Beta-Lactam Mechanism of Effects Clinical Pharmacokinetics Toxicities and Interaction

Compound Action Applications

1. Penicillin Prevents bacterial Rapid Streptococcal IV administration | rapid renal Degraded by Beta-lactamases.
cell wall synthesis bactericidal infections, clearance with half-life of 30 Toxicities include immediate
(which occurs via activity against meningococcal minutes, 90% of which is via hypersensitivity, rash, seizures
transpeptidation susceptible infections, tubular secretion while the
rxn) by covalently bacteria. neurosyphilis remaining is through glomerular
binding to and filtration | Excreted into the
inhibiting cell wall sputum and breast milk to levels
transpeptidases 3-15% of those in serum | Poorly
penetrates eye, prostate, and CNS
2. Cephalospor Prevents bacterial Rapid Skin and soft IV administration | renal clearance Rash, drug fever
in cell wall synthesis bactericidal tissue | poorly penetrates CNS except
by covalently activity against infections, Ceftriaxone
binding to and susceptible urinary tract
inhibiting cell wall bacteria. infections,
transpeptidases surgical
prophylaxis
3. Carbapenem Prevents bacterial Rapid Serious IV administration | renal clearance Cilastatin added to prevent
cell wall synthesis bactericidal infections such hydrolysis by renal
by covalently activity against as pneumonia dehydropeptidase. Toxicities
binding to and susceptible and sepsis include seizures especially in
inhibiting cell wall bacteria. renal failure or with high doses
transpeptidases (>2 g/d)
4. Monobacta Prevents bacterial Rapid Infections IV administration | renal clearance No cross allergenicity with
m cell wall synthesis bactericidal caused by penicillin
by covalently activity against aerobic, gram-
binding to and susceptible negative
inhibiting cell wall bacteria. bacteria in
transpeptidases patients with
immediate
hypersensitivity
to penicillin
5. Glycopeptid Inhibits cell wall Bactericidal Infections Oral, IV administration | renal Red man syndrome,
e synthesis by activity against caused by gram- clearance nephrotoxicity
binding to the D- susceptible positive bacteria
ala D-Ala bacteria, including sepsis,
terminus of slower kill than endocarditis,
nascent beta-lactam and meningitis
peptidoglycan antibiotics
6. Lipopeptide Binds to cell Bactericidal Infections IV administration | renal clearance Inactivated by pulmonary
membrane, activity against caused by gram- surfactant so it cannot be used to
causing susceptible positive bacteria treat pneumonia. Toxicities
depolarization bacteria; more including sepsis include Myopathy whereas
and rapid cell rapidly and endocarditis monitoring of weekly creatinine
death bactericidal phosphokinase levels is
than recommended.
vancomycin
 The Penicillin
Derivatives of 6-aminopenicillanic acid
Contains beta-lactam ring, a four-membered cyclic amide which is the core component of several antibiotics,
and thiazolidine ring.
Blood levels of all penicillin can be raised by simultaneous administration of Probenecid, 0.5 g every 6 hours
orally, which impairs renal tubular secretion of weak acids such as -lactam compounds.
Penicillin inhibits bacterial growth by interfering transpeptidation reaction of bacterial cell wall synthesis
thereby halting peptidoglycan synthesis which is one of the components of the cell wall.
Transpeptidation cross links two polymer chains of peptidoglycans containing amino hexoses N-
acetylglucosamine and N-acetylmuramic acid whose peptide chain terminates in D-alanyl-D-alanine. When
cross-linking occurs the terminal alanine is removed by penicillin-binding protein and the exposed alanyl
links with a pentapeptide side chain of another N-acetylmuramic acid of the other polymer thereby giving
rigidity to the cell wall.
Generally, like any other -lactam antibiotics, they are hydrolyzed by -lactamases which are produced by
bacteria.
Mechanisms of Resistance:
i. Inactivation of antibiotic by -lactamase
ii. Modification of target PBPs
iii. Impaired penetration of drug to target PBPs
iv. Antibiotic efflux
Mechanism I is the most common mechanism of resistance.
Mechanism II is the basis of methicillin resistance in staphylococci and of penicillin resistance in
pneumococci and enterococci. These resistant organisms produce PBPs that have low affinity for binding
lactam antibiotics, and consequently they are not inhibited except at relatively high drug concentrations
which is often clinically unachievable.
Mechanism III occurs only in gram-negative species because of the impermeable outer membrane of the cell
wall which is absent in gram-positive bacteria. -lactam antibiotics cross the membrane via outer-membrane
protein channels called as porins. The absence of such channel or down-regulation of production greatly
impairs drug entry to the cell.
Mechanism IV occurs when gram-negative species produce efflux pump, which consists of cytoplasmic and
periplasmic protein components that efficiently transport some -lactam antibiotics from the periplasm back
across the cell wall outer membrane.
A. Normal Penicillin
1. Penicillin G
Less protein-bound penicillin
Intravenous route of administration
Used against streptococci, meningococci, susceptible pneumococci, non--lactamase producing
staphylococci bacteria
Used in Treponema pallidum and other spirochetes, Actinomyces and certain gram-positive rods, and in
some Clostridium species.
Also used in non--lactamase producing gram-negative anaerobic bacteria
2. Penicillin V
Oral form of penicillin
Poor bioavailability
Narrow antibacterial spectrum
Given 1-2 hours before or after meals
B. Long-Acting Penicillin formulated to delay absorption to prolong blood and tissue drug concentrations
however, yields lower drug levels compared to the normal penicillin drugs.
1. Benzathine Penicillin
2.4 million units of Benzathine Penicillin G administered Intramuscularly once a week for 1-3 weeks is
effective against syphilis
Intramuscular injection of 1.2 million units is effective against -hemolytic streptococcal pharyngitis
2. Procaine Penicillin G
was used for pneumococcal pneumonia and gonorrhea treatment
rarely used now against gonorrhea because many of gonococcal strains are penicillin-resistant
Rarely used now against pneumococcal pneumonia because many pneumococci require higher doses of
Penicillin G or more potent -lactams
C. Anti-staphylococcal Penicillin semisynthetic penicillin which are resistant to staphylococcal -lactamase
- Listeria monocytogenes, enterococci, and methicillin-resistant strains of staphylococci are resistant
1. Nafcillin
Intravenously administered
Highly protein-bound penicillin
Achieve lower free-drug concentration in serum
 2. Methicillin
3. Oxacillin
4. Isoxazoyl Penicillin
a. Cloxacillin
b. Dicloxacillin
D. Extended-Spectrum Penicillin
1. Amoxicillin
2. Ampicillin
3. Carboxypenicillin
a. Carbenicillin
b. Ticarcillin
c. Ureidopenicillin
d. Pherpacillin
e. Mezlocillin
f. Azlocillin

The Cephalosporin
7-aminocephalosphoric acid as the nucleus wherein various R groups may attach
More stable against B-Lactamase compared to Penicillin
Can be hydrolyzed by extended-spectrum -lactamases expressed by strains of E. coli and Klebsiella sp
Inactive against L monocytogenes
Only Ceftaroline has some activity against enterococci
Lower toxicity
A. First Generation Cephalosporin
1. Orally Administered
a. Cephalexin
b. Cephradine
c. Cefadroxil
2. Parenteral Administration
a. Cefazolin (IV) only first-gen parenteral cephalosporin still in general use
b. Cephalothin (IV)
c. Cephapirin / Cefapirin (IV)
B. Second Generation Cephalosporin
1. Orally Administered
a. Cefaclor
b. Cefuroxime acetyl
c. Cefprozil
d. Loracarbef
2. Parental Administration
a. Cefoxitin (Cephamycin)
b. Cefmetazole (Cephamycin)
c. Cefotetan (Cephamycin)
d. Cefmandole
e. Cefonicid
f. Ceforanide
g. Cefuroxime
C. Third Generation Cephalosporin
1. Orally Administered
a.
2. Parenteral Administration
D. Fourth Generation Cephalosporin