ANTIBIOTICS
-by RAHUL SHIVNIKAR
SOME GENERAL PRINCIPLES
• Antibiotics can be naturally produced,
semi-synthetic, or synthetic substances
• Designed to hav...
EXAMPLES OF SELECTIVE
ACTION
• Penicillin on bacterial cell wall (organisms
without cell wall won’t be inhibited eg
Mycopl...
ANTIBIOTICS ACTING ON CELL
WALL OF BACTERIA
• Beta lactams:
• Penicillins, cephalosporins, carbapenems,
monobactam
• Glyco...
THE IDEAL
ANTIBIOTIC?:PENICILLIN
•
•
•
•
•
•

Narrow spectrum
Bactericidal
Very selective mode of action
Low serum protein...
THE DEVELOPMENT OF THE
BETA LACTAMS
• Benzylenicillin and early cephalosporins mainly
active against gram positive bacteri...
BENZYLPENICILLIN: MAIN
INDICATIONS
 Strep pyogenes sepsis (from sore throat to
fasciitis)
 Pneumococcal pneumonia, menin...
Broader spectrum penicillins
• Ampicillin, amoxycillin cover most
organisms hit by penicillin but also Esch
coli, some Pro...
Organisms producing TEM1beta
lactamase
•
•
•
•
•

Haemophilus influenzae
Neisseria gonorrhoeae
Bacteroides fragilis
Staph ...
Carbapenems
• Imipenem, meropenem: have a very broad
spectrum activity against gram-negative
bacteria, anaerobes, streps
•...
PENICILLIN IS GENERALLY
VERY SAFE BUT….
• Allergic reactions not uncommon-rashes
• Most severe reaction being anaphylaxis
...
What antibiotics can be used in
penicillin allergy?
• Macrolides: erythromycin, clarithromycin
• (mainly gram positive cov...
REMEMBER WHAT THE OTHER
BETA LACTAMS ARE:
• All penicillins: ampicillin, augmentin,
piperacillin, cloxacillin
• Cephalospo...
CLOXACILLIN
•
•
•
•
•

Narrow spectrum: Staph aureus (MSSA)
Stable to TEM1 beta lactamase
Similar antibiotics are methicil...
Cephalosporins: main uses
• Cefuroxime: surgical prophylaxis
• Cefotaxime/ceftriaxone: meningitis
nosocomial infections ex...
Problems with antibiotic resistance:
how does it happen?
• Some bacteria are naturally resistant to
particular antibiotics...
Current major antibiotic resistance
problems: community infections
• Respiratory tract: penicillin resistance in
pneumococ...
Current major resistance problems:
hospital infections
• MRSA: current strains are often multiplyantibiotic resistant
• VI...
Other major antibiotic groups:
aminoglycosides
• Gentamicin, amikacin (tobramycin,
streptomycin)
• Mainly active against g...
How we give aminoglycosides
• For serious nosocomial infections:
“extended interval” or once daily dosing
• 5 or 7mg/kg fo...
Some indications and limitations
of particular antibiotics
Community acquired pneumonia
• Pneumococcus (and H influenzae) are most
likely: therefore ampicillin, amoxycillin or
augme...
Community acquired urinary
infections
•
•
•
•
•
•
•

Ampicillin, amoxycillin, augmentin
Oral cephalosporin: cephradine
Tri...
Skin and soft tissue infections
• Cellulitis ? Streptococcal: penicillin or
augmentin
• Infected eczema ? Staphylococccal/...
Where there is deep-seated
infection: bone, abscess
• Need an antibiotic with good tissue and
phagocyte penetration
• Exam...
Why do we use combination
therapy?
• When treating serious infection empirically
we want to cover a broad spectrum
(severe...
Factors to consider when
prescribing an antibiotic
• Any history of allergy, toxicity?
• Is it appropriate for the spectru...
Some other antibiotics occasionally
used
• Co-trimoxazole (Stenotrophomonas)
• Chloramphenicol (typhoid fever,
meningitis)...
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Antibiotics

  1. 1. ANTIBIOTICS -by RAHUL SHIVNIKAR
  2. 2. SOME GENERAL PRINCIPLES • Antibiotics can be naturally produced, semi-synthetic, or synthetic substances • Designed to have as much selective toxicity on the bacteria as possible • This is more likely to be achieved compared to antimicrobials acting against eukaryotic cells (fungi, protozoa)
  3. 3. EXAMPLES OF SELECTIVE ACTION • Penicillin on bacterial cell wall (organisms without cell wall won’t be inhibited eg Mycoplasma pneumoniae) • Sulphonamides prevent bacteria synthesising folic acid whereas humans can use preformed folate • Generally drugs acting on cell membranes or protein synthesis are more toxic to humans
  4. 4. ANTIBIOTICS ACTING ON CELL WALL OF BACTERIA • Beta lactams: • Penicillins, cephalosporins, carbapenems, monobactam • Glycopeptides: • Vancomycin, teicoplanin
  5. 5. THE IDEAL ANTIBIOTIC?:PENICILLIN • • • • • • Narrow spectrum Bactericidal Very selective mode of action Low serum protein binding Widely distributed in body esp. CNS Excreted by the kidneys
  6. 6. THE DEVELOPMENT OF THE BETA LACTAMS • Benzylenicillin and early cephalosporins mainly active against gram positive bacteria (strep and staph) • Then “broad spectrum” penicillins appeared: ampicillin, ureidopenicillins and cephalosporins: cefuroxime, cefotaxime • Carbapenems and latest generation of cephalosporins, eg ceftazidime more active against gram negatives
  7. 7. BENZYLPENICILLIN: MAIN INDICATIONS  Strep pyogenes sepsis (from sore throat to fasciitis)  Pneumococcal pneumonia, meningitis  Meningococcal meningitis, sepsis  Infective endocarditis (strep)  Strep group B sepsis  Diphtheria  Syphilis, leptospirosis
  8. 8. Broader spectrum penicillins • Ampicillin, amoxycillin cover most organisms hit by penicillin but also Esch coli, some Proteus (cause UTI’s) • Augmentin stable to TEM1 beta lactamase because of the clavulanic acid therefore more active than ampicillin • Tazocin: broader coverage than augmentin against gram negatives including Pseudomonas
  9. 9. Organisms producing TEM1beta lactamase • • • • • Haemophilus influenzae Neisseria gonorrhoeae Bacteroides fragilis Staph aureus Esch coli
  10. 10. Carbapenems • Imipenem, meropenem: have a very broad spectrum activity against gram-negative bacteria, anaerobes, streps • Now used to treat gram negative infections due to so called ESBL producing organisms eg, E coli, Klebsiella • Ertapenem is a new member of the group but its not active against Pseudomonas
  11. 11. PENICILLIN IS GENERALLY VERY SAFE BUT…. • Allergic reactions not uncommon-rashes • Most severe reaction being anaphylaxis • A history of anaphylaxis, urticaria, or rash immediately after penicillin indicates risk of immediate hypersensitivity after a further dose of any penicillin or cephalosporin (therefore these must be avoided) • Allergy is not dependent on the dose given ie, a small dose could cause anaphylaxis • Very high doses of penicillin can cause neurotoxicity • Never give penicillin intrathecally
  12. 12. What antibiotics can be used in penicillin allergy? • Macrolides: erythromycin, clarithromycin • (mainly gram positive cover) • Quinolones: ciprofloxacin, levofloxacin (mainly gram positive cover) • Glycopeptides (serious infections) • Fusidic acid, rifampicin, clindamycin (mainly gram positive)
  13. 13. REMEMBER WHAT THE OTHER BETA LACTAMS ARE: • All penicillins: ampicillin, augmentin, piperacillin, cloxacillin • Cephalosporins: cefuroxime, cefotaxime, ceftriaxone, ceftazidime (5-10% cross sensitivity) • Monobactam: aztreonam (low cross sensitivity) • Carbapenems: imipenem, meropenem
  14. 14. CLOXACILLIN • • • • • Narrow spectrum: Staph aureus (MSSA) Stable to TEM1 beta lactamase Similar antibiotics are methicillin, nafcillin Similar safety profile to benzylpenicillin MRSA emerged in the early 1970’s (MecA gene encoding additional pbp)
  15. 15. Cephalosporins: main uses • Cefuroxime: surgical prophylaxis • Cefotaxime/ceftriaxone: meningitis nosocomial infections excluding Pseudomonal, • Ceftazidime: nosocomial infections including Pseudomonal
  16. 16. Problems with antibiotic resistance: how does it happen? • Some bacteria are naturally resistant to particular antibiotics (Pseudomonas has permeability barrier to many antibiotics) • Some typically susceptible species have minority populations which are resistant by virtue of mutational resistance (pneumococcus) • Other species acquire resistance via plasmids (“infectious resistance”) eg Neisseria gonorrhoeae, many gram negatives
  17. 17. Current major antibiotic resistance problems: community infections • Respiratory tract: penicillin resistance in pneumococcus (5-10%) • Gastrointestinal: quinolone resistance in Campylobacter • Sexually transmitted: penicillin, quinolone resistance in gonococcus • Urinary tract: beta lactam resistance in Esch coli • MRSA and MDRTB • Tropical: multidrug resistance in Salmonella typhi, Shigella spp
  18. 18. Current major resistance problems: hospital infections • MRSA: current strains are often multiplyantibiotic resistant • VISA/GISA: intermediate resistance to glycopeptides (thickened cell wall) • VRSA/GRSA: highly resistant (transferable on plasmids) from enterococci • VRE: enterococci (multiply resis tant) • Broad spectrum beta lactam resistant (ESBL) Esch coli, Klebsiella • Multiply antibiotic resistant enterobacteria: Acinetobacter, Stenotrophomonas, Serratia
  19. 19. Other major antibiotic groups: aminoglycosides • Gentamicin, amikacin (tobramycin, streptomycin) • Mainly active against gram negative bacteria • Mainly used to treat nosocomial infections: pneumonia in ITU, septicaemia • Limiting factors are nephrotoxicity (and ototoxicity) and resistance • Also used in combination
  20. 20. How we give aminoglycosides • For serious nosocomial infections: “extended interval” or once daily dosing • 5 or 7mg/kg for gentamicin (Hartford nomogram) • Rationale based on concentrationdependent killing and post-antibiotic effect • Reduced risk of nephrotoxicity • In infective endocarditis use lower doses to give synergy with penicillin
  21. 21. Some indications and limitations of particular antibiotics
  22. 22. Community acquired pneumonia • Pneumococcus (and H influenzae) are most likely: therefore ampicillin, amoxycillin or augmentin • Severe pneumonia: cefotaxime • Severe atypical pneumonia (Legionella): macrolide or quinolone • Resistant pneumococcus: vancomycin or linezolid (new antibiotic!) • A new quinolone moxifloxacin covers most of these pathogens (likely to be used more in community)
  23. 23. Community acquired urinary infections • • • • • • • Ampicillin, amoxycillin, augmentin Oral cephalosporin: cephradine Trimethroprim Nalidixic acid Nitrofurantoin Ciprofloxacin Mecillinam
  24. 24. Skin and soft tissue infections • Cellulitis ? Streptococcal: penicillin or augmentin • Infected eczema ? Staphylococccal/mixed: penicillin+flucloxacillin or augmentin • Necrotising fasciitis: penicillin+clindamycin • Septic arthritis: fluclox+fusidic acid • Gangrene: metronidazole
  25. 25. Where there is deep-seated infection: bone, abscess • Need an antibiotic with good tissue and phagocyte penetration • Examples are rifampicin, clindamycin, fusidic acid, ciprofloxacin, metronidazole • So for treatment of Staph aureus osteomyelitis: flucloxacillin+ fusidic acid
  26. 26. Why do we use combination therapy? • When treating serious infection empirically we want to cover a broad spectrum (severe pneumonia:cefotaxime+erythromycin) • To prevent the emergence of drug resistance: tuberculosis regimens • For synergy: infective endocarditis (aminoglycoside) • For mixed infections eg, abdominal sepsis (tazocin+metronidazole)
  27. 27. Factors to consider when prescribing an antibiotic • Any history of allergy, toxicity? • Is it appropriate for the spectrum I want to cover? • What route of admin: oral or i.v? • Any factors affecting absorption ? • Is it going to reach the site of infection? • Any drug interactions? • Any serious toxicity eg, hepatic, renal? • Does it need monitoring eg aminoglycosides, vancomycin, streptomycin?
  28. 28. Some other antibiotics occasionally used • Co-trimoxazole (Stenotrophomonas) • Chloramphenicol (typhoid fever, meningitis) • Colistin (resistant Pseudomonas) topical • Neomycin: gut decontamination, topical
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