The document provides a comprehensive overview of beta-lactam antibiotics, detailing their classes, historical development, mechanisms of action, spectrum of antibacterial activity, and adverse effects. It emphasizes the significance of penicillins, cephalosporins, monobactams, and carbapenems, and highlights their clinical uses and limitations. Additionally, it discusses the resistance mechanisms and pharmacokinetics of these antibiotics.

1. BETA LACTAM ANTIBIOTICS
DR PRERANA KADAM (JR-3)
GUIDE: DR SMITA TIWARI
Dr. Prerana Manik Kadam 1

2. OVERVIEW
Classes
History
Classification
Structure and Properties
Mechanism of Action
Antibacterial Spectrum
Uses
Adverse Effects
Dr. Prerana Manik Kadam 2

3. CLASSES
PENICILLINS
CARBEPENEMS
MONOBACTAMS
CEPHALOSPORINS
Dr. Prerana Manik Kadam 3

4. PENICILLINS
Dr. Prerana Manik Kadam 4

5. HISTORY
Sir Alexander Fleming
• Discovered penicillin
accidentally while studying
properties of Staphylococcus
• Named it Penicillin coz the
mould belonged to the genus
Penicillium
• Florey , Chain and Abraham developed a systematic
therapeutic agent from penicillin extract
• Mass production of new drug in World War II;
saved many lives.
• Penicillin is the first antibiotic to be used clinically.
• Fleming won the Nobel Prize in 1945
WORLD WAR II
Penicillium notatum
Penicillium chrysogenum
SERENDIPITY !!
Dr. Prerana Manik Kadam 5

6. STRUCTURE
 Side chains can be split off by amidase
 Other side chains can be attached
 Beta Lactamase breakdown Beta lactam ring and render the penicillin ineffective
Dr. Prerana Manik Kadam 6

7. MECHANISM OF ACTION
Courtesy : Goodman & Gilman’s The Pharmacological Basis of Therapeutics 13th Edition
Dr. Prerana Manik Kadam 7

8. MECHANISM OF ACTION
Cell wall
Peptidoglycan
layer 50-100
molecules thick
Cell wall
Peptidoglycan
layer 1-2
molecules
thick
Only
peptidoglycan
layer
Alternate
lipoprotein
and
peptidoglycan
layer
Extensively
crosslinked
Little
crosslinking
GRAM POSITIVE GRAM NEGATIVE
Courtesy : Goodman & Gilman’s The Pharmacological Basis of Therapeutics 13th Edition
BETA
LACTAMASES
PORIN
CHANNELS
Dr. Prerana Manik Kadam 8

9. Alterations in PBPs
Inability of the agent to penetrate to its site of action
Active efflux pumps - removing the antibiotic from its site of action
Producing β-lactamases
MECHANISM OF RESISTANCE
Dr. Prerana Manik Kadam 9

10. Acid labile – orally inactive
Rapid and complete absorption – i.m.
Shorter t1/2 – 30 min
Rapid excretion by glomerular filtration and tubular secretion
Narrow spectrum
PHARMACOKINETIC PROPERTIES
Dr. Prerana Manik Kadam 10

11. LIMITATIONS OF PENICILLIN G
 Poor oral efficacy
 Short duration of action
 Susceptibility to penicillinase
 Narrow spectrum
 Hypersensitivity reactions
Dr. Prerana Manik Kadam 11

12. Acid-resistant alternative to Penicillin G
 Penicillin G (PnG) = Penicillin V similar spectrum
 Penicillin V is Acid resistant  Given orally
 Plasma t1/2 : 30-60 min
 Dose 250-500 mg 6 hrly
PHENOXYMETHYL PENICILLIN ( PENICILLIN V)
Dr. Prerana Manik Kadam 12

13. LIMITATIONS OF PENICILLIN G
 Poor oral efficacy
 Short duration of action
 Susceptibility to penicillinase
 Narrow spectrum
 Hypersensitivity reactions
Dr. Prerana Manik Kadam 13

14. BENZATHINE PENICILLIN PROCAINE PENICILLIN
0.6 – 2.4 MU im
2-4 weeks
Prophylaxis upto 4 weeks
Dry powder in vial
0.5– 1 MU im
12 – 24 hrly
Fortified: 3 Lac U procaine penicillin
plus 1 Lac U sodium penicillin G for
rapid action
Dry powder in vial
BENZATHINE PENICILLIN PROCAINE PENICILLIN
Dr. Prerana Manik Kadam 14

15. LIMITATIONS OF PENICILLIN G
 Poor oral efficacy
 Short duration of action
 Susceptibility to penicillinase
 Narrow spectrum
 Hypersensitivity reactions
Dr. Prerana Manik Kadam 15

16. INDICATION/MICRO
ORGANISM
DURATION REMARKS
Pneumococcal infection **
• Pneumococcal pneumonia
5days (2-3
days after
fever
subsides)
PnG
• Pneumococcal meningitis 10-14 days
Treat with vancomycin and third generation
cephalosporin until it is proved pneumococcus is
penicillin sensitive.
PnG 24 million units daily divided doses
Dexamethasone – improves treatment outcomes
USES
Dr. Prerana Manik Kadam 16

17. INDICATION/MICRO
ORGANISM
DURATION
REMARKS
Beta Hemolytic Streptococci
infection **
• Streptococcal pyogenes –
pharyngitis , scarlet fever
10 days
Penicillin V 500mg twice daily
Reduces the risk of subsequent acute rheumatic
fever
Prophylaxis
• Toxic shock and necrotising
fascitis
-
PnG plus Clindamycin to decrease toxin
production
• Pneumonia, meningitis,
arthritis, endocarditis
2-4 weeks PnG 12-24 million units
Streptococci viridans** 4-6 weeks
Endocarditis : 20 million units iv PnG with
Gentamicin
Aminoglycoside sensitive 
24 million units PnG with 12g ampicillin daily
with low dose Gentamicin
Dr. Prerana Manik Kadam 17

18. INDICATION/MICRO
ORGANISM
DURATION REMARKS
Anaerobic infection
Pulmonary and periodontal
infections
7-10 days
Clindamycin preferred
Mild : Penicillin V 250 mg four times daily
Severe : PnG 20 million units iv
Meningococcal infection** -
PnG DOC
But it does not eliminate carrier state
Not given prophylactically
Neisseria gonorrhoea -
PnG i.m. 2 divided doses, 2 different sites,
after 1g of probenecid orally.
Dr. Prerana Manik Kadam 18

19. INDICATION/MICRO
ORGANISM
DURATION REMARKS
Syphilis
Primary, Secondary and Latent 1-3 weeks
PnG 2.4 million units
Prophylaxis
Neurosyphilis or cardiovascular
syphilis
10-14 days
18-24 million units PnG
Safe in pregnant patients
Secondary syphilis: Jarisch Herxheimer
reaction
Actinomycosis 6 weeks PnG 18-24 million units iv per day
Anthrax** 2 weeks 24 million units per day
Dr. Prerana Manik Kadam 19

20. INDICATION/MICRO
ORGANISM
DURATION REMARKS
Clostridial infections
Gas gangrene 1-3 weeks
PnG or Benzathine Penicillin
2.4 million units
Tetanus
10-14 days
18-24 million units PnG
Safe in pregnant patients
Secondary syphilis: Jarisch
Herxheimer reaction
Diphtheria 12 days
Specific antitoxin is the only
antidote
PnG eliminates the carrier
state
2.3 million units per day
Dr. Prerana Manik Kadam 20

21. NARROW
SPECTRUM
GRAM POSITIVE GRAM NEGATIVE RESISTANT
Streptococci
Neisseria gonorrheae
Neisseria meningitis
Streptococci viridans ,
group D, Enterococci
S. aureus and S.
epidermidis
Bacillus anthracis Pneumococci
Corneybacterium
diphtheriae
Bacteroides fragilis
All Clostridia Amebae
Listeria Plasmodia
Spirochetes Rickettssiae
Actinomycetes israeli Fungi
Viruses
Dr. Prerana Manik Kadam 21

22. ADVERSE REACTIONS
Hypersensitivity Jarisch Herxheimer reaction Superinfection
Nephrotoxicity Neurotoxicity
Dr. Prerana Manik Kadam 22

23. CLASSIFICATION
Courtesy : Essentials of Medical Pharmacology, KD Tripathi. 8th Edition
Dr. Prerana Manik Kadam 23

24.  Poor oral efficacy
 Short duration of action
 Susceptibility to penicillinase
 Narrow spectrum
 Hypersensitivity reactions
WHY SEMISYNTHETIC?
Dr. Prerana Manik Kadam 24

25. Penicillinase resistant Penicillins
• Have side chains - protect Beta lactam ring from attack by staphylococcal penicillinase
• Non-penicillinase producing organisms are less sensitive to these drugs than PnG
METHICILLIN, CLOXACILLIN, DICLOXACILLIN
Not resistant to the beta – lactamases produced by gram negative organisms
ONLY INDICATION
Infections due to Penicillinase
producing Staphylococcal
which are not Methicillin
resistant
Dr. Prerana Manik Kadam 25

26. Methicillin
Cloxacillin
/Dicloxacillin
Acid labile Penicillinase and acid
resistant - PO
Nafcillin Oxacillin/Flucloxacillin
Acid labile Penicillinase and acid
resistant - PO
MRSA(METHICILLIN-RESISTANT STAPH AUREUS
Insensitive to Penicillinase resistant penicillins and other Beta Lactam
antibiotics
Dr. Prerana Manik Kadam 26

27. PENICILLINS
Dr. Prerana Manik Kadam 27

28. Beta Lactamase Inhibitors
Beta Lactamases -- family of enzymes -- many gram-positive
and gram-negative bacteria that inactivate beta-lactam antibiotics
by opening the beta-lactam ring.
CLAVULANIC ACID
Nil intrinsic
antimicrobial activity
‘Suicide’ inhibitor
Combined with
amoxicillin as an oral
preparation
Combined with
ticarcillin as a
parenteral preparation.
SULBACTAM
 structure = Clavulanic
acid
intravenous or
intramuscular use
Ampicillin +
Intrinsic activity against
Acinetobacter ++
High doses -- treat
multidrug-resistant
Acinetobacter infections
TAZOBACTAM
 activity against many of
the plasmid β-lactamases,
including some of the extended
spectrum class +++
 Tazobactam+ piperacillin –
parenteral
AVIBACTAM
 non–β-lactam β-lactamase
inhibitor that provides clinically
useful inhibition against narrow-
spectrum, ESBL-type,
chromosomal AmpC, and KPC-
type β-lactamases (although not
metallo-β-lactamases).
 Avibactam + ceftazidime –
parenteral
Dr. Prerana Manik Kadam 28

29.  Poor oral efficacy
 Short duration of action
 Susceptibility to penicillinase
 Narrow spectrum
 Hypersensitivity reactions
WHY SEMISYNTHETIC?
Dr. Prerana Manik Kadam 29

30. Extended Spectrum Penicillin
Dr. Prerana Manik Kadam 30

31. 1) AMINOPENICILLINS : AMPICILLIN, BACAMPICILLIN
AMOXICILLIN
PARAMETER AMPICILLIN AMOXICILLIN BACAMPACILLIN
Acid stable Yes
Yes
Not a prodrug
Yes
Ester prodrug of
ampicillin
Frequency of
administration
QID TID QID
Oral absorption ++ ++++ ++++
Diarrhoea
++++
Unabsorbed drug
irritates lower
intestine, causes
marked alteration in
bacterial flora
++ ++
Dr. Prerana Manik Kadam 31

32. PARAMETER AMPICILLIN AMOXICILLIN BACAMPACILLIN
Spectrum  PnG plus S. viridans, enterococci
and Listeria
Less active  Shigella
and H. influenza
More active  penicillin
resistant S. pneumoniae
S. viridans, enterococci
and Listeria
Excretion
Bile excreted &
Primary excretion through
kidney
DDI
Enterohepatic circulation
If affected by alternation
in colonic flora, failure of
OCP can occur
Clinically relevant DDI
- -
1) AMINOPENICILLINS : AMPICILLIN, BACAMPICILLIN
AMOXICILLIN
Dr. Prerana Manik Kadam 32

33. PARAMETER AMPICILLIN AMOXICILLIN BACAMPACILLIN
Uses
UTI : FQs DOC
Not empirical therapy
RTI : Higher doses
Meningitis** :
combine with third
generation
Cephalosporin
Gonorrhea: 1st line
drug
Cholecystitis :
Ampicillin preferred
due to higher
concentration in bile
H pylori kit
ANUG :
Aminopenicillins
combined with
metronidazole
Preferred by
physicians in
UTI
Bronchitis
SABE
Gonorrhea
Seldom used now
1) AMINOPENICILLINS : AMPICILLIN, BACAMPICILLIN
AMOXICILLIN
Dr. Prerana Manik Kadam 33

34. 2) CARBOXYPENICILLINS : CARBENECILLIN, TICARCILLIN
CARBENECILLIN TICARCILLIN
Pseudomonas aeruginosa ++++
Indole positive Proteus ++++
More active
Im  1-2 g
Iv  1-5 g every 4-6 hrs (Na salt)
Not a sodium salt
A/E –
Higher doses
• fluid retention and CHF in pts of borderline
cardiac functions ( Na salt)
• Bleeding by interfering with platelet function
Produces fewer side effects
Severe infections-
Pseudomonas , Proteus
Burns, UTI, septicimia
Combined with clavulanic acid – covers beta
lactamase producing organisms
Pseudomonas - used with gentamicin
Dr. Prerana Manik Kadam 34

35. 3) UREIDOPENICILLIN : PIPERACILLIN
 Anti-pseudomonal penicillin, Activity against Klebsiella ++++
 Not active against MRSA
 More active than carbenicillin
 Piperacillin  serious gram-negative infections in neutropenic /
immunocompromised or burn patients.
 Piperacillin + tazobactam covers beta -lactamase producing strains
Dr. Prerana Manik Kadam 35

36. • Poor oral efficacy
• Short duration of action
• Susceptibility to penicillinase
• Narrow spectrum
• Hypersensitivity reactions
WHY SEMISYNTHETIC?
SCRATCH
TEST
i.d.
PENICILLOY
POLYLYSINE
Dr. Prerana Manik Kadam 36

37. CEPHALOSPORINS
Dr. Prerana Manik Kadam 37

38. INTRODUCTION
 Prof Brotzu Cultures of sea water at sewage
outfall  fungus Cephalosporium acremonium
 antagonistic to intestinal pathogen Florey
1955 extracted and refined.
 7-aminocephalosporanic acid
Beta lactam ring and dihydrothiazine ring
 MOA  Same as Penicillin alters cell wall
synthesis
 MOR  Same as Penicillin Cephalosporinase
Dr. Prerana Manik Kadam 38

39. Dr. Prerana Manik Kadam 39

40. CLASSIFICATION
Courtesy : Essentials of Medical Pharmacology, KD Tripathi. 8th Edition
Dr. Prerana Manik Kadam 40

41. FIRST
GENERATION
SECOND
GENERATION
• Spectrum  Gram positive+++
Gram negative ++
Salmonella, Shigella, B. fragilis,
Pseudomonas ××××
• Beta Lactamases sensitive
• CEFALEXIN / CEFADROXIL 
Community acquired , respiratory, urinary
tract infections and Sx prophylaxis
• CEFAZOLIN  DOC Sx prophylaxis
Given i.m. or i.v.
• Spectrum  Gram positive ++
Gram negative ++++
• Beta Lactamases resistant
• Pseudomonas, anaerobes ××××
• Indication  Beta lactamase producing bacteria
including H. Influenzae
• CEFFOXITIN / CEFOTETAN
• B. fragilis ++++
Replaced by Third Generation cephalosporins
Dr. Prerana Manik Kadam 41

42. THIRD GENERATION
• Spectrum  Gram positive +
Gram negative +++++++
• Beta Lactamases resistant
• Pseudomonas, anaerobes ++++
• Indication  Beta lactamase producing bacteria including H. Influenzae (better CNS
penetration)
• CEFTRIAXONE
Long t1/2 once daily dosing
Indication  Routine Sx prophylaxis
Aminoglycoside resistant or MDR Gram negative infections (replaced 2nd Gen)
Serious Gram negative infections– combined with Gentamicin or Amikacin
Dr. Prerana Manik Kadam 42

43. FOURTH
GENERATION
FIFTH
GENERATION
• Spectrum  same as 3rd Gen
• Beta Lactamases more resistant
• Activity against MSSA and streptococci ++++
• CEFIPIME  Serious Gram negative
infections (enterobacter, citrobacter and serratia
infections)
Excellent CNS penetration
Dose 2g iv 12 hrly
• CEFPIROME  higher CNS penetration
• Activity against MRSA and streptococcus
pneumoniae  ++++ used in skin and soft tissue
infections
• CEFTAROLINE  Extended spectrum
• Aerobic and anaerobic Gram positive and
aerobic Gram negative
Dose 600mg iv 12 hrly
• CEFTOBIPROLE  binds to PBP 2a
MRSA, penicillin resistant Streptococcus
pneumoniae, Pseudomonas and enterococci
++++
Indication  Community and hospital acquired
pneumonia, ventilator associated pneumonia
Dose  500 mg iv 12hrly
Dr. Prerana Manik Kadam 43

44. ADVERSE REACTIONS
Hypersensitivity Diarrhoea Bleeding
Neutropenia
Nephrotoxicity Disulfiram like reaction
Dr. Prerana Manik Kadam 44

45. MONOBACTAMS
Dr. Prerana Manik Kadam 45

46. Single ring produced by bacteria  beta lactam antibiotic  acts by binding to
specific PBPs
Narrow spectrum Gram negative aerobic species , H. influenzae,
E.coli, Klebsiella, Proteus, Pseudomonas++++
Gram positive cocci or anaerobes ××××
Resembles aminoglycosides
Resistant to gram-negative beta lactamases
Indication :-
Hospital-acquired infections  urinary, biliary, gastrointestinal and female genital
tracts
AZTREONAM
Dr. Prerana Manik Kadam 46

47. Advantages
• Lack of cross sensitivity with other beta lactam antibiotics except ceftazidime
(which has chemical similarity to aztreonam)
• Used in patients allergic to penicillins or cephalosporins
A/E  Rashes
Rise in serum aminotransferases
Dose: 1- 2 g i.m or i.v. 8-12 hourly
AZTREONAM
Dr. Prerana Manik Kadam 47

48. Carbapenems
Dr. Prerana Manik Kadam 48

49. • Derivative of thienamycin  Imipenem  first member
• Extremely potent and broad-spectrum beta lactam antibiotic
Gram positive cocci, Enterobacteriaceae, P. aeruginosa, Listeria
anaerobes - B. fragilis and C. difficile.
resistant to most beta lactamases; inhibits penicillinase producing staphylococci (not reliable for
MRSA infections)
• Limiting feature of imipenem  rapid hydrolysis by the enzyme dehydropeptidase
 innovative solution - combination with cilastatin (reversible
inhibitor of dehydropeptidase)
All carbapenems are eliminated by the kidney (dose reduction in renal failure)
IMEPENEM, MEROPENEM, FAROPENEM, DORIPENEM,
ERTAPENEM
Dr. Prerana Manik Kadam 49

50. • Dose  Imipenem-cilastatin 0.5 g i.v. 6 hourly (max 4 g/day)
• Indication
serious hospital-acquired respiratory,
urinary, abdominal, pelvic, infections
skin and soft tissue infections including those in neutropenic, cancer and AIDS
patients
P. aeruginosa infection imipenem + gentamicin
• A/E
propensity to induce seizures
Diarrhoea, vomiting, skin rashes
IMEPENEM, MEROPENEM, FAROPENEM, DORIPENEM,
ERTAPENEM
Dr. Prerana Manik Kadam 50

51. PARAMETERS MEROPENEM FAROPENEM DORIPENEM ERTAPENEM
Dihydropeptidase ××× ++ ××× ++
Spectrum
Gram positive +
Gram negative
+++
Gram positive +
Gram negative
+++
Same as
Meropenem
Pseudomonas ++
Less broad
spectrum
Uses
Nosocomial
infections 
septicaemia,
intraabdominal,
pelvic infections,
diabetic foot.
P. aeruginosa
infections
meropenem +
aminoglycoside
Strep. pneumoniae,
H. influenzae,
Moraxella
cafarrhalis  +++
Hence,
Respiratory, ET
Genitourinary
infections.
Same as
Meropenem
E.coli,H.influenzae,
K.pneumoniae,
Moraxella, Proteus,
many anaerobes 
++++
Pseudomonas,
Acinetbacter,
MRSA, PR S.
pneumoniae  ----
IMEPENEM, MEROPENEM, FAROPENEM, DORIPENEM,
ERTAPENEM
IMEPENEM, MEROPENEM, FAROPENEM, DORIPENEM,
ERTAPENEM
Dr. Prerana Manik Kadam 51

52. PARAMETERS MEROPENEM FAROPENEM DORIPENEM ERTAPENEM
Seizure
propensity
+ - ++ ++
Dose
0.5 - 2.0 g i. v.
8 hourly.
150-300 mg oral
TDS
500 mg iv TDS 500 mg iv OD
A/E
Abdominal pain,
diarrhoea , rashes
Nausea,
diarrhoea,
superinfections,
thrombophlebitis
Resistance Efflux pump
IMEPENEM, MEROPENEM, FAROPENEM, DORIPENEM,
ERTAPENEM
IMEPENEM, MEROPENEM, FAROPENEM, DORIPENEM,
ERTAPENEM
Dr. Prerana Manik Kadam 52

53. SUMMARY
1. Beta lactam antibiotics are four major bactericidal classes of drugs:
Penicillin Cephalosporins Monobactams Carbapenems
2. These narrow spectrum antibiotics which are chemically altered to increase
their
spectrum, thus giving birth to extended spectrum antibiotics
3.They should be appropriately used with respect to their spectrum to ensure
proper treatment.
4. These antibiotics should be used cautiously to avoid growing concern of
‘antibiotic resistance’
Dr. Prerana Manik Kadam 53

54. Dr. Prerana Manik Kadam 54