Antmicrobial Agent
Antmicrobial Agent
Antmicrobial Agent
resistant pattern
Dr. Israe A Ali
Specialist Medical microbiology
2022
Antimicrobial agents
An antimicrobial agent is
defined as a natural or
synthetic substance that kills or
inhibits the growth of
microorganisms such as
bacteria, fungi and algae
Antimicrobial activity
Not all antimicrobials, at the
concentration required to be
effective are completely non –
toxic to human cells. Most,
however, show sufficient selective
toxicity to be of value in the
treatment of microbial diseases.
Mechanisms Of Action Of
Antimicrobial Drugs
Antimicrobial drugs act in
one of several ways:
1.Selective toxicity
2.Inhibition
Selective Toxicity
An ideal antimicrobial agent exhibits
selective toxicity, which means
that the drug is harmful to a pathogen
without being harmful to the host.
Often, selective toxicity is relative
rather than absolute, this implies that a
drug in a concentration tolerated by the
host may damage an infecting
microorganism.
Selective toxicity may be a
function of:
A. A specific receptor required
for drug attachment,
B. It may depend on the
inhibition of biochemical
events essential to the
pathogen but not to the host.
Mechanisms Of Action Of Antimicrobial Drugs
inhibition
. Extended-spectrum penicillin:
➢ Ampicillin and amoxicillin for are broad spectrum
penicillins active against G+ve (including
Enterococcus), H. influenzae, and many coliform.
• Antistaphylococcal penicillins :
✓ Dicloxacillin ,Nafcillin ,Oxacillin
• Natural penicillin
✓ Pencillin G ,Pencillin V
• Antipseudomonal penicillins:
✓ Pipracillin, Pipracillin+ tazobactam, Ticracillin
✓ lactamase inhibitor + antibiotic combinations
Clavulanic acid + amoxicillin
anti – bacterial Resistance to
penicillin
• anti – bacterial Resistance to penicillin may occur due
to Beta- Lactamase production , cell membrane
alteration reducing antibiotic uptake (G-VE bacteria).
• Or change in PBP (Penicillin-binding proteins are generally enzymes
involved in peptidoglycan biosynthesis, so contribute essential roles in bacterial
cell wall biosynthesis)
as occur in MRSA ( MRSA are usually
resist to many antibiotic as penicillin, erythromycin
,tetracycline and some times gentamycin , sever
infection require treatment with vancomycin ,which
also reported as resist .
Inhibition Of Cell Wall Synthesis
# Cephalosporin
Bactericidal and have beta-lactam ring.
They are used to treat sever systemic
infection caused by
aerobic Gram –ve .
1.1.Non-Gentic origin
2.2.Gentic origin
Non-gentic origin
1. Active replication of bacteria is
required for most antibacterial drug
actions. Consequently,
microorganism that are metabolically
inactive (non-multiplying) may be
phenotypically resistance to drug.
However their offspring are fully
susceptible.
Examples: Mycobacterium
often survive in tissues for
many years after infection
yet are restrained by the
hosts defenses and do not
multiply. Such “persisting”
organism are resistant to
treatment and cannot be
eradicated by drugs.
2.Microorganisms may .2
lose the specific target
structure for a drug for
several generations and
thus be resistant.
Example: Penicillin-susceptible
organisms may change to cell
wall-deficient. L-forms during
penicillin administration.
Lacking cell walls, they are
resistant to cell wall-inhibitor
drugs (penicillins,
cephalosprins) and may remain
so for several generations.
3.Microorganisms .3
may infect the host at
sites, where
antimicrobials are
excluded or are not
active.
Examples: Aminoglycosides
such as gentamicin are not
effective in treating
salmonella enteric fevers
because the salmonellae
are intracellular and the
aminoglycosides do not
enter the cells.
Genetic origin
Most drug-resistant microbes
emerge as a result of genetic
change and subsequent
selection processes by
antimicrobial drugs.
A.Chromosomal Resistance:
This develops as result of
spontaneous mutation in a locus
that controls susceptibility to a
given antimicrobial drug. The
presence of the antimicrobial drug
serves as a selecting mechanism to
suppress susceptible organisms and
favor the growth of drug-resistant
mutants.
Spontaneous mutation occurs
with a frequency of 10ˉ¹² and
thus is an infrequent cause of
the emergence of clinical
drug resistance in a given
patient. However,
chromosomal mutants
resistant to rifampin occur
with high frequency.
Consequently, treatment of
bacterial infections with
rifampin as the sole drug often
fails. Chromosomal mutants
are most commonly resistant
by virtue of a change in a
structural receptor for a
drug.
Thus, the P12 protein on the 30S
subunit of bacterial ribosome
serves as a receptor for
streptomycin attachment.
Mutation in the gene controlling
that structural protein results in
streptomycin resistance. Mutation
can also result in the loss of PBPs
making such mutants resistant to
β-lactam drugs.
B- Extrachromosomal Resistance
Bacteria often contain extrachromosomal
genetic elements called plasmids. Some
plasmids carry genes for resistance to
one – and often several – antimicrobial
drugs. Plasmid genes for antimicrobial
resistance often control the formation
of enzymes capable of destroying the
antimicrobial drugs.
Thus, plasmids determine resistance to
penicillins and cephalosporins by carrying
genes for the formation of β-lactamases.
Plasmids code for enzymes that acetylate,
adenylate, or phosphorylate various
aminoglycosides; for enzymes that determine
the active transport of tetracyclines across the
cell membrane; and for others.
Genetic material and plasmids can be
transferred by transduction, transformation,
and conjugation.
Antimicrobial
Sensitivity Test
Sensitivity (susceptibility)
testing is used to select
effective antimicrobial
drugs. Sensitivity test is not
usually indicated when the
sensitivity reactions of a
pathogen can be predicted
for example:
• Proteus species are generally
resistant to nitrofurantoin and
tetracyclines.
• S.pyogenes is usually sensitive to
penicillin
• K.pneumoniae is generally
ampicillin resistant.
• Anaerobes are sensitive to
metronidazole.
• Organism that are susceptible to tetracycline are
also consider susceptible to doxycycline and
minocycline.
• However , some organism that are intermediate
or resistant to tetracycline may be susceptible to
doxycycline ,minocycline or both.
• RX: Refampin should not used alone for
antimicrobial therapy.
•
❑When fecal sample isolates of
salmonella and shigella spp. ,are tested
only ampicillin, a fluoroquinolone ,and
trimethoprim /sulfamethoxazole should
be reported routinely.
❑In additional for extra intestinal isolates of
salmonella spp. , a third –generation of
cephalosporin should be tested and reported
,and chloramphenicol may be tested and
reported , if requested.
• Resistance to cephalosporins
can attributed to:
1. poor permeation of
bacteria by the drug
2. lack of PBP for a specific
drug
3. degradation of drug by β-
lactamases
Antimicrobial Subclass
1.First-Generation Cephalosporins:
Very active against gram-positive
cocci – except enterococci and
methicillin-resistant
staphylococci(MRSA), and
moderately active against some
gram-negative rods – primarily E.
coli, Proteus, and Klebsiella.
None of the 1st generation drugs
penetrate the CNS and they are
not drugs of choice for any
infection
a)Cephalothin
b)Cephapirin
c)Cefazolin
d)Cephradine
2. Second Generation Cephalosporins:
All are active against organisms
covered by 1st generation drugs
but have extended coverage
against gram-negative rods
a)Cefamandole
b)Cefuroxime (Parenteral)
c) Cefonicid
3. Third-Generations Cephalosporins:
Have decreased activity against gram-positve
cocci, except for Strep. Pneumoniae,
enterococci but enhanced activity against
gram-negative rods .
3rd generation drugs – except Cefoperazone is
ability to reach the CNS
a)Cefotaxime
b)Ceftizoxime
c) Ceftriaxone
d)Ceftazidime
e) Cefoperazone
4. Fourth – Generation Cephalosporins:
Cefepime is the only 4 th –
generation cephalosporin. It
has enhanced activity against
Enterobacter and Citrobacter
species that resistant to 3rd
generation cephalosporins.
5. Cephalosporins with Anti-MRSA activity:
Ceftaroline
Ceftobiprole
Cross Resistance
• Microorganisms resistant to a certain drug may
also be resistance to other drugs that share a
mechanism of action. Such relationships exist
mainly between agents that are closely related
chemically (eg, different aminoglycosides) or
that have a similar mode of binding or action
( eg, macrolides-lincomycins)
Cross Resistance
In certain classes of drugs, the
active nucleus of the chemical is
so similar among many
congeners (eg, tetracyclines) that
extensive cross-resistance is to be
expected.
Warning: the following antimicrobial /organism may
appear active in vitro, but are not effective clinically
and should not reported as susceptible.