1. Lecture 23-Antibiotic Therapy-2-Lecture Objectives
Penicillins
Cephalosporins
Broad Spectrum Antibiotics
Aminoglycoside Antibiotics

2. Lecture 23-Antibiotic Therapy-2-Lecture Outcomes
At the end of this lecture, you should be able to:
Classify giving examples &
Discuss the Pharmacological actions ADRs & uses of:
Penicillins
Cephalosporins
Broad Spectrum Antibiotics(Chloramphenicol, Tetracyclines)
Aminoglycoside Antibiotics

3. Beta Lactams(Penicillins)
Interfere with bacterial cell-wall synthesis
Have high therapeutic index (remarkably non-toxic)
Safe during pregnancy
Allergy is the main adverse event, rarely anaphylaxis

4. Penicillins Four Classes Standard penicillins
Antistaphylococcal penicillins
Aminopenicillins
Antipseudomonal penicillins

5. (A) Standard Penicillins
Penicillin G - for parenteral therapy
Penicillin V – for oral therapy
Depot/Repository Penicillin:
Procaine penicillin G– once a day
Benzathine penicillin G – once a month
Penicillin remains drug of choice for streptococcal, meningococcal infections,syphilis
Penicillin with aminoglycoside for enterocococci

6. (B)Antistaphylococcal Penicillins
Staphylococci resistant to std. penicillin
Produce Pencillinase or β-lactamase
Methicillin first developed but not used (due to nephro toxicity)
Cloxacillin, Dicloxacillin, Oxacillin,Nafcillin
All relatively acid-stable
Used to treat staphylococcal infections

7. (C) Extended-Spectrum Penicillins (Aminopenicillins)
Broad-spectrum penicillin
Not effective against staphylococci,
E. coli, Enterobacter, P. aeruginosa,
Proteus, H. influenzae, Klebsiella,
Salmonella etc.
Ampicillin –preferred for IV therapy
Amoxicillin- for oral therapy (better absorbed from gut)
Uses: Respiratory tract infections, UTI,
Meningitis- large IV dose of Ampicillin

8. (D) Antipseudomonal Penicillins
Carboxypenicillins(Carbenicillin, Carbenicillin indanyl sodium, Ticarcillin)
Ureidopenicillins (Azlocillin, Mezlocillin, Piperacillin)
Spectrum same as aminopenicillin plus Pseudomonas aeruginosa
Given parenterally

9. Penicillins-Adverse Reactions
Local irritation
Hypersensitivity(all penicillins are cross- sensitizing & cross-reacting)
Seizures(in patients with renal insufficiency who are given very high doses)
Suprainfections
Jarisch–Herxheimer reaction

10. Salient Features: Carbapenems Imipenem, Meropenem
Spectrum: streptococci, staphylococci, enterobacteriaceae, pseudomonas,B.fragilis
May cause seizures in susceptible individuals
Useful to treat infections resistant to other antibiotics

11. Four generations of Cephalosporins
First generation:
Active against streptococci and staphylococci
Active against most E.coli, Proteus mirabilis
and Klebsiella pneumoniae
Cephalexin, Cefazolin, Cephalothin,Cephradine
Used as alternative to penicillin in penicillin allergic individuals

12. Cephalosporins Second generation: Third generation:
Cefaclor, Cefamandole, Cefuroxime
Useful in Streptococcal, Staphylococcal and H.influenzae infections
Third generation:
Cefoperazone, Ceftazidime, Cefotaxime
Enterobacteriaceae and H. influenzae
Beta lactamase resistant
Good CSF concentration
Useful in meningitis and nosocomial pneumonia

13. Cephalosporins Fourth generation: Cefepime, Cefpirome
Extended spectrum
Good activity against P aeruginosa, Enterobacteriaceae, S aureus, S pneumoniae, Hemophilus, Neisseria, etc.
Highly resistant to hydrolysis by many chromosomal β-lactamases & some extended-spectrum β-lactamases

14. Macrolides (Erythromycin- Structure)
All macrolides contain a large 14- membered macrocyclic lactone ring with 1 or more deoxy sugars attached

15. Macrolides (Azithromycin- Structure)
Azithromycin is a azalide
Azithromycin has a 15-membered macrocyclic lactone ring

16. Macrolides-Salient Features
Possess similar mechanism of action, resistance, and antimicrobial activity
Reversibly bind to 50S ribosomal subunits and inhibit protein synthesis
Macrolides- large lactone ring
Erythromycin – prototype
Others-Clarithromycin, Azithromycin, Telithromycin
Usually given orally

17. Macrolides-Therapeutic Uses
Active against-Streptococci/Staphylococci/B. pertussis/C. diphtheriae/H. pylori/M. pneumonia /Legionella & Chlamydia
Drug of choice for community acquired pneumonia(Mycoplasma/Legionella/ Chlamydia)
Used in respiratory tract infections
Pertussis
Campylobacter jejuni gastroenteritis
MAC (Azalides)
Alternative agents for Group A,C,G streptococcal infections, rheumatic fever prophylaxis, C. trachomatis urethritis, anthrax

18. Chloramphenicol Binds to 50S ribosomal subunit reversibly
Prevents attachment of aminoacyl-tRNA to its binding site
Amino acid substrate is unavailable for peptidyl transferase & peptide bond formation

19. Chloramphenicol(contd.)
Broad spectrum and bacteriostatic
Exerts dose dependent myelosuppression
1 in develop irreversible aplastic anemia
Newborn infants lack effective glucuronide conjugation mechanism for chloramphenicol biotransformation(gray baby syndrome when dosage > 50 mg/kg/d given to infants)
Seldom used now
Low cost, broad spectrum and efficacy in enteric fever

20. Chloramphenicol-Therapeutic Uses
Bacterial meningitis, alternative cephalosporin
Brain abscess
Enteric fever, majority are resistant
Rocky Mountain spotted fever, alternative to tetracycline

21. Tetracyclines
Broad spectrum and bacteriostatic
Have four fused cyclic rings
Usually used orally, IV and topical preparation are available
Tetracycline/Doxy-cycline/Minocycline

22. Tetracyclines (contd.)
Bind to 30 S ribosomal subunit
Prevent binding of tRNA to mRNA
Inhibit protein synthesis
Chelated by cations- calcium, magnesium and aluminum containing antacids, dairy products, calcium supplementation and sucralfate

23. Tetracyclines(contd.)
Gram +ve and Gram –ve bacteria
Chlamydiae, mycoplasmas, spirochetes, rickettsial infections, Legionella species and Brucella species
Useful in acne vulgaris
Strong affinity for developing bone and teeth, to which they give yellow color
Contraindicated in pregnant and breast feeding women and children under 8 years of age

24. Tetracyclines(contd.)
All tetracyclines produce –ve nitrogen balance & increased BUN levels
Clinically important in patients with impaired renal function
Tetracyclines NOT to be used in anuric patients (with the exception of doxycycline)

25. Aminoglycosides-Salient Features
Streptomycin, Neomycin, Gentamicin
Bind to 30 S ribosomal subunit & inhibit protein synthesis
Decrease accuracy of genetic code translation
Proteins containing improper sequence of amino acids (nonsense proteins) are often non-functional
Bactericidal action

26. Aminoglycosides-Salient Features
Active against
Gram –ve bacilli
staphylococci and
mycobacteria
For enterococci they are combined with penicillin G or ampicillin or vancomycin

27. Aminoglycosides-PK
Not absorbed from GIT (Minimal absorption following oral administration)
Given parenterally (i.m., i.v.)
Limited tissue distribution due to polarity
Not metabolized & excreted unchanged by the kidney
Toxicities
Nephro toxicity
Ototoxicity

28. Aminoglycosides-Therapeutic Uses
Gentamicin is most frequently used against enterococci(e.g., enterococcal endocarditis) as synergistic combination with penicillins/ Vancomycin
Ophthalmic preparation of gentamicin available
Streptomycin can be used as part of multi drug regimen for tuberculosis and it is the drug of choice for plague, tularemia
Neomycin not used parenterally but given orally in hepatic encephalopathy