Most important antibiotic drugs

1. M.A.A.Al-Maqrashi
Antibiotic
MOA & Resistance
mechanism
Pharmacokinetics & Uses A.E
InhibitorsofCellWallSynthesis
β-Lactam
[Penicillins]
Natural
penicillin G
penicillin V
±
cidial
interfere with the last step of
bacterial cell wall synthesis
(transpeptidation or cross-
linkage), resulting in less stable
membrane:
- covalently bind to the active
site of PBPs → inhibit the
transpeptidation reaction
and stop peptidoglycan
synthesis.
Penicillin-binding proteins
[PBP]:
- are membrane proteins that
cross-link peptidoglycan.
- removes the terminal
alanine in the process of
forming a cross-link with a
nearby peptide.
Resistance:
- β lactamase
- modification of PBP
[MRSA+MRSE]
- Impaired penetration of
drug to target PBPs [G-
]
- antibiotic efflux
- Penicillin G:
- inactivated by gastric juice
& low oral absorbtion.
- IV
- Depot forms: IM
[e.g. Procaine penicillin G
and benzathine penicillin G]
- Penicillin V: orally
- incompletely absorbed after oral
administration, and they reach
the intestine in sufficient amounts
to affect the composition of the
intestinal flora.
- cross the placental barrier
- no penetration into bone or CSF
[unless they are inflamed]
- Penicillin levels in the prostate &
eye are insufficient
- excreted in urine & breast milk
- effective against rapidly growing
organisms that synthesize a
peptidoglycan cell wall.
- hypersensitivity
[maculopapular rash,
angioedema, anaphylactic
shock etc.]
- GIT upsets
[nausea, vomiting, diarrhea,
pseudomembranous colitis.]
- Nephritis
- Neurotoxicity [even
epilepsy]
- Hematologic toxicities
[neutropenia]
Anti-staphyl.C
penicillins
methicilli,
cloxacillin
+
- IM or IV
- Penicillinase-producing S.
aureus.
- Penicillinase-producing S.
epidermis.
Broad spectrum
Aminopenicillins
(e.g. amoxicillin)
-
- Orally
- Similar to that of penicillin G
– e.g. Haemophilus
influenzae, Escherichia coli,
and Proteus mirabilis
Anti-
pseudomonal
piperacillin
-
- IM or IV
- against Pseudomonas
aeruginosa [Bacilli]
[Cephalosporins]
1st
g.: cephalexin
±
cidial
- have same mode of action as
penicillins and they are
affected by same resistant
methods.
- IV or IM
- Higher generations increase efficiency against gram -ve
- Ceftaroline: 5th gen. against MRSA (S. aureus)
- Allergy
- Thrombophlebitis [after IV
injection]
- Renal toxicity.
- Hypo-prothrombinemia and
bleeding disorders
2nd
g.: cefoxitin
3rd
g.:
Cefotaxime
4th
g.: Cefopime
[β-lactamase inhibitors]
Clavulanic acid
tazobactam
- Resemble β-lactam molecules but very weak antibacterial action.
- Available only in a fixed-dose combination with penicillins and cephalosporins.
- potent inhibitors of most of bacterial β lactamases → protect hydrolyzable penicillins from inactivation
Penicillin-β-lactamase inhibitor combinations:
- empiric therapy for infections caused by a wide range of potential pathogens.
- treatment of mixed aerobic and anaerobic infections, such as intra-abdominal infections.
- Amoxicillin + clavulanic acid [o-amoxiclav]
- Piperacillin + Tazobactam: the combination is must

2. M.A.A.Al-Maqrashi
Cont.ICWS
[Glycopeptides]
Vancomycine
+
cidial
- Binds to the terminal two D-
alanine residues of
pentapeptide → inhibiting
peptidoglycan backbone
elongations.
Resistance:
- Replacement of D-Ala by D-
lactate in resistant
organisms.
- Given by slow IV infusion (not absorbed orally) for systemic
infections
- Oral vancomycin is limited to treatment for antibiotic-associated
colitis by Clostridium difficile [anaerobic bacteria]
- Used in the treatment of MRSA, MRSE, enterococcal infections
- Red Man Syndrome
- shock from histamine
release associate with rapid
infusion.
- Ototoxicity
- Nephrotoxicity
Inhibitorsofproteinsynthesis
[Macrolides]
Erythromycin
+
static
- Bind irreversibly to a site on
the 50S subunit of the
bacterial ribosome → inhibits
the translocation step
- against many of the same organisms as penicillin G
- An alternative to penicillin in allergic individuals
- GIT disturbance.
- Cholestatic jaundice.
- Ototoxicity.
[Aminoglycosides]
Gentamycin
-
cidial
- irreversible inhibitors of
protein synthesis.
- Passive diffusion via porin
channels across the outer
membrane.
- Actively transported across
the cell membrane into the
cytoplasm by an oxygen-
dependent process.
- they bind the 30S subunit:
- interfere with assembly of
the functional ribosomal
- misread the genetic code
- Block of translocation on
mRNA.
- Concentration dependent.
- has postantibiotic effect.
- mostly used against aerobic G-
bacteria including Pseudomonas
aeruginosa.
- Their structure prevents adequate oral absorption.
- Must be given parenterally to achieve adequate serum levels.
- Mostly, Combined with a β-lactam antibiotic to:
- extend coverage to include potential gram-positive pathogens.
- take advantage of the synergism between these two classes of
drugs.
- Streptomycin is used as a second-line agent for treatment of
tuberculosis.
- Ototoxicity:
- deafness.
- vertigo and loss of
balance.
- Nephrotoxicity.
- Neuromuscular paralysis
[decrease in release of Ach.]
[Tetracyclines]
Tetracycline
±
static
- Bind reversibly to the 30S
subunit:
- Blocking the binding of
aminoacyl-tRNA to the
acceptor site on the
mRNA-ribosome complex.
- This prevents addition of
amino acids to the growing
peptide.
- broad-spectrum antibiotics
- Against Rickettsia, Chlamydia, Mycoplasma.
- used in combination regimens to treat gastric and duodenal ulcer
disease caused by Helicobacter pylori
- GIT upsets
[nausea, vomiting and
diarrhea.]
- Discoloration of teeth in
growing children.
- Phototoxicity
[sunburn occurs when a
patient receiving a
tetracycline is exposed to
sun.]
- Nephrotoxicity.
- Superinfections
[overgrowth with Candida or
resistant staphylococci]

3. M.A.A.Al-Maqrashi
Cont.IPS
[Chloramphenicol] ±
static
- potent inhibitor of microbial
protein -synthesis.
- binds reversibly to the 50S
subunit of the bacterial
ribosome and inhibits
peptide bond formation
(step 2).
- broad-spectrum antibiotic: against both aerobic and anaerobic
- Against Rickettsiae
- toxic: it is restrictly used.
- GIT upset:
[nausea, vomiting, diarrhea.]
- Anemia: [aplastic anemia.]
- Gray baby syndrome in
neonates:
[newborn infants lack an
effective glucuronic acid
conjugation mechanism for
the degradation and
detoxification of
chloramphenicol.]
- Inhibits hepatic microsomal
enzymes.
ActingonNucleicAcid
[Fluoroquinolones]
1st
g.: Nalidixic acid
±
cidial
- Enter the bacteria by passive diffusion through porins in the outer membrane.
- They inhibit the replication of bacterial DNA by interfering with the action of DNA gyrase
(topoisomerase II) and topoisomerase IV during bacterial growth and reproduction.
- Binding of the quinolone to both enzymes and the DNA forms a complex that can cause cell death by
inducing cleavage of the DNA.
Resistance:
- mutation of the target
- ↓porin molecules
- active transport out.
- Higher generations increase efficiency against gram +ve
- GIT upset:
[nausea, vomiting, diarrhea.]
- CNS:
[headache, dizziness, light-
headedness.]
- Phototoxicity.
- Connective tissue problems:
[tendinitis or tendon
rupture.]
2nd
g.:
Ciprofloxacin
Norflaxacin
Oflaxicin
3rd
g.: Cefotaxime
4th
g.: Cefopime
[Sulfonamides]
Sulfadiazine
±
static
- inhibit the synthesis of
bacterial dihydrofolic
Acid ← compete with PABA for
dihydropteroate synthase.
- synthetic analogs of PABA.
- Only organisms that synthetize their folate requirements de novo
are sensitive to the sulfonamides.
- inhibit Nocardia sp, Chlamydia trachomatis, and some protozoa.
- Crystalluria:
[sulfonamides can precipitate
in urine, especially at neutral
or acid pH. ]
- Hypersensitivity.
- Hemopoietic disturbances:
[hemolytic anemia in G6PD
deficiency.]
- Kernicterus:
[occur in newborns,
sulfonamides can displace
bilirubin from binding sites on
serum albumin → Bilirubin
pass into the CNS (BBB is not
fully developed) ]

4. M.A.A.Al-Maqrashi
Cont.ANA
[Trimethoprim]
static
- Selectively inhibits bacterial
dihydrofolic acid reductase
- less efficient inhibitor of mammalian dihydrofolic acid reductase.
- Sulfonamide (PABA competitor) + Trimethoprim (dihydrofolate reductase inhibitor) = bactericidal
synergistic activity: treating UTI and respiratory tract infections.
[Metronidazole]
cidial
- inflicts breaks in the DNA
itself.
- active against a wide range of anaerobes. [e.g. Clostridium difficile]
- a second antimicrobial (eg, β-lactam) is usually added to cover aerobic and facultative bacteria.
[Rifampin] ±
cidial
- Inhibits the synthesis of RNA
from DNA by inhibiting RNA
polymerase.
- Active against most Gram-positive bacteria and selected Gram-negative organisms.
- Used to treat tuberculosis.