A presentation i made for a few colleagues... i couldnt add all the antibacterials.. Some of the most important ones are here

1. Antibiotics
In Obstetrics and Gynaecology
Dr. Insaf Imthiyaz

2. Antibiotic or Antibacterial?
The term antibiotic was first used in 1942 by Selman Waksman to describe any
substance produced by a microorganism that is antagonistic to the growth of other
microorganisms.
What about drugs that “kill” microbes?
A better term would be Antibacterials.
This term includes the other antimicrobial agents such as antifungals, and
synthetic and semi synthetic agents.

3. Classification
Antibacterials
Natural Semi - Synthetic Synthetic
Beta-Lactams Sulphanomides
Penicillins
Aminoglycasides • Cephalosporins Quinolones
• Carbapenams Oxazolidinones
2.
1. Bacteriocidal
2. Bacteriostatic

5. Penicillin

6. About
Penicillins are beta-lactam compounds which have a 4 membered beta-lactam
ring that is fused to a 5-membered thiazolidine ring. Side chain modifications of
this structure confers:
1) An improved spectrum of activity.
2) Pharmacokinetic advantages.
Six classes of penicillins are now available.

7. Classification of Penicillin
1. NATURAL PENCILLINS 5. UREIDO-PENICILLIN
Aqueous penicillin G Mezlocillin
Penicillin G Piperacillin
Pencillin VK
6. PENICILLIN/INHIBITOR
2. PENICILLINASE-RESISTANT COMBINATIONS
PENICILLINS
Ampicillin/sulbactam
Methicillin Ticarcillin/clavulanate
Oxacillin Piperacillin/tazobactam
Naficllin 1-2 gm
Amoxicillin/clavulanate
Dicloxacillin
Cloxacillin MONOBACTAM
Aztreonam
3 . AMINOPENICILLINS
CARBAPENEM
Ampicillin
Imipenem
4 . CARBOXY-PENICILLINS Meropenem
Carcenicillin GLYCOPEPTIDE
Ticarcillin Vancomycin

8. MECHANISM OF ACTION & PHARMACOLOGIC PROPERTIES
1. Prevents cell wall synthesis by binding to enzymes called penicillin binding proteins (PBPs).
These enzymes are essential for the synthesis of the bacterial cell wall.
2. Bactericidal.
3. Concentration-independent bactericidal activity.

10. Penicillin attacks bacterial cells by inactivating an enzyme that is essential for
bacterial growth. The enzyme is peptidoglycan transpeptidase and it catalyses the
cross-linking of the peptidoglycan, which forms the cell wall of the bacteria.
The peptidoglycan transpeptidase enzyme is not needed in animals as their cells
do not have cell walls.
Therefore, the penicillin can safely disrupt the bacterial cell wall biosynthesis
without harming existing cells in the body.
The penicillin stops the growth of the bacterial cell wall, causing the pressure
inside the cell to rise considerably until the cell lyses and thus the cell is
destroyed.

11. Penicillin G and V are only active against Gram Positive bacterial cells, which
have an exposed layer of peptidoglycan around the outside of the cell wall,
as shown below. Gram Negative bacteria have a more complicated
composition, which Penicillin G and V can not destroy, although there are
other antibiotics that can.

12. Penicillin binds at the active site of the transpeptidase enzyme that cross-links the
peptidoglycan strands. It does this by mimicking the D-alanyl-D-alanine residues
that would normally bind to this site.
The similarity between the structures of the residues and the penicillin molecule
can be seen below:
The labile β-lactam ring in penicillin reacts with a serine residue in the transpeptidase
as shown below.
This reaction is irreversible and so the growth of the bacterial cell wall is inhibited. The
resulting complex is stable to water and remains attached to the polypeptide chain.

13. Sensitivity and Activity
SPECTRUM OF ACTIVITY:
Gram-positive aerobic cocci: Streptococci pyogenes (Group A strep),
Streptococcus agalactiae (Group B strep), viridans streptococci, Enterococci.
Staphylococci are usually resistant.
Penicillin resistant S. pneumoniae with variable degrees of resistance
(intermediately resistant, highly resistant) to penicillin is becoming a worldwide
problem. Potential therapies for these resistant isolates include cefotaxime,
ceftriaxone, vancomycin, imipenem.
Gram-negative aerobes: Neisseria meningitidis, Pasteurella multocida.
Anaerobes: Clostridium species, Fusobacterium species, Actinomyces israelii.
Other: Treponema pallidum, Listeria monocytogenes.

14. Pharmacokinetics of Penicillin
Distributes well into the urine; synovial, pleural, and pericardial fluids; cerebral spinal fluid
(CSF).
Elimination is primarily via the kidneys and dosage adjustment is necessary to minimize
the potential for seizures.
Clinical Uses
Useful for skin and soft tissue infections caused by Streptocccus pyogenes,
meningitis caused by susceptible N. meningitidis and Streptococcus
pneumoniae, oral or dental infections which frequently involve anaerobic
streptococci, and syphilis which is caused by Treponema pallidum.

15. GENERAL SIDE EFFECTS/PRECAUTIONS:
A. Hypersensitivity reactions manifested by rashes, eosinophilia, fever,
interstitial nephritis.
B. Central nervous stimulation including myoclonic twitching and seizures.
Risk factors include high doses, particularly when doses are not modified for renal
dysfunction, lowered seizure threshold as may occur with meningitis.
MISCELLANEOUS:
A. Probenecid (usual dose of 500mg four times daily) blocks renal tubular transport of
penicillin resulting in usually a 2-fold increase in penicillin blood levels.
Useful in alternative regimens for syphilis in combination with amoxicillin; or in
circumstances when higher blood levels of penicillin are desired.

16. SPECIFIC AGENTS:
A. Aqueous penicillin G. This formulation is usually used in patients who require intravenous
penicillin for more severe or complicated infections (eg: meningitis, pneumonia). 3.4 meq of K+
accompany each 1 million unit (1MU) of penicillin G and hyperkalemia may occur particularly
when high doses are give to patients with renal dysfunction.
B. Procaine penicillin G. Repository, intramuscular formulation that provides prolonged blood
levels of penicillin. May be used for treatment of uncomplicated pneumonia caused by penicillin-
susceptible Streptococcus pneumoniae; syphilis.
"Procaine reaction" characterized by dizziness, palpitations, auditory or visual disturbances,
fear of impending death. Symptoms usually resolve within 5-10 minutes.
C. Benzathine penicillin G. Long acting intramuscular formulation that provides low, blood
levels for 3-4 weeks. Used for syphilis (primary, secondary, latent); rheumatic fever prophylaxis;
Streptococcal pharyngitis.
D. Penicillin G/Penicillin VK. Oral forms of penicillin. Penicillin G is susceptible to breakdown
by gastric acid which is why it has been largely replaced by penicillin VK which is stable in the
acid environment of the stomach.

17. PENICILLINASE-RESISTANT PENICILLINS
Side chain modification prevents destruction of beta-lactam ring by beta-
lactamases produced by Staphylococci. Thus, unlike penicillin G, penicillinase-
resistant penicillins are useful for Staphylococcal infections.
SPECTRUM OF ACTIVITY
Gram-positive aerobic cocci: Methicillin-susceptible Staphylococcus aureus
(MSSA); viridans streptococci; less potent than penicillin against Streptococcus
pyogenes (Group A strep) and Streptococcus pneumoniae; not active against
Enterococci.
Gram-negative aerobes: Not active.
Anaerobes: Compared to penicillin, less active or inactive against penicillin-
susceptible anaerobes.

18. GENERAL CLINICAL USES:
Primarily used to treat infections involving MSSA such as bacteremia
associated with:
1) indwelling devices
2) injection drug use
3) skin and soft tissue infections; and endocarditis which may be a
complication of bacteremia.
Sometimes used in combination with an aminoglycoside (usually
gentamicin) for their synergistic effect against Staphylococci.
GENERAL SIDE EFFECTS/PRECAUTIONS:
A. Hypersensitivity reactions manifested by rashes, eosinophilia, fever, interstitial nephritis.

19. SPECIFIC AGENTS:
A. Nafcillin. IV/IM/PO formulations . Phlebitis, neutropenia.
B. Methicillin. IV/IM formulations. Less commonly used because of increased risk of
interstitial nephritis; signs and symptoms which include eosinophilia, rash, renal
failure, proteinuria, fever.
C. Oxacillin. IV/IM/PO. Hepatitis occurs more frequently than with nafcillin.
D. Dicloxacillin and Cloxacillin. PO formulations. These oral formulations are
preferred over oral forms of nafcillin or oxacillin because their blood levels are higher.

20. Amino-Penicillins
Side chain modification (addition of amino group) to basic benzylpenicillin molecule
increases spectrum of activity to include aerobic gram-negative bacilli.

21. Activity
Gram-positive aerobic cocci: Same activity as for penicillin G but is more
active than penicillin against Enterococci. Like penicillin G, Staphylococci are
usually resistant to ampicillin.
Gram-negative aerobes: Active against most beta-lactamase negative
Hemophilus influenzae; Escherichia coli and Proteus mirabilis, particularly if
involved with community-acquired infections; Salmonella and Shigella species.
Usually not active against aerobic gram-negative bacteria causing hospital-
acquired infections.
Anaerobes: Clostridium species, Fusobacterium species, Actinomyces israelii.
Other: Listeria monocytogenes.

22. Clinical Usage
Used as empiric therapy in many community-acquired infections involving the
respiratory tract
(eg: bronchitis, sinusitis, otitis media) where frequent pathogens include
Streptococcus pneumoniae, Hemophilus influenzae; urinary tract infections caused
by susceptible Escherichia coli.
A high prevalence of beta-lactamase producing aerobic gram-negative bacteria may
preclude the empiric use of amino-penicillins for these community-acquired infections.
Side Effects
A. Hypersensitivity reactions manifested by rashes, eosinophilia, fever, interstitial
nephritis.
B. Ampicillin rash is a generalized erythematous, maculopapular rash that occurs in
patients taking ampicillin and who have a concurrent viral illness (eg: mononucleosis,
cytomegalovirus, viral respiratory tract infection).

23. Specific Agents
A. Ampicillin. IV/IM/PO formulations. More effective than Amoxicillin
against Shigella.
B. Amoxicillin. PO formulation. More active than ampicillin against
Salmonella. Favored over ampicillin because:
1) better absorption,
2) food does not interfere with absorption,
3) less frequent dosing (8Hourly vs 6Hourly for Ampicillin).

24. Carboxy-Penicillins
Side chain modification (substitution of amino group with a carboxy group and others) increases
spectrum of activity to include other aerobic gram-negative bacilli.

25. SPECTRUM OF ACTIVITY
Gram-positive aerobic cocci:
Less active than ampicillin against Enterococci, Streptococcus pneumoniae,
Streptococcus pyogenes. Not active against methicillin-susceptible
Staphylococcus aureus (MSSA).
Gram-negative aerobes:
Active against many hospital-acquired pathogens such as Pseudomonas
aeruginosa, Enterobacteriaceae (indole positive Proteus, Enterobacter,
Morganella). Similar activity to ampicillin against Hemophilus species,
Escherichia coli, Proteus mirabilis. Inactive against Klebsiella.
Anaerobes:
Bacteroides fragilis (at high concentrations)

26. Clinical Use
Usually in combination with another antibiotic
(generally an aminoglycoside) for aerobic gram-
negative infections (especially P. aeruginosa).

27. Specific Agents
A. Carbenicillin indanyl sodium. PO formulation. An indanyl ester which
releases active carbenicillin after breakdown in the liver. Low blood levels
preclude its use for infections outside the urinary tract.
B. Ticarcillin. IV/IM formulations. Similar spectrum to carbenicillin except
that it is 2-4 times more active than carbenicillin against Pseudomonas
aeruginosa.
Side effects include occasional bleeding due to platelet dysfunction. Each
gram of ticarcillin is accompanied by 5.2meq of sodium. .

28. Ureido-Penicillins
Structure of Pipercillin

29. Spectrum of Activity
Gram-positive aerobic cocci: More active than carboxy-
penicillins against Enterococci, Streptococcus pneumoniae,
Streptococcus pyogenes.
Gram-negative aerobes: Active against many hospital-acquired
pathogens such as Pseudomonas aeruginosa (more active than
carboxy-penicillins); Enterobacteriaceae (eg: Klebsiella, indole
positive Proteus, Enterobacter, Morganella). More active than
ticarcillin against Hemophilus influenzae.

30. Specific Agents
A. Mezlocillin (MezlinR). IV/IM formulations. Similar spectrum of activity
to ticarcillin including comparable activity against Pseudomonas
aeruginosa; invitro may be more active against Klebsiella pneumoniae.
Each gram contains 1.85meq of sodium.
B. Piperacillin (PipracilR). IV/IM formulations. It is 4-fold more
active than mezlocillin against Pseudomonas aeruginosa.

31. Penicillin/ Inhibitor Combinations
In order to overcome resistance due to beta-lactamase enzymes, various
penicillins have been combined with beta-lactamase inhibitors that irreversibly
inhibits beta-lactamases. Unfortunately, not all beta-lactamase enzymes can be
neutralized by the currently available beta-lactamase inhibitors.
These inhibitors generally do not have any clinically useful antibacterial activity.
Currently available products combine ampicillin, amoxicillin, ticarcillin, or
piperacillin with a beta-lactamase inhibitor.
The intrinsic antibacterial activity of the penicillin is an important factor in the
effectiveness of the penicillin/inhibitor combinations.

32. Clinical Use
As monotherapy for mixed aerobic/anaerobic infections caused by
susceptible bacteria (eg: intraabdominal/gynecologic infections, skin
and soft tissue infections such as diabetic ulcers).
For serious infections or infections in which resistant gram-negative
bacteria are suspected a second agent (eg: aminoglycoside) can be
added.

33. A. Ampicillin/sulbactam (UnasynR). IV/IM formulations.
Has the spectrum of ampicillin plus beta-lactamase producing organisms such as
Hemophilus influenzae, Moraxella catarrhalis, Bacteroides fragilis, Escherichia coli
(although susceptibilities to Escherchia coli is variable), Proteus species,
Klebsiella species, Enterobacter aerogenes, Acinetobacter calcoaceticus,
methicillin-susceptible Staphylococcus aureus (MSSA). Useful for infections due to
these beta-lactamase producing bacteria (sinusitis, otitis); mixed
aerobic/anaerobic infections, bite wounds.
B. Amoxicillin/clavulanate (AugmentinR). PO formulation. Similar to
ampicillin/sulbactam with respect to spectrum of activity and clinical usefulness.

34. C. Ticarcillin/clavulanate (TimentinR). IV/IM formulations.
Has the spectrum of ticarcillin plus beta-lactamase producing bacteria such as
`
Staphylococcus aureus, Escherichia coli, Klebsiella species, Proteus, Hemophilus
species, Bacteroides fragilis.
Clavulante does not increase the activity of ticarcillin against gram-negative
bacteria that produce Class 1 Richmond-Sykes beta-lactamases (eg:
Pseudomonas, Serratia, Citrobacter, Enterobacter).
D. Piperacillin/tazobactam (ZosynR). IV/IM formulations.
Has the spectrum of piperacillin plus beta-lactamase producing bacteria such as
Escherichia coli, Enterobacter, Citrobacter, Providencia, methicillin-susceptible
Staphylococcus aureus, Bacteroides fragilis, Hemophilus species.

35. Dosage and Administration
Aqueous penicillin G 1-4 million IV 4-6
Penicillin G units PO 6
Pencillin VK 250-500 mg PO 6
250-500 mg
Ampicillin 1-2 gm IV/IM 4-6
250-500 mg PO 6
Ampicillin/sulbactam 3 gm IV/IM 6
Ticarcillin/clavulanate 3.1 gm IV 4-6
Piperacillin/tazobactam 3.75/ 4.5gm IV 4-6
Amoxicillin/clavulanate 375mg / PO 8h - 12h
625mg

36. Cephalosporins

37. Structure of Cephalosporins
Cephalosporins are structurally related to Penicillins, they contain a B-lactamase ring
attached to a dihydrothiazaline ring.

38. Classification of Cephalosporins
Cephalosporins have been divided in 5 generations depending on there antibacterial activity.
Generation Range of Activity
Aerobic gram-positive organisms and some
1 Generation
st community-acquired gram-negative organisms
(Cephalexin, Cephradine, and Cefadroxil) (P mirabilis, Escherichia coli, Klebsiella species)
2nd Generation Extended Gram negative coverage,
(Cefuroxime,Cefprozil,Cefeclor,) (Indole-positive Proteus ,Klebsiella M catarrhalis
and Neisseria species)
3rd Generation Active against staphylococci, Serratia
(Cefexime,Cefpodoxime,Cefotaximem marcescens, Providencia, Haemophilus, and
Ceftriaxone) Neisseria, including -lactamase–producing
strains
4th Generation Effective against pseudomonas aeroginosa
(Cefepime)
5th Generation

39. Mechanism of Action
1. Cephalosporins are bactericidal and have the same mode of action as other
beta-lactam antibiotics (such as penicillins)
2. but are less susceptible to penicillinases.
3. Cephalosporins disrupt the synthesis of the peptidoglycan layer of bacterial
cell walls. The peptidoglycan layer is important for cell wall structural integrity.
4. The final transpeptidation step in the synthesis of the peptidoglycan is
facilitated by transpeptidases known as penicillin-binding proteins (PBPs).
5. PBPs bind to the D-Ala-D-Ala at the end of muropeptides (peptidoglycan
precursors) to crosslink the peptidoglycan.
6. Beta-lactam antibiotics mimic the D-Ala-D-Ala site, thereby competitively
inhibiting PBP crosslinking of peptidoglycan.

40. 1st Generation Of Cephalosporins
Antimicrobial Activity
Gram-positive: Activity against penicillinase-producing, methicillin-susceptible staphylococci and streptococci
(though they are not the drugs of choice for such infections). No activity against methicillin-resistant
staphylococci or enterococci.
Gram-negative: Activity against Proteus mirabilis, some Escherichia coli, and Klebsiella pneumoniae
("PEcK"), but have no activity against Bacteroides fragilis, Pseudomonas, Acinetobacter, Enterobacter, indole-
positive Proteus, or Serratia

41. Drug, Route and Dosage (1st Gen)
Name Route of Administration Dosage
Cefadroxil Oral
Cefradine Oral
Cephalexin Oral
Cefazolin IV (Preferred) /IM
Cefalonium
Cefaloridine

42. Clinical Use
Oral drugs :
1. Urinary tract infections,
2. Minor skin and soft tissue infections (eg, cellulitis, soft tissue
abscess).
Intravenous :
1. Most clean surgical prophylaxis
The second-generation cephalosporins cefoxitin and cefotetan have
expanded anaerobic activity and are superior to first-generation agents as
prophylaxis for colorectal surgery or for hysterectomy.
N.B : First-generation cephalosporins do not adequately penetrate into
cerebrospinal fluid and are less potent than second- and third-generation
agents and cannot be used to treat meningitis.

43. 2nd Generation of Cephalosporins
Gram-positive: Less than first-generation.
Gram-negative: Greater than first-generation: HEN (Haemophilus
influenzae, Enterobacter aerogenes and some Neisseria + the PEcK
described above

44. Drug, Route and Dosage (2nd Gen)
Name Route of Administration Dosage
Cefaclor Oral
Cefonicid
Cefuroxime Oral/IV O : 12h IV : 8H
Cefmetazole Antianaerobic
Cefotetan
Cefoxitin

45. Clinical Use
Because of their activity against -lactamase–producing H influenzae and
M catarrhalis, cefprozil and cefuroxime axetil have a role in the
treatment of sinusitis and otitis media in those patients unresponsive to
amoxicillin.
Because of their activity against B fragilis, cefoxitin and cefotetan can be
used to treat mixed anaerobic infections, eg, peritonitis and diverticulitis.
Cefoxitin and cefotetan are useful as prophylaxis in colorectal surgery,
vaginal or abdominal hysterectomy, and appendectomy due to their
moderate to strong activity against B fragilis.

46. 3rd Generation Cephalosporins
Gram-positive: Some members of this group (in particular, those
available in an oral formulation, and those with antipseudomonal activity)
have decreased activity against Gram-positive organisms.
Gram-negative: Third-generation cephalosporins have a broad
spectrum of activity.
They may be particularly useful in treating hospital-acquired infections.
They are also able to penetrate the CNS, making them useful against
meningitis caused by pneumococci, meningococci, H. influenzae, and
susceptible E. coli, Klebsiella, and penicillin-resistant N. gonorrhoeae.
Since 2007, third-generation cephalosporins (ceftriaxone or cefixime)
have been the only recommended treatment for gonorrhea in the United
States.

47. Drug, Route and Dosage (3nd Gen)
Name Route of Administration Dosage
Cefotaxime
Ceftriaxone
Ceftazidime
Cefixime
Cefpimizole

48. Clinical Use
Because of their penetration into the cerebrospinal fluid and potent in vitro
activity, intravenous third-generation cephalosporins are useful to treat
meningitis due to susceptible pneumococci, meningococci, H influenzae, and
susceptible enteric gram-negative rods.
In meningitis in older patients, third-generation cephalosporins should be
combined with ampicillin or trimethoprim-sulfamethoxazole until L
monocytogenes has been excluded as the etiologic pathogen
Ceftazidime has been used to treat meningitis due to Pseudomonas. The
dosage for meningitis should be at the upper limits of the recommended range,
because cerebrospinal fluid levels of these drugs are only 10–20% of serum
levels.
Ceftazidime is frequently administered empirically in the febrile neutropenic
patient.

49. Ceftriaxone is indicated for gonorrhea, chancroid, and more serious
forms of Lyme disease.
Because of its long half-life and once-daily dosing requirement,
ceftriaxone is an attractive option for the outpatient parenteral
therapy of infections due to susceptible organisms..
Cefdinir, cefditoren pivoxil, and cefpodoxime proxetil are the
best third-generation oral agents against pneumococci and S
aureus.
Cefixime is available in an oral suspension and 400-mg tablets.
This latter dosage form is important because it is the only oral agent
recommended by the Centers for Disease Control and Prevention
(CDC) for the treatment of uncomplicated urogenital or rectal
gonorrhea.

50. 4th Generation Cephalosporins
Gram-positive: They are extended-spectrum agents with similar
activity against Gram-positive organisms as first-generation
cephalosporins.
Gram-negative: Fourth-generation cephalosporins are
zwitterions that can penetrate the outer membrane of Gram-
negative bacteria.
They also have a greater resistance to beta-lactamases than the
third-generation cephalosporins. Many can cross the blood–brain
barrier and are effective in meningitis. They are also used
against Pseudomonas aeruginosa.

51. Drug, Route and Dosage (4th Gen)
Name Route of Administration Dosage
Cefclidine
Cefepime
Cefozopran
Cefpirome

52. 5th Generation Cephalosporins
Ceftobiprole has powerful antipseudomonal characteristics and
appears to be less susceptible to development of resistance.

53. Drug, Route and Dosage (5th Gen)
Name Route of Administration Dosage
Ceftobiprole
Ceftaroline

54. Clinical Use
Ceftaroline is a novel cephalosporin that has activity against MRSA with
phase III clinical trials for complicated skin and skin structure infections
with reported non-inferior efficacy against MRSA compared to
vancomycin and aztreonam

55. Carbepenams
`

56. Structure
A structure that gives It a high resistance to beta-lactamases

57. Type of Carbepenams
1. Imipenem
Experimental
2. Meropenem
1. Razupenam
3. Ertapenem
2. Tebipenam
4. Doripenem
5. Panipenem/betamipron
6. Biapenem

58. Mechanism of Action
Similiar to the other B-lactamases.
It has a wide spectrum of activity that includes that includes
most gram-negative rods (including P aeruginosa) and gram-
positive organisms and anaerobes, with the exception of
Burkholderia cepacia,
Stenotrophomonas maltophilia,
Enterococcus faecium,
and methicillin-resistant S aureus and Staphylococcus
epidermidis.

59. Drug Route of Dosage
Administration
Imepenam IV 1 - 2g 8hourly
Merapenam IV 1 - 2g 8hourly
Ertapenam IV 1 g every 24 hours

60. Clinical Use
In patients hospitalized for a prolonged period with presumed
infection with a multidrug-resistant organism.
Not used alone for serious pseud.infections
Not used for MRSA infections

61. Quinolones
The quinolones are synthetic analogs of nalidixic acid with a broad spectrum of
activity against many bacteria.

62. Classification
Earlier Newer
- Fluoroquinolones
Nalidixic Ciprofloxacin
Oxolinic Acid Levofloxacin
Cinoxacin Gemifloxacin
Moxifloxacin

63. Mechanism Of Action
Quinolones inhibit the action of DNA gyrase and topoisomerase IV and
kill bacteria by binding to these enzyme-DNA complexes, thereby
disrupting DNA replication.

64. Spectrum Of Activity
Enterobacteriaceae
Haemophilus
Neisseria
Moraxella Fluoroquinolones are less
Brucella potent against gram-positive
Legionela than against gram-negative
Salmonella organisms
Shigella
Campylobacter
Yersinia
Vibrio
and Aeromonas organisms

65. Gemifloxacin, levofloxacin, and moxifloxacin have the best
gram-positive activity, including against streptococci,
pneumococci and S aureus and S epidermidis, and some
methicillin-resistant strains.
T pallidum and Nocardia are resistant to all fluoroquinolones.
Moxifloxacin also provides the most reliable coverage of M tuberculosis.

66. Pharmacokinetics and Administrations
After oral administration, the fluoroquinolones are well-
absorbed and widely distributed in body fluids and tissues
and are concentrated intracellularly.
Fluoroquinolones bind some heavy metals; thus, absorption
is inhibited when administered concomitantly with iron,
calcium, and other multivalent cations.
Optimal oral bioavailability is achieved if fluoroquinolones are
taken 1 hour before or 2 hours after meals.

67. Drug Route Of Dosage
Administration
Norfloxacin PO 400mg /12 Hrly
Ciprofloxacin PO 250 – 750 mg / 12hrly
IV 200 – 400 mg / 12hrly
Ofloxacin PO 200 – 400 mg / 12hrly
IV 200 – 400 mg / 12hrly
Lomefloxacin PO 400mg / 24 hrly

68. Clinical Use
Urinary tract infections: Uncomplicated, complicated urinary tract
infections,prostatitis. Only ofloxacin and ciprofloxacin are approved for prostatitis.
Sexually transmitted diseases :
Neisseria gonorrhea. single doses of ciprofloxacin and ofloxacin can be used for
uncomplicated urethritis, cervicitis, or rectal infections.
Reports of fluoroquinolone-resistant gonococci are emerging.
Chlamydia trachomatis : Ofloxacin is the only approved quinolone.
Chancroid : Ciprofloxacin approved.
Community-acquired (eg: pneumonia, bronchitis, otitis).
Should not be used alone as empiric therapy because of their inadequate activity against
Streptococcus pneumoniae, one of the common pathogens in these infections.
Quinolones would be effective alternatives when infections are caused by gram-
negative bacteria such as Hemophilus influenzae, and Moraxella catarrhalis that are
resistant to agents such as amoxicillin, trimethoprim/sulfamethoxazole.

69. Contd...
Hospital-acquired (eg:pneumonia). Have been effective for gram-
negative pneumonia.
Aspiration pneumonia. Should not be used because of their lack of activity
against anaerobes.
Atypical pneumonia (eg: Mycoplasma, Chlamydia, Legionella). Further
studies are needed to determine the role of quinolones in these infections.
Bone and Joint. Gram-positive bacteria. Although data exists to
demonstrate their effectiveness, quinolones are not the drugs of choice
because of their moderate activity against Staphylococci, and tendency for
resistance to develop.

70. Metronidazole

71. Contraindicated in Pregnancy (1st trimester for trichomoniasis).

72. Metronidazole is an antiprotozoal drug, active against most
anaerobic gram-negative bacilli (ie, Bacteroides, Prevotella,
Fusobacterium) as well as Clostridium species but has
minimal activity against many anaerobic gram-positive and
microaerophilic organisms.
It is well absorbed after oral administration and is widely
distributed in tissues.
It penetrates well into the cerebrospinal fluid, yielding levels
similar to those in serum.
The drug is metabolized in the liver, and dosage reduction is
required in severe hepatic insufficiency or biliary dysfunction.

73. Mechanism Of Action
Metronidazole is cytotoxic to facultative anaerobic bacteria
Four Step Process of Action
1. Entry into the microorganism — Metronidazole is a low molecular
weight compound that diffuses across the cell membranes of anaerobic and
aerobic microorganisms. However, antimicrobial activity is limited to
anaerobes.
2. Reductive activation by intracellular transport proteins — Metronidazole is
reduced by the pyruvate:ferredoxin oxidoreductase system in the mitochondria of
obligate anaerobes, which alters its chemical structure. Pyruvate:ferredoxin
oxidoreductase normally generates ATP via oxidative decarboxylation of pyruvate.
With metronidazole in the cellular environment, its nitro group acts as an electron
sink, capturing electrons that would usually be transferred to hydrogen ions in this
cycle. Reduction of metronidazole creates a concentration gradient that drives
uptake of more drug, and promotes formation of intermediate compounds and free
radicals that are toxic to the cell.

74. 3. Reduced intermediate particle interacts with intracellular targets —
Cytotoxic intermediate particles interact with host cell DNA, resulting in DNA
strand breakage and fatal destabilization of the DNA helix.
4. Breakdown of cytotoxic intermediate products — The toxic intermediate
particles decay into inactive end products

77. Clinical Use
Vaginitis caused by Trichomonas vaginalis :
Single dose of either metronidazole or tinidazole (2 g) or 500 mg orally three times
daily for 7 days.
Bacterial vaginosis
500 mg twice daily for 7 days.
Metronidazole vaginal cream (0.75%) applied twice daily for 5 days is also effective.
Anaerobic infections,
Metronidazole can be given orally or intravenously, 500 mg three times daily (30
mg/kg/d).
Metronidazole is active against virtually all of B fragilis isolates.

78. Clinical Use Contd:
Preparation of the colon before bowel surgery.
Therapy of brain abscess, often in combination with penicillin or a
third-generation cephalosporin.
In combination with clarithromycin and omeprazole for therapy of
H pylori infections.

79. Adverse Reactions
Seizures, peripheral neuropathy, GI upset, anorexia, constipation,
headache, metallic taste, dysuria
High doses and/or long-term systemic treatment with
metronidazole is associated with the development of leukopenia,
neutropenia, increased risk of peripheral neuropathy and/or
CNS toxicity.

80. Macrolides

81. Drugs
Erythromycin
Clarithromycin
Azithromycin

82. Mechanism of Action
Erythromycins inhibit protein synthesis by binding to the
50S subunit of bacterial ribosomes.Which causes
dissociation of t-RNA from the ribosome inhibits protein
synthesis.
They generally are bacteriostatic and sometimes bactericidal
for gram-positive organisms, including most streptococci and
corynebacteria

83. Spectrum Of Activity
Gram positive aerobes - Active against streptococcus
pneumoniae and other streptococci, staphylococci, and
corynebacterium diphtheriae.
Gram negative aerobes - Active against Legionella
pneumophila, Neisseria gonorrhoeae, Moraxella catarrhalis,
Bordetella pertussis.
Enterobacteriaceae are resistant.
Anaerobes - Bacteroides fragilis are usually resistant.
Other - Mycoplasma pneumoniae, chlamydia
trachomatis/pneumoniae, Treponema pallidum.

84. Clinical Use
Community-acquired Pneumonias - where atypical
pathogens such as Mycoplasma pneumoniae and Legionella
pneumophilia are common.
Chlamydial infections (ie. chlamydia pneumoniae
pneumonia or chlamydia trachomatis pelvic infections,
especially in pregnancy.)
Bordetella pertussis

85. Streptococcal infections in patients with Penicillin allergy
Minor staphylococcal skin infections
Campylobacter gastroenteritis
Syphilis in pregnancy
Prophylaxis of bacterial endocarditis

86. Dosage
Oral - Several oral preparations are available: Available as
capsules and film-coated tablets.
Dose is 250-500 mg po q6 hours, 500 mg po q12h depending
on the severity of illness and the indication.
Parenteral - Used for patients with serious infections or
patients unable to take oral medications. Dose is 250-1000 mg
iv q6h.
Must be given as an intravenous infusion.

87. Clarithromycin and Azithromycin
Gram positive aerobes - Clarithromycin is 2-4 times more active in vitro
than erythromycin against most streptococci and staphylococci.
Azithromycin is 2-4 times less active against the gram positives compared
to erythromycin.
Gram negative aerobes - Azithromycin has greater activity than both
erythromycin and clarithromycin against Moraxella catarrhalis and
Hemophilus influenzae.

88. Clinical Use
Upper and lower respiratory tract infections (ie. pharyngitis,
sinusitis, bronchitis and pneumonia) - to cover pathogens usually
seen in these infections such as S. pneumoniae, H. influenzae,
M. pneumoniae, M. catarrhalis.
Skin infections – uncomplicated
Non-gonococcal urethritis and cervicitis due to Chlamydia
trachomatis (Azithromycin only).
Mycobacterium Avium Complex in patients with AIDS -
Clarithromycin is approved for treatment, and must be used in
combination with at least one other drug. Both clarithromycin and
azithromycin are approved for MAC prophylaxis.
Helicobacter pylori - Clarithromycin

89. Dosage
Clarithromycin
Dose is 250-500 mg po q12 hours depending on infection being
treated, usually upto 7 days
Azithromycin
500 mg once daily for 3 days or
500 mg on first day and 250mg once daily for 4 days

90. Thank you!!