The document covers the pharmacology of antibiotics, including their classification into bacteriostatic and bactericidal types, pharmacokinetics, pharmacodynamics, and different mechanisms of antibiotic action such as time-dependent and concentration-dependent killing. It outlines principles of antibiotic prescribing to prevent resistance, watch for adverse reactions, and choose appropriate treatment based on infection type, while highlighting the significance of susceptibility tests and various routes of administration. The document emphasizes the importance of patient-specific factors in prescribing and optimizing antibiotic therapy for better treatment outcomes.

1. PRESENTED BY: MR. SHAAN
SINOJIA

2. CONTENTS:
• Pharmacology of antibiotics
• Pharmacokinetics and pharmacodynamics
• Concentration dependent killing vs Time dependent killing
• Adverse reactions
• Resistance
• Principles of prescribing
• Treatment of existing infections
• Route of administration
• Susceptibility tests
• Antibiotic assays

3. PHARMACOLOGY OF ANTIBIOTICS:
❑ Antibiotic defined as agents that selectively kill or inhibit
the growth of bacterial cells, while having little or no
effect on the mammalian host.
❑ Antibiotics are divided into two types on their action on
bacteria ie bacteriostatic and bacterio-cidal
❑ Bacteriostatic (-Static – inhibit) – antibiotics which prevent
the replication of bacteria, rely on an impact immune
system to clear the infection.
❑ Bacterio-cidal (-cide – to kill) – antibiotics which kill the
bacteria.
❑ For example, use of a bactericidal agent is mandatory
when treating infective endocarditis since the bacteria are
protected from host immune functions within valve
vegetations.
❑ Cidal activity can sometimes be achieved by a combination
of antibiotics.

4. PHARMACOKINETICS AND
PHARMACODYNAMICS:
❑ Pharmacokinetics and pharmacodynamics are two crucial aspects of pharmacology that help us
understand how drugs work in the body.
❑ Pharmacokinetics deals with what the body does to the drug. It involves the processes of absorption,
distribution, metabolism, and excretion (ADME) of a drug within the body. Essentially, pharmacokinetics
studies how the body absorbs, distributes, metabolizes, and eliminates a drug over time.
❑ On the other hand, pharmacodynamics focuses on what the drug does to the body. It encompasses the
study of the biochemical and physiological effects of drugs and their mechanisms of action.
Pharmacodynamics explores how drugs interact with specific receptors or target sites to produce their
therapeutic effects, as well as any side effects or adverse reactions they may cause.
❑ In summary, pharmacokinetics is about the movement of drugs within the body, while
pharmacodynamics is about the effects of drugs on the body. Understanding both aspects is crucial for
optimizing drug therapy and ensuring safe and effective treatment outcomes.

5. CONCENTRATION DEPENDENT KILLING vs TIME
DEPENDENT KILLING:
Concentration dependent killing
• Complement-dependent killing refers to a mechanism by which the
complement system, a part of the immune system, helps in the
destruction of pathogens such as bacteria and infected cells. The
complement system is a complex cascade of proteins that play a critical
role in immune defense against pathogens.
• In complement-dependent killing, activation of the complement system
leads to the formation of the membrane attack complex (MAC), which
forms pores in the membrane of target cells. These pores disrupt the
integrity of the target cell membrane, leading to cell lysis (bursting) and
ultimately cell death. This process is particularly effective against
bacteria and other microorganisms that lack protection against
complement-mediated attack.
• Complement-dependent killing can occur through various pathways,
including the classical pathway, the lectin pathway, and the alternative
pathway, all of which converge at the formation of the MAC.
Additionally, certain antibodies, such as IgM and IgG, can activate the
complement system by binding to their target antigens, initiating the
complement cascade and leading to complement-dependent killing.
• Overall, complement-dependent killing is an important mechanism of
the immune system for eliminating pathogens and maintaining
homeostasis in the body.
Time dependent killing
⮚ Time-dependent killing refers to the relationship between the duration of exposure to an
antimicrobial agent (such as antibiotics) and its effectiveness in killing or inhibiting the
growth of bacteria or other microorganisms. In time-dependent killing, the efficacy of the
antimicrobial agent is directly related to the duration of time that the concentration of the
drug remains above a certain threshold level at the site of infection.
⮚ In other words, for some antimicrobial agents, the key factor determining their
effectiveness is not the peak concentration achieved but rather the length of time that the
concentration remains above the minimum inhibitory concentration (MIC) or another
effective threshold level. This means that maintaining a sufficient concentration of the
antimicrobial agent in the body over a prolonged period is crucial for achieving optimal
bacterial killing.
⮚ Time-dependent killing is often observed with antimicrobial agents like beta-lactam
antibiotics (e.g., penicillins, cephalosporins) and vancomycin. For these drugs, it is
important to administer doses at intervals that maintain therapeutic concentrations above
the MIC for a sufficient duration to effectively kill or inhibit bacterial growth.
⮚ In contrast, concentration-dependent killing is another pharmacodynamic property where
the effectiveness of the antimicrobial agent is primarily related to the peak concentration
achieved rather than the duration of exposure. Examples of concentration-dependent
killing antimicrobials include aminoglycosides and fluoroquinolones.
⮚ Understanding whether an antimicrobial agent exhibits time-dependent or concentration-
dependent killing is crucial for optimizing dosing regimens to achieve maximal therapeutic
efficacy while minimizing the risk of resistance and adverse effects.

7. ADVERSE REACTIONS:
Antibiotics, while valuable in treating bacterial infections, can also cause adverse reactions in some individuals. These adverse reactions can range from mild
to severe and may affect various organ systems. Some common adverse reactions associated with antibiotic use include:
1.Allergic reactions: These can range from mild rashes to severe allergic reactions such as anaphylaxis. Penicillin antibiotics are notorious for causing
allergic reactions, but allergies can occur with any antibiotic.
2.Gastrointestinal disturbances: Antibiotics can disrupt the normal balance of bacteria in the gastrointestinal tract, leading to symptoms such as nausea,
vomiting, diarrhea, or abdominal pain. This is a common side effect of many antibiotics.
3.Clostridium difficile infection: Some antibiotics, particularly broad-spectrum antibiotics, can disrupt the normal gut flora and predispose individuals to
Clostridium difficile infection, which can cause severe diarrhea and colitis.
4.Photosensitivity: Certain antibiotics, such as tetracyclines and fluoroquinolones, can make the skin more sensitive to sunlight, leading to sunburn or rash
upon sun exposure.
5.Hepatotoxicity: Some antibiotics can cause liver damage, particularly in individuals with pre-existing liver conditions or when taken in high doses or for
prolonged periods.
6.Nephrotoxicity: Certain antibiotics, such as aminoglycosides and vancomycin, can cause kidney damage, especially when used at high doses or in
individuals with pre-existing kidney problems.
7.Neurotoxicity: Some antibiotics, such as certain cephalosporins or fluoroquinolones, can cause neurological side effects such as dizziness, confusion, or
peripheral neuropathy.
8.Hematological effects: Rarely, antibiotics can cause blood disorders such as anemia, leukopenia, or thrombocytopenia.
9.Tendon damage: Fluoroquinolone antibiotics have been associated with an increased risk of tendonitis and tendon rupture, particularly in older adults.
10.Cardiotoxicity: Some antibiotics, such as macrolides, can prolong the QT interval on the electrocardiogram, which may lead to arrhythmias in susceptible
individuals.
These are just some examples of adverse reactions associated with antibiotic use. The risk of adverse reactions can vary depending on factors such as the
specific antibiotic used, the dose and duration of treatment, individual patient characteristics, and any underlying health conditions. It's important for
healthcare providers to consider these factors when prescribing antibiotics and to monitor patients closely for any signs of adverse reactions.

8. RESISTANCE:
❑ Some bacteria may not be inhibited adequately by drug concentration that are safely
achievable at the affected body site.
❑ For example: Penicillin remains effective for the treatment of pneumonia, but not
meningitis, caused by pneumococci with intermediate susceptibility to penicillin.
❑ Resistance – intrinsic or acquired.
❑ Intrinsic resistance - arises if the drug target is not present in the bacterium’s metabolic
pathways or drug impermeability. For example, Beta – lactams has no effect against
mycoplasma.
❑ Acquired resistance – by mutation or by transfer of genetic material from resistant to
susceptible organisms.
❑ Mutations occur frequently with rifampicin and fusidic acid.
❑ Transfer of genetic material occurs via plasmids and transposons, bacteriophages or
direct conjugation.
❑ Niederman defined 4 main factors driving microbial resistance:
1. Excess antibiotic usage
2. Incorrect use of broad spectrum agents

10. PRINCIPLES OF PRESCRIBING:
Prescribing antibiotics is a critical aspect of medical practice, and following certain principles helps ensure their appropriate and
effective use while minimizing the risk of antibiotic resistance and adverse effects. Here are some key principles of prescribing
antibiotics:
1. Indication-based prescribing: Antibiotics should only be prescribed when there is a clear indication of bacterial infection. They
are not effective against viral infections, such as the common cold or flu. Prescribing antibiotics unnecessarily contributes to
antibiotic resistance.
2. Selection of the appropriate antibiotic: Choose the most narrow-spectrum antibiotic that is effective against the suspected or
confirmed pathogen. This helps minimize disruption to the normal microbiota and reduces the risk of selecting for antibiotic-
resistant bacteria.
3. Empirical therapy: In some situations, antibiotics may need to be initiated before the results of microbiological testing are
available. When prescribing empiric therapy, consider factors such as the most likely pathogens based on the clinical
presentation, local antibiotic resistance patterns, and patient-specific factors (e.g., age, comorbidities).
4. Dose optimization: Prescribe antibiotics at the appropriate dose and dosing interval to achieve therapeutic drug concentrations
at the site of infection. Factors such as renal function, hepatic function, and body weight should be taken into account when
determining the dose.

11. PRINCIPLES OF PRESCRIBING:
5. Duration of therapy: Prescribe antibiotics for the shortest effective duration necessary to treat the infection. Unnecessarily
prolonged courses of antibiotics can contribute to antibiotic resistance and increase the risk of adverse effects, such as
Clostridium difficile infection.
6. Consideration of patient factors: Take into account patient-specific factors when prescribing antibiotics, including allergies,
comorbidities (e.g., renal or hepatic impairment), concomitant medications, and previous antibiotic exposure.
7. Review and de-escalation: Regularly review the need for continued antibiotic therapy based on clinical response and
microbiological data. De-escalate or stop antibiotics when they are no longer necessary or when a more targeted therapy
becomes available based on culture and susceptibility results.
8. Patient education: Provide patients with information about the appropriate use of antibiotics, including the importance of
completing the full course as prescribed, potential side effects, and the risks of antibiotic resistance. Encourage adherence to
prescribed treatment regimens.
9. Infection prevention and control: Emphasize the importance of infection prevention measures, such as hand hygiene,
vaccination, and appropriate wound care, to reduce the spread of infections and minimize the need for antibiotics. By adhering to
these principles, healthcare providers can optimize the use of antibiotics, improve patient outcomes, and contribute to efforts to
combat antibiotic resistance.

12. TREATMENT OF EXISTING INFECTIONS:
Choice of emoirical therapy:
❑ Clinical assessment and a reasonable estimate of etiology.
❑ Imp clinical factors include the severity of illness, immune status, other co-morbidities, and infected prosthetic implants.
❑ Before commencing antibiotic therapy, it is vitally important to obtain appropriate samples for culture except in meningitis.
Broad spectrum vs narrow spectrum:
1.Broad-Spectrum Antibiotics:
1. Broad-spectrum antibiotics are effective against a wide range of bacteria, including both Gram-positive and Gram-negative bacteria.
2. They are often used when the infecting organism is unknown or when there is a need to cover a broad range of potential pathogens.
3. Broad-spectrum antibiotics may be prescribed empirically before the results of microbiological testing are available.
4. Examples of broad-spectrum antibiotics include fluoroquinolones, cephalosporins (such as ceftriaxone and cefepime), carbapenems (such as
meropenem and imipenem), and some penicillins (such as amoxicillin-clavulanate).
2.Narrow-Spectrum Antibiotics:
1. Narrow-spectrum antibiotics are effective against a limited range of bacteria, either Gram-positive or Gram-negative.
2. They are often preferred when the infecting organism is known or when there is a need to target specific bacteria while minimizing disruption to
the normal microbiota.
3. Narrow-spectrum antibiotics are less likely to contribute to antibiotic resistance and may have fewer adverse effects compared to broad-spectrum
antibiotics.
4. Examples of narrow-spectrum antibiotics include penicillin G (effective mainly against Gram-positive bacteria), vancomycin (effective against
Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus), and first-generation cephalosporins (such as cefazolin, effective
against Gram-positive cocci).
The choice between broad-spectrum and narrow-spectrum antibiotics depends on several factors, including the suspected or identified pathogen, local
resistance patterns, the site and severity of infection, and individual patient characteristics (such as allergies and comorbidities). While broad-spectrum
antibiotics may provide coverage against a wider range of pathogens, they are associated with a higher risk of selecting for antibiotic-resistant bacteria and

13. Route of administration:
Antibiotics can be administered via various routes depending on factors such as the type of infection, the
severity of the condition, and the patient's age and clinical status. Here are the common routes of antibiotic
administration:
1.Oral: Oral administration is one of the most common routes for antibiotics. Antibiotics are typically available in
tablet, capsule, liquid, or suspension forms that can be swallowed. Oral antibiotics are convenient for outpatient
treatment and are often prescribed for mild to moderate infections. Examples include amoxicillin, azithromycin,
and ciprofloxacin.
2.Intravenous (IV): Intravenous administration involves delivering antibiotics directly into the bloodstream
through a vein. IV antibiotics are used for severe infections, infections that do not respond to oral antibiotics, or
when rapid and reliable drug delivery is required. They are administered in hospitals or outpatient settings
under medical supervision. Examples of IV antibiotics include vancomycin, ceftriaxone, and meropenem.
3.Intramuscular (IM): Intramuscular administration involves injecting antibiotics into the muscle tissue. IM
antibiotics are used when IV access is not readily available or when prolonged drug action is desired. They are
often administered in outpatient settings or emergency situations. Examples include ceftriaxone, penicillin G
benzathine, and gentamicin.
4.Topical: Topical antibiotics are applied directly to the skin or mucous membranes to treat localized infections
or prevent infection in wounds, burns, or surgical incisions. They are available as creams, ointments, gels, or
sprays. Examples include mupirocin, bacitracin, and neomycin.

14. Route of administration:
5.Inhalation: Inhalation antibiotics are delivered directly to the lungs via
inhalation devices, such as nebulizers or inhalers. They are used to treat
respiratory tract infections, such as pneumonia or cystic fibrosis
exacerbations. Examples include tobramycin inhalation solution and
colistimethate sodium inhalation solution.
6.Intrathecal or Intraventricular: In certain cases of central nervous
system infections, antibiotics may be administered directly into the
cerebrospinal fluid via intrathecal or intraventricular routes. This route is
used to achieve high drug concentrations at the site of infection. Examples
include intrathecal administration of antibiotics such as amphotericin B for
fungal meningitis.
The choice of antibiotic route depends on factors such as the site and severity of
infection, the pharmacokinetic properties of the drug, the patient's clinical
condition, and the availability of administration facilities. Healthcare providers
consider these factors to determine the most appropriate route of antibiotic
administration for each patient.

15. SUSCEPTIBILITY TESTS:
⮚Disc diffusion tests: Discs
with known antibiotic
concentrations are applied
to the agar plate and
incubated in standard
conditions for 18-24hr.
Intepretation of
susceptibility is determined
by comparing the diameter
of the zones of inhibition
around the antibiotic disc
with published data for
susceptible and resistant

16. ⮚ Broth and agar dilution methods: use a
standardized amount of organism
incubated in doubling dilutions of
culture media in standard conditions
for 18-24hr. The lowest concentration
at which no growth occurs is referred
to as the MIC.
⮚ E-test: uses a pre-defined gradient of
antibiotic within a plastic strip; applied
onto an agar plate inoculated with the
test organism and incubated. This test
gives an accurate MIC comparable
with agar or broth dilution tests and is
technically less demanding.

17. ANTIBIOTIC ASSAYS:
❖Antibiotic serum levels are performed for:
i. To prevent the development of toxic levels.
ii. To ensure that levels are therapeutic.
iii. To assess compliance with drug regimes ( predominantly TB
treatment courses).
❖Commonly performed during aminoglycoside therapy.
❖Alternatively, they can be more complex ‘microbiological assays’ or
‘back-assays’ in which samples of a patient’s plasma containing the
administered antibiotics are combined with standardized
concentration of the infecting organism; rarely performed because
results are inconsistent and difficult to interpret.