DISCUSSION

Aminoglycosides

The aminoglycosides are a large group of broad-spectrum antibiotics processing significant

activity against many Gram-negative bacteria and a more limited range of Gram-positive
organisms. The antibiotics are all bactericidal and administered by injection because they are
poorly absorbed from the GI tract. They are cationic, water-soluble drugs that interfere with
protein synthesis in bacteria by binding to the 30S subunit (which is not possessed by
mammals). Streptomycin was the earliest aminoglycoside discovered in 1944. Streptomycin was
the first effective antibiotic for the treatment of tuberculosis and still used as a second-line drug
although it now has few other applications. Neomycin (1940s) has high toxicity curtailed its use
as a systemic drug and it now largely restricted to ophthalmic and topical products, although in
this limited field its used is widespread. . Oral preparations of neomycin are employed, again
often in combination with other antibiotics, to reduce the bacterial population of the colon prior
to surgery. Three of the most important aminoglycosides currently available are gentamicin,
tobramycin and amikacin. The first two of these are naturally occurring drugs discovered in the
1960s, whilst amikacin is a semisynthetic derivative of kanamycin, which it has superseded.
Gentamycin, is used alone or in combination with - lactam antibiotics (with which it exhibits
synergy) both for blind therapy of infections prior to identification of the infecting organism,
and for the treatment of bacterial endocarditis and serious Gram - negative infections; it has no
activity with anaerobes. Amikacin has similar applications, but is more stable to inactivation by
bacterial enzymes, though rather less potent, than gentamicin. All three antibiotics possess
useful activity against Ps. aeruginosa and are particularly valuable, again with - lactams, for
the eradication or suppression of this organism in the lungs of cystic fibrosis patients; tobramycin
is slightly more active than gentamicin against Ps. aeruginosa and for this reason it is more
frequently used for this purpose than any other. Aminoglycosides have in the past often been
administered twice or three times per day, but the more recent trend has been towards a single,
higher, daily dose. Although not suitable in all situations, once - daily dosing is undoubtedly more
convenient and considered to be at least as safe and efficacious.

GLYCOPEPTIDES

The only two important glycopeptide antibiotics currently available are vancomycin and
teicoplanin. Like many of the other antibiotics in current use, vancomycin is a relatively old drug,
having been introduced in 1958, but its activity against MRSA resulted in it becoming
progressively more valuable as MRSA became more prevalent. It has a complex tricyclic
glycopeptide structure and its large molecular size means that it cannot penetrate through the
outer membrane of most Gram- negative bacteria, so its use is effectively restricted to the
treatment of infections by aerobic or anaerobic Gram - positive species. In addition to Staph.
aureus, it is active against Staph. epidermidis , streptococci, Cl. difficile and Ent. faecalis,
although resistant enterococci are posing an increasing clinical problem. Vancomycin is
bactericidal to most susceptible bacteria at concentrations near its minimum inhibitory
concentration (MIC) and is an inhibitor of bacterial cell wall peptidoglycan synthesis, although at
a site different from that of - lactam antibiotics. Employed as the hydrochloride and
administered by dilute intravenous injection, vancomycin is indicated in potentially life -
threatening infections that cannot be treated with other, less toxic, antibiotics. Oral vancomycin,
which is not absorbed from the gastrointestinal tract, is the drug of choice in the treatment of
antibiotic - induced pseudomembranous colitis associated with the administration of antibiotics
such as clindamycin and lincomycin. Teicoplanin (1990s) has the same mode of action and
antimicrobial spectrum as vancomycin, as well as a similar chemical structure, but, crucially,
teicoplanin possesses more fatty acid side chains which (1) make the molecule more acidic,
thereby permitting the formulation of a sodium salt that can be given both by intravenous and
intramuscular injection, and (2) make teicoplanin more lipophilic, which affords better tissue
penetration and a longer half - life; as a consequence, teicoplanin is normally administered once
daily rather than twice. Other advantages over vancomycin are a slightly higher potency against
most target organisms and a better toxicity profi le, thereby eliminating the need for routine
blood monitoring.