Antibiotics are common agents used in modern healthcare. This was not always the case. From ancient times, people sought ways to treat those who were afflicted with infections. Dyes, molds, and even heavy metals were thought to hold promise for healing.[1] Various microorganisms hold medical significance, including bacteria, viruses, fungi, and parasites. Antibiotics are compounds that target bacteria and thus, are intended to treat and prevent bacterial infections.

1. ANTI INFECTIVE AGENTS
❏ AMINOGLYCOSIDES
❏ CARBAPENEMS
❏ MONOBACTAMS
❏ OXAZOLIDINONE
❏ FLUOROQUINOLONES
Guided by -
Prof. Gayatri Sapkale
Department of Pharmaceutical Chemistry
YTIP, University Of Mumbai
Prepared by -
Rohan Jagdale
T. Y. B. Pharm
2020-21

2. What are antibiotics
● Antibiotics, also known as antibacterials, are medications that destroy or slow
down the growth of bacteria.
● They include a range of powerful drugs and are used to treat diseases caused
by bacteria.
● Antibiotics cannot treat viral infections, such as cold, flu, and most coughs.
● The first antibiotic was penicillin. Penicillin-based antibiotics, such as
ampicillin, amoxicillin, and penicillin G, are still available to treat a variety of
infections and have been around for a long time.
● Several types of modern antibiotics are available, and they are usually only
available with a prescription in most countries. Topical antibiotics are
available in over-the-counter (OTC) creams and ointments.

3. Resistance
● Some medical professionals have concerns that people are overusing
antibiotics. They also believe that this overuse contributes toward the growing
number of bacterial infections that are becoming resistant to antibacterial
medications.
● Alexander Fleming, speaking in his Nobel Prize acceptance speech in 1945,
said::-“Then there is the danger that the ignorant man may easily underdose
himself and by exposing his microbes to non-lethal quantities of the drug,
make them resistant.”
● As the man who discovered the first antibiotic almost 70 years ago predicted,
drug resistance is starting to become commonplace.

4. CONTENTS
❏ AMINOGLYCOSIDES - Gentamicin &
Neomycin
❏ CARBAPENEMS - Imipenem &
Meropenem
❏ MONOBACTAMS - Aztreonam &
Tigemonam
❏ OXAZOLIDINONES - Linezolid
❏ FLUOROQUINOLONES -
❖ Norfloxacin
❖ Ciprofloxacin
❖ Sparfloxacin
❖ Gatifloxacin
❖ Levofloxacin
❖ Lomefloxacin

5. AMINOGLYCOSIDES

6. Defination & Introduction
● Aminoglycosides are a group of natural and semisynthetic antibiotics
having polybasic amino groups linked glycosidically with two or more
aminosugars.
● Aminoglycosides are used to treat various bacterial infections caused by
gram negative bacteria.
● Aminoglycosides can be combined with penicillins or cephalosporins to
show prolonged attack on gram-ve bacterial infections.
● They shows antibiotic action by inhibiting the bacterial protein synthesis.
● The drug will break down in the stomach without showing antibiotic
activity through oral route but it shows better activity through parentral
route.

7. ▪Examples of aminoglycosides are:-
Streptomycin, Amikacin Neomycin, Kanamycin,Gentamycin, Netilmycin
▪ Topical aminoglycosides - Neomycin & Framycetin
▪The above drugs are various aminoglycosides used to treat gram-ve
bacterial infections.
▪Widely in combination with B-lactum antibiotic.
_ serious infections with gram - ve bacteria
_ Combination with vancomycin gram +ve endocarditis.
▪Treatment of Tuberculosis

8. Mechanism of action
● Aminoglycosides inhibit protein synthesis in bacteria by binding irreversibly to
the 30S ribosomal subunit.
● This inhibits transfer of aminoacyl-tRNA to the peptidyl site, causing
premature termination of the peptide chain; it also increases the frequency of
misreading of mRNA.
● Aminoglycosides may also damage bacterial cell membranes, causing
leakage of intracellular contents. They are bactericidal.
● Aminoglycosides are potent bactericidal antibiotics that act by creating
fissures in the outer membrane of the bacterial cell. They are particularly
active against aerobic, gram-negative bacteria and act synergistically against
certain gram-positive organisms.

10. Mechanism of resistance
▪Synthesis of plasmid mediated bacterial
transferase enzyme: Inactivate aminoglycosides
▪ transport into bacterial cytosol
▪Deletion/alteration of receptor protein on 30 S
ribosomal unit by mutation: prevents attachment

12. Gentamicin
● Drug class: Aminoglycoside antibiotic
● Protein binding: 0–10%
● Formula: C21H43N5O7
● Bioavailability: limited bioavailability by mouth
● Elimination half-life: 2 h

13. Gentamicin
▪Obtained from Micromonospora purpurea
▪Most commonly used aminoglycoside
- More potent than Streptomycin
- Broader spectrum: pseudomonas, proteus, E.coli, klebsiella, enterobacter,
serratia
- Low cost, reliability of use, long experience
- Acts synergistically with ampicillin, penicillin G,Ticarcillin, ceftriaxone,
Vancomycin
▪Ineffective against M.tuberculosis
▪Relatively more nephrotoxicc

14. Gentamicin uses
▪Use restricted to serious Gm-ve bacillary infections
▪Septicaemia, sepsis, fever in immunocompromised patients
- Used with penicillins
▪Pelvic infections :with metronidazole
▪SABE: with Penicillin G or ampicillin or vancomycin
▪Coliform infection: with ampicillin or ceftriaxone
▪Pseudomonal infections: with ticarcillin
▪Meningitis by Gm-ve bacilli: Il generation cephalosporin alone or with gentamicin

15. Neomycin

16. Neomycin
▪wide spectrum active against Gram-ve bacilli and some gram+ve cocci
▪Pseudomonas and strep.pyogenes not sensitive
▪Too toxic for parenteral use, limited to topical use
▪Formula: C23H46N6O13
▪Trade name: Neo-rx
▪Elimination half-life: 2 to 3 hours

17. Neomycin uses
▪Topically used in skin, eye and external ear infections combined with bacitracin or
polymyxin-B to widen antibacterial spectrum and to prevent emergence of
resistant strains
▪Orally
- Preparation of bowel before surgery 1gm TDS
-Hepatic coma: Supresses ammonia forming
-coliforms prevents encephalopathy (Lactulose more preferred)
▪Bladder irrigation along with polymyxin B

18. CARBAPENEMS

19. What are carbapenems
Carbapenems are a class of beta-lactam antibiotics with
a broad spectrum of antibacterial activity. They have a
structure that renders them highly res istant to
beta-lactamases. Carbapenem antibiotics were originally
developed from thienamycin,a naturally-derived product
of Streptomyces cattleya.

20. ● Mechanism of action :Inhibits bacterial cell wall synthesis , bind to
penicillin binding protein and inhibit transpeptidation of peptidoglycan.
● Examples :-Imipenem, Meropenem, Ertapenem and Doripenem
● Converge:
● _Aerobic gram negatives (including ESBLs), aerobic gram positives
(MSSA, Streptococcus),anaerobes except MRSA, VRE and Atypical
● _Ertapenem do Not cover Enterococcus, Acinetobacter,
Pseudomonas, and MRSA
● It is a bactericidal, time dependent
● Mechanism of resistance: poor binding affinity for PBP 2a (found on
MRSA) and PBP 5 (found on E faecium).
● Alteration of targets, decreased accumulation due to decreased
permeability, and enzymatic inactivation.

21. ● Contraindications: Hypersensitivity ,ertapenerm(Infants less than 3
months),
● Side effects: Nausea, vomiting, diarrhea ,seizures(imipenem)
● Pregnancy category: B
● Dosage Form: IV, IM

22. ▪EFFECTIVE AGAINST:
Aerobic and anaerobic, Gram
positive and gram negative
bacteria
▪CHARACTERISTICS:
Broad Spectrum
Intravenous
Resistant to beta-lactamase
enzymes
▪SIDE-EFFECT:
Seizuregenic at high doses
Imipenem

23. Meropenem
▪EFFECTIVE AGAINST:
Aerobic and anaerobic, Gram
positive and gram negative
bacteria
▪CHARACTERISTICS:
Ultra Broad Spectrum
Intravenous
Resistant to beta-lactamase
enzymes
▪SIDE-EFFECT:
Diarrhoea
Vomiting
headache

24. Carbapenems common uses
▪Imipenem
Broad spectrum, covers Gram-positive, Gram-negative (including ESBL-producing
strains), Pseudomonas and anaerobes
▪Meropenem
Less seizure-inducing potential, can be used to treat CNS infections
▪Ertapenem
- Lacks activity vs. Acinetobacter and Pseudomonas
-Has limited activity against penicillin-resistant pneumococci

25. MONOBACTAMS

26. ● Monobactams are monocyclic and bacterially-produced β-lactam
antibiotics. The β-lactam ring is not fused to another ring, in
contrast to most other β-lactams.
● The main monobactum is aztreonam, which is resistant to most
B-lactamases
● Plasma half life is 2 hours.
● Aztreonam has an unusual spectrum of activity & is effective only
against Gram-ve Aerobic bacilli such as pseudomonas species,
Neisseria meningitidis and Haemophilus influenzae.
● It has no action against Gram positive organisms or anaerobes.

28. Aztreonam
▪It is a monocyclic B- Lactam compound (monobactam)
▪Mechanism:
-Interacts with penicillin-binding proteins of susceptible
micro-organisms and induces the formation of long filamentous
bacterial structures
▪It is resistant to many of the B- Lactamases that are elaborated by
most gram-negative bacteria

29. ▪ Adverse effects :-
- Usually well tolerated
- Patients with penicillins or cephalosporins allergy not to react to
aztreonam
▪ Uses :-
- Active against Gram-ve - aerobes only
- Alternative for penicillins and cephalosporins.
- Safe alternative to aminoglycosides, esp. in elderly and patients with
renal impairments.

31. ▪Tigemonam is a
monobactam antibiotic .
▪It has Gram-positive
activity, and is stable
against β-lactamases,
but has no activity
against Psedomonas.
▪SQ-30836 (tigemonam
dicholate) is an orally
absorbed salt of
tigemonam

32. OXAZOLIDINONES

33. What are Oxazolidinone antibiotics?
Oxazolidinone antibiotics are a class of synthetic antibacterial agents that act as a
protein synthesis inhibitor on the ribosomal 50S subunit of the bacteria. This
prevents the formation of the 70S initiation complex which is a prerequisite for
bacterial reproduction. Oxazolidinones are used for gram-positive infections and
can be bacteriostatic or bactericidal depending on bacteria being treated.
▪Effective against Organisms -
gram-positive bacteria including MRSA, VRE and Streptococcus
pneumoniae.Mycobacterium tuberculosis and Nocardia.
▪In clinical use :- Linezolid. ▪In clinical trials - Radezolid, Torezolid

34. Linezolid-1st to be approved
▪Indicated
_VRE infection
_nosocomial and com munity-acquired pneumonia
_skin and soft tissue infections.(SSTIs)
▪bacteriostatic against drug-resistant organisms like MRSA and VRE. Inhibits bacterial
protein synthes is at an early stage and inhibits the formation of a function al initiation
complex.
▪Resistance- Mutations in the peptidyl transferase centre of the rRNA
▪Serious adverse effects bone marrow suppression, peripheral and optic neuropathy, lactic
acidos is, and serotonin syndrome.

36. Structure - activity relationship leading to development of linezolid

37. FLOUROQUINOLONES

38. Quinolones
▪The quinolones are a family of synthetic broad-spectrum
antibiotics. The term quinolone(s) refers to potent synthetic
chemotherapeutic antibacterial agent.
▪The first generation of the quinolones begins with the introduction
of nalidixic acid in 1962 for treatment of urinary tract infections in
humans. Nalidixic acid was discovered by George Lesher and
co-workers in a distillate during an attempt at chloroquine
synthesis.
▪They prevent bacterial DNA from unwinding and duplicating

39. Fluoroquinolones
The Fluoroquinolones are a
relatively new group of antibiotics.
first Fluroquinolones were
introduced in 1986, but they are
really modified quinolones, a class
of antibiotics, whose accidental
discovery occurred in the early
1960.

40. ▪The fluoroquinolones are a family of synthetic, broad-spectrum
antibacterial agents with bactericidal activity. The first
fluoroquinolones were widely used because they were the only
orally administered agents available for the treatment of
serious infections caused by gram-negative organisms,
including Pseudomonas species.

41. Classification

42. Fourth generation
● Fourth generation fluoroquinolones act at DNA gyrase and
topoisomerase IV. This dual action slows development of
resistance.
● clinafloxacin
● gatifloxacin
● gemifloxacin
● moxifloxacin
● sitafloxacin
● trovafloxacin
● Prulifloxacin
In development
● garenoxacin (Geninax) (application withdrawn due to toxicity)
● delafloxacin

43. Mechanism of action
▪It blocks bacterial DNA synthesis by
- Inhibition of bacterial Topoisomerase lI (DNAGyrase)
- Inhibition of Topoisomerase IV
▪Inhibition of ATP dependent DNA gyrase; which nicks doule stranded
DNA, introduces negative supercoils and then reseals the nicked ends.
This is required to prevent excessive positive supercoiling of DNA strands
when they seperate to permit replication or transcription.

44. ▪Inhibition of DNA gyrase also prevents the relaxation of positively supercoiled
DNA.
▪Inhibition of DNA nicking-closing enzyme responsible for DNA elongation, which
leads to break in double stranded DNA.
▪Inhibition of topoisomerase IV interferes with the separation of replicated
chromosomal DNA into respective daughter cells during cell division.
▪The critical imbalance in cellular metabolism resulting from the inhibition of
enzymes precipitates a sequence of cellular events which may lead to:
- Premature cell division.
- Delayed cell division.
- Total failure of cell division leading to lysis of the cell

46. Schematic representation of mechanism of action of fluoroquinolones

47. Complex formed between DNA, topoisomerase and fluoroquinolones

48. Mechanism of resistance

49. Mechanism of resistance
Resistance to fluoroquinolones mostly occurs by two
mechanisms that are mutations in the both target
enzymes DNA gyrase in Gram-negative bacteria and
topoisomerase IV in Gram-positive bacteria. The
second way that reduced accumulation of the
fluoroquinolones can occur is through an efflux system.
Resistance is due to increased expression of
chromosomal gene leading to increased efflux of the
fluoroquinolones

51. Norfloxacin

52. Medical use
● It was patended in 1977 and approved in 1983.
● Trade names - Noroxin, Chibroxin, Trizolin
● Route of administration - Oral, opthalmic.
● Bioavailability - 30 to 40%
● Elimination half-life - 3 to 4 hours.
▪ Complicated urinary tract infections.
▪Uncomplicated urethral and cervical gonorrhea
▪Prostatitis due to E. coli
▪Syphilis treatment

53. Contraindication-
Norfloxacin is contraindicated in those with history of tendonitis, tendon
rupture and those with hypersensitivity of flouroquinolones.
Adverse effects -
Common side effects include gastrointestinal effects, such as
nausea, vomiting and diarrhea as well as headache and insomnia

55. Ciprofloxacin

56. ▪2nd generation fluoroquinolone. ▪Most
potent fluoroquinolone against P. aeruginosaNot effective against Gram +ve and
anaerobes. ▪Mainly effective
against Gram -ve bacteria :-
H. Influenzae Enterobacteriacae
Campylobacter. M. Catarrhalis
Pseudomonas. N. Gonorrhea
▪Intracellular Pathogen :-
M. Tuberculosis. Mycoplasma
Legionella Chlamydia
Brucella

57. Pharmacokinetics
● Well absorbed orally ( available i.v. )
● Di&tri-valent cations interfere with its absorption (milk, Mg, Al, Ca,
antacid)
● Concentrates in many tissues, esp. kidney, prostate,lung & bones/ joints
● Do not cross Blood brain barrier
● Excreted mainly through the kidney (tubular & glomerular) (probencid
interferes with tubular secretion)
● Accumulate in renal insufficiency
● Up to 20% metabolized by liver
● Half life - 3.3 hours

58. Clinical uses
● Urinary tract infections (Paeruginosae,E.coli,Klebsiella)
● Osteomyelitis due to Paeruginosa
● Gonorrhea
● Travellers' diarrhea- ciprofloxacin commonly used (if there's a bloody
diarrhea)
● Prostatitis
● Legionnaires' disease
● Brucellosis
● Diabetic foot infections
● Anthrax
● Eradication of menengiococci from carriers

59. ▪Side effects
- Nausea, vomiting & diarrheaa
- CNS effects :confusion, insomnia, headache, dizziness &
anxiety.(indirectly by modifying GAPA transmitter in the CNS)
- May damage growing cartilage
- Tendinitis ( rare but more serious) (irreversible) (may lead to
tendon rupture)

60. ▪Contraindications :-
Children/ adolescents (under 18), pregnancy and lactation (secreted in
milk)
It's not contraindicated in adolescents it's not preferred so you have to
measure benfits vs. risks
▪Drug interaction :-
Iron or antacids containing Mg, Ca, or Al> reduce oral absorption
Elevates serum levels of theophylline, warfarin & glibenclamide

62. Sparfloxacin
● It was patended in 1985 &
approved for medical use in
1993
● Trade names - Spacin,
Zagam
● Route of administration -
mouth
● Bioavailability - 92 %
● Elimination half-life - 16 to
30 hours

63. , ▪Pharmacological properties
● Sparfloxacin is about 37-45% bound to proteins in the blood.
● Sparfloxacin achieves a high degree of penetration into most tissues, except
for the central nervous system.
▪Mechanism of action
Sparfloxacin, like other quinolones and fluoroquinolones, are
bactericidal drugs, actively killing bacteria.
▪Medical uses
The compound is indicated for treating community-acquired lower
respiratory tract infections (acute sinusitis, exacerbations of chronic
bronchitis caused by susceptible bacteria, community-acquired
pneumonia)

65. Gatifloxacin
● It was patented in 1986 and
approved for medical use in
1999.
● Fourth generation antibiotic
● Route of administration - Oral
(Discontinued), Intravenous
(discontinued), now Opthalmic
only.
● Elimination half-life - 7 to 14
hours

66. Clinical use
Gatifloxacin ophthalmic solution is used to treat bacterial conjunctivitis
(pinkeye; infection of the membrane that covers the outside of the
eyeballs and the inside of the eyelids) in adults and children 1 year of age
and older.This medication treats only bacterial eye infections. It will not
work for other types of eye infections.
Side effects
Blurred vision, watery eyes, headache, eye
irritation/pain/dryness/redness, bad taste in mouth may occur. Use
of this medication for prolonged or repeated periods may result in a
new fungal eye infection.

67. Availability
Gatifloxacin is currently available in
the US and Canada only as an
ophthalmic solution.
In 2011, the Union Health and Family
Welfare Ministry of India banned the
manufacture, sale, and distribution of
gatifloxacin because of its adverse
side effects.
In China, gatifloxacin is sold in tablet
as well as in eye drop formulations.

68. Levofloxacin

69. ▪Brand name - leflox, 1-cyn, qumic
▪3rd generation fluoroquinolone
▪Spectrum: Gram-ve, Gram+ve (S. aureus including MRSA & S.
pneumoniae) and Legionella pneumophila, atypical resp. pathogens,
Mycobacterium tuberculosis
▪Indications:
- Chronic bronchitis and CAP
- Nosocomial pneumonia
- Intra-abdominal infections

70. ▪Adverse reaction.
- Blood glucose disturbances in DM patients
- QTC prolongation, torsades de pointes, arrhythmias
- Nausea, Gl upset
- Interstitial nephritis
Oral Parentral Opthalmic
100mg 5mg/ml iv 5mg/ml solution
250 mg 25mg/ml iv
500 mg
▪Available forms

72. Lomefloxacin
● 2nd generation.
● Equal in activity to
Ciprofloxacin.
● Single daily administration.
● High incidence of
Phototoxicity and QT
prolongation.
● Brand name - Maxaquin

73. ● used to treat chronic bronchitis, as well as complicated and
uncomplicated urinary tract infections. Also used in-
● Escherichia coli Infections
● Klebsiella Infections
● Proteus Infections
● Pseudomonas Infections
● Staphylococcal Infections
▪Clinical uses
▪Lomefloxacin is available in the following forms:
- Ophthalmic Solution
- Oral Tablet (Lomefloxacin 400 Mg Oral Tablet)

75. References
https://www.drugs.com
https://www.medindia.net
https://drugs.ncats.io/
https://www.researchgate.net
https://en.wikipedia.org
https://go.drugbank.com/drugs