This is my 52nd powerpoint...deals with various drugs that inhibit cell-wall synthesis, their spectrum of activity, ADRs & important applications in infections. Newer molecules have also been elucidated here. HAPPY READING!!

1. PRESENTED BY,
VISHNU.R.NAIR,
5TH YER PHARM.D,
NATIONAL COLLEGE OF PHARMACY(NCP).

2. GENERAL INTRODUCTION

3. - Here, primarily, important catchpoints on the following will be made:
A. BETA-LACTAM ANTIBIOTICS
B. BETA-LACTAMASES
C. OTHER CELL-WALL SYNTHESIS INHIBITORS.
- Very precise insight into individual drugs, their do’s and dont’s & special
information has been elucidated
- For extensive insight, substantial referring of textbooks is advised!!!
HAPPY READING!!!

4. BETA-LACTAM
ANTIBIOTICS

5. Consist of drugs, that contain BETA-LACTAM RING in their
structure
Act, by inhibiting cell-wall synthesis
Include:
A. PENICILLINS
B. CEPHALOSPORINS
C. MONOBACTAMS
D. CARBAPENEMS

6.  All BETA-LACTAM antibiotics are BACTERICIDAL in nature
 Drugs  bind to specific receptors on bacterial cell membrane(Penicillin Binding
Proteins, PBPs)  inhibit TRANSPEPTIDASE enzyme  prevents CROSS-
LINKING of PEPTIDOGLYCAN chains
 Bacteria formed in the presence of beta-lactams  lack CELL-WALL
 Since cell-wall is vital for providing rigidity to the cell  lack of cell-wall in
susceptible bacteriae causes IMBIBITION of water  causes death of susceptible
organisms!
 Bacteria like MYCOPLASMA  lack CELL-WALL  thus, INTRINSICALLY
RESISTANT TO BETA-LACTAMS & VANCOMYCIN!!

7. PENICILLINS

8.  PENICILLIN G  commercially obtained from Penicillium chrysogenum
 PENICILLIN G  only NATURAL OCCURRING PENICILLIN!!!
 Important limitations of clinical use of Penicillin G include:
1. Drug  undergoes rapid breakdown by acid inside stomach  hence, NOT
EFFECTIVE ORALLY!
2. Drug  rapidly excreted from kidney, via TUBULAR SECRETION  thus, has
SHORT DURATION OF ACTION!
3. Drug  covers mainly GRAM-POSITIVE BACTERIA  has NARROW
SPECTRUM OF ACTIVITY!
4. Most of the Gram-positive bacteria have become resistant to Penicillin G, due
to the following reasons:
a. Development of BETA-LACTAMASE(penicillinase)
b. Development of altered PBPs!!
5. Penicillin G  can cause severe hypersensitivity reactions!!

9.  To overcome above shortcomings of Penicillin G  newer penicillins have been
designed!
 STRATEGIES to overcome Penicillin G shortcomings:
a. Development of ACID-RESISTANT PENICILLINS:
- Pn G(Penicillin G) is not effective orally due to high acid lability
- Newer penicillins have been developed that are ACID-RESISTANT  thus can be
given orally!
- Include OXACILLIN, PENICILLIN V, DICLOXACILLIN, CLOXACILLIN,
AMOXICILLIN, AMPICILLIN, etc
b. Pn G is SHORT-ACTING. Strategies to overcome this problem include:
- Addition of BENZATHINE/ PROCAINE group to Pn G  can make it long-acting
- BENZATHINE PN G  longest-acting penicillin!
- PROBENECID  if given with Penicillin G  tubular secretion of latter will be
inhibited!

10. - Since Pn G has WIDE THERAPEUTIC INDEX  HIGH INITIAL doses of drug
can be used!!
c. Strategy, to overcome narrow-spectrum activity of Pn G:
- Several new penicillins, with extended-spectrum have been developed
- Include AMINOPENICILLINS, CARBOXYPENICILLINS,
UREIDOPENICILLINS
d. Strategy to overcome resistance issues with Penicillin G:
- Beta-lactamase inhibitors  if added to Penicillin G  causes inhibition of
bacterial enzyme  penicillins escape degradation!
- Administration of PENICILLINASE-RESISTANT PENICILLINS, like
CLOXACILLIN OXACILLIN, NAFCILLIN, DICLOXACILLIN &
METHICILLIN.

11. e. Strategies, to prevent risk of hypersensitivity with Pn G:
- Hypersensitivity reactions can occur with ANY PENICILLIN
- PENICILLINS  most common drugs responsible for ANAPHYLACTIC SHOCK
- If a person is severely allergic to any penicillin  NO BETA-LACTAM
ANTIBIOTIC SHOULD BE ADMINISTERED TO THAT PERSON!!(Except
AZTREONAM)
- To prevent severe allergic reactions  INTRA-DERMMAL SKIN TESTING can
be opted!

12. HOW TO REMEMBER NAMES OF ACID-RESISTANT
PENICILLINS???
USE THE CODE “VODKA”!!
“V”: Penicillin V
“O”: Oxacillin
“D”: Dicloxacillin
“K”: Cloxacillin
“A”: Amoxicillin, ampicillin!!

13. HOW TO REMEMBER THE NAMES OF PENICILLINASE-
RESISTANT PENICILLINS??
USE THE CODE: “CONDOM”!!
“C”: Cloxacillin
“O”: Oxacillin
“N: Nafcillin
“DO”: Dicloxacillin
“M”: Methicillin!!

14. HOW TO REMEMBER NAMES OF EXTENDED-
SPECTRUM PENICILLINS??
USE THE CODE: “ACT MAP”!!
1. AMINOPENICILLINS:
“A”: Ampicillin, amoxicillin
2. CARBOXYPENICILLINS:
“C”: Carbenicillin
“T” : Ticarcillin
3. UREIDOPENICILLINS:
“M”: Mezlocillin
“A”: Azlocillin
“P”: Piperacillin!!

15. All extended-spectrum penicillins  effective against Gram-
negative bacteria like E.coli, salmonella, shigella(except
AMOXICILLIN!!)
CT-MAP Penicillins  effective against PSEUDOMONAS!!
MAP-penicillins  effective against KLEBSIELLA!!

16. PHARMACOKINETICS:
- 1 gram of PENICILLIN  equivalent to 1.6 million units
- Gastric acid  breaks down penicillins  results in reduced oral bioavailability
- Pn G  used ORALLY only for those infections, in which clinical experience has
proven efficacy!
- AMPICILLIN & NAFCILLIN  excreted partly in bile
- Benzyl penicillin is given by i.m injection
- Drug  has short t1/2 thus given 6-12 hourly
- Procaine & benzathine penicillin are LONG-ACTING(due to slow release)

17. CLINICAL USES OF DIFFERENT PENICILLINS:
A. PENICILLIN G:
- DOC for SYPHILIS
- Role of BENZATHINE PENICILLIN in SYPHILIS:
i. For PRIMARY, SECONDARY & EARLY LATENT SYPHILIS : 2.4 million units
i.m, as single dose
ii. For LATE LATENT & TERTIARY SYPHILIS: Duration of treatment is 3
weeks(once weekly!)
- DOC for NEUROSYPHILIS: Aq. Pn G(Since benzathine Pn has little CNS
permeability)
- Given also, for GRAM(+) cocci, MENINGOCOCCI, etc
- Most staphylococci & gonococci are now resistant
- Effective against ANAEROBES (except Bacteroides)!

18. B. METHICILLIN, NAFCILLIN, OXACILLIN & CLOXACILLIN:
- Although mainly given for S.aureus infections  resistant organisms have been
isolated
- MRSA  developed, due to formation of ALTERNATIVE PBPs  possess less
affinity for drugs
- In cases of MRSA  treatment of choice is VANCOMYCIN/ TEICOPLANIN
- In case of VANCOMYCIN resistance(VRSA)  treatment of choice is
LINEZOLID/ STREPTOGRAMINS.

19. C. AMPICILLIN, AMOXICILLIN:
- Wide-spectrum, penicillinase-sensitive antibiotics
- In addition to Gram (+) organisms  they are also effective against:
i. Enterococci
ii. Listeria
iii. Hemophilus organisms!
- Activity of above drugs  enhanced, when used in combination with BETA-
LACTAMASE INHIBITORS(sulbactam, clavulanic acid).
- Special uses of AMPICILLIN:
i. DOC for Listeria meningitis(cephalosporins are ineffective here!)
ii. DOC for UTI caused by E.faecalis.

20. D. PIPERACILLIN, TICARCILLIN, CARBENICILLIN, AZLOCILLIN,
MEZLOCILLIN:
- Possess activity against GRAM-NEGATIVE RODS (including Pseudomonas
species!)
- Used along with BETA-LACTAMASE INHIBITORS & along with
AMINOGLYCOSIDES
- UREIDOPENICILLINS  highly effective against KLESIELLA species!!

21. HOW TO REMEMBER IMPORTANT USES OF
PENICILLIN G(DOC)???
USE THE CODE : “LAST MAN”!!!
“L” : Leptospira
“A”: Actinomyces
“S”: Streptococcus, staphylococcus(non-penicillinase
producing)
“T”: Treponema, Tetanus(also gas gangrene!)
“M”: Meningococcus
“AN”: Anthrax(Ciprofloxacin is also 1st line agent!)

22. TOXICITY ISSUES WITH PENICILLINS:
1. HYPERSENSITIVITY REACTIONS:
- Serum sickness
- Anaphylaxis
- It is MANDATORY to conduct INTRA-DERMAL SENSITIVITY TESTING before
giving PENICILLINS!
- If a patient develops hypersensitivity reaction to Penicillins  ALL OTHER
BETA-LACTAM ANTIBIOTICS are CONTRAINDICATED(except
AZTREONAM!!!)
2. AMPICILLIN  if used in patients with viral diseases like “infectious
mononucleosis”  can cause development of MACULOPAPULAR SKIN RASHES!
3. METHICILLIN  can cause ACUTE INTERSTITIAL NEPHRITIS
4. NAUSEA & DIARRHEA with oral drugs like AMOXICILLIN & AMPICILLIN

23. 5. AMPICILLIN  incompletely absorbed  causes increased suppression of
normal microbial flora  can cause higher incidence of DIARRHEA!
6. AMPICILLIN  can also cause PSEUDOMEMBRANOUS COLITIS
7. PROCAINE PENICILLIN  given in high doses  can cause SEIZURES &
CNS ABNORMALITIES
8. OXACILLIN  can cause HEPATITIS
9. NAFCILLIN  can cause NEUTROPENIA
10. CARBENICILLIN  given in high dose  can cause BLEEDING!

24. CEPHALOSPORINS

25. BETA-LACTAM antibiotics, having 7-
AMINOCEPHALOSPORANIC ACID nucleus
Classified into 5 generations.

26. CEPHALOSPORIN GENERATION ORAL PARENTERAL
FIRST Cephalexin, cefadroxil, cephradine Cefazolin
SECOND Cefaclor, cefuroxime axetil,
loracarbef, cefprozil
Cefuroxime, cefotetan, cefoxitin,
cefmetazole
THIRD Cefixime, cefopodoxime, ceftibuten,
cefditoren, cefdinir
Ceftriaxone, cefoperazone,
ceftizoxime, cefotaxime,
ceftazidime, moxalactam
FOURTH Cefepime, cefpirome
FIFTH Ceftaroline fosamil, ceftobiprole,
ceftolozane.

27. PHARMACOKINETICS:
- Most cephalosporins  excreted via kidney through TUBULAR SECRETION
- CEFOPERAZONE & CEFTRIAXONE  secreted in the BILE
- Nephrotoxicity of cephalosporins  enhanced with concurrent use of LOOP
DIURETICS!

28. SPECIAL USES & IMPORTANT FEATURES OF
CEPHALOSPORIN GENERATIONS:
A. FIRST-GENERATION CEPHALOSPORINS:
- Active against Gram(+) cocci, including STAPHYLOCOCCI
- MRSA is resistant to cephalosporins as well!
- DOC for SURGICAL PROPHYLAXIS : CEFAZOLIN!

29. B. SECOND-GENERATION CEPHALOSPORINS:
- Has less activity against Gram(+) organisms(compared to 1st generation)
- Extended Gram(-) coverage
- Drugs active against BACTEROIDES FRAGILIS(anaerobe):
i. Cefotetan
ii. Cefmetazole
iii. Cefoxitin.
- CEFUROXIME  attains higher CSF levels (compared to other 2nd generation
drugs)  thus, can be used for BACTERIAL MENINGITIS!(Ceftriaxone is
preferred as empirical, though).
- LORACARBEF  chemically similar to CEFACLOR

30. C. THIRD GENERATION CEPHALOSPORINS:
- Active against GRAM-NEGATIVE ORGANISMS(resistant to other BETA-
LACTAM ANTIBIOTICS)
- Penetrate BBB easily (except CEFOPERAZONE & CEFIXIME)
- Third-generation drugs, active against PSEUDOMONAS:
i. Cefoperazone
ii. Ceftazidime(most active, when used along with aminolglycosides!)
- CEFTAZIDIME  DOC for MELIOIDOSIS (caused by Burkholderia
pseudomallei)
- CEFTIZOXIME  has maximum activity against BACTEROIDES!
- CEFOTAXIME  metabolized to an active metabolite (desacetyl-cefotaxime)

31. - CEFTRIAXONE:
• FIRST-CHOICE DRUG for:
a. Gonorrhea
b. Salmonellosis(including typhoid)
c. E.coli sepsis
d. Proteus species
e. Serratia
f. Hemophilus
g. Bacterial meningitis(empirical therapy).
• Long-term use of > 2g/day of CEFTRIAXONE can result in :
a. Biliary sludging syndrome
b. Cholelithiasis(due to drug precipitation in bile).

32. D. FOURTH-GENERATION CEPHALOSPORINS:
- Possess activity against Gram(-ve) organisms(including PSEUDOMONAS),
resistant to 3rd generation ones!
- Efficacy against G(+) cocci  similar as that of 3rd generation ones!
- Inactive against ANAEROBES!

33. E. FIFTH-GENERATION CEPHALOSPORINS:
- Indicated for CAP & MRSA infections
- Ceftolozane & ceftobiprole  also effective against PSEUDOMONAS!!

34. TOXICITY ISSUES WITH CEPHALOSPORINS:
1. Hypersensitivity reactions
2. Drugs, containing METHYLTHIOTETRAZOLE group can cause
HYPOPROTHROMBINEMIA & DISULFIRAM-LIKE REACTION with
ALCOHOL, that include:
- Cefamandole
- Cefoperazone
- Moxalactam
- Cefotetan
3. CEFTAZIDIME  can cause NEUTROPENIA!!
4. LORACARBEF  in high doses  can cause SEIZURES!

35. MONOBACTAMS

36.  Includes AZTREONAM
 Active against GRAM-NEGATIVE RODS(including Pseudomonas)
 Inactive against Gram-positive organisms/anaerobes
 Given i.v
 T1/2 prolonged in renal failure
 ONLY BETA-LACTAM ANTIBIOTIC, that can be used in patients having
SEVERE ALLERGY TO PENICILLINS/ CEPHALOSPORINS(since it is not
cross-allergenic!!)

37. CARBAPENEMS

38.  Includes:
a. Imipenem
b. Meropenem
c. Doripenem
d. Ertapenem
• Have wide activity against:
a. Gram (+) cocci
b. Gram (-) rods
c. Anaerobes.

39.  MEROPENEM  most active against PSEUDOMONAS
 ERTAPENEM  least active against PSEUDOMONAS
 CARBAPENEMS  BETA-LACTAMASE RESISTANT!!
 For activity against Pseudomonas infections  carbapenems should be given in
combination with AMINOGLYCOSIDES!!
 DOC for :
i. Enterobacter
ii. Klebsiella
iii. Acinobacter species
• Since CARBAPENEMS are the ONLY BETA-LACTAM ANTIBIOTICS that are
efficacious against ESBL(Extended Spectrum Beta-Lactamases)  they are also
DOC for ESBL-producing bacteria!!

40.  IMIPENEM  rapidly inactivated by RENAL DEHYDROPEPTIDASE I  thus
given in combination with CILASTATIN(cilastatin inhibits this enzyme)!
 Additional benefits of CILASTATIN when given with IMIPENEM:
a. Cilastatin  increases t1/2 of imipenem
b. Cilastatin  prevents formation of nephrotoxic metabolite
• Main ADRs of IMIPENEM-CILASTATIN combination:
a. Seizures
b. GI distress.
• MEROPENEM, DORIPENEM & ERTAPENEM  not metabolized by RENAL
DEHYDROPEPTIDASE  less risk of SEIZURES!!
• ERTAPENEM  very long-acting!!

41. BETA-LACTAMASES

42. Refer to “enzymes, that HYDROLYZE beta-lactam
antimicrobials, by acting on BETA-LACTAM ring”
There are 2 basic types of BETA-LACTAMASE
classifications:
A. MOLECULAR CLASSIFICATION(AMBER
CLASSIFICATION):
- Based on STRUCTURE(amino acid sequence)
- Classified into 4 categories: A,B,C & D
- Class “A”, “D” & “C” enzymes  require serine residue to
hydrolyze beta-lactams
- Class “B” enzymes  require ZINC IONS  hence also
known as “METALLO-BETA LACTAMASES”!

43. B. FUNCTIONAL CLASSIFICATION(BUSH
CLASSIFICATION):
- Based on the type of SUBSTRATE of BETA-
LACTAMASE(i.e, which beta-lactam is hydrolyzed)
- Also takes into consideration whether THE ENZYME IS
INHIBITED BY CLAVULANIC ACID(CA)/ OTHER DRUGS

44. BETA-LACTAMASE MOLECULAR GROUP INHIBITED BY SUBSTRATES
CEPHALOSPORINASE C NONE Cephalosporins,
aztreonam
SERINE BETA-
LACTAMASES
A/D CA & TZB
PENICILLINASE A CA & TZB Penicillin G & early
cephalosporins
ESBL A CA & TZB Penicillins,
cephalosporins(NOT
CARBAPENEMS!)
CARBENICILLINASE A CA & TZB Cloxacillin, oxacillin
OXACILLINASE A/D CA & TZB Cloxacillin, oxacillin,
most cephalosporins(not
aztreonam),
carbapenems, cefamycins,
etc
METALLO-BETA
LACTAMASES
B EDTA Carbapenems

45. EXTENDED-SPECTRUM BETA-LACTAMASES: A BRIEF
INSIGHT:
- Enzymes , that offer resistance to MOST BETA-LACTAM antibiotics (Penicillins,
cephalosporins, monobactams)
- Mainly found in G(-ve) organisms, like KLEBSIELLA & E.coli
- Important features include:
a. Can be inhibited by CLAVULANIC ACID/TAZOBACTAM
b. Can hydrolyze:
i. Penicillins
ii. Cephalosporins
iii. Monobactams

46. c. Cannot hydrolyze:
- CEFAMYCINS(Cefoxitin, cefotetan, cefmetazole)
- CARBAPENEMS
d. CARBAPENEMS  DOC for infections caused by bacteria producing ESBL!!

47. BETA-LACTAMASE INHIBITORS

48.  Include:
1. Clavulanic acid
2. Sulbactam
3. Tazobactam
4. Vaborbactam
• More active against PLASMID-ENCODED BETA-LACTAMASES(produced by
gonococci & E.Coli), than against INDUCIBLE CHROMOSOMAL BETA-
LACTAMASES(produced by PSEUDOMONAS & ENTEROBACTER)!
• AMOXICILLIN  combined with clavulanic acid
• AMPICILLIN  combined with SULBACTAM
• PIPERACILLIN  combined with TAZOBACTAM

49.  CEFTAZIDIME-AVIBACTAM combination  FDA-approved for :
a. Complicated UTI (including PYELONEPHRITIS)
b. Complicated intra-abdominal infections
• MEROPENEM-VABORBACTAM  new combination, approved for
COMPLICATED UTI!!!

50. OTHER CELL-WALL
SYNTHESIS INHIBITORS

51.  Includes:
1. GLYCOPEPTIDES
2. FOSFOMYCIN
3. BACITRACIN
4. CYCLOSERINE

52. GLYCOPEPTIDES

53.  Includes:
1. Vancomycin
2. Teicoplanin
3. Oritavancin
4. Telavancin
5. Dalbavancin

54. A. VANCOMYCIN:
- Drug  inhibits “bacterial transglycosylase enzyme”  prevents CHAIN
ELONGATION  causes inhibition of bacterial cell-wall synthesis
- Narrrow-spectrum antibiotic
- Mainly effective against G(+ve) organisms, including MRSA, pneumococci &
C.difficile
- Generally administered via i.v route
- Excreted unchanged in urine
- Rapid i.v infusion of high doses of Vancomycin  results in RED MAN
SYNDROME(diffuse flushing, due to HISTAMINE release)
- Vancomycin  not absorbed from GIT  thus higher concentration of drug can
reach the colon  thus it can BE USED ORALLY FOR THE TREATMENT OF
PSEUDOMEMBRANOUS COLITIS

55.  Toxic effects of vancomycin include:
1. Chills
2. Ototoxicity
3. Nephrotoxicity
• Dose should be reduced in RENAL FAILURE
• In VANCOMYCIN RESISTANCE(to S.aureus & Enterococci) terminal
ALANINE-ALANINE is replaced by ALANINE-LACTATE(of peptidoglycan) 
this reduces affinity of drug for TRANSGLYCOSYLASE.
• Vancomycin is DOC for:
1. MRSA
2. Corynebacterium jeikeium
3. Serious infection in PENICILLIN-ALLERGIC PATIENTS!!

56. B. TEICOPLANIN:
- Similar features as that of vancomycin
- Given once daily, due to long half-life(45-70 hours)
- Given by either i.v/i.m route
- Excreted unchanged in urine
- Does not cause RED MAN SYNDROME/NEPHROTOXICITY!!
C. ORITAVANCIN:
- Newer glycopeptide
- Used for MRSA infections!

57. D. TELAVANCIN:
- Approved for COMPLICATED SKIN & SKIN STRUCTURE INFECTIONS
- Effective against MRSA
- Other than that of vancomycin MOA  it also DISRUPTS MEMBRANE
POTENTIAL of susceptible organisms!!
E. DALBAVANCIN:
- Given as ONCE-WEEKLY DRUG
- Same mechanism as vancomycin
- Additional benefits: Effective against MRSA & VRSA!!!!

58. FOSFOMYCIN

59. - Drug  inhibits ENOLPYRUVATE TRANSFERASE 
prevents cell-wall synthesis
- Most-common ADR: Diarrhea
- DOC(along with NTU) for UNCOMOLICATED UTI!!

60. BACITRACIN

61. Potent cell-wall synthesis inhibitor
Due to high risk of NEPHROTOXICITY  indicated ONLY
FOR TOPICAL USE!
Selectively active against G(+ve) bacteria!

62. CYCLOSERINE

63. Causes NEUROTOXICITY(tremors, seizures)
Can also precipitate NEUROPSYCHIATRIC
MANIFESTATIONS
One of the second-line agent for treatment of
TUBERCULOSIS!

64. CONCLUSION:
- Basically, drugs that inhibit BACTERIAL CELL-WALL SYNTHESIS has been
explained here
- Summarized names/classes of drugs include:
a. BETA-LACTAM ANTIBIOTICS(Penicillins, cephalosporins, monobactams,
carbapenems)
b. GLYCOPEPTIDE ANTIBIOTICS
c. FOSFOMYCIN
d. BACITRACIN
e. CYCLOSERINE!

65. THANK YOU!!!!