PENICILLINS,

CEPHALOSPORINS, AND
OTHER Β-LACTAM ANTIBIOTICS
GERALDINE JACA-CORPORAL, MD, DPBA
Β-lactam Antibiotics

Cephalospor Carbapene
Penicillins Monobactams
ins ms

Mechanism of Action: inhibition of synthesis of the

bacterial peptidoglycan cell wall
PENICILLINS
MECHANISM OF ACTION
• Peptidoglycan is a heteropolymeric component of the cell wall that
provides rigid mechanical stability by virtue of its highly cross-
linked latticework structure

N-acetylglucosamine
N-acetylmuramic acid
MECHANISM OF ACTION

• Inhibit the transpeptidation reaction (last step in peptidoglycan

synthesis), preesumably by acylating the transpeptidase via
cleavage of the –CO-N- bond of the B-lactam ring
• Penicillin-binding Protein (PBP) – e.g. Transpeptidase - targets of
action of β-lactam antibiotics
MECHANISMS OF BACTERIAL RESISTANCE TO
PENICILLINS AND CEPHALOSPORINS

• Mutations that decrease the affinity of PBPs for the antibiotic

• Acquisition of an additional high-molecular-weight PBP (via a

transposon) with a very low affinity for all β-lactam antibiotics
** Methicillin-resistant Staphylococcus aureus
MECHANISMS OF BACTERIAL RESISTANCE TO
PENICILLINS AND CEPHALOSPORINS

• Inability of the agent

to penetrate to its site
of action

• Active efflux pumps

remove the antibiotic
from its site of action
before it can act
MECHANISMS OF BACTERIAL RESISTANCE TO
PENICILLINS AND CEPHALOSPORINS

• Destruction of antibiotics enzymatically via the action of β-

lactamases (4 classes: A to D; gram +: penicillinase)
• Microorganisms adhering to implanted prosthetic devices (e.g.
catheters, artificial joints, prosthetic heart valves) produce biofilms
– produce extracellular polysaccharides – less sensitive to
antibiotic
MECHANISMS OF BACTERIAL RESISTANCE TO
PENICILLINS AND CEPHALOSPORINS

• Bacteria that survive inside viable cells of the host generally are
protected from the action of β-lactam antibiotics.
Classification of Penicillins

Penicillin G Highly active against Gram +

Penicillin V Readily hydrolyzed by Penicillinase
Ineffective against S. aureus

PENICILLINASE-RESISTANT First choice for treatment of penicillinase-

Methicillin, Nafcillin, producing S. aureus and S. epidermidis
Oxacillin, Cloxacillin,
Dicloxacillin –
 Classification of Penicillins
AMINOPENICILLINS Antimicrobial activity against Gram – organisms
Ampicillin, Amoxicillin (H. influenzae, E. coli & Proteus mirabiis)
+
Clavulanate or Sulbactam
(β-lactamase inhibitor)
Mezlocillin, Carbenicillin, Antimicrobial activity against Pseudomonas,
Carbenicillin indanyl Na, Enterobacter, Proteus spp
Ticarcillin Inferior to Ampicillin against Gram + cocci &
Listeria monocytogenes
Less active than Piperacillin against
Pseudomonas
 Classification of Penicillins

Piperacillin ; Piperacillin + Excellent antimicrobial activity against

Tazobactam Pseudomonas, Klebsiella, & certain other Gram
– microorganisms
Retains activity of Ampicillin against Gram +
cocci and L. monocytogenes
General Common Properties of Penicillins
• Therapeutic concentrations – tissues; secretions (joint fluid, pleural
fluid, pericardial fluid, bile)
• Do not penetrate living phagocytic cells to a significant extent
• Low concentrations in prostatic secretions, brain tissue, IOC fluid
• Normal meninges - <1% concentration of penicillin
• Meningitis - ⬆ 5% of plasma value
• Elimination: GFR & renal tubular secretion
 Penicillin G / Penicillin V: ABSORPTION
ORAL PARENTERAL
Penicillin G 1/3 absorbed in 30-60 mins; Peak: 15-30 mins
taken 20 mins before a meal or 2 PenicillinG benzathine – slow
hours after release (low but persistent
Gastric pH 2 – destroys antibiotic blood level)
IM –once monthly for
Rheumatic Fever prophylaxis
Penicillin V More stable in acidic medium (2-
5x > plasma concentration than
Penicillin G)
 Penicillin G / Penicillin V
DISTRIBUTION PENETRATION INTO CSF
Penicillin G 60% reversibly bound to albumin penetrates when meninges
Liver, bile, kidney, semen, joint are inflamed
fluid, lymph & intestine
Probenecid: inhibits transport
Probenecid: ↓ tubular secretion of Penicillin from CSF to
of Penicillin -- ↑ plasma bloodstream
conc. Uremia: organic acids
: produces ↓ in volume of accumulate in the CSF &
distribution of Penicillin compete w/ Penicillin for
secretion
 Penicillin G / Penicillin V
EXCRETION
Penicillin G Main: Kidney; bile
Neonates / Infants: ↓ clearance due to incomplete
development of renal function
THERAPEUTIC USES
DISEASE
Pneumococcal Penicillin G: agent of choice
Infections
Pneumococcal 3RD Generation cephalosporins / 20-24 M units of
Pneumonia Penicilin F for 7-10 days
Pneumococcal 20-24 M units for 14 days of Pen G; Vancomycin + 3rd
Meningitits generation Cephalosporin
Streptococcal S. Pyogenes (group A β-hemolytic Streptococcus) –
Pharyngitis cause RHD
(including Scarlet Pen V 500 mg q6 PO for 10 days
Fever)
THERAPEUTIC USES
DISEASE
Streptococcal Toxic Shock Penicillin + Clindamycin
& Necrotizing Fascitis
Streptococcal Pneumonia, Pen G 12-20M units IV 2-4 weeks
Arthritis, Meningitis & Endocarditis: for 4 weeks
Endocarditis (S. pyogenes)
Streptococcus viridans Pen G 12-20 M units IV Pen G for 2 weeks (4
weeks if alone) + Gentamycin 1mg /kg q8
Enterococcal endocarditis Pen G 20M units or Ampicillin 12g IV +
Gentamicin for 6 weeks
THERAPEUTIC USES
DISEASE
Staphylococcal Infections Penicillinase producing organism; resistant to
Penicillin; Vancomycin, Linezolid, Daptomycin
MRSA Trimethoprim-Sulfamethoxazole, Doxycycline,
Clindamycin
Meningococcal Infections Penicillin – drug of choice

Gonococcal Urethritis Resistant to Penicillin; Ceftriaxone 250mg IM

Gonococcal Arthritis, Ceftriaxone 1g IM/IV for 7-10 days
Disseminated Gonococcal
Infection, Gonococcemia
Ophthalmia neonatorum Ceftriaxone 25-50mg/kg/day IM/IV for 7-10 days
THERAPEUTIC USES

DISEASE
10, 20 & Latent Syphilis < 1 Pen G Procaine 2.4M units/day IM + Probenecid
year duration for 10 days

Late latent syphilis, Pen G 20M units for 10 days

neurosyphilis, CV syphilis

Congenital Syphilis Aqueous Pen G 50,000/kg in 2 divided doses or

Procaine Pen G 50,000/kg OD for 10 days
JARISCH-HERXHEIMER REACTION
• 70-90% with secondary syphilis
• Several hours after the 1st injection of penicillin: chills, fever,
headache, myalgias, and arthralgias
: syphilitic cutaneous lesions may become more prominent,
edematous, brilliant in color
: rash begins to fade w/in 48h
• Does not recur w/ subsequent injections
• Due to release of spirochetal antigens ➜ host reactions to product
• TX: Aspirin ; Therapy w/ Penicillin should NOT be discontinued
THERAPEUTIC USES
DISEASE
Actinomycosis Pen G 10-20M units/day IV for 6 weeks – agent
of choice
Diphtheria Pen G eliminates the carrier state
Pen G 2-3M units/day for 10-12 days
Clostridial Infections (Gas Pen G agent of choice as adjunct to antitoxin
Gangrene)
Fusospirochetal Infection Pen V 500mg q6
(Trench mouth)
THERAPEUTIC USES
DISEASE
Rat-bite fever (Spirillum Pen G – therapeutic agent of choice
minor, Stretobacillus
moniliformis)

Listeria monocytogenes Pen G & Ampicillin + Gentamicin – therapeutic

agent of choice
T
Lyme disease etracycline – drug of choice for early disease
Pen G or 3rd gen cephalosporin - severe disease
Oxacillin, Cloxacillin, Dicloxacillin, Nafcillin
PENICILLINASE-RESISTANT PENICILLINS
Isoxazolyl Penicillins:
OXACILLIN, CLOXACILLIN, DICLOXACILLIN

• Potent inhibitors of the growth of most penicillinase-producing

staphylococci
• Dicloxacillin – most active
NAFCILLIN
• most active of the penicillinase-
resistant penicillins
• Treatment of staphylococcal meningitis
Methicillin-Resistant Staphylococcus aureus

Resistance to penicillinase-resistant penicillins & cephalosporins

Hospital-acquired: resistant to aminoglycosides, tetracyclines,

erythromycin, & clindamycin

Community-acquired: resistant to macrolides

Vancomycin (drug of choice) + Rifampin

Ampicillin,Amoxicillin, & their Congeners
AMINOPENICILLINS
AMPICILLIN
• Prototype of the group
• Ampicillin + Sulbactam (β-lactamase inhibitor) –
Enterobacteriacea (E. coli)

AMOXICILLIN
• less effective than Ampicillin for Shigellosis
• Amoxicillin + Clavulanate – Enterobacteriacea (E. coli)
THERAPEUTIC USES OF AMINOPENICILLINS
•Upper Respiratory Infections – S. pyogenes, S. pneumoniae and
H. influenzae

• Urinary Tract Infection

• Meningitis – S. pneumoniae, N. meningitidis, L. monocytogenes

(Ampicillin + Vancomycin + 3rd gen cephalosporin)

• Salmonella infections – High dose of Ampicillin

Carboxypenicillins (Carbenicillin, Ticarcillin)
Ureidopenicillins (Mezlocillin, Piperacillin)
ANTI-PSEUDOMONAL PENICILLINS
CARBOXYPENICILLINS

• Carbenicillin - supplied as disodium salt; CHF results from excessive Na+

: Hypokalemia – obligatory excretion of cation w/ large amount of
nonreabsorbable anion in distal renal tubule
: Bleeding - interferes w/ platelet function
UREIDOPENICILLINS

• Piperacillin + Tazobactam (β-lactamase inhibitor ) ➜ broadest

antibacterial spectrum of the penicillins
UNTOWARD REACTIONS TO PENICILLINS

Hypersensitivity Bone marrow

Granulocytopenia
Reactions depression

Hepatitis Pain, Sterile

Inflammatory
(Oxacillin, reactions at IM
Nafcillin) site
CEPHALOSPORINS
CEPHALOSPORINS
• Cephalosporium acremonium - first source isolated in 1948 by
Brotzu from the sea near a sewer outlet off the Sardinian
coast
• Mechanisms of Bacterial Resistance
* inability of the antibiotic to reach its sites of action
* alterations in the penicillin-binding proteins (PBPs) – antibiotics
bind to bacterial enzymes (β-lactamases) that can hydrolyze the
β-lactam ring and inactivate the cephalosporin
Carbapenems
OTHER Β-LACTAM ANTIBIOTICS
CARBAPENEMS • Broader spectrum of
activity
• Binds to Penicillin-binding
Imipenem Meropenem Proteins
• Disrupts bacterial cell wall
synthesis
• Death of susceptible
microorganisms
Doripenem Ertapenem • Very resistant to hydrolysis
by most β-lactamases
MONOBACTAM

• (+) activity against Gram negative bacteria

• (-) activity against Gram positive bacteria
Aztreonam • Administered IM or IV
• Lack of allergic cross-reactivity with other
beta lactam antibiotics except with
ceftazidime
Β-LACTAMASE INHIBITORS
OTHER Β-LACTAM ANTIBIOTICS
Β-LACTAMASE INHIBITORS
• inactivate β-lactamases -- preventing the destruction of β-lactam
antibiotics
• most active against plasmid-encoded β-lactamases

CLAVULANIC
SULBACTAM TAZOBACTAM AVIBACTAM
ACID
GOOD MORNING 😊😊😊