beta lactam drugs ppt pharmacology drugs

BETA LACTAM
ANTIBIOTICS (PENICILLIN
AND CEPHALOSPORIN)

CONTENTS
 INTRODUCTION
 MECHANISM OF ACTION
 PENICILLIN
 CEPHALOSPORINS

ANTIBIOTICS :
substances produced by microorganisms which
selectively supress the growth or kill other
microorganisms at low concentration.

ANTIBIOTICS USEFUL FOR OROFACIAL
INFECTION
 PENCILLINS
 CEPHALOSPORINS
 ERTHROMYCINS
 CLINDAMYCIN AND LINCOMYCIN
 METRONIDAZOLE
 AMINOGLYCOSIDES
 NEWER BETA LACTAM ANTIBIOTICS
-CARBAPENEMS
-MONOBACTAMS

 FLUOROQUINOLONES- CIPROFLOXACIN
 SULFONAMIDES AND TRIMETHOPRIM

HISTORY
 First antibiotic, discovered by
ALEXENDER FLENNINGS
 Obtained from pencillin notatum,
presently P. chrysogenum
 It is bactericidal
 Effective against gram positive
bacteria and less against gram
negative
 Nucleus – thiazolidone and beta
lactam ring
- side chains via amide
linkage

CLASSIFICATION
 NATURAL
a) Pencillin G and benzathine penicillin
 SEMISYNTHETIC
a) Acid resistance – pencillin –V, phenoxyethyl
penicillin
b) Pencillinase- resistant penicillins- methicillin,
cloxacillin, flucloxacillin
 Pencillin effective against Gm+ve and Gm -ve
organisms: ampicillin, amoxicillin
 Extented spectrum penicillins:
1) Aminopenicillins : ampicillin, bacampicillin ,
amoxicillin
2) Carboxypencillin : carbenicillin
3) Ureidopencillins : piperacillin, mezlocillin

BETA LACTAM INHIBITORS:
 Sublactam, tazobactam, clavulinic acid

MECHANISM OF ACTION OF BETA
LACTAM DRUGS
 All beta lactam antibiotics interfere with the
synthesis of bacterial cell wall
 The bacteria synthesis UDP –N-acetyl muramic
acid pentapeptide called park nucleotide and UDP-
N-acetyl glucosamines
 The peptidolycan residues are linked together
forming long strands and UDP is split off
 The final step is cleavage of the terminal D-alanine
of the peptide chains by transpeptidases; energy so
released is utilized for the establishment of cross
linkages between peptide chains of the
neighbouring strands
 This cross linking provides stability and rigidity to
the cell wall

 The beta lactam antibiotics inhibits the
transpeptidases so that cross linking does not
take place
 These enzymes and related proteins constitute
the pencillin binding proteins (PBP) which have
been located in the bacterial cell membrane
 Each organisms have several PBPs and PBPs
obtained from different species differ in their
affinity towards different beta lactam antibiotics
 This fact probably explains their differing
sensitivity to the various beta lactam antibiotics

 When bacteria divide in the presence of the beta
lactam antibiotic- cell wall deficient (CWD) forms
are produced
 Because the interior of the bacterium is hyper
osmotic, the CWD forms swell and burst;
bacterial lysis occurs
 This is how beta lactam antibiotics exert
bactericidal action
 Lytic effects of theses antibiotics may also be due
to depression of some bacterial autolysins which
normally function during cell division

 The peptidoglycan is unique to the bacteria. No
such substance is seen in higher animals.
 This is why penicillin are practically non toxic to
man
 In gram positive bacteria, the cell wall is almost
made up of peptidoglycan, which is >50 layers
thick and extensively cross linked
 In gram negative bacteria, it consists of
alternating layers of lipoprotein and
peptidoglycan
 This may be the reason for higher susceptibility
of the gram positive bacteria to PnG

PENICILLIN –G (BENZYL
PENICILLIN)
 PnG is a narrow spectrum antibiotic,
activity is to limited primarily to gram
positive bacteria and few others
 BACTERIAL RESISTANCE – many
bacterias are inherently insensitive to
PnG because in them the target
enzymes and PBPs are located deeper
under lipoprotien barrier where PnG is
unable to penetrate or they have the
less affinity for PnG
 The primary mechanism of acquired
resistance is production of penicillinase

PENICILLINASE
 It is a narrow spectrum beta lactamse which
opens the beta lactam ring to inactivate PnG and
some closely related cogeners.
 Majority of Staphylococci and some strains of
gonococci, B. subtilis, E. coli, H. influenzae and
few other bacteria produce penicillinase.
 The gram positive penicillinase producers
elaborate large quantities of the enzyme which
diffuses into the surrounding and can protect
other inherently sensitive bacteria as well
 Staphylococcal pencillinase is inducible, and
methicillin is an important inducer; while in
gram-negative organisms, it is mostly a
constitute enzymes

 Some resistant bacteria become penicillin
tolerant and not pencillin destroying . Their
target enzymes are altered to have low affinity
for pencillin , e.g. highly resistant pneumococci
isolated in some areas have altered PBPs.
 The gram negative bacteria have porin channels
formed by specific protiens located in their outer
membrane. Permeability of various beta lactam
antibiotics through these channels differs:
ampicillin and other members which are active
against gram negative bacteria across the porin
channels much better than PnG

PHARMACOKINETICS
 Penicillin –G is acid labile
 It is destroyed by gastric acid
 As such 1/3rd
of an oral dose is absorbed in the
active form
 Absorption of sod. PnG from i.m. site is rapid and
complete; peak plasma level is attained in 30 min
 It is distributed mainly extracellularly; reaches
most body fluids but penetration in serous
cavities and CSF is poor
 The pharmacokinetics of PnG is dominated by
very rapid real excretion; about 10% by
glomerular filtration and the rest by tubular
secretion

ADVERSE EFFFECTS
 Pain at i.m. injection site
 Nausea on oral ingestion
 Thrombophlebitis of injected veins
 Accidental i.v. injection of procaine penicillin
produces CNS stimulation, hallucination and
convulsions due to procaine. Due to insoluble it
may cause microembolism

HYPERSENSITIVTY :
 These reactions are the major problem in the use
of the penicillins
 Individuals with an allergic diathesis are more
prone to develop pencillin reactions
 PnG is the most common drug implicated in the
drug allergy
 MANIFESTATIONS of penicillin allergy are-
rashes, itching ,urticaria and fever
 Wheezing, angioneurotic edema, serum
sickness and exfoliative dermatitis are less
common
 Anaphylaxis is rare but may be fatal
 Fear of causing anaphylatic shock has severely
restricted the use of injected PnG

 All forms of natural and semisynthetic pencillins
can cause allergy , but it is more commonly seen
after parentral than oral administration
 Incidence is highest with procaine pencillin:
procaine is itself allergic

USES
 DENTAL INFECTIONS: parentral PnG remains
effective in majority of common infections
encountered in dentistry, particularly those arising
as a sequelae of carious lesions and are caused by
both aerobic and anaerobic bacteria such as
Streptococci, Peptostreptococci , fusoform bacteria
 GENERAL MEDICAL USES:
-streptococcal infections
-pnuemococcal infections
-Meningococcal infections
-gonorrhoea caused by non penicillinase producing N.
gonorrhoea
-syphilis
-diphtheria, tetanus and other rare diseases - anthrax

SEMI SYNTHETIC PENICILLIN
 Are produced by chemically combining specific
side chains or incorporating specific precursors in
the mould cultures
 The aim of producing semisynthetic pencillins is
to overcome the shortcoming of PnG, which are:
1. Poor oral efficacy
2. Suscepibility to penicillinase
3. Narrow spectrum of activity
4. Hypersenstivity reactions

PHENOXYMETHYL
PENICILLIN( PENCILLIN V)
 It differs from PnG only in that it is acid stable , oral
absorption is better; peak blood level is reached in 1
hour and plasma t ½ is 30-60 min
 The antibacterial spectrum of pencillin V is identical
to that of PnG, but it is less active against Neisseria,
other gram negative bacteria and anaerobes
 Oral pencillin V is suitable drug to treat many non
serious dental infections and trench mouth , but it
cannot be depended upon for more serious infections.
 Other conditions treated with pencillin V are
streptococcal pharyngitis, sinusitis , otitis media and
pneumococcal infections

PENICILLIN REISITANT PENCILLIS
 These congeners have side chains that protect
the beta lactam ring from attack by
staphylococcal penicillinase
 However this also partially protects the bacteria
from beta lactam ring: non pencillinase
producing organisms are much less sensitive to
these drugs than to PnG .
 Their only indication is infections caused by
pencillinase producing Staphylococci for which
they are the drugs of choice except in areas
where methicillin resistant staph aureus has
become prevalent

CLOXACILLIN
 ACTIVITY:
a) penicillinase as well as acid
resistant pencillin
b)Has weaker antibacterial activity
than pencillin G. so it is used in
conjucation with ampicillin, or
amoxicillin to enhance the
synergism
 ABSORPTION:
food interfere with the absorption
of the drug.
High concentration occurs in kidney
and liver, approximately 90-95%
bound to plasma protiens

 It is more active than methicillin against
penicillinase producing Staph, but not against
MRSA
 Because staphylococcal infections are rare in the
oral cavity , cloxacillin is infrequently used in
dentistry

DOSAGE:
The initial dosage varies from 0.5 to 1 gm qid and the
maintenance dose is 250 qid
The drug should be administered 1 hour before or 2
hours after a meal to ensure adequate absorption .
It can also be given IM and by slow IV 250-500mg 4-6
hourly.

USES:
It is used to treat infections of the skin, bone, heart
valve, blood, lungs
SIDE EFFECTS:
-upset stomach
-nausea
-vomiting
-diarrhoea
-mouth sores

EXTENDED SPECTRUM PENICILLIN
 These semi synthetic penicillins are active
against a variety of gram negative bacilli as well
 They can be grouped according to the nature of
the side chain substitution and spectrum of
activity into amino -/ carboxy/- ureido - penicillin

AMINOPENICILLIN
 this group , led by ampicillin , has an amino
substitution in the side chain
 some are prodrugs and all have quite similar
antibacterial spectra
 none is resistant to penicillinase or to other beta
lactamase

AMPICILLIN
 ACTIVITY:
It is effective against Gm+ve and Gm
-ve organisms
The antibacterial activity is similar to
benzyl penicillin, but it is more
effective than benzyl penicillin
against a variety of Gm-ve bacteria.
Gm+ve cocci are less sensitive to
ampicillin than benzyl penicillin
Ampicillin is inactivated by
penicillinases

ABSORPTION:
It is incompletely absorbed on oral adminstration.
Food doesn’t interfere with its absorption.
Plasma levels are reached at a peak within 2 hours and
1 hour after oral and IM administration respectively
ADVERSE EFFECTS:
-skin rashes usually maculo papular and not urticial
-diarrhoea is common with oral ampicillin

DOSAGE:
Ampicillin capsule contains ampicillin hydrate
equivalent to 250 mg of the base.
Usual adult dose of ampicillin is 250 to 500 mg 6 hourly
(qid); dose as large as 1 gm qid may be required for
more refractory Gm-ve infections.
High doses for IM/IV injections are used in the
treatment of meningitis and bacterial endocarditis

USES:
- Gall bladder infections
- Pneumonia
- Gonorrhoea
- Meningitis
- Urinary tract infections’
- Bacillary dysentery
- Typhoid
- Cholecystitis
- Sub acute bacterial endocarditis
- Septicaemias
- Respiratory tract infection
- H.pylori

ADVERSE EFFECTS
 Diarrhoea after oral administration
 Rashes especially with the patients with AIDS
 Sometimes rashes may not be allergic but toxic in
nature

INTERACTIONS
 Hydrocortisone inactivates ampicillin if mixed in
the i.v. solution
 By inhibiting colonic flora, it may interfere with
deconjugation and enterohepatic cycling of oral
contraceptives; may result in failure of oral
contraception
 Probenecid retards renal excretion of ampicillin

AMOXICILLIN
 ACTION:
This is effective against Gm+ve and Gm-ve organism
This is semi synthetic penicillin with broad spectrum of
antibacterial activity and having substantial
advantages over ampicillin
 ABSORPTION:
It is effective on oral administration and blood levels are
twice as high as those after similar dose of ampicillin

IT IS SIMILAR TO AMPICILLIN
EXCEPT:
 Oral administration is better ;food does not
interfere with absorption; higher and more
sustained blood levels are produced
 Incidence of diarrhoea is lower
 It is less active against Shigella and H.influenzae
 It is more active against penicillin resistant
strep. pneumoniae

The incidence of skin rashes and diarrhoea is less than
ampicillin
 DOSAGE: 250-500mg (tid) in adults .
It can also be give IM/IV
 ADVERSE EFFECTS :
- Allergic reactions such as maculopapular rashes,
urticaria, fever, broncospasm, vasculitis, serum
sickness , exfoliative dermatitis, and anaphylaxis.
- In highly sensitized patients, anaphylaxis may occur
and can result in death.

Broad spectrum pencillins may alter the natural
bacterial flora of the oral cavity and GIT resulting in
superinfection with resistant bacteria , colonisation by
opportunistic pathogens, fungal infections or
pseudomembranous colitis
 DRUG INTERACTION: concurrent therapy of
penicillin and aminoglycosides are not advised since
the former may inactivate the latter

BACAMPICILLIN
 It is an ester of ampicillin which is nearly
completely absorbed from g.i.t
 It is a prodrug and is largely hydrolysed during
absorption
 Thus higher plasma level are attained
 Since little active drug is present in the drug is
present in the gut , it does not markedly disturb
intestinal ecology- incidence of diarrhoea is
claimed to be lower
 DOSE: 400-800mg BD

CARBOXY PENCILLINS
 CARBENICILLIN: the special feature of this
penicillin congener is its activity against
Pseudomonas aeruginosa and indole positive proteus
which are not inhibited by PnG or aminopenicillins .
 It is less active against Salmonella, E.coli and
Enterobacter while Klebsiella and gram positive
cocci are unaffected by it Pseudomonas strains less
sensitive to carbenicillin have developed in some
areas, especially when inadequate doses have been
used

 Carbenicillin is neither penicillinase resistant
nor acid resistant . It is inactive orally and has to
be administered i.m. or i.v.
 The t ½ is 1 hour
 High doses have caused bleeding by interfering
with platelet function
 This appears to result from perturbation of
agonist receptors on platelet surface
INDICATION:
-serious infections caused by pseudomonas or
proteus, e.g. burns, urinary tract infection,
septicaemia, but piperacillin is preferred now
-orodental infections are rarely caused by
pseudomonas, it at all they occur in immuno
compromised patients

NEWER PENCILLINS
AZLOCILLIN: it is an acyl
ampicillin antibiotic with an
extended spectrum of activity and
greater in vitro potency than the
carboxy pencillins.
Azlocillin is similar to mezlocillin and
piperacillin.
It demonstrates antibacterial activity
against a broad spectrum of
bacteria, including Pseudomonas
aeruginosa and in contrast to most
cephalosporin, exhibits activity
against enterococci

DICLOXACILLIN: it is a
narrow spectrum beta-lactam
antibiotic of penicillin class
it is used to treat infections
caused by susceptible gram +ve
bacteria
Notably it is active against beta
lactamase producing organisms
such as Staphylococcus aureus,
which would otherwise be
resistant to most penicillins
It is very similar to flucloxacillin
and these two agents are
considered interchangeable.

Dicloxacillin is commercially available as the sodium
salt dicloxacillin sodium in capsules 250-500 mg and
injections (powder for reconstitution 500 and 1000 mg
per vial)

FLUCLOXACILLIN: it is a
narrow spectrum beta lactam
antibiotic of the pencillin class.
o It is used to treat infections
caused by susceptible Gram +ve
bacteria .
o Nowadays, it is no longer
recommended against beta
lactamase producing organisms
such as Staphylococcus aureus,
since like in other penicillins, it is
not active against such infections
o It is very similar to Dicloxacillin
and these two agents are
considered interchangeable

Flucloxacillin is commercially available as the sodium
salt flucloxacillin sodium, capsule 250-500mg, oral
suspensions 125mg/5ml or 250mg/5ml and injection
( powder for reconstitution 250, 500, 1000 mg per vial)

MECILLINAM: it is an extended spectrum penicillin
antibiotic that binds specifically to penicillin binding
protein 2(PBP2), and is only considered to be active
against gram –ve bacteria .
It is used primarily in the treatment of urinary tract
infections and has also been used to treat typhoid and
paratyphoid fever

NAFCILLIN: it is a narrow spectrum beta lactam
antibiotic of the pencillin class
As a beta lactamase resistant penicillin, it is used to
treat infections caused by gram positive bacteria,
particularly species of staphylococci, that are resistant
to other pencillins

OXACILLIN: it is narrow
spectrum beta lactam antibiotic
of the penicillin class
It is effective against penicillinase
enzymes such as that produced
by Staphylococcus aureus
However resistant strains are
now emerging that are called
oxacillin- resistant
Staphylococcus aureus

UREIDOPENCILLINS
 PIPERACILLIN: it is an extended
spectrum beta lactam antibiotic of
the uriedopenicillin class
It is normally used together with beta
lactamase inhibitor
The combination has activity against
many gram positive and gram
negative pathogens and anaerobes,
including Pseudomonas aeruginosa.
Piperacillin is not absorbed orally and
must therefore be given by
intravenous and intramuscular
every 6 or 8 hours , the drug may
also given by continuous infusion ,
but this has not been shown to be
superior

TICARCILLIN: it is a
Carboxypencillin
It is almost invariably sold and used in
combination with alavulanate
Because it is pencillin, it also falls
within the larger class of beta
lactam antibiotics
Its main clinical use is an injectable
antibiotic for the treatment of gram
negative bacteria, in particular,
Pseudomonas aeruginosa .
Ticarcillin is not absorbed orally and
therefore must be given by
intraveneous or intramuscular
injection
The usual adult dose of Ticarcillin is
3.5 gm four times a day

BETA LACTAMASE INHIBITORS
 Beta lactamases are a family of enzymes
produced by many gram positive and gram
negative bacteria that inactivate beta lactam
antibiotics by opening the beta lactam ring
 Different beta lactamases differ in their
substrate affinities. The inhibitors of this enzyme
clavulanic acid, sublactam and tazolactam are
available for clinical use

CLAVULANIC ACID
 Obtained from streptomyces clavuligerus it has a
beta lactam ring but no antibacterial activity of its
own
 It inhibits a wide variety ( classII to class V ) of beta
lactamases produced by both gram positive and
gram negative bacteria
 Clavulanic acid is a progressive inhibitor : binding
with beta lactamse is reversible initially , but
becomes covalent later –inhibition increasing with
time
 Called a suicide inhibitor, it gets inactivated after
binding to the enzymes
 It permeates the outer layers of the cell wall of gram
negative bacteria and inhibits the periplasmically
located beta lactamse

PHARMACOKINETICS
 Has rapid oral absorption and bioavailability of
60% can also be injected
 Its elimination t ½ of 1 hour and tissue
distribution matches amoxicillin with which it is
combined
 However it is eliminated mainly by glomerular
filtration and its excretion is not affected by
Probenecid
 Moreover, it is largely hydrolysed and
decarboxylated before excretion , while
amoxicillin is primarily excreted unchanged by
tubular secretion

 USES:
-Skin and soft tissues infections, intra abdominal
and gynaecological sepsis, urinary, biliary and
respiratory tract infections: especially when
empiric antibiotic therapy is to be given for
hospital acquired infections
-dental infections caused by beta lactamse
producing bacteria
-gonorrhoea

ADVERSE EFFECTS
 Tolerance is poorer –especially in children
 Other side effects are candida stomatitis
/vaginitis and rashes
 Some cases of hepatic injury have reported with
the combination

SALBACTAM
 It is semisynthetic beta lactamase
inhibitor , related chemically as well as
in activity to clavulanic acid
 It is also a progressive inhibitor , highly
active against classII to V but poorly
active against class I beta lactamase
 On weight basis , it is 2-3 times less
potent than clavulanic acid for most
types of the enzymes but the same level
of inhibition can be obtained at the
higher concentration achieved clinically
 Sublactam does not induce
chromosomal beta lactamase , while
clavulanic acid can induce some of them

INDICATION
 PPNG gonorrhoea; sublactam per se as well
inhibitor N. gonorrhoea
 Mixed aerobic –anaerobic infections, tooth
abscess, intra- abdominal , gynaecological ,
surgical , skin /soft tissue infections, especially
those acquired in the hospital
 ADVERSE EFFECTS:
- Pain at the side of injection
- Thrombophlebitis of injected vein, rash,
diarrhoea

TAZOBACTAM
 Is another beta lactamase inhibitor similar to
sublactam
 Its pharmacokinetics matches with that of piperacillin
with which it has been combined for use in severe
infections like pericornitis, pelvic/ urinary /respiratory
infections caused by beta lactamse producing bacilli
 However combination is not active against piperacillin
resistant Pseudomonas , and against Pseudomonas that
develop resistant by losing permeability to piperacillin

HISTORY: In 1945, Prof.G.Brotzu isolated a fungus
called as cephalosporium acremonium.
Cephalosporins are extracted from this fungus.
Cephalosporins have 7-amino cephalosporemic acid
nucleus which bears close resemblance to the 6-APA
nucleus of penicillins.

 They are chemically related to penicillins; the
nucleus consists of beta lactam ring fused to a
dihydrothiaazine ring
 By addition of different side chains at position 7
of beta lactam ring and a position 3 of
dihydrothiazine ring, a large number of semi
synthetic compounds have been produced

 ANTIBACTERIAL ACTIVITY: cephalosporins posses
a wide range of activity against Gram +ve and Gram –
ve bacteria
Cephalosporins act by inhibiting bacterial cell wall
synthesis and are bactericidal
 ABSORPTION, FATE AND EXCRETION :
cephalosporins are administered either orally or IV
(IM is painful)
Cephalosporins are eliminated mainly by renal excretion

 AQUIRED RESISTANT TO CEPHALOSPORINS
COULS HAVE THE SAME BASIS AS FOR
PENICILLINS i.e. :
-alteration in target protiens reducing affinity for
the antibiotic
-impermeability to the antibiotic so that it does not
reach its side of action
-elaboration of beta lactamases which destroy
specific cephalosporins, the most important
mechanism

 ADVERSE EFFECTS:
- Allergy like skin rashes
- Fever
- Serum sickness
- Anaphylactic reaction (rare)
- Eosinophilia
- Neutrophilia
- Transient spleenomegaly
- Increased SGOT levels
- Some of the newer cephalosporins cause disulfiram
like effect when combined with alcohol

 FIRST GENERATION CEPHALOSPORINS:
First cephalosporin introduced into medical practise was
cephalothin.
This compound is active against both pencillin- sensitive
and resistant staphylococci, pneumonia, streptococci
and the most common Gm-ve pathogens, but are not
effective against anaerobes .
Other first generation cephalosporins are
cephacetrile and cefazolin
The first orally active cephalosporin for medical used
was cephaloglycin

CEPHALEXIN
 It is orally effective first generation
cephalosporin similar in spectrum to
cefazolin, but less active against H.
influenzae
 It is little bound to plasma protiens ,
attains high concentration in bile and
is excreted unchangable in urine t ½ -
60 min
 It finds place in dentistry as an
alternative to amoxicillin
 DOSE: 0.25-1g 6-8hourly
Children 25-100mg/kg/day

CEFADROXIL
 A closer congener of cephalexin; has
good tissue penetration including
that in alveolar bone
 It exerts more sustained action at
the site of infection and can be given
12 hourly despite a t ½ of 1 hour
 It is excreted unchanged in urine but
dose needs to be reduced only if
creatinine clearance is <50ml/min
 The antibacterial activity of
cefadroxil and indications are similar
to those of cephalexin; frequently
selected for dental infections
 DOSE: 0.5-1g BD

 SECOND GENERATION CEPHALOSPORINS :
These offer a wide range against Gm-ve bacilli
Their main use would appear to be in the Gm-ve
infections, especially those caused by beta lactamase
producing organisms.
But they have less activity against most pathogens that
cause infection of wounds

CEFUROXIME
 It is resistant to gram negative
beta lactamases
 Has high activity against PPNG
and penicillin resistant H.
influenzae, while retaining
significant activity on gram
positive cocci and certain
anaerobes
 It is well tolerated by i.m. route
and has been used in some mixed
infections as well as for single
dose i.m. therapy of gonorrhoea
due to PPNG
 DOSE: 250-750 mg/ vial inj; 0.75-
1.5g i.m or i.v 8 hourly

CEFACLOR
 It can be given orally and is more active than the
first generation compounds against H.influenzae,
E. coli, Pr.mirabilis and anaerobes found in the
oral cavity
 DOSE: 250mg cap, 125-250 mg distab,
125mg/5ml dry syr, 50 mg/ml ped drops

CEFPROZIL
 Oral absorption of this
cephalosporin is good >90% and it
has augmented activity against
Strept. pyogens, Strep.
Pneumoniae, H. influenzae,
Moraxella and Klebsiella
 Primary indications are bronchitis,
ENT, and skin infection
 DOSE: 250-500mg BD

 THIRD GENERATION CEPHALOSPORINS:
they have poor activity the Gm+ve cocci; but are more
active against Gm-ve bacilli than the first and second
generation cephalosporin .
This generation includes ceftazidime, cefsulodin,
ceftriaxone (once a day)

CEFOTAXIME
 It is the protype of the third generation
cephalosporins; exerts potent action on
aerobic gram negative as well as gram
positive bacteria , but is not active on
anaerobes, Staph. aureus, and Ps. Aeruginosa
 Prominent indications are meningitis caused
by gram negative bacilli, life threatening
resistant/ hospital acquired infections,
septicaemia, and infections in
immunocompromised patients
 Cefotaxime is deacetylated in the body ;the
metabolite exerts weaker but synergistic
action with parent drug
 The plasma t ½ of cefotaxime is 1 hr
 DOSE: 1-2 g i.m. or i.v. 6-12 hourly

CEFTIZOXIME
 It is similar in antibacterial activity and
indications to cefotaxime but it is not
metabolised- excreted by the kidney at a slower
rate; t ½ 1.5 to 2 hour
 DOSE : 0.5-1 g i.m./ i.v., 8 hourly

CEFTRIAXONE
 The distinguishing feature of this
cephalosporin is its longer duration of
action(t ½ 8 hr), permitting once or at
the most twice daily dosing
 Penetration into CSF is good, and it is
eliminated equally in urine and bile
 Ceftriaxone has shown high efficacy in a
wide range of serious infection including
bacterial meningitis, multiresistant
typhoid fever, abdominal sepsis and
septicemias
 Hypothrombinaemia and bleeding are
the specific adverse effects
 Haemolysis is reported

 DOSE: 0.25, 0.5, 1 g per vial inj
 1-2 g i.v. or i.m./day

CEFTAZIDIME
 The most prominent feature of this
third generation cephalosporin is
its high activity against
Pseudomonas aeruginosa, and
specific indications a febrile
neutropenic patients, burns , etc.
 Its activity against
Enterobacteriaceae is similar to
that of cefotaxime but it is less
active on Staph. aureus , other
gram positive cocci and anaerobes
like Bact.fragilis
 Its plasma t ½ is 1.5- 1.8 hr

ADVERSE EFFECTS
 Neutropenia
 Thrombocytopenia
 Rise in plasma transamines and blood urea
DOSE: 0.5-2g i.m. or i.v. every 8 hr
Children 30mg/kg/day
Resistant typhoid 30mg/kg/day

CEFOPERAZONE
 Like ceftazidime, it differs from
other third generation compounds in
having stronger activity on
Pseudomonas and weaker activity
on other organisms.
 It is good for S. typhi and B. fragilis
also, but more susceptible to beta
lactamases
 The indications are – severe urinary
, biliary, respiratory, skin-soft tissue
infections, meningitis and
septicemias
 It is primarily excreted in bile t ½ is
2hr
 It has hypoprothrombinaemic action
but does not affect platelet function

 A disulfiram- like reaction with alcohol has been
reported
 DOSE : 1-2g i.m. /i.v. 12 hourly

CEFIXIME
 It is an orally active third
generation cephalosporin highly
active against
enterobacteriaceae, H.influenzae,
Strept. Pyogens, Strept.
Pneumoniae and is resistant to
amino beta lactamases
 However it is not active on Staph.
aureus and pseudomonas
 It is longer acting (t ½ 3 hr) and
has been used in a dose of 200-
400 mg BD for respiratory,
urinary and biliary infections
 Stool changes and diarrhoea are
the most prominent side effects

CEFPODOXIME PROXETIL
 It is orally active ester prodrug
of 3rd
generation cephalosporin
cefpodoxime
 In addition to being highly
active against Enterobacteriacea
and streptococci, it inhibits
Staph. Aureus
 It is used mainly for respiratory,
urinary , skin and soft tissue
infection
 DOSE: 200mg BD ( max 800
mg/day)

CEFDINIR
 This orally active 3rd
generation
cephalosporin has good activity
against many beta lactamase
producing organisms
 Most respiratory pathogens
including gram positive cocci are
susceptible
 Its indications are pneumonia,
acute exacerbations of chronic
bronchitis, ENT and skin
infections
 DOSE: 300 mg BD

CEFTBUTEN
 Another oral 3rd
generation
cephalosporin, active against gram
positive and few gram negative
bacteria but not Staph aureus
 It is indicated in respiratory, ENT
and orodental infections
 DOSE: 200mg BD or 400mg OD

 FOURTH GENERATION CEPHALOSPORINS:
Cefepime is more resistant to some beta lactamase
It is active against streptococci, and methicillin-
sensitive staphylococci
Its main use is in serious Gm-ve infections including
infections of CNS into which has excellent penetration
Dose :2gm IV bid

CEFEPIME
 Developed in 1990s , it has
antibacterial spectrum similar to that
of 3rd
generation compounds, but is
highly resistant to beta lactamases,
hence active against many bacteria
resistant to the earlier drugs
 Ps. Aeruginosa and Staph. Aureus
are also inhibited but not MRSA
 Due to high potency and extended
spectrum, it is effective in many
serious infections like hospital-
acquired pneumonia, febrile
neutropenia , bacteraemia,
septicaemia etc
 DOSE: 1-2g i.v. ,8-12 hourly

CEFPRIOME
 This 4th
generation cephalosporin has
become available for the treatment of
serious and resistant hospital
acquired infections including
septicaemias, lower respiratory tract
infection, etc
 Its zwitterion character permits
better penetration through porin
channels of gram negative bacteria
 It is resistant to many beta
lactamases and is more potent; than
the 3rd
generation compounds
 DOSE: 1-2g i.m / i.v. 12 hourly

ADVERSE EFFECTS
 Cephalosporins are generally well tolerated but
are more toxic than penicillin:
- Pain after i.m. infection occurs with some
cephalosporins. Thrombophlebitis can occur on
i.v. injections
-Diarrhoea due to alterations of gut ecology or
irritative effect is more common with oral
cephalexin, cefixime and parenteral cefoperazone
which is largely excreted in bile
- Hypersensitive reactions are the most important
adverse effects of cephalosporins. The
manifestation are similar to those with penicillin
but incidence is lower. Rashes are the most
frequent reactions, while anaphylaxis ,

 Angioedema, asthma and urticaria are occasional
 About 10% patients allergic to penicillin show
cross reactivity with cephalosporins
 Those with a history of immediate type of
reactions to penicillin should better not be given
a cephalosporin
 Skin tests for sensitivity to cephalosporins are
unreliable
- Nephrotoxicity some cephalosporins have low
grade nephrotoxicity which may be accentuated
by pre existing renal disease concurrent
administration of an aminoglycoside or loop
diuretics
- Bleeding occurs with cephalosporins having a
methylthiotetrazole or similar substitution at
position 3 (cefoperazone ,ceftriaxone)

This is due to hypoprothrombinaemia caused by
the same mechanism are warfarin
- Neutropenia, and thrombocytopenia are rare
adverse effects reported with ceftazidime and
some others
- A disulfiram like interaction with alcohol has
been reported with cefoperazone

USES
 DENTAL INFECTIONS: there are no compelling
indications for cephalosporins in dentistry except
as alternative to penicillin/ amoxicillin, especially
in patients who develop rashes or other milder
allergic reactions, and in cases with penicillin/
amoxicillin- resistant infection. As such they are
used to a lesser extent than penicillins. Therefore
they are used, one of the orally active 1st
or 2nd
generation cephalosporin is mostly selected for
orodental infection
-the first generation agents like cephalexin,
cephadroxil are used because of their high
activity against gram positive aerobic bacteria
and their good penetration into alveolar bone

-the 2nd
generation compounds like cefuroxime
axetil and cefaclor are the only ones with good
activity against oral anaerobes and are preferred
cephalosporins for dental indication
o GENERAL MEDICAL USES:
-as an alternatives to PnG in allergic patients one
of the first generation compounds may be used
-respiratory, urinary and soft tissue infections
caused by negative organisms especially
Klebsiella, proteus , Enterobacter, serrate
-penicillinase producing staphylococcal infections
-septicaemias caused by gram negative organisms;
an aminoglycoside may be combined with
cephalosporin

- Surgical prophylaxis: cefazolin is employed for most
types of surgeries
- Meningitis caused by H. influenzae,
Enterobacteriaceae : cefuroxime, cefotaxime and
ceftiaxone have been specially used
- Ceftazidime + gentamycin is the most effective
therapy for pseudomonas meningitis
- Gonorrhoea caused by penicillinase producing
organism: ceftriaxone is a first choice drug for
single dose therapy. For chancroid also, a single
dose is as effective as cotrimoxazole or
erythromycin given for 7 days
- Typhoid : ceftriaxone and cefoperazone are the
fastest acting drug
- Mixed aerobic- anaerobic infections seen in cancer
patients

 Hospital acquired infections especially of
respiratory tract, resistant to commonly used
antibiotics: cefotaxime, ceftizoxime or a fourth
generation drug may work
 Prophylaxis and treatment of infections ,
especially of respiratory tract , in neutrpenic
patients: ceftazidime or another third generation
compound alone or in combination with an
aminoglycosides

 FIFTH GENERATION CEPHALOSPORINS:
This is recently discovered cephalosporin and it is used
in severe infection
Example of this generation cephalosporin is
ceftobiprole

CEFTOBIPROLE
 The adult dose of ceftobiprole is 500mg every 8 hourly
given intravenously
 Ceftobiprole cannot be given by mouth
 Ceftobiprole is not licensed to be used in children

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