 PENICILLINS

 CEPHALOSPORINS
 MONOBACTAMS
 CARBAPENEMS
 ORIGINALLY OBTAINED FROM FUNGUS PENICILLIUM
NOTATUM.
 DISCOVERED IN 1928.

 AL. FLEMMING WAS WORKING IN HIS LAB TRYING

TO KILL A DEADLY BACTERIA WHEN HE NOTICED A
BLUE MOULD GROWING ON THE DISH (NOTATUM),
AROUND THAT BACTERIA WERE GETTING KILLED.
 PENICILLIN FOUND IN THIS MOULD
 NOW FROM P.CHRYSOGENUM BECAUSE AMOUNT
GOT FROM NOTATUM NOT SUFFICIENT.
The mould Penicillum
notatum
 amidase

B A

A THIAZOLIDINE RING ( A ) ATTACHED TO β –LACTAM

RING ( B) THAT CARRIES A SECONDARY AMINO GROUP
 β LACTAM RING CARRIES A SECONDARY
AMINO GROUP TO WHICH SIDE CHAINS
ATTACHED THROUGH AN AMIDE LINKAGE.
 PEN.G ( PROTOTYPE)
– BENZYL SIDE CHAIN.
 SIDE CHAINS SPLIT OFF BY AN AMIDASE TO
PRODUCE –
 6-AMINOPENCILLANIC ACID.
 A narrow spectrum antibiotic
 Mainly against gram positive bacteria
 Streptococci
 Pneumococci
 B.Anthracis
 Corynebacterium diphtheriae
 Clostridia
 Listeria
 Treponema pallidum
 Actinomyces israelii
 Gram negative cocci - N.gonorroeae and
meningitidis
 Pen.G is acid labile.
Give 30 min before or 2 hrs after meals.
 Very rapid renal excretion
 10% by glomerular filteration
 Rest by tubular secretion (ts)
 Ts can be blocked by probenecid
 To get higher and longer lasting plasma
conc.
 Insoluble salts of pen.G.
 Repository prep : release pen.G slowly.
 Given deep i/m.

 Procaine pen. 0.5 – 1mu,12-24 hrly as aq.

suspension.
 Plasma conc. Sustained for 1-2 days.
 BENZATHINE PEN. –
 Extremely slow release of pen.
 0.6-2.4 mu every 2- 4 wks.
 Effective for prophylactic purposes for upto 4
wks.
1. Streptococcal infections: Pharyngitis, otitis
media, scarlet fever, rheumatic fever.
2. Pneumococcal infections
3. Meningococcal infections
4. Anthrax, gas gangrene, diphtheria, syphilis,
tetanus.
5. Gonorrhoea
6. Prophylactic use-
A) Rheumatic fever: Benzathine pen. : 1.2 MU
every 4 wks till 18 years of age.

B) Gonorrhoea or syphilis : Procaine or

Benzathine pen. 2.4 MU single dose within 12 hrs
of contact .
7. Bacterial endocarditis-
extractions, endoscopies,catheterization,
surgical procedures.
8. Agranulocytosis - alone or in
combination.
9. Surgical infections - Procaine pen. 1 MU
with an aminoglycoside injected i.m 1 hr
before and 8-12 hrs after surgery can
reduce wound infections.
 Interferes with last step of synthesis of cell
wall that is - transpeptidation or cross
linkage
 Cell wall deficient forms of bact. Are formed
which swell and burst-
bacterial lysis.
 Bactericidal action
 Inhibits ENZYME, PENICILLIN BINDING
PROTEINS, pbps, INVOLVED IN SYN.Of cell
wall.
 PBPS catalyse formation of cross linkages
between peptidoglycan chains.

 Penicillins inhibit transpeptidase-catalysed

reactions ,thus hindering the formation of
cross links essential for cell wall integrity
and close knit structure of cell wall.

 Effective only against multiplying org. As

resting org. are not making new cell wall
 Polysaccharides in the cell wall contain
alternating amino sugars ---
 N-acetylglucosamine & N- acetylmuramic
acid.
 A five amino acid peptide is linked to N-
acetylmuramic acid sugar.
 This peptide terminates in D-alanyl-D-
alanine.
 PBP removes the terminal alanine in the
process of forming a cross link with a
nearby peptide .
 Cross- links give the cell wall its structural
rigidity.
 Beta lactam antibiotics, structural analogs
of the D-ala-D-ala substrate, bind to active
site of PBP.
 This inhibits the trans-peptidation reaction
 Preventing the peptidoglycan synthesis and
cell dies.
 Figure 49.2 Schematic diagram of a single layer of peptidoglycan from a bacterial cell (e.g. Staphylococcus aureus), showing the site of action of the β-lactam
antibiotics. In S. aureus, the peptide crosslinks consist of five glycine residues. Gram-positive bacteria have several layers of peptidoglycan. (NAG, N-acetylglucosamine;
NAMA, N-acetylmuramic acid; more detail in Fig. 49.3.)

Downloaded from: StudentConsult (on 27 July 2012 06:36 AM)

© 2005 Elsevier
 TARGET INSENSITIVE
PBPs WITH LOW AFFINITY FOR BINDING BETA
LACTAMS,
 LOCATED DEEPER UNDER LIPOPROTEIN BARRIER.

 IMPAIRED PENETRATION OF DRUG TO TARGET PBP.

 OCCURS IN GRAM NEGATIVE BACT DUE TO
IMPERMEABLE OUTER CELLWALL MEMBRANE
 PENICILLINASE PRODUCTION
 INACTIVATION OF ANTIBIOTIC BY β
LACTAMASES
 STAPH, GONOCOCCI, B.SUBTILIS, E.COLI,
H.INFLUENZAE PRODUCE PENCILLINASE.

 EFFLUX- GRAM NEGATIVE ORGANISMS MAY

PRODUCE AN EFFLUX PUMP WHICH TRANSPORT
β LACTAM ANTIBIOTICS FROM THE PERIPLASM
BACK ACROSS THE OUTER MEMBRANE.
 Hypersensitivity
 Most common drug implicated in drug
allergy
 Rash, itching, urticaria , fever, wheezing,
angioneurotic edema , serum sickness
exfoliative dermatitis and anaphylaxis,Rare
but fatal.
 More common with parenteral
administration.
 Highest with procaine penicillin .
 Partial cross sensitivity b/w different types
 A scratch test or intradermal test
 TEST WITH BENZYL- PENICILLOYL
POLYLYSINE , serves as a hapten to cause
an immune reaction.
 Topical use highly sensitising,
 Contact dermatitis and other reactions, so
banned.
 Pain at inj site
 Thrombophlebitis of injected vein
 Nausea on oral use
 Diarrhoea – with extended spectrum
penicllin, caused by a disruption of the
normal balance of intestinal organisms.
Ampicillin has been associated with
pseudo-membranous colitis.
 Toxicity to brain :
 mental confusion, Muscle twitchings
 Convulsions & coma
 Epileptics are at risk particularly.
 Nephritis – all can cause but seen particularly
with methicillin, so not used.

 Hematologic toxicities - decreased

coagulation with antipseudomonal ,to some
extent with Pen.G . caution in pts who are
predisposed to hemorrhage , or receiving
anticoagulants.
 JARISCH-HERXHEIMER REACTION-

PENICILLIN INJECTED IN A SYPHILITIC

PATIENT - SHIVERING , FEVER , MYALGIA ,
EXACERBATION OF LESIONS & VASCULAR
COLLAPSE.
DUE TO SUDDEN RELEASE OF SPIROCHAETAL
LYTIC PRODUCTS AND LASTS FOR 12- 24 HRS
ASPIRIN AND SEDATION HELP.
 PRODUCED BY CHEMICALLY COMBINING
SPECIFIC SIDE CHAINS
 AIM IS TO OVERCOME SHORTCOMINGS OF
PnG –
 POOR ORAL EFFICACY
 SUSCEPTIBILITY TO PENCILLINASE
 NARROW SPECTRUM OF ACTIVITY
 HYPERSENSITIVITY
 ACID RESISTANT ALTERNATIVE TO PnG
 Penicillin V
 PENICILLINASE RESISTANCE PENICILLINS
 Methicilin, oxacillin, cloxacillin, dicloxacillin
 EXTENDED SPECTRUM PENICILLINS
 a) AMINOPENICILLINS : Ampicillin,
Bacampicillin, Amoxicillin
 b) CARBOXYPENICILLINS: Carbenicillin,
carbenicillin indanyl & phenyl, Ticarcillin
 c) UREIDOPENICILLINS : Piperacillin,
Mezlocillin
 ACID STABLE
 1/5th AS ACTIVE AG.NEISSERIA, OTHER
GRAM NEGATIVE BACTERIA AND ANEROBES.
 USED ONLY FOR-
 STREP.PHARYNGITIS, SINUSITIS & OTITIS
MEDIA
 PROPHYLAXIS OF RHEUMATIC FEVER
 PNEMOCOCCAL INFECTIONS
 ANTI - STAPHYLOCOCCAL PEN.
Have side chains that protect beta lactam ring from
attack by staphylococcal penicillinase.

 Indication - Penicillinase producing staph

 METHICILLIN -
 HIGHLY PENICILLINASE RESISTANT
 NOT ACID RESISTANT- MUST BE INJECTED
 MRSA ( Methicillin resistant staph aureus)
 INSENSITIVE TO ALL PENCILLINASE RESISTANT
PEN.
 HAVE ALTERED PBPs WHICH DO NOT BIND
PENICILLINS
 DRUG OF CHOICE-
 VANCOMYCIN / LINEZOLID
 CIPROFLOXACIN
 HAEMATURIA
 ALBUMINURIA
 REVERSIBLE INTERSTITIAL NEPHRITIS
 LARGELY REPLACED BY CLOXACILLIN
 OXA ,CLOXACILLIN , DICLOXACILLIN
 ALL RELATIVELY STABLE IN ACIDIC MEDIUM
 ADEQUATELY ABSORBED AFTER ORAL
ADMINISTRATION
 DICLOXACILLIN MOST ACTIVE
 ALL LESS ACTIVE AG. ORGANISMS SENSITIVE
TO PENICILLIN G
 ISOXAZOLYL SIDE CHAIN

 Highly penicillinase resistant

 More active than methicillin against
penicillinase resistant staph
 Relatively acid resistant.
 However food interferes with absorption
so give one hour before or after meals.
 0.25- 0.5 g orally every 6 hourly
 For serious infections 0.25 -1 g injected
i.m. or i.v.
 RAPIDLY ABSORBED FROM GIT
 RAPIDLY EXCRETED BY KIDNEY
 HALF LIFE - 30-60 MIN
 DAILY DOSE OF OXACILLIN- 2-4 g in 4
DIVIDED DOSES
 DICLOXA - 250 mg EVERY 6 HOURS
 USED TO TREAT INFECTIONS SUCH AS
OSTEOMYLITIS, SEPTICAEMIA ,
ENDOCARDITIS AND CELLULITIS CAUSED BY
SUSCEPTIBLE STRAINS OF STAPH.

 CLOXACILLIN CAN ALSO BE USED TO TREAT

MILD STAPHYLOCOCCAL SKIN INFECTIONS
SUCH AS IMPETIGO.
 AMINO SUBSTITUTION IN SIDE CHAIN
 AMPICILLIN
 SAME ORGANISMS AG. WHICH PEN.G IS EFFECTIVE
 GRAM –VE : E.COLI , SALMONELLA,
 PROTEUS, SHIGELLA
 MORE ACTIVE THAN PEN.G AGAINST :
 STREPT.VIRIDANS & ENTEROCOCCI
 P/K – NOT DEGRADED BY GASTRIC ACID
 ADEQUATE ORAL ABSORPTION BUT INCOMPLETE
 FOOD INTERFERS WITH ABSORPTION
 PLASMA HALF LIFE – ONE HOUR
USES - UTI – RESISTANCE,
FLUOROQUINOLONES/COTRIMOXAZOLE
 RTI – SINUSITIS , OTITIS MEDIA, BRONCHITIS
 DOSE- 0.5-2 g ORAL /I.M. /I.V. 6 HOURLY
 MENINGITIS - ALONG WITH THIRD
GEN.CEPH.
 GONORRHEA - NPPG
 TYPHOID FEVER - RESISTANCE
 BACILLARY DYSENTRY- SHIGELLA
(QUINOLONES PREFERRED)
 CHOLECYSTITIS- HIGH CONC. IN BILE
 S/Es – diarrhoea, rashes resembling measles
or rubella
 BACAMPICILLIN
 PRODRUG, largely hydrolysed during
absorption . Nearly completely absorbed
from git.
 Tissue penetration better.
 Diarrhoea less ( does not disturb intestinal
ecology much )
 ORAL ABSORPTION IS BETTER. FOOD DOES NOT
INTERFERE. HIGHER BLOOD LEVELS FOR LONGER
TIME.
 DIFFERENCES FROM AMPICILLIN-
 DIARRHEA IS LESS.
 LESS ACTIVE AG. SHIGELLA AND H.INFLUENZAE.
 PREFFERED FOR – TYPHOID, UTI , GONORRHEA,
BRONCHITIS , SABE.
 EMPLOYED PROPHYLACTICALLY BY DENTISTS FOR
PATIENTS WITH HEART VALVE DS, WHO HAVE TO
UNDERGO ORAL SURGERY.
 DOSE- 250 mg - 1g tds oral
 CARBENICILLIN
 ACTIVITY Ag. - PSEUDOMONAS AERUGINOSA
 - INDOLE POSITIVE PROTEUS
 USED IN SERIOUS INFECTIONS CAUSED BY THE TWO
e.g. Burns, UTI, Septicemia.
 NEITHER PENICILLINASE RESISTANT NOR ACID
RESISTANT.
 Inactive orally, excreted rapidly in urine .
 Used as sodium salt
 Not preffered. Piperacillin preffered.
 As sodium salt, can cause fluid retention, CHF in
patients with borderline renal or cardiac function.
 Bleeding problems.
 A DERIVATIVE CARBENICILLIN INDANYL
SODIUM GIVEN ORALLY FOR UTI AND
OTHER LESS SERIOUS INFECTIONS.
 ACID STABLE ESTER OF CARBENICILLIN.

TICARCILLIN
 MORE POTENT AG. PSEUDOMONAS
 LESS ACTIVE THAN AMPICILLIN AGAINST
ENTEROCOCCI.
 PIPERACILLIN

 8 times more active than carbenicillin

 Good activity ag. Klebsiella
 Used mainly in immuno-compromised
patients, having gram negative infections and
in burns.
 Because of resistance problem
antipseudomonal penicillin is combined with
an aminoglycoside or fluoroquinolone.
 INHIBITS KLEBSIELLA
 GIVEN PARENTERALLY FOR INFECTIONS
CAUSED BY ENTERIC BACILLI.
 ACTIVITY SIMILAR TO TICARCILLIN AG.
PSEUDOMONAS
 BETA LACTAMASES : Enzymes produced
by gram positive and gram negative
bacteria that inactivate beta lactam
antibiotics by opening beta lactam ring .

 BETA LACTAMASE INHIBITORS

CLAVULANIC ACID
SULBACTAM
TAZOBACTAM
 FROM streptomyces clavuligerus
 Has beta lactam ring
 No antibacterial activity of its own
 Inhibits many beta lactamases
 Inhibition increases with time, initially reversible
becomes covalent with time-Progressive inhibitor
 Irreversible binder
 Suicide inhibitor , gets inactivated after binding to
the enzyme .
 Well absorbed by mouth, also given parenterally
 COMBINED WITH AMOXICILLIN AS AN ORAL
PREP.
 WITH TICARCILLIN AS A PARENTERAL.
 AMOXICILLIN + CLAVULANATE EFFECTIVE FOR
BETA LACTAMASE PRODUCING STRAINS OF
STAPH (NOT MRSA) , H. INFLU, GONOCOCCI,
E.COLI .
 EFFECTIVE IN TREATMENT OF:
 Skin & soft tissue infections
 Gynae infections
 Urinary & biliary infections
 Acute otitis media in children
 Sinusitis
 Bite wounds, cellulitis, diabetic foot infections.
 Addition of clavulanic acid to ticarcillin extends its
spectrum such that it resembles imepenem to
include aerobic gram negative bacilli, S. Aureus,
bacteriodes .
 Dosage should be adjusted for patients
with renal insufficiency.
 Combination is especially useful for mixed
nosocomial infections, often used with
aminoglycosides.
 Activity ag. Pseudomonas is not increased.
 Git tolerance is poorer.
 Super-infections are more.
 Amoxicillin 250 + clavulanate 125 mg
 Semisynthetic Beta-lactamase inhibitor .
- given orally/parenterally along with beta lactam
antibiotic.
Combined with ampicillin.
- Dosage adjusted in patients with impaired renal
fxn.
- Good activity ag.Gram positive cocci, including
beta-lactamase producing strains of staph aureus,
gram negative aerobes and anaerobes.
- Used effectively for mixed intra-abdominal and
pelvic infections.
 Beta lactamase inhibitor
 Has been combined with Piperacillin as a parenteral
prep.
 3 g Piperacillin, 375 mg Tazobactam every 4- 8
hourly.
 Equal to Ticarcillin plus clavulanate.
 BETA LACTAMS THAT CONTAIN A FUSED β-
lactam ring and a 5-membered ring syst
that differs from pen. In being unsaturated
and containing a carbon atom instead of
sulphur atom.

 Have a broader spectrum of activity than

do most other β-lactam antibiotics have.
 IMIPENEM
 MEROPENEM
 ERTAPENEM
 DERIVED FROM A COMPOUND PRODUCED
BY STREPTOMYCES CATTLEYA
 BINDS TO PBPs, DISRUPTS BACTERIAL CELL
WALL SYNTHESIS.
 VERY RESISTANT TO HYDROLYSIS BY MOST
BETA LACTAMASES.
 NOT ABSORBED ORALLY
 IS RAPIDLY HYDROLYSED BY A DEHYDRO-
PEPTIDASE FOUND IN THE BRUSH BORDER OF
PROXIMAL RENAL TUBULES.
 GIVEN WITH AN INHIBITOR OF DEHDROPEPTIDASE,
CILASTATIN . A PREPRATION WITH EQUAL
AMOUNTS OF BOTH.
 BOTH HAVE A HALF LIFE OF ONE HOUR.
 DOSE - 0.5 g i.v. 6 hourly.
 DOSAGE SHOULD BE MODIFIED FOR PATIENTS
WITH RENAL INSUFFICIENCY.
 IMIPENEM / CILASTATIN AND MEROPENEM ARE THE
BROADEST SPECTRUM BETA LACTAM ANTIBIOTICS.
 PLAYS A ROLE IN EMPERICAL THERAPY BECAUSE IT
IS ACTIVE AGAINST PENICILLINASE PRODUCING
GRAM- POSITIVE AND GRAM NEGATIVE
ORGANISMS, ANAEROBES, AND P. AERUGINOSA.
 STREPTOCOCCI (INCL. PENICILLIN RESISTANT
S.PNEUMONIAE), ENTEROCOCCI, STAPH, LISTERIA,
SOME STRAINS OF MRSA, ACINETOBACTER, B.
FRAGILIS.
 NAUSEA & VOMITING
 SEIZURES , WHEN HIGH DOSES GIVEN IN
PATIENTS WITH CNS LESIONS AND THOSE
WITH RENAL INSUFFICIENCY.
 ALLERGIC TO PEN. MAY SHOW
HYPERSENSITIVITY.
 LESSER EOSINOPHILIA AND NEUTROPENIA
 IMIPENEM / CILASTATIN FOR
 UTI , LOWER RESPIRATORY TRACT INFECTIONS,
INTRAABDOMINAL AND GYNAECOLOGICAL
INFECTIONS.
 SKIN AND SOFT TISSUE , BONE AND JOINT
INFECTIONS .
 DRUG COMBINATION ESP. USEFUL FOR
INFECTIONS CAUSED BY CEPHALOSPORIN-
RESISTANT NOSOCOMIAL BACT, SUCH AS
CITROBACTER AND ENTEROBACTER
 FOR EMPERICAL TREATMENT OF SERIOUS INF. IN
HOSPITALISED PT .
 SHOULD NOT DE USED ALONE - RESISTANCE RISK
 DOES NOT REQUIRE CO-ADMINISTRATION
WITH CILASTATIN, NOT SENSITIVE TO
RENAL DIPEPTIDASE.
 LESS LIKELY TO CAUSE SEIZURES.
 ACTIVITY AG. P. AERUGINOSA.
 LESS ACTIVITY AG GRAM + VE COCCI.
 THERAPEUTICALLY EQ.TO IMIPENEM
 AZTREONAM
 MONOCYCLIC BETA LACTAM COMP.
 BETA LACTAM RING IS NOT FUSED TO
ANOTHER RING .
 ISOLATED FROM CHROMOBACTERIUM
VIOLACEUM
 INTERACTS WITH PBPs OF SUSCEPTIBLE
BACT, INDUCES THE FORMATION OF LONG
FILAMENTOUS BACT. STRUCTURES.


 DIFFERS FROM BETA LACTAM, RESEMBLES
AMINOGLYCOSIDES
 GRAM +VE AND ANAEROBES ARE
RESISTANT .
 EXCELLENT ACT. AG. -
ENTEROBACTERIACEAE , PSEUDOMONAS,
H.INFLU (At very low conc.) , GONOCOCCI .
 RES.TO ACTION OF MANY BETA
LACTAMASES.
 ADM. I/M OR I/V
 ELIMINATION HALF LIFE 1.7 HOURS
 CAN ACCUMULATE IN PTs. WITH RENAL
FAILURE.
 USUAL DOSE FOR SERIOUS INFECTIONS - 2 g
6-8 HOURLY, BUT DECREASED IN RENAL DS
PTs.
 WELL TOLERATED
 LOW IMMUNOGENIC POT.
 MAIN ADVANTAGE - PATIENTS WHO ARE
ALLERGIC TO PENICILLINS OR
CEPHALOSPORINS DO NOT REACT TO
AZTREONAM.
 QUITE USEFUL FOR TREATING GRAM
NEGATIVE INFECTIONS, THAT COULD BE
TREATED WITH ABOVE DRUGS, BUT H/O
ALLERGY WAS THERE.
 Produced semisynthetically by chemical
attachment of side chains to
7-aminocephalosporanic acid.
Same mode of action , same resistance mech.
But tend to be more resistant than penicillins
to certain beta –lactamases .
 CLASSIFIED AS FIRST,SECOND,THIRD OR FOURTH
GENERATION BASED ON :
-- BACTERIAL SUSCEPTIBILITY PATTERNS
-- RESISTANCE TO BETA –LACTAMASES

 NOT EFFECTIVE AGAINST -

 MRSA , L. MONOCYTOGENES , C. DIFFICLE ,
ENTEROCOCCI
 FIRST GENERATION
 PARENTERAL –
 CEPHALOTHIN
 CEFAZOLIN
 ORAL –
 CEPHALEXIN
 CEPHRADINE
 CEFADROXIL
 PARENTERAL
 CEFUROXIME
 CEFOXITIN

 ORAL
 CEFACLOR
 CEFUROXIME AXETIL
 PARENTERAL
 CEFOTAXIME CEFTIZOXIME
 CEFTRIAXONE CEFTAZIDIME
 CEFOPERAZONE

 ORAL
 CEFIXIME CEFPODOXIME
 CEFDINIR CEFTIBUTEN
 PARENTERAL
 CEFEPIME
 CEFPIROME
 CEPHALOTHIN
 ACTIVE AGAINST MOST Penicilln G SENSITIVE
ORG. i.e.
 Streptococci (pyogenes & viridans),
staphylococcus (including those producing
penicillinase), not MRSA
 Gonococci, meningococci, C.diphtheriae
Clostridia, actinomyces
 Main indication – penicillinase producing staph
 i.v. 1 -2 g 6 hrly ( i/m Painful)
 MORE ACTIVE AG. KLEBSIELLA & E.COLI
 SUSCEPTIBLE TO STAPH BETA-LACTAMASE
 PREFFERED PARENTERAL FIRST GEN
SPECIALLY FOR SURGICAL PROPHYLAXIS
 Can be given i.m. also, less painful
 0. 25 g 8 hourly, 1 g 6 hrly i.m , i.v.
 Orally effective
 Similar to cephalothin in spectrum , but less
active ag. Penicillinase producing staph and
ag. H .influenzae.
 Little bound to plasma proteins, attains
high conc. In bile.
 Excreted unchanged in urine
 0.25 – 1 g 6-8 hrly
 ORALLY ACTIVE , SIMILAR TO CEPHALEXIN
 DIARRHOEA
 PARENTERAL ALSO

 CEFADROXIL
 A CLOSE CONGENER OF CEPHALEXIN
 GOOD TS. PENETRATION
 MORE SUSTAINED ACTION AT THE SITE OF
INFECTION
 CAN BE GIVEN 12 HRLY, EXCRETED UNCHANGED IN
URINE
 CEFOXITIN
 MORE ACTIVE AGAINST SERRATIA, INDOLE
POSITIVE PROTEUS, B.FRAGILIS
 HIGHLY RESISTANT TO B-LACTAMASES
PRODUCED BY GRAM –VE BACT.
 ANEROBIC & MIXED OBS/ SURGICAL INF.
 LUNG ABSCESS
 DOSE – 1-2 g I.M / I.V EVERY 6-8 HRS
 RESISTANT TO BETA-LACTAMASES PRODUCED
BY GRAM –VE BACTERIA .
 HIGH ACTIVITY AG. ORG. PRODUCING THESE
ENZYMES INCL. PPNG AND AMPICILLIN
RESISTANT H.INFLUENZAE .
 HAVE SIGNIFICANT ACTIVITY ON GRAM POSITIVE
COCCI.
 ATTAINS HIGH CSF LEVELS
 MOST IMP. USE IS MENINGITIS CAUSED BY
H.INFLUENZAE , MENINGOCOCCI , PNEUMOCOCCI
 HIGHLY SIGNIFICANT ACTIVITY BY ORAL
ROUTE
 MORE ACTIVE THAN FIRST GEN. COMP.
AGAINST H.INFLUENZAE , E.COLI , P.MIRABILIS
 HIGH ACTIVITY AGAINST GRAM NEGATIVE
ENTEROBACTERIACEAE
 PSEUDOMONAS
 RESISTANT TO BETA-LACTAMASES FROM
GRAM NEGATIVE BACT.
 LESS ACTIVE ON GRAM POSITIVE COCCI
 PROTOTYPE
 AEROBIC GRAM NEGATIVE & GRAM POSITIVE
BACT.
 NOT VERY ACTIVE ON ANEROBES , STAPH , Ps.
AERUGINOSA
 INDICATIONS – MENINGITIS BY GRAM –VE
 LIFE THREATENING HOSPITAL ACQUIRED
INFECTION, SEPTICEMIAS
 INFECTION IN IMMUNOCOMPROMISED PATIENTS
 1-2 g i.m. or i.v. 6-12 hrly
 Single dose therapy (1g i.m. and 1g
probenecid ) for PPNG urethritis.
 De-acetylated in the body
 Metabolite exerts weaker but synergistic
action with the parent drug .
 Longer duration of action ( half life 8 hrs )
 Once or twice daily dosing
 Good CSF penetration
 High efficacy in bacterial meningitis
 Multi- resistant typhoid fever
 Complicated UTI
 Abdominal sepsis ,Septicemias
 A single dose of 250 mg. i.m. - curative in
gonorrhea including PPNG and chancroid .
 High activity ag. Pseudomonas
 Sp. useful in febrile neutropenic pts. with
hematological malignancy, burn.
 Enterobacteriaceae
 Less active on staph. aureus and gram
positive cocci.
 Half life 1.5-1.8 hr.
 Neutropenia, thrombocytopenia , rise in
plasma trans-aminases and blood urea has
been reported.
 STRONGER ACTIVITY ON PSEUDOMONAS
 GOOD FOR S.TYPHI & B. FRAGILIS
 MORE SUSCEPTIBLE TO β-LACTAMASES
 INDICATIONS --
 SEVERE URINARY, BILIARY, RESPIRATORY, SKIN-
SOFT TS. INFECTIONS, MENINGITIS, SEPTICAEMIAS
.
 EXCRETED MAINLY IN BILE
 DISULFIRAM LIKE REACTION WITH ALCOHOL.
 ORALLY ACTIVE WITH HIGH ACTIVITY ag.
Entero-bacteriaceae, H.Influenzae, strep.
Pyogenes , strep. Pneumoniae
 Resistant to many beta lactamases.
 Longer acting .
 200-400 mg b.d. For respiratory, urinary &
biliary infections .
 Diarrhea common side effect.
 ORALLY ACTIVE , PRODRUG
 ENTEROBACT, STREP, STAPH
 RESPIRATORY , URINARY , BILIARY INF.
 GOOD ACTIVITY Ag. BETA LACTAMASE
PRODUCING ORG.
 PNEUMONIA , ACUTE EXACERBATIONS OF
CHRONIC BRONCHITIS , ENT, SKIN
INFECTIONS .
 ACTIVE AG.BOTH GRAM POSITIVE AND
NEGATIVE
 STABLE TO BETA LACTAMASES
 INDICATED IN RESPIRATORY, URINARY , GI
INFECTIONS
 CEFEPIME
 HIGHLY RESISTANT TO BETA- LACTAMASES
 SPECTRUM SIMILAR TO THIRD GEN
 ADDITIONAL ACTIVITY AG. BACTERIA RESISTANT
TO OTHER DRUGS .
 P. AERUGINOSA, STAPH ALSO INHIBITED
 EFFECTIVE IN MANY SERIOUS INFECTIONS LIKE
NOSOCOMIAL , FEBRILE NEUTROPENIA ,
BACTEREMIA, SEPTICAEMIA
 1-2 g i.v. 8-12 hrly
 SERIOUS AND RESISTANT HOSPITAL
ACQUIRED INFECTIONS
 SEPTICEMIAS
 LOWER RESP. TRACT INFECTIONS
 BETTER PENETRATION THROUGH PORIN
CHANNELS OF GRAM NEGATIVE BACTERIA
 RESISTANT TO MANY BETA-LACTAMASES
 Local irritation can produce severe pain after i.M.
Injection, thrombophlebitis after i.v.
 Diarrhoea due to disturbed gut ecology

 Hypersensitivity reactions similar to Penicillins

including anaphylaxis, fever, skin rashes, nephritis,
granulocytopenia and hemolytic anemia. Cross
allergenicity around 5-10 % .
 Nephrotoxicity including interstitial nephritis and
even tubular necrosis, highest with cephaloridine
(withdrawn) cephalothin also causes.
 Hypoprothrombinemia and bleeding disorders by
cefamandole , cefmetazole, cefotetan ,
cefoperazone
vit. K 10 mg twice weekly can prevent it.

 A disulfiram like interaction with alcohol with

cefoperazone .

 Neutropenia and thrombocytopenia rarely, with

ceftazidime.
 Figure 49.3 Schematic diagram of the biosynthesis of peptidoglycan in a bacterial cell (e.g. Staphylococcus aureus), with the sites of action of various antibiotics. The
hydrophilic disaccharide-pentapeptide is transferred across the lipid cell membrane attached to a large lipid (C55 lipid) by a pyrophosphate bridge (-P-P-). On the outside,
it is enzymically attached to the 'acceptor' (the growing peptidoglycan layer). The final reaction is a transpeptidation, in which the loose end of the (Gly) 5 chain is
attached to a peptide side-chain of an M in the acceptor and during which the terminal amino acid (alanine) is lost. The lipid is regenerated by loss of a phosphate group
(Pi) before functioning again as a carrier. G, N-acetylglucosamine; M, N-acetylmuramic acid; UDP, uridine diphosphate; UMP, uridine monophosphate.

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