This document provides information on beta lactam antibiotics and cell wall synthesis inhibitors. It discusses the classification, properties, mechanisms of action and resistance, kinetics, adverse effects and individual agents of penicillins and cephalosporins. Penicillins are derivatives of benzylpenicillin and inhibit the last step of peptidoglycan synthesis in bacterial cell walls. Cephalosporins are similar to penicillins in their mechanism of action but have greater antimicrobial spectra due to modifications at the C7 and C3 positions. Both classes face resistance from bacterial production of beta-lactamases.

1. BETA LACTAM
ANTIBIOTICS AND OTHER
CELL WALL SYNTHESIS
INHIBITORS
Ma. Shiela Cano-Guiking, M.D.

3. ♦PENICILLINS
♦ I. CLASSIFICATION
♦ A. PenicillinaseResistant
( Antistaphylococcal Penicillins)
♦ 1. Methicillin ( Staphcillin)
2. Nafcillin (Unipen, Nafcil, Nallpen)
3. Isoxazolyl penicillins
♦ a. Oxacillin
b. Cloxacillin
c. Dicloxacillin
d. Flucloxacillin

4. ♦ B. Penicillinase-Susceptible
♦ 1. Narrow-Spectrum
♦ a. Benzylpenicillin – Penicillin G
b. Phenoxymethyl penicillin –
♦ Penicillin V
♦ 2. Extended Spectrum
♦ A. Aminopenicillins
♦ a.1 Ampicillin
a.2 Esters
a.2.1. Bacampicillin
a.2.2. Pivampicillin
a.2.3. Talampicillin
a.3. Amoxicillin

5. ♦ B. Carboxypenicillins
♦ a.1 Carbenicillin
♦ a.1.1. Indanyl carbenicillin
e.g Geopen
a.1.2. Disodium carbenicillin
e.g. Pyopen
a.2. Ticarcillin
a.3. Temocillin
♦ C. Ureido-penicillins
c.1. Mezlocillin
c.2. Azlocillin
c.3. Piperacillin
c.4. Apalcillin

6. ♦ II. GENERAL PROPERTIES
♦ A. Chemical Properties
♦ Penicillins are derivatives of
benzylpenicillin, from which the
methyl benzene radical is split off
by amidase producing
6-aminopenicillanic acid,
the parent compound of all
semisynthetic penicillins

7. ♦ The compound consists of 2 basic structures:
♦ 1 Thiazolidine Ring (A)
♦ 2.Beta-Lactam Ring (B)
♦ - Site of action of Beta-lactamase
♦ - Site of action of Amidase
♦ - Site of attachment of side chain ®, which
determines many of the antibacterial and
pharmacologic characteristics of a derivative
( spectrum and penicillin-resistance)

9. ♦ Mechanisms of Action:
♦ Specific:
♦ inhibit the last step in the
♦ peptidoglycan synthesis of
the cell wall
♦ Underlying:
♦ 1. inhibition of transpeptidase
♦ enzymes
2. activation of penicillin binding
♦ proteins (PBPs)
3. activation of autolysins
♦ (murein hydrolases)

15. •
♦ C. Mechanisms of Resistance
♦ 1. inactivation of antibiotic by Beta lactamases
♦ 2. modification of PBPs
♦ 3. impaired penetration of drug to target PBPs
♦ 4. presence of an efflux pump
♦ Kinetics:
♦ - absorption vary with the preparation depending
on their acid stability and protein binding
♦ - absorption of most oral penicillins (except
amoxicillin) impaired by food and drugs
should be given 1-2 hours before or after
meal; parenteral – complete and rapid

16. ♦ - cannot penetrate the blood-brain barrier; but
50% of the plasma concentration can pass through
in the presence of inflammation:
♦ Probenecid and certain organic acids can inhibit
transfer from cerebrospinal fluid (CSF) to blood
stream; may lead to increase CSF level.
♦ - Metabolized by the liver to
penicillanic/penicillenic acid; penicillamine,
penicilloic acid and other penicilloyl derivatives
(allergenic metabolites)
♦ - Excreted primarily by the kidneys (90% tubular
secretion, 10% glomerular filtration) small amount
through bile and feces, sputum and milk; renal
excretion inhibited by probenecid

17. ♦ E. Adverse Effects:
♦ 1. Hypersensitivity reactions
♦ most common adverse effects - cause the highest
incidence of antibiotic allergy
♦ a. major antigenic determinant- penicilloyl
metabolite skin testing( penicilloyl polylysine
(PPL) )
♦ b. Signs and symptoms:
- varied skin rashes and purpuric
reactions
- angioedema and anyaphylactic
reactions
- fever
- eosinophilia
- interstitial nephritis

18. ♦ 2.Gastrointestinal disturbances after oral
administration
♦ 3.Convulsions following rapid IV administration
♦ 4. Accidental injection into the
sciatic nerve – severe pain and nerve
dysfunction persisting for weeks
5. Chronic use may cause: hepatitis
overgrowth of minor/atypical organisms following
use of broad spectrum preparations

19. ♦6. Specific toxicities:
♦a. Procaine Penicillin G after accidental IV
injection: pulmonary embolism
acute psychotic reactions
♦b. Oxacillin and Nafcillin
hepatitis
granulocytopenia, bone marrow depression
♦c. Disodium Carbenicillin and high dose
Penicillin G Na
-hypernatermia
♦d. Penicillin G Potassium
hyperkalemia with high doses

20. ♦ e. Penicillin G Sodium
Jarisch_herxheimer reaction with high doses
in secondary syphilis
♦ f. Carbenicillin and Ticarcillin
bleeding diathesis
♦ g. Methicillin
interstitial nephritis
♦ h. Ampicillin
associated with pseudomembranous colitis

23. ♦ III. INDIVIDUAL AGENTS
♦ A. Penicillin G
♦ 1. Antimicrobial Spectrum
- Streptococci, meningococci, enterococci, pen.
susceptible pneumococci, non-B lactamase
producing staph, Treponema, spirochetes, B.
anthracis, Clostridium, Actinomyces, G(+) rods and non
B lactamase producing G (-)anaerobic organisms
♦ 2.Kinetics
- 1/3 of oral dose absorbed from intestinal tract
rapidly; food impair absorption
- maximal concentration: 30-60 min.

27. ♦ - intravenous
a. Aqueous Penicillin G
- peak in 15-30 min
-T ½ - 0.5-2 hrs.
♦ - intramuscular
♦ B. Procaine Penicillin G
peak in 1-3 hrs.
T1/2 – 12 hrs.
♦ C. Benzathine Penicillin G
♦ mean duration of antimicrobial activity - 26 days
- 60% albumin bound
♦ - widely distributed to the tissues and body fluids
- does not readily enter the cerebrospinal
fluid when meninges are not inflamed
♦ - probenecid and uremia inhibits active
transport secretion into the blood stream

28. ♦ Preparations:
♦ “ International Units “ – measure of strength
♦ Oral Preparations:
♦ Penicillin G Sodium
Penicillin G Potassium
♦ Parenteral Preparations
♦ 1.short acting
a. aqueous Penicillin G Potassium – 1.7 meq K/1M “u”
b. aqueous Penicillin G Sodium – 2.4. meq Na/1M “u”
♦ 2. long acting
a. Procaine Penicillin G – 300,000 – 600,000 “u”
120 mg procaine/vial
b. Benzathine Penicillin G – 600,000 “u”
1.2 M “u”/vial

29. ♦ 4. Doses and Therapeutic Uses
♦ a. Aqueous Penicillin G
♦ Child: mild infections –
50,000 “u” – 100,000 “u”/kg/day in equally
divided Doses every 4-6 hrs. for 7 days
♦ Severe infections –
200,000 “u” – 600,000 “u”/kg/day in
equally divided Doses every 2-6 hrs.
for 14 days.

30. ♦ a. Procaine Penicillin G – 300,000 – 600,000 “u” IM
OD or BID for 7 days for Adults
♦ b. Benzathine Penicillin G – 1.2 million – 2.4 “u” IM
monthly
♦ Syphilis – less than 1 year duration –
2.4 M “u” IM + Probenicid 1 gm/day for 10 days
or 2.4 M “u” Benzathine Penicillin G IM single
dose
♦ late latent, complicated – 20 M “u” aqueous Penicillin
G/day for 10 days
♦ congenital syphilis – 50,000 “u”/kg/day aqueous
Penicillin G for 10 days

42. ♦ Staphylococcal infections
Gram (+) anaerobes
Meningococcal infections
Gonococcal infections
Carrier state diphtheria
♦ Other unusual infections – actinomycosis,
Anthrax, rat bite fever, listeria,
pasteurella, lyme disease, erysipeloid
♦ Prophylaxis – recurrences of streptococcal,
rheumatic fever, gonorrhea, syphilis,
bacterial endocarditis

43. ♦ D . Penicillin V
♦ Oral form indicated only in minor infections
Relative poor bioavailability; need for
dosing 4x a day
♦
Gram (+) aerobic activities similar to
Penicillin G
5-10x less active against gram(-)
microbes, esp. Neisseria and certain
anaerobes
better absorbed from the gastrointestinal

44. ♦ D. Ampicillin
♦ 1. Microbial Spectrum
Somewhat less active than Penicillin G against
gram (+) cocci Enterococcal grp. D and viridans
grp. Of streptococci
- Listeria monocytogenes
- H. influenza
♦ Effective for Shigellosis
♦ Should not be used for uncomplicated salmonella
gastroenteritis – may prolong the carrier state

45. ♦ 2. Kinetics:
♦ Gastric acid stable and well absorbed from
the gastrointestinal tract
Orally absorbed drug peaks in 2 hrs.
♦ Intramuscular administered drug peaks in
1 hour
Mainly excreted by the kidneys; also thru
the bile and feces
♦ Undergoes enterohepatic circulation
♦ Other kinetic properties similar to
Penicillin G Sodium

46. ♦ 3. Adverse Effects:
♦ “Ampicillin skin rash” – occurs in 7-8%
others similar to Pen G
♦ 4. Preparations
♦ a. Oral
♦ Capsules – 250-500 mg
Suspension – 125 mg, 250 mg/5 ml
Drops – 100 mg/ml
♦ b. parenteral
250 mg; 500 mg/ml vial

47. ♦ 5. Doses
♦ a. mild infections
Newborn – 25-50 mg every 12 hrs.
Child – 50-100 mg/kg/d in 4-6 divided doses
Adult – 1-4 gm/day
♦ b. severe infections
Child – 200-600 mg/kg/day
Adult – 6-12 gm/day
♦ E. Esters of Ampicillin
♦ No inherent antimicrobial activity as esters, but
pharmacologically active following hydrolysis to
Ampicillin
50% higher blood concentration than
Ampicillin and Amoxicillin

48. ♦
F. Amoxicillin
♦ Closely related to Ampicillin in chemical
and pharmacologic properties
♦ More rapidly and completely absorbed
from gastrointestinal tract
Attains higher serum levels than
ampicillin

49. ♦ G. CARBOXYPENICILLINS AND
UREIDOPENICILLINS
♦ 1. Antimicrobial Spectrum
Gram (-) aerobes
Pseudomonas aeroginosa
Bacteroides fragilis; but in higher
amount/dose
♦ Carboxypenicillins – certain indole (-)
Proteus
Ureidopenicillins – Klebsiella
Azlocillin – 10x more active than
carbenicillin against Pseudomonas

50. 2.Preparations
a. Carbenicillin Disodium salt – contains
approximately 5 meq sodium/gm for
parenteral administration
Indanyl esters – 500 mg tablets
b.Ureidopenicillins
Parenteral preparations

51. ♦ H. Penicillinase-Resistant
♦ 1. Methicillin -15-80x more active against
penicillinase producing microbes than Penicillin G;
only parenterally available; currently many
resistant strains of Staph. Aureus have emerged,
no longer used because of nephrotoxicity
♦ 2. Nafcillin – slightly more active than Cloxacillin
against penicillinase producing Staph. Aureus,
available in oral and parenteral preparations: GIT
absorption is erratic
♦ 3. Isoxazolyl Penicillins
Stable in gastric acid and adequately absorbed
after oral administration
Dicloxacillin is most active against penicillinase

52. ♦ CEPHALOSPORINS
♦ I. CLASSIFICATION
♦ A. First Generation
♦ 1. Cephaloridine-Loridine, Ceporan
♦ 2. Cephalothin-Keflin
♦ 3. Cephalexin-Keflex, Ceporex
♦ 4. Cefazolin-Cefacidal
♦ 5. Cephradine-Velosef
♦ 6. Cepharpirin-Cefadyl
♦ 7. Cephadroxil-Doricef, Cefamox

53. – B. Second Generation
♦ 1. Cefaclor-Ceclor
♦ 2. Cefoxitin – Mefoxin
♦ 3. Cefuroxime – Zinacef, Zinnat
♦ 4. Cefonicid – Monocid
♦ 5. Cefotetan - Cefotan
♦ 6. Cefamdandole – Mandol
♦ 7. Cefprozil – Cefzil
♦ 8. Loracarbef – Lorabid
♦ 9. Cefmetazole – Zefazone
♦ 10. Ceforanide

54. ♦ C. Third Generation
♦ 1. Cefotaxime – Claforan
♦ 2. Cefoperazone – Cefobid
♦ 3. Moxolactam – Moxam
♦ 4. Ceftizoxime – Cefizox
♦ 5. Ceftriaxone – Rocephin
♦ 6. Ceftazidime – Fortum
♦ 7. Cefotiam – Ceradolan
♦ 8. Cefixime – Suprax
♦ 9. Cefetamet – Globocef
♦ 10. Cefpodoxime – Vantin
♦ 11. Ceftibuten – Cedax
♦ 12. Cefdinir –Omnicef
♦ 13. Cefditoren

55. ♦ D. Fourth Generation
1. Cefepime – Maxipime
2. Cefpirome – Cefrom
♦ II. BASIS FOR CLASSIFICATION
A. Antimicrobial Spectrum
B. Pharmacokinetic Properties

56. ♦ III. GENERAL PROPERTIES
♦ A. Chemistry
♦ 7-amino cephalosporanic acid – parent
compound
♦ contains an R2 that makes the compound
stable in dilute acid and highly
penicillinase resistant
* MW – 400-450
*Soluble to water and relatively stable to
ph and temperature changes

58. ♦ C7 modifications alter antibacterial activity
♦ C3 substitutes change metabolism and kinetic
properties
♦ B. MECHANISM OF ACTION AND RESISTANCE
Similar to penicillins
♦ C. Antimicrobial Spectrum
Generally broader spectrum than Penicillins
Generally more effective than Penicillins
against B- lactamase-producing microbes
(except enterococci, Methicillin-resistant Staph.
aureus and Staph. epidermis)

59. ♦ D. SPECIFIC GROUPS/INDIVIDUAL
AGENTS
♦ 1. FIRST GENERATION
♦ Good activity against gram (+) and modest
against gram (-) microbes
♦ Penetration of the cerebrospinal fluid (CSF) is
inadequate
♦ UTI, minor staph lesions, minor polymicrobial
infections – cellulitis, soft tissue abscess

60. ♦ 2. SECOND GENERATION
♦ Better activity against anaerobes and
gram (-) aerobes
♦ Only Cefuroxime can produce sufficient
CSF level
♦ Sinusitis, otitis, LRTI, mixed anaerobic
infections such as
peritonitis/diverticulitis

61. ♦ 3. THIRD GENERATION
♦ Generally less active than the first
generation against gram (+) cocci
but most active against gram (-)
including B-lactamase- producing strains
♦ Cefoperazone, Ceftazidime –
(more active) against Pseudomonas

62. ♦ Active against anaerobes – Cefoperazone,
Cefotaxime
♦ Ceftizoxime, Moxolactam – B. fragilis
♦ Cefoperazone & Ceftriaxone
♦ -excreted primarily in the bile;
♦ Probenecid does not affect
renal excretion
♦ Cross BBB except Cefoperazone,
Cefixime, Ceftibuten and
Cefpodoxime proxetil

63. ♦ Ceftriaxone, 125 mg inj.,
♦ Cefixime, single 400 mg oral dose -N. gonorrhea
♦ Cefoperazone –(T1/2 – 2 hrs. ) 25-100 mg/kg/d
injected q 8-12 hrs
♦ Cefixime 200 mg orally twice a day or 400 mg OD
Cefpodoxime proxetil & Ceftibuten –
200 mg 2x/day
Meningitis caused by pneumococci,
meningococci, H. influenza & susceptible
enteric gram (-) rods but not by L.
monocytogenes;
♦ should be used in combination with aminoglycoside for the
treatment of meningitis caused by P. aeruginosa.

64. ♦ 4. FOURTH GENERATION
♦ More resistant to hydrolysis by chromosomal
beta lactamases (eg. Those produced by
enterobacter)
♦ Good activity against P. aeruginosa,
enterobacteriaceae, staph. aureus,
S. pneumoniae
Highly active against Haemophilus & Neisseria
♦ Penetrates well into CSF
Cleared by kidneys
T1/2 – 2 hrs
Good activity against most penicillin resistant
strains of streptococci
Useful in the treatment of enterobacter
infections

65. ♦ E. ADVERSE EFFECTS
1. Allergy
2. Toxicity:
3. Renal toxicity
– interstitial nephritis and even tubular
necrosis
♦ Cephalosporin that contains a methyl thiotetrazole
group ( Cefamandole, Cefmetazole, Cefotetan,
Cefoperazone)
♦ – cause disulfiram like
reactions, hypoprothrombinemia
and bleeding disorders-
♦ Antidote: Vit K, 10 mg 2x/week
♦ Moxolactam – interferes with platelet

66. MONOBACTAMS
Monocyclic beta lactam ring
Resistant to B-lactamase
Active against gram (-) rods including
Pseudomonas and Serratia
Aztreonam – resembles aminoglycosides in
spectrum of activity
Given 1-2 g IV q 8 hrs.; T1/2 – 1-2 hrs

67. ♦ BETA LACTAMASE INHIBITORS ( CLAVULANIC
ACID, SULBACTAM & TAZOBACTAM)
♦ Resemble B- lactam molecules
Bind to Beta-lactamase, inactivate them and
prevent the destruction
♦ Synergistic with other beta-lactams
♦ A. Clavulanic Acid – produced by S. Clavuligerul
potentnt inhibitor of beta-lactamases (plasmid
encoded)
weak antibacterial action combined with
Amoxicillin (Augmentin) or
Ticarcillin( Timentin):
the combination widens the antimicrobial
spectrum
B. Sulbactam Pivoxil and Ampicillin ( Unasyn)

68. ♦ CARBAPENEMS
♦ - structurally related to Beta lactam
antibiotics
♦ 1. Imipenem – gram (-) rods, gram (+) org. &
anaerobes inactivated by dehydropeptidases in
renal tubules resulting in low urinary
concentration
combined with Cilastatin ( dehydropeptidase
inhibitor ) to reduce inactivation
♦ penetrates body tissues and fluids well including
the CSF
.25-0.5 g IV q 6-8 hrs
Adverse effects include nausea, vomiting,
diarrhea, reactions to infusion site; excessive
in renal failure –
seizures
♦ 2. Meropenem – slightly greater activity
against gram (-) aerobes
does not require an inhibitor

69. ♦ ERTAPENEM
-Less active than meropenem or imipenem
against Pseudomonas aeruginosa and
acinetobacter species
- It is not degraded by renal dehydropeptidase

70. ♦ OTHER CELL WALL SYNTHESIS
INHIBITORS
♦ 1. VANCOMYCIN
♦ Gram (+) staph
Water soluble and quite stable
♦ MOA - Inhibits cell wall synthesis by binding
firmly to D-Ala-D-Ala terminus of nascent
peptidoglycan pentapeptide
♦ Resistance – modification of the D-Ala-D-Ala
binding site of the peptidoglycan building block in
which the terminal D-Ala is replaced by D-
lactate resulting to loss of a critical H bond that
facilitates high affinity binding of vancomycin to
its target and loss of activity

71. ♦ Synergistic with gentamicin and Streptomycin
against E. faecium and E. faecalis strains that do
not exhibit high levels of aminoglycoside
resistance
♦ Poorly abosorbed from the GIT
Administered orally for the treatment of
antibiotic associated enterocolitis caused by C.
difficile; 0.125 – 0.25 g q 6 hrs
♦ 99% excreted by glomerular filtration
T1/2 6-10 days – not removed by dialysis

72. ♦ - Sepsis or endocarditits caused by Methicillin
resistant staph
Combined with Cefotaxime, Ceftriaxone or
Rifampicin for the treatment of meningitis
suspected or known to be caused by a highly
penicillin resistant strain of pneumococcus.
♦ - Recommended dosage is 30 mg/kg/day in two
or three divided doses
- Adults with normal renal function – 1 g every
12 hrs
Children – 40 mg/kg/d in 3 to 4 divided dose -
♦ Causes phlebitis, chills and fever, ototoxicity,
nephrotoxicity, red man or red neck syndrome

74. ♦ 2. FOSFOMYCIN
♦ - inhibits a very early stage of bacterial cell
wall synthesis
- inhibits cytoplasmic enzyme enol pyruvate transferase by
covalently binding to the cysteine residue of the active
site and blocking the phosphoenolpyruvate to UDP-N-
acetylglucosamine – 1st step in the formation
of UDP-N- acetylmuramic acid, the
precursor of acetylmuramic acid – found
only in bacterial cell walls.
♦

75. ♦ - Drug is transported into the cell by
glycerophosphate or glucose 6 phosphate
transport systems
- Resistance is due to inadequate transport of drug
into the cell
♦ - Active against both Gram (+) and Gram (-)
- In vitro synergism with beta lactams,
aminoglycosides or fluoroquinolones
- Available orally ( 2-4 g, single dose in
uncomplicated UTI) and parenterally
- Excreted through the kidneys
- Safe in pregnancy

76. 4. BACITRACIN
- cyclic peptide mixture
- active against Gram (+) organisms
- inhibits cell wall formation by interfering
with dephosphorylation
- in cycling of the lipid carrier that transfers
peptidoclycan subunits to the growing cell
wall
nephrotoxic
- poorly absorbed; limited to topical use
500 units/g ointment + Polymyxin B or
Neomycin

78. ♦ 5. CYCLOSERINE
♦ - water soluble; very unstable at acid ph
treat tuberculosis caused by M. tuberculosis
resistant to first line agents
- structural analogs of D-alanine and inhibits
incorporation of D-alanine into peptidoglycan
pentapeptide by inhibiting alanine racemase
which converts L alanine to D alanine and D-
alanyl- D-alanine ligase
♦ - widely distributed into tissues
- excreted through the urine
- 0.5 – 1 g /d in 2 – 3 divided doses
- causes dose related CNS toxicity,
headaches, tremors, acute psychocis,
convulsions

81. THANK YOU
VERY MUCH
AND
STUDY WELL!

82. PROTEIN SYNTHESIS
INHIBITORS
Ma. Shiela Cano-Guiking, M.D.

83. The 30 S Inhibitors:
I. AMINOGLYCOSIDES
Older Aminoglycosides:
Streptomycin
Kanamycin
Newer Aminoglycosides:
Gentamicin
Tobramycin
Neomycin
Amikacin
Netilmicin
Sisomicin

84. Antimicrobial Spectrum:
1. Gram (-) Aerobic Bacilli
2. Beta-lactamase producers:
Staph. aureus
N. gonorrhea
3. Mycobacteria
Mechanism of Action:
- interferes with initiation complex of peptide
formation
- induces misreading of mRNA causing
incorporation of incorrect AA
causes breakup of polysomes into nonfunctional
monosomes
- Requires oxygen uptake, therefore ineffective
against anaerobes.
- Bactericidal

85. Microbial Resistance:
1. enzyme inactivation
2. Cell surface alteration
3. receptor protein alteration
4. oxygen requirement related
Kinetics:
minimally absorbed from the GIT, well absorbed thru
IM, IV
poorly penetrate the BBB
not significantly metabolized
primarily executed unchanged through GF
Clinical Uses:
severe gram (-) rod infections
Mycobacterial infections

87. Toxicity:
Ototoxicity (esp. with loop diuretics)
Auditory damage – Neomycin, Kanamycin
and Amikacin
Vestibular Damage – Streptomycin,
Gentamicin
Nephrotoxicity (esp. with cephalosporins)
Neomycin, Tobramycin, Gentamicin- most
nephrotoxic

88. STREPTOMYCIN
- ribosomal resistance to this agent develops readily, limiting its
role as a single agent
- mainly used as a second line agent for treatment of
tuberculosis
- given at 0.5-1 g/d (7.5-15 mg/kg/day for children) IM or IV
should be used only in combination with other agents to
prevent emergence of resistance
- In plague, tularemia and sometimes brucellosis, 1 g/d
(15 mg/kg/day for children) IM or IV + oral tetracycline
+Penicillin; effective for enterococcal endocarditis and 2 week
therapy of viridans streptococcal endocarditis
- Can cause fever, skin rashes and other allergic reactions, pain
at injection site, vestibular dysfunction – most serious toxic
effect
If given during pregnancy, can cause deafness in the newborn

89. GENTAMICIN
employed mainly in severe infections (sepsis and
pneumonia) caused by gram (-) bacteria in
combination with a cephalosporin or a penicillin
may be life saving
given at 5-6 mg/kg/day IV in three equal doses
+ Penicillin G for bactericidal activity in endocarditis
due to viridans streptococci or enterococci and in
combination with Nafcillin in selected cases of
staphylococcal endocarditis
Serum concentrations and renal function should be
monitored if administered for more than a few days
or if renal function is changing (eg. Sepsis; often
complicated by acute renal failure)

90. Gentamicin sulfate 0.1% -0.3% cream, ointment – for the
treatment of infected burns, wounds, or skin lesions and the
prevention of intravenous catheter infections
Topical gentamicin is partly inactivated by purulent exudates
Ten milligrams can be injected subconjunctivally for
treatment of ocular infections.
Nephrotoxicity is reversible and usually mild; Irreversible
ototoxicity manifested as vestibular dysfunction,
hypersensitivity reactions are uncommon

91. TOBRAMYCIN
Antimicrobial spectrum and pharmacokinetic
properties virtually identical to gentamicin
Given at 5-6 mg/kg IM or IV into three equal
amounts q 8 hours
Blood levels should be monitored in renal
insufficiency
Slightly more active against pseudomonas but not E.
faecium
Ototoxic and nephrotoxic

92. AMIKACIN
semisynthetic derivative of kanamycin
resistant to many inactivating enzymes
for tuberculosis; given at 7.5 – 15 mg/kg/d as a once
daily or 2- 3x weekly
Serum concentrations should be monitored
Nephrotoxic and ototoxic

93. NETILMICIN
shares many characteristics with gentamicin and
tobramycin
dosage and the routes of administration are the same,
completely therapeutically interchangeable with
gentamicin or tobramycin and has similar
toxicities

94. KANAMYCIN AND NEOMYCIN
Paromomycin is also a member of this group and all have
similar properties
Used for bowel preparation for elective surgery
There is complete cross-resistance between kanamycin and
neomycin
Not significantly absorbed from the GIT; excretion of any
absorbed drug is mainly through GF into the urine
Too toxic for parenteral use, now limited to topical and oral use
Solutions 1-5 mg/ml – used on infected surfaces or injected into
joints, pleural cavity, tissue spaces or abscess cavities where
infection is present (15 mg/kg/day)

95. Ointments (Neomycin-Polymyxin-Bacitracin combination)
applied to infected skin lesions or in the nares for suppression of
staphylococci
In preparation for elective bowel surgery, 1 g of Neomycin
given orally q 6-8 hours + 1 g of erythromycin base;
Paromomycin, 1 g q 6 hours orally for 2 weeks; effective in
intestinal amoebiasis
Sudden absorption of postoperatively instilled kanamycin from
the peritoneal cavity (3-5 g) has resulted in curare-like
neuromuscular blockade and respiratory arrest (Calcium gluconate
and neostigmine can act as antidotes)
Prolonged application to skin and eyes-severe allergic reactions

99. SPECTINOMYCIN
chemically related to the aminoglycosides
binds at the 30 S subunit (bacteriostatic)
Dispensed as the dihydrochloride pentahydrate for IM
injection
Used almost solely as an alternative treatment for
gonorrhea in patients who are allergic to penicillin
or whose gonococci are resistant to other drugs
Single dose of 2 g ( 40 mg/kg )

101. II.TETRACYCLINES:
Short Acting:
Tetracyline, Oxytetracycline, Chlortetracycline
Intermediate Acting:
Demeclocycline, Methacycline
Long Acting:
Doxycycline, Minocycline
Antimicrobial Spectrum:
Rickettsia, V. cholera, M. pneumonia, Chlamydia, Shigella, H.
pylori, P.tularensis, P. pseudomallei, Brucella, Psittacosis, Borrelia
Minocycline – carrier state of Meningococcal infections,
N. asteroides
N. gonorrhea

102. Mechanism of Action:
- enter microorganisms in part by passive diffusion and in part by
an energy dependent process of active transport
binds to 30 S and prevents attachment of aminoacyl tRNA,
prevents the addition of amino acids to the growing peptide
Bacteriostatic
Resistance:
decreased intracellular accumulation due to impaired influx or
increased efflux by an active transport protein pump
ribosome protection due to production of proteins that interfere
with tetracycline binding to the ribosome
enzymatic inactivation

103. Kinetics:
limited CNS penetration
absorption occurs mainly in the upper small intestine
and is impaired by food ( except Doxycycline and
Minocycline)
Must not be taken with milk or antacids
Cross placenta, excreted in milk
Carbamazepine, phenytoin, barbiturates, and chronic
alcohol ingestion may shorten the half life of
doxycycline
Excreted mainly in bile and urine ( Doxycycline
fecally eliminated; can be used in renal failure

104. Clinical Uses:
Borrelia burgdorfi (Lyme disease), Chlamydia, Ureaplasma, M.
pneumonia, Rickettsia, Acne, Tularemia, Cholera,
Leptospirosis, Protozoal infections
Minocycline, 200 mg orally daily for 5 days, can eradicate the
meningococcal carrier state
Demeclocycline – inhibits the action of ADH in the renal tubule and has
been used in the treatment of inappropriate secretion of ADH or
similar peptides by certain tumors
Tetracycline – 250-500 mg 4x/day adults
20-40 mg/kg/d – children above 8 y/0
600 mg daily dose for Demeclocycline and Methacycline
100 mg 1-2x/d for Doxycycline and Minocycline
Toxicity: Renal toxicity, local tissue toxicity, photosensitization, GI
distress, discolors teeth, inhibits bone growth in children, potentially
teratogencic, hepatotoxicity, vestibular toxicity

106. THE 50 S INHIBITORS:
CHLORAMPHENICOL
MACROLIDES
CLINDAMYCIN/LINCOMYCIN
STREPTOGRAMINS
OXAZOLADINONES

107. I CHLORAMPHENICOL
Bactericidal – H. influenzae, N. meningitides, B. fragilis
Bacteriostatic – S. epidermidis, S. aureus, , M. pneumonia, L.
monocytogenes, diphtheria, L. multocida, Salmonella sp., Shigella
sp., E. coli, Rickettsia, Anaerobes,ineffective for chlamydial
infections
Mechanism of Action:
attaches at P sites of 50 S subunit of microbial ribosomes and
inhibits functional attachment of amino-acyl end of AA-t-RNA to
50 S subunit
inhibits peptidyl transferase step

108. Spectrum:
broad spectrum antibiotic
more effective than Tetracyclines against Typhoid Fever and
other Salmonella infections
Kinetics:
well absorbed after oral administration
Chloramphenicol succinate used for parenteral administration is
highly water soluble
distributed into total body water
excellent penetration into CSF, ocular and joint fluids
rapidly excreted in urine, 10% as chloramphenicol; 90% as
glucuronide conjugate
systemic dosage need not be altered in renal insufficiency but
must be reduced markedly in hepatic failure
Newborns less than a week old and premature infants also clear
Chloramphenicol less well, dosage should be reduced at 25
mg/kg/d

109. Uses: meningitis, rickettsia, Salmonella and anaerobic
infections
ineffective against chlamydial infections
occasionally used topically in the treatment of eye
infections for its well penetration to ocular tissues
and the aqeous humor
Adverse Effects: GIT, oral or vaginal candidiasis,
irreversible aplastic anemia, reversible bone
marrow depression, Gray Baby Syndrome

112. II. MACROLIDES:
Old Generation: Erythromycin, Oleandomycin, Troleandomycin,
Spiramycin, Josamycin
New Generation: Rosaramycin, Roxithromycin, Clarithromycin,
Azithromycin, Dirithromycin
Mechanism of Action:
binds to the P site of the 50 S bacterial ribosomal subunit.
Aminoacyl translocation and formation of initiation complex are
blocked
Inhibitory or bactericidal
RESISTANCE:
reduced permeability of the cell membrane or active efflux
production (by Enterobacteriaceae) of esterases that hydrolyze
macrolides
modification of the ribosomal binding site by chromosomal
mutation

113. Spectrum: Erythromycin has a narrow Gram (+) spectrum similar to Pen.
G.
Also active against Chlamydia and Legionella organisms
1. Erythromycin:
prototype
distributed into total body water
poor CSF penetration
food interferes with absorption
serum half life is app. 1.5 h normally and 5 hours in patients with
anuria
not removed by dialysis
metabolized in the liver
traverses the placenta and reaches the fetus

114. Commercial Preparations:
Oral-stearate, ethyl succinate, estolate salts – 250-500 mg q 6 h
adults
40 mg/kg/d - children
Parenteral- lactobionate, gluceptate – 0.5-1 g q 6 hours for adults
20-40 mg/kg/d for children
Adverse Effects: GIT dysfunction, intrahepatic cholestatic jaundice
- Erythromycin metabolites can inhibit cytochrome p450
enzymes and thus increase the serum concentrations of
theophylline, oral anticoagulants, cyclosporine and
methylprednisolone;also oral digoxin by increasing its
bioavailability

115. 2. Clarithromycin
- hydroxylated derivative of erythromycin
- more active against Gram (+) pathogens, Legionella
and Chlamydia than Erythromycin
- lower frequency of GIT effects, less frequent dosing
- Half life of 6 hours
- given at 250-500 mg twice daily

116. 3.Azithromycin
- more active than erythromycin against several Gram (-)
pathogens
- maintains high concentrations for prolonged periods into a
number of tissues (lungs, tonsil, cervix)
- tissue half life – 2-4 days
- long half-life allows once daily oral administration and
shortening of treatment in many cases ( a single 1 g dose of
azithromycin is as effective as a 7 day course of
doxycycline for chlamydial cervicitis and urethritis)
-Community acquired pneumonia – 500 mg loading dose,
followed by a 250 mg
- single daily dose for the next 4 days
-Should be administered 1 hour before or 2 hours after meals;
aluminum and magnesium delay absorption and reduce peak serum
concentrations
Does not inactivate cytochrome p450 enzymes and free of the
drug interactions that occur with erythromycin and clarithromycin

117. AZITHROMYCIN

118. KETOLIDES
♦ - semisynthetic 14 membered ring
macrolides
♦ Telithromycin –
♦ active in vitro against S pyogenes, S.
penumoniae, S. aureus, H. influenzae,
Moraxella catarrhalis, mycopasmas,
legionella sp, chlamydia sp, Helicobacter
pylori, N. gonorrhoaea, B. fragilis, T gondii
and nontuberculosis mycobacteria

119. -Oral bioavailability – 57%
- good tissue and intracellular
penetration
- metabolized in the liver
- eliminated by a combination of biliary and
urinary routes of excretion
- administered as a once daily dose of 800 mg
- indicated for treatment of respiratory tract
infections, including community acquired bacterial
pneumonia, acute exacerbations of chronic
bronchitis, sinusitis and streptococcal pharyngitis
- a reversible inhibitor of the CYP3A4 enzyme
system

120. TELITHROMYCIN

121. III. CLINDAMYCIN/LINCOMYCIN
Mechanism of Action: attach to 50 S
ribosomal subunit, inhibits protein synthesis by
interfering with the formation of initiation
complexes and translocation reaction
Spectrum: Narrow Gram (+) spectrum,
excellent activity against anaerobic bacteria;
strep, pneumococci, staphylococci
Resistance:
mutation of the ribosomal receptor site
modification of the receptor by a
constitutively expressed methylase
enzymatic inactivation

122. Clindamycin is more clinically used than Lincomycin:
excellent absorption
given at 150-300 mg q 6 hrs – adults; 10-20 mg/kg/d
for children
low concentration in CSF
well bone penetration
excreted mainly via the liver, bile and urine
half life is 2.5 hours normally and 6 hours in patients
with anuria
more toxic than erythromycin
prophylaxis of endocarditis in patients with valvular
heart disease for dental procedures

123. most important indication is the treatment of severe
anaerobic infection caused by bacteroides and other
anaerobes that often participate in mixed infections
+ aminoglycoside or cephalosporin used to treat
penetrating wounds of the abdomen and the gut
Septic abortion, pelvic abscesses, aspiration
pneumonia
+ primaquine – effective alternative to trimethoprim
sulfamethoxazole for moderate to moderately severe
Pneumocystis carinii pneumonia in AIDS patients
+ Pyrimethamine for AIDS – related toxoplasmosis
of the brain

124. ADVERSE EFFECTS:
Diarrhea, nausea, skin rashes, impaired liver
function and neutropenia; Antibiotic
associated colitis caused by toxigenic C.
difficile

125. NEWER AGENTS:
STREPTOGRAMINS:
Quinuprisitn-Dalfopristin (Synercid)
action is similar to macrolides except bactericidal for staph and
most organisms except Enterococcus faecium
prolonged postantibiotic effect up to 10 h for Staph. aureus
administered IV at 7.5 mg/kg q 8-12 h
eliminated through fecal route, < 20% urine
inhibits CYP 3A4, which metabolizes warfarin, diazepam,
astemizole, terfenadine, cisapride, nonnucleoside reverse
transcriptase inhibitors and cyclosporine.
Clinical Uses: infections caused by Vancomycin resistant strains of E
faecium but not E. faecalis, bacteremis or respiratory tract infections
caused by methicillin-resistant staphylococci and penicllin susceptibe
and resistant strains of S. pheumonia
Toxicities: infusion related events, pain at the injection site, arthralgia,
myalgia synd

126. STREPTOGRAMIN A

127. STREPTOGRAMIN B

128. OXAZOLADINONES: Linezolid (Zyvox)
inhibits protein synthesis by preventing formation of
the ribosome complex that initiated protein
synthesis.
Its unique binding site located on 23 S ribosomal
RNA of the 50 S subunit, results in no cross resistance with
other drug classes
Has high oral bioavailability, half life of 4-6 h
Uses : staph, strep, enterococci, G(+) anaerobic cocci, G (+)
rods, Corynebacterium, L. monocytogenes
- treatment of infections caused by vancomycin
resistant E. faecium and other infections caused by multiple
drug resistant organisms

130. METABOLIC INHIBITORS:
SULFONAMIDES
- structurally similar to p-aminobenzoic acid (PABA) that
competitively inhibits dihydropteroate synthase
- inhibits growth by reversibly blocking folic acid synthesis
- mammalian cells do not make folic acid and are not affected
- cross the placenta and secreted in breast milk and should not
be given to pregnant Women
- highly bound to plasma proteins esp, albumin
- penetrates CNS well

131. SPECTRUM:
- Gram (+) & Gram (-) Bacteria
- Nocardia
- C. trachomatis
- Enteric bacteria (E. coli, Klebsiella, Salmonella, Shigella
Enterobacter)
Ricketssia – sulfonamides do not inhibit these organisms
but stimulate its growth
Resistance:
- occurs as a result of mutations that:
1. cause overproduction of PABA
2. cause production of a folic acid synthesizing enzyme that has a low
affinity for Sulfonamides
3. cause a loss of permeability to the sulfonamides

132. Pharmacokinetics:
- 3 MAJOR GROUPS:
1. ORAL, ABSORBABLE
2. ORAL, NON-ABSORBABLE
3. TOPICAL
Intravenous Preparation:
- Na salts of sulfonamides in D5W
Oral, absorbable sulfonamides:

133. DRUGS HALF LIFE ORAL ABS
1.short acting
Sulfacytine
Sulfisoxazole
Sulfamethizole
Short
Short (6 h)
Short (9 h)
Prompt (peaks in
1-4h)
Prompt
Prompt
2. Medium acting
Sulfadiazine
Sulfamethoxazole
Sulfapyridine
Intermediate(10-17h)
Intermediate (10-12h)
No data
Slow (peak in 4-8h)
Slow
Slow
Long Acting
Sulfadoxine Long (7-9 days) Intermediate

134. absorbed from stomach and small intestine
- distributed widely to tissues and body fluids
(CSF), placenta and fetus
- protein binding 20% to over 90%
- therapeutic concentration – 40-100 ug/ml of
blood
- peak blood levels – 2h to 6 h after oral
ingestion
- metabolism: glucoronidation or acetylation
in liver
- eliminated in urine-mainly by glomerular
filtration

135. CLINICAL USES:
1. Urinary tract infection
Sulfisoxazole – 1 gm 4x daily }combined with PHENAZOPYRIDINE
Sulfamethoxazole – 1 g 2-3 x daily } (U.T. anesthetic)
2. Respiratory infections
3. Sinusitis, bronchitis, pneumonia
4. Otitis media
5. Dysentery
6. Acute Toxoplasmosis
Sulfadiazine + Pyrimethamine – Synergistic
Block sequential steps in folate synthesis:
Sulfadizine- inhibits dihydropteroate synthase
Pyrimethamine – inhibits dihydrofolate reductase
Dosage – Sulfadiazine – 1 g 4x daily
Sulfadiazine + pyrimethamine – 75 mg loading dose ffd by 25 mg
OD
Folinic Acid – administered to minimize bone marrow
suppression
7. Malaria
- sulfadoxine + pyrimethamine – 2nd line agent in the treatment
for malaria

136. ORAL, NONABSORBABLE AGENTS
Sulfasalazine (Salicylazosulfapyridine)
more effective than soluble sulfonamides or other antimicrobials
taken orally in inflammatory bowel disease
ulcerative colitis
enteritis
other inflammatory bowel disease
split by intestinal microflora to yield:
Sulfapyridine – absorbed and may lead to toxic symptoms
If more than 4 g of sulfasalazine is taken per day esp. in persons
who are slow acetylators
5-aminosalicylate (5-ASA) – released in the colon in high
concentrations and is responsible for an anti-inflammatory effect

137. TOPICAL AGENTS:
Sodium Sulfacetamide ophthalmic solution or ointment
effective for bacterial conjunctivitis
adjunct therapy for trachoma
Mafenide acetate
used topically to prevent bacterial colonization and infection of
burn wounds
inhibits also carbonic anhydrase – cause metabolic acidosis
Silver Sulfadiazine
less toxic topical sulfonamide
preferred to mafenide for prevention of infection of burn woulds
ADVERSE REACTIONS:
Cross allergy with the ffg.
carbonic anhydrase inhibitors, thiazides, furosemide,
bumetanide, furosemide, diazoxide, sulfonylureas, hypoglycemics
Most common adverse effects:
Fever, skin rashes, exfoliative dermatitis, nausea, vomiting,
urticaria, photosensitivity

138. Urinary tract disturbances:
sulfas may ppt. in urine at neutral or acid ph-
Crystalluria – treated with sod. Bicarbonate to alkalinize urine and fluids to
maintain adequate hydration
Hematuria
Obstruction
implicated in nephrosis and allergic nephritis
OTHER SIDE EFFECTS:
Stevens-Johnson Syndrome – uncommon but serious and
potentially fatal type of skin & mucous membrane eruptions
Hematopoietic disturbances:
hemolytic or aplastic anemia, thrombocytopenia, granulocytopenia,
leukemoid reaction, provoke hemolytic reactions in patients with
deficient rbc glucose 6 phosphate dehydrogenase
increased risk of kernicterus in newborns when sulfonamides were
taken near the end of pregnancy
Stomatitis, Conjunctivitis, Arthritis, Hepatitis
Polyarteritis nodosa – rare
Psychosis – rare

139. STEVENS JOHNSON
SYNDROME

142. TOXIC EPIDERMAL
NECROLYSIS

143. TRIMETHOPRIM
well absorbed from the gut
widely distributed in body fluids and tissues incldg. CSF
found in high concentrations in prostatic & vaginal fluids
Even if given orally alone or in combination with sulfonamides,
it will have the same half-life
More lipid soluble – larger volume of distribution than
sulfonamides
RESISTANCE TO TM:
due to reduced cell permeability
due to overproduction of dihydrofolate reductase
due to production of an altered reductase & reduced drug binding
CLINICAL USES:
Oral TM:
acute UTI 100 mg BID
community acquired organisms – 200 ug to 600 ug/ml
concentration of TM in urine
ADVERSE EFFECTS:
megaloblastic anemia, leucopenia, granulocytopenia
Prevention of adverse effects:
simultaneous administration of folinic acid 6 mg-8 mg/day

144. TRIMETHOPRIM-SULFAMETHOXAZOLE (CO-
TRIMOXAZOLE)
synergistically active antimicrobial agent which
blocks two sequential steps in the obligate
enzymatic reaction in bacteria preventing the
formation of nucleotides:
Sulfamethoxazole – competitively inhibits the
incorporation of PABA into folic acid
Trimethoprim inhibits dihydrofolate reductase
preventing the reduction of dihydrofolate to
tetrahydrofolate

145. ADVANTAGES OF THE COMBINATION:
increased potency
increases spectrum
decreased incidence of resistance
exhibits selective toxicity for bacteria which must
synthesize their own folic acid
Trimethoprim is more potent, more lipid soluble and has a
greater volume of distribution than sulfa drugs
Penetrates CSF well
65-70% of each drug is protein bound
Eliminated in the urine within 24 h – reduce dose by
half if creatinine clearance is 15-30 ml/min
CLINICAL USES:
Oral TMP-SMX
urinary tract infection:

146. complicated UTI – 2 double strength tabs (TM-160 mg+SM 800
mg) q 12 hours
Recurrent UTI prophylaxis – ½ of regular size (single strength)
3x weekly
Prostatitis – 2 double strength tabs (TM 160 mg + SM 800 mg) q 12 h
Susceptible strains of shigella and salmonella
2 double strength tabs q 12 h
Children with shigellosis, UTI, otitis media-8mg/kg TM and 40 mg/kg
SM q 12 hours
P. carinii and other pathogens – orally 15-20 mg/kg
in immunosuppressed patients – one double strength tab daily or
3x weekly
Nontuberculous mycobacterial infection
Respiratory tract pathogens – useful alternative to B lactamase for
community acquired bacterial pneumonia

147. CLINICAL USES:
Inravenous TMP-SMX:
drug of choice for moderately severe to severe pneumocystis
pneumonia esp. patients with AIDS
TM 80 mgs + SM 400mg/5 ml diluted in 125 ml of D5W
Folinic acid increases morbidity and treatment failures so not used
Used for Gram (-) bacterial sepsis – incldg. Those caused by some
multiple drug resistant species such as Enterobacter and Serratia
Shigellosis
Typhoid fever
UTI caused by susceptible organisms if patient is unable to take drug
orally
Dosage- 10-20 mg/kg/day of TM component
Oral Pyrimethamine + Sulfadiazine= used in the treatment of
leishmaniasis and toxoplasmosis
Pyrimethamine + Sulfadoxine = used in the treatment of Falciparum
malaria

148. ADVERSE EFFECTS:
mostly due to untoward reactions to SMX
dermatological effects
GI effects: glossitis, stomatitis, nausea and vomiting
CNS disturbances: headache, depression, hallucinations
Hematologic reactions- aplastic, hemolytic and macrocytic
anemia, coagulation disorders
Vasculitis
Renal impairment or damage
AIDS PATIENTS
more sensitive to increased frequency of reactions toward TMP-
SMX drug:
-rashes, hemtologic effects-leukopenia, fever, diarrhea, elevated
hepatic aminotransterases, hyperkalemia, hyponatremia

149. FLUOROQUINOLONES
QUINOLONES
synthetic fluorinated analogs of nalidixic acid
block bacterial DNA synthesis by inhibiting bacterial
topoisomerase II (DNA Gyrase) and topoisomerase IV
INHIBITION OF DNA GYRASE
prevents relaxation of positively supercoiled DNA that is
required for normal transcription and replication
INHIBITION OF TOPOISOMERASE IV
interferes with separation of replicated chromosomal DNA into
the respective daughter cells during cell division

150. EARLY QUINOLONES (Nalidixic Acid, Oxolinic acid, Cinoxacin)
did not achieve systemic antibacterial levels
useful only for treatment of lower UTI
ANTIBACTERIAL ACTIVITY:
Gram (-) aerobic bacteria- excellent activity
Gram (+) organism – limited activity
NORFLOXACIN – least active against gm (+) and Gm (-)
SECOND GROUP
excellent gm (-) activity, moderate gm (+) activity
Ciprofloxacin (prototype), Enoxacin, Lomefloxacin,
Levofloxacin, Ofloxacin, Pefloxacin
Methicillin susceptible S. aureus – susceptible to
fluoroquinolones
Methicillin resistant S. aureus – resistant to fluoroquinolones
Ciprofloxacin – most active against gm (-) expecially P.
aeroginosa
Levofloxacin – 2x more potent than ofloxacin
superior activity against gm (+) org. incldg S. pneumoniae

151. THIRD GROUP:
improved activity against gm (+) organism particularly S.
pneumoniae and some staph
Clinafloxacin – best activity against gm (+) activity
Gatifloxacin
Sparfloxacin – some activity against anaerobes
not as active as ciprofloxacin against gm (-)
FOURTH GROUP
enhanced gm (+) activity
good activity against anaerobic bacteria
Moxifloxacin, Trovafloxacin
Other activities:
Atypical pneumoniae ( Mycoplasma, Chlamydia
Intracellular pathoges (Legionella, Mycobacteria tb, and M.
avium complex)
RESISTANCE:
Due to one or more point mutations in the quinolone binding
region of the target enzyme
Due to a change in the permeability of the organism

152. DNA GYRASE – primary target in E. coli with single step
mutants exhibiting amino acid substitution in the alpha
subunit of the gyrase
TOPOISOMERASE IV – secondary target in E. coli that is
alerted in mutants expressing higher levels of
resistance
IN STAPH AND STREP
Topoisomase IV – primary target
DNA gyrase – secondary target
cross resistance to other members

153. PHARMACOKINTEICS:
well absorbed after oral intake
bioavailability 80-95%
distributed widely in body fluids and tissues
Half life
3 hrs- norfloxacin and ciprofloxacin
10 hrs. – pefloxacin & Fleroxacin
> 10 hrs. – sparfloxacin
Long half life : Levofloxacin, moxifloxacin, sparfloxacin,
trovafloxacin
Ofloxacin and Levofloxacin – identical pharmacokinetics
Oral absorption impaired by divalent cations including those
antacinds
Alatrovafloxacin – inactive prodrug of trovafloxacin for
parenteral administration
Concentration is higher in prostate, kidney, neutrophiles and
macrophages than in serum

154. ELIMINATION:
Renal – tubular secretion, Glomerular filtration
- If creatinine clearance < 50%ml/min – adjust dosage
Sparfloxacin – a50 % fecal, 50% renal
If creatinine clearance <50 ml/min -400 mg LD followed by 200 mg q
other day
Non renal – trovafloxacin and moxifloxacin
_ CI in patients with hepatic failure
CLINICAL USES:
UTI – even when caused by multi drug resistant bacteria like
pseudomonas
Norfloxacin 400 mg Bid
Ciprofloxacin 500 mg BID
Ofloxacin 400 mg BID
Prostatitis – 4-6 wks
Norfloxacin, Ciprofloxacin, Ofloxacin
Bacterial Diarrhea

155. Shigella, Salmonella, toxigenic E. coli, campylobacter
Infection of soft tissues, bones, joints, intraabdomina and respiratory
tract infection even caused by Pseudomonas and Enterobacter
Gonococcal infection, including disseminated disease
Ciprofloxacin, ofloxacin oral single dose
Chlamydia urethritis or cervicitis
ofloxacin x 7 days
Legionellosis
Ciprobay – 2nd line agent
TB and atypical mycobacteria infection
Eradication of meningococci carrier
Prophylaxis in neutropenic patient
Upper and lower RTI
Newer fluoroquinolones enhanced gm (+) activity and atypical
pneumonia

156. ADVERSE EFFECTS:
most common – nausea, vomiting and diarrhea
Others – headache, dizziness, insomnia, skin rash, abn liver function test
Trovafloxacin – associated rarely with acute hepatitis and hepatic failure
Photosensitivity – lomefloxacin, pefloxacin
CV toxicity – Grepafloxacin
Damage growing cartilage and cause arthrpathy- not recommended < 18
y/o
Tendinitis – may rupture
DRUG INTERACTION:
Theophylline – increase metabolism of theophylline –
elevated concentration-seizures
CONTRAINDICATIONS:
Nursing mothers, children, pregnancy

157. NALIDIXIC ACID
First antibacterial quinolone introduced in 1963
Not fluorinated
Very rapid elimination, no systemic bacterial effects
Used only for UTI
Oxolinic Acid and Cinoxacin – similar structure
NOVOBIOCIN:
Acidic antibiotic prod. By Streptococcus niveius
Inhibitor of B subunit of DNA gyrase
Active mainly against gm (+) bacteria
Rapid emergence of resistance; inc. incidence of adverse
effects
No clear indication

158. URINARY ANTISEPTICS:
Methenamine Mandelate and Hippurate
releases mandelic acid, hippuric acid or formaldehyde in
sufficiently acidic urine
bactericidal or bacteriostatic to most organisms causing UTI
except Proteus
Nalidixic Acid and Cinoxacin:
interferes with DNA polymerization by binding to DNA
gyrase
causes nausea, vomiting, skin rashes and CNS effects

159. Nitrofurantoin
well absorbed after ingestion
excreted into the urine
100 mg q 6 h with food or milk
contraindicated in severe renal insufficiency
bactericidal or bacteriostatic for many gram (+) and gram (-)
antagonizes the action of nalidixic acid
causes hypersensitivity, nausea, vomiting, neuropathies and hemolytic
anemia in G6PD
Trimethoprim
selective inhibition of bacterial dihydrofolate reductase
may be bacteriostatic or bacteridial
+ Sulfamethoxazole – P. carinii, shigellosis, prostatitis, some
nontuberculous mycobacterial infections, systemic salmonella infections,
complicated UTI

160. MISCELLANEOUS ANTIBACTERIAL DRUGS:
Metronidazole
penetrates CSF, metabolism-liver
treatment of amoebic infections, intraabdominal infections,
vaginitis, antibiotic associate enterocolitis, brain abscess
oral, IV, rectal suppository
causes metallic taste, glossitis and anorexia

161. Polymyxin B
group of basic peptides active against Gram (-), bactericidal
treatment of serious enteric infections(Pathogenic E. coli,
Shigella, Enterobacter, Klebsiella and Pseudomonas , not
Proteus)
poor tissue distribution
attach to and disrupt bacterial cell membrane, bind and
inactivate endotoxin
toxicity includes neurological and renal effects
topical (+Bacitracin+Neomycin)

162. Mupirocin
ointment for topical application
active against staph aureus; inh. Isoleucyl tRNA
synthetase
indicated for impetigo, intranasal application for
elimination of methicillin resistant S. aureus
carriage by patient or health care workers