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In the search for a new generation of quinolone antibiotics,
a complicated balancing act is emerging. The challenge for
third generation quinolones is to provide successful weapons
in the battle against the most resistant
bacteria whilst attaining an improved side effect profile.
There
are a number of promising potent and safer quinolones in
development and the study of structure
activity relationships has played a major role in their
development.
Whether
these will offer the answer to a number of key
problems experienced with the older drugs and fulfil
their early promise remains to be seen. If the conundrum
is cracked then quinolones could quickly become blockbusters
in the antibiotic arena.
At
present there are still significant gaps in activity against
the most serious and resistant pathogens, and some lingering
doubts about side effect potential. But a number of quinolones
in development seem to be showing promise according to IMS
HEALTH's Pioneer:
Gemifloxacin
One
of the most interesting is SmithKline Beecham's gemifloxacin
(licensed from LG Chemical), currently in Phase III trials
worldwide. Reported to have activity against: S. pneumoniae;
H. influenzae; M. catarrhalis and Acinetobacter. If it has
no chondrotoxicity then this might well expand its potential
market considerably.
T
3811/ BMS 284756
Another
promising fluoroquinolone developed by Toyama and quickly
licensed-in by Bristol-Myers Squibb is currently in Phase
I trials in the USA and reported to be free of chondrotoxicity.
PGE
9262932
Procter
& Gamble is working on a series of nonfluorinated quinolones
(NFQs). These NFQs are reported to have a broad antibacterial
spectrum with a focus on resistant Gram-positive organisms
such as multidrug resistant Staphylococcus aureus and penicillin-resistant
Streptococcus pneumoniae.
MC
207110
Daiichi
and Microcide have joined forces in their bid to combat
quinolone resistance with a bacterial efflux pump inhibitor,
MC 207110, currently in preclinical development. MC 207110
has minimal intrinsic antibacterial activity, but potentiates
the activity of levofloxacin 8-fold. It could have potential
in treating various bacterial infections where fluoroquinolone
resistance has caused treatment failure.
WQ
2942
The
Japanese company, Wakunaga Pharmaceuticals has a substituted
8-methyl quinolone, WQ 2942. This showed good activity against
S. aureus MRSA, S. pneumoniae and Pseudomonas aeruginosa.
More
information can be obtained from IMS HEALTH’s R&D
Focus and Pioneer
services.
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