RATIONALE USE OF ANTIBIOTICS

1. GENERAL PRINCIPLES OF
ANTIBIOTIC THERAPY
DR ANTHONY KWAW, RESIDENT PHARMACIST
ACCIDENT AND EMERGENCY
TAMALE TEACHING HOSPITAL
TAMALE, GHANA
Email: kwawanthony7@gmail.com
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2. Outline
Introduction
Classification of bacteria
Important pathogens
Selective toxicity
Classification of antibiotics
Selecting antibiotic therapy
Empiric antibiotic therapy
Combination antibiotic therapy
Antimicrobial resistance
Conclusion
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3. Introduction
Antibiotics have been one of the most important and successful
groups of therapeutic agents introduced.
Many infections that once caused high mortality, such as TB,
pneumonia, and sepsis, became controllable and surgical procedures
improved because the high risks of post-surgical infections were
reduced
Antibiotics disrupt essential processes or structures in the bacterial
cell.
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4. Introduction
This either kills the bacterium or slows down bacterial growth.
A bactericidal antibiotic kills the bacteria
A bacteriostatic antibiotics stops bacterial growth but does not kill the
cells.
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5. Classification of bacteria
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6. Important Pathogens
Staphylococcus aureus: gram-positive bacteria, facultative anaerobe, skin,
URT
Disease resulting from direct organ invasion by the bacteria:
Pneumonia
Meningitis
Osteomyelitis
Acute bacterial endocarditis
Septic arthritis
Skin infections
Bacteremia/sepsis
Urinary tract infection
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7. Important Pathogens
Streptococcus pnuemoniae: gram-positive bacteria, facultative
anaerobe, RT, sinuses, nasal cavity
It is the commonest cause of
Pneumonia in adults
Meningitis in adults
Otitis media in children
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8. Important Pathogens
Enterobacteriace: a large family of gram-negative bacteria
They form part of the normal intestinal flora and cause
gastrointestinal disease.
Salmonella, E. coli, Klebsiella, Shigella, Enterobacter, Citrobacter
etc.
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9. Important Pathogens
Escherichia coli: gram-negative bacteria, facultative anaerobe
It normally resides in the colon without causing disease
Diseases caused by Escherichia coli in the presence of virulence
factors include the following:
Diarrhea.
Urinary tract infection.
Neonatal meningitis.
Gram-negative sepsis, occurring commonly in debilitated hospitalized
patients.
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10. Important Pathogens
Klebsiella pneumoniae: gram-negative, non motile facultative
anaerobe
It causes
Sepsis
Urinary tract infections in hospitalized patients with Foley catheters.
Pneumonia
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11. Important Pathogens
Enterobacter spp.: a highly motile gram-negative rod which is part of
the normal flora of the intestinal tract.
Facultative anaerobe
It is occasionally responsible for hospital-acquired infections usually
causing respiratory and urinary infections
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12. Important Pathogens
Acinetobacter spp: is a group of bacteria commonly found in the
environment
Most common cause of infections is Acinetobacter baumannii
Acinetobacter baumannii can cause infections in the blood, urinary
tract, and lungs (pneumonia), or in wounds in other parts of the body
Acinetobacter infections are usually HAI.
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13. Important Pathogens
• Pseudomonas aeruginosa: obligate aerobic gram-negative rod
• It colonizes and infects sick, immunocompromised hospitalized patients
• Resistant to almost every antibiotic
• It causes;
• Pneumonia
• Osteomyelitis
• Burn-wound infections
• Sepsis( high mortality rate)
• Urinary tract infections
• Pyelonephritis
• Endocarditis
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14. Selective toxicity
Toxicity to the parasite or the unwanted cell but non-toxic to the host
(leaves the host or environment relatively unharmed)
Feasibility of the selective toxicity depends on exploitation of
biochemical differences between the parasite and the host cell
Selective toxicity is the PIVOT of antibiotic therapy
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15. Structural elements and biochemical processes
in the bacterial cell
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16. Classification of antibiotics
There are several different classes of antibiotics
Chemical structure
Mechanism of action
Bactericidal or bacteriostatic
Spectrum of activity
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17. Classification of antibiotics
Chemical structure
Beta-lactam antibiotics: penicillins (amoxicillin, ampicillin, benzylpenicillin, oxacillin,
dicloxacillin), cephalosporins (Cefaclor, cefuroxime, ceftriaxone, ceftazidime etc.)
Quinolones: nalidixic acid, ciprofloxacin, levofloxacin, moxifloxacin
Aminoglycosides: amikacin, neomycin, gentamicin, streptomycin
Macrolides: azithromycin, erythromycin, clarithromycin
Tetracyclines: tetracycline, doxycycline, minocycline
Lincosamides: clindamycin
Chloramphenicol
Glycopepetides: vancomycin, teicoplanin (MRSA)
Sulphonamides: sulfamethoxazole, trimethoprim, sulphadiazine, sulphasalazine
Carbapenems: ertapenem, meropenem, imipenem, doripenem
Monobactams: aztreonam
Rifamycins: rifampin, rifampicin
Others: linezolid , metronidazole, nitrofurantoin, bacitracin, polymyxins (colistin)
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18. Classification of antibiotics
Mechanism of action
Cell wall synthesis inhibitors: penicillins, cephalosporins, glycopeptides,
monobactams, cabapenems, cycloserine, bacitracin
Protein synthesis inhibitors:
30S: aminoglycosides, tetracyclines
50S: chloramphenicol, macrolides, linezolid, clindamycin
Bacterial DNA inhibitors: quinolones, metronidazole, nitrofurantoin
Folate antagonists: sulphonamides, trimethoprim
Cell membrane inhibitors: polymixins (colistin)
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19. PTERIDINE + P-AMINOBENZOIC ACID
DIHYDROPTEROIC ACID
DIHYDROFOLIC ACID
TETRAHYDROFOLIC ACID
PURINES/PYRIMIDINES
PRECURSORS
Dihydropteroate synthetase
DNA
Dihydrofolate reductase
Sulphonamides
Trimethoprim
Mechanism of action of sulphonamides
sulphadiazine
sulphamethoxazole
cotrimoxazole
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20. Classification of antibiotics
Bactericidal: penicillins, cephalosporins, quinolones, glycopeptides,
macrolides , chloramphenicol, metronidazole, polymixins
Bacteriostatic: sulphonamides, macrolides, tetracyclines,
chloramphenicol
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21. Classification of antibiotics
Spectrum of activity
Narrow-spectrum antibiotics are more specific and only active against certain
groups or strains of bacteria.
Broad-spectrum antibiotics instead inhibit a wider range of bacteria.
Narrow-spectrum antibiotics are to prefer since the effect on other, non-disease
causing bacteria are more limited.
Unfortunately broad-spectrum antibiotics are often used since it can be difficult
for doctors to diagnose the correct bacteria in time or when knowledge about
how to correctly treat an infection is lacking 21

22. Classification of antibiotics
Gram positive coverage:
Penicillins (ampicillin, amoxicillin) penicillinase resistant (Dicloxacillin,
Oxacillin)*
Cephalosporins (1st and 2nd generation)
Macrolides (Erythromycin, Clarithromycin, Azithromycin)
Quinolones (gatifloxacin, moxifloxacin, and less so levofloxacin)
Vancomycin(MRSA)
Sulfonamide/trimethoprim
Clindamycin
Tetracyclines
Chloramphenicol
Other: Linezolid, (VRE)
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23. Classification of antibiotics
Gram negative coverage:
Broad spectrum penicillins (Ticarcillin-clavulanate, piperacillin-tazobactam)
Cephalosporins (2nd, 3rd, and 4th generation)
Aminoglycosides (renal and ototoxicity)
Macrolides (Azithromycin)
Quinolones (Ciprofloxacin)
Monobactams (Azetreonam)
Sulfonamide/trimethoprim
Carbapenems (Imipenem)
Chloramphenicol
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24. Classification of antibiotics
Anaerobic coverage:
Metronidazole
Clindamycin
Quinolones (Gatifloxacin, Moxifloxacin)
Carbapenems
Chloramphenicol
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25. Classification of antibiotics
Atypical coverage:
Macrolides (Legionella, Mycoplasma, chlamydiae)
Tetracyclines (rickettsiae, chlamydiae)
Quinolones (Legionella, Mycoplasma, Chlamydia)
Chloramphenicol (rickettsiae, chlamydiae, mycoplasma)
Ampicillin (Listeria)
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26. Understanding Cephalosporins
4 generations based on coverage with improving gram negative coverage as
generation number increases
1st generation (Cefazolin, Cephalexin. Cephadroxil, Cephradine):
Good gram positive coverage, inexpensive, and used primarily to treat skin and soft tissue
infections.
2nd generation (Cefuroxime, Cefaclor, Cefamandole, Cefoxitin, Cefmetazole):
Some gram positive and gram negative coverage, expensive, and rarely used as 1st line therapy
except sometimes for PID.
3rd generation (Ceftriaxone, Cefixime, Cefotaxime, Ceftazidime):
Good gram negative coverage except Pseudomonas, long half-life (q24 hr dosing), crosses
blood-brain barrier, biliary and renal clearance.
4th generation (Cefepime, Cefluprenam, Cefozopran, Cefpirome, Cefquinone):
Good gram positive (except MRSA) and gram negative coverage, including Pseudomonas,
crosses blood-brain barrier, good for nosocomial infections.
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28. Selecting antibiotic therapy
Antibiotics can be used prophylactically or therapeutically.
Factors to be considered during selection include:
Bacterial
Host
Drug
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29. Bacterial factors
Antibiotic therapy initiated for bacterial infections only.
Identifying the causative organism
Reasonable guess based on statistical probabilities
e.g.. UTI in sexually active premenopausal women is due to E.coli in 85%
cases
Cellulitis of arm or leg due to Streptococcus pyogenes or Staph aureus
The following will help in making a good guess:
Site of infection
Community or hospital acquired
Age, underlying illness, and predisposing factors of the host
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30. Host factors
Site of infection
Allergy
Renal & hepatic function
Concomitant medications
Age
Route of administration
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31. Drug factors
Activity against the bacteria
Available route of administration
Adverse effects profile
Dosing frequency
Compliance factors including taste for children medication
Cost of treatment
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32. Empiric Antibiotic Therapy
Important considerations when prescribing antimicrobial therapy include
obtaining an accurate diagnosis of infection;
understanding the difference between empiric and definitive therapy;
identifying opportunities to switch to narrow-spectrum, cost-effective oral agents
for the shortest duration necessary;
understanding drug characteristics that are peculiar to antimicrobial agents (such
as pharmacodynamics and efficacy at the site of infection);
accounting for host characteristics that influence antimicrobial activity;
recognizing the adverse effects of antimicrobial agents on the host.
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33. 1. Decide if an antibiotic is indicated: does the
patient have a bacterial infection?
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34. 2. Perform cultures before administering
antibiotics in hospitalized patients or in
outpatients with recurrent infections
This allows de‐escalation to a narrow spectrum antibiotic once the
antibiogram is available & is a cornerstone of antibiotic stewardship
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35. 3. Choose an appropriate empiric antibiotic
Target the most likely pathogen(s) for the site of infection
This can be predicted by understanding the broad groups of pathogens that most
commonly cause infections at various sites
Assess likelihood of antibiotic resistance
Risk factors include known colonization with a resistant pathogen, HCAI, recent
antibiotic exposure.
Local resistance patterns inform prescribing.
Review potential contraindications
Allergy
Toxicity
Choose drug with adequate target tissue penetration
Aim for a single drug with the desired spectrum of activity
Monotherapy is preferred unless combination therapy is required for synergy (e.g.
endocarditis) or extended spectrum beyond what can be obtained with a single drug (e.g.
atypical pathogens in severe CAP) 35

36. 4. Ensure correct dose and route of administration
The oral/enteral route is preferred whenever possible for patients
with mild to moderate infections.
Intravenous antibiotics should be reserved for severe infection or for
certain sites such as the CSF, bacteremia, endocarditis, bone and joint
infections.
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37. 5. Start the appropriate antibiotic rapidly in severe
infections
Mortality increases by 8% for every hour antibiotic administration is
delayed in septic shock
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38. 6. Practice early and effective source control
Search for and remove any persistent foci of infection
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39. 7. Evaluate antibiotic appropriateness every day
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40. Combination antibiotic therapy
A combination of two antibacterial agents may produce the following
responses ;
synergism, where the joint effect is greater than the sum of the effects of each
drug acting alone.
additive effect, in which the combined effect is equal to the arithmetic sum of
the effects of the two individual agents
antagonism (interference), in which there is a lesser effect of the mixture than
that of the more potent drug action alone
Amoxicillin + Clavulanic acid, Piperacillin + Tazobactam,
Imipenem+cilastatin, Imipenem+ Cilastatin+Relebactam,
Sulphametoxazole +Trimethoprim (Co-trimoxazole)
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41. Combination antibiotic therapy
There are four possible justifications as to the use of antibiotics in
combination
Synergism:e.g. Co-trimoxazole
wider spectrum of cover may be obtained, which may be (a) desirable as an
emergency measure in life-threatening situations; or (b) of use in treating
mixed infections. E.g. Ceftriaxone + metronidazole, ceftriaxone +
Clindamycin
emergence of resistant organisms may be prevented. E.g. HRZE in TB,
Dapsone + Rifampicin in tuberculoid leprosy, Dapsone +Rifampicin+
Clofazimine in lepromatous leprosy, HAART in HIV/AIDS
possible reduction in dosage of a toxic drug may be achieved. E.g. Quinine +
Clinamycin in malaria treatment in pregnancy
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43. Antimicrobial Resistance (AMR)
AMR is the ability of a microorganism to survive the lethal effects of
an antimicrobial, resulting in a situation where standard treatments
become ineffective and infections persist which may spread to others
E.g. Multi-drug resistant TB, resistance to ARTs, methicillin-resistant
Staphylococcus aureus (MRSA), gonorrhea resistant to quinolones and
cephalosporins
Miserably low rate of discovery of new antimicrobials compared to
the rate of development of AMR
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44. Drivers of antimicrobial Resistance
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45. Misuse of Antibiotics
Prescribed un-necessarily
Delayed in critically ill patients
Broad spectrum antibiotics over-used
Narrow spectrum antibiotics misused
Dose and Regimen
Duration
Lack of use of microbiology data
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46. Consequences of AMR
Treatment failure
Morbidity and Mortality
Risk of Hospitalization
Length of hospital stay
Need for expensive and broad spectrum antibiotics
Costs associated with increased bacterial resistance
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47. Why should we care about AMR
Increased health care
cost
Longer hospital stay
Treatment failure

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49. Conclusion
Pharmaceutical companies are no producing antibiotics for treatment
of infections
We must limit emergence and transmission of antimicrobial resistance
bacteria by ensuring rationale use of antibiotics
Antibiotic use must be supported by microbiology report
Infection prevention and control measure should also be emphasized
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50. THANK YOU FOR YOUR AUDIENCE
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51. QUESTIONS?
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