1. Prof. Mohammad Alhumayyd Dr. Aliah Pharmacology Department
Introduction to Antibiotics
Prof. Mohammad Alhumayyd Dr. Aliah Pharmacology Department

2. Objectives of the Lecture
Classification of antibiotics
Misuses of antibiotics
Choice of antibiotics
Bacterial resistance and ways to prevent it
General principles of antibiotic therapy
Indications for antibiotics prophylaxis.
The major learning objectives of this lecture are:

3. What is Antibiotic? Nobel prize in 1945
Any body recognize this person?
He is a scotich physician who
He noticed that colony on the top & the bacteria that is nearest to this colony started to die. Then he further studied what was excreted in this area to inhibit the growth of bacteria ? A cpd later name penicillin which is a mould or a fungus contamination
The technology at that time was still weak, so about 10 yrs later by the help of Florey & Chain who were able to extract the cpd which is later called penicillin & be able to clinically apply it on patients
Nobel prize in 1945

4. Definition of Antibiotics
Chemical substances produced by various microorganisms (bacteria, fungi, actinomycetes) that have the capacity to inhibit the growth or destroy other microorganisms.
Nowadays they are chemically synthesized.
They either kill bacteria (bactericidal) or hold bacteria from growing (bacteriostatic)
Antibiotics will not cure infections caused by viruses.
Actinomycetes any member of heterogenous gp of gm+ve, generally anaerobic bacteria noted as filamentous or branch growth pattern.
Of the specific types of actinomycetes, Nocardia asteroides, an aerobic species, is the primary cause of nocardiosis, an infection of the lungs, brain, or skin in humans. Dermatophilus congolensis causes dermatophilosis, a severe dermatitis of cattle, sheep, horses, and occasionally humans. Several species of Actinomyces cause the disease actinomycosis in humans and cattle.
Many of the actinomycetes are sources of antibiotics such as streptomycin.
Antibacterial or antimicrobial agents
Microorganisms = microscopic organisms
Statics: inh bacteria from reproducing but doesn’t kill them

5. Mechanism of action of Antibiotics
Protein
synthesis
Cell wall synthesis or function
BACTERIA
Nucleic acid synthesis or function e-
Folate

6. CLASSIFICATION OF ANTIBIOTICS ACCORDING TO MECHANISM OF ACTION
INHIBITION OF bacterial CELL WALL SYNTHESIS e.g. Penicillins, Cephalosporins
INHIBITION OF bacterial PROTEIN SYNTHESIS e.g. Macrolides, Tetracyclines, Aminoglycosides
INHIBITION OF bacterial DNA SYNTHESIS e.g. Quinolones
INHIBITION OF FOLATE METABOLISM e.g. Sulfonamides, Trimethoprim
INHIBITION OF RNA synthesis by binding to RNA polymerase e.g. Rifampicin.
Use of cephalosporins in patients with penicillin hypersensitivity begins with detailed history and physical examination.

7. According to spectrum Narrow spectrum , e.g.:
penicillin G, aminoglycosides
Broad spectrum , e.g.:
ampicillin, amoxicillin
Narrow: primarily effective against 1 type of organism or vs narrow range of bacteria
Penicillin activity is limited to gm+ve organisms
Penicillin is a group of ABs which include penicillin G (IV use), penicillin V (used po), procaine penicillin, and benzathine penicillin (IM use). Penicillin ABs were among the first medications to be effective against many bacterial infections caused by staphylococci & streptococci.
Aminoglycosides vs most gm-ve aerobic bacteria but not gm-ve anerobic
Broad: effective against both gm+ & -ve organisms
Ampicillin is used to treat infections by many Gm+ive & Gm-ive bacteria. Ampicillin was the first 'broad spectrum' penicillin with activity against Gm+ive bacteria including Streptococcus pneumoniae, Streptococcus pyogenes, some isolates of Staphylococcus aureus & some Enterococcus. Activity against Gm-ive bacteria includes Neisseria meningitidis, some Haemophilus influenzae, & some of the Enterobacteriaceae. Its spectrum of activity is enhanced by co-administration of sulbactam, a drug that inhibits beta lactamase, an enzyme produced by bacteria to inactivate ampicillin & related ABs.
Amoxicillin is active against gm+ive bacteria like Enterococcus faecalis, Staphylococcus species, Streptococcus species, Streptococcus pneumonia & gm-ve bacteria like Escherichia coli, Haemophilus influenza, Proteus mirabilis, Neisseria gonorrhoeae. Amoxicillin is also active against Helicobacter pylori but it is not effective against Pseudomonas, Klebsiella, Serratia, Citrobacter & some Gm-ive aerobes.

8. Choice of Antibiotic A) Clinical diagnosis (e.g. Syphilis)
B) Microbiological information
The patient comes with clear S & S
Blood. Blood tests can confirm the presence of antibodies that the body produces to fight infection. The antibodies to the bacteria that cause syphilis remain in your body for years, so the test can be used to determine a current or past infection.
Syphilis is a sexually transmitted infection (STI) caused by a type of bacteria known as Treponema pallidum.
People who are allergic to penicillin will likely be treated with a different antibiotic, such as: doxycycline, azithromycin, ceftriaxone
Penicillin was established as an effective treatment for syphilis before the widespread use of randomized clinical trials.
Microbiological information: is the effect of drug on m.o in petri dish. But of course when the drug is taken in infected human the response might be different,
So they usually make blood test for C & S. culture & sensitivity is to test which AB will work best
C) Pharmacological consideration

9. B) Bacteriological informations
Advantages
The exact antibiotic to be used
The most effective and reject the one with little or no activity
The least toxic
The cheapest.

10. The bacteria isolated may not be the prime cause of the disease
B) Bacteriological informations (Cont’)
Disadvantages
The bacteria isolated may not be the prime cause of the disease
do not take in consideration site of infection
some bacteria cannot be cultivated or take time to grow (e.g. M. Leprae, M. Tuberculosis)
Bacteriological services are not available at all hospitals.
Location of the infection like some bacteria located in poorly vascularized tissues & TF > difficult to tr. it is very important to reach the site of the infection

11. Choice of Antibiotics (cont’)
C) Pharmacological consideration 1. Site of infection 2. Host factors a) Immune system e.g. Alcoholism, diabetes, HIV, malnutrition, anticancer drugs, advanced age- (higher than usual doses or longer courses are required) b) Genetic factors e.g. Patients with G-6-PD deficiency treated with sulfonamides (Hemolysis).
The AB should reach the site of infection. & we should chose the best route to attack bacteria in certain area of the body
ABs vary in their ability to be absorbed orally or to cross the BBB & these factors will affect their routes of administration. The ability of the AB to achieve therapeutic concentrations at the site of infection is another important consideration thus ABs used for treating urinary infections should ideally be concentrated in urine. Some ABs have very severe toxic effects & are best avoided in certain conditions.
Drug abuse and alcohol intake known to decrease the immune system
Glucose-6-phosphate dehydrogenase deficiency (G6PDD) is an inborn error of metabolism that predisposes to RBCs breakdown. Sulfonamides antagonize folate synthesis.

12. Choice of Antibiotics (Cont’)
c) Pregnancy and Lactation
Aminoglycosides (hearing loss)
Tetracyclines (bone deformity)
d) Extreme Age
Neonates and elderly
e) Renal function
e.g. Aminoglycosides (renal failure)
f) Liver function
e.g. Erythromycin (hepatic failure)
3. Drug Allergy.
The very young & the very old tend to be more prone to the adverse effects of the antibiotics.

13. MISUSES OF ANTIBIOTICS
Treatment of diseases caused by viruses
Improper dosage
Therapy of fever of unknown origin
Presence of pus or necrotic tissues, or blood at the surgical site
Excessive use of prophylactic antibiotics in travelers
Lack of adequate bacteriological information
Overuse as growth promoters in animals & agriculture
Pts do not take them according to their doctor’s instructions
Some pts save unused antibiotics for another illness, or pass to others.
perception of need - is an antibiotic necessary ? ii) choice of antibiotic - what is the most appropriate antibiotic ? iii) choice of regimen : what dose, route, frequency and duration are needed ? iv) monitoring efficacy : is the treatment effective ?
If there is a collection of pus that should be drained surgically or a foreign body
ABs are administered to animals in feed to marginally improve growth rates & to prevent infections. There is growing evidence that antibiotic resistance in humans is promoted by the widespread use of nontherapeutic ABs in animals. However, the inappropriate overuse of antibiotics in animals also should be addressed as another important source of AB resistance. To the degree that AB overuse in food animals exacerbates problems with resistance, this overuse is a factor contributing to the increased costs to treat antibiotic-resistant infections in humans.

14. Reasons for MISUSES of ANTIBIOTICS
A consequence of many factors:
1- Availability of a very wide selection
2- Limitation of physician’s time
3- Physician shortage and expenses
4- Availability without Rx in pharmacies
3- Public demand (pressure to prescribe).
Physicians with inadequate knowledge may prefer prescribing maximal broad-spectrum treatment. Therefore, educating physicians is certainly required

15. Bacterial Resistance
One result of the widespread use of antibiotics has been the emergence of resistant pathogens that have been sensitive in the past
Definition
Conc of antibiotic required to inhibit or kill the bacteria is greater than the conc that can safely be achieved in the plasma.

16. Mechanisms of Acquired Antibiotic Resistance
1. Inactivation by enzyme produced by bacteria Bacterial β-lactamase inactivates penicillins & cephalosporins by cleaving the β-lactam ring of the drug 2. Bacteria develops an altered receptor for the drug 3. Bacteria develops an altered metabolic pathway 4. Reduced bacterial permeability to antibiotic 5. Actively transporting the drug out of the cell.

17. Prevention of Resistance
*Use antibiotics only when absolutely required *Use antibiotics in adequate dosage for sufficient period of time Not too brief therapy Not too prolonged therapy (exceptions, e.g. TB ) *Combination of antibiotics may be required to delay resistance (e.g. TB).
Stopping the medication too early may allow bacteria to continue to grow, which may result in a return of the infection

18. General Principles of antibacterial therapy
Administer drug in full dose, at proper interval and by the best route
When apparent cure achieved, continue antibiotic for about 3 days further to avoid relapse
Skipping doses may decrease effectiveness of antibiotic & increase the incidence of bacterial resistance.
In some infections, bacteriological proof of cure is
desirable (e.g. TB, UTI)
Measurement of plasma conc. of antibiotics is seldom needed, except for systemic aminoglycosides (e.g., streptomycin, gentamicin).

19. General Principles of antibacterial therapy (cont’)
2 or > antimicrobial drugs should not be used without good reason, e.g.:
- Mixed bacterial (polymicrobial) infections
- Desperately ill patient of unknown etiology
- To prevent emergence of resistance (e.g. TB )
- To achieve synergism
e.g. piperacillin + gentamicin (p. aeruginosae)
Disadvantages of multiple antibiotics
Increased risk of sensitivity or toxicity
Increased risk of colonization & infection with a resistant bacteria
Possibility of antagonism
Higher cost.
The potential synergistic effect of piperacillin with gentamicin was examined against five isolates each of Pseudomonas aeruginosa, Staphylococcus aureus and Streptococcus faecalis isolated from patients with endocarditis. Piperacillin and gentamicin synergistically inhibited all strains of P. aeruginosa and S. aureus tested.
piperacillin, B-lactam Ab a broad-spectrum penicillin.
Gentamicin: This medication is used to prevent or treat a wide variety of bacterial infections. Gentamicin belongs to a class of drugs known as aminoglycoside antibiotics. It works by stopping the growth of bacteria. Used IM or IV

20. Indications for antibiotics prophylaxis
Surgical prophylaxis, e.g.: bowel surgery, joint replacement, etc. to prevent postoperative infections Immunosuppressed Patients, e.g.: Very old, Very young, Diabetics, Anaemics, AIDS, Cancer pts Dental extractions, e.g.: Pts with total joint replacements Pts with cardiac abnormalities.
The benefits of prophylactic antibiotics must be balanced against the risks of drug side-effects and the emergence of antibiotic resistance.
Pre-surgical tr in GI procedure.
One area that has been the subject of much controversy is the need for AB prophylaxis for patients with total joint replacements who are undergoing outpatient urologic, GI, dental, or cardiac interventions.
Transient bacteremia, which leads to the seeding of a prosthetic joint & resultant joint infection, is a hypothesized mechanism of infection during various interventions; this has never been definitively proven.
Cardiac abnormalities Like rheumatic heart disease. Also, the data are mixed as to whether prophylactic ABs taken before a dental procedure prevent infective endocarditis. The guidelines note that people who are at risk for infective endocarditis are regularly exposed to oral bacteria during basic daily activities such as brushing or flossing. Persons at risk of developing bacterial infective endocarditis establish & maintain the best possible oral health to reduce potential sources of bacterial seeding. They state, “Optimal oral health is maintained through regular professional dental care & the use of appropriate dental products, such as manual, powered, & ultrasonic toothbrushes; dental floss; & other plaque-removal devices.” Like in patient with current infective endocarditis/valvular heart disease guidelines state that use of preventive ABs before certain dental procedures is reasonable for patients with: prosthetic cardiac valves, including transcatheter-implanted prostheses & homografts; prosthetic material used for cardiac valve repair, such as annuloplasty rings & chords; a history of infective endocarditis; a cardiac transplant.