ANTIMICROBIAL THERAPY

INHIBITORS OF CELL WALL

SYNTHESIS

IRENE L. GARDINER, MD
 INHIBITORS OF CELL WALL
SYNTHESIS
 Bactericidal
 Interferes with the ability of the
susceptible bacteria to build their cell
walls when they are dividing
 Bacteria with weakened cell walls swell
and burst from osmotic pressure within
the cell
 Selective toxicity - do not affect humans
inhibitors of cell wall IRENE L. GARDINER, MD 2
synthesis
 PENICILLINS
(Beta-lactam antibiotics)
 First antibiotic introduced for clinical use
 Natural antibacterial agent obtained from the
mold genus Penicillium
 The “miracle drug” in the 1940s
 Contains a BETA-LACTAM RING that interferes
with bacterial cell wall synthesis by inhibiting the
bacterial enzyme necessary for cell division and
synthesis → cell lysis
inhibitors of cell wall IRENE L. GARDINER, MD 3
synthesis
 PENICILLINS
(Beta-lactam antibiotics)
 Bacteria produces enzymes, called BETA -
LACTAMASES, that can inactivate Beta-lactam
antibiotics
 Penicillinase – enzyme that destroys penicillin
 First used for treatment of S. aureus
 Absorption is decreased if taken with food except
for amoxicillin & bacampicillin
 Cross-allergenicity occurs
inhibitors of cell wall IRENE L. GARDINER, MD 4
synthesis
BASIC PENICILLINS

 These original penicillins are effective

against:
– Gram (+) cocci
– Neiserria
– Most anaerobes but not gram (-) aerobes

inhibitors of cell wall IRENE L. GARDINER, MD 5

synthesis
 BASIC PENICILLINS
PENICILLIN G (BENZYLPENICILLIN)
 First Penicillin administered orally and
parenterally
 The cornerstone of therapy for bacterial infections
 Only 1/3 is absorbed orally so that IV/IM is more
effective – acid unstable
 Short-acting and very painful at injection site
 Treatment of cellulitis, gonorrhea, bacterial
endocarditis, etc
inhibitors of cell wall IRENE L. GARDINER, MD 6
synthesis
BASIC PENICILLINS
PENICILLIN V POTASSIUM
(PHENOXYMETHYLPENICILLIN)
 The orally-active form of Pen – acid stable
 2/3 can be absorbed in the GIT but is less
potent than Pen G
 Effective against mild to moderate infections
 Treatment of S. pyogenes infections like
tonsillitis, pharyngitis, skin infections;
prophylaxis of RF
inhibitors of cell wall IRENE L. GARDINER, MD 7
synthesis
BASIC PENICILLINS

PROCAINE PEN G (PROCAINE

BENZYLPENICILLIN)
 Longer-acting, milky in color
 Procaine decreases the pain related to
injection site
 For moderately serious infections like
syphilis, cellulites, erysipelas, RTI
inhibitors of cell wall IRENE L. GARDINER, MD 8
synthesis
BASIC PENICILLINS

BENZATHINE PENICILLIN G
 Poorly absorbed orally because of
gastric acidity and food
 Oral/IM/IV

inhibitors of cell wall IRENE L. GARDINER, MD 9

synthesis
BROAD-SPECTRUM PENICILLINS
(AMINOPENICILLINS)

 Broad spectrum and semi-synthetic

 Used to treat Gram (+) and (-) infections
 Degraded by penicillinase
 Not effective against S. aureus

inhibitors of cell wall IRENE L. GARDINER, MD 10

synthesis
BROAD – SPECTRUM PENICILLINS
(AMINOPENICILLINS)
AMOXICILLIN
 For treatment of respiratory tract infections,
UTI, otitis media, sinusitis, prophylaxis for
dental procedures

AMPICILLIN
 First broad-spectrum penicillin
 Useful form if switch from parenteral to oral is
anticipated
inhibitors of cell wall IRENE L. GARDINER, MD 11
synthesis
BROAD – SPECTRUM PENICILLINS
(AMINOPENICILLINS)

AMPICILLIN - SULBACTAM
 Presence of sulbactam inhibits beta
-lactamases thus extending the
spectrum
BACAMPICILLIN
 Same as ampicillin; 90% absorbed
 It is hydrolyzed to ampicillin during
absorption in the GIT
inhibitors of cell wall IRENE L. GARDINER, MD 12
synthesis
 PENICILLINASE – RESISTANT
PENICILLINS
 Antistaphylococcal penicillins
 Used to treat penicillinase-producing S.
aureus
 Not effective against gram (-) organisms
 Less effective than Pen G against gram
(+) organisms

inhibitors of cell wall IRENE L. GARDINER, MD 13

synthesis
PENICILLINASE – RESISTANT
PENICILLINS
METHICILLIN
 First penicillinase-resistant penicillin for S. aureus

NAFCILLIN
 Highly effective against Pen G-resistant S. aureus
 Oral use not recommended, highly unstable in gastric
juices

OXACILLIN
 For penicillin-resistant Staphyloccocal infection
inhibitors of cell wall IRENE L. GARDINER, MD 14
synthesis
PENICILLINASE-RESISTANT
PENICILLINS

CLOXACILLIN
 For most gram (+) bacterial infections
 Most commonly used oral preparation

DICLOXACILLIN SODIUM
 For S. aureus infection
 Oral preparation

inhibitors of cell wall IRENE L. GARDINER, MD 15

synthesis
EXTENDED-SPECTRUM
PENICILLINS

 Antipseudomonas penicillins
 For gram (-) infections
 Ineffective against gram (+) and
susceptible to penicillinases

inhibitors of cell wall IRENE L. GARDINER, MD 16

synthesis
EXTENDED – SPECTRUM
PENICILLINS
CARBENICILLIN
 First penicillin-like drug developed to treat
Pseudomonas

MEZLOCILLIN
 For serious infections caused by
Pseudomonas
 May be given with aminoglycosides &
cephalosporins = synergy
inhibitors of cell wall IRENE L. GARDINER, MD 17
synthesis
EXTENDED – SPECTRUM
PENICILLINS

PIPERACILLIN
 Most potent, reserved for serious infections
 Can be given before and after surgery
 Primarily used for gram (-) organisms
 Treatment of septicemia; bone, joint,
respiratory & urinary infection

inhibitors of cell wall IRENE L. GARDINER, MD 18

synthesis
BETA-LACTAMASE INHIBITORS
(Enzyme Inhibitors)
 InhibitsBeta-lactamase enzymes, thus
making the antibiotic effective and
extending its antimicrobial effects
 Oral : Amoxicillin + CLAVULANIC ACID
 Parenteral : Ampicillin + SULBACTAM
 Piperacillin + TAZOBACTAM

inhibitors of cell wall IRENE L. GARDINER, MD 19

synthesis
SIDE and ADVERSE EFFECTS
 Hypersensitivity reactions
 Diarrhea – most common in amoxicillin
 Nephritis – Methicillin
 Neurotoxicity – Nafcillin
 Hematologic reactions – hemolysis
 Hepatitis – Oxacillin
 Potassium load – Pen V K
 Sodium load – Ticarcillin
 Seizures and GI distress
inhibitors of cell wall IRENE L. GARDINER, MD 20
synthesis
CEPHALOSPHORINS
 Isolated form the fungus
Cephalosporium acremonium
 Active against gram (+) and (-) bacteria
 Some generations are resistant to beta-
lactamases
 Bactericidal and bacteriostatic

inhibitors of cell wall IRENE L. GARDINER, MD 21

synthesis
 CEPHALOSPHORINS
 MOA : prevents transpeptidation
 Side Effects
– Hypersensitivity
– GI disturbances
 Precautions
– Renally-impaired patients
– Cross-sensitivity with penicillins
– Alcohol drinkers

inhibitors of cell wall IRENE L. GARDINER, MD 22

synthesis
FIRST GENERATION
CEPHALOSPHORINS
– Effective against gram (+) bacteria like
Streptococcus and Staphylococcus
– Effective against most gram (-) PEcK –
Proteus, E. coli, Klebsiella
– Alternative treatment for impetigo,
pharyngitis, osteomyelitis
– May be used for surgical prophylaxis

inhibitors of cell wall IRENE L. GARDINER, MD 23

synthesis
FIRST GENERATION
CEPHALOSPHORINS
ORAL PARENTERAL
 CEPHALEXIN  CAPHAZOLIN

 CEPHADROXIL  CEPHALOTHIN
 CEPHAPIRIN

ORAL /
PARENTERAL
 CEPHRADINE

inhibitors of cell wall IRENE L. GARDINER, MD 24

synthesis
 SECOND GENERATION
CEPHALOSPHORINS

 Broader spectrum against Gram (-)

 HENPEcK – Haemophilus influenzae,
Enterobacter aerogenes, Neisseria
 No activity against Pseudomonas

inhibitors of cell wall IRENE L. GARDINER, MD 25

synthesis
 SECOND GENERATION
CEPHALOSPHORINS
ORAL PARENTERAL
 CEFACLOR  CEFAMANDOLE
 CEFPROZIN  CEFOTETAN
 CEFOXITIN
ORAL/  CEFPROZIL
PARENTERAL  CEFMETAZOLE
 CEFUROXIME
inhibitors of cell wall IRENE L. GARDINER, MD 26
synthesis
THIRD GENERATION
CEPHALOSPHORINS

 Effectiveagainst gram (-) bacteria -

HENPEcKS – Serratia marcescens
 Less effective against gram (+)
bacteria

inhibitors of cell wall IRENE L. GARDINER, MD 27

synthesis
THIRD GENERATION
CEPHALOSPHORINS
ORAL PARENTERAL
 CEFDINIR  CEFOTAXIME
 CEFIXIME  CEFTAZIDIME
 CEFPODOXIME  CEFTRIAXONE
 CEFOPERAZONE

inhibitors of cell wall IRENE L. GARDINER, MD 28

synthesis
 FOURTH GENERATION
CEPHALOSPHORINS
 Similar to the third generation
 Resistant to most beta-lactamase bacteria
 Broader gram (+) coverage than 3rd gens
 Effective against E.coli, Proteus,
Streptococci, certain Staph, Pseudomonas
 Parenteral
– CEFEPIME
– CEFPIROME
inhibitors of cell wall IRENE L. GARDINER, MD 29
synthesis
BACITRACIN
 Acts by inhibiting bacterial cell wall synthesis
and damaging the cell wall membrane
 Static or cidal depending on dose
 Not absorbed by the GI tract; given IV or IM
 Crosses the BBB – effective for treating
meningitis in children
 For respiratory infections in infants
 Topical and ophthalmic preparations
inhibitors of cell wall IRENE L. GARDINER, MD 30
synthesis
 IMIPENEM / CILASTATIN

 For treatment if septicemia and severe

infections of the lower respiratory tract,
urinary tract, skin, bones, joints
 Effective against most gram (-) including
Pseudomonas

inhibitors of cell wall IRENE L. GARDINER, MD 31

synthesis
 LORACARBEF

 Synthetic beta-lactam antibacterial

 Treatment of respiratory, skin and
urinary tract infection
 Commonly classified under the 2nd
generation cephalosporins

inhibitors of cell wall IRENE L. GARDINER, MD 32

synthesis
AZTREONAM

 Only monobactam antibiotic

 Unique structure, little cross resistance
 Treatment of gram negative infections in
the lower respiratory, urinary tract, skin
and vagina
 Not effective against gram(+) organisms
 May be used in combination with other
antibiotics
inhibitors of cell wall IRENE L. GARDINER, MD 33
synthesis
MEROPENEM
 Similar to cephalosporins
 Effective against gram (-) including
Pseudomonas
 Effective against complicated
intraabdominal infections like appendicitis,
peritonitis, meningitis and soft tissue
infections
 Adverse effect : pseudomembranous colitis
inhibitors of cell wall IRENE L. GARDINER, MD 34
synthesis
VANCOMYCIN
– A glycopeptide bacterial antibiotic used to treat
staphylococcal infections
– Not commonly used because of the high
incidence of nephrotoxicity and ototoxicity
– May be used for methicillin-resistant S. aureus
and in cardiac surgical prophylaxis for clients
allergic to penicillins
– SE : ototoxicity, nephrotoxicity, red neck / man
syndrome (erythema)
inhibitors of cell wall IRENE L. GARDINER, MD 35
synthesis