Beruflich Dokumente
Kultur Dokumente
Antibiotic Classes
Matthias Maiwald
Consultant in Microbiology
KK Women’s and Children’s Hospital, Singapore
• History, definition
• Classes of antibiotics
• Beta-lactams (penicillins, cephalosporins, etc.)
• Aminoglycosides, quinolones, macrolides,
tetracyclines, lincosamides, glycopeptides,
sulfonamides and trimethoprim
• Routes of administration (oral, IV, etc.)
• Concept of broad and narrow spectrum
• Resistance: mechanisms and impact
2
Definitions
Antimicrobial substances:
• Antibiotics
• Chemotherapeutic agents
• Antimycotic (antifungal) substances
• Antiviral substances
• Antiparasitic substances, etc.
3
History
4
Recreation of
Alexander Fleming’s
original experiment
(1928)
5
Concept of
Selective Toxicity
6
Targets for antibiotics
• Protein synthesis
• Metabolic pathways
7
Sites of anti-
biotic activity
Source: Wikipedia
8
Important
characteristics
of
antimicrobials
9
Principle of antibiotic spectrum
11
Action of beta-lactams:
Inhibition of penicillin binding proteins
(act as transpeptidases for crosslinking
of peptidoglycan)
14
Beta-lactamase inhibitors & penicillins
15
Cephalosporins
• Products from fungus Cephalosporium sp.
• Derivatives of 7-aminocephalosporanic acid with
beta-lactam ring and 6-membered dihydrothiazine
ring
• Similar action to penicillins; generally broader
antibacterial spectrum (exceptions)
• Three (-four)
generations
17
Carbapenems
• Unique beta-lactam antibiotics
• Broadest spectrum of all antibiotics
(Except Mycoplasma, Chlamydia)
• Examples: Imipenem, Meropenem
• Expensive;
only IV
administered
Mims C et al.
Medical Microbiology.
2004.
18
Glycopeptides
• Aminoglycosides
• Tetracyclines
• Macrolides
• Lincosamides
20
Aminoglycosides
Prototype
structure
of amino-
glycosides
Modifying
enzymes, i.e.,
resisance
mechanisms
22
Macrolides
23
Macrolides
Erythromycin
Mims C et al.
Medical Microbiology.
1998.
24
Tetracyclines
25
Tetracycline
structure
Mims C et al.
Medical Microbiology.
1998.
26
Inhibitors of
nucleic acid synthesis
• Synthetic agents
• Inhibit enzyme gyrase
• Prevent supercoiling of the bacterial
chromosome
• Used for systemic infections with Gram-
negative bacteria, urinary tract infections, etc.
28
Quinolone
Mechanism
of Action
Mims C et al.
Medical Microbiology.
1998.
29
Quinolones
• Synthetic agents
• Inhibit folic acid pathway leading to nucleic acids
(purines and pyrimidines)
• Often used in combination because of synergy
• Example: Trimethoprim + Sulfamethoxazole
= Cotrimoxazole
• Broad spectrum, but many Gram-negatives now
resistant
31
32
Structure and Action of
Trimethoprim and Sulfonamides
Med. Microbiology.
Mims C et al.
1998.
Antimycobacterial treatment
Rifampicin:
- inhibits DNA-dependent
RNA polymerase
Pyrazinamide (PZA)
- inhibits mycobacterial
Ethambutol (EMB) fatty acid synthase
- bacteriostatic inhibition
of cell wall synthesis
• Metronidazole
• Rifampicin
• Fusidic acid
• Chloramphenicol
• Colistin
• Quinupristin-dalfoprisitin
• Linezolid
35
Antibiotic
resistance
sensitive
Mercy !!
resistant
http://www.joachim-czichos.de
Antibiogram of multiresistant
Pseudomonas aeruginosa
de la Maza LM et al.
Color Atlas of med. Bacteriology 2004
36
Antibiotic Resistance
in Bacteria
39
Factors promoting
antibiotic resistance
• Incorrect selection of abx for target organism
• Antibiotics for non-bacterial infections
• Inappropriate use of broad-spectrum abx where
narrow-spectrum abx would suffice
• Prolonged therapy where shorter tx suffices
• Underdosing (or skipping doses of) abx
• Lack of good infection control (allowing spread)
• Antibiotics in animal feeds
40
Now, if you ask me,
I think it would be a good idea
if we could also take our cocktail
of antibiotics with ice, lemon
and a bit of angostura
41 Marunde
Impact of antibiotic resistance
• Infections that used to be treatable with standard
antibiotics now need revised, complex regimens:
• e.g., pen.-resistant Strep. pneumoniae may
require broad-spec. ceph. or vancomycin
• In some instances, hardly any antibiotics left:
• e.g., Multiresistant Pseudomonas aeruginosa,
Acinetobacter baumannii, vancomycin-resistant
Staph. aureus, new “NDM-1” bacteria
• Resistance rates worldwide increasing
• Companies not developing new antibiotics
42
Antibiotic susceptibility testing
in the laboratory
43
Disk diffusion testing
44
MIC testing with E-test on agar
45
Determination of MIC and MBC