1. Inhibitors of cell wall synthesis (β-Lactam Antibiotics )
1. PENICILLINS 2.Cephalosporins
3.Carbapenems ( Imipenem )
4. Monobactams ( Aztreonam)

2. Penicillins Classification Narrow spectrum penicillins
Antistaphylococcal penicillins
Extended –spectrum penicillins .

3. Mechanism of action
Like all β-lactam antibiotics , inhibit the synthesis of bacterial cell wall .
They are bactericidal on the actively growing bacteria.

4. Pharmacokinetics Absorption
Depending on acid stability & protein binding
Absorption of most oral penicillins is impaired by food except amoxicillin .

5. Metabolism & Excretion
Not metabolised
Excreted unchanged in urine
Probenecid blocks their secretion
Nafcillin is mainly cleared by biliary route
Oxacillin by both kidney & biliary route.

6. Distribution Relatively insoluble in lipid
Poor penetration into cells and BBB Inflammation permits entrance into CSF.
Proteins binding vary from 20%-90%

7. Narrow spectrum penicillins
Penicillin G
Short duration
Acid unstable
Penicillinase (β- lactamase ) sensitive
Used in infections caused by streptococci, meningococci, enterococci & non-β- lactamase – producing staphylococci.

8. Phenoxymethyl penicillin (P. V)
Less effective than penicillin G
Acid stable
Penicillinase sensitive
Short acting ( four times/day)
Used in minor infections

9. Procaine penicillin Long acting (every 12 h ) .
Acid unstable ( I.M.I )
Penicillinase sensitive
Used to prevent subacute bacterial endocarditis due to dental extraction or tonsillectomy in patients with congenital or acquired valve disease .

10. Benzathine penicillin
Long acting (every 3-4 weeks )
Acid unstable ( I.M.I )
Penicillinase sensitive
Treatment of β-hemolytic streptococcal pharyngitis.
Used as prophylaxis against reinfection with β- hemolytic streptococci so prevent rheumatic fever .
Once a week for 1-3 weeks for treatment of syphilis (2.4 million units I.M.)

11. Penicillinase resistant to staphylococcal β-lactamase producer
Methicillin acid unstable
Nafcillin its absorption is erratic
Oxacillin, Cloxacillin,Dicloxacillin (acid stable ).
Used in minor & severe Stap. infections

12. Extended spectrum penicillins
Aminopenicillins
Carboxypenicillins
Ureidopenicillins
Retain the spectrum of Penicillin G, but having greater activity against gram –negative bacteria.

13. Aminopenicillins(Ampicillin &Amoxicillin)
Therapeutic uses
H. influenza infections
E. coli
Ampicillin ( not amoxicillin) is effective for shigellosis & complicated salmonella infections.
Prophylaxis of infective endocarditis
Urinary tract infections
Effective against penicillin –resistant pneumococci

14. Carboxypenicillins(Ticarcillin)&Ureidopenicillin(Piperacillin)
Effective against pseudomonas aeruginosa & Enterobacter organisms.
Ampicillin , amoxicillin , ticarcillin & piperacillin are available in combination with β-lactamase inhibitors as clavulanic acid ,sulbactam or tazobactam.

15. Adverse effects of penicillins
Hypersensitivity reactions
High dose in renal failure ---seizure
Naficillin (neutropenia)
Oxacillin (hepatitis)
Methicillin(nephritis)
Oral penicillins may lead to GIT upset. Ampicillin has been associated with pseudomembraneous colitis

16. Cephalosporins First-Generation Cefazolin, Cephalexin, cephradin.
Are very effective against gram- positive cocci
Are given orally ,except cefazolin given I.V.I ,or I.M.

17. Excretion & Distribution
Through kidney
Probenecid block tubular secretion and increase plasma level .
Can not cross B.B.B.

18. Clinical uses Urinary tract infections
Minor Staph.infections or minor polymicrobial infections as cellulitis or soft tissue abscess.
Cefazolin is the drug of choice for surgical prophylaxis, also as alternative to antistaph.penicillin in allergic patients .

19. Second -Generations Cefaclor ,Cefamandole, Cefonicid, cefuroxime
Less active against gram-positive bacteria than first generation
Have extended gram –negative effect
No effect on P-aeruginosa or enterococci.

20. Pharmacokinetics Given orally or parenterally Can not cross B.B.B.
Excreted through kidney
Cefonicid is highly protein binding

21. Clinical uses β -lactamase-producing H-influenza infections
Mixed anaerobic infections as peritonitis .
Community acquired pneumonia

22. Third -Generations Cefoperazone,Ceftazidime ,Ceftriaxone
Have extended gram- negative spectrum.
Some of them have an effect on P-aeruginosa ( ceftazidme ) .
No effect on E-coli.

23. Pharmacokinetics Main route I.V.I.
Ceftriaxone has a long half- life (7-8h).can be given once every 24h.
Cross B.B.B.
Excreted through kidney .(Ceftriaxone & cefoperazone through bile ).

24. Clinical uses Serious infections
Cceftriaxone is first line for treatment of gonorrhea & drug of choice in meningitis.
P-aeruginosa infections ( ceftazidime ).
In penicillin-resistant pneumococci

25. Fourth -Generations Cefepime
More resistant to hydrolysis by β-lactamase
Active against P-aeruginosa & E-coli
Clinical use as third generations.

26. Adverse Effects of cephalosporins
Allergy
Thrombophilibitis
Interstitial nephritis and tubular necrosis mainly with cephaloridine.
Cephalosporins that contain a methylthiotetrazole group as cefamandole ,cefoperazone cause :hypoprothrombinemia & bleeding disorders

27. Vitamin K twice weekly can prevent this. .
Methylthiotetrazole ring causes severe disulfiram-like reaction ( alcohol or alcohol medication must be avoided ).
Superinfections.
Diarrhea.

28. Carbapenems
Imipenem
Bctericidal, inhibit bacterial cell wall synthesis.
Has a wide spectrum of activity
Resistant to most β lactamases except metallo-β lactamase .

29. Pharmacokinetics Not absorbed orally,taken by I.V.I.
Inactivated by dehydropeptidases in renal tubules, so it is given with an inhibitor cilastatin for clinical use.
Penetrates body tissues and fluids including C.S.F.

30. Clinical uses Mixed aerobic and anaerobic infections
Is the β lactam of choice for treatment of enterobacter infections.
Pseudomonal infections
Intrabdominal infections
Febrile neutropenic patient
Septicaemia.

31. Meropenem
Similar to imipenem but it is highly active against gram-negative aerobes .
Not degraded by renal dehydropeptidase

32. Adverse effects Nausea,vomiting,diarrhea
Skin rash and reaction at the site of infusion
High doses in patients with renal failure may lead to seizures
Patients allergic to penicillins may be allergic to carbapenems .

33. Monobactams
Aztronam
Active only against gram-negative aerobic bacteria.
Given I.V.
Similar to β-lactam in mechanism of action
Penicillin-allergic patients tolerate aztronam
Skin rash & elevation of liver enzymes may occur