that kill the
microorganism, for example, Penicillin,
Ciprofloxacin, Co-trimoxazole etc.

14. According to Types of Organism
1. Antibacterial: Penicillin, Aminoglycosides
etc.
2. Antiviral: Acyclovir, Zidovudine etc.
3. Antifungal: Ketoconazole, Griseoflovin etc.
4. Antihelminthics: Albendazole, Mebendazole
etc.
5. Antiprotozoals: Metronidazole, Tinidazole,
Chloroquine etc.

15. General Principle 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;
i.e.,
– They have the ability to injure or kill an invading
microorganism without harming the cells of the host.
• In most instances, the selective toxicity is relative
rather than absolute, requiring that the
concentration of the drug be carefully controlled
to attack the microorganism, while still being
tolerated by the host.

16. Selection of Anti-microbial Agents
Identification of the infecting organism
 it is generally necessary to culture the infective organism to arrive
at a conclusive diagnosis and determine the susceptibility to
antimicrobial agents.
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 prove fatal,
and immediate empiric therapy is indicated.
Determining antimicrobial susceptibility of infective organisms
After a pathogen is cultured, its susceptibility to specific
antibiotics serves as a guide in choosing antimicrobial therapy.

17. Patient factors
In selecting an antibiotic, attention must be paid to the
condition of the patient. For example:
The status of the patient’s immune system, kidneys, liver,
circulation, and age must be considered.
In women, pregnancy or breast-feeding also affects selection of
the antimicrobial agent.
Safety of the agent
Antibiotics such as the penicillin are among the least toxic of
all drugs because they interfere with a site or function unique
to the growth of microorganisms.
Other antimicrobial agents (for example, chloramphenicol)
have less specificity and are reserved for life-threatening
infections because of the potential for serious toxicity to the
patient.
Cost of therapy
Often several drugs may show similar efficacy in treating an
infection but vary widely in cost.

18. Route of Administration
The oral route of administration is appropriate for mild
infections that can be treated on an outpatient basis.
In hospitalized patients requiring IV therapy initially, the
switch to oral agents should occur as soon as possible.
However, some antibiotics, such as vancomycin, the
aminoglycosides, and amphotericin B are so poorly
absorbed from the gastrointestinal (GI) tract that adequate
serum levels cannot be obtained by oral administration.
Parenteral administration is used for drugs that are poorly
absorbed from the GI tract and for treatment of patients
with serious infections, for whom it is necessary to
maintain higher serum concentrations of antimicrobial
agents.

19. Determinants of Rational Dosing
• Rational dosing of antimicrobial agents is based on:
• Pharmacodynamics (the relationship of drug concentrations )
• Pharmacokinetic properties (the ADME)
• Three important properties that have a significant
influence on the frequency of dosing are:
– Concentration dependent killing
– Time-dependent killing, and
– Post-antibiotic effect (PAE).
• Utilizing these properties to optimize antibiotic
dosing regimens can improve clinical outcomes and
possibly decrease the development of resistance.

20. Combination of Anti-microbial Agents
It is therapeutically advisable to treat patients
with a single agent that is most specific to the
infecting organism as well as minimizes resistant
and toxicity.
However, some situations require combinations
of antimicrobial drugs (for example, the
treatment of TB includes multiple antibiotics).

21. Advantage
Certain combinations of antibiotics, such as β-lactams and
aminoglycosides, show synergism; that is, the combination is more
effective than either of the drugs used separately.
Because such synergism among antimicrobial agents is rare,
multiple drugs used in combination are only indicated in special
situations (for example, when an infection is of unknown origin or in
the treatment of enterococcal endocarditis).
Disadvantage
A number of antibiotics act only when organisms are multiplying.
Thus, co-administration of an agent that causes bacteriostatic plus a
second agent that is bactericidal may result in the first drug
interfering with the action of the second. For example, bacteriostatic
tetracycline drugs may interfere with the bactericidal effects of
penicillins and cephalosporins.
Another concern is the risk of selection pressure and the
development of antibiotic resistance by giving unnecessary
combination therapy.

22. Prophylactic Use of Anti-microbial Agents
Pre-surgical Antimicrobial Prophylaxis
Antimicrobial prophylaxis is used to reduce the
incidence of postoperative surgical site infections.
This practice targets the most likely organisms
(i.e., skin flora), while avoiding unnecessary broad-
spectrum antimicrobial therapy.
Duration of prophylaxis for surgical site infection
should not exceed 24 hours in most cases.
Example: A single dose of a cephalosporin (such as
cefazolin) administered within 1 hour before the
initial incision is appropriate for most surgical
procedures.

23. Antimicrobial Prophylaxis in Immunocompromised Patients
Immunocompromised patients, particularly those with
HIV infection/AIDS, those who are undergoing
chemotherapy for cancer, or those who are receiving
immunosuppressive therapy after organ transplant, are at
increased risk of infection.
In these specific settings, evidence supports the use of
prolonged antimicrobial prophylaxis until immune markers
are restored.
Example: co-trimoxazole to prevent pneumocystis
pneumonia.
Antimicrobial Prophylaxis to Prevent Transmission of
Communicable Pathogens to Susceptible Contacts
Antimicrobial agents can be prescribed prophylactically to
prevent transmission of pathogens to susceptible contacts.
Example: ciprofloxacin can be given to close contacts of a
patient with meningitis caused by N meningitides.

24. Antimicrobial Prophylaxis Before Dental and Other
Invasive Procedures in Patients Susceptible to
Bacterial Endocarditis.
The antimicrobial prophylaxis in this setting have
recently been updated and limit such use to only a few
very high-risk scenarios, prior endocarditis, or
congenital heart disease before surgical correction.
Traumatic Injuries With a High Probability of
Infectious Complications
Certain types of injuries pose a particularly high risk
of infection because of disruption of normal barriers
and/or delivery of a high inoculum of pathogenic
organisms.

25. Non-antimicrobial Therapy for Infections
• Antimicrobial therapy is usually, but not always, the most important
therapy for infectious diseases.
• The best-recognized example of non-antimicrobial therapy in the
treatment of infections is the use of operative drainage.
• This procedure is useful when the organism burden is very high or in
the management of abscesses, for which the penetration and
activity of antimicrobial agents are often inadequate.
• Other therapies used in the treatment of infectious diseases involve
modulating the host inflammatory response to infection.
• Systemic corticosteroids, thought to act by decreasing the
deleterious effects of the host inflammatory response, have been
found beneficial when used in conjunction with antimicrobial
therapy for the treatment of bacterial meningitis, tuberculous
meningitis, and Pneumocystis pneumonia in patients with AIDS.

26. Complication of Antimicrobial therapy
Even though antibiotics are selectively toxic to an
invading organism, it does not protect the host against
adverse effects.
The drug may produce an allergic response or may be
toxic in ways unrelated to the antimicrobial activity.
Hypersensitivity
Hypersensitivity or immune reactions to antimicrobial
drugs or their metabolic products frequently occur.
For example, penicillins can cause serious
hypersensitivity problems, ranging from urticaria (hives)
to anaphylactic shock !

27. Direct toxicity
High serum levels of certain antibiotics may cause
toxicity by directly affecting cellular processes in the host.
For example, aminoglycosides can cause ototoxicity by
interfering with membrane function in the auditory hair
cells.
Super infections
Drug therapy, particularly with broad-spectrum
antimicrobials or combinations of agents, can lead to
alterations of the normal microbial flora of the upper
respiratory, oral, intestinal, and genitourinary tracts,
permitting the overgrowth of opportunistic organisms,
especially fungi or resistant bacteria.
These infections usually require secondary treatments
using specific anti-infective agents.

28. Judicious Use of Antimicrobial Agents
Cost Considerations in Antimicrobial Selection
The “cost” of an antimicrobial agent is dependent
on many factors in addition to the purchase price of
a particular agent and may include administration
costs, prolonged hospitalization as a consequence of
adverse effects, and clinical efficacy.
One strategy that can significantly reduce cost is
the switch from IV to oral therapy. Oral therapy is
generally less expensive, potentially associated with
fewer adverse effects, and can result in considerable
cost savings by facilitating earlier dismissal and a
shortened hospital stay.

29. Preventing Emergence of Antibiotic Resistance
The widespread—and often inappropriate—use of
antimicrobial agents is the single most important
cause of the emergence of drug resistance, both in the
community and hospital settings.
The emergence of antimicrobial resistance can be
prevented or delayed through judicious prescribing,
such as:
Avoidance of antibiotic treatment for community-
acquired, mostly viral, upper respiratory tract infections;
Use of narrow-spectrum antibiotics when possible; and
Use of antibiotics for the shortest duration that is
effective for the treatment of a particular clinical
syndrome.

30. Common Misuses of Antibiotics
One of the most common mistakes in antimicrobial use is
continuing to add or switch antibiotics when a patient does
not appear to be responding to therapy, even though there
is no clear evidence of an infectious disease.
The frequent use of antimicrobial agents in a hospital or
other health care setting can result in selection of
organisms that are resistant to that particular antibiotic.
An increase in levofloxacin use as initial therapy for UTI
as a result to a rapid increase in fluoroquinolone resistance.
For this reason, those involved in antimicrobial
stewardship should avoid the excessive prescribing of a
single class of antibiotic.

31. Appropriate use of antimicrobial agents involves :
Obtaining an accurate diagnosis,
Determining the need for and timing of antimicrobial
therapy,
Understanding how dosing affects the antimicrobial
activities of different agents,
Tailoring (adapting) treatment to host characteristics,
Using the narrowest spectrum and shortest duration of
therapy,
Switching to oral agents as soon as possible.
In addition, non-antimicrobial interventions, such
as abscess drainage, are equally or more important
in some cases and should be followed carefully in
comprehensive infectious disease management.

34. Antibiotic Resistance
• The ability of microorganism to develop
mechanisms that block the action of
antimicrobials is usually known as microbial
resistance.
• Bacteria are said to be resistant to an antibiotic if
the maximal level of that antibiotic that can be
tolerated by the host does not halt their growth
• Antibiotic resistance occurs when an antibiotic has
lost its ability to effectively control or kill bacterial
growth;
• If bacteria are "resistant" they continue to
multiply in the presence of therapeutic levels of
an antibiotic.

35. Causes
The use of antibiotics at any time in any setting
puts biological pressure on bacteria that
promotes the development of resistance.
When antibiotics are needed to prevent or treat
disease, they should always be used.
But research has shown that as much as 50% of
the time, antibiotics are prescribed when they are
not needed or they are misused (for example, a
patient is given the wrong dose).
This inappropriate use of antibiotics
unnecessarily promotes antibiotic resistance.

36. Mechanisms by which microorganisms exhibit
resistance to antibiotics are:
1. Drug inactivation or modification: e.g. enzymatic
deactivation of Penicillin G in some penicillin-resistant
bacteria through the production of β-lactamases.
2. Alteration of target site: e.g. alteration of PBP—the
binding target site of penicillins—in Methicillin-
resistant Staphylococcus aureus (MRSA) and other
penicillin-resistant bacteria.
3. Alteration of metabolic pathway: e.g. some
sulfonamide-resistant bacteria do not require para-
aminobenzoic acid (PABA), an important precursor for
the synthesis of folic acid and nucleic acids in bacteria
inhibited by sulfonamides. Instead, like mammalian
cells, they turn to utilizing preformed folic acid.
4. Reduced drug accumulation: by decreasing drug
permeability and/or increasing active efflux (pumping
out) of the drugs across the cell surface.

37. Mechanism of Resistance
37

38. Types of Resistance
Drug resistance occurs in several classes of pathogens:
bacteria
Endo-parasites
viruses
fungi
cancer cells
Normally there are 4 types of microbial resistance
occurs:
Natural resistance
Acquired resistance
Cross resistance
Super infection

39. Natural Resistance
If the microorganism lacks the metabolic
process or the target site or action of drug, in
such case the drug cannot show its action.
 These types of resistance are known as
natural resistance
Example: gram negative bacteria have
resistance to penicillin.

40. Acquired ResistanceIf a microorganism initially sensitive to an anti-
microbial agent develops resistance later.
These types of resistance are known as acquired
resistance.
Mostly occurs:
Due to change in genetic material, e.g., Staphylococci to
Rifampicin
Creating absence of target site for binding with drug,
e.g., Staphylococcus aureous an E.Coli develops RNA
polymerase that does not bind Rifampicin.
Due to production of enzyme that inactivate drug, e.g.,
production of beta lactamase from staphylococcus
aureous, pseudomonas, N. gonococci
Change in structure of cell wall, e.g., Aminoglycoside
resistance to streptococcus

41. Cross Resistance
If the resistance of one drug causes the
resistance of next drug, the process is said to be
cross resistance.
This type of resistance mainly associated with
among chemically and mechanically related
drugs.
Example:
If one sulfonamide have resistant in body then all
groups develops resistance but sometime among two
drugs from same group one may have resistance while
next may be sensitive, i.e. gentamycin resistant
microorganisms may have sensitive to amikacin.

42. Super Infection
• Normal flora in alimentary canal produces
substance bacteriocins.
• These substances kill as well as stop the
development of pathogenic bacteria.
• If a person taken many antibiotics for longer
period of time, then the normal microbial flora of
the canal may decrease or loss due to decreases
immunity power of the individuals.
• In this case pathogenic bacteria may cause
infection which is commonly known as super
infection.

43. Safety Measures to Resistant
Use of specific antibiotics (Unless Required)
Avoid broad spectrum antibiotics
Avoid use of antibiotics in viral infection
Avoid long term use of antibiotics
Avoid multi antibiotic therapy
Complete antibiotic dose for given period !