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Targeted approaches
Empirical screening
Nalidixic acid
Fluoroquinolones
Fusidic acid
Mupirocin
Erythromycin
Newer macrolides
Rifamycin
Trimethoprim
lactamase inhibitors
Vancomycin
Carbapenems
Bacitracin
Monobactams
Cephalosporin
Semi-synthetic penicillins
Chloramphenicol
and cephalosporins
Neomycin
Newer aminoglycosides
Penicillin Streptomycin
Prontosil Chlortetracycline Newer tetracyclines
1910 1920 1930 1940 1950 1960 1970 1980 1990 2000
Adapted from Knowles 1997
ANTIBIOTICS SPECTRUM OF
COVERAGE
Narrow Spectrum effective against
a few organisms
Broad Spectrum effective against
many organisms
TYPES OF ANTIBIOTIC
Bactericidal
kills the infecting organisms
Bacteriostatic
Slow their growth
Protein synthesis
inhibition
Macrolides
erythromyci
n
midecamyci
n, etc.
Chlorampheni
col
Aminoglycosid
es kanamycin
dibekacin
amikacin
streptomycin
Tetracycline
s
Cytoplasmic
membrane
inhibition
Polypeptides
polymixin B,
etc.
Cell wall
synthesis
inhibition
FOM
(Fosfomycin)
Cephems
cephalosporin
s
cephamycins
Inhibition of nucleic
acid synthesis
Penicillins
penicilin-G
ampicillin
cloxacillin,
etc.
DNA synthesis
inhibition Quinolones
RNA synthesis
inhibition rifampicin
CLASSIFICATION OF CHEMOTHERAPEUTIC
AGENTS BY MECHANISM OF ACTION
Herdiman T Pohan, Jakarta 2005
PENICILLIN
MOA: Inhibition of cell wall synthesis
Resistance: Common and due to Blactamase production
Toxicity: Hypersensitivity can occur
CEPHALOSPORINS
group of Beta-Lactam antibiotics similar to penicillins but more
stable to many B-lactamases; thus has broader spectrum
BACTERICIDAL
Elimination: Renal (70% via Glomerular Filtration &
Tubular Secretion)
*except Ceftriaxone (Biliary)
Caution: Nephrotoxicity
Spectrum of Activity
Class
G (+)
G (-)
Beta Lactatamase
Stability
First Gen
+++
+/-
Easily hydrolyzed
Second
Gen
++
Third Gen
+/-
++
++
Fourth Gen
+++
+++
+++
CLINICAL USES
Activity against B-lactamase producing H.
influenzae & M. catarrhalis = treatment for sinusitis,
otitis & LRTIs
Activity against anaerobes (ex: Cefoxitin) =
treatment for intra-abdominal infections
(peritonitis, diverticulitis) & GYN infections (pelvic
inflammatory disease)
Activity against S. aureus = treatment of skin & soft
tissue infections
THIRD GENERATION
CEPHALOSPORINS
Very good gram (-) activity & pseudomonas activity.
Used to treat RTIs, UTIs, bacteremia, meningitis, FUO.
Ceftriaxone
Cefotaxime
Ceftazidime
Cefepime
Cefixime
CLINICAL USES
serious infections caused by :
Klebsiella
Enterobacter
Proteus
Providencia
Serratia
Haemophilus
Ceftriaxone is the therapy of choice for all forms of gonorrhea and for severe
forms of Lyme disease. The third-generation cephalosporins cefotaxime or
ceftriaxone are used for the initial treatment of meningitis in
nonimmunocompromised adults and children older than 3 months of age
FOURTH-GENERATION
CEPHALOSPORINS
Aminoglycosides
- Administration: IM, IV, Topical
- Mode of action: Inhibition of bacterial protein synthesis
Resistance:
Due to bacterial enzymes decreasing drug transport in the organism.
- Toxicity: Vertigo, deafness, renal
Tetracycline
- Administration: Oral
- Mode of action: Inhibition of bacterial protein synthesis
- Antibacterial activity: Mycoplasma, Chlamydia, urethritis
- Toxicity: Gastric irritation, diarrhea, inhibition of bone
development, yellow staining of teeth.
Metronidazole
- Administration: Oral, IV, Rectal
- Mode of action: Inhibition of DNA synthesis
- Antibacterial activity: Anaerobic infections in abdominal
and gynecological lesions
- Toxicity: Gastric irritation, metallic taste
Macrolides
- Administration: Oral, IV
- Mode of action: Inhibition of protein synthesis
- Antibacterial activity: Atypical microorganism
- Toxicity: Gastric irritation
MECHANISM OF
ANTIMICROBIAL RESISTANCE
Production of structure altering or inactivating
enzymes e.g lactamase.
Alteration of penicillin binding protein.
Altered DNA gyrase targets.
Mutational change or acquisition of resistance
encoding genetic material.
EMERGENCE OF RESISTANCE IS
DUE TO:
IMPORTANCE OF ANTIBIOTIC
RESISTANCE
Infections/communicable diseases are a
major cause of mortality and morbidity
worldwide
Rapid increase in organisms resistance to
commonly used antibiotics
Many common pathogens are resistant to a
variety of -lactam agents
Sulbactam/Cefoperazone:
Achieves and sustains high therapeutic concentrations
in many tissues/fluids after IV/IM administration
No evidence of accumulation after multiple dosing
Suitable for use in elderly patients, children and individuals
with mild-to-moderate renal impairment
Low level of drugdrug interactions
Sulbactam is less likely to induce -lactamase than
clavulanic acid
PROFILAKSIS ANTIMICROBIAL
consists of the administration of an antimicrobial agent or
agents prior to initiation of certain specific types of surgical
procedures in order to reduce the number of microbes that
enter the tissue or body cavity
By definition, prophylaxis is limited to the time prior to and
during the operative procedure; in the vast majority of cases
only a single dose of antibiotic is required, and only for
certain types of procedures (see Surgical Site Infections)
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