INTRODUCTION

Quinolones and cephalosphorins have a lot in common in history and development,

they have been the focal point of scientific furthermore, clinical discovery since
their discovery in the beginning 1960s. This is on the findings that they conceivably
offer many of the attributes of an ideal antibiotic, combining high potency, a broad
spectrum of activity, great bioavailability, oral and intravenous formulations, high
serum levels, a large volume of distribution indicating concentration in tissues and a
potentially low incidence of side-effects. Nalidixic acid was developed to treat
urinary tract infections, with other first degree quinolones like cinoxacin, acrosoacin,
and pipemidic acid. It was largely restricted to E.coli and Enterobacteriaceae.

Folate is a water-soluble B-vitamin that occurs naturally in foods. The synthetic form
of folate that is found in supplements and added to fortified foods such as white
flour, white bread and a variety of pastas and nutrition bars is the folic acid. In order
to synthesize the nucleic acids that make up the bacterias DNA, they use folic acid.
Based on the Marshall Pathogenesis (MP), eating foods with supplemental folic acid
may strengthen the bacteria that MP patients are trying to kill. MP patients must
avoid supplements and multivitamins containing supplemental folic acid. MP
patients must try to limit intake of foods containing enriched flour or folic acid.
Excess folic acid can allow bacteria to proliferate. Trimethoprim is an antibiotic drug
that blocks the activity of DHFR which is used to create Bactrim.

Sulphonamides were discovered by Domagk in 1935 when protonsil, a red azo dye
was converted into sulphonamide. This was because it had been shown that
protonsil had a curative effect on mice infected with B-haemolytic streptococci.
Sulphonamides are structurally similar to p-aminobenzoic acid (PABA), which is an
integral part of the vitamin B, folic acid. Folic acid synthesis is reduced when
sulphonamides compete with PABA in sensitive bacteria. This also leads to a
reduction of bacterial growth, since the vitamin is essential for the manufacture of
nucleic acid (and other important biochemicals.)
DISCUSSION
Quinolones were derived from quinine. The distinguishing feature of the first
generation is the absence of a fluorine atom at position 6, so they are simply
designated quinolones, whereas the second, third and fourth generations are
termed fluoroquinones. The first generation is now rarely used but those that
followed in the 1980s are still currently used. Third generation quinolones possess
attributes of their attributes of their predecessors but exhibit greater activity
against Strep.pnuemoniae. The fourth generation is also active against anaerobes.
All the quinolones are bactericidal, and act by inhibiting the bacterial enzymes
responsible for coiling of the DNA. The quinolone class of antibacterial agents has a
unique mechanism of action and bactericidal properties that made them attractive
therapeutic agents. They had proven a track record for the treatment of bacterial
infections for several decades. Research efforts continue until this day in both
academia and industry resulting to a number of promising drug candidates for
further development. This review examines quinolones that have been approved,
entered into clinical trials or reported in the literature during 2005-2010. For over 40
years of research, quinolones continuously provide new analogs for both scientific
and clinical interest. Compounds with improved pharmacokinetic and safety profiles
are goals for current and future programs in this area. In terms of anti-Gram-
negative potency, the activity of quinolones against Enterobacteriaceae such as
Escherichia coli and Klebsiella spp. has not changed significantly since the
development of norfloxacin. The early drugs (nalidixic acid and cinoxacin) did not
have very good anti-pseudomonal potency. In general, the newer agents have
improved activity against pathogens such as Mycoplasma pneumoniae and other
atypical bacteria, and some have improved activity against Gram-negative
anaerobes, such as Bacteroides fragilis. However, many of the newer agents, such
as gatifloxacin, gemifloxacin, garenoxacin and moxifloxacin, are not as potent as
ciprofloxacin against P. aeruginosa. One of the more interesting developments in
terms of potency is the area of anti-Gram-positive activity. Although it is unlikely
any fluoroquinolone will have activity against ciprofloxacin-resistant Staphylococcus
aureus, a major development has been in the activity of these drugs against
ciprofloxacin-sensitive S. aureus, Streptococcus pneumoniae and Group A
streptococci. This is one of the key advances in terms of the development of these
agents.

Trimethoprim is an integral part of a dihydrofolate reductase inhibitor, and were

found to act synergistically with sulphonamides. Trimethoprim blocks the successive
steps in the synthesis of reduced folic acid that can help sulphonamides in
performing its action.Trimethoprim was introduced in 1969 in combination with
sulphamethoxazole (co-timoxazole) for the treatment of urinary tract and
respiratory infections. Pharmacokinetic differences between the two drugs resulted
in relative concentrations in the body which were far from optimal for synergy.In
mid-1970s trimethoprim was used alone, due to increasing evidences that the
antibacterial activity of co-trimoxazole was mainly due to the trimethoprim
component with a little contribution of the more toxic sulphamethoxazole.
Trimethoprim remains one of the least expensive orally active agents available for
treatment of urinary tract infections. Trimethoprim is suffering from increasing
resistance development resulting to replacement of the drug with fluoroquinolones.
Trimethoprim analogues have been introduced, but have not demonstrated
advantages over trimethoprim. Folic acid is important to the growth of bacteria that
many therapies for infections slow disease progress by blocking activity of folic acid.
A conventional treatment for sarcoidosis confirms that folic acid affects the activity
of L-form bacteria. Difficult to culture bacteria that lacks cell wall are not detectable
by traditional culturing processes (Sometimes referred to as cell wall deficient
bacteria. Methotrexate (MTX) are sometimes prescribed to patients with sarcoidosis.
It temporarily slows down progression of the disease by blocking folic acid activity
and the activity of DHFR. Trimethoprim is an antibiotic drug that blocks the activity
of DHFR which is used to create Bactrim. It is often used as part of the Marshall
Protocol. It was observed emperically that sarcoidosis patients tend to be able to
tolerate the folic acid in their diets but their serum folates tend to be low. FDA
supplementation policy In March 1996, the FDA instituted a mandate for fortification
of flour and uncooked grains to a level of 140g/100g to be fully instituted by
January 1998, the reason being that B-vitamin deficiency had been linked to spina
bifida and anencephaly in children born to women with poor diets. Clinical evidence
Clinical trials found that treatment with folic acid plus Vit B12 was associated with
increased cancer outcomes and all-cause mortality in patients with ischemic heart
disease in Norway, where no folic acid fortification of foods happens.
Epidemiological evidence Epidemiological studies on the issue of whether folic acid
is harmful in chronic disease have been somewhat equivocal. However, one recent
Chilean study analyzed hospital-discharge data for two 4-year periods before folic
acid fortification (19921996) and after (20012004) and found a significant
increase in reported cases of colon cancer. The increase was 162% in people 45 to
64 years and 190% in people 65 to 79 years.2) A pair of commentaries appearing in
the November 2007 issue of Nutrition Reviews argue that folic acid benefits some
and harms others. Dr. Solomons advises that a careful reconsideration of the
fortification program is needed. One size of dietary folic acid exposure does not fit
all. It can be beneficial to some and detrimental to others at the same time, writes
Solomons. According to Kim, exposure to high intakes of folic acid in early life and
young adulthood may provide life-long protection from the tendency for cancer
formation in different organs, such as the large intestines, whereas such exposures
later in life, when cell damage has occurred, can spur on the advance of the tumor.
A 2010 study by House et al. has shown substantial adverse outcomes associated
with high-dose B vitamins in patients with advanced diabetic nephropathy. These
side effects included myocardial infarction, stroke, revascularization, and all-cause
mortality. According to one commentator, unless other explanations come to light in
further analyses of the study, these findings make repetition of a similar trial in this
high-risk patient group unethical. The conclusions expressed in these studies and
reviews are consistent with the contention that supplemental folic acid is most
harmful for people who are older and presumably have higher microbial loads. The
following are the side effects of Trimethoprim: upset stomach, vomiting, diarrhea. Its
side effects are as follows: rash (hives), itching, difficulty breathing or swallowing,
sore throat, fever or chills, mouth sores, unusual bruising or bleeding, yellowing of
the skin or eyes, paleness, joint aches, bluish-colored fingernails, lips, or skin.