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Penicillins work by inhibiting peptidoglycan cross-linkage. Modifications
to the penicillins have extended their antibacterial spectrum
and improved absorption. Penicillins now include:
- natural penicillins (e.g. benzylpenicillin, penicillin V);
- penicillinase-resistant penicillin (e.g. flucloxacillin);
- aminopenicillins (e.g. ampicillin-like agents);
- expanded-spectrum penicillins (e.g. piperacillin);
- penicillins combined with ß-lactamase inhibitors (e.g. amoxicillin
and clavulanate, known as co-amoxiclav).
Oral absorption varies: benzylpenicillin (penicillin G) is unstable
in the presence of gastric acid and must be given intravenously,
but penicillin V is stable and can be given orally. The aminopenicillins
and flucloxacillin are also absorbed orally, while the remaining
agents must be given intravenously.
Penicillins are secreted by the kidney and have a short half-life.
They are distributed in extracellular fluid, but do not cross the
blood-brain barrier unless the meninges are inflamed.
Cephalosporins are closely related to penicillins. They are all active
against Gram-positive organisms and later compounds have activity
against Gram-negative bacteria including Pseudomonas.
The monobactams are related to penicillins and cephalosporins.
They have a broad spectrum of activity, including against anaerobes.
Imipenem and meropenem have antipseudomonal effects.
They must be given intravenously.
Aminoglycosides act by preventing translation of mRNA into
proteins. They are given parenterally, are limited to the extracellular
fluid and are excreted in the urine. Aminoglycosides are toxic
to the kidney and eighth cranial nerve at amounts close to therapeutic
levels, which necessitates careful monitoring of serum
The glycopeptides (vancomycin and teicoplanin) have the following
- They inhibit peptidoglycan cross-linking in Gram-positive
- Resistance to them is rare but sometimes found in enterococci
(glycopeptide-resistant enterococci - GRE) and in some Staphylococcus
- Administration is intravenous or intraperitoneal; they are not
absorbed orally. The exception is the oral use of vancomycin to
treat pseudomembranous colitis.
- They are distributed in the extracellular fluid, but do not cross
the blood-brain barrier unless there is meningeal inflammation.
- Excretion is via the kidney.
Daptomycin, a new agent with a long half-life, is very active
against Gram-positive organisms demonstrating more rapid killing
in vitro. Its mode of action is uncertain.
- Quinolones act by inhibiting bacterial DNA gyrase.
- The early quinolones did not attain high tissue levels and were
used only for urinary tract infections.
- Fluorine modification (fluoroquinolones) has made them active
against Gram-negative pathogens including Chlamydia.
- Ciprofloxacin has activity against Pseudomonas spp.
- Quinolones are well absorbed orally, are widely distributed and
penetrate cells well.
- Newer agents (e.g. moxifloxacin) are active against Gram-positive
pathogens, including Streptococcus pneumoniae and Mycobacterium
The macrolides (erythromycin, azithromycin and clarithromycin)
bind to the 50S ribosome, interfering with protein synthesis; they
are active against Gram-positive cocci, many anaerobes (but not
Bacteroides), Mycoplasma and Chlamydia. They are absorbed
orally, distributed in the total body water, cross the placenta, are
concentrated in macrophages, polymorphs and the liver and are
excreted in the bile. Erythromycin may cause nausea. The newer
macrolides (e.g. azithromycin) have more favourable pharmacokinetic
and toxicity profiles.
Pristinamycin is a bactericidal semisynthetic streptogramin consisting
of quinupristin and dalfopristin. It acts by preventing
peptide bond formation, which results in release of incomplete
polypeptide chains from the donor site. It is active against a broad
range of Gram-positive pathogens and some Gram-negatives, such
as Moraxella, Legionella, Neisseria meningitidis and Mycoplasma.
It is used mainly for the treatment of resistant Gram-positive infections
(e.g. GRE and glycopeptide-intermediate S. aureus [GISA]).
The oxazolidinones (e.g. linezolid) inhibit protein synthesis at the
50S ribosomal subunit. They are most active against Gram-positive
bacteria and are used mainly for the treatment of resistant
Gram-positive infections. Linezolid is well absorbed orally and
concentrated in the skin.
The main features of metronidazole are that it is:
- active against all anaerobic organisms;
- a receiver of electrons under anaerobic conditions, so forms
toxic metabolites that damage bacterial DNA;
- also active against some species of protozoa, including Giardia,
Entamoeba histolytica and Trichomonas vaginalis;
- absorbed orally and can be administered parenterally;
- widely distributed in the tissues, crossing the blood-brain barrier
and penetrating into abscesses;
- metabolized in the liver and excreted in the urine;
- well tolerated, except that it cannot be taken with alcohol.
Sulphonamides and trimethoprim
- Tetracyclines act by inhibition of protein synthesis by locking
tRNA to the septal site of mRNA.
- They are active against many Gram-positive and some Gramnegative
pathogens, Chlamydia, Mycoplasma, Rickettsia and
treponemes, Plasmodium and Entamoeba histolytica.
- Doxycycline is absorbed orally, has a long half-life and is widely
distributed; adequate therapeutic levels may be obtained by a
- The newer tetracyclines such as tigecycline are used to treat
multiresistant Gram-negative infections.
Sulphonamides and trimethoprim act by inhibiting the synthesis
of tetrahydrofolate. They are now rarely used in the treatment of
bacterial infections but have an important role in the management
of Pneumocystis jiroveci and protozoan infections including
malaria. Sulphonamides can be given intravenously and are well
absorbed when given orally. They are widely distributed in the
tissues and cross the blood-brain barrier. They are metabolized in
the liver and excreted via the kidney.