Simple Guide to

Antibiotic Classes
Matthias Maiwald

Consultant in Microbiology
KK Women’s and Children’s Hospital, Singapore

With materials and contributions from Tan Thean Yen

(Changi Hospital) and Nancy Tee (KK Hospital)

Microbiology Technical Workshop on Antimicrobial Susceptibility Testing,

Singapore 21-23 Sept. 2010
1
 Overview

• 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

Paul Ehrlich (1909): Arsenic compound in

the therapy of syphilis (Salvarsan)

Alexander Fleming (1928): Discovery of

penicillin from fungus Penicillium notatum

Gerhard Domagk (1935): Discovery of

sulfonamide “prontosil” from textile dye

4
Recreation of
Alexander Fleming’s
original experiment
(1928)

From the Cover page:

Australian Antibiotic
Guidelines.

5
 Concept of
Selective Toxicity

• Antimicrobials are selective inhibitors of

metabolic pathways in microorganisms

• Are nontoxic to mammalian cells

(or minimally toxic; i.e., side effects)

6
 Targets for antibiotics

• Cell wall synthesis

• Protein synthesis

• Nucleic acid synthesis

• Metabolic pathways

• Cell membrane function

7
Sites of anti-
biotic activity

Source: Wikipedia
8
 Important
characteristics
of
antimicrobials

Mims CA et al. 1998

Medical Microbiology
(textbook)

9
 Principle of antibiotic spectrum

• Different antibiotics target different kinds of

bacteria
• i.e., different spectrum of activity
• Examples:
• Penicillin G (= original pen.) mainly
streptococci (narrow spectrum)
• Vancomycin only Gram-positive bacteria
(intermediate spectrum)
• Carbapenems many different bacteria
(very broad spectrum)
10
 The beta-lactam
family:
Inhibitors of
peptidoglycan
(cell wall)
crosslinking

Mims C et al. Medical Microbiology. 2004.

11
 Action of beta-lactams:
Inhibition of penicillin binding proteins
(act as transpeptidases for crosslinking
of peptidoglycan)

Brandis H et al. Medizinische Mikrobiologie. 1994.

12
 Penicillins

• Derivatives of 6-aminopenicillanic acid with

beta-lactam ring and 5-membered thiazolidine ring
• Naturally occurring or semisynthetic
• Different antibacterial spectrum
• Different susceptibility to
bacterial penicillinases
(enzymes destroying
penicillins)

13 Nester EW et al. 2001. Microbiology: a human perspective.

 Examples of Penicillins

• Natural penicillins: e.g., Penicillin G

• narrow spectrum: e.g., Strep, Staph w/out p’ases)
• Aminopenicillins: e.g., Amoxycillin
• broader spectrum, incl. some Gram-negatives
• “Antistaphylococcal” penicillins, e.g., Flucloxacillin
• narrow spectrum: Staphs with penicillinases
• Penicillin + ß-lactamase inhibitor: e.g., Augmentin®
• broad spectrum: many Gram-negs & pos.

14
 Beta-lactamase inhibitors & penicillins

• Have no antimicrobial activity on their own

• Inhibit beta-lactamases produced by various bacteria
• Combined with penicillins antibiotics to create ‘broad-
spectrum’ antibiotics:
Mims C et al. Medical Microbiology. 1998.
• Amoxicillin-clavulanate
(Augmentin®)
• Active against S. aureus
(not MRSA), most Gram-positive
organisms, most Gram-negative
organisms (not Pseudomonas),
and anaerobes
• Piperacillin-tazobactam
(Tazocin®)
• As above, incl. Pseudomonas

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

Nester EW et al. 2001.

Microbiology:
16 a human perspective.
 Cephalosporin generations

• 1st Generation (e.g., Cephazolin, Cephalexin) :

• Good against Gram-positive bacteria
• Mainly oral, some IV
• 2nd Generation (e.g. Cefaclor, Cefuroxime):
• Good Gram-pos. activity, increased Gram-neg. cover
• Various admin. routes (oral, IV, IM)
• 3rd Generation (e.g. Cefotaxime, Ceftriaxone):
• Less Gram-pos., but good Gram-neg. activity
• 4th Generation (e.g. Cefepime, Cefpirome):
• Very broad spectrum, only IV

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

• Other inhibitors of cell wall synthesis

• e.g., vancomycin and teicoplanin
• Active against Gram-positive aerobes,
e.g., staphylococci, streptococci, enterococci
• Side effects:
fever, chills,
phlebitis at
infusion site
• Rapid vanc.
Infusion -->
“red man
syndrome” Mims CA et al.
Medical Microbiology. 1998.
19
 Inhibitors of
protein synthesis

• Aminoglycosides
• Tetracyclines
• Macrolides
• Lincosamides

20
 Aminoglycosides

• Biosynthetic products from

• Streptomycetes (-mycin ending)
e.g., Streptomycin, Tobramycin
• Micromonospora (-micin ending)
e.g., Gentamicin, Netilmicin
• and semisynthetic derivatives
e.g., Amikacin
• Consist of 3 aminosugars
• No oral absorption (only IV)
• Side effects: oto- and nephrotoxic
21
 Mims C et al. Med. Microbiology. 1998.

Prototype
structure
of amino-
glycosides

Modifying
enzymes, i.e.,
resisance
mechanisms
22
 Macrolides

• Prototype Erythromycin from Streptomyces

erythraeus
• Inhibit polypeptide chain elongation at the
ribosome
• Semisynthetic derivatives, e.g., Clarithromycin
• Active against e.g., streptococci, legionella
• Very good side effect profile

23
Macrolides

Erythromycin

Mims C et al.
Medical Microbiology.
1998.

24
 Tetracyclines

• Inhibit protein synthesis

• Relatively broad spectrum
• Enrichment in bone and teeth
• Not indicated for small children and in pregnancy
• Several derivatives,
e.g., doxycycline, minocycline

25
Tetracycline
structure

Mims C et al.
Medical Microbiology.
1998.

26
 Inhibitors of
nucleic acid synthesis

• Inhibitors of synthesis of precursors

• Sulfonamides
• Trimethoprim
• Inhibitors of DNA replication
• Quinolones
• Inhibitors of RNA polymerase
• Rifampicin
27
 Quinolones

• 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

Mims C et al. Medical Microbiology. 1998.

30
 Sulfonamides and Trimethoprim

• 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

• Mycobacteria divide slowly; chronic disease

• Slow: M. tuberculosis; very slow: M. leprae
• Single drug: resistance likely under therapy
• Combination of drugs: resistance unlikely
• Standard short-course therapy for tuberculosis
• Isoniazid + rifampicin -- 6 months
• Ethambutol + pyrazinamide -- 2 months
• i.e. combination of 4 (2 mo.), of 2 (6 mo.)
33
 Isoniazid (INH)
- inhibits of mycolic acid synthesis

Rifampicin:
- inhibits DNA-dependent
RNA polymerase

Pyrazinamide (PZA)
- inhibits mycobacterial
Ethambutol (EMB) fatty acid synthase
- bacteriostatic inhibition
of cell wall synthesis

34 Murray PR et al. 2003. Manual of clinical microbiology

 Some other Antibiotics

• Metronidazole
• Rifampicin

• Fusidic acid

• Chloramphenicol

• Colistin

• Quinupristin-dalfoprisitin

• Linezolid

• (Listing not complete)

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

• Natural (intrinsic resistance)

• i.e., species-specific
• Acquired resistance
• i.e., mutation + selection
or transfer of genetic traits
37
38
 Mims C et al. Medical Microbiology. 1998.

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

• Bacterial cultures tested on artificial media

• Tests the ability to grow (or: be killed) in the
presence of defined antibiotics
• Provides guidance for ongoing therapy
• Provides resistance rates for empiric therapy
• Problems: not all results correspond with clinical
success or failure

43
 Disk diffusion testing

Cohen & Powderly 2004;

http://www.idreference.com/

44
 MIC testing with E-test on agar

Cohen & Powderly 2004;

http://www.idreference.com/

45
 Determination of MIC and MBC

Mims C et al. Medical Microbiology. 1998.

46