BACTERIAL

CELL WALL INHIBITORS

BETA-LACTAM ANTIBIOTICS
DR. SHAFAQ ZAFAR
 PENICILLINS
 CEPHALOSPORINS
 CARBAPENEMS
 MONOBACTAMS
 β-LACTAM RING

CHEMICAL STRUCTURES OF
BETA-LACTAM ANTIBIOTICS
PENICILLIN
NUCLEUS
6-AMINOPENICILLANIC ACID A B
A = BETA-LACTAM RING
B = THIAZOLIDINE RING BETA-LACTAMASE
(cleaves amide bond)
1 R group

CEPHALOSPORIN NUCLEUS

7-AMINOCEPHALOSPORONIC ACID A B
A = BETA-LACTAM RING
B = DIHYDROTHIAZINE RING BETA-LACTAMASE

2 R groups
MONOBACTAM
NUCLEUS

BETA-LACTAMASE RESISTANT
 CARBAPENEM NUCLEUS

CARBON
SUBSTITUTED
FOR SULFUR

CARBACEPHEM NUCLEUS

HIGHLY RESISTANT TO BETA-LACTAMASE

 CLAVULANIC ACID

INHIBITS MANY BETA-LACTAMASES

BACTERIAL CELL WALL
PEPTIDOGLYCAN LAYER OF A CELL
CONFORMATION
SIMILAR TO BETA-
LACTAM
ANTIBIOTIC

L-Ala
D-Glu
L-
Lys
D-Ala
D-Ala

TRANS-
PEPTIDATI
ON
TETRAPEPTIDE
SIDE-CHAIN

PENTAGLYCINE CROSS-
LINKS

N-ACETYLMURAMIC ACID (NAM)

N-ACETYLGLUCOSAMINE
(NAG)
PEPTIDOGLYCAN
 MECHANISM OF ACTION

 BETA-LACTAM ANTIBIOTICS INHIBIT THE SYNTHESIS

OF PEPTYDOGLYCAN LAYER OF THE BACTERIA BY
BINDING TO PENICILLIN BINDING PROTEINS (PBPs)

 TRANSPEPTIDASE

 CARBOXYPEPTIDASE
 TRANSGLYCOSYLASE

1. THUS INHIBITING THE FINAL TRANSPEPTIDATION

THAT ESTABLISHES THE CROSS-LINKS
2. INHIBITION OF SOME PBPs LEAD TO
BREAKING OF PEPTIDE LINKS BY
AUTOLYSINS OR MUREIN
3. HYDROLASES
CHANGE OF BACTERIA TO SPHEROPLAST OR A
FILAMENTOUS FORM
 L-Ala
D-Glu
L-
Lys
D-Ala

TETRAPEPTIDE
SIDE CHAIN

PENTAGLYCINE
CROSS-LINKS

N-ACETYLMURAMIC ACID (NAM)

N-ACETYLGLUCOSAMINE
(NAG)
 WEEK CELL WALL RESULTS
IN OSMOTIC LYSIS

PEPTIDOGLYCAN

A AS THE
EXPOSURE TO β-LACTAM AUTOLYSINS
ANTIBIOTICS
CONTINUE TO
WEAK POINTS LACKING
PEPTIDOGLYCAN
BREAK THE
B PEPTIDE
EXPOSURE TO HYPOTONIC CROSS-LINKS
ENVIRONMENT
AND NEW
CROSS-LINKS
MEMBRANE BULGES FAIL TO
C OUT AS WATER DIFFUSES
INTO CELL FORM, THE
MEMBRANE BREAKS BACTERIUM
BURST FROM
CELL LYSES
OSMOTIC
LYSIS
D
 RESITANCE

 INACTIVATION OF ANTIBIOTIC BY β-LACTAMASE

 CLEAVE AMIDE BOND
 EXPRESSED BY CHROMOSOMAL AND PLASMID
GENES
 SOME ARE CONSTITUTIVE, OTHERS INDUCED BY
BETA-LACTAM ANTIBIOTICS
 STAPH, GONO, AND OTHER GRAM -VE BACTERIA
 MODIFICATION OF TARGET PBPs
 IMPAIRED PENETRATION OF ANTIBIOTICS
 PRESENCE OF EFFLUX PUMP
1. PENICILLINS
 CLASSIFICATION

A. NARROW-SPECTRUM PENICILLINS

1. BETA-LACTAMASE SENSITIVE

NATURALLY OCCURRING PENICILLIN & ITS

CONGENERS

 PENICILLIN G (BENZYL PENICILLIN)

 PENICILLIN V (PHENOXYMETHYL
PENICILLIN)
REPOSITORY FORMS

 PENICILLIN G PROCAINE SUSPENSION

PENICILLIN G BENZATHINE SUSPENSION

LIMITATIONS:
• Acid labile
• Short duration of action
• Narrow spectrum
• Penicillinase susceptible
• Anaphylaxis
2. PENICILLINASE-RESISTANT PENICILLIN
(ANTISTAPHYLOCOCCAL)

 METHICILLIN
 NAFCILLIN

 OXACILLIN
 CLOXACILLIN
ISOXAZOLYL PENICILLINS
 DICLOXACILLIN
 FLOXACILLIN
 B. BROAD-SPECTRUM OR EXTENDED-
SPECTRUM PENICILLINS

I. AMINOPENICILLINS

 AMPICILLIN
 AMOXICILLIN
 CYCLACILLIN

 EPICILLIN
 TEMOCILLIN (FOR ENTEROBACTERIACEAE BUT
CEPHALOSPORINS ARE IST CHOICE)
ESTERS OF AMPICILLIN

 BACAMPICILLIN
 PIVAMPICILLIN
 TALAMPICILLIN
II. CARBOXYPENICILLINS
(ANTIPSEUDOMONAL PENICILLINS)

 TICARCILLIN
 CARBENICILLIN

ESTERS OF CARBENICILLIN
 CARBENICILLIN INDANYL
 CARBENICILLIN PHENYL SODIUM
III. UREIDOPENICILLINS
(ANTIPSEUDOMONAL
)

 AZLOCILLIN
 MEZLOCILLIN
 PIPRACILLIN
 BETA-LACTAMASE INHIBITORS

 CLAVULANIC ACID

AMOXICILLIN + CLAVULANIC ACID

(CO-AMOXICLAV)

TICARCILLIN + CLAVULANIC ACID

(TIMENTIN)
 SULBACTUM
AMPICILLIN + SULBACTAM
(UNASYN)

 TAZOBACTUM
PIPERACILLIN + TAZOBACTAM
(ZOSYN)
ANTIBACTERIAL SPECTRUM
&
CLINICAL USES
A. NARROW-SPECTRUM PENICILLINS

BENZYLPENICILLIN

1. GRAM +VE COCCI

2. DRUG OF CHOICE OR ADJUVANT THERAPY FOR

 MENINGOCOCCAL MENINGITIS
 ANTHRAX
 GAS GANGRENE (PENICILLIN + ANTITOXIN)
 TETANUS (PENICILLIN + ANTITOXIN)
 DIPHTHERIA (PENICILLIN + ANTITOXIN)
 SYPHILIS( First choice)
 ACTINOMYCOSIS
 LYME DISEASE (SPIROCHETAL DISEASE)

3. PROPHYLACTIC USE (RHEUMATIC FEVER BY

STREP. PYOGENES AND BACTERIAL
ENDOCARDITIS)
B. BROAD-SPECTRUM PENICILLIN

 H. INFLUENZAE
 E. COLI
 PROTEUS MIRABILIS
 ENTEROBACTERIACEAE
 Penicillin resistant Strep.Pneumoniae (Amoxacillin)
UTI
SINUSITIS
OTITIS
LRTI
SHIGELL
C. CARBOXYPENICILLINS/ UREIDOPENICILLINS
(ANTIPSEUDOMONAL)
 PSEUDOMONAS (IN COMBINATION WITH AN
AMINOGLYCOSIDE)

 PROTEUS

 ENTEROBACTER

 KLEBSIELLA (UREIDOPENICILLIN)
CO-AMOXICLAV

BACTERIA SUSCEPTIBLE TO AMOXICILLIN

 MOST STAPHYLOCOCCUS AUREUS

 MOST E. COLI
 MANY BACTEROIDES
 MANY KLEBSIELLA
 SOME H. INFLUENZAE
 PHARMACOKINETICS

• ACID LABILE PENICILLINS

• ACID STABLE PENICILLINS
• EXCRETION THROUGH KIDNEYS
• NAFCILLIN AND AMPICILLIN IN THE BILE
• OXACILLIN, CLOXACILLIN IN URINE AND BILE
ADVERSE REACTIONS
&
TOXICITIES
I. HYPERSENSITIVITY PATIENT POSITION IN

REACTIONS ANAPHYLACTIC SHOCK

 ANAPHYLACTIC SHOCK
 SERUM SICKNESS TYPE REACTIONS
(URTICARIA, FEVER, JOINT SWELLING,
ANGIOEDEMA, INTENSE PRURITUS)
 VARIETY OF SKIN RASHES
Anaphylaxis RASH URTICARIA ANGIOEDEMA
Loss of
consciousness
Hives

Swelling of
tongue,
inability to
swallow
Rapid swelling
of throat tissue
 ORAL LESIONS
 INTERSTITIAL NEPHRITIS
 EOSINOPHILIA
 HEMOLYTIC ANEMIA
 VASCULITIS
II. GIT DISTURBANCES

III. OTHER ADVERSE EEFECTS AND TOXICITIES

NAFCILLIN ------ NEUTROPENIA, SODIUM LOAD

OXACILLIN ------ HEPATITIS
METHICILLIN --- INTERSTITIAL NEPHRITIS
AMPICILLIN ----- PSEUDOMEMBRANOUS
COLITIS, CANDIDIASIS
PENICILLIN G -- POTASSIUM LOAD
TICARCILLIN --- SODIUM LOAD
DRUG INTERACTIONS

1. NOT TO BE GIVEN IN SAME SYRINGE OR INFUSION

AMINOGLYCOSIDE + CARBOXYPENICILLIN
AMINOGLYCOSIDE + UREIDOPENICILLIN
2. PROBENECID INCREASES DURATION OF ACTION OF
PENICILLIN

3. THERAPEUTIC FAILURE OF OCPS BY AMPICILLIN

 2. CEPHALOSPORINS
(CEPHALOSPORIUM) – 2 R groups
AND
CEPHAMYCIN
S
(STREPTOMYCES) – 3 R
groups
 CLASSIFICATION

FIRST GENERATION

 CEPHALOTHIN
 CEPHRADINE
 CEPHALEXIN A B

 CEFADROXIL
 CEFAZOLIN
 CEPHAPIRIN
7-AMINOCEPHALOSPORONIC ACID
A = BETA-LACTAM RING
B = DIHYDROTHIAZINE RING
 SECOND
GENERATION
 CEFACLOR
 CEFAMANDOLE
 CEFUROXIME
 CEFUROXIME AXETIL
STRUCTURE SIMILAR
 LORACARBEF (CARBACEPHEM)
TO CEFACLOR
 CEFOXITIN (CEPHAMYCIN)
 CEFOTETAN (CEPHAMYCIN)
 CEFMETAZOLE (CEPHAMYCIN)
 CEFONICID
 CEFORANIDE
 CEFPROZIL
 THIRD
GENERATION
 CEFIXIME
 CEFTRIAXONE
 CEFOTAXIME
 CEFTAZIDIME
 CEFOPERAZONE
 CEFPODOXIME PROXETIL
 CEFTIBUTEN
 CEFTIZOXIME
 CEFDINIR
 MOXALACTAM (CEPHAMYCIN)
 CEFETAMET PIVOXIL
 FOURTH
GENERATION
 CEFIPIME
 CEFPIROME
ANTIMICROBIAL SPECTRUM
FIRST GENERATION
 VERY ACTIVE AGAINST AEROBIC GRAM-POSITIVE
COCCI
PNEUMOCOCCI
STREPTOCOCCI
STAPHYLOCOCCI

 ACTIVE AGAINST
AEROBIC GRAM-
NEGATIVE RODS

E. COLI
KLEB.
PNEUMONIAE
PROTEUS
 USUALLY ACTIVE AGAINST ANAEROBIC GRAM-
POSITIVE COCCI
PEPTOCOCCUS
PEPTOSTREPTOCOCCUS
SECOND GENERATION
 SAME AS 1ST GENERATION + EXTENDED GRAM-
NEGATIVE COVERAGE

 LESS ACTIVE AGAINST GRAM-POSITIVE BACTERIA

THAN 1ST GENERATION

 KLEBSIELLAE (RESISTANT TO CEPHALOTHIN)

 SOME ACTIVE AGAINST H. INFLUENZAE

 SOME ACTIVE AGAINST B. FRAGILIS

THIRD GENERATION
 HIGHLY AUGMENTED ACTIVITY AGAINST AEROBIC
GRAM-NEGATIVE RODS

ENTEROBACTERIACEAE (Cefixime)
OTHERS + CITROBACTER, SERRATIA,
PROVIDENCIA
PSEUDOMONAS (Ceftazidime) HAEMOPHILUS
(Ceftriaxone and Cefixime)
 AEROBIC GRAM-NEGATIVE COCCI
NEISSERIA GONORRHOEAE (Cefixime)
 AEROBIC GRAM-POSITIVE COCCI
PNEUMOCOCCI (Cefotaxime but not
enterococcus)
STREPTOCOCCUS(Beta lactamase Positive)
(Cefixime)
 ANAEROBIC GRAM-NEGATIVE RODS
BACTEROIDES
FOURTH GENERATION
 ENTEROBACTERIACEAE
OTHERS + ENTEROBACTER

 PSEUDOMONAS AERUGINOSA

 HAEMOPHILUS INFLUENZAE

 STAPHYLOCOCCUS AUREUS

 STREPTOCOCCUS PNEUMONIAE
 RESISTANCE

 INACTIVATION OF ANTIBIOTIC BY β-LACTAMASE

 MODIFICATION OF TARGET PBPs

 IMPAIRED PENETRATION OF ANTIBIOTICS

 PRESENCE OF EFFLUX PUMP

CLINICAL USES
FIRST
GENERATION
 UTI

 CELLULITIS CELLULITIS

 SOFT TISSUE ABSCESS

 SURGICAL PROPHYLAXIS

 IN CASE OF MILD HYPER-

ABSCESS
SENSITIVITY,
ALTERNATIVE
TO PENICILLINS IN STAPH. & STREP. INFECTIONS
SECOND GENERATION

 SINUSITIS, OTITIS, LRTIs BY

H. INFLUENZAE OR
BRANHAMELLA CATARRHALIS

 PERITONITIS, DIVERTICULITIS BY
MIXED ANAEROBIC
INFECTIONS

 COMMUNITY-ACQUIRED
PNEUMONIA BY
H. INFLUENZAE
STREP. PNEUMONIAE OR
KLEBSIELLA (CEFUROXIME)
THIRD GENERATION (CEFTRIAXONE & CEFIXIME)

PENICILLIN-RESISTANT GONORRHEA

 MENINGITIS BY
PNEUMOCOCCI
MENINGOCOCCI
H. INFLUENZAE
SOME ENTERIC GRAM-NEGATIVE RODS

 ENTERIC FEVER
 MENINGITIS CAUSED BY PSEUDOMONAS
IN COMBINATION WITH AMINOGLYCOSIDE

 MENINGITIS CAUSED BY PENICILLIN-RESISTANT

PNEUMOCOCCI
IN COMBINATIN WITH VANCOMYCIN

 EMPIRICAL THERAPY FOR SEPSIS OF UNKNOWN

CAUSE IN IMMUNO-COMPETENT AND IMMUNO-
COMPROMISED PATIENTS
FOURTH GENERATION (CEFEPIME)

 SIMILAR TO THIRD GENERATION CEPHALOSPORINS

 GOOD ACTIVITY AGAINST MOST PENICILLIN-

RESISTANT STREPTOCOCCI

 MAY BE USEFUL IN ENTEROBACTER INFECTIONS

 PHARMACOKINETICS
CEFUROXIME AXETIL ORAL ESTER
CEFPODOXIME PROXETIL PRODRUGS

INTERACTION WITH
FOOD
CEFTRIAXONE
CEFEPIME
CEFUROXIME
APPEAR IN CSF
CEFTAZIDIME
CEFOTAXIME CEFTRIAXONE
(HAS AN ACTIVE
METABOLITE) CEFOPERAZONE
URINARY EXCRETION CEFOXITIN
BILIARY EXCRETION CEFMETAZOLE
ADVERSE REACTIONS
&
TOXICITIES
 ALLERGIC
ANAPHYLAXIS, URTICARIA, SERUM
SICKNESS, RASH, FEVER

 SUPERINFECTIONS
CLOSTRIDIUM DIFFICILE
ENTEROCOCCI
S. AUREUS
CANDIDA ALBICANS

 DIARRHEA
 HEMATOLOGIC
ANEMIA, THROMBOCYTOPENIA, ANTI-PLATELET
ACTIVITY, HYPOPROTHROMBINEMIA
(CEZAMANDOLE, MOXALACTAM WITH METHYLTHIO-
TETRAZOLE [MTT] GROUP INHIBIT PRODUCTION OF
ACTIVE
VIT K)

 BILIARY SLUDGING AND STONES REPORTED WITH

CEFTRIAXONE
 CEFTRIAXONE MAY DISPLACE BILIRUBIN FROM
SERUM ALBUMIN (↑RISK OF KERNICTERUS IN
JAUNDICED NEONATES)
 PHLEBITIS
 DISULFIRAM REACTION (CEPH. WITH MTT GROUP)
 NEPHRITIS

 ENCEPHALOPATHY (CEFEPIME)
 DRUG INTERACTIONS

 SOME FIRST GENERATION CEPHALOSPORINS

ARE NEPHROTOXIC, PARTICULARLY WHEN GIVEN
WITH
FRUSEMIDE
AMINOGLYCOSIDES OR
OTHER NEPHROTOXIC
AGENTS

 DURATION OF ACTION
INCREASES WITH
PROBENECID

 I/V CEFTRIAXONE AND CALCIUM CONTAINING

3. CARBAPENEMS
 IMIPENEM PLUS CILASTATIN
( A REVERSIBLE INHIBITOR OF DEHYDROPEPTI-
DASE I)

 MEROPENEM

 ERTAPENEM
CARBON SUBSTITUTED
FOR SULFUR
 DORIPENEM

N
 ANTIBACTERIAL SPECTRUM

 VERY BROAD SPECTRUM OF ANTIMICROBIAL

ACTIVITY

 ACTIVE AGAINST MANY AEROBIC AND

ANAEROBIC GRAM-POSITIVE AND GRAM-
NEGATIVE ORGANISMS

 ACTIVE AGAINST MANY HIGHLY

PENICILLIN-
RESISTANT STRAINS OF PNEUMOCOCCI
 BETA-LACTAM ANTIBIOTIC OF CHOICE FOR
ENTEROBACTER INFECTIONS

 IMIPENEM + AMINOGLYCOSIDE FOR

PSEUDOMONAS AERUGINOSA INFECTIONS
 CLINICAL USES

DRUG OF CHOICE FOR THE EMPIRICAL THERAPY

OF MANY POLYMICROBIAL INFECTIONS

 SEPTICEMIA
 INTRAABDOMINAL INFECTION
 NOSOCOMIAL PNEUMONIA AND OTHER
HOSPITAL ACQUIRED INFECTIONS INCLUDING
THOSE IN NEUTROPENIC, CANCER AND AIDS
PATIENTS
 ADVERSE EFFECTS

 GIT DISTURBANCES
 SKIN RASHES
 CROSS-SENSITIVITY WITH OTHER β-LACTAM AB
 REACTIONS AT THE INFUSION SITE
 HYPOTENSION
 SEIZURES
 LESS COMMONLY CAN CAUSE PENIAS AND ANEMIA
4. MONOBACTAMS
AZTREONAM

ANTIBACTERIAL SPECTRUM N

 ACTIVE AGAINST AEROBIC GRAM-NEGATIVE

ORGANISMS
H. INFLUENZAE
PSEUDOMONAS
SERRATIA
NEISSERIA MENINGITIDIS
NEISSERIA
GONORRHEA
CLINICAL USES

 SEPTICEMIA
 COMPLICATED UTIs
 GRAM-NEGATIVE LOWER UTIs
 GONORRHEA
 ALTERNATIVE TO OTHER BETA-LACTAM
ANTIBIOTICS DUE TO LACK OF CROSS-SENSITIVITY
ADVERSE REACTIONS

 OCCASIONAL SKIN RASHES

 HEPATITIS
 THROMBOCYTOPENIA
 NEUTROPENIA
B. OTHER CELL WALL
OR
MEMBRANE-ACTIVE
ANTIBIO
TICS
I. FOSFOMYCIN
AN ANALOG OF PHOSPHOENOLPYRUATE

MECHANISM OF ACTION

IT INHIBITS A VERY EARLY STAGE OF BACTERIAL

WALL SYNTHESIS (IN CYTOPLASM)

PHOSPHOENOLPYRUATE + UDP-N-ACETYLGLUCOSAMINE

UDP-N-ACETYLMURAMIC ACID,
ENOLPYRUATE TRANSFERASE
(THE PRECURSOR OF
_ N-ACETYLMURAMIC ACID)

FOSFOMYCIN
ANTIBACTERIAL SPECRUM
ENTEROCOCCI AND MANY GRAM-NEGATIVE ENTERIC
BACILLI

CLINICAL USES
GIVEN ORALLY OR PARENTERALLY
• AS A SINGLE DOSE FOR LOWER URINARY TRACT
INFECTIONS IN WOMEN
THE DRUG IS SAFE DURING PREGNANCY
II. CYCLOSERINE

IT IS A STRUCTURAL
CYCLOSERINE D-ALANINE

ANALOG OF D-
ALANINE
MECHANISM OF ACTION

PREVENTS THE ADDITION OF TWO TERMINAL

ALANINES TO THE INITIAL TRIPEPTIDE SIDE-CHAIN ON
N-ACETYL MURAMIC ACID

IT INHIBITS ALANINE RACEMASE WHICH CONVERTS

L-ALANINE TO D-ALANINE AND D-ALANLY-D-ALANINE
LIGASE WHICH COMBINES TWO D-ALANINE
 4

1
D-cycloserine
3

MECHANISM OF ACTION
OF CYCLOSERINE
ANTIMICROBIAL SPECTRUM/CLINICAL USES
• IT INHIBITS MANY GRAM-POSITIVE AND GRAM-
NEGATIVE BACTERIA
• IT IS SECOND-LINE DRUG FOR THE
TREATMENT OF
TUBERCULOSIS BY MYCOBACTERIUM
TUBERCULOSIS
PHARMACOKINETIS
• IT IS GIVEN ORALLY
• IT IS WIDELY DISTRIBUTED IN TISSUES
• MOST OF THE DRUG IS EXCRETED IN ACTIVE FORM
IN URINE

ADVERSE EFFECTS
• SERIOUS DOSE-RELATED CNS TOXICITY
HEADACHE, TREMORS, ACUTE PSYCHOSIS
AND CONVULSIONS
III. GLYCOPEPTIDE ANTIBIOTICS
1. VANCOMYCIN
2. TEICOPLANIN
3. DALBAVANCIN
4. TELAVANCIN
VANCOMYCIN
IT IS GLYCOPEPTIDE

MECHANISM OF ACTION

• INHIBITOR OF CELL WALL SYNTHESIS

• BINDS TO D-ALANYL-D-ALANINE TERMINUS OF THE

NAG AND NAM PEPTIDE

• THUS PREVENTS POLYMERIZATION OF THE

LINEAR PEPTIDOGLYCAN, LEADING TO WEAK CELL
WALL
 7
1

6 5
VANCOMYCIN
ANTIBACTERIAL ACTIVITY
• NARROW-SPECTRUM AGENTS, ACTIVE AGAINST
GRAM-POSITIVE ORGANISMS (COCCI & RODS)

• BACTERIOSTATIC AGAINST STAPH., STREP.,

ENTERO.
• RODS, SUCH AS B. ANTHRACIS, C. DIPHTHERIAE, C.
TETANI, C. PERFERINGENS, C. DIFFICILE

• MOST PATHOGENIC STAPH., INCLUDING THOSE

PRODUCING β-LACTAMASE AND THOSE RESISTANT
TO NAFCILLIN, METHICILLIN
RESISTANCE ( IN
ENTEROCOCCI)
• DUE TO MODIFICATION OF THE D-Ala-D-Ala BINDING
SITE OF THE PEPTIDOGLYCAN BUILDING BLOCK
 PHARMACOKINETICS
 ORALLY, POORLY ABSORBED (ONLY FOR C.
DIFFICILE)
 GIVEN I/V, WIDELY DISTRIBUTED, POORLY CROSSES
BBB
 90 % IS EXCRETED BY GLOMERULAR FILTERATION
CLINICAL USES

1. SEPSIS OR ENDOCARDITIS CAUSED BY METHICILLIN-

RESISTANT STAPHYLOCOCCI

2. ALTERNATIVE (IN COMBINATION WITH GENTAMICIN)

FOR TREATMENT OF ENTEROCOCCAL ENDOCARDITIS

3. IN COMBINATION WITH CEFOTOXIME, CEFTRIAXONE,

OR RIFAMPICIN FOR PENICILLIN-RESISTANT PNEUMO-
COCCAL MENINGITIS

4. ORALLY FOR ANTIBIOTIC-INDUCED ENTEROCOLITIS

CAUSED BY C. DIFFICILE (METRONIDAZOLE IS FIRST
CHOICE)
ADVERSE REACTIONS
• MOST REACTIONS ARE MINOR

PHILIBITIS AT THE SITE OF INJECTION

CHILLS AND FEVER
• RARE
OTOTOXICITY
NEPHROTOXICITY
‘RED MAN’ OR ‘RED NECK’ SYNDROME (INFUSION
RELATED FLUSHING CAUSED BY RELEASE OF
HISTAMINE)
 IV. BACITRACIN

• CYCLIC PEPTIDE MIXTURE

• ACTIVE AGAINST GRAM-POSITIVE ORGANISMS

•MECHANISM OF ACTION
• IT INHIBITS CELL WALL SYNTHESIS
• BY INTERFERING WITH DEPHOSPHORYLATION IN CYCLING OF THE LIPID
CARRIER THAT TRANSFERS PEPTIDOGLYCAN SUBUNITS TO THE
GROWING CELL WALL
BACITRACIN – INTERFERES WITH
THE REGENERATION
ASSEMBLY TRANSPORT
POLYMERIZATION

OF LIPID CARRIER BY BLOCKING ITS

DEPHOSPHORY-
LATION ASSEMBLY TRANSPORT POLYMERIZATION

EMBL NSPORT
POLYMERIZATION

6
REGENERATION
1

NAM ADDED TO THE

GROWING END OF
2 5 PEPTIDOGLYCAN
NAG LAYE
3 R

4
LIPID CARRIER

CYTOPLASM INNER MEMBRANE PERIPLASM

CLINICAL USES
IT IS NEPHROTOXIC WHEN USED SYSTEMICALLY AND
IS ONLY USED TOPICALLY
1. FOR SUPPRESSION OF MIXED BACTERIAL FLORA
(IN COMBINATION WITH POLYMYXIN OR NEOMYCIN)
IN SURFACE LESIONS OF SKIN, OR MUCOUS
MEMBRANES
2. SOLUTION OF BACITRACIN IN SALINE CAN BE USED
TO IRRIGATE JOINTS, WOUND, OR THE PLEURAL
CAVITY
MECHANISM OF ACTION OF CELL
WALL INHIBITORS
B

E
D

C
V.
DAPTOMYCIN
CYCLIC LIPOPEPTIDE

MECHANISM OF ACTION
 IT BINDS TO CELL MEMBRANE VIA CALCIUM-
DEPENDENT INSERTION OF ITS TAIL AND FORMATION
OF A PORE
 THIS RESULTS IN DEPOLARIZATION OF THE CELL
WITH POTASSIUM EFFLUX AND RAPID CELL DEATH
DAPTOMYCIN

EXTRACELLULAR
SPACE

PLASMA
MEMBRANE

INTRACELLULAR
SPACE
SPECTRUM OF ACTIVITY

• ITS SPECTRUM OF ACTIVITY IS SIMILAR TO THAT OF

VANCOMYCIN

• VANCOMYCIN-RESISTANT STRAINS OF
ENTEROCOCCI
AND STAPHYLOCOCCI

ADVERSE EFFECTS

• MYOPATHY

• NOT TO BE USED TO TREAT PNEUMONIAS (IT IS

ANTAGONIZED BY PULMONARY SURFACTANT)
THANK YOU
TRUE OR FALSE

Penicillins:

a. Are highly lipid soluble

b. Are excreted by glomerular filtration
c. Can all be destroyed by b-lactamase producing
bacteria
d. Some may be given orally
e. Are usually effective against streptococcal
infection
MCQ

A woman with documented penicillin allergy is

treated with a beta-lactam antibiotic that rarely cross-
reacts with penicillins. Her infection is most likely
due to which organism?

1. Staphylococcus aureus
2. Enterococcus faecium
3. Streptococcus pneumoniae
4. Psedomonas aeruginosa
5. Bacillus anthracis